#10#
Revisiones-Ciencias
Básicas-Molecular, Bioquímica, Metabolismo & Genética *** Reviews-Basic
Sciences-Molecular, Biochemistry, Metabolism & Genetics
INMUNOSUPRESIÓN
*** IMMUNOSUPPRESSION
(Conceptos
/ Keywords: Immunosuppression; Immunosuppressive ag.; Transpl. immunol.; GVH;
Antirejection therapy; Lymphocyte depletion; Transpl. conditioning; etc).
Enero /
January 2001 --- Marzo / March 2004
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Only articles written in Spanish and/or English are included.
[1]
TÍTULO / TITLE: - Hepcidin: a putative
iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia
of chronic disease.
REVISTA
/ JOURNAL: - Proc Natl Acad Sci U S A. Acceso gratuito
al texto completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.pnas.org/
●●
Cita: Proc Natl Acad Sci USA (PNAS): <> 2001 Jul 17;98(15):8160-2.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.161296298
AUTORES
/ AUTHORS: - Fleming RE; Sly WS
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Saint Louis
University School of Medicine, St. Louis, MO 63014, USA. N. Ref:: 30
----------------------------------------------------
[2]
TÍTULO / TITLE: - Beta lactam monotherapy
versus beta lactam-aminoglycoside combination therapy for sepsis in
immunocompetent patients: systematic review and meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2004 Mar 20;328(7441):668. Epub 2004
Mar 2.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.38028.520995.63
AUTORES
/ AUTHORS: - Paul M; Benuri-Silbiger I; Soares-Weiser
K; Leibovici L
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine E and Infectious
Diseases Unit, Rabin Medical Centre, Beilinson Campus, Petah-Tikva 49100,
Israel. mica@zahav.net.il
RESUMEN
/ SUMMARY: - OBJECTIVE: To compare beta lactam
monotherapy with beta lactam-aminoglycoside combination therapy for severe
infections. DATA SOURCES: Medline, Embase, Lilacs, Cochrane Library, and
conference proceedings, to 2003; references of included studies; contact with
all authors. No restrictions, such as language, year of publication, or
publication status. STUDY SELECTION: All randomised trials of beta lactam
monotherapy compared with beta lactam-aminoglycoside combination therapy for
patients without neutropenia who fulfilled criteria for sepsis. DATA SELECTION:
Two reviewers independently applied selection criteria, performed quality
assessment, and extracted the data. The primary outcome assessed was all cause
fatality by intention to treat. Relative risks were pooled with the random
effect model (relative risk < 1 favours monotherapy). RESULTS: 64 trials
with 7586 patients were included. There was no difference in all cause fatality
(relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared
the same beta lactam (1.02, 0.76 to 1.38), and 31 studies compared different
beta lactams (0.85, 0.69 to 1.05). Clinical failure was more common with
combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing
different beta lactams (0.76, 0.68 to 0.86). There was no advantage to combination
therapy among patients with Gram negative infections (1835 patients) or
Pseudomonas aeruginosa infections (426 patients). There was no difference in
the rate of development of resistance. Nephrotoxicity was significantly more
common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not
significant for these comparisons. CONCLUSIONS: In the treatment of sepsis the
addition of an aminoglycoside to beta lactams should be discouraged. Fatality
remains unchanged, while the risk for adverse events is increased. N. Ref:: 26
----------------------------------------------------
[3]
TÍTULO / TITLE: - Immunopathogenesis and
immunotherapy in AIDS virus infections.
REVISTA
/ JOURNAL: - Nat Med 2003 Jul;9(7):861-6.
●●
Enlace al texto completo (gratuito o de pago) 1038/nm0703-861
AUTORES
/ AUTHORS: - Letvin NL; Walker BD
INSTITUCIÓN
/ INSTITUTION: - Division of Viral Pathogenesis, Beth
Israel Deaconess Medical Center, Massachusetts General Hospital, Harvard
Medical School, Boston, Massachusetts 02114, USA.
RESUMEN
/ SUMMARY: - The heterogeneity of HIV and the different
human leukocyte antigen (HLA) backgrounds of infected individuals have posed
challenges to understanding the pathogenesis of HIV infection. But continuing
advances in our knowledge of the role of immune responses in controlling HIV
viremia should help to define goals for immune-based therapies and vaccine
strategies against AIDS. N.
Ref:: 106
----------------------------------------------------
[4]
TÍTULO / TITLE: - Integration of growth
factor and nutrient signaling: implications for cancer biology.
REVISTA
/ JOURNAL: - Mol Cell 2003 Aug;12(2):271-80.
AUTORES
/ AUTHORS: - Shamji AF; Nghiem P; Schreiber SL
INSTITUCIÓN
/ INSTITUTION: - Harvard Biophysics Program, Harvard
University, 12 Oxford Street, Cambridge, MA 02138, USA.
RESUMEN
/ SUMMARY: - Signaling networks that promote cell
growth are frequently dysregulated in cancer. One regulatory network, which
converges on effectors such as 4EBP1 and S6K1, leads to growth by promoting
protein synthesis. Here, we discuss how this network is regulated by both
extracellular signals, such as growth factors, and intracellular signals, such
as nutrients. We discuss how mutations amplifying either type of signal can
lead to tumor formation. In particular, we focus on the recent discovery that a
tumor suppressor complex whose function is lost in tuberous sclerosis patients
regulates the nutrient signal carried by the critical signaling protein TOR to
the effectors 4EBP1 and S6K1. Finally, we describe how the small molecule
rapamycin, which inhibits TOR and thereby the activation of these effectors,
could be useful to treat tumors that have become dependent upon this pathway
for growth. N. Ref:: 80
----------------------------------------------------
[5]
TÍTULO / TITLE: - Defying death—HIV
mutation to evade cytotoxic T lymphocytes.
REVISTA
/ JOURNAL: - N Engl J Med. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://content.nejm.org/
●●
Cita: New England J Medicine (NEJM): <> 2002 Oct 10;347(15):1203-4.
●●
Enlace al texto completo (gratuito o de pago) 1056/NEJMcibr022067
AUTORES
/ AUTHORS: - Lieberman J
INSTITUCIÓN
/ INSTITUTION: - Center for Blood Research, Boston, MA
02115, USA. N. Ref:: 5
----------------------------------------------------
[6]
TÍTULO / TITLE: - Genetic and functional
relationships between MHC and NK receptor genes.
REVISTA
/ JOURNAL: - Immunity 2001 Sep;15(3):363-74.
AUTORES
/ AUTHORS: - Trowsdale J
INSTITUCIÓN
/ INSTITUTION: - Immunology Division, Pathology Department,
University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
RESUMEN
/ SUMMARY: - HLA class I and NK receptors are encoded
within dense clusters of immune loci. The MHC, at 6p21.3, and the complex
containing the KIR loci, at 19q13.4, both feature variation in the number of
genes, as well as sequence polymorphism. In addition to T cell receptors,
several variable class I-related molecules interact with polymorphic NK
receptors. Some of the lectin-related NK receptor genes, at 12p13.1, also have
ligands belonging to the extended class I family. The expanding clusters of
class I-related sequences and their receptors, some of which evolved recently,
reveal further complexity in immune recognition of disease. N. Ref:: 85
----------------------------------------------------
[7]
TÍTULO / TITLE: - Impact of shared
epitope genotype and ethnicity on erosive disease: a meta-analysis of 3,240
rheumatoid arthritis patients.
REVISTA
/ JOURNAL: - Arthritis Rheum 2004 Feb;50(2):400-12.
●●
Enlace al texto completo (gratuito o de pago) 1002/art.20006
AUTORES
/ AUTHORS: - Gorman JD; Lum RF; Chen JJ; Suarez-Almazor
ME; Thomson G; Criswell LA
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
CA 94143-0500, USA. lac@itsa.ucsf.edu
RESUMEN
/ SUMMARY: - OBJECTIVE: The strongest known genetic
association in rheumatoid arthritis (RA) is with HLA-DRB1 alleles that share a
similar amino acid sequence, termed the shared epitope (SE). Although many
studies have examined the association of the SE with disease severity, the
results have been inconsistent, which may reflect the relatively small sample
sizes or ethnic differences. The aim of this study was to assess the
association of HLA-DRB1 SE alleles and genotype with the development of bony
erosions in RA by meta-analysis. METHODS: We identified English-language
articles published between January 1, 1987 and June 1, 1999 through Medline,
EMBase, and manual searches of 6 relevant journals. Included were studies in
which molecular typing of HLA-DRB1 alleles was performed and in which the
presence or absence of bony erosions was reported. Data were extracted from the
studies, and erosions were coded as present or absent. Authors were contacted
for missing information and data on individual patients. RESULTS: A total of 29
studies and 3,240 patients were available for analysis. The summary odds ratios
(ORs), when all patients were evaluated as a single group, demonstrated a
significant association of the presence of the SE (2 or 1 versus 0 SE alleles)
with erosions (OR 2.0; 95% confidence interval [95% CI] 1.8-2.2), although
significant heterogeneity was present (P = 0.002). Subgroup analyses demonstrated
the important influence of ethnic background. For example, no association of
the SE with erosions was demonstrated in Greeks (OR 0.8 [95% CI 0.2-1.5]). In
contrast, there was a striking dose-dependent relationship in southern European
Caucasians and Asians, with ORs as high as 6.2 and 5.4, respectively, in
patients with 2 SE alleles. Although our ability to assess the relationship
between SE genotype and erosions was limited, particular importance of the
DRB1*0401 SE allele was suggested in an analysis restricted to northern
European Caucasians. CONCLUSION: The SE is associated with the development of
erosive disease in many ethnic groups; however, striking exceptions exist.
These variations may be due to allele differences between populations, such as
the frequency of DRB1*0401 among different ethnic groups. Further study to
better understand the genetic and environmental differences between these
populations may provide insight into mechanisms that influence the clinical
expression of RA.
----------------------------------------------------
[8]
TÍTULO / TITLE: - Routes to transplant
tolerance versus rejection; the role of cytokines.
REVISTA
/ JOURNAL: - Immunity 2004 Feb;20(2):121-31.
AUTORES
/ AUTHORS: - Walsh PT; Strom TB; Turka LA
INSTITUCIÓN
/ INSTITUTION: - University of Pennsylvania, 700 Clinical
Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
RESUMEN
/ SUMMARY: - The alloimmune response can be divided
into specific junctures where critical decisions between tolerance and immunity
are made which define the outcome of the transplant. At these “decision nodes”
various cytokines direct alloresponsive T cells to develop either a
proinflammatory response aimed at graft destruction or an immunoregulatory
response facilitating graft acceptance. This review will focus on the role of
these cytokines in influencing the progression of an alloimmune response
leading ultimately to either allograft survival or rejection. N. Ref:: 97
----------------------------------------------------
[9]
TÍTULO / TITLE: - Microchimerism: an
investigative frontier in autoimmunity and transplantation.
REVISTA
/ JOURNAL: - JAMA. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl
●●
Cita: JAMA: <> 2004 Mar 3;291(9):1127-31.
●●
Enlace al texto completo (gratuito o de pago) 1001/jama.291.9.1127
AUTORES
/ AUTHORS: - Adams KM; Nelson JL
INSTITUCIÓN
/ INSTITUTION: - Program in Human Immunogenetics, Clinical
Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
98109-1024, USA.
RESUMEN
/ SUMMARY: - Recent studies indicate cells transfer
between fetus and mother during pregnancy and can persist in both decades
later. The presence within one individual of a small population of cells from
another genetically distinct individual is referred to as microchimerism.
Naturally acquired microchimerism has recently been investigated in autoimmune
diseases, including scleroderma, thyroiditis, primary biliary cirrhosis,
Sjogren syndrome, systemic lupus, dermatomyositis, and neonatal lupus.
Iatrogenic chimerism has been investigated in transplantation and following
blood transfusion. Considering findings of naturally acquired microchimerism
along with iatrogenic microchimerism suggests microchimerism can have
detrimental and/or beneficial effects in both settings. Recent identification
of tissue-specific microchimerism either from naturally acquired or iatrogenic
microchimerism (eg, cardiac myocytes) raises the possibility that
microchimerism can be a target of autoimmunity or alternatively contribute to
tissue repair. Advances in this new frontier of research with varied and numerous
implications for human health are summarized.
N. Ref:: 26
----------------------------------------------------
[10]
TÍTULO / TITLE: - The allogeneic response
and tumor immunity.
REVISTA
/ JOURNAL: - Nat Med 2001 Jun;7(6):649-52.
●●
Enlace al texto completo (gratuito o de pago) 1038/89008
AUTORES
/ AUTHORS: - Fabre JW
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Sciences, Institute
of Liver Studies Guy’s, King’s and St Thomas’ School of Medicine, London, UK. john.fabre@kcl.ac.uk
RESUMEN
/ SUMMARY: - The strong allogeneic response to donor
MHC molecules in transplantation and the weak response to tumor antigens
represent two important and divergent but potentially interactive immune
responses. A patient’s response to allogeneic MHC molecules might promote an
effective T-cell response to self MHC-restricted tumor peptides and the
possibilities for this are discussed here. These allogeneic responses might
successfully be harnessed to promote the immune eradication of metastatic
cancer. N. Ref:: 45
----------------------------------------------------
[11]
TÍTULO / TITLE: - Lack of association of
the HLA-DRB1 shared epitope with rheumatoid nodules: an individual patient data
meta-analysis of 3,272 Caucasian patients with rheumatoid arthritis.
REVISTA
/ JOURNAL: - Arthritis Rheum 2004 Mar;50(3):753-62.
●●
Enlace al texto completo (gratuito o de pago) 1002/art.20119
AUTORES
/ AUTHORS: - Gorman JD; David-Vaudey E; Pai M; Lum RF;
Criswell LA
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
and School of Public Health, University of California, Berkeley.
RESUMEN
/ SUMMARY: - OBJECTIVE: The objective of this
individual patient data (IPD) meta-analysis was to examine the relationship of
rheumatoid nodules to the HLA-DRB1 shared epitope (SE) and to individual SE
genotypes. METHODS: English-language studies that enrolled adult non-Hispanic
Caucasian patients with rheumatoid arthritis (RA) were identified by searches
of Medline and Embase, and by manual searches of medical journals. All authors
were contacted for IPD. Meta-analysis was performed to assess the association
of SE presence, dose, and genotype with rheumatoid nodules. Meta-analyses
adjusted for disease duration and cumulative meta-analyses were also performed
to assess the influence of RA duration and year of study publication on the
results. RESULTS: A total of 24 studies and 3,272 patients were available for
analysis. IPD were obtained for 22 of the studies. There was a nonsignificant
association between the presence of the SE (i.e., 1 or 2 alleles versus 0
alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence
interval [95% CI] 0.97-1.6). Analysis by SE genotype, however, demonstrated a
weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95%
CI 1.1-1.8). No other genotypes achieved statistical significance in the
adjusted or unadjusted analyses. CONCLUSION: The presence of the HLA-DRB1 SE
does not appear to significantly increase the risk of rheumatoid nodules among
Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative,
suggesting only a potential (and at most modest) role of the DRB1*0401 SE
allele. Results from this IPD meta-analysis implicate other genetic,
stochastic, and/or environmental factors in the susceptibility to rheumatoid
nodules.
----------------------------------------------------
[12]
TÍTULO / TITLE: - Genetic control of MHC
class II expression.
REVISTA
/ JOURNAL: - Cell 2002 Apr;109 Suppl:S21-33.
AUTORES
/ AUTHORS: - Ting JP; Trowsdale J
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology and Immunology
and The Lineberger Comprehensive Cancer Center, University of North Carolina,
Chapel Hill, NC 27599, USA. panyun@med.unc.edu
RESUMEN
/ SUMMARY: - The presentation of peptides to T cells by
MHC class II molecules is of critical importance in specific recognition by the
immune system. Expression of class II molecules is exquisitely controlled at
the transcriptional level. A large set of proteins interact with the promoters
of class II genes. The most important of these is CIITA, a master controller
that orchestrates expression but does not bind directly to the promoter. The
transcriptosome complex formed at class II promoters is a model for induction
of gene expression. N.
Ref:: 108
----------------------------------------------------
[13]
TÍTULO / TITLE: - Interferon-gamma
reduces interleukin-4- and interleukin-13-augmented transforming growth
factor-beta2 production in human bronchial epithelial cells by targeting Smads.
REVISTA
/ JOURNAL: - Chest. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.chestjournal.org/
●●
Cita: Chest: <> 2003 Mar;123(3 Suppl):372S-3S.
AUTORES
/ AUTHORS: - Wen FQ; Liu XD; Terasaki Y; Fang QH;
Kobayashi T; Abe S; Rennard SI
INSTITUCIÓN
/ INSTITUTION: - Pulmonary and Critical Care Medicine
Section, University of Nebraska Medical Center, Omaha, NE 68198-5125, USA. N. Ref:: 0
----------------------------------------------------
[14]
TÍTULO / TITLE: - When the lymphocyte
loses its clothes.
REVISTA
/ JOURNAL: - Immunity 2003 Apr;18(4):453-7.
AUTORES
/ AUTHORS: - Nekrep N; Fontes JD; Geyer M; Peterlin BM
INSTITUCIÓN
/ INSTITUTION: - Institute of Biochemistry, Medical Faculty
of the University of Ljubljana, Slovenia.
RESUMEN
/ SUMMARY: - The type II bare lymphocyte syndrome (BLS)
or major histocompatibility complex class II (MHCII) deficiency is a severe
combined immunodeficiency (SCID) that is characterized by the absence of
constitutive and inducible expression of MHCII determinants on immune cells.
Four complementation groups of BLS have been defined, and they result from
mutations in DNA-bound activators and the coactivator for MHCII transcription.
Recently, all complementation groups of BLS patients have been accounted for.
Studies of the syndrome and specific mutations reveal important lessons for the
genetics of the immune response. N.
Ref:: 35
----------------------------------------------------
[15]
TÍTULO / TITLE: - Ex vivo selection of
recipient-type alloantigen-specific CD4(+)CD25(+) immunoregulatory T cells for
the control of graft-versus-host disease after allogeneic hematopoietic
stem-cell transplantation.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1
Suppl):S32-4.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106470.07410.CA
AUTORES
/ AUTHORS: - Trenado A; Fisson S; Braunberger E;
Klatzmann D; Salomon BL; Cohen JL
INSTITUCIÓN
/ INSTITUTION: - Biologie et Therapeutique des Pathologies
Immunitaires, Hopital Pitie-Salpetriere, Paris, France.
RESUMEN
/ SUMMARY: - Allogeneic hematopoietic stem-cell
transplantation (HSCT) is the treatment of choice for many malignant and
nonmalignant hematologic disorders. Donor T cells present in the hematopoietic
stem-cell transplant improve engraftment and immune reconstitution and
contribute to the graft-versus-leukemia effect, but are also responsible for
the life-threatening graft-versus-host disease (GVHD). CD4(+)CD25(+)
immunoregulatory T cells, which play a pivotal role in preventing
organ-specific diseases, can also modulate GVHD if administered in equal
numbers of T cells at the time of grafting. In this article, the authors
describe a procedure of ex vivo selection and expansion of regulatory T cells
specific for recipient-type alloantigens. These expanded regulatory T cells
controlled GVHD. Their therapeutic use in HSCT should allow specific
suppression of the activation of donor alloreactive T cells involved in GVHD
while preserving the beneficial effects of other T cells. N. Ref:: 27
----------------------------------------------------
[16]
TÍTULO / TITLE: - Hemochromatosis gene
modifies course of hepatitis C viral infection.
REVISTA
/ JOURNAL: - Gastroenterology 2003 May;124(5):1509-23.
AUTORES
/ AUTHORS: - Pietrangelo A
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Centre
for Hemochromatosis and Metabolic Liver Diseases, University of Modena and
Reggio Emilia, Modeno, Italy. antonello@unimore.it N. Ref:: 161
----------------------------------------------------
[17]
TÍTULO / TITLE: - T cell receptor-MHC
interactions up close.
REVISTA
/ JOURNAL: - Cell 2001 Jan 12;104(1):1-4.
AUTORES
/ AUTHORS: - Hennecke J; Wiley DC
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular and Cellular
Biology, Harvard University and Howard Hughes Medical Institute, Cambridge, MA
02138, USA. hennecke@crystal.harvard.edu N. Ref:: 18
----------------------------------------------------
[18]
- Castellano -
TÍTULO / TITLE:La ruta de senalizacion CA++/calcineurina/NFAT
en activacion endotelial y angiogenesis: efectos de la ciclosporina A. CA++/
calcineurin/NFAT signaling in endothelial activation and angiogenesis: effects
od cyclosporin A .
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 3:44-8.
AUTORES
/ AUTHORS: - Quesada AJ; Redondo JM
INSTITUCIÓN
/ INSTITUTION: - Centro de Biologia Molecular Severo Ochoa,
Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid
y Centro Nacional de Investigaciones Cardiovasculares (CNIC), Sinesio Delgado,
4 28049 Cantoblanco, Madrid. jmredondo@cbm.uam.es N. Ref:: 31
----------------------------------------------------
[19]
TÍTULO / TITLE: - Disease modifying
therapies in multiple sclerosis: report of the Therapeutics and Technology
Assessment Subcommittee of the American Academy of Neurology and the MS Council
for Clinical Practice Guidelines.
REVISTA
/ JOURNAL: - Neurology 2002 Jan 22;58(2):169-78.
AUTORES
/ AUTHORS: - Goodin DS; Frohman EM; Garmany GP Jr;
Halper J; Likosky WH; Lublin FD; Silberberg DH; Stuart WH; van den Noort S
----------------------------------------------------
[20]
TÍTULO / TITLE: - Identification of TOR
signaling complexes: more TORC for the cell growth engine.
REVISTA
/ JOURNAL: - Cell 2002 Oct 4;111(1):9-12.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road,
La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - The Target of Rapamycin (TOR) proteins
function in signaling pathways that promote protein synthesis and cell growth.
In yeast, TOR signaling is regulated by nutrient availability, whereas in
metazoan cells TOR activities may be controlled by both nutrients and growth
factors. The recent identification of novel TOR-interacting proteins has
provided crucial insights into TOR regulation and function. N. Ref:: 20
----------------------------------------------------
[21]
TÍTULO / TITLE: - Immune tolerance after
long-term enzyme-replacement therapy among patients who have
mucopolysaccharidosis I.
REVISTA
/ JOURNAL: - Lancet 2003 May 10;361(9369):1608-13.
AUTORES
/ AUTHORS: - Kakavanos R; Turner CT; Hopwood JJ; Kakkis
ED; Brooks DA
INSTITUCIÓN
/ INSTITUTION: - Lysosomal Diseases Research Unit,
Department of Chemical Pathology, Women’s and Children’s Hospital, North
Adelaide, South Australia, Australia
RESUMEN
/ SUMMARY: - BACKGROUND: Enzyme-replacement therapy has
been assessed as a treatment for patients who have mucopolysaccharidosis I
(alpha-L-iduronidase deficiency). We aimed to investigate the humoral immune
response to recombinant human alpha-L-iduronidase among these patients.
METHODS: We characterised the antibody titres and specific linear sequence
epitope reactivity of serum antibodies to alpha-L-iduronidase for ten patients
with mucopolysaccharidosis I, at the start of treatment and after 6, 12, 26,
52, and 104 weeks. We compared the values for patients’ samples with those for
samples from normal human controls. FINDINGS: Before enzyme-replacement
therapy, all patients had low serum antibody titres to recombinant human
alpha-L-iduronidase that were within the control range. Five of the ten
patients produced higher-than-normal titres of antibody to the replacement
protein during the treatment course (serum antibody titres 130000-500000 and
high-affinity epitope reactivity). However, by week 26, antibody reactivity was
reduced, and by week 104 all patients had low antibody titres and only
low-affinity epitope reactivity. Patients who had mucopolysaccharidosis I with
antibody titres within the normal range at 6-12 weeks did not subsequently
develop immune responses. INTERPRETATION: After 2 years of treatment, patients
who initially had an immune reaction developed immune tolerance to
alpha-L-iduronidase. This finding has positive implications for long-term
enzyme-replacement therapy in patients who have mucopolysaccharidosis I. N. Ref:: 32
----------------------------------------------------
[22]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[23]
TÍTULO / TITLE: - Stress management: MHC
class I and class I-like molecules as reporters of cellular stress.
REVISTA
/ JOURNAL: - Immunity 2003 Oct;19(4):469-77.
AUTORES
/ AUTHORS: - Gleimer M; Parham P
INSTITUCIÓN
/ INSTITUTION: - Program in Immunology, Stanford University
School of Medicine, Stanford, CA 94305, USA.
RESUMEN
/ SUMMARY: - The evolutionarily ancient intracellular
stress response protects cells from the effects of external and internal forces
which perturb cellular metabolism. Members of the major histocompatibility
complex (MHC) class I-like superfamily act as cell surface indicators of the
intracellular stress response. Cellular immunity employs these indicators as a
cue for elimination of damaged, infected, and malignant cells, promoting the
health of the individual and the evolutionary success of the species. N. Ref:: 77
----------------------------------------------------
[24]
TÍTULO / TITLE: - Interleukin 2 receptor
antagonists for renal transplant recipients: a meta-analysis of randomized trials.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):166-76.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000109643.32659.C4
AUTORES
/ AUTHORS: - Webster AC; Playford EG; Higgins G;
Chapman JR; Craig JC
INSTITUCIÓN
/ INSTITUTION: - Cochrane Renal Group, Centre for Kidney
Research, Children’s Hospital at Westmead, Westmead, NSW, Australia.
RESUMEN
/ SUMMARY: - BACKGROUND: Interleukin 2 receptor
antagonists (IL-2Ra) are increasingly used to treat renal transplant
recipients. This study aims to systematically identify and summarize the
effects of using IL-2Ra as induction immunosuppression, as an addition to
standard therapy, or as an alternative to other antibody therapy. METHODS:
Databases, reference lists, and abstracts of conference proceedings were
searched extensively to identify relevant randomized controlled trials in all
languages. Data were synthesized using the random effects model. Results are
expressed as relative risk (RR), with 95% confidence intervals (CI). RESULTS: A
total of 117 reports from 38 trials involving 4,893 participants were included.
When IL-2Ra were compared with placebo (17 trials; 2,786 patients), graft loss
was not significantly different at 1 year (14 trials: RR 0.84; CI 0.64-1.10) or
3 years (4 trials: RR 1.08; CI 0.71-1.64). Acute rejection was significantly
reduced at 6 months (12 trials: RR 0.66; CI 0.59-0.74) and at 1 year (10
trials: RR 0.67; CI 0.60-0.75). At 1 year, cytomegalovirus infection (7 trials:
RR 0.82; CI 0.65-1.03) and malignancy (9 trials: RR 0.67; CI 0.33-1.36) were
not significantly different. When IL-2Ra were compared with other antibody
therapy, no significant differences in treatment effects were demonstrated, but
IL-2Ra had significantly fewer side effects. CONCLUSIONS: Given a 40% risk of
rejection, seven patients would need treatment with IL-2Ra in addition to
standard therapy, to prevent one patient from undergoing rejection, with no
definite improvement in graft or patient survival. There is no apparent
difference between basiliximab and daclizumab.
----------------------------------------------------
[25]
TÍTULO / TITLE: - Genetic interaction of
CTLA-4 with HLA-DR15 in multiple sclerosis patients.
REVISTA
/ JOURNAL: - Ann Neurol 2003 Jul;54(1):119-22.
●●
Enlace al texto completo (gratuito o de pago) 1002/ana.10617
AUTORES
/ AUTHORS: - Alizadeh M; Babron MC; Birebent B; Matsuda
F; Quelvennec E; Liblau R; Cournu-Rebeix I; Momigliano-Richiardi P; Sequeiros
J; Yaouanq J; Genin E; Vasilescu A; Bougerie H; Trojano M; Martins Silva B;
Maciel P; Clerget-Darpoux F; Clanet M; Edan G; Fontaine B; Semana G
INSTITUCIÓN
/ INSTITUTION: - Laboratoire Universitaire d’Immunologie
(UPRES EA 1257, IFR 97) and Etablissement Francais du Sang Bretagne, Faculte de
Medecine, Rennes, France.
RESUMEN
/ SUMMARY: - Multiple sclerosis is a chronic
inflammatory disease of the central nervous system with a genetic component.
Until now, the more consistent association with the disease is found with the
major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype.
In this report, we demonstrate the interaction of Cytotoxic T
Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in
multiple sclerosis genetic susceptibility. Our data were obtained from two
European independent family-based studies including 610 multiple sclerosis
family trios. Ann Neurol 2003;54:119-122
N. Ref:: 20
----------------------------------------------------
[26]
TÍTULO / TITLE: - Novel therapeutic
molecular targets for prostate cancer: the mTOR signaling pathway and epidermal
growth factor receptor.
REVISTA
/ JOURNAL: - J Urol 2004 Feb;171(2 Pt 2):S41-3;
discussion S44.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7
AUTORES
/ AUTHORS: - Tolcher AW
INSTITUCIÓN
/ INSTITUTION: - Director Clinical Research, Institute for
Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.
RESUMEN
/ SUMMARY: - PURPOSE: The scientific rationale and
existing evidence for the use of novel molecular targets in the chemoprevention
of cancer are reviewed, with special attention to prostate cancer. MATERIALS
AND METHODS: A search for relevant literature on basic science and clinical
trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of
molecularly targeted therapies for advanced malignancies creates an important
opportunity to examine these agents for the chemoprevention of prostate cancer.
Two critical targets in the proliferation and malignant transformation of
normal cells, the PI3/Akt signal transduction pathway and the epidermal growth
factor receptor, are currently the focus of several novel investigational
therapies that are in late stage phase II and phase III studies. CONCLUSIONS:
Research to date supports consideration of these novel molecular targets as
future agents in the chemoprevention of prostate cancer. N. Ref:: 28
----------------------------------------------------
[27]
TÍTULO / TITLE: - Tolerogenic dendritic
cells induced by vitamin D receptor ligands enhance regulatory T cells
inhibiting allograft rejection and autoimmune diseases.
REVISTA
/ JOURNAL: - J Cell Biochem 2003 Feb 1;88(2):227-33.
●●
Enlace al texto completo (gratuito o de pago) 1002/jcb.10340
AUTORES
/ AUTHORS: - Adorini L; Penna G; Giarratana N;
Uskokovic M
INSTITUCIÓN
/ INSTITUTION: - BioXell, SpA, 20132 Milano, Italy. luciano.adorini@bioxell.com
RESUMEN
/ SUMMARY: - Dendritic cells (DCs) not only induce but
also modulate T cell activation. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]
induces DCs with a tolerogenic phenotype, characterized by decreased expression
of CD40, CD80, and CD86 costimulatory molecules, low IL-12 and enhanced IL-10
secretion. We have found that a short treatment with 1,25(OH)(2)D(3) induces
tolerance to fully mismatched mouse islet allografts that is stable to
challenge with donor-type spleen cells and allows acceptance of donor-type
vascularized heart grafts. This effect is enhanced by co-administration of
mycophenolate mofetil (MMF), a selective inhibitor of T and B cell
proliferation that has also effects similar to 1,25(OH)(2)D(3) on DCs. Graft
acceptance is associated with an increased percentage of CD4(+)CD25(+)
regulatory cells in the spleen and in the draining lymph node that can protect
100% of syngeneic recipients from islet allograft rejection. CD4(+)CD25(+)
cells, able to inhibit the T cell response to a pancreatic autoantigen and to
significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells, are
also induced by treatment of adult nonobese diabetic (NOD) mice with 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor
vitamin D(3) (BXL-698). This treatment arrests progression of insulitis and Th1
cell infiltration, and inhibits diabetes development at non-hypercalcemic
doses. The enhancement of CD4(+)CD25(+) regulatory T cells, able to mediate
transplantation tolerance and to arrest type 1 diabetes development by a short
oral treatment with VDR ligands, suggests possible clinical applications of
this approach. N.
Ref:: 41
----------------------------------------------------
[28]
TÍTULO / TITLE: - Immune activation:
death, danger and dendritic cells.
REVISTA
/ JOURNAL: - Curr Biol 2004 Jan 6;14(1):R30-2.
AUTORES
/ AUTHORS: - Pulendran B
INSTITUCIÓN
/ INSTITUTION: - Emory Vaccine Center, 954 Gatewood Road,
Atlanta, Georgia 30329, USA. bpulend@rmy.emory.edu
RESUMEN
/ SUMMARY: - Dendritic cells are critical for host
immunity, and sense microbes with pathogen recognition receptors. New evidence
indicates that these cells also sense uric acid crystals in dead cells,
suggesting that the immune system is conscious not only of pathogens, but also
of death and danger. N.
Ref:: 20
----------------------------------------------------
[29]
TÍTULO / TITLE: - Pathways for
self-tolerance and the treatment of autoimmune diseases.
REVISTA
/ JOURNAL: - Lancet 2001 Jun 30;357(9274):2115-21.
AUTORES
/ AUTHORS: - Goodnow CC
INSTITUCIÓN
/ INSTITUTION: - Australian Cancer Research Foundation,
Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical
Research, Australian National University, Canberra, Australia.
RESUMEN
/ SUMMARY: - Antigen delivers both immunogenic and
tolerogenic signals to lymphocytes. The outcome of antigen exposure represents
a complex integration of the timing of antigen binding with signals from many
other immunogenic and tolerogenic costimulatory pathways. A road map of these
signalling pathways is only beginning to be charted, revealing the mechansim of
action and limitations of current immunotherapeutic agents and the points of
attack for new agents. Ciclosporin and tacrolimus interfere with tolerogenic
signals from antigen in addition to blocking immunogenic signals, thus
preventing active establishment of tolerance. Corticosteroids inhibit a key
immunogenic pathway, NFkappaB, and more specific inhibitors of this pathway may
allow tolerance to be actively established while immune responses are blocked.
New experimental therapies aim to mimic tolerogenic antigen signals by
chronically stimulating antigen receptors with antigen or antibodies to the
receptor, or aim to block costimulatory pathways involving CD40 ligand, B7, or
interleukin 2. Obtaining the desired response with these strategies is
unpredictable because many of these signals have both tolerogenic and
immunogenic roles. The cause of autoimune diseases has been determined for
several rare monogenic disorders, revealing inherited deficiencies in
tolerogenic costimulatory pathways such as FAS. Common autoimmune disorders may
have a biochemically related pathogenesis.
N. Ref:: 52
----------------------------------------------------
[30]
- Castellano -
TÍTULO / TITLE:Guia de consenso sobre tuberculosis
y tratamiento de la enfermedad inflamatoria intestinal con infliximab.
Consensus guideline on tuberculosis and treatment of inflammatory bowel disease
with infliximab. Spanish Working Group on Crohn Disease and Ulcerative Colitis.
REVISTA
/ JOURNAL: - Gastroenterol Hepatol. Acceso gratuito al
texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Gastroenterología & Hepatología: <> 2003 Jan;26(1):29-33.
AUTORES
/ AUTHORS: - Obrador A; Lopez San Roman A; Munoz P;
Fortun J; Gassull MA
INSTITUCIÓN
/ INSTITUTION: - Servicio de Digestivo. Hospital Son
Dureta. Palma de Mallorca. España. N.
Ref:: 19
----------------------------------------------------
[31]
TÍTULO / TITLE: - Chemokines, chemokine
receptors, and allograft rejection.
REVISTA
/ JOURNAL: - Immunity 2001 Apr;14(4):377-86.
AUTORES
/ AUTHORS: - Nelson PJ; Krensky AM
INSTITUCIÓN
/ INSTITUTION: - Medizinishe Poliklinik, Klinikum
Innenstadt, Ludwig-Maximilians-University, Schillerstrasse 42, 80336, Munich,
Germany. nelson@medpoli.med.uni-muenchen.de N. Ref:: 40
----------------------------------------------------
[32]
TÍTULO / TITLE: - The target of rapamycin
(TOR) proteins.
REVISTA
/ JOURNAL: - Proc Natl Acad Sci U S A. Acceso gratuito
al texto completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.pnas.org/
●●
Cita: Proc Natl Acad Sci USA (PNAS): <> 2001 Jun 19;98(13):7037-44.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.121145898
AUTORES
/ AUTHORS: - Raught B; Gingras AC; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and McGill
Cancer Centre, McGill University, 3655 Promenade Sir-William-Osler, Montreal,
QC H3G 1Y6 Canada.
RESUMEN
/ SUMMARY: - Rapamycin potently inhibits downstream
signaling from the target of rapamycin (TOR) proteins. These evolutionarily
conserved protein kinases coordinate the balance between protein synthesis and
protein degradation in response to nutrient quality and quantity. The TOR
proteins regulate (i) the initiation and elongation phases of translation, (ii)
ribosome biosynthesis, (iii) amino acid import, (iv) the transcription of
numerous enzymes involved in multiple metabolic pathways, and (v) autophagy.
Intriguingly, recent studies have also suggested that TOR signaling plays a
critical role in brain development, learning, and memory formation. N. Ref:: 132
----------------------------------------------------
[33]
TÍTULO / TITLE: - Coeliac disease:
dissecting a complex inflammatory disorder.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2002 Sep;2(9):647-55.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri885
AUTORES
/ AUTHORS: - Sollid LM
INSTITUCIÓN
/ INSTITUTION: - Institute of Immunology, Rikshospitalet,
University of Oslo, 0027 Oslo, Norway. l.m.sollid@labmed.uio.no
RESUMEN
/ SUMMARY: - The disease mechanisms of complex
inflammatory disorders are difficult to define because of extensive
interactions between genetic and environmental factors. Coeliac disease is a
typical complex inflammatory disorder, but this disease is unusual in that
crucial genetic and environmental factors have been identified. This knowledge
has allowed functional studies of the predisposing HLA molecules, the
identification of antigenic epitopes and detailed studies of disease-relevant T
cells in coeliac disease. This dissection of the pathogenic mechanisms of
coeliac disease has uncovered principles that are relevant to other chronic
inflammatory diseases. N.
Ref:: 101
----------------------------------------------------
[34]
TÍTULO / TITLE: - Alpha E: no more
rejection?
REVISTA
/ JOURNAL: - J Exp Med. Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jem.org/
●●
Cita: J. Exp Med: <> 2002 Oct 7;196(7):873-5.
AUTORES
/ AUTHORS: - Kilshaw PJ; Higgins JM
INSTITUCIÓN
/ INSTITUTION: - The Babraham Institute, Cambridge, CB2
4AT, United Kingdom. peter.kilshaw@bbsrc.ac.uk N. Ref:: 25
----------------------------------------------------
[35]
TÍTULO / TITLE: - HLA DNA typing and
transplantation.
REVISTA
/ JOURNAL: - Immunity 2001 Apr;14(4):347-56.
AUTORES
/ AUTHORS: - Erlich HA; Opelz G; Hansen J
INSTITUCIÓN
/ INSTITUTION: - Roche Molecular Systems, Alameda, CA
94501, USA. henry.erlich@roche.com N. Ref:: 26
----------------------------------------------------
[36]
TÍTULO / TITLE: - Regulation of
translation initiation by FRAP/mTOR.
REVISTA
/ JOURNAL: - Genes Dev. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.genesdev.org/
●●
Cita: Genes & Development: <> 2001 Apr 1;15(7):807-26.
●●
Enlace al texto completo (gratuito o de pago) 1101/gad.887201
AUTORES
/ AUTHORS: - Gingras AC; Raught B; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry, McGill
University, Montreal, Quebec H3G 1Y6, Canada.
N. Ref:: 236
----------------------------------------------------
[37]
TÍTULO / TITLE: - Innate immune responses
to transplants: a significant variable with cadaver donors.
REVISTA
/ JOURNAL: - Immunity 2001 Apr;14(4):369-76.
AUTORES
/ AUTHORS: - Baldwin WM 3rd; Larsen CP;
Fairchild RL
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, Johns Hopkins
Medical Institutes, Baltimore, MD 21205, USA. wbaldwin@jhmi.edu N. Ref:: 70
----------------------------------------------------
[38]
TÍTULO / TITLE: - Rapamycin plays a new
role as differentiator of vascular smooth muscle phenotype. focus on “The
mTOR/p70 S6K1 pathway regulates vascular smooth muscle differentiation”.
REVISTA
/ JOURNAL: - Am J Physiol Cell Physiol. Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://ajpcell.physiology.org/contents-by-date.0.shtml
●●
Cita: Am J Physiol Cell Physiol: <> 2004 Mar;286(3):C480-1.
●●
Enlace al texto completo (gratuito o de pago) 1152/ajpcell.00526.2003
AUTORES
/ AUTHORS: - Lucchesi PA N. Ref:: 12
----------------------------------------------------
[39]
TÍTULO / TITLE: - CD3-specific antibody-induced
active tolerance: from bench to bedside.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Feb;3(2):123-32.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1000
AUTORES
/ AUTHORS: - Chatenoud L
INSTITUCIÓN
/ INSTITUTION: - Centre de l’Association Claude Bernard sur
les Maladies Autoimmunes and Hopital Necker Enfants Malades IRNEM, 161 Rue de
Sevres, 75015 Paris, France. chatenoud@necker.fr
RESUMEN
/ SUMMARY: - Although they were used initially as
non-specific immunosuppressants in transplantation, CD3-specific monoclonal
antibodies have elicited renewed interest owing to their capacity to induce
immune tolerance. In mouse models of autoimmune diabetes, CD3-specific
antibodies induce stable disease remission by restoring tolerance to pancreatic
beta-cells. This phenomenon was extended recently to the clinic—preservation of
beta-cell function in recently diagnosed patients with diabetes was achieved by
short-term administration of a CD3-specific antibody. CD3-specific antibodies
arrest ongoing disease by rapidly clearing pathogenic T cells from the target.
Subsequently, they promote long-term T-cell-mediated active tolerance. Recent
data indicate that transforming growth factor-beta-dependent CD4+CD25+
regulatory T cells might have a central role in this effect. N. Ref:: 117
----------------------------------------------------
[40]
TÍTULO / TITLE: - Antigen presentation to
naive CD4 T cells in the lymph node.
REVISTA
/ JOURNAL: - Nat Immunol 2003 Aug;4(8):733-9.
●●
Enlace al texto completo (gratuito o de pago) 1038/ni957
AUTORES
/ AUTHORS: - Itano AA; Jenkins MK
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology and the Center
for Immunology, University of Minnesota, MMC 334, 420 Delaware St. SE, Minneapolis,
Minnesota 55455, USA.
RESUMEN
/ SUMMARY: - Although the presentation of peptide-major
histocompatibility complex class II (pMHC class II) complexes to CD4 T cells
has been studied extensively in vitro, knowledge of this process in vivo is
limited. Unlike the in vitro situation, antigen presentation in vivo takes
place within a complex microenvironment in which the movements of antigens,
antigen-presenting cells (APCs) and T cells are governed by anatomic
constraints. Here we review developments in the areas of lymph node
architecture, APC subsets and T cell activation that have shed light on how
antigen presentation occurs in the lymph nodes. N. Ref:: 88
----------------------------------------------------
[41]
TÍTULO / TITLE: - Effects of MHC class I
on HIV/SIV disease in primates.
REVISTA
/ JOURNAL: - AIDS 2002;16 Suppl 4:S105-14.
AUTORES
/ AUTHORS: - Carrington M; Bontrop RE
INSTITUCIÓN
/ INSTITUTION: - Basic Research Program, SAIC Frederick,
National Cancer Institute, Frederick, MD 21702, USA. carringt@ncifcrf.gov
RESUMEN
/ SUMMARY: - Data indicate that resistance to HIV-1
disease involves an array of contrasting HLA genotypic effects that are subtle,
but significant, particularly when these genetic effects are considered as a
whole. Numerous reports attributing a role for HLA genotype in AIDS outcomes
have been reported, and a few of these have been affirmed in multiple studies.
Functional studies of immune cell recognition have provided clues to the
underlying mechanisms behind some of the strongest HLA associations, suggesting
the means by which relative resistance or susceptibility to the virus may
occur. SIV infection in non-human primates has served as an invaluable model
for understanding AIDS pathogenesis (in rhesus monkeys) and viral resistance
(in chimpanzee). The effect of rhesus MHC class I molecules on the evolution of
SIV has been convincingly described [19], and a recent study in humans has
suggested that selection pressure conferred by HLA molecules is responsible for
specific genetic variation in HIV-1 [114]. HIV-1 may eventually have
conspicuous evolutionary effects on HLA and other AIDS restriction genes, a
prolonged process that could have occurred in chimpanzee [92].To prevent such
an outcome, it will be necessary to approach the disease from many
perspectives, andapply comprehensively the knowledge gained to the successful
control of the virus. N.
Ref:: 114
----------------------------------------------------
[42]
TÍTULO / TITLE: - IL-6: a magic potion
for liver transplantation?
REVISTA
/ JOURNAL: - Gastroenterology 2003 Jul;125(1):256-9.
AUTORES
/ AUTHORS: - Selzner M; Graf R; Clavien PA N. Ref:: 42
----------------------------------------------------
[43]
TÍTULO / TITLE: - Neuroimmunophilins:
novel neuroprotective and neuroregenerative targets.
REVISTA
/ JOURNAL: - Ann Neurol 2001 Jul;50(1):6-16.
AUTORES
/ AUTHORS: - Guo X; Dillman JF 3rd; Dawson
VL; Dawson TM
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, The Johns Hopkins
University School of Medicine, Baltimore, MD 21287, USA.
RESUMEN
/ SUMMARY: - Cyclosporin A (CsA) and FK506 (tacrolimus)
are immunosuppresants that are widely used in organ transplantation. CsA is an
11-member cyclic peptide, whereas FK506 is a macrolide antibiotic. Recently,
these powerful and useful compounds have become of great interest to
neuroscientists for their unique neuroprotective and neuroregenerative effects.
These drugs and nonimmunosuppressive analogs protect neurons from the effects
of glutamate excitotoxicity, focal ischemia, and
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell
death. They also stimulate functional recovery of neurons in a variety of
neurologic injury paradigms. These drugs exert their effects via immunophilins,
the protein receptors for these agents. The immunophilin ligands show
particular promise as a novel class of neuroprotective and neuroregenerative
agents that have the potential to treat a variety of neurologic disorders. N. Ref:: 102
----------------------------------------------------
[44]
TÍTULO / TITLE: - The TCR triggering
puzzle.
REVISTA
/ JOURNAL: - Immunity 2001 Jun;14(6):665-8.
AUTORES
/ AUTHORS: - van der Merwe PA
INSTITUCIÓN
/ INSTITUTION: - Sir William Dunn School of Pathology,
University of Oxford, Oxford OX1 3RE, United Kingdom. anton.vandermerwe@path.ox.ac.uk N. Ref:: 28
----------------------------------------------------
[45]
TÍTULO / TITLE: - Gene therapy progress
and prospects: gene therapy in organ transplantation.
REVISTA
/ JOURNAL: - Gene Ther 2003 Apr;10(8):605-11.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.gt.3302020
AUTORES
/ AUTHORS: - Bagley J; Iacomini J
INSTITUCIÓN
/ INSTITUTION: - Transplantation Biology Research Center,
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129,
USA.
RESUMEN
/ SUMMARY: - One major complication facing organ
transplant recipients is the requirement for life-long systemic
immunosuppression to prevent rejection, which is associated with an increased
incidence of malignancy and susceptibility to opportunistic infections. Gene
therapy has the potential to eliminate problems associated with
immunosuppression by allowing the production of immunomodulatory proteins in
the donor grafts resulting in local rather than systemic immunosuppression.
Alternatively, gene therapy approaches could eliminate the requirement for
general immunosuppression by allowing the induction of donor-specific
tolerance. Gene therapy interventions may also be able to prevent graft damage
owing to nonimmune-mediated graft loss or injury and prevent chronic rejection.
This review will focus on recent progress in preventing transplant rejection by
gene therapy. N.
Ref:: 47
----------------------------------------------------
[46]
TÍTULO / TITLE: - Making sense of mass
destruction: quantitating MHC class I antigen presentation.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Dec;3(12):952-61.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1250
AUTORES
/ AUTHORS: - Yewdell JW; Reits E; Neefjes J
INSTITUCIÓN
/ INSTITUTION: - Laboratory of Viral Diseases, National
Institute of Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, Maryland 20892-0440, USA. N.
Ref:: 92
----------------------------------------------------
[47]
TÍTULO / TITLE: - The HFE Cys282Tyr
mutation as a necessary but not sufficient cause of clinical hereditary
hemochromatosis.
REVISTA
/ JOURNAL: - Blood. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.bloodjournal.org/
●●
Cita: Blood: <> 2003 May 1;101(9):3347-50.
●●
Enlace al texto completo (gratuito o de pago) 1182/blood-2002-06-1747
AUTORES
/ AUTHORS: - Beutler E
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular and Experimental
Medicine, Scripps Research Institute, La Jolla, CA 92037, USA. beutler@scripps.edu N. Ref:: 47
----------------------------------------------------
[48]
TÍTULO / TITLE: - Molecular aspects of
iron absorption and HFE expression.
REVISTA
/ JOURNAL: - Gastroenterology 2001 Dec;121(6):1489-96.
AUTORES
/ AUTHORS: - Parkkila S; Niemela O; Britton RS; Fleming
RE; Waheed A; Bacon BR; Sly WS
INSTITUCIÓN
/ INSTITUTION: - Department of Anatomy and Cell Biology,
University of Oulu, Oulu, Finland.
RESUMEN
/ SUMMARY: - Hereditary hemochromatosis, a disease of
iron overload, occurs in about 1 in 200-400 Caucasians. The gene mutated in
this disorder is termed HFE. The product of this gene, HFE protein, is
homologous to major histocompatibility complex class I proteins, but HFE does
not present peptides to T cells. Based on recent structural, biochemical, and
cell biological studies, transferrin receptor (TfR) is a ligand for HFE. This
association directly links HFE protein to the TfR-mediated regulation of iron
homeostasis. Although evidence is accumulating that binding of HFE to TfR is
critical for the effects of HFE, the final pieces in the HFE puzzle have not
been established. This review focuses on recent advances in HFE research and
presents a hypothetical model of HFE function.
N. Ref:: 69
----------------------------------------------------
[49]
TÍTULO / TITLE: - Mhc-guided processing:
binding of large antigen fragments.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Aug;3(8):621-9.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1149
AUTORES
/ AUTHORS: - Sercarz EE; Maverakis E
INSTITUCIÓN
/ INSTITUTION: - Torrey Pines Institute for Molecular
Studies, San Diego, California 92121, USA. esercarz@tpims.org
RESUMEN
/ SUMMARY: - Ever since the emergence of models for the
processing and presentation of antigenic determinants by MHC class II
molecules, the main view has been that proteins are unfolded, enzymatically
cleaved into peptide lengths of about 12-25 amino acids and then loaded onto
MHC class II molecules. There is, however, an alternative model stating that
partially intact unfolding antigens are first bound by MHC class II molecules
and then trimmed to fragments of a smaller size while remaining bound to the
MHC class II molecule. In this analysis, we make the case that a considerable
portion of the elutable peptide cargo belongs to this latter class. N. Ref:: 61
----------------------------------------------------
[50]
TÍTULO / TITLE: - Specialization in
tolerance: innate CD(4+)CD(25+) versus acquired TR1 and TH3 regulatory T cells.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1
Suppl):S12-5.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106471.23410.32
AUTORES
/ AUTHORS: - Cottrez F; Groux H
INSTITUCIÓN
/ INSTITUTION: - Institut national de la sante et de la
recherche medicale, Hopital de l’Archet, Nice, France.
RESUMEN
/ SUMMARY: - The regulation of immune responses to
self-antigens is a complex process that involves maintaining self-tolerance
while retaining the capacity to mount robust immune responses against invading
microorganisms. Over the past few years, many new insights into this process
have been gained, leading to the reemergence of the idea that regulatory T
cells (Treg) are key players in immune regulation. These insights have raised
fundamental questions concerning the definition of a Treg and what exactly constitutes
T-cell-mediated suppression, identification of the signals and the cellular
environment that promote the development and differentiation of these cells,
and which signals maintain the homeostasis of the immune system. Thus far, the
different models where Treg have been characterized cannot fully account for
CD(4+)CD(25+) T cells. In this article, the authors propose the coexistence of
two specialized types of CD(4+) Treg-innate and acquired-that differ in terms
of their development, specificity, mechanisms, and sites of action. N. Ref:: 33
----------------------------------------------------
[51]
TÍTULO / TITLE: - Interventions for
mucous membrane pemphigoid and epidermolysis bullosa acquisita.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev 2003;(1):CD004056.
AUTORES
/ AUTHORS: - Kirtschig G; Murrell D; Wojnarowska F;
Khumalo N
INSTITUCIÓN
/ INSTITUTION: - Dermatology, Vrije Universiteit Medisch
Centrum, PO Box 7057, Amsterdam, Netherlands, 1007 MB. G.Kirtschig@vumc.nl
RESUMEN
/ SUMMARY: - BACKGROUND: Mucous membrane pemphigoid and
epidermolysis bullosa acquisita are acquired autoimmune blistering diseases of
the skin. Although they are rare, both can result in scarring of mucous
membranes, which may lead to blindness and life threatening respiratory
complications. OBJECTIVES: To assess the effects of treatments for mucous
membrane pemphigoid and epidermolysis bullosa acquisita. SEARCH STRATEGY:
Randomised Controlled Trials (RCTs) of patients with MMP or EBA were identified
from MEDLINE and EMBASE from their inception to March 2000. The Cochrane Skin
Group Specialised Register and the Cochrane Controlled Trials Register (CCTR)
were last examined in February 2002. The bibliographies from identified studies
were searched. The author who has conducted clinical trials in the field was
contacted to identify unpublished trials. SELECTION CRITERIA: RCTs involving
participants of any ages, and with a diagnosis confirmed by immunofluorescence.
Where no RCTs were located, studies with other designs were considered. DATA
COLLECTION AND ANALYSIS: Data were extracted from all included studies using a
defined electronic data extraction protocol. Two reviewers evaluated the
studies in terms of the inclusion criteria. The data from identified RCTs was
extracted independently by three reviewers and subsequently checked for
discrepancies. Any disagreements were resolved by discussion with each other
and the fourth reviewer. Meta-analysis was not appropriate due to a lack of
data. MAIN RESULTS: We found two small RCTs of MMP, both conducted in patients
with severe eye involvement. The same author conducted both trials. In the
first trial cyclophosphamide was superior to prednisone after six months of
treatment; all 12 patients responded well to cyclophosphamide versus a good
response in only five of 12 patients treated with prednisone (relative risk
2.40, 95% confidence interval 1.23 to 4.69). In the second trial all 20
patients treated with cyclophosphamide responded well to it after three months
of treatment, but only 14 of 20 patients responded to the treatment with
dapsone (relative risk 1.4, 95% confidence interval 1.07 to 1.90). We were not
able to identify a RCT of therapeutic interventions in EBA. Thirty reports of uncontrolled
studies of treatment for MMP involving five or more patients and 11 reports of
treatment for EBA involving two or more patients were found, but were difficult
to interpret. REVIEWER’S CONCLUSIONS: There is limited evidence (from two small
trials) that severe ocular mucous membrane pemphigoid responds best to
treatment with cyclophosphamide combined with corticosteroids, and that mild to
moderate disease in most patients seems effectively suppressed by treatment
with dapsone. It is difficult to make any treatment recommendations for EBA in
the absence of reliable evidence sources.
N. Ref:: 59
----------------------------------------------------
[52]
TÍTULO / TITLE: - Genetically modified
immunocompetent cells in HIV infection.
REVISTA
/ JOURNAL: - Gene Ther 2001 Nov;8(21):1593-600.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.gt.3301569
AUTORES
/ AUTHORS: - Palu G; Li Pira G; Gennari F; Fenoglio D;
Parolin C; Manca F
INSTITUCIÓN
/ INSTITUTION: - Department of Histology, Microbiology and
Medical Biotechnologies, University of Padua, Italy.
RESUMEN
/ SUMMARY: - Even in the era of highly active
antiretroviral therapy (HAART), gene therapy (GT) can remain a promising
approach for suppressing HIV infection, especially if complemented with other
forms of pharmacological and immunological intervention. A large number of
vectors and targets have been studied. Here we discuss the potential of
genetically treated, antigen-specific immunocompetent cells for adoptive autologous
immunotherapy of HIV infection. Cellular therapies with gene-modified CD8 and
CD4 lymphocytes are aimed at reconstituting the antigen-specific repertoires
that may be deranged as a consequence of HIV infection. Even if complete
eradication of HIV from the reservoirs cannot be achieved, reconstitution of
cellular immunity specific for opportunistic pathogens and for HIV itself is a
desirable option to control progression of HIV infection and AIDS pathogenesis
better. N. Ref:: 103
----------------------------------------------------
[53]
TÍTULO / TITLE: - Gorillas with
spondyloarthropathies express an MHC class I molecule with only limited
sequence similarity to HLA-B27 that binds peptides with arginine at P2.
REVISTA
/ JOURNAL: - J Immunol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jimmunol.org/
●●
Cita: J. of Immunology: <> 2001 Mar 1;166(5):3334-44.
AUTORES
/ AUTHORS: - Urvater JA; Hickman H; Dzuris JL;
Prilliman K; Allen TM; Schwartz KJ; Lorentzen D; Shufflebotham C; Collins EJ;
Neiffer DL; Raphael B; Hildebrand W; Sette A; Watkins DI
INSTITUCIÓN
/ INSTITUTION: - Wisconsin Regional Primate Research
Center, University of Wisconsin, Madison, WI 53715, USA.
RESUMEN
/ SUMMARY: - The human MHC class I gene, HLA-B27, is a
strong risk factor for susceptibility to a group of disorders termed
spondyloarthropathies (SpAs). HLA-B27-transgenic rodents develop SpAs,
implicating HLA-B27 in the etiology of these disorders. Several nonhuman
primates, including gorillas, develop signs of SpAs indistinguishable from
clinical signs of humans with SpAs. To determine whether SpAs in gorillas have
a similar HLA-B27-related etiology, we analyzed the MHC class I molecules
expressed in four affected gorillas. Gogo-B01, isolated from three of the
animals, has only limited similarity to HLA-B27 at the end of the alpha1
domain. It differs by several residues in the B pocket, including differences
at positions 45 and 67. However, the molecular model of Gogo-B*0101 is consistent
with a requirement for positively charged residues at the second amino acid of
peptides bound by the MHC class I molecule. Indeed, the peptide binding motif
and sequence of individual ligands eluted from Gogo-B*0101 demonstrate that,
like HLA-B27, this gorilla MHC class I molecule binds peptides with arginine at
the second amino acid position of peptides bound by the MHC class I molecule.
Furthermore, live cell binding assays show that Gogo-B*0101 can bind HLA-B27
ligands. Therefore, although most gorillas that develop SpAs express an MHC
class I molecule with striking differences to HLA-B27, this molecule binds
peptides similar to those bound by HLA-B27.
N. Ref:: 61
----------------------------------------------------
[54]
TÍTULO / TITLE: - Clinical consequences
of iron overload in hemochromatosis homozygotes.
REVISTA
/ JOURNAL: - Blood. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.bloodjournal.org/
●●
Cita: Blood: <> 2003 May 1;101(9):3351-3; discussion 3354-8.
●●
Enlace al texto completo (gratuito o de pago) 1182/blood-2002-11-3453
AUTORES
/ AUTHORS: - Ajioka RS; Kushner JP
INSTITUCIÓN
/ INSTITUTION: - Division of Hematology, Department of
Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT
84132, USA. N. Ref:: 58
----------------------------------------------------
[55]
TÍTULO / TITLE: - Insulin/IGF and target
of rapamycin signaling: a TOR de force in growth control.
REVISTA
/ JOURNAL: - Trends Cell Biol 2003 Feb;13(2):79-85.
AUTORES
/ AUTHORS: - Oldham S; Hafen E
INSTITUCIÓN
/ INSTITUTION: - The Burnham Institute, La Jolla, CA 92037,
USA.
RESUMEN
/ SUMMARY: - ‘They come in all sizes.’ Apart from its
origin and use in the clothing industry, this saying reflects the fact that the
size of organisms spans an enormous range. Whether destined to be large or
small, species grow in an organized fashion to reach their final specified
size. For growth to proceed, food must be metabolized to liberate energy in the
form of adenosine triphosphate (ATP) and protein building blocks in the form of
amino acids. One major orchestrator of this complex growth process in diverse
metazoan species is the insulin/insulin-like growth factor (IGF) system. This
review summarizes current studies primarily from Drosophila regarding the
function of the insulin/IGF system in the control of growth. N. Ref:: 75
----------------------------------------------------
[56]
TÍTULO / TITLE: - Review article: medical
treatment of moderate to severe Crohn’s disease.
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2003 Jun;17 Suppl
2:23-30.
AUTORES
/ AUTHORS: - Scribano M; Prantera C
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, Azienda
Ospedaliera S.Camillo-Forlanini, Rome, Italy.
RESUMEN
/ SUMMARY: - The treatment for patients with Crohn’s
disease of moderate to severe activity includes traditional drugs, such as
corticosteroids, the primary therapy for these forms of disease, able to induce
the remission of symptoms in a high percentage of patients. Because of the side-effects
produced by systemic steroids, a new glucocorticoid derivative, budesonide,
which acts locally in the mucosa, has recently been introduced with positive
results. On the assumption that intestinal bacteria play a role in the causing
Crohn’s disease symptoms, antibiotics are often used in the treatment of active
phases, as an alternative to or in association with steroids. The most widely
employed antibiotics are metronidazole and ciprofloxacin. Immunosuppressors,
such as azathioprine and 6-mercaptopurine, are useful for the treatment of
chronic active disease and for maintaining remission, but they have only a
marginal role in the therapy of an acute flare-up of Crohn’s disease.
Methotrexate acts more rapidly and its use in patients with active disease
resistant to standard therapy is of interest. The discovery of biological
agents represents a new era in the management of patients. To date, infliximab
is the more extensively studied biological therapy in the treatment of Crohn’s
disease and clinical studies have demonstrated its efficacy in inducing
remission of refractory disease. N.
Ref:: 59
----------------------------------------------------
[57]
TÍTULO / TITLE: - Sarcoidosis.
REVISTA
/ JOURNAL: - Lancet 2003 Mar 29;361(9363):1111-8.
AUTORES
/ AUTHORS: - Baughman RP; Lower EE; du Bois RM
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine,
University of Cincinnati, Cincinnati Medical Center, Cincinnati, OH 45267-0565,
USA. bob.baughman@uc.edu
RESUMEN
/ SUMMARY: - There have been several new insights into
the cause and treatment of sarcoidosis. Studies of genetic variation have shown
that specific genetic polymorphisms are associated with increased risk of
disease or affect disease presentation. These polymorphisms include variation
of MHC and cytokines such as tumour necrosis factor (TNF). Not all
investigators have come to the same conclusion, suggesting an interaction of
various factors, including the patient’s ethnic origin. Treatment of sarcoidosis
varies considerably. Patients with symptomatic disease for more than 2-5 years
have been of particular interest. Corticosteroids remain the standard of care
in such cases, but immunosuppressive drugs have proved steroid-sparing in many
patients. New agents, including pentoxifylline, thalidomide, and infliximab
have proved useful in selected cases. The effectiveness of these agents seems
to lie in their ability to block TNF, especially in the treatment of chronic
disease. N. Ref:: 117
----------------------------------------------------
[58]
TÍTULO / TITLE: - The tolerant recipient:
looking great in someone else’s genes.
REVISTA
/ JOURNAL: - J Clin Invest. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.jci.org/
●●
Cita: J Clinical Investigation: <> 2001 Jan;107(1):33-4.
AUTORES
/ AUTHORS: - Rosengard BR; Turka LA
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Pennsylvania, Philadelphia, Pennsylvania, USA.
N. Ref:: 18
----------------------------------------------------
[59]
TÍTULO / TITLE: - Human CD(4+)CD(25+)
regulatory T cells and infectious tolerance.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1
Suppl):S23-5.
AUTORES
/ AUTHORS: - Stassen M; Schmitt E; Jonuleit H
INSTITUCIÓN
/ INSTITUTION: - Institute of Immunology, Johannes
Gutenberg-University, Mainz, Germany. michael.stassen@gmx.de.
RESUMEN
/ SUMMARY: - Control of autoaggressive T cells by
regulatory T cells (Treg) is essential to ensuring peripheral tolerance.
Several subsets of CD(4+) T cells with suppressive properties have been
described, including induced T helper (Th) type 3 and T regulatory (Tr) type 1
cells and naturally occurring CD(4+)CD(25+) Treg. CD(4+)CD(25+) Treg suppress
the response of conventional T cells in a cell contact-dependent manner,
whereas Th3 and Tr1 cells produce immunosuppressive cytokines. Two subsets of
human CD(4+)CD(25+) Treg, characterized by expression of the integrins
alpha4beta7 or alpha4beta1, are able to convey suppressive capacity to
conventional CD(4+) T cells, thereby generating Th suppressor cells (Th(sup)).
One outstanding feature is the generation of Th(sup) with distinct properties.
alpha4beta7 Treg induce Tr1-like interleukin (IL)-10-producing Th(sup), whereas
alpha4beta1 Treg induce Th3-like Th(sup), which produce transforming growth
factor (TGF)-beta. Thus, our findings reconcile contradictory results clearly
demonstrating that suppression is contact dependent in vitro but mediated by
soluble factors (IL-10 and TGF-beta) in vivo.
N. Ref:: 21
----------------------------------------------------
[60]
TÍTULO / TITLE: - Glucocorticoids and
invasive fungal infections.
REVISTA
/ JOURNAL: - Lancet 2003 Nov 29;362(9398):1828-38.
AUTORES
/ AUTHORS: - Lionakis MS; Kontoyiannis DP
INSTITUCIÓN
/ INSTITUTION: - Department of Infectious Diseases,
Infection Control and Employee Health, University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA.
RESUMEN
/ SUMMARY: - Since the 1990s, opportunistic fungal
infections have emerged as a substantial cause of morbidity and mortality in
profoundly immunocompromised patients. Hypercortisolaemic patients, both those
with endogenous Cushing’s syndrome and, much more frequently, those receiving
exogenous glucocorticoid therapy, are especially at risk of such infections.
This vulnerability is attributed to the complex dysregulation of immunity
caused by glucocorticoids. We critically review the spectrum and presentation
of invasive fungal infections that arise in the setting of hypercortisolism,
and the ways in which glucocorticoids contribute to their pathogenesis. A
better knowledge of the interplay between glucocorticoid-induced
immunosuppression and invasive fungal infections should assist in earlier
recognition and treatment of such infections. Efforts to decrease the intensity
of glucocorticoid therapy should help to improve outcomes of opportunistic
fungal infections. N.
Ref:: 135
----------------------------------------------------
[61]
TÍTULO / TITLE: - Cell survival and
clinical outcome following intrastriatal transplantation in Parkinson disease.
REVISTA
/ JOURNAL: - J Neuropathol Exp Neurol 2001
Aug;60(8):741-52.
AUTORES
/ AUTHORS: - Hagell P; Brundin P
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Neuroscience,
University Hospital, Lund University, Sweden.
RESUMEN
/ SUMMARY: - Intrastriatal transplantation of embryonic
dopaminergic neurons is currently explored as a restorative cell therapy for
Parkinson disease (PD). Clinical results have varied, probably due to
differences in transplantation methodology and patient selection. In this
review, we assess clinical trials and autopsy findings in grafted PD patients
and suggest that a minimum number of surviving dopaminergic neurons is required
for a favorable outcome. Restoration of [18F]-fluorodopa uptake in the putamen
to about 50% of the normal mean seems necessary for moderate to marked clinical
benefit to occur. Some studies indicate that this may require mesencephalic
tissue from 3-5 human embryos implanted into each hemisphere. The volume,
density and pattern of fiber outgrowth and reinnervation, as well as functional
integration and dopamine release. are postulated as additional important
factors for an optimal clinical outcome. For neural transplantation to become a
feasible therapeutic alternative in PD, graft survival must be increased and
the need for multiple donors of human embryonic tissue substantially decreased
or alternate sources of donor tissue developed. Donor cells derived from
alternative sources should demonstrate features comparable to those associated
with successful implantation of human embryonic tissue before clinical trials
are considered. N.
Ref:: 62
----------------------------------------------------
[62]
TÍTULO / TITLE: - Anatomical basis of
tolerance and immunity to intestinal antigens.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Apr;3(4):331-41.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1057
AUTORES
/ AUTHORS: - Mowat AM
INSTITUCIÓN
/ INSTITUTION: - Department of Immunology and Bacteriology,
Western Infirmary, Glasgow G11 6NT, UK. a.m.mowat@clinmed.gla.ac.uk
RESUMEN
/ SUMMARY: - The intestinal immune system has to
discriminate between harmful and beneficial antigens. Although strong
protective immunity is essential to prevent invasion by pathogens, equivalent
responses against dietary proteins or commensal bacteria can lead to chronic
disease. These responses are normally prevented by a complex interplay of
regulatory mechanisms. This article reviews the unique aspects of the local
microenvironment of the intestinal immune system and discuss how these promote
the development of regulatory responses that ensure the maintenance of
homeostasis in the gut. N.
Ref:: 99
----------------------------------------------------
[63]
TÍTULO / TITLE: - Scaffolding of antigen
receptors for immunogenic versus tolerogenic signaling.
REVISTA
/ JOURNAL: - Nat Immunol 2003 Nov;4(11):1057-64.
●●
Enlace al texto completo (gratuito o de pago) 1038/ni1001
AUTORES
/ AUTHORS: - Jun JE; Goodnow CC
INSTITUCIÓN
/ INSTITUTION: - Australian Cancer Research Foundation
Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical
Research, Australian National University, Canberra ACT 2601, Australia.
RESUMEN
/ SUMMARY: - Lymphocyte antigen receptors are
responsible for inducing the opposite responses of immunity or tolerance. How
the correct polarity of antigen receptor signaling is encoded has been an
enduring enigma. Here we summarize recent advances defining key scaffolding
molecules, CARMA1 (also known as CARD11) and the Cbl family of ubiquitin
ligases, required for either immunogenic or tolerogenic signaling by antigen
receptors. These scaffolding proteins may determine the polarity of response to
antigen by promoting assembly around antigen receptors of competing
multiprotein signal complexes: immunosomes versus tolerosomes. Each of the
factors that influence immunogenicity or tolerogenicity—stage of lymphocyte
differentiation, concurrent engagement of inhibitory or costimulatory
receptors, extent of receptor crosslinking, and prior antigen experience—may be
integrated in lymphocytes through their capacity to influence the probability
of assembling immunosomes versus tolerosomes.
N. Ref:: 111
----------------------------------------------------
[64]
TÍTULO / TITLE: - Effect of dexamethasone
on beta2-adrenergic desensitization in airway smooth muscle: role of the ARG19
polymorphism.
REVISTA
/ JOURNAL: - Chest. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.chestjournal.org/
●●
Cita: Chest: <> 2003 Mar;123(3 Suppl):368S-9S.
AUTORES
/ AUTHORS: - Moore PE; Calder MM; Silverman ES;
Panettieri RA Jr; Shore SA
INSTITUCIÓN
/ INSTITUTION: - Departments of Pediatrics and Pharmacology
(Dr. Moore and Mr. Calder), Vanderbilt University School of Medicine,
Nashville, TN 37232-2586, USA. N.
Ref:: 1
----------------------------------------------------
[65]
TÍTULO / TITLE: - Antiadhesion molecule
therapy in inflammatory bowel disease.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2002 Jul;8(4):291-300.
AUTORES
/ AUTHORS: - van Assche G; Rutgeerts P
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, University
Hospital Leuven, Belgium. gert.vanassche@uz.kuleuven.ac.be
RESUMEN
/ SUMMARY: - Adhesion molecules regulate the influx of
leukocytes in normal and inflamed gut. Some of these molecules such as MadCAM-1
are specific for the gastrointestinal endothelium, but in inflammatory bowel
diseases most of the adhesion factors are up-regulated. Adhesion molecules also
are involved in local lymphocyte stimulation and antigen presentation within
the intestinal mucosa. Recently, therapeutic compounds directed against
trafficking of lymphocytes toward the gut mucosa have been designed, and are
being developed as a novel class of drugs in the treatment of Crohn’s disease
(CD) and ulcerative colitis. This review deals with the immunological aspects
of leukocyte trafficking focused on gut homing of T cells. Secondly, the
changes in adhesion molecules and T-cell trafficking during intestinal
inflammation are discussed. Finally, we review the clinical data that have been
gathered in trials of biological therapies directed against adhesion molecules.
Both antiintercellular adhesion molecule-1 (ICAM-1) and anti-alpha4 integrin
strategies are being developed. Trials with the anti-ICAM-1 antisense
oligonucleotide, ISIS-2302, in steroid-refractory CD have provided conflicting
efficacy data. The anti-alpha4 integrin antibodies natalizumab (Antegren) and
LDP-02 are in phase III and phase II trials, respectively. In the near future,
these novel biological agents may prove valuable therapeutic tools in the
management of refractory IBD. N.
Ref:: 56
----------------------------------------------------
[66]
TÍTULO / TITLE: - New agents in acute
myeloid leukemia and other myeloid disorders.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 1;100(3):441-54.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.11935
AUTORES
/ AUTHORS: - Ravandi F; Kantarjian H; Giles F; Cortes J
INSTITUCIÓN
/ INSTITUTION: - Department of Leukemia, The University of Texas
M D Anderson Cancer Center, Houston, Texas 77030, USA. fravandi@mdanderson.org
RESUMEN
/ SUMMARY: - Over the past several decades,
improvements in chemotherapeutic agents and supportive care have resulted in
significant progress in treating patients with acute myeloid leukemia (AML).
More recently, advances in understanding the biology of AML have resulted in
the identification of new therapeutic targets. The success of
all-trans-retinoic acid in acute promyelocytic leukemia and of imatinib
mesylate in chronic myeloid leukemia have demonstrated that targeted therapy
may be more effective and less toxic when well defined targets are available.
At the same time, understanding mechanisms of drug resistance and means to
overcome them has led to modification of some of the existing cytotoxic agents.
Rational design and conduct of clinical trials is necessary to ensure that the
full potential of these new agents is realized. N. Ref:: 140
----------------------------------------------------
[67]
TÍTULO / TITLE: - Effects of glatiramer
acetate on relapse rate and accumulated disability in multiple sclerosis:
meta-analysis of three double-blind, randomized, placebo-controlled clinical
trials.
REVISTA
/ JOURNAL: - Mult Scler 2003 Aug;9(4):349-55.
AUTORES
/ AUTHORS: - Boneschi FM; Rovaris M; Johnson KP; Miller
A; Wolinsky JS; Ladkani D; Shifroni G; Comi G; Filippi M
INSTITUCIÓN
/ INSTITUTION: - Department of Neuroscience, Scientific
Institute, University H San Raffaele, Milan, Italy.
RESUMEN
/ SUMMARY: - Three randomized, double-blind,
placebo-controlled trials have shown that glatiramer acetate (GA) is effective
in reducing relapse rate in patients with relapsing-remitting (RR) multiple
sclerosis (MS). Using raw data pooled from 540 patients, we performed a
meta-analysis of these three trials, to investigate whether the extent of GA
efficacy varies according to disease-related variables at study entry. Three
regression models were developed to assess the efficacy of GA on the annualized
relapse rate (primary outcome measure), on the total number of on-trial
relapses and on the time to first relapse. We also explored the efficacy of GA
on accumulated disability and the potential role of baseline clinical variables
as predictors of relapse-rate variables and treatment efficacy. The mean
adjusted annualized relapse rate on study was 1.14 in the pooled
placebo-treated subjects and 0.82 in the pooled GA group (P = 0.004),
indicating an average reduction in annualized relapse rate of 28%. About a one
third reduction of the total number of on-trial relapses was also observed in
patients receiving GA (P < 0.0001), who had a median time to the first
relapse of 322 days versus a median time to the first relapse of 219 days seen
in those receiving placebo (P = 0.01). A beneficial effect on accumulated
disability was also found (risk ratio of 0.6; 95%; CI = 0.4-0.9; P = 0.02). The
drug assignment (P = 0.004), baseline EDSS score (P = 0.02) and number of
relapses during the two years prior to study entry (P = 0.002) were significant
predictors of on-trial annualized relapse rate. No other demographic or
clinical variable at baseline significantly influenced the treatment effect.
This meta-analysis reaffirms the effectiveness of GA in reducing relapse rate
and disability accumulation in RRMS, at a magnitude comparable to that of other
available immunomodulating treatments. It also suggests that GA efficacy is not
significantly influenced by the patients’ clinical characteristics at the time
of treatment initiation.
----------------------------------------------------
[68]
TÍTULO / TITLE: - Virus evasion of MHC
class I molecule presentation.
REVISTA
/ JOURNAL: - J Immunol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jimmunol.org/
●●
Cita: J. of Immunology: <> 2003 Nov 1;171(9):4473-8.
AUTORES
/ AUTHORS: - Petersen JL; Morris CR; Solheim JC
INSTITUCIÓN
/ INSTITUTION: - Eppley Institute for Research in Cancer
and Allied Diseases, Omaha, NE 68198-6805, USA. N. Ref:: 97
----------------------------------------------------
[69]
TÍTULO / TITLE: - HLA complex genes in
type 1 diabetes and other autoimmune diseases. Which genes are involved?
REVISTA
/ JOURNAL: - Trends Genet 2001 Feb;17(2):93-100.
AUTORES
/ AUTHORS: - Undlien DE; Lie BA; Thorsby E
INSTITUCIÓN
/ INSTITUTION: - Institute of Immunology, The National
Hospital and University of Oslo, N-0027, Oslo, Norway. d.e.undlien@rh.uio.no
RESUMEN
/ SUMMARY: - The predisposition to develop a majority
of autoimmune diseases is associated with specific genes within the human
leukocyte antigen (HLA) complex. However, it is frequently difficult to
determine which of the many genes of the HLA complex are directly involved in
the disease process. The main reasons for these difficulties are the complexity
of associations where several HLA complex genes might be involved, and the
strong linkage disequilibrium that exists between the genes in this complex.
The latter phenomenon leads to secondary disease associations, or what has been
called ‘hitchhiking polymorphisms’. Here, we give an overview of the complexity
of HLA associations in autoimmune disease, focusing on type 1 diabetes and
trying to answer the question: how many and which HLA genes are directly
involved? N. Ref:: 40
----------------------------------------------------
[70]
TÍTULO / TITLE: - Quality control of MHC
class I maturation.
REVISTA
/ JOURNAL: - Faseb J. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.fasebj.org/
●●
Cita: FASEB Journal: <> 2004 Jan;18(1):31-8.
●●
Enlace al texto completo (gratuito o de pago) 1096/fj.03-0846rev
AUTORES
/ AUTHORS: - Paulsson KM; Wang P
INSTITUCIÓN
/ INSTITUTION: - Rayne Institute, Centre for Molecular
Medicine, Department of Medicine, University College of London, 5 University
St., London WC1E 6JJ, UK. k.paulsson@ucl.ac.uk
RESUMEN
/ SUMMARY: - Assembly of MHC class I molecules in the
ER is regulated by the so-called loading complex (LC). This multiprotein
complex is of definite importance for class I maturation, but its exact
organization and order of assembly are not known. Evidence implies that the
quality of peptides loaded onto class I molecules is controlled at multiple
stages during MHC class I assembly. We recently found that tapasin, an
important component of the LC, interacts with COPI-coated vesicles. Biochemical
studies suggested that the tapa-sin-COPI interaction regulates the retrograde
transport of immature MHC class I molecules from the Golgi network back to the
ER. Also other findings now propose that in addition to the peptide-loading
control, the quality control of MHC class I antigen presentation includes the
restriction of export of suboptimally loaded MHC class I molecules to the cell
surface. In this review, we use recent studies of tapasin to examine the
efficiency of TAP, the LC constitution, ER quality control of class I assembly,
and peptide optimization. The concepts of MHC class I recycling and ER
retention are also discussed. N.
Ref:: 73
----------------------------------------------------
[71]
TÍTULO / TITLE: - The transplantation of
hematopoietic stem cells after non-myeloablative conditioning: a cellular
therapeutic approach to hematologic and genetic diseases.
REVISTA
/ JOURNAL: - Immunol Res 2003;28(1):13-24.
AUTORES
/ AUTHORS: - Maris M; Storb R
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
and University of Washington, Seattle, WA, USA. mmaris@fhcrc.org
RESUMEN
/ SUMMARY: - Originally, allogeneic hematopoietic stem
cell transplantation (HSCT) was viewed as a form of rescue from the marrow
lethal effects of high doses of chemo-radiotherapy used to both eradicate
malignancy and to provide sufficient immunosuppression to ensure allogeneic
engraftment. Clear evidence of a therapeutic graft-versus-tumor (GVT) effect
mediated by allogeneic effector cells (T cells) has prompted the exploration of
HSCT regimens that rely solely upon host immunosuppression (non-myeloablative)
to facilitate allogeneic donor engraftment. The engrafted donor effector cells
are then used to accomplish the task of eradicating host malignant cells. The
non-myeloblative regimen developed in Seattle uses 2 Gy total body irradiation
(TBI) before transplant followed by postgrafting cyclosporine (CSP) and
mycophenolate mofetil (MMF). This regimen resulted in initial mixed donor-host
chimerism in all patients with hematologic malignancies and genetic disorders
who received HLA-matched sibling allografts. The 17% incidence of graft
rejection was reduced to 3% with the addition of fludarabine, 30 mg/m2/day on d
-4, -3, and -2. The non-myeloablative combination of fludarabine/TBI has also
been successful at achieving high engraftment rates in recipients of 10 of 10
HLA antigen matched unrelated donor HSCTs in patients with hematologic
malignancies. By reducing acute toxicities relative to conventional HSCT, most
patients have received their pre- and post-HSCT therapy almost exclusively as
outpatients. Acute and chronic GVHD occur after non-myeloablative HSCT, but the
incidence and severity appear less compared to conventional HSCT. As in
conventional transplants, immune dysregulation from GVHD and its treatment and
delayed reconstitution of immune function continue to present risks to patients
who have otherwise undergone successful non-myeloablative HSCT. Cellular
therapeutic effects have been observed after non-myeloablative HSCT such as
correction of inherited genetic disorders, and eradication of hematologic
malignant diseases and renal cell carcinoma via GVT responses. N. Ref:: 52
----------------------------------------------------
[72]
TÍTULO / TITLE: - Sublingual
immunotherapy for allergic rhinitis.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2003;(2):CD002893.
AUTORES
/ AUTHORS: - Wilson DR; Torres LI; Durham SR
INSTITUCIÓN
/ INSTITUTION: - Upper Respiratory Medicine, Imperial
College School of Medicine at the National Heart & Lung Institute, Dovehouse
Street, London, UK, SW3 6LR. duncw 99@yahoo.co.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Allergic rhinitis is a common
condition which, at its most severe, can significantly impair quality of life
despite optimal treatment with antihistamines and topical nasal
corticosteroids. Allergen injection immunotherapy significantly reduces
symptoms and medication requirements in allergic rhinitis but its use is
limited by the possibility of severe systemic reactions. There has therefore
been considerable interest in alternative routes for delivery of allergen
immunotherapy, particularly the sublingual route. OBJECTIVES: To evaluate the
efficacy of sublingual immunotherapy (SLIT), compared with placebo, for
reductions in symptoms and medication requirements. SEARCH STRATEGY: The
Cochrane Controlled Trials Register, MEDLINE (1966-2002), EMBASE (1974-2002)
and Scisearch were searched, up to September 2002, using the terms (Rhin* OR
hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). SELECTION
CRITERIA: All studies identified by the searches were assessed by the reviewers
to identify randomised controlled trials involving participants with symptoms
of allergic rhinitis and proven allergen sensitivity, treated with SLIT or
corresponding placebo. DATA COLLECTION AND ANALYSIS: Data from identified
studies were abstracted onto a standard extraction sheet and subsequently
entered into RevMan 4.1. Analysis was performed by the method of Standardised
Mean Differences (SMD) using a random effects model. P values <0.05 were
considered statistically significant. Subgroup analyses were performed
according to the type of allergen administered, the age of participants and the
duration of treatment. MAIN RESULTS: Twenty two trials involving 979 patients
were included. There were 6 trials of SLIT for House Dust Mite allergy, 5 for
Grass Pollen, 5 for Parietaria, 2 for Olive and one each for, Ragweed, Cat,
Tree and Cupressus. Four studies enrolled exclusively children. Seventeen
studies administered the allergen by sublingual drops subsequently swallowed, 3
by drops subsequently spat out and 2 by sublingual tablets. Eight studies
involved treatment for less than 6 months, 10 studies for 6-12 months and 4
studies for greater than 12 months. All included studies were double-blind
placebo-controlled trials of parallel group design. Concealment of treatment
allocation was considered adequate in all studies and the use of identical
placebo preparations was almost universal. There was significant heterogeneity,
most likely due to widely differing scoring systems between studies, for most
comparisons. Overall there was a significant reduction in both symptoms (SMD
-0.34, 95% confidence interval -0.69 to -0.15; p=0.002) and medication
requirements (SMD -0.43 [-0.63, -0.23]; p=0.00003) following immunotherapy.
Subgroup analyses failed to identify a disproportionate benefit of treatment
according to the allergen administered. There was no significant reduction in
symptoms and medication scores in those studies involving only children but
total numbers of participants were small, casting doubt on the validity of the
conclusion. Increasing duration of treatment does not clearly increase
efficacy. The total dose of allergen administered may be important but
insufficient data were available to analyse this factor. REVIEWER’S
CONCLUSIONS: SLIT is a safe treatment which significantly reduces symptoms and
medication requirements in allergic rhinitis. The size of this benefit compared
to that of other available therapies, particularly injection immunotherapy, is
not clear, having been assessed directly in very few studies. Further research
is required concentrating on optimising allergen dosage and patient
selection. N. Ref:: 41
----------------------------------------------------
[73]
TÍTULO / TITLE: - DR, DQ, and you: MHC
alleles and autoimmunity.
REVISTA
/ JOURNAL: - J Clin Invest. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.jci.org/
●●
Cita: J Clinical Investigation: <> 2001 Apr;107(7):795-6.
AUTORES
/ AUTHORS: - Sonderstrup G; McDevitt HO
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology and Immunology,
Stanford University School of Medicine, Stanford, California 94305-5124, USA. gretes@stanford.edu N. Ref:: 12
----------------------------------------------------
[74]
TÍTULO / TITLE: - Potential roles of
protein oxidation and the immunoproteasome in MHC class I antigen presentation:
the ‘PrOxI’ hypothesis.
REVISTA
/ JOURNAL: - Arch Biochem Biophys 2004 Mar
1;423(1):88-96.
●●
Enlace al texto completo (gratuito o de pago) 1016/j.abb.2003.12.001
AUTORES
/ AUTHORS: - Teoh CY; Davies KJ
INSTITUCIÓN
/ INSTITUTION: - Ethel Percy Andrus Gerontology Center and
Division of Molecular and Computational Biology, The University of Southern
California, Los Angeles, CA 90089-0191, USA.
RESUMEN
/ SUMMARY: - The major histocompatibility complex (MHC)
class I (MHC-I) antigen presentation system is responsible for the cell-surface
presentation of self-proteins and intracellular viral proteins. This pathway is
important in screening between self, and non-self or infected cells. In this
pathway, proteins are partially degraded to peptides in the cytosol and
targeted to the cell surface bound to an MHC-I receptor protein. At the cell
surface, T cells bypass cells displaying self-peptides but destroy others
displaying foreign antigens. Cells contain several isoforms of the proteasome,
but it is thought that the immunoproteasome is the major form involved in
generating peptides for the MHC-I pathway. How all intracellular proteins are
targeted for MHC-I processing is unclear. Oxidative stress is experienced by
all cells, and all proteins are exposed to oxidation. We propose that oxidative
modification makes proteins susceptible to degradation by the immunoproteasome.
This could be called the protein oxidation and immunoproteasome or ‘PrOxI’
hypothesis of MHC-I antigen processing. Protein oxidation may, thus, be a
universal mechanism for peptide generation and presentation in the MHC-I
pathway. N. Ref:: 123
----------------------------------------------------
[75]
TÍTULO / TITLE: - Current directions in
hemochromatosis research: towards an understanding of the role of iron overload
and the HFE gene mutations in the development of clinical disease.
REVISTA
/ JOURNAL: - Nutr Rev 2003 Jan;61(1):38-42.
AUTORES
/ AUTHORS: - Neff LM
INSTITUCIÓN
/ INSTITUTION: - Jean Mayer USDA Human Nutrition Research
Center on Aging, Tufts University, New England Medical Center, Boston, MA, USA.
RESUMEN
/ SUMMARY: - Since the discovery of a candidate gene
(HFE) thought to be involved in the development of hereditary hemochromatosis,
there has been much interest in the potential use of genetic testing as a screening
tool for the disease in the general population. However, a recent study
suggests that less than 1% of subjects who are homozygous for the gene
mutations will go on to develop the full-blown disease of hereditary
hemochromatosis, historically termed “bronzed diabetes.” The study also
suggests that homozygotes have no higher risk of mortality or of any clinically
significant morbidity than normal control subjects. This conclusion contradicts
earlier findings that linked iron overload and HFE mutations to a number of
devastating diseases, including cardiovascular disease, diabetes, and
cancer. N. Ref:: 15
----------------------------------------------------
[76]
TÍTULO / TITLE: - Endothelial expression
of MHC class II molecules in autoimmune disease.
REVISTA
/ JOURNAL: - Curr Pharm Des 2004;10(2):129-43.
AUTORES
/ AUTHORS: - Turesson C
INSTITUCIÓN
/ INSTITUTION: - Department of Rheumatology, Malmo
University Hospital, Malmo, Sweden. turesson.carl@mayo.edu
RESUMEN
/ SUMMARY: - Major histocompatibility complex (MHC)
class II molecules are up-regulated on endothelial cells in human allografts,
and are thought to be involved in graft rejection. The MHC class II subtypes
HLA-DR, DQ and DP regulate T cell dependent immune responses, and aberrant
expression could be important in autoimmunity. Increased endothelial MHC class
II expression has been demonstrated in several autoimmune diseases, including
myocarditis with dilated cardiomyopathy, rheumatoid arthritis (RA) and systemic
lupus erythematosus (SLE). Recent data suggest that there is an association
between endothelial expression of MHC class II molecules and diffuse
endothelial dysfunction, which may be part of the explanation of the increased
risk of cardiovascular disease in patients with RA, SLE and other chronic
inflammatory conditions. MHC class II transcription is in part genetically
determined. Cytokine induced up-regulation of MHC class II molecules can be
inhibited in vitro by antioxidants and different drugs, such as cyclosporin and
statins. Research on the development of new treatments for systemic autoimmune
diseases and cardiovascular disease should include evaluation of effects on
endothelial activation, including MHC class II expression. This review also
discusses the genetic basis of MHC class II expression and its implications for
understanding MHC genotype associations with autoimmune diseases. Recent
studies of interactions between endothelial cells and T cells are reviewed.
Such interactions could be of major importance in the pathogenesis of
autoimmune and vascular diseases. N.
Ref:: 217
----------------------------------------------------
[77]
TÍTULO / TITLE: - Valacyclovir provides
optimum acyclovir exposure for prevention of cytomegalovirus and related
outcomes after organ transplantation.
REVISTA
/ JOURNAL: - J Infect Dis. Acceso gratuito al texto
completo a partir de los 2 años de la publicación; - http://www.journals.uchicago.edu/
●●
Cita: J. of Infectious Diseases: <> 2002 Oct 15;186 Suppl 1:S110-5.
AUTORES
/ AUTHORS: - Fiddian P; Sabin CA; Griffiths PD
INSTITUCIÓN
/ INSTITUTION: - Royal Free and University College Medical
School (Royal Free Campus), London NW3 2PF, United Kingdom. paul.fiddian@which.net
RESUMEN
/ SUMMARY: - A meta-analysis of 12 randomized trials
(1574 patients) examined herpesvirus and related outcomes following organ
transplantation over a range of acyclovir exposures (including valacyclovir).
Overall, cytomegalovirus (CMV) infection (odds ratio [OR], 0.44; 95% confidence
interval [CI], 0.34-0.57; P<.001), CMV disease (OR, 0.41; 95% CI, 0.31-0.54;
P<.001), death (OR, 0.60; 95% CI, 0.40-0.90; P=.01), opportunistic infection
(OR, 0.70; 95% CI, 0.53-0.91; P=.009), acute graft rejection (OR, 0.67; 95% CI,
0.52-0.86; P<.001), herpes simplex virus disease (OR, 0.17; 95% CI,
0.12-0.24; P<.001), and varicella-zoster virus disease (OR, 0.06; 95% CI,
0.01-0.25; P<.001) were significantly reduced. Increased acyclovir exposure
influenced more end points: Maximum efficacy resulted from valacyclovir (8
g/day). Increasing acyclovir exposure to that achieved with valacyclovir
extends benefits of prophylaxis to include impact on graft rejection and
opportunistic infections.
----------------------------------------------------
[78]
TÍTULO / TITLE: - Dendritic cells
transduced with viral interleukin 10 or Fas ligand: no evidence for induction
of allotolerance in vivo.
REVISTA
/ JOURNAL: - Transplantation 2002 Jan 15;73(1
Suppl):S27-30.
AUTORES
/ AUTHORS: - Buonocore S; Van Meirvenne S; Demoor FX;
Paulart F; Thielemans K; Goldman M; Flamand V
INSTITUCIÓN
/ INSTITUTION: - 2 Laboratory of Physiology, Medical School
of Vrije Universiteit Brussel.
RESUMEN
/ SUMMARY: - Dendritic cells (DC) are the most potent
presenters of alloantigens and therefore are responsible for the induction of
allograft rejection. Genetic modifications of DC allowing the expression of a
tolerogenic molecule may render them immunosuppressive. We transduced bone
marrow-derived DC with recombinant MFG retrovirus encoding either viral
interleukin (vIL)-10 or Fas ligand (FasL) to induce transplantation tolerance.
Up to 10 ng/ml of bioactive vIL-10 was produced by DC after transfer of the
corresponding gene. Although the inhibitory properties of vIL-10-transduced DC
were revealed in vitro in a mixed lymphocyte culture, no clear down-regulation
of the allogeneic response was observed in vivo after single or multiple injections
of those DC overexpressing vIL-10. When we transduced wild-type bone
marrow-derived DC with recombinant MFG retrovirus encoding murine FasL, cells
quickly died, probably because of suicidal or fratricidal Fas-dependent death.
Indeed, only DC from Fas-deficient lpr mice survived to FasL gene transfer.
Those FasL-transduced lpr DC exhibited a strong cytotoxic activity against
Fas-positive targets in vitro. DC overexpressing FasL did not behave as
immunosuppressive DC in vivo. The subcutaneous injection of FasL+ lpr DC in MHC
class II-disparate mice hyperactivated the allospecific proliferation of T
cells in the draining lymph nodes compared with mice treated with
control-transduced DC. These results argue against the development of FasL+ DC
or vIL-10-secreting DC as immunosuppressive tools in vivo. The alternative
pathways of T-cell activation triggered by these genetically modified DC need
to be investigated. N.
Ref:: 20
----------------------------------------------------
[79]
TÍTULO / TITLE: - Treatment of idiopathic
nephrosis by immunophillin modulation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Aug;18 Suppl
6:vi79-86.
AUTORES
/ AUTHORS: - Meyrier A
INSTITUCIÓN
/ INSTITUTION: - Service de Nephrologie, Hopital Europeen
Georges Pompidou, 20 rue Leblanc, F-75015 Paris, France. alain.meyrier@brs.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - Until 1985, glucocorticoids and cytotoxic
drugs were the only treatments available for idiopathic nephrotic syndrome
(nephrosis), that is, minimal change disease (MCD) and focal segmental
glomerulosclerosis (FSGS). Trials of cyclosporine (CsA) treatment of nephrosis,
the rationale of which was based on pathophysiologic considerations, have shown
that this immunophillin modulator is effective in inducing and maintaining
remission in patients suffering from idiopathic nephrotic syndrome. It appears
that the best results, in the order of 80% remission rate, are obtained in
steroid-sensitive cases, essentially MCD, and that in steroid-resistant FSGS
the drug obtains remission in no more than 20% of the cases. Addition of
glucocorticoids increases the success rate to approximately 30% of cases. Renal
toxicity is proportional to previous impairment of renal function, primary
renal disease (FSGS vs MCD) dosage >5.5 mg/kg/day and duration of treatment.
The better bioavailability of the new formulation of CsA (Neoral), implies that
the former dosage recommendations be reconsidered for distinctly lower figures.
Repeat renal biopsy after 1 year of continuous CsA treatment is advisable, as
stable serum creatinine levels may be falsely reassuring. CsA dependency is the
rule during the first year of treatment. However, in some 25% of cases stable
remission may be maintained after slow tapering off following 3-4 years of
treatment. Other immunophillin modulators have been tried in the treatment of
idiopathic nephrotic syndrome. Despite few preliminary reports indicating some
success of tacrolimus the effects of this drug do not seem convincingly
superior to CsA in terms of remission rate, toxicity and dependency. Rapamycin
has not been tried in the treatment of nephrosis. Anecdotal cases of de novo
FSGS induced by rapamycin in transplanted patients might indicate that this
drug is in fact contraindicated in the treatment of nephrosis. N. Ref:: 36
----------------------------------------------------
[80]
TÍTULO / TITLE: - In vitro generation of
IL-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs
and inhibited by Th1- and Th2-inducing cytokines.
REVISTA
/ JOURNAL: - Immunol Lett 2003 Jan 22;85(2):135-9.
AUTORES
/ AUTHORS: - O’Garra A; Barrat FJ
INSTITUCIÓN
/ INSTITUTION: - Division of Immunoregulation, The National
Institute for Medical Research (NIMR), The Ridgeway, Mill Hill, NW7 1AA,
London, UK. N. Ref:: 40
----------------------------------------------------
[81]
TÍTULO / TITLE: - Treating human
autoimmune disease by depleting B cells.
REVISTA
/ JOURNAL: - Ann Rheum Dis 2002 Oct;61(10):863-6.
AUTORES
/ AUTHORS: - Looney RJ
INSTITUCIÓN
/ INSTITUTION: - University of Rochester, Rochester, New
York 14642, USA. John_looney@URMC.Rochester.edu N. Ref:: 40
----------------------------------------------------
[82]
TÍTULO / TITLE: - The future of
antigen-specific immunotherapy of allergy.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2002 Jun;2(6):446-53.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri824
AUTORES
/ AUTHORS: - Valenta R
INSTITUCIÓN
/ INSTITUTION: - Department of Pathophysiology, University
of Vienna Medical School, Vienna General Hospital-AKH, Australia. Rudolf.valenta@akh-wein.ac.at
RESUMEN
/ SUMMARY: - More than 25% of the population in
industrialized countries suffers from immunoglobulin-E-mediated allergies. The
antigen-specific immunotherapy that is in use at present involves the
administration of allergen extracts to patients with the aim to cure allergic
symptoms. However, the risk of therapy-induced side effects limits its broad
application. Recent work indicates that the epitope complexity of natural
allergen extracts can be recreated using recombinant allergens, and
hypoallergenic derivatives of these can be engineered to increase treatment
safety. It is proposed that these modified molecules will improve the current
practice of specific immunotherapy and form a basis for prophylactic
vaccination. N.
Ref:: 120
----------------------------------------------------
[83]
TÍTULO / TITLE: - Indoleamine
2,3-dioxygenase-expressing antigen-presenting cells and peripheral T-cell
tolerance: another piece to the atopic puzzle?
REVISTA
/ JOURNAL: - J Allergy Clin Immunol 2003
Nov;112(5):854-60.
●●
Enlace al texto completo (gratuito o de pago) 1016/S0091
AUTORES
/ AUTHORS: - von Bubnoff D; Hanau D; Wenzel J; Takikawa
O; Hall B; Koch S; Bieber T
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology,
Friedrich-Wilhelms University, Bonn, Germany.
RESUMEN
/ SUMMARY: - There is growing evidence that dendritic
cells, the major antigen-presenting cells and T-cell activators, have a broad
effect on peripheral T-cell tolerance and regulation of immunity. Very
recently, a new feature of regulatory antigen-presenting cells was observed.
Certain dendritic cells, monocytes, and macrophages express the enzyme
indoleamine 2,3-dioxygenase, and thus because of enhanced degradation of the
essential amino acid tryptophan, they modulate T-cell activity in specific
local tissue environments. In this review we discuss the various and apparently
disparate effects of indoleamine 2,3-dioxygenase induction in cells of the
immune system. We place current knowledge about this mechanism in the context
of atopy. We introduce the hypothesis that tryptophan degradation might add to
the ability to control and downregulate allergen-specific T-cell responses in
atopic individuals. N.
Ref:: 44
----------------------------------------------------
[84]
TÍTULO / TITLE: - Cross-presentation in
viral immunity and self-tolerance.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2001 Nov;1(2):126-34.
●●
Enlace al texto completo (gratuito o de pago) 1038/35100512
AUTORES
/ AUTHORS: - Heath WR; Carbone FR
INSTITUCIÓN
/ INSTITUTION: - Immunology Division, The Walter and Eliza
Hall Institute, Melbourne Hospital, Parkville, Victoria, Australia. heath@wehi.edu.au
RESUMEN
/ SUMMARY: - T lymphocytes recognize peptide antigens
presented by class I and class II molecules encoded by the major
histocompatibility complex (MHC). Classical antigen-presentation studies showed
that MHC class I molecules present peptides derived from proteins synthesized
within the cell, whereas MHC class II molecules present exogenous proteins
captured from the environment. Emerging evidence indicates, however, that
dendritic cells have a specialized capacity to process exogenous antigens into
the MHC class I pathway. This function, known as cross-presentation, provides
the immune system with an important mechanism for generating immunity to
viruses and tolerance to self. N.
Ref:: 83
----------------------------------------------------
[85]
TÍTULO / TITLE: - Scedosporium
prolificans osteomyelitis in an immunocompetent child treated with voriconazole
and caspofungin, as well as locally applied polyhexamethylene biguanide.
REVISTA
/ JOURNAL: - J Clin Microbiol. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://jcm.asm.org/
●●
Cita: J. Clinical Microbiology: <> 2003 Aug;41(8):3981-5.
AUTORES
/ AUTHORS: - Steinbach WJ; Schell WA; Miller JL;
Perfect JR
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Duke University,
Durham, North Carolina 27710, USA. stein022@mc.duke.edu
RESUMEN
/ SUMMARY: - Scedosporium species are increasingly
isolated from immunocompromised and immunocompetent patients. Unfortunately,
Scedosporium infections are generally resistant to amphotericin B, and
Scedosporium prolificans strains are particularly resistant to the antifungal
agents now in use. We report here on an immunocompetent child with S. prolificans-associated
osteomyelitis successfully treated with debridement, local irrigation with
polyhexamethylene biguanide, and the systemic administration of voriconazole
and caspofungin despite poor in vitro activity of voriconazole alone against
the isolate. We also review the treatments and outcomes of 28 reported cases of
osteomyelitis or septic arthritis caused by Scedosporium species in
immunocompetent patients. N.
Ref:: 62
----------------------------------------------------
[86]
TÍTULO / TITLE: - To DRiP or not to DRiP:
generating peptide ligands for MHC class I molecules from biosynthesized
proteins.
REVISTA
/ JOURNAL: - Mol Immunol 2002 Oct;39(3-4):139-46.
AUTORES
/ AUTHORS: - Yewdell J
INSTITUCIÓN
/ INSTITUTION: - Laboratory of Viral Diseases, National
Institute of Allergy and Infectious Diseases, National Institutes of Health,
Room 211 Bldg 4, 4 Center Drive, Bethesda, MD 20892-0440, USA. jyewdell@nih.gov N. Ref:: 75
----------------------------------------------------
[87]
TÍTULO / TITLE: - Renal transplantation:
can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol
biopsy findings.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Mar;14(3):755-66.
AUTORES
/ AUTHORS: - Gotti E; Perico N; Perna A; Gaspari F;
Cattaneo D; Caruso R; Ferrari S; Stucchi N; Marchetti G; Abbate M; Remuzzi G
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine and
Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for
Pharmacological Research, Italy.
RESUMEN
/ SUMMARY: - How to combine antirejection drugs and
which is the optimal dose of steroids and calcineurin inhibitors beyond the
first year after kidney transplantation to maintain adequate immunosuppression
without major side effects are far from clear. Kidney transplant patients on
steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol
biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA
were discontinued or reduced on the basis of biopsy to establish effects on
drug-related complications, acute rejection, and graft function over 3 yr of
follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal
clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were
monitored yearly. At the end, patients underwent a second biopsy. Per-protocol
biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA
nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n =
12, standard therapy). Reducing the drug regimen led to overall fewer side
effects related to immunosuppression as compared with standard therapy or
no-biopsy. Steroids were safely stopped with no acute rejection or graft loss.
Complete CsA discontinuation was associated with acute rejection in the first
four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led
to acute rejection or major renal function deterioration. Biopsy patients on
conventional regimen had no acute rejection, one graft loss, no significant
change in GFR, and significant RPF decline. No-biopsy controls: no acute
rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy
analysis, severe lesions did not develop in patients with steroid
discontinuation in contrast to patients on standard therapy over follow-up. CsA
reduction did not adversely affect histology. Per-protocol biopsy more than 1
yr after kidney transplantation is a safe procedure to guide change of drug
regimen and to lower the risk of major side effects.
----------------------------------------------------
[88]
TÍTULO / TITLE: - Clinical protocol.
Purging of autologous stem cell sources with bcl-x(s) adenovirus for women
undergoing high-dose chemotherapy for stage IV breast carcinoma.
REVISTA
/ JOURNAL: - Hum Gene Ther 2001 Nov 1;12(16):2023-5.
AUTORES
/ AUTHORS: - Ayash LJ; Clarke M; Adams P; Ferrara J;
Ratanatharathorn V; Reynolds C; Roessler B; Silver S; Strawderman M; Uberti J;
Wicha M
RESUMEN
/ SUMMARY: - High-dose chemotherapy (HDCT) and
autologous bone marrow transplantation (BMT) is frequently used to treat
patients with metastatic cancer including breast cancer and neuroblastoma.
However, the bone marrow of such patients is often contaminated with tumor
cells. Recently, we have found that a recombinant adenovirus vector that
contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family),
called the bcl-x(s) adenovirus, is lethal to cancer cells derived from
epithelial tissues, but not to normal human hematopoietic cells. To determine
the mechanism, by which this virus spares normal hematopoietic cells, we
isolated normal mouse hematopoietic stem cells and infected them with an
adenovirus that contains a beta-galactosidase minigene. Such cells do not
express beta-galactosidase, indicating that hematopoietic stem cells do not express
transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system.
When breast cancer cells mixed with hematopoietic cells were infected with the
bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide
adenoviruses. Hematopoietic cells exposed to the suicide vectors were able to
reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation.
These studies suggest that adenovirus suicide vectors may provide a simple and
effective method to selectively eliminate cancer cells derived from epithelial
tissue that contaminate bone marrow to be used for autologous BMT. We therefore
propose to initiate a phase I clinical trial to test the safety of this virus
in women with breast cancer undergoing high does chemotherapy and autologous
BMT.
----------------------------------------------------
[89]
TÍTULO / TITLE: - Regulation of gene
expression in lymphocytes and antigen-presenting cells by measles virus:
consequences for immunomodulation.
REVISTA
/ JOURNAL: - J Mol Med 2002 Feb;80(2):73-85. Epub 2001
Nov 15.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00109-001-0299-x
AUTORES
/ AUTHORS: - Schneider-Schaulies S; Bieback K; Avota E;
Klagge I; ter Meulen V
INSTITUCIÓN
/ INSTITUTION: - Institute for Virology and Immunobiology,
University of Wurzburg, Versbacher Strasse 7, 97078 Wurzburg, Germany. s-s-s@vim.uni-wuerzburg.de
RESUMEN
/ SUMMARY: - Acute measles, a well known disease
usually contracted during early childhood, is still the major cause of
vaccine-preventable infant deaths worldwide. There are about 40 million cases
of acute measles per year, with more than one million cases of infant death as
a consequence of measles. These are mainly due to opportunistic infections
which develop on the basis of a generalized suppression of the cellular
immunity in the course and after the acute disease. Lymphopenia, a general
proliferative unresponsiveness of T cells ex vivo and cytokine imbalance, are
considered as major hallmarks of measles virus (MV) induced immunosuppression.
These findings are compatible with modulation of T cell responses by viral
interference with professional antigen-presenting cells such as dendritic cells
or direct effects on T cells by suppression of survival or proliferation
signals. In vitro, MV interaction causes a variety of effects on dendritic
cells, including maturation and loss of their allostimulatory functions.
Whether there is an additional impact on the quality of T cell responses is
unknown as yet. It is clear, however, that surface interaction of lymphocytes
with the MV glycoprotein complex is necessary and sufficient to induce a state
of proliferative unresponsiveness in T cells. This surface contact mediated
signal essentially interferes with the propagation of the interleukin 2
receptor signal by blocking the activation of the protein kinase B, also called
Akt kinase, both in vitro and after experimental infection. N. Ref:: 122
----------------------------------------------------
[90]
TÍTULO / TITLE: - Mammalian target of
rapamycin inhibition as therapy for hematologic malignancies.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 15;100(4):657-66.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.20026
AUTORES
/ AUTHORS: - Panwalkar A; Verstovsek S; Giles FJ
INSTITUCIÓN
/ INSTITUTION: - Section of Developmental Therapeutics,
Department of Leukemia, University of Texas M. D. Anderson Cancer Center,
Houston, Texas, USA.
RESUMEN
/ SUMMARY: - The mammalian target of rapamycin (mTOR)
is a downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt
(protein kinase B) signaling pathway, which mediates cell survival and
proliferation. mTOR regulates essential signal-transduction pathways, is
involved in the coupling of growth stimuli with cell cycle progression, and
initiates mRNA translation in response to favorable nutrient environments. mTOR
is involved in regulating many aspects of cell growth, including membrane
traffic, protein degradation, protein kinase C signaling, ribosome biogenesis,
and transcription. Because mTOR activates both the 40S ribosomal protein S6
kinase (p70s6k) and the eukaryotic initiation factor 4E-binding protein 1, its
inhibitors cause G1-phase cell cycle arrest. Inhibitors of mTOR also prevent
cyclin dependent kinase (CDK) activation, inhibit retinoblastoma protein
phosphorylation, and accelerate the turnover of cyclin D1, leading to a
deficiency of active CDK4/cyclin D1 complexes, all of which may help cause
G1-phase arrest. It is known that the phosphatase and tensin homologue tumor
suppressor gene (PTEN) plays a major role in embryonic development, cell migration,
and apoptosis. Malignancies with PTEN mutations, which are associated with
constitutive activation of the PI3K/Akt pathway, are relatively resistant to
apoptosis and may be particularly sensitive to mTOR inhibitors. Rapamycin
analogs with relatively favorable pharmaceutical properties, including CCI-779,
RAD001, and AP23573, are under investigation in patients with hematologic
malignancies. N.
Ref:: 116
----------------------------------------------------
[91]
TÍTULO / TITLE: - Cholesteryl ester transfer
protein facilitates the movement of water-insoluble drugs between lipoproteins:
a novel biological function for a well-characterized lipid transfer protein.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2002 Dec
15;64(12):1669-75.
AUTORES
/ AUTHORS: - Kwong M; Wasan KM
INSTITUCIÓN
/ INSTITUTION: - Division of Pharmaceutics and
Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British
Columbia, 2146 East Mall Avenue, Vancouver, BC, Canada V6T 1Z3.
RESUMEN
/ SUMMARY: - This review article addresses the recently
discovered finding that cholesteryl ester transfer protein (CETP) can
facilitate the transfer of water-insoluble drugs between different lipoprotein
subclasses. This protein, which is often referred to as lipid transfer protein
I (LTP I), is involved in the lipid regulation of lipoproteins. It is
responsible for the facilitated transfer of core lipoprotein lipids,
cholesteryl ester and triglycerides, and approximately one-third of the coat
lipoprotein lipid, phosphatidylcholine, between different plasma lipoproteins.
The human body appears to recognize exogenous water-insoluble drugs as
lipid-like particles, which suggests that these compounds may interact with
lipoproteins just like endogenous plasma lipids, and thus their transfer
between lipoproteins may be facilitated by plasma CETP. Patients with a variety
of diseases (i.e. diabetes, cancer, AIDS) often exhibit hypo- and/or
hypercholesterolemia and triglyceridemia, commonly referred to as
dyslipidemias, which result in changes in their plasma lipoprotein-lipid
composition and concentration. The interaction of water-insoluble drugs with
these dyslipidemic lipoproteins may be responsible for the differences seen in
the pharmacokinetics and pharmacodynamics of the drug within different diseased
patient populations. It is possible that these differences may be linked to the
ability of CETP to transfer these compounds from one lipoprotein to another.
This review examines the current understanding of the relationship between CETP
activity and the lipoprotein distribution of a number of compounds (e.g.
amphotericin B and cyclosporine A). It further suggests that additional
research will expand our understanding of the role of CETP to explain other
functions in lipophilic drug distribution and metabolism. N. Ref:: 45
----------------------------------------------------
[92]
TÍTULO / TITLE: - Heme oxygenase in liver
transplantation: heme catabolism and metabolites in the search of function.
REVISTA
/ JOURNAL: - Hepatology 2003 Aug;38(2):286-8.
●●
Enlace al texto completo (gratuito o de pago) 1053/jhep.2003.50360
AUTORES
/ AUTHORS: - Bauer M
N. Ref:: 31
----------------------------------------------------
[93]
TÍTULO / TITLE: - Clinical development of
mammalian target of rapamycin inhibitors.
REVISTA
/ JOURNAL: - Hematol Oncol Clin North Am 2002
Oct;16(5):1101-14.
AUTORES
/ AUTHORS: - Dancey JE
INSTITUCIÓN
/ INSTITUTION: - Cancer Treatment Evaluation Program,
Division of Cancer Treatment and Diagnosis, Investigational Drug
Branch/CTEP/DCTD/NCI, 6130 Executive Boulevard, EPN 7131, Rockville, MD 20854,
USA. danceyj@ctep.nci.nih.gov
RESUMEN
/ SUMMARY: - Rapamycin and CCI-779 have significant in
vitro and in vivo anti-proliferative activity against a broad range of human
tumor cell lines, justifying the clinical evaluation of this class of agent in
cancer patients. Preliminary results from phase I studies of CCI-779 suggest
that the agent is well tolerated and has anti-tumor activity. The challenge to
investigators is to efficiently determine what role this class of agent will
play in the treatment of cancer patients.
N. Ref:: 69
----------------------------------------------------
[94]
TÍTULO / TITLE: - Regulatory T cells in
kidney transplant recipients: active players but to what extent?
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Jun;14(6):1706-8.
AUTORES
/ AUTHORS: - Zhai Y; Kupiec-Weglinski JW N. Ref:: 20
----------------------------------------------------
[95]
TÍTULO / TITLE: - The bare lymphocyte
syndrome and the regulation of MHC expression.
REVISTA
/ JOURNAL: - Annu Rev Immunol 2001;19:331-73.
●●
Enlace al texto completo (gratuito o de pago) 1146/annurev.immunol.19.1.331
AUTORES
/ AUTHORS: - Reith W; Mach B
INSTITUCIÓN
/ INSTITUTION: - Jeantet Laboratory of Molecular Genetics,
Department of Genetics and Microbiology, University of Geneva Medical School, 1
rue Michel-Servet, Geneva 4, 1211 Switzerland. Walter.Reith@medecine.unige.ch
RESUMEN
/ SUMMARY: - The bare lymphocyte syndrome (BLS) is a
hereditary immunodeficiency resulting from the absence of major histocompatibility
complex class II (MHCII) expression. Considering the central role of MHCII
molecules in the development and activation of CD4(+) T cells, it is not
surprising that the immune system of the patients is severely impaired. BLS is
the prototype of a “disease of gene regulation.” The affected genes encode
RFXANK, RFX5, RFXAP, and CIITA, four regulatory factors that are highly
specific and essential for MHCII genes. The first three are subunits of RFX, a
trimeric complex that binds to all MHCII promoters. CIITA is a non-DNA-binding
coactivator that functions as the master control factor for MHCII expression.
The study of RFX and CIITA has made major contributions to our comprehension of
the molecular mechanisms controlling MHCII genes and has made this system into
a textbook model for the regulation of gene expression. N. Ref:: 183
----------------------------------------------------
[96]
TÍTULO / TITLE: - Prediction of an
HLA-DR-binding peptide derived from Wilms’ tumour 1 protein and demonstration
of in vitro immunogenicity of WT1(124-138)-pulsed dendritic cells generated
according to an optimised protocol.
REVISTA
/ JOURNAL: - Cancer Immunol Immunother 2002
Jul;51(5):271-81. Epub 2002 Apr 26.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00262-002-0278-2
AUTORES
/ AUTHORS: - Knights AJ; Zaniou A; Rees RC; Pawelec G;
Muller L
INSTITUCIÓN
/ INSTITUTION: - University of Tubingen, Section for
Transplantation Immunology and Immunohaematology, Second Department of Internal
Medicine, Zentrum fur Medizinische Forschung ZMF, Waldhornlestrasse 22, 72072
Tubingen, Germany.
RESUMEN
/ SUMMARY: - The Wilms’ tumour 1 (WT1) protein is
over-expressed in several types of cancer including leukaemias and might
therefore constitute a novel target for immunotherapy. Recently, human
leucocyte antigen (HLA) class I-binding WT1 peptides have been identified and
shown to stimulate CD8(+) T cells in vitro. For maximal CD8 cell efficacy,
CD4(+) helper T cells responding to major histocompatibility complex (MHC)
class II-binding epitopes are required. Here, we report that scanning the WT1
protein sequence using an evidence-based predictive computer algorithm
(SYFPEITHI) yielded a peptide WT1(124-138) predicted to bind the HLA-DRB1*0401
molecule with high affinity. Moreover, synthetic WT1(124-138)-peptide-pulsed
dendritic cells (DC), generated according to a protocol optimised in the
present study, sensitised T cells in vitro to proliferate and secrete interferon-gamma
(IFN-gamma) when rechallenged with specific peptide-pulsed DC, but not with
peripheral blood mononuclear cells (PBMC). These results suggest that the WT1
protein may yield epitopes immunogenic to CD4 as well as CD8 T cells, and
therefore constitute a novel potential target for specific immunotherapy.
----------------------------------------------------
[97]
TÍTULO / TITLE: - Induction of T cell
alertness by bacterial colonization of intestinal epithelium.
REVISTA
/ JOURNAL: - Proc Natl Acad Sci U S A. Acceso gratuito
al texto completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.pnas.org/
●●
Cita: Proc Natl Acad Sci USA (PNAS): <> 2002 Mar 5;99(5):2584-6.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.062058399
AUTORES
/ AUTHORS: - Spies T
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
tspies@fhcrc.org N. Ref:: 32
----------------------------------------------------
[98]
TÍTULO / TITLE: - Interleukin 2 receptor
antagonists for kidney transplant recipients.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2004;1:CD003897.
●●
Enlace al texto completo (gratuito o de pago) 1002/14651858.CD003897.pub2
AUTORES
/ AUTHORS: - Webster A; Playford E; Higgins G; Chapman
J; Craig J
INSTITUCIÓN
/ INSTITUTION: - Centre for Kidney Research, The Children’s
Hospital at Westmead, Locked Bag 4001, Westmead, NSW, AUSTRALIA, 2145.
RESUMEN
/ SUMMARY: - BACKGROUND: Interleukin 2 receptor
antagonists (IL2Ra) are used as induction therapy for prophylaxis against acute
rejection in kidney transplant recipients. Use of IL2Ra has increased steadily,
with 38% of new kidney transplant recipients in the United States, and 23% in
Australasia receiving IL2Ra in 2002. OBJECTIVES: This study aims to
systematically identify and summarise the effects of using an IL2Ra, as an
addition to standard therapy, or as an alternative to other antibody therapy.
SEARCH STRATEGY: The Cochrane Renal Group’s specialised register (June 2003),
the Cochrane Controlled Trials Register (in The Cochrane Library issue 3,
2002), MEDLINE (1966-November 2002) and EMBASE (1980-November 2002). Reference
lists and abstracts of conference proceedings and scientific meetings were
hand-searched from 1998-2003. Trial groups, authors of included reports and
drug manufacturers were contacted. SELECTION CRITERIA: Randomised controlled
trials (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other
IL2Ra or other antibody therapy. DATA COLLECTION AND ANALYSIS: Data was
extracted and quality assessed independently by two reviewers, with differences
resolved by discussion. Dichotomous outcomes are reported as relative risk (RR)
with 95% confidence intervals (CI). MAIN RESULTS: One hundred and seventeen
reports from 38 trials involving 4893 participants were included. Where IL2Ra
were compared with placebo (17 trials; 2786 patients), graft loss was not
significantly different at one (RR 0.83, 95% CI 0.66 to 1.04) or three years
(RR 0.88, 95% CI 0.64 to 1.22). Acute rejection (AR) was significantly reduced
at six months (RR 0.66, 95% CI 0.59 to 0.74) and at one year (RR 0.67, 95% CI
0.60 to 0.75). At one year, cytomegalovirus (CMV) infection (RR 0.82, 95% CI
0.65 to 1.03) and malignancy (RR 0.67, 95% CI 0.33 to 1.36) were not
significantly different. Where IL2Ra were compared with other antibody therapy
no significant differences in treatment effects were demonstrated, but adverse
effects strongly favoured IL2Ra. REVIEWER’S CONCLUSIONS: Given a 40% risk of
rejection, seven patients would need treatment with IL2Ra to prevent one
patient having rejection, with no definite improvement in graft or patient
survival. There is no apparent difference between basiliximab and daclizumab.
IL2Ra are as effective as other antibody therapies and with significantly fewer
side effects
----------------------------------------------------
[99]
TÍTULO / TITLE: - Treatment of nephrotic
syndrome in children and controlled trials.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Aug;18 Suppl 6:vi75-8.
AUTORES
/ AUTHORS: - Filler G
INSTITUCIÓN
/ INSTITUTION: - Department of Paediatrics, Division of
Nephrology, Children’s Hospital of Eastern Ontario, University of Ottawa,
Canada. filler@cheo.on.ca
RESUMEN
/ SUMMARY: - AIM: To determine the sequential therapy
of childhood nephrotic syndrome (NS) with presumed minimal change nephropathy
using the evidence from clinical trials. METHODS: Meta-analysis of 22
randomized controlled trials was performed, using frequency of relapse and side
effects of therapeutic regimes. RESULTS: A meta-analysis of seven trials
comparing duration of therapy for initial onset showed that duration of at
least 3 months significantly reduced the risk of relapse at 12-24 months
(relative risk 0.73; 95% confidence interval 0.60-0.89) without an increase in adverse
events. Five trials were performed for steroid treatment of relapse.
Deflazacort reduced relapses during therapy, but is not generally available. No
difference was observed when comparing single and divided dosing of prednisone.
Frequency of relapses could not be influenced by duration of relapse therapy.
Alternate day therapy was more effective than intermittent use of prednisone.
Two studies out of five on cyclophosphamide or chlorambucil showed consistently
that alkylating agents should be used before cyclosporine as alternative
therapy to steroids. CONCLUSIONS: Children with initial onset of NS should be
treated with prednisone at a dose of 60 mg/m(2)/day for 6 weeks, followed by a
dose of 40 mg/m(2)/48 h for at least another 6 weeks. If steroid toxicity for
treatment of relapsing NS requires alternative treatment, cyclophosphamide (2
mg/kg/day for at least 8 weeks) remains the drug of choice with a curative
potential. If children still relapse after alkylating agents, levamisole may
serve as an alternative only for frequent relapsing NS, whereas
steroid-dependent NS should be treated with cyclosporine.
----------------------------------------------------
[100]
TÍTULO / TITLE: - Interventions for
bullous pemphigoid.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2003;(3):CD002292.
●●
Enlace al texto completo (gratuito o de pago) 1002/14651858.CD002292
AUTORES
/ AUTHORS: - Khumalo N; Kirtschig G; Middleton P;
Hollis S; Wojnarowska F; Murrell D
INSTITUCIÓN
/ INSTITUTION: - Dermatology Department, Groote Schuur
Hospital, Cape Town, South Africa, Anzio Road, Observatory, Cape Town, Western
Cape, South Africa.
RESUMEN
/ SUMMARY: - BACKGROUND: Bullous pemphigoid is the most
common autoimmune bullous disease in the West. Oral steroids are considered the
standard treatment. OBJECTIVES: To assess the effects of treatments for bullous
pemphigoid. SEARCH STRATEGY: We searched the Skin Group Specialised Register,
the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE to March
2003 and bibliographies from identified studies. SELECTION CRITERIA: Randomised
controlled trials of treatments for patients with immunofluorescence confirmed
bullous pemphigoid. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the
studies in terms of the inclusion criteria, five extracted data independently;
disagreements were resolved by discussion. Statistical pooling of the data was
inappropriate because of heterogeneity of treatments. MAIN RESULTS: We found
seven randomised controlled trials with a total of 634 patients. All studies
involved different comparisons, none included a placebo group.Different doses,
different formulations of corticosteroids and the addition of azathioprine
failed to show significant differences in measures of disease control. However,
patients who took azathioprine were able to almost halve the amount of
prednisone required for disease control. Plasma exchange plus prednisone
achieved significantly better disease control than prednisone alone; this
favourable effect was not apparent in another study. The latter study also
compared plasma exchange or azathioprine plus prednisone, but failed to show
significant differences for disease control or mortality, although total
adverse events at six months almost reached statistical significance in favour
of plasma exchange plus prednisone. Comparing tetracycline plus nicotinamide
with prednisolone, no significant difference for disease response was shown. A
very potent topical corticosteroid was compared to oral prednisone in patients
with moderate and extensive disease. In patients with extensive disease, the
topical steroid group showed significantly better survival and disease control,
and less severe complications, while no significant differences for these
outcomes were seen in patients with moderate disease.Most of the reported
deaths were in patients taking high doses of oral corticosteroids. REVIEWER’S
CONCLUSIONS: Very potent topical steroids are effective and safe treatments for
bullous pemphigoid; their use in extensive disease may be limited by side
effects and practical factors.Starting doses of prednisolone greater than 0.75
mg/kg/day do not seem to give additional benefit, lower doses may be adequate
for disease control; this could reduce the incidence and severity of adverse
reactions.The effectiveness of the addition of plasma exchange or azathioprine
to corticosteroids has not been established.Combination treatment with
tetracycline and nicotinamide may be useful; this needs further
validation. N. Ref:: 38
----------------------------------------------------
[101]
TÍTULO / TITLE: - Pumping iron: the
strange partnership of the hemochromatosis protein, a class I MHC homolog, with
the transferrin receptor.
REVISTA
/ JOURNAL: - Traffic 2001 Mar;2(3):167-74.
AUTORES
/ AUTHORS: - Enns CA
INSTITUCIÓN
/ INSTITUTION: - Department of Cell and Developmental
Biology, L-215, Oregon Health Sciences University, Portland, OR 97201, USA. ennsca@ohsu.edu
RESUMEN
/ SUMMARY: - People suffering from hereditary
hemochromatosis (HH) can not regulate the uptake of iron properly and gradually
accumulate iron in their body over their lifetime. The protein involved in HH,
HFE, has been recently identified as a class I major histocompatibility complex
(MHC) homolog. The wild-type HFE associates and co-traffics with the
transferrin receptor (TfR). The mutation responsible for 83% of HH (C260Y)
results in the failure of HFE to form a critical disulfide bond, bind beta2
microglobulin, bind TfR, and traffic to the cell surface. In non-polarized
cells, the partnership of HFE and TfR results in decreased iron uptake into
cells. The mechanism whereby a class I MHC homolog modifies the function of a
membrane receptor and how this dynamic complex of molecules regulates iron
transport across intestinal epithelial cells is the subject of this
review. N. Ref:: 66
----------------------------------------------------
[102]
TÍTULO / TITLE: - Nutritional
pharmacology in surgical patients.
REVISTA
/ JOURNAL: - Am J Surg 2002 Apr;183(4):349-52.
AUTORES
/ AUTHORS: - Alexander JW
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Cincinnati College of Medicine, 231 Albert B. Sabin Way, Cincinnati, Ohio
45267-2558, USA. jwesley.alexander@uc.edu
RESUMEN
/ SUMMARY: - The use of pharmaconutrition for
supportive care of surgical patients is now well established, but the field is
still in its infancy. Complex pharmaconutrient formulas containing arginine,
glutamine, and n-3 fatty acids have been proven to shorten hospital stay,
decrease the incidence of infection, and reduce hospital costs in selected
groups of patients. The effects are greatest in those patients with severe
trauma including burn injury, those undergoing major surgical procedures,
especially when malnourished, and those who are critically ill ICU patients
including patients with existing infection. The complex interaction of
pharmaconutrients and other pharmacologic agents are just now beginning to be
investigated. N.
Ref:: 22
----------------------------------------------------
[103]
TÍTULO / TITLE: - IL-10 and its related
cytokines for treatment of inflammatory bowel disease.
REVISTA
/ JOURNAL: - World J Gastroenterol. Acceso gratuito al
texto completo.
●●
Enlace a la Editora de la Revista http://www.wjgnet.com/1007-9327/wj.htm
●●
Cita: World Journal of Gastroenterology: <> 2004 Mar 1;10(5):620-5.
AUTORES
/ AUTHORS: - Li MC; He SH
INSTITUCIÓN
/ INSTITUTION: - Allergy and Inflammation Research
Institute, Shantou University Medical College, 22 Xin Ling Road, Shantou
515041, Guangdong Province, China.
RESUMEN
/ SUMMARY: - Inflammatory bowel diseases (IBDs),
including Crohn’s disease and ulcerative colitis are chronic inflammatory
disorders of gastrointestinal tract. Although the etiology is incompletely
understood, initiation and aggravation of the inflammatory process seem to be
due to a massive local mucosal immune response. Interleukin-10 (IL-10) is a
regulatory cytokine which inhibits both antigen presentation and subsequent
pro-inflammatory cytokine release, and it is proposed as a potent
anti-inflammatory biological therapy in chronic IBD. Many methods of IL-10 as a
treatment for IBD have been published. The new strategies of IL-10 treatment,
including recombinant IL-10, the use of genetically modified bacteria, gelatine
microsphere containing IL-10, adenoviral vectors encoding IL-10 and combining
regulatory T cells are discussed in this review. The advantages and
disadvantages of these IL-10 therapies are summarized. Although most results of
recombinant IL-10 therapies are disappointing in clinical testing because of
lacking efficacy or side effects, therapeutic strategies utilizing gene therapy
may enhance mucosal delivery and increase therapeutic response. Novel
IL-10-related cytokines, including IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and
IL-29, are involved in regulation of inflammatory and immune responses. The use
of IL-10 and IL-10-related cytokines will provide new insights into cell-based
and gene-based treatment against IBD in near future. N. Ref:: 54
----------------------------------------------------
[104]
TÍTULO / TITLE: - Potential role of major
histocompatibility complex class II peptides in regulatory tolerance to
vascularized grafts.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1
Suppl):S35-7.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106472.91343.8D
AUTORES
/ AUTHORS: - LeGuern C
INSTITUCIÓN
/ INSTITUTION: - Transplantation Biology Research Center,
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. leguern@helix.mgh.harvard.edu
RESUMEN
/ SUMMARY: - The inactivation of persisting T
lymphocytes reactive to self- and non-self-antigens is a major arm of
operational immune tolerance in mammals. Silencing of such T cells proceeds
mostly by means of suppression, a process that is mediated by regulatory T-cell
subsets and especially by CD4(+)CD(25high) regulatory T cells (Treg). Although
Treg activation and ensuing suppressive activity appear to be major
histocompatibility complex class II dependent, the fine specificity of Treg
T-cell receptors has not yet been elucidated. Recent data from the author’s
laboratory on a class II gene therapy induction of tolerance to allogeneic
kidney grafts suggest that class II peptides are involved as generic signals
for Treg activation. A brief compilation of results that would support this
hypothesis is discussed in the present article. N. Ref:: 31
----------------------------------------------------
[105]
TÍTULO / TITLE: - Natural killer cell
receptors: new biology and insights into the graft-versus-leukemia effect.
REVISTA
/ JOURNAL: - Blood. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.bloodjournal.org/
●●
Cita: Blood: <> 2002 Sep 15;100(6):1935-47.
●●
Enlace al texto completo (gratuito o de pago) 1182/blood-2002-02-0350
AUTORES
/ AUTHORS: - Farag SS; Fehniger TA; Ruggeri L; Velardi
A; Caligiuri MA
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Division
of Hematology/Oncology, The Ohio State University, A433A Starling Loving Hall,
320 W Tenth Avenue, Columbus, OH 43210, USA. farag-1@medctr.osu.edu
RESUMEN
/ SUMMARY: - Natural killer (NK) cells have held great
promise for the immunotherapy of cancer for more than 3 decades. However, to
date only modest clinical success has been achieved manipulating the NK cell
compartment in patients with malignant disease. Progress in the field of NK
cell receptors has revolutionized our concept of how NK cells selectively
recognize and lyse tumor and virally infected cells while sparing normal cells.
Major families of cell surface receptors that inhibit and activate NK cells to
lyse target cells have been characterized, including killer cell
immunoglobulinlike receptors (KIRs), C-type lectins, and natural cytotoxicity
receptors (NCRs). Further, identification of NK receptor ligands and their
expression on normal and transformed cells completes the information needed to
begin development of rational clinical approaches to manipulating receptor/ligand
interactions for clinical benefit. Indeed, clinical data suggest that mismatch
of NK receptors and ligands during allogeneic bone marrow transplantation may
be used to prevent leukemia relapse. Here, we review how NK cell receptors
control natural cytotoxicity and novel approaches to manipulating NK
receptor-ligand interactions for the potential benefit of patients with
cancer. N. Ref:: 134
----------------------------------------------------
[106]
TÍTULO / TITLE: - Donor chimerism and stem
cell function in a murine congenic transplantation model after low-dose
radiation conditioning: effects of a retroviral-mediated gene transfer protocol
and implications for gene therapy.
REVISTA
/ JOURNAL: - Exp Hematol. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.medicinedirect.com/journal
●●
Cita: Experimental Hematology: <> 2002 Nov;30(11):1324-32.
AUTORES
/ AUTHORS: - Goebel WS; Yoder MC; Pech NK; Dinauer MC
INSTITUCIÓN
/ INSTITUTION: - Herman B. Wells Center for Pediatric
Research and Department of Pediatrics, Hematology/Oncology, James Whitcomb
Riley Hospital for Children, Indiana University School of Medicine,
Indianapolis, IN, USA.
RESUMEN
/ SUMMARY: - OBJECTIVE: We investigated low-dose
radiation conditioning for the transplantation of retrovirus-transduced cells
in a C57Bl6/J murine model. MATERIALS AND METHODS: The effect of low-dose
radiation on stem cell function was investigated using a competitive
repopulation assay. Stem cell function of marrow cells that underwent a
retroviral-mediated gene transfer (RMGT) protocol was examined by this assay,
and donor chimerism of these cells when transplanted into 160-cGy conditioned
syngeneic hosts was compared to fresh marrow. RESULTS: Irradiation with 300 or
160 cGy substantially decreased stem cell function as measured by competitive
repopulation. Animals conditioned with 160 cGy and transplanted with 20 x 10(6)
fresh marrow cells permitted donor cell engraftment of 53.6% +/- 11.4% 6 months
after transplant compared to 100% donor cell engraftment after 1100 cGy
irradiation. Lymphoid and myeloid engraftment did not significantly differ from
total engraftment in submyeloablated hosts. When transplanted into lethally
irradiated hosts, the competitive repopulating activity of marrow treated with
a single dose of 5-fluorouracil followed by ex vivo culture according to a
standard RMGT protocol was equal to 5-fluorouracil-only treated marrow.
However, cells treated with 5-fluorouracil or 5-fluorouracil plus ex vivo
culture for RMGT repopulated less well than fresh marrow cells in 160 cGy
conditioned hosts. CONCLUSIONS: Low-dose irradiation decreases host stem cell
function, allowing engraftment of both fresh and RMGT protocol-treated marrow,
although the engraftment of 5-fluorouracil-treated cells was reduced at least
two-fold, and 5-fluorouracil plus RMGT protocol-treated cells at least
three-fold, compared to fresh marrow. Modification of current RMGT protocols may
be important for optimizing engraftment under these conditions.
----------------------------------------------------
[107]
TÍTULO / TITLE: - T-cell activation
through the antigen receptor. Part 2: role of signaling cascades in T-cell
differentiation, anergy, immune senescence, and development of immunotherapy.
REVISTA
/ JOURNAL: - J Allergy Clin Immunol 2002
Jun;109(6):901-15.
AUTORES
/ AUTHORS: - Nel AE; Slaughter N
INSTITUCIÓN
/ INSTITUTION: - Division of Clinical Immunology/Allergy,
Department of Medicine, UCLA School of Medicine, University of California, Los
Angeles 90095-1680, USA.
RESUMEN
/ SUMMARY: - Part 2 of this review on cellular
activation by the T-cell antigen receptor (TCR) will highlight how TCR
signaling pathways are adapted to achieve specific biologic outcomes, including
different states of T-cell differentiation and the induction of T-cell
tolerance. We will also explore how treatment with altered peptide ligands
affects TCR signaling to change T-cell differentiation or to induce an anergy
state. These changes are accomplished through alteration of protein tyrosine
kinase activity, the stoichiometry of phosphorylation of immunoreceptor
tyrosine-based activation motifs, intracellular free ionized calcium flux,
mitogen-activated protein kinase activity, and transcriptional activation of
key cytokine promoters. The CTLA-4 plays an important role in the induction and
maintenance of anergy. The second theme will highlight how altered TCR signal
transduction, including changes in the compartmentalization of signaling
components at the TCR synapse, contributes to decreased T-cell activation
during immune senescence. Finally, we will illustrate how the molecular details
of TCR activation can be used to modify the function of the immune system. This
includes a description of the mechanism of action of altered peptide ligands,
CTLA-4Ig, and pharmacologic inhibitors of mitogen-activated protein kinases,
nuclear factor kappaB, and protein kinase C cascades. N. Ref:: 128
----------------------------------------------------
[108]
TÍTULO / TITLE: - HLA in coeliac disease:
unravelling the complex genetics of a complex disorder.
REVISTA
/ JOURNAL: - Tissue Antigens 2003 Feb;61(2):105-17.
AUTORES
/ AUTHORS: - Louka AS; Sollid LM
INSTITUCIÓN
/ INSTITUTION: - Institute of Immunology, Rikshospitalet,
University of Oslo, Norway.
RESUMEN
/ SUMMARY: - Coeliac disease (gluten sensitive
enteropathy) is a common, polygenic and multifactorial disorder that serves as
a pioneering model for the study of inflammatory disease. A major environmental
factor is known (ingested gluten from wheat), and there is unprecedented
genetic and functional evidence pinpointing HLA-DQA1*05-DQB1*02 ( DQ2) and
DQA1*03-DQB1*0302 ( DQ8) in disease predisposition. We discuss the current
state of play in coeliac disease genetics, focussing particularly on the HLA
complex. Emerging evidence suggests that additional HLA risk loci exert weak
effects, independent of DQA1*05-DQB1*02, on the B8-DR3-DQ2 haplotype. There is
also good evidence from linkage studies of disease gene(s) on chromosome 5q. We
discuss the role and implications of linkage disequilibrium and haplotype
blocks in complex disease gene mapping. We briefly address findings from
studies of animal models for chronic inflammatory disease, and consider roles
for both common genes associated with multiple inflammatory diseases, and genes
unique to coeliac disease. The coeliac genetics research community has
established a sound foundation for the identification of additional disease
genes in the not-too-distant future. Functional studies will play a critical
role, and coeliac disease has a promising future in this respect. Coeliac
disease continues to function as a model disorder, facilitating the development
and implementation of complex disease gene mapping strategies. N. Ref:: 59
----------------------------------------------------
[109]
TÍTULO / TITLE: - HLA-DPB1 and chronic
beryllium disease: a HuGE review.
REVISTA
/ JOURNAL: - Am J Epidemiol 2003 Mar 1;157(5):388-98.
AUTORES
/ AUTHORS: - McCanlies EC; Kreiss K; Andrew M; Weston A
INSTITUCIÓN
/ INSTITUTION: - Biostatistics and Epidemiology Branch,
Health Effects Laboratory Division, National Institute for Occupational Safety
and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505,
USA. eim4@cdc.gov
RESUMEN
/ SUMMARY: - The human leukocyte antigen (HLA) complex
is a series of genes located on chromosome 6 that are important in normal
immune function. Susceptibility to chronic beryllium disease, a granulomatous
lung disease that appears in workers exposed to beryllium, is modified by
genetic variants of the HLA-DP subregion. Evaluation of HLA-DPB1 sequence
motifs in current and former beryllium workers implicated a glutamic acid
residue at position 69 (HLA-DPB1(Glu69)) in chronic beryllium disease. This
finding has since been extended to specific HLA-DPB1(Glu69) alleles. Specific
job tasks have also been implicated in degree of risk, and in this paper the
authors explore gene-environment interaction. The utility of this genetic
information for prospective, current, and former beryllium workers must be
weighed against the potential for employment and insurance discrimination.
Continued research in the beryllium-exposed population will be important for
improving personal risk assessment and identifying high-risk genes associated
with disease progression. N.
Ref:: 79
----------------------------------------------------
[110]
TÍTULO / TITLE: - Donor-specific
tolerance in fully major histocompatibility major histocompatibility
complex-mismatched limb allograft transplants under an anti-alphabeta T-cell
receptor monoclonal antibody and cyclosporine A protocol.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec 27;76(12):1662-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000105343.49626.6F
AUTORES
/ AUTHORS: - Siemionow MZ; Izycki DM; Zielinski M
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery, Cleveland
Clinic Foundation, A60, 9500 Euclid Avenue, Cleveland, OH 44195, USA. siemiom@ccf.org
RESUMEN
/ SUMMARY: - BACKGROUND: Recent studies have
demonstrated that treatment with alphabeta-T-cell receptor (TCR) monoclonal
antibody and cyclosporine A (CsA) can extend survival in composite tissue
allografts (CTA). The purpose of this study was to induce tolerance in fully
major histocompatibility complex (MHC)-mismatched rat limb allografts under 7 days
of a combined alphabeta-TCR-CsA protocol. METHODS: The authors performed 30
hind-limb allotransplantations across the MHC barrier between Brown Norway
donors (BN; RT1n) and Lewis recipients (LEW; RT1l). Isograft and allograft
controls received no treatment. The experimental groups received monotherapy of
alphabeta-TCR and CsA or a combination of alphabeta-TCR and CsA for 7 days
only. Donor-specific tolerance and immunocompetence were determined by standard
skin grafting in vivo and mixed lymphocyte reaction (MLR) in vitro. The
efficacy of immunosuppressive therapy and the level of donor-specific chimerism
were determined by flow cytometry. RESULTS: Long-term survival (>350 days)
was achieved in allograft recipients (n=6) under the 7-day protocol of combined
alphabeta-TCR-CsA. Donor-specific tolerance and immunocompetence of long-term
chimeras were confirmed by acceptance of skin grafts from the donors and
rejection of the third-party alloantigens (AxC Irish). At day 120, MLR
demonstrated unresponsiveness to the host and donor antigens but strong
reactivity against third-party alloantigens. Flow cytometry confirmed the high
efficacy of immunosuppressive treatment and the development of donor-specific
chimerism (7.6% of CD4+-RT1n+ cells, 1.3% of CD8+-RT1n+ cells, and 16.5% of
CD45RA+-RT1n+ cells) in the periphery of tolerated recipients. CONCLUSIONS:
Combined therapy of alphabeta-TCR-CsA for 7 days resulted in tolerance
induction in fully MHC-mismatched rat hind-limb allografts. Tolerance was
directly associated with stable, donor-specific chimerism.
----------------------------------------------------
[111]
TÍTULO / TITLE: - Perioperative
single-dose glucocorticoid administration: pathophysiologic effects and
clinical implications.
REVISTA
/ JOURNAL: - J Am Coll Surg 2002 Nov;195(5):694-712.
AUTORES
/ AUTHORS: - Holte K; Kehlet H
INSTITUCIÓN
/ INSTITUTION: - Department of Surgical Gastroenterology,
Hvidovre University Hospital, Denmark. N.
Ref:: 138
----------------------------------------------------
[112]
TÍTULO / TITLE: - The genetics of
autoimmune endocrine disease.
REVISTA
/ JOURNAL: - Clin Endocrinol (Oxf) 2003 Jul;59(1):1-11.
AUTORES
/ AUTHORS: - Tait KF; Gough SC
INSTITUCIÓN
/ INSTITUTION: - Division of Medical Sciences, University
of Birmingham, Edgbaston and Birmingham Heartlands Hospital, Bordesley Green
East, Birmingham, UK.
RESUMEN
/ SUMMARY: - The common autoimmune endocrinopathies
result from an interaction between environmental factors and genetic
predisposition. Several chromosomal gene regions have been shown to contribute
to more than one disease, supporting the clinical observation that the
autoimmune endocrine diseases cluster within individuals and families. Genetic
studies have implicated the major histocompatability complex (MHC)-human
leucocyte antigen (HLA) genes on chromosome 6p21, although this chromosomal
region does not explain all of the genetic contribution to the various
disorders. Non-MHC-HLA genes, including disease-specific loci, are beginning to
be identified and the publication of the draft sequence of the human genome
will undoubtedly expediate future discoveries. Combined with the establishment
of large cohorts of subjects with disease and the development of technology
capable of performing high-throughput genotyping, genetic studies are likely to
impact on the future treatment and prevention of the common autoimmune
endocrine diseases. N.
Ref:: 107
----------------------------------------------------
[113]
TÍTULO / TITLE: - Liposomal amphotericin
B in the treatment of visceral leishmaniasis in immunocompetent patients.
REVISTA
/ JOURNAL: - Fundam Clin Pharmacol 2003
Apr;17(2):183-8.
AUTORES
/ AUTHORS: - Minodier P; Retornaz K; Horelt A; Garnier
JM
INSTITUCIÓN
/ INSTITUTION: - Pediatric Emergency Unit, CHU Nord, Chemin
des Bourrelly, 13915 Marseille Cedex 20, France. philippe.minodier@ap-hm.fr
RESUMEN
/ SUMMARY: - The leishmaniases are protozoan diseases
caused by Leishmania parasites. The first-line treatment of its visceral forms
is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but
toxicity is frequent with this drug. Moreover antimony unresponsiveness is
increasing in Leishmania infantum and L. donovani foci, both in immunocompetent
and in immunosuppressed patients. Amphotericin B is a polyene macrolide
antibiotic that binds to sterols in cell membranes. It is the most active
antileishmanial agent in use. Its infusion-related and renal toxicity may be
reduced by lipid-based delivery. Liposomal amphotericin B (AmBisome); Gilead
Science, Paris, France) seems to be less toxic than other amphotericin B lipid
formulations (Amphocil); Liposome Technology Inc., Menlo Park, CA, USA,
Amphotec); Ben Venue Laboratories Inc., Bedford, OH, USA). Optimal drug
regimens of AmBisome) vary from one geographical area to another. In the
Mediterranean Basin, a total dose of 18 mg/kg (3 mg/kg on days 1-5 and 3 mg/kg
on day 10) could be used as first-line treatment of visceral leishmaniasis in
immunocompetent patients. In immunocompromised patients, especially those
co-infected with HIV, relapses are frequent with AmBisome), as with other
drugs. N. Ref:: 55
----------------------------------------------------
[114]
TÍTULO / TITLE: - Hepatosplenic
gamma/delta T-cell lymphoma in immunocompromised patients. Report of two cases
and review of literature.
REVISTA
/ JOURNAL: - Am J Clin Pathol 2001 Jul;116(1):41-50.
AUTORES
/ AUTHORS: - Khan WA; Yu L; Eisenbrey AB; Crisan D; al
Saadi A; Davis BH; Hankin RC; Mattson JC
INSTITUCIÓN
/ INSTITUTION: - Clinical Pathology Department, William
Beaumont Hospital, 3601 W 13 Mile Rd, Royal Oak, MI 48073, USA.
RESUMEN
/ SUMMARY: - We describe 2 male patients in whom
hepatosplenic gamma/delta T-cell lymphoma (HSTL) developed 6 and 10 years after
renal transplantation. The onset was abrupt with systemic symptoms, cytopenia,
and hepatosplenomegaly. The histologic examination of the spleen (case 1),
liver, and bone marrow revealed sinusoidal infiltrates of markedly abnormal
lymphocytes. The neoplastic cells in these cases were CD2+, CD3+, CD4-, CD5-,
CD7+, CD8+, CD16+, CD56+, beta F1-negative, and TIA-1-negative. Both cases
displayed clonal rearrangement of the T-cell receptor (TCR) delta gene and the
TCR beta gene. The spleen in case 1 was positive for Epstein-Barr virus genome
and showed TCR-gamma gene rearrangement by polymerase chain reaction.
Isochromosome 7 [i(7)(q10)] was found in each case. Both patients died within 4
months of diagnosis. HSTL has been reported in only 5 renal transplant
recipients. HSTL may be relatively more frequent in immunocompromised patients
compared with the general population. N.
Ref:: 35
----------------------------------------------------
[115]
TÍTULO / TITLE: - Human
plasmacytoid-derived dendritic cells and the induction of T-regulatory cells.
REVISTA
/ JOURNAL: - Hum Immunol 2002 Dec;63(12):1149-55.
AUTORES
/ AUTHORS: - Gilliet M; Liu YJ
INSTITUCIÓN
/ INSTITUTION: - DNAX Research Institute, Palo Alto,
California, USA. m.gilliet@usz.ch
RESUMEN
/ SUMMARY: - Suppression by T-regulatory (Tr) cells is
essential for the induction of T-cell tolerance and the prevention of
autoimmune diseases, organ rejection, and graft-versus-host disease. Increasing
attention has been devoted to understand the role of dendritic cells (DC) in
the control of Tr-cell differentiation. Here we review the recent evidence that
cluster designation (CD)40-ligand activated plasmacytoid-derived DCs (DC2) have
the ability to induce primary Tr-cell differentiation. We propose that in
addition to the regulatory functions of immature myeloid DC, Tr-cell induction
by DC2 represents a nonredundant mechanism for the safeguard of peripheral
T-cell tolerance. DC2 can be used as tool to drive potent antigen specific
Tr-cell differentiation and expansion in vitro and in vivo. N. Ref:: 51
----------------------------------------------------
[116]
TÍTULO / TITLE: - HFE, the MHC and
hemochromatosis: paradigm for an extended function for MHC class I.
REVISTA
/ JOURNAL: - Tissue Antigens 2003 Apr;61(4):263-75.
AUTORES
/ AUTHORS: - Cardoso CS; de Sousa M
INSTITUCIÓN
/ INSTITUTION: - Molecular Immunology, Institute for
Molecular and Cell Biology, Oporto, Portugal Molecular Pathology and
Immunology, Instituto de Ciencias Biomedicas Abel Salazar, OPorto, Portugal.
RESUMEN
/ SUMMARY: - HFE was discovered as the hereditary
hemochromatosis (HH) gene. It is located on chromosome 6 (6p21.3), 4Mb
telomeric to the HLA-A locus, and its product has a structure similar to MHC
class I molecules. HFE encodes two frequent mutations: C282Y and H63D. One of
these (C282Y) is present in a large proportion of Caucasian HH patients. HFE
has a tissue distribution compatible with a role in iron absorption
(intestine), recycling (macrophages) and transport to the fetus
(placenta). N. Ref:: 97
----------------------------------------------------
[117]
TÍTULO / TITLE: - Cytokine-based
immunointervention in the treatment of autoimmune diseases.
REVISTA
/ JOURNAL: - Clin Exp Immunol 2003 May;132(2):185-92.
AUTORES
/ AUTHORS: - Adorini L
INSTITUCIÓN
/ INSTITUTION: - BioXell, Via Olgettina 58, 20132 Milan,
Italy. luciano.adorini@bioxell.com N. Ref:: 99
----------------------------------------------------
[118]
TÍTULO / TITLE: - Dimerizer-regulated
gene expression.
REVISTA
/ JOURNAL: - Curr Opin Biotechnol 2002
Oct;13(5):459-67.
AUTORES
/ AUTHORS: - Pollock R; Clackson T
INSTITUCIÓN
/ INSTITUTION: - ARIAD Gene Therapeutics, 26 Landsdowne
Street, Cambridge, MA 02139, USA. roy.pollock@ariad.com
RESUMEN
/ SUMMARY: - Control of gene expression using small
molecules is a powerful research tool and has clinical utility in the context
of regulated gene therapy. Use of chemical inducers of dimerization, or
dimerizers, for this purpose has several advantages, including tight
regulation, modularity to facilitate iterative improvements, and assembly from
human proteins to minimize immune responses in clinical applications. Recent
developments include the use of the rapamycin-based dimerizer system to
regulate the expression of endogenous genes, the generation of new chemical
dimerizers based on FK506, dexamethasone and methotrexate, and progress towards
the clinical use of adeno-associated virus and adenovirus vectors regulated by
rapamycin analogs. N.
Ref:: 40
----------------------------------------------------
[119]
TÍTULO / TITLE: - DNA methylation and
expression of major histocompatibility complex class I and class II
transactivator genes in human developmental tumor cells and in T cell
malignancies.
REVISTA
/ JOURNAL: - Clin Immunol 2003 Oct;109(1):46-52.
AUTORES
/ AUTHORS: - van den Elsen PJ; Holling TM; van der
Stoep N; Boss JM
INSTITUCIÓN
/ INSTITUTION: - Division of Molecular Biology, Department
of Immunohematology and Blood Transfusion, Leiden University Medical Center,
Leiden, The Netherlands. pjvdelsen@lumc.nl
RESUMEN
/ SUMMARY: - Major histocompatibility complex (MHC)
class I and class II molecules play essential roles in the immune response by
virtue of their ability to present peptides to T lymphocytes. Given their
central role in adaptive immunity, the genes encoding these peptide-presenting
molecules are regulated in a tight fashion to meet with local requirements for
an adequate immune response. In contrast to MHC class I gene products, which
are expressed on almost all nucleated cells, constitutive expression of MHC
class II molecules is found in specialized antigen presenting cells of the
immune system only. Transcription of both MHC class I and class II genes can be
induced by immune regulators and upon cell activation. Transcription of MHC
class I genes is mediated by a set of conserved cis acting regulatory elements
in their promoters. Of these regulatory elements, MHC class II promoters share
the SXY-module. Essential for activation of MHC class II promoters is the class
II transactivator (CIITA), which acts through protein/protein interactions with
regulatory factors bound to the SXY module. In this review, we discuss the role
of DNA methylation in relation to altered expression of MHC class I and CIITA
genes as observed in malignancies and in development. N. Ref:: 68
----------------------------------------------------
[120]
TÍTULO / TITLE: - Alicaforsen. Isis
Pharmaceuticals.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2001
Oct;2(10):1401-6.
AUTORES
/ AUTHORS: - Gewirtz AT; Sitaraman S
INSTITUCIÓN
/ INSTITUTION: - Emory University School of Medicine,
Department of Pathology and Laboratory Medicine, Atlanta, GA 30322, USA. agewirt@emory.edu
RESUMEN
/ SUMMARY: - Alicaforsen (ISIS-2302) is an RNase
H-dependent antisense inhibitor of the intercellular adhesion molecule ICAM-1
under development by Isis Pharmaceuticals, for the potential treatment of a
variety of inflammatory disorders [175741]. As of April 1997 it was in phase
III trials for Crohn’s disease (CD); however, the trial failed and, in December
1999, the company suspended development for this indication [352801]. In
October 2000, the company re-initiated development in CD [384820] and new phase
III trials had begin by May 2001 [409704]. In August 2000, phase II studies of
alicaforsen in an enema formulation for ulcerative colitis and a topical
formulation for psoriasis were ongoing [378715]. Development of the compound
for the potential treatment of rheumatoid arthritis (RA) was discontinued in
1999 [347579]. By the end of 1998, alicaforsen was in phase II trials for
kidney transplant rejection. At this time, these trials were expected to finish
in mid-1999 [343460]. However, they were ongoing in September 1999, although no
further development has been reported for this indication since that time
[338672]. In February 1995, Isis Pharmaceuticals and Boehringer Ingelheim (BI)
signed a collaborative agreement on cell adhesion inhibitors, including
alicaforsen [174111]. By early 1999, Isis and BI were to decide on the next developmental
step for alicaforsen following further analyses of its performance against CD
[292915], [315439]. Their joint development agreement was terminated in 1999;
Isis regained rights to the product and by September 1999 was in talks to
license alicaforsen to another partner for CD [338672]. In June 2000, Cytogenix
entered into a sponsored research agreement with Baylor College of Medicine at
the Texas Medical Center Houston for the use of its ssDNA expression system for
the development of antisense strategies directed against intercellular adhesion
molecules for the purpose of reducing lung inflammation and injury in disease
states and conditions [369677]. US-05514788, and other patents, cover antisense
cell adhesion molecule inhibitors [212289], [234792]. N. Ref:: 45
----------------------------------------------------
[121]
TÍTULO / TITLE: - Accessory proteins that
control the assembly of MHC molecules with peptides.
REVISTA
/ JOURNAL: - Immunol Res 2001;23(2-3):205-14.
AUTORES
/ AUTHORS: - Van Kaer L
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology and Immunology,
Vanderbilt University School of Medicine, Nashville, TN 37232-0295, USA. luc.vankaer@mcmail.vanderbilt.edu
RESUMEN
/ SUMMARY: - The stable assembly of Major
Histocompatibility Complex (MHC) molecules with peptides is controlled by a
number of cofactors, including proteins with general housekeeping functions and
proteins with dedicated functions in MHC assembly. Recent work in my laboratory
has focused on two chaperones, tapasin (tpn) and DM, that play critical roles
in the loading of peptides onto MHC class I and MHC class II molecules,
respectively. Tapasin is a transmembrane protein that tethers empty class I
molecules in the endoplasmic reticulum to the transporter associated with
antigen processing. DM is a peptide exchange factor that binds with empty and
peptide-loaded class II molecules in endosomal and lysosomal compartments.
Although a number of different functions for tapasin and DM have been proposed,
emerging evidence suggests that both of these chaperones retain unstable MHC
molecules in peptide-loading compartments until they bind with high-affinity
peptides. These cofactors therefore promote the surface expression of
long-lived MHC-peptide complexes. N.
Ref:: 39
----------------------------------------------------
[122]
TÍTULO / TITLE: - The fission yeast TOR
proteins and the rapamycin response: an unexpected tale.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:85-95.
AUTORES
/ AUTHORS: - Weisman R
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Microbiology and
Biotechnology, Faculty of Life Sciences, Tel-Aviv University, 69978 Tel-Aviv,
Israel. ronitt@post.tau.ac.il
RESUMEN
/ SUMMARY: - The TOR proteins are known as key
regulators of cell growth in response to nutritional and mitogenic signals and
as targets for the immunosuppressive and anti-cancerous drug rapamycin. The
fission yeast Schizosaccharomyces pombe has two TOR homologues, tor1+ and
tor2+. Despite their structural similarity, these genes have distinct
functions: tor1+ is required under starvation, extreme temperatures, and
osmotic or oxidative stress conditions, whereas tor2+ is required under normal
growth conditions. Surprisingly, rapamycin does not seem to inhibit the S.
pombe TOR-related functions. Rapamycin specifically inhibits sexual development
in S. pombe, and this seems to stem from direct inhibition of the S. pombe
FKBP12 homologue. Why S. pombe cells are resistant to rapamycin during the
growth phase is as yet unclear and awaits further analysis of the TOR-dependent
signaling pathways. N.
Ref:: 27
----------------------------------------------------
[123]
TÍTULO / TITLE: - Current treatments for
CIDP.
REVISTA
/ JOURNAL: - Neurology 2003 Apr 1;60(8 Suppl 3):S16-22.
AUTORES
/ AUTHORS: - Ropper AH
INSTITUCIÓN
/ INSTITUTION: - Saint Elizabeth’s Medical Center/Tufts
University School of Medicine, Boston, MA, USA. Allan_Ropper_MD@cchcs.org
RESUMEN
/ SUMMARY: - This article reviews the efficacy and
tolerability of currently available therapies, including intravenous
immunoglobulin (IVIg), corticosteroids, and plasma exchange (PE), for treatment
of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Data show
that current therapies are effective in approximately two-thirds of patients.
However, they fail to provide a durable clinical response. Furthermore, current
treatments have several limitations that make them problematic for long-term
therapy. IVIg dosing is required approximately every 2 to 8 weeks in most
patients to maintain improvement. It is expensive, time-consuming to
administer, and availability can be a problem. Furthermore, IVIg is a blood
product that is associated with rare thromboembolic events. Corticosteroids
have poor safety and tolerability profiles, and PE is invasive, time-consuming,
expensive, and can be performed only at specialized centers. An alternative to
single-agent therapy with current treatments is the use of combination therapy.
Combination therapy may increase the duration of response, provide increased
efficacy or independent efficacy in unresponsive patients, and reduce the need
for standard therapies. Research is needed to find agents suitable for single
and combination therapy in CIDP. N.
Ref:: 50
----------------------------------------------------
[124]
TÍTULO / TITLE: - Immunologic and genetic
factors in type 1 diabetes.
REVISTA
/ JOURNAL: - J Biol Chem. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jbc.org/
●●
Cita: J. of Biological Chemistry: <> 2002 Nov 15;277(46):43545-8. Epub
2002 Sep 20.
●●
Enlace al texto completo (gratuito o de pago) 1074/jbc.R200012200
AUTORES
/ AUTHORS: - Notkins AL
INSTITUCIÓN
/ INSTITUTION: - Experimental Medicine Section, Oral
Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda,
Maryland 20892-4322, USA. anotkins@mail.nih.gov N. Ref:: 28
----------------------------------------------------
[125]
TÍTULO / TITLE: - Hematopoietic cell
transplantation for inherited metabolic diseases: an overview of outcomes and
practice guidelines.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2003
Feb;31(4):229-39.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703839
AUTORES
/ AUTHORS: - Peters C; Steward CG
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, University of
Minnesota School of Medicine, Minneapolis, 55455, USA.
RESUMEN
/ SUMMARY: - For the past two decades, hematopoietic
cell transplantation (HCT) has been used as effective therapy for selected
inherited metabolic diseases (IMD) including Hurler (MPS IH) and Maroteaux-Lamy
(MPS VI) syndromes, childhood-onset cerebral X-linked adrenoleukodystrophy
(X-ALD), globoid-cell leukodystrophy (GLD), metachromatic leukodystrophy (MLD),
alpha-mannosidosis, osteopetrosis, and others. Careful pre-HCT evaluation is
critical and coordinated, multidisciplinary follow-up is essential in this
field of transplantation. The primary goals of HCT for these disorders have
been to promote long-term survival with donor-derived engraftment and to
optimize the quality of life. Guidelines for HCT and monitoring are provided; a
brief overview of long-term results is also presented. N. Ref:: 131
----------------------------------------------------
[126]
TÍTULO / TITLE: - Composite tissue
allotransplantation in chimeric hosts part II. A clinically relevant protocol
to induce tolerance in a rat model.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec
15;76(11):1548-55.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000085288.12571.65
AUTORES
/ AUTHORS: - Prabhune KA; Gorantla VS; Perez-Abadia G;
Francois CG; Vossen M; Laurentin-Perez LA; Breidenbach WC; Wang GG; Anderson
GL; Pidwell DJ; Barker JH; Maldonado C
INSTITUCIÓN
/ INSTITUTION: - Division of Plastic and Reconstructive
Surgery, University of Louisville, Louisville, Kentucky, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: We and others have shown that
mixed allogeneic chimerism induces donor-specific tolerance to composite tissue
allografts across major histocompatibility complex barriers without the need
for immunosuppression. However, a delay period between bone marrow
transplantation and limb allotransplantation is required, making such protocols
impractical for clinical application. This study eliminates this delay period in
a rat hind limb allotransplantation model by performing mixed allogeneic
chimerism induction and transplantation “simultaneously.” METHODS: Group 1
included controls in which naive Wistar Furth (WF) hosts received ACI hind
limbs. Group 2 included (ACI-->WF) chimeras that received limbs from
third-party donors (Fisher), and group 3 included chimeras that received
irradiated (1,050 cGy) ACI limbs. In group 4, WF hosts conditioned with 950 cGy
received irradiated (1,050 cGy) ACI limbs followed by infusion of 100 x 10(6)
ACI T-cell-depleted bone marrow cells and immunotherapy (tacrolimus and
mycophenolate mofetil) for 28 days. Group 5 animals received the same treatment
as group 4 animals without immunotherapy. RESULTS: The rats in groups 1 and 2
rejected their limbs within 10 days. Only one rat in group 4 survived to the
end of the study. Groups 3 and 5 demonstrated long-term limb survival without
rejection or graft-versus-host disease. High levels of donor chimerism
(>80%) were achieved and maintained throughout the study. Mixed lymphocyte
reaction assays in both groups revealed donor-specific hyporesponsiveness with
vigorous third-party reactivity. CONCLUSIONS: This study demonstrated that
infusion of donor bone marrow cells into conditioned hosts immediately after
limb transplantation results in stable mixed chimerism, robust tolerance, and
reliable limb allograft survival.
----------------------------------------------------
[127]
TÍTULO / TITLE: - Clinical outcomes and
insulin secretion after islet transplantation with the Edmonton protocol.
REVISTA
/ JOURNAL: - Diabetes. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://diabetes.diabetesjournals.org/
●●
Cita: Diabetes: <> 2001 Apr;50(4):710-9.
AUTORES
/ AUTHORS: - Ryan EA; Lakey JR; Rajotte RV; Korbutt GS;
Kin T; Imes S; Rabinovitch A; Elliott JF; Bigam D; Kneteman NM; Warnock GL;
Larsen I; Shapiro AM
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Surgical Medical
Research Institute, University of Alberta, Edmonton, Canada. edmond.ryan@ualberta.ca
RESUMEN
/ SUMMARY: - Islet transplantation offers the prospect
of good glycemic control without major surgical risks. After our initial report
of successful islet transplantation, we now provide further data on 12 type 1
diabetic patients with brittle diabetes or problems with hypoglycemia previous
to 1 November 2000. Details of metabolic control, acute complications
associated with islet transplantation, and long-term complications related to
immunosuppression therapy and diabetes were noted. Insulin secretion, both
acute and over 30 min, was determined after intravenous glucose tolerance tests
(IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest
was 20 months. Glucose control was stable, with pretransplant fasting and meal
tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l,
respectively, but decreased significantly, with posttransplant levels of
6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have
sustained insulin production, as evidenced by the most current baseline
C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min
after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5%
to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients
have normal glucose tolerance, five have impaired glucose tolerance, and three
have post-islet transplant diabetes (two of whom need oral hypoglycemic agents
and low-dose insulin (<10 U/day). Three patients had a temporary increase in
their liver-function tests. One patient had a thrombosis of a peripheral branch
of the right portal vein, and two of the early patients had bleeding from the
hepatic needle puncture site; but these technical problems were resolved. Two
patients had transient vitreous hemorrhages. The two patients with elevated
creatinine levels pretransplant had a significant increase in serum creatinine
in the long term, although the mean serum creatinine of the group was
unchanged. The cholesterol increased in five patients, and lipid-lowering
therapy was required for three patients. No patient has developed
cytomegalovirus infection or disease, posttransplant lymphoproliferative
disorder, malignancies, or serious infection to date. None of the patients have
been sensitized to donor antigen. In 11 of the 12 patients, insulin
independence was achieved after 9,000 islet equivalents (IEs) per kilogram were
transplanted. The acute insulin response and the insulin area under the curve
(AUC) after IVGTT were consistently maintained over time. The insulin AUC from
the IVGTT correlated to the number of islets transplanted, but more closely
correlated when the cold ischemia time was taken into consideration (r = 0.83,
P < 0.001). Islet transplantation has successfully corrected labile type 1
diabetes and problems with hypoglycemia, and our results show persistent
insulin secretion. After a minimum of 9,000 IEs per kilogram are provided,
insulin independence is usually attained. An elevation of creatinine appears to
be a contraindication to this immunosuppressive regimen. For the subjects who
had labile type 1 diabetes that was difficult to control, the risk-to-benefit
ratio is in favor of islet transplantation.
----------------------------------------------------
[128]
- Castellano -
TÍTULO / TITLE:Terapia individualizada con
azatioprina o 6-mercaptopurina mediante monitorizacion de la actividad de la
tiopurina metiltransferasa (TPMT). Individualized therapy with azathioprine or
6-mercaptopurine by monitoring thiopurine methyl-transferase (TPMT) activity.
REVISTA
/ JOURNAL: - Rev Clin Esp. Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Revista Clínica Española: <> 2002 Oct;202(10):555-62.
AUTORES
/ AUTHORS: - Gisbert JP; Gomollon F; Mate J; Pajares JM
INSTITUCIÓN
/ INSTITUTION: - Servicio de Aparato Digestivo. Hospital
Universitario de La Princesa. Madrid. España. gisbert@meditex.es N. Ref:: 83
----------------------------------------------------
[129]
TÍTULO / TITLE: - Metabolic and autocrine
regulation of the mammalian target of rapamycin by pancreatic beta-cells.
REVISTA
/ JOURNAL: - Diabetes. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://diabetes.diabetesjournals.org/
●●
Cita: Diabetes: <> 2002 Oct;51(10):2877-85.
AUTORES
/ AUTHORS: - McDaniel ML; Marshall CA; Pappan KL; Kwon
G
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology and Immunology,
Washington University School of Medicine, St. Louis, Missouri 63110, USA. mcdaniel@pathology.wustl.edu
RESUMEN
/ SUMMARY: - Mammalian target of rapamycin (mTOR) is a
serine and threonine protein kinase that regulates numerous cellular functions,
in particular, the initiation of protein translation. mTOR-mediated
phosphorylation of both the translational repressor eukaryotic initiation
factor 4E binding protein-1 and p70 S6 kinase are early events that control the
translation initiation process. Rapamycin, an inhibitor of mTOR, is a potent
immunosuppressant due, in part, to its ability to interfere with T-cell
activation at the level of translation, and it has gained a prominent role in
preventing the development and progression of rejection in pancreatic islet
transplant recipients. The characterization of the insulin signaling cascade
that modulates mTOR in insulin-sensitive tissues has been a major focus of
investigation. Recently, the ability of nutrients, in particular the
branched-chain amino acid leucine, to activate mTOR independent of insulin by a
process designated as nutrient signaling has been identified. The beta-cell
expresses components of the insulin signaling cascade and utilizes the
metabolism of nutrients to affect insulin secretion. These combined
transduction processes make the beta-cell an unique cell to study metabolic and
autocrine regulation of mTOR signaling. Our studies have described the ability
of insulin and IGFs in concert with the nutrients leucine, glutamine, and
glucose to modulate protein translation through mTOR in beta-cells. These
findings suggest that mitochondria-derived factors, ATP in particular, may be
responsible for nutrient signaling. The significance of these findings is that
the optimization of mitochondrial function is not only important for insulin
secretion but may significantly impact the growth and proliferation of
beta-cells through these mTOR signaling pathways. N. Ref:: 51
----------------------------------------------------
[130]
TÍTULO / TITLE: - The Tubingen approach:
identification, selection, and validation of tumor-associated HLA peptides for
cancer therapy.
REVISTA
/ JOURNAL: - Cancer Immunol Immunother 2004
Mar;53(3):187-95. Epub 2004 Jan 31.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00262-003-0480-x
AUTORES
/ AUTHORS: - Singh-Jasuja H; Emmerich NP; Rammensee HG
INSTITUCIÓN
/ INSTITUTION: - Department of Immunology, Institute for
Cell Biology, University of Tubingen, Auf der Morgenstelle 15, 72076, Tubingen,
Germany.
RESUMEN
/ SUMMARY: - There is substantial need for molecularly
defined tumor antigens to prime cytotoxic T cells in vivo for cancer
immunotherapy, especially in the case of tumor entities for which only a few
tumor antigens have been defined so far. In this review, we present the
“Tubingen approach” to identify, select, and validate large numbers of MHC/HLA
class I-associated peptides derived from tumor-associated antigens. Step 1 is
the identification of naturally presented HLA-associated peptides directly from
primary tumor cells. Step 2 is selection of tumor-associated peptides from step
1 by differential gene expression analysis and data mining. Step 3 is
validation of selected candidates by monitoring in vivo T-cell responses in the
context of patient-individualized immunizations. Our approach combines methods
from genomics, proteomics, bioinformatics, and T-cell immunology. The aim is to
develop effective immunotherapeutics consisting of multiple tumor-associated
epitopes in order to induce a broad and specific immune response against cancer
cells. N. Ref:: 67
----------------------------------------------------
[131]
TÍTULO / TITLE: - Peptide register
shifting within the MHC groove: theory becomes reality.
REVISTA
/ JOURNAL: - Mol Immunol 2004 Feb;40(14-15):1033-9.
●●
Enlace al texto completo (gratuito o de pago) 1016/j.molimm.2003.11.016
AUTORES
/ AUTHORS: - Bankovich AJ; Girvin AT; Moesta AK; Garcia
KC
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology &
Immunology, Stanford University School of Medicine, Fairchild D319, Stanford,
CA 94305-5124, USA.
RESUMEN
/ SUMMARY: - Degeneracy in immune recognition is
usually thought of in terms of the astonishing ability of the T cell receptor
to recognize an enormously diverse array of peptides bound to major
histocompatibility complex (MHC) molecules. However, in this essay we discuss
an alternative aspect of degeneracy in T cell recognition: the notion that
peptides can assume different “registers” in the groove of a single MHC
molecule, as first suggested and demonstrated by Sercarz and co-workers
(reviewed in [J. autoimmun. 16 (2001) 201]). There is now abundant evidence,
derived from functional, biochemical and structural studies, that single peptides
can assume alternative, unpredictable binding registers by frameshifting within
the MHC groove [Nat. Immunol. 3 (2002) 175;; J. Exp. Med. 187 (1998) 1505; J.
Mol. Biol. 304 (2000) 177; Biochemistry 38 (1999) 16663; J. Exp. Med. 197
(2003) 1391; Eur. J. Immunol. 19 (1989) 681]. Hence, register shifting adds an
additional dimension to the concept of degeneracy. In fact, the possibility of
register shifting multiplies the universe of peptide-MHC (pMHC) surfaces that a
TCR must recognize by an unknown, perhaps enormous factor. Register shifting
also has profound implication for autoimmunity: (1) as a mechanism to “mask”
autoantigenic epitopes during thymic education [Immunol. Rev. 169 (1999) 147;
Immunity 17 (2002) 83]; and (2) as a possible source for pMHC complexes capable
of molecular mimicry. N.
Ref:: 45
----------------------------------------------------
[132]
TÍTULO / TITLE: - mTOR as a positive
regulator of tumor cell responses to hypoxia.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:299-319.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - Rapamycin is a clinically approved
immunosuppressive agent that has recently shown promising antitumor activities
in human patients. In contrast to many conventional chemotherapeutic agents,
rapamycin displays a remarkably high level of selectivity for certain types of
tumors. The pharmacological activities of rapamycin are attributable to the
functional inhibition of a single target protein, termed the mammalian target
of rapamycin (mTOR). Because mTOR is widely expressed in both normal and
transformed cells, variations in mTOR expression levels are likely not a
primary determinant of tumor sensitivity to rapamycin. However, recent studies
highlighted an intriguing link between cancer cell sensitivity to rapamycin and
deregulated signaling through the phosphoinositide (PI) 3-kinase pathway. These
findings have prompted a search for cancer-related responses that are jointly
regulated by the PI 3-kinase signaling cascade and mTOR. The oxygen-regulated
transcription factor, hypoxia-induced factor (HIF)-1, has emerged as a
candidate target for both of these two highly interactive signaling proteins.
Here we review evidence that mTOR functions as a positive regulator of
HIF-1-dependent responses to hypoxic stress in human cancer cells. N. Ref:: 71
----------------------------------------------------
[133]
TÍTULO / TITLE: - TGF-beta expression in
protocol transplant liver biopsies: a comparative study between cyclosporine-A
(CyA) and tacrolimus (FK 506) immunosuppression.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):1378-80.
AUTORES
/ AUTHORS: - Mohamed MA; Burt AD; Robertson H; Kirby
JA; Talbot D
INSTITUCIÓN
/ INSTITUTION: - Transplant Immunobiology Group, Department
of Surgery, University of Newcastle, NE2 4HH, Newcastle Upon Tyne, UK.
----------------------------------------------------
[134]
TÍTULO / TITLE: - HLA class II tetramers:
tools for direct analysis of antigen-specific CD4+ T cells.
REVISTA
/ JOURNAL: - Arthritis Rheum 2002 Jan;46(1):5-12.
AUTORES
/ AUTHORS: - Nepom GT; Buckner JH; Novak EJ;
Reichstetter S; Reijonen H; Gebe J; Wang R; Swanson E; Kwok WW
INSTITUCIÓN
/ INSTITUTION: - Virginia Mason Research Center and
University of Washington School of Medicine, Seattle 98101-2795, USA. nepom@vmresearch.org
RESUMEN
/ SUMMARY: - Immunotherapies for human autoimmune and
immune-mediated diseases are proliferating rapidly, and with these changes
comes the opportunity to monitor patients for immune responses to therapy based
on early surrogate markers for clinical responses. Class II tetramers have the
potential to serve as these sorts of markers for immune monitoring, and thereby
assist with patient management, therapy selection, and improved outcomes.
However, important issues of TCR avidity require resolution, because much is
still unknown regarding location, quantitation, and characterization of the
human T cell response. Opportunities for application of tetramer technologies
in the near future will enable both clinical progress and the development of
new insights into human CD4+ T cell biology in vivo. N. Ref:: 39
----------------------------------------------------
[135]
TÍTULO / TITLE: - Alternative concepts of
suicide gene therapy for graft-versus-host disease after adoptive
immunotherapy.
REVISTA
/ JOURNAL: - Acta Haematol 2003;110(2-3):132-8.
●●
Enlace al texto completo (gratuito o de pago) 1159/000072462
AUTORES
/ AUTHORS: - Kramm CM
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatric Hematology,
Oncology, and Immunology, University Hospital Dusseldorf, Dusseldorf, Germany. kramm@uni-duesseldorf.de
RESUMEN
/ SUMMARY: - T-cell suicide gene therapy represents a
promising novel treatment strategy for graft-versus-host disease following
adoptive immunotherapy after allogeneic hematopoietic stem cell
transplantation. The clinical efficiency of this approach is still hampered by
several obstacles including induction of alloresponses due to the use of
immunogenic suicide and selection genes, genetic inactivation of suicide genes,
and functional immunological impairment after retroviral transduction with
extensive in vitro stimulation. New concepts as possible solutions to these
limitations are discussed. N.
Ref:: 36
----------------------------------------------------
[136]
TÍTULO / TITLE: - Not such a dismal
science: the economics of protein synthesis, folding, degradation and antigen
processing.
REVISTA
/ JOURNAL: - Trends Cell Biol 2001 Jul;11(7):294-7.
AUTORES
/ AUTHORS: - Yewdell JW
INSTITUCIÓN
/ INSTITUTION: - Cellular Biology Section, Laboratory of
Viral Diseases, National Institute of Allergy and Infectious Disease,
20892-0440, Bethesda, MD, USA. jyewdell@nih.gov
RESUMEN
/ SUMMARY: - There is a pronounced tendency among cell
biologists to focus on qualitative aspects of cell physiology. The remarkable
accomplishments of evolution in creating cells can only be fully appreciated,
however, by combining this qualitative analysis with a quantitative assessment
of cellular constituents and processes. Here, I consider the overall protein
economy of cells as it relates to recent advances in understanding protein
folding, ubiquitin-targeted proteasome-mediated degradation of proteins and the
generation of peptide ligands for major histocompatibility complex (MHC) class
I molecules. N.
Ref:: 29
----------------------------------------------------
[137]
TÍTULO / TITLE: - MHC class II
deficiency: a disease of gene regulation.
REVISTA
/ JOURNAL: - Medicine (Baltimore) 2001
Nov;80(6):405-18.
AUTORES
/ AUTHORS: - Villard J; Masternak K;
Lisowska-Grospierre B; Fischer A; Reith W
INSTITUCIÓN
/ INSTITUTION: - Immunology and Transplant Unit, Division
of Immunology and Allergology, Geneva University Hospital, Geneva, Switzerland.
Jean.Villard@hcuge.ch N. Ref:: 115
----------------------------------------------------
[138]
TÍTULO / TITLE: - Dendritic cells and
second signal blockade: a step toward allograft tolerance?
REVISTA
/ JOURNAL: - Transplantation 2002 Jan 15;73(1
Suppl):S1-2.
AUTORES
/ AUTHORS: - Rifle G; Mousson C
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology-Intensive
Care-Transplantation and UPRES EA563, Faculty of Medicine, University of
Bourgogne, Dijon, France. gerard.rifle@chu-dijon.fr
RESUMEN
/ SUMMARY: - The ultimate goal of clinical organ
transplantation is to induce immunological tolerance to the allograft.
Dendritic cells, the main antigen-presenting cells, are a complex system
including numerous subsets, capable of inducing T-cell activation, and thus
initiating an immune response, but also of inducing tolerance. In organ
transplantation, the problem is even more complex because of the coexistence of
dendritic cells from the donor, responsible for direct recognition of foreign
antigens by T cells, and dendritic cells from the recipient, responsible for
indirect antigen presentation to host T cells. Among the various methods of
immunomanipulation aiming at inducing tolerance, blockade of the second signal
pathway by monoclonal antibodies (anti-CD28, anti-B7, anti CD40, anti-CD40L,
CTLA4-Ig) has yielded promising but incomplete results. Viral transfection of
recipient immature dendritic cells encoding for immunosuppressive or apoptotic
molecules, such as interleukin 10, transforming growth factor-beta, CTLA4-Ig,
or Fas ligand, is also able to induce hyporesponsiveness. Another very
promising method consists of associating donor cells (bone marrow cells, CD34+
cells, dendritic cells) and polyclonal or monoclonal antibodies (anti-CD4,
anti-CD40L, CTLA4-Ig) to induce microchimerism and partial tolerance.
Reflecting on these data would seem to be an interesting direction for future
prospects. N. Ref:: 24
----------------------------------------------------
[139]
TÍTULO / TITLE: - At the crossroads of
cell biology and immunology: DRiPs and other sources of peptide ligands for MHC
class I molecules.
REVISTA
/ JOURNAL: - J Cell Sci. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://jcs.biologists.org/
●●
Cita: J. of Cell Science: <> 2001 Mar;114(Pt 5):845-51.
AUTORES
/ AUTHORS: - Yewdell JW; Schubert U; Bennink JR
INSTITUCIÓN
/ INSTITUTION: - Laboratory of Viral Diseases, National
Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0440, USA.
RESUMEN
/ SUMMARY: - CD8(+) T cells are a critical element of
vertebrate immune responses to viruses and other intracellular parasites. They
roam the body, monitoring cells for the presence of foreign peptides associated
with MHC class I molecules of the major histocompatibility complex (MHC).
Although it is clear that most of these peptides are generated through the
action of proteasomes, the nature of the substrates degraded by proteasomes is
an open question. Recent findings indicate that the major pool of substrates
consists of a heterogeneous subset of proteins that are degraded within minutes
of their synthesis. Evidence suggests that the fraction of newly synthesized
proteins targeted for destruction is remarkably high - 30% or more, depending
on cell type - possibly because they are defective in some way and cannot reach
their intended conformation or location cellular in a time frame deemed
appropriate by cells. N.
Ref:: 47
----------------------------------------------------
[140]
TÍTULO / TITLE: - CD30+ T-cell lymphoma
in a patient with psoriasis treated with ciclosporin and infliximab.
REVISTA
/ JOURNAL: - Br J Dermatol 2003 Jul;149(1):170-3.
AUTORES
/ AUTHORS: - Mahe E; Descamps V; Grossin M; Fraitag S;
Crickx B
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Bichat-Claude
Bernard Hospital, 46 Rue Henri-Huchard, Paris Cedex 18, France. emmanuel.mahe@bch.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - There is a known relationship between the
use of immunosuppressive therapies and the development of lymphoproliferative
malignancies. These lymphomas are mainly B-cell nonHodgkin’s lymphomas
associated with Epstein-Barr virus. Most cases concern classical
immunosuppressive treatments including ciclosporin and methotrexate. A
relationship between the new antitumour necrosis factor (TNF)-alpha agents and
lymphoproliferative malignancies is debated. Patients with psoriasis on
immunosuppressive therapies, mainly ciclosporin, are considered to have a low
risk of developing lymphoid proliferation. We report a patient with
erythrodermic psoriasis treated with ciclosporin and infliximab who developed a
CD30+ T-cell lymphoma. This lymphoma regressed after stopping these treatments.
In this case, the anti-TNF-alpha agent may have played a role in association
with ciclosporin in the development of the lymphoproliferative disorder.
Whereas the combination of anti-TNF-alpha therapies with methotrexate has been
well studied, their combination with ciclosporin has been evaluated only in a
few patients. Psoriatic patients who may require anti-TNF-alpha treatment have
often been or will be treated with ciclosporin. The combination of ciclosporin
and anti-TNF-alpha warrants further investigation. N. Ref:: 17
----------------------------------------------------
[141]
TÍTULO / TITLE: - Efficacy of
pneumococcal polysaccharide vaccine in immunocompetent adults: a meta-analysis
of randomized trials.
REVISTA
/ JOURNAL: - Vaccine 2001 Sep 14;19(32):4780-90.
AUTORES
/ AUTHORS: - Cornu C; Yzebe D; Leophonte P; Gaillat J;
Boissel JP; Cucherat M
INSTITUCIÓN
/ INSTITUTION: - Service of Clinical Pharmacology, EA643,
Lyon University Hospital, Faculte de Medicine RTH Laennec, BP 8071, 69376,
Cedex 08, Lyon, France. catherine.cornu@upcl.univ-lyon1.fr
RESUMEN
/ SUMMARY: - The use of pneumococcal polysaccharide
vaccine (PPV) is low in some countries, maybe because of doubts regarding its
efficacy. This meta-analysis aims at combining evidence from randomized trials
of PPV assessing its efficacy in preventing Streptococcus pneumoniae related
diseases in immunocompetent adults. In the fourteen trials totalling 48,837
patients retrieved, PPV prevents definite pneumococcal pneumonia by 71%,
presumptive pneumococcal pneumonia by 40%, and mortality due to pneumonia by
32%, but not all-cause pneumonia or death. No preventive effect was seen in the
subgroup of patients aged 55 years or more, possibly due to a lack of
statistical power.
----------------------------------------------------
[142]
TÍTULO / TITLE: - The value of pulse
cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical
review.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2001 Oct;16(10):2018-27.
AUTORES
/ AUTHORS: - de Groot K; Adu D; Savage CO
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Medical School
Hannover, Germany. kirsten@de-grot.de
RESUMEN
/ SUMMARY: - BACKGROUND: The study aimed at studying
efficacy and adverse effects of pulse cyclophosphamide (pCyc) treatment and to
compare it to continuous cyclophosphamide (cCyc) for induction of remission in
ANCA-associated vasculitides from data in the published literature. METHODS: A
Medline search identified 14 studies, containing more than five patients. From
the 11 non-randomized studies, data on outcome following pCyc treatment were
extracted. Results were given as fraction of the number of evaluable patients.
A meta-analysis was performed on the three prospective, randomized controlled
trials to compare outcomes concerning remission, relapses, infection,
leucopenia, death and renal failure in patients treated with pCyc as opposed to
cCyc. RESULTS: The 11 non-randomized studies comprised 202 patients receiving
pCyc. Cyc pulses of 375-1000 mg/sqm/pulse were applied at weekly to monthly
intervals with different concomitant prednisolone regimens and variable
adjunctive therapy. Complete remission was achieved in 112/191, partial
remission in 23/191 evaluable patients. Relapses occurred in 68/135 patients,
40/115 patients were non-responders. Leucopenia, infections, haemorrhagic
cystitis, and deaths were rare. The meta-analysis, comprising 143 patients,
showed that pCyc compared with cCyc treatment was significantly less likely to
fail to induce remission (OR 0.29; 95% CI 0.12-0.73) and had a significantly
lower risk of infection (OR 0.45; 95% CI 0.23-0.89) and leucopenia (OR 0.36;
95% CI 0.17-0.78). Relapses occurred slightly, although not statistically
significantly, more often under pCyc treatment (OR 1.79; 95% CI 0.85-3.75).
There were no differences in end-stage renal failure or deaths between the two
regimens. CONCLUSIONS: The currently available, rather sparse data show that
pCyc is less toxic than cCyc therapy and is an at least equally potent inductor
of remission, but possibly at the expense of a higher relapse rate. The
existing data do not give sufficient information on outcomes as time to
remission and relapse, irreversible damage or quality of life without which a
treatment regimen cannot satisfactorily be evaluated today. A large prospective
randomized controlled trial is needed to address these issues and their
relative importance.
----------------------------------------------------
[143]
TÍTULO / TITLE: - Immune tolerance
induction in patients with haemophilia A with inhibitors: a systematic review.
REVISTA
/ JOURNAL: - Haemophilia 2003 Jul;9(4):436-63.
AUTORES
/ AUTHORS: - Wight J; Paisley S; Knight C
INSTITUCIÓN
/ INSTITUTION: - ScHARR, University of Sheffield,
Sheffield, S1 4DA, UK. j.p.wight@sheffield.ac.uk
RESUMEN
/ SUMMARY: - In some patients with haemophilia A,
therapeutically administered factor VIII (FVIII) comes to stimulate the
production of antibodies (inhibitors) which react with FVIII to render it
ineffective. As a result, FVIII cannot be used prophylactically and patients
become liable to recurrent bleeds. There are two elements to the management of
patients with inhibitors: the treatment of bleeding episodes, and attempts to
abolish inhibitor production through the induction of immune tolerance. This
paper reports a systematic review of the best available evidence of clinical
effectiveness in relation to immune tolerance induction (ITI) in patients with
haemophilia A with inhibitors. Owing to the lack of randomized controlled
trials on this topic, broad inclusion criteria with regard to study design were
applied in order to assess the best available evidence for each intervention.
As a result of the clinical and methodological heterogeneity of the evidence,
it was not appropriate to pool data across studies; instead, data were
synthesized using tabulation and qualitative narrative assessment. The
International Registry provides the most reliable estimate of the proportion of
successful cases of ITI [48.7%, 95% confidence interval (CI) 42.6-52.7%]. The
duration of effect is unclear, but relapses appear to be infrequent. The
International Registry shows a rate of relapse of 15% at 15 years. The
comparative effectiveness of different protocols is uncertain, as no trials
have been undertaken which compare them directly. However, the evidence
suggests that the Bonn protocol may be more effective than the Malmo or
low-dose protocols. There is no good evidence that immunosuppressive drug regimens
are effective. N.
Ref:: 54
----------------------------------------------------
[144]
TÍTULO / TITLE: - Elucidating TOR
signaling and rapamycin action: lessons from Saccharomyces cerevisiae.
REVISTA
/ JOURNAL: - Microbiol Mol Biol Rev. - Acceso gratuito
al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://mmbr.asm.org/
●●
Cita: Microbiology & Molecular Biology Reviews: <> 2002
Dec;66(4):579-91, table of contents.
AUTORES
/ AUTHORS: - Crespo JL; Hall MN
INSTITUCIÓN
/ INSTITUTION: - Division of Biochemistry, Biozentrum,
University of Basel, CH-4056 Basel, Switzerland.
RESUMEN
/ SUMMARY: - TOR (target of rapamycin) is a
phosphatidylinositol kinase-related protein kinase that controls cell growth in
response to nutrients. Rapamycin is an immunosuppressive and anticancer drug
that acts by inhibiting TOR. The modes of action of TOR and rapamycin are
remarkably conserved from S. cerevisiae to humans. The current understanding of
TOR and rapamycin is derived largely from studies with S. cerevisiae. In this
review, we discuss the contributions made by S. cerevisiae to understanding
rapamycin action and TOR function. N.
Ref:: 171
----------------------------------------------------
[145]
TÍTULO / TITLE: - Structures of
calcineurin and its complexes with immunophilins-immunosuppressants.
REVISTA
/ JOURNAL: - Biochem Biophys Res Commun 2003 Nov
28;311(4):1095-102.
AUTORES
/ AUTHORS: - Ke H; Huai Q
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and Biophysics
and Lineberger Comprehensive Cancer Center, The University of North Carolina,
Chapel Hill, NC 27599-7260, USA. hke@med.unc.edu
RESUMEN
/ SUMMARY: - Calcineurin (CN) is a
Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase and is
involved in many physiological processes such as T-cell activation and cardiac
hypertrophy. The crystal structures of CN and its complexes with FKBP12-FK506
and cyclophilin-cyclosporin showed that the two structurally unrelated
immunophilins-immunosuppressants bind to a common composite surface made up of
the residues from both catalytic subunit and regulatory subunit of CN. The
recognition of the immunophilins and immunosuppressive drugs is achieved by
common but few distinct CN residues. However, the binding pattern of
FKBP12-FK506 such as hydrogen bonding is significantly different from that of
CyPA-CsA. This common but distinct recognition may indicate capacity of the
composition surface for binding of other inhibitory proteins. The recognition
site and the active site are adjacent and form an “L” shaped cleft. This
implies that the immunophilin recognition site may also serve as a recognition
site to define the narrow substrate specificity of calcineurin. N. Ref:: 61
----------------------------------------------------
[146]
TÍTULO / TITLE: - Tryptophan catabolism
and regulation of adaptive immunity.
REVISTA
/ JOURNAL: - J Immunol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jimmunol.org/
●●
Cita: J. of Immunology: <> 2003 Jun 15;170(12):5809-13.
AUTORES
/ AUTHORS: - Mellor AL; Munn DH
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Medical College of
Georgia, Augusta GA 30912, USA. N.
Ref:: 40
----------------------------------------------------
[147]
TÍTULO / TITLE: - Interventions for
mucous membrane pemphigoid/cicatricial pemphigoid and epidermolysis bullosa
acquisita: a systematic literature review.
REVISTA
/ JOURNAL: - Arch Dermatol 2002 Mar;138(3):380-4.
AUTORES
/ AUTHORS: - Kirtschig G; Murrell D; Wojnarowska F;
Khumalo N
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Oxford
Radcliffe Hospital, England. G.Kirtschig@vumc.nl
RESUMEN
/ SUMMARY: - OBJECTIVE: To identify and critically
evaluate evidence from randomized controlled trials for the efficacy of
treatments for mucous membrane pemphigoid (MMP)/cicatricial pemphigoid (CP) and
epidermolysis bullosa acquisita (EBA). SEARCH STRATEGY: Review of MEDLINE from
1966 through March 2000, EMBASE from 1980 through March 2000, and the Cochrane
Controlled Trials Register (February 28, 2001) to identify randomized controlled
trials for the efficacy of treatments in MMP/CP and EBA. SELECTION CRITERIA:
All randomized controlled trials of therapeutic interventions that included
patients with MMP/CP or EBA confirmed by immunofluorescence study findings. All
age groups were included. RESULTS: We found 2 small randomized controlled
trials of MMP/CP, both conducted in patients with severe eye involvement. We
were not able to identify a randomized controlled trial of therapeutic
interventions in EBA. CONCLUSIONS: There is evidence from 2 small trials that
severe ocular CP responds best to treatment with cyclophosphamide, and mild to
moderate disease seems effectively suppressed by treatment with dapsone. No
treatment recommendations can be made for EBA because to our knowledge no randomized
controlled trials are published. Even though systemic corticosteroids are
regarded as the gold standard in the treatment of MMP/CP and EBA, there is poor
evidence from the literature that they are the best treatment for these
diseases. N. Ref:: 50
----------------------------------------------------
[148]
TÍTULO / TITLE: - Multidrug resistance
reversal agents.
REVISTA
/ JOURNAL: - J Med Chem 2003 Nov 6;46(23):4805-17.
●●
Enlace al texto completo (gratuito o de pago) 1021/jm030183a
AUTORES
/ AUTHORS: - Robert J; Jarry C
INSTITUCIÓN
/ INSTITUTION: - Institut Bergonie, 229, Cours de
l’Argonne, 33076 Bordeaux Cedex, France. robert@bergonie.org N. Ref:: 151
----------------------------------------------------
[149]
TÍTULO / TITLE: - Structure and function
of major histocompatibility complex (MHC) class I specific receptors expressed
on human natural killer (NK) cells.
REVISTA
/ JOURNAL: - Mol Immunol 2002 Feb;38(9):637-60.
AUTORES
/ AUTHORS: - Borrego F; Kabat J; Kim DK; Lieto L;
Maasho K; Pena J; Solana R; Coligan JE
INSTITUCIÓN
/ INSTITUTION: - Receptor Cell Biology Section, Laboratory
of Allergic Diseases, NIAID, NIH, Twinbrook II, Room 205, 12441 Parklawn Dr.,
Rockville, MD 20852, USA.
RESUMEN
/ SUMMARY: - Natural killer (NK) cells express
receptors that are specific for MHC class I molecules. These receptors play a
crucial role in regulating the lytic and cytokine expression capabilities of NK
cells. In humans, three distinct families of genes have been defined that
encode for receptors of HLA class I molecules. The first family identified
consists of type I transmembrane molecules belonging to the immunoglobulin (Ig)
superfamily and are called killer cell Ig-like receptors (KIR). A second group
of receptors belonging to the Ig superfamily, named ILT (for immunoglobulin
like transcripts), has more recently been described. ILTs are expressed mainly
on B, T and myeloid cells, but some members of this group are also expressed on
NK cells. They are also referred to as LIRs (for leukocyte Ig-like receptor)
and MIRs (for macrophage Ig-like receptor). The ligands for the KIR and some of
the ILT receptors include classical (class Ia) HLA class I molecules, as well
as the nonclassical (class Ib) HLA-G molecule. The third family of HLA class I
receptors are C-type lectin family members and are composed of heterodimers of
CD94 covalently associated with a member of the NKG2 family of molecules. The
ligand for most members is the nonclassical class I molecule HLA-E. NKG2D, a
member of the NKG2 family, is expressed as a homodimer, along with the adaptor
molecule DAP10. The ligands of NKG2D include the human class I like molecules
MICA and MICB, and the recently described ULBPs. Each of these three families
of receptors has individual members that can recognize identical or similar
ligands yet signal for activation or inhibition of cellular functions. This
dichotomy correlates with particular structural features present in the
transmembrane and intracytoplasmic portions of these molecules.In this review
we will discuss the molecular structure, specificity, cellular expression
patterns, and function of these HLA class I receptors, as well as the
chromosomal location and genetic organization.
N. Ref:: 224
----------------------------------------------------
[150]
TÍTULO / TITLE: - Prevention by dietary
(n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced
by cyclosporine A in animals.
REVISTA
/ JOURNAL: - Life Sci 2003 Jun 13;73(4):381-92.
AUTORES
/ AUTHORS: - Chanussot F; Benkoel L
INSTITUCIÓN
/ INSTITUTION: - INSERM U. 476, Faculte de Medecine, 27 bd
Jean Moulin, 13385 Marseille cedex 05, France. Francoise.Chanussot@medecine.univ-mrs.fr
RESUMEN
/ SUMMARY: - Previous findings showed that dietary
(n-6) polyunsaturated phosphatidylcholines (vegetable lecithin) could
efficiently prevent intrahepatic cholestasis induced by cyclosporine A in rats.
Mechanistic studies showed that expressions in rat liver of Na(+), K(+)-ATPase,
Ca(2+), Mg(2+)-ATPase and F-actin were both decreased by drug administration
and both enhanced by (n-6) lecithin enriched diet. There is a possible direct
effect of phosphatidylcholines, vectors of polyunsaturated fatty acids provided
by the metabolism of the dietary lecithin, on the aforesaid hepatic parameters.
Such modulations by drug and diet result in reversed modifications of membrane
composition and fluidity. Final outcome is decreased and enhanced bile lipid
secretion by cyclosporine and vegetable lecithin enriched diet respectively.
Moreover, we advance the hypothesis of a bypass process including a separate
and functional actin-independent way for the non micellar and
phospholipid-dependent secretion of bile lipids. The relationships between the
ATPases, the microfilament components such as F-actin and the different
transporters still remain to be clarified. Furthermore, one can speculate on
beneficial effects in humans of diets enriched in vegetable lecithins that
might prevent cholestasis induced by cyclosporine A. N. Ref:: 75
----------------------------------------------------
[151]
TÍTULO / TITLE: - Oxidized LDL
autoantibodies, endothelial dysfunction, and transplant-associated
arteriosclerosis.
REVISTA
/ JOURNAL: - Arterioscler Thromb Vasc Biol. Acceso
gratuito al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://atvb.ahajournals.org/
●●
Cita: Arteriosclerosis & Thrombosis :
A J. Vasc Biol: <> 2002 Dec 1;22(12):1950-1.
AUTORES
/ AUTHORS: - Alexander RW N. Ref:: 19
----------------------------------------------------
[152]
TÍTULO / TITLE: - Alloantibody and
xenoantibody cross-reactivity in transplantation.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1):1-5.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000105116.74032.63
AUTORES
/ AUTHORS: - Cooper DK; Tseng YL; Saidman SL
INSTITUCIÓN
/ INSTITUTION: - Transplantation Biology Research Center,
Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA. David.Cooper@tbrc.mgh.harvard.edu
RESUMEN
/ SUMMARY: - The recent availability of pigs homozygous
for alpha1,3-galactosyltransferase gene knockout, and improved
immunosuppressive regimens that prevent an elicited antibody response, are
expected to contribute to significantly increased survival of pig organs
transplanted into primates, bringing clinical trials of xenotransplantation
closer. Patients highly sensitized to human leukocyte antigens, who may be
precluded from obtaining a human donor organ, would be one group that might
benefit from xenotransplantation. However, there have been few studies on
whether there is cross-reactivity of anti-human leukocyte antigen antibodies
with pig antigens. What data there are suggest that such cross-reactivity
exists and that this may be detrimental to the outcome after transplantation of
a pig organ. Neither is it known whether sensitization after a pig xenograft would
preclude subsequent allotransplantation, although the data available suggest
that this will not be the case. Further investigation on allo- and xenoantibody
cross-reactivity is required. N.
Ref:: 44
----------------------------------------------------
[153]
TÍTULO / TITLE: - Shared epitopes and
rheumatoid arthritis: disease associations in Greece and meta-analysis of
Mediterranean European populations.
REVISTA
/ JOURNAL: - Semin Arthritis Rheum 2002
Jun;31(6):361-70.
AUTORES
/ AUTHORS: - Ioannidis JP; Tarassi K; Papadopoulos IA;
Voulgari PV; Boki KA; Papasteriades CA; Drosos AA
INSTITUCIÓN
/ INSTITUTION: - Clinical and Molecular Epidemiology Unit,
Department of Hygiene and Epidemiology and the Division of Rheumatology,
University of Ioannina School of Medicine, Ioannina, Greece.
RESUMEN
/ SUMMARY: - OBJECTIVES: To assess the strength of the
associations between HLA shared epitopes (SE) and rheumatoid arthritis (RA)
susceptibility, articular disease severity, and extra-articular features in
Mediterranean European populations. METHODS: One hundred and seventy-four Greek
RA patients and 103 controls were evaluated. Data were then included in a
meta-analysis of 9 studies of Mediterranean European populations (959 RA
patients and 1,405 controls). RESULTS: In our study population, SE alleles were
significantly more common in RA patients than in controls (odds ratio [OR],
2.5; 95% confidence interval [CI], 1.4-4.3). Larsen radiologic score was
predicted by SE and disease duration. SE did not increase the risk of any
extra-articular manifestation. The meta-analysis showed a pooled OR of 3.7 (95%
CI, 2.6-5.2) for susceptibility to RA conferred by SE (OR, 3.4 v 3.9 in Greek v
non-Greek populations). CONCLUSIONS: SE determine articular destruction without
increasing the risk of extra-articular manifestations. The immunogenetic
associations of RA susceptibility are consistent, but their strength may depend
on the SE prevalence in different ethnic groups.
----------------------------------------------------
[154]
TÍTULO / TITLE: - Heat shock proteins,
anti-heat shock protein reactivity and allograft rejection.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11):1503-7.
AUTORES
/ AUTHORS: - Pockley AG
INSTITUCIÓN
/ INSTITUTION: - Division of Clinical Sciences (NGH),
Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5
7AU, UK.
RESUMEN
/ SUMMARY: - Heat shock proteins are families of highly
conserved immunodominant molecules, reactivity to which has been implicated in
the pathogenesis of a number of autoimmune and vascular disease states.
However, heat shock proteins are cytoprotective, and in clinical and
experimental arthritis, anti-heat shock protein reactivity can down modulate
immune responses via a self-Hsp reactive, Th2-type mechanism. Despite a number
of studies associating heat shock protein expression and anti-heat shock
protein reactivity with allograft rejection, the balance between protective and
damaging effects and the precise influence of these responses on graft outcome
is unclear. This article reviews current knowledge surrounding heat shock
proteins, autoimmunity, and allograft rejection and presents a perspective on
the potential influence of these proteins and the stress response on allograft
outcome. N. Ref:: 90
----------------------------------------------------
[155]
TÍTULO / TITLE: - Infliximab as
disease-modifying therapy.
REVISTA
/ JOURNAL: - Eur J Gastroenterol Hepatol 2003
Mar;15(3):233-7.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.meg.0000049995.68425.94
AUTORES
/ AUTHORS: - D’Haens GR
INSTITUCIÓN
/ INSTITUTION: - Department of Gastroenterology, University
Hospital Gasthuisberg, Leuven, Belgium. geert.dhaens@uz.kuleuven.ac.be
RESUMEN
/ SUMMARY: - Recent insights in the pathophysiology of
Crohn’s disease have revealed that tumour necrosis factor (TNF) plays a pivotal
role in mucosal inflammation. Infliximab is a chimeric anti-TNF monoclonal
antibody with potent anti-inflammatory effects, probably based on apoptosis of
inflammatory cells. Numerous controlled trials have demonstrated efficacy in
both active and fistulating Crohn’s disease. Appropriate indications for using
infliximab and growing experience with safety aspects have made this treatment
a highly valuable tool in the management of Crohn’s disease. N. Ref:: 31
----------------------------------------------------
[156]
TÍTULO / TITLE: - Prevention of and treatment
for hepatitis B virus infection after liver transplantation in the nucleoside
analogues era.
REVISTA
/ JOURNAL: - Am J Transplant 2003 Mar;3(3):250-8.
AUTORES
/ AUTHORS: - Papatheodoridis GV; Sevastianos V;
Burroughs AK
INSTITUCIÓN
/ INSTITUTION: - 2nd Academic Department of
Medicine, Hippokration General Hospital, Athens, Greece. gpapath@cc.uoa.gr
RESUMEN
/ SUMMARY: - Post-transplant prophylaxis with hepatitis
B immune globulin (HBIG) has significantly reduced hepatitis B virus (HBV)
recurrence rates, but it is rather ineffective in patients with pretransplant
viremia. Moreover, long-term HBIG administration is very expensive and may be
associated with emergence of escape HBV mutants. Lamivudine has been widely
used in the management of HBV transplant patients. Pretransplant lamivudine
lowers HBV viremia, decreasing the risk of post-transplant HBV recurrence, but
to try and minimize development of resistant HBV strains, it should start
within the last 6 months of the anticipated transplantation timing. Preemptive
post-transplant lamivudine monotherapy is associated with progressively
increasing HBV recurrence rates, but combined therapy with lamivudine and HBIG
at relatively low dosage is currently the most effective approach in this
setting, even in HBV-DNA-positive patients, who also receive lamivudine in the
pretransplant period. The most frequent therapy for post-transplant HBV
recurrence is lamivudine, but the increasing resistance rates represent a rather
challenging problem. Adefovir dipivoxil and entecavir are currently the most
promising agents for lamivudine-resistant HBV strains. All these advances in
anti-HBV therapy have made HBV liver disease an indication for liver
transplantation irrespective of viral replication status, a complete turn
around from 10 years ago. N.
Ref:: 93
----------------------------------------------------
[157]
TÍTULO / TITLE: - Treatment of the
bleeding inhibitor patient.
REVISTA
/ JOURNAL: - Semin Thromb Hemost 2003 Feb;29(1):77-86.
●●
Enlace al texto completo (gratuito o de pago) 1055/s-2003-37972
AUTORES
/ AUTHORS: - Astermark J
INSTITUCIÓN
/ INSTITUTION: - Department of Coagulation Disorders, Malmo
University Hospital, Malmo, Sweden. Jan.astermark@medforsk.mas.lu.se
RESUMEN
/ SUMMARY: - The development of inhibitory antibodies
to factor (F) VIII and FIX continues to be a major challenge in the treatment
of patients with hemophilia. In patients with low-responding inhibitors, it is
usually possible to saturate the inhibitor with the deficient factor and to
achieve hemostasis, but in patients with high-responding inhibitors, two major
tasks have to be considered. One is how to treat the acute bleedings and the
other is how to permanently eliminate the immune response, in other words, to
induce tolerance. There are several hemostatic agents available for bleeding
patients with high-responding inhibitors. Nonactivated and activated
prothrombin complex concentrates (PCCs) have been used for almost 30 years, and
since the beginning of the 1980s, porcine FVIII has also been used. In more
recent years, recombinant FVIIa has been added to the therapeutic armamentarium
and has been shown to control hemostasis in most patients. Immunoadsorption may
temporarily reduce the inhibitor, enabling replacement therapy for several
days. Available data on these alternative regimens will be discussed with a
focus on the mechanisms of action, pharmacokinetics, safety, monitoring, and
clinical experience. N.
Ref:: 76
----------------------------------------------------
[158]
TÍTULO / TITLE: - Use of the A(2A)
adenosine receptor as a physiological immunosuppressor and to engineer
inflammation in vivo.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2003 Feb
15;65(4):493-501.
AUTORES
/ AUTHORS: - Sitkovsky MV
INSTITUCIÓN
/ INSTITUTION: - Laboratory of Immunology, National
Institute of Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, MD 20892-1892, USA. mvsitkov@helix.nih.gov
RESUMEN
/ SUMMARY: - Inflammation must be inhibited in order to
treat, e.g., sepsis or autoimmune diseases or must be selectively enhanced to improve,
for example, immunotherapies of tumors or the development of vaccines.
Predictable enhancement of inflammation depends upon the knowledge of the
“natural” pathways by which it is down-regulated in vivo. Extracellular
adenosine and A(2A) adenosine (purinergic) receptors were identified recently
as anti-inflammatory signals and as sensors of excessive inflammatory tissue
damage, respectively (Ohta A and Sitkovsky M, Nature 2001;414:916-20). These
molecules may function as an important part of a physiological “metabolic
switch” mechanism, whereby the inflammatory stimuli-produced local tissue
damage and hypoxia cause adenosine accumulation and signaling through cyclic
AMP-elevating A(2A) adenosine receptors in a delayed negative feedback manner.
Patterns of A(2A) receptor expression are activation- and
differentiation-dependent, thereby allowing for the “acquisition” of an
immunosuppressive “OFF button” and creation of a time-window for
immunomodulation. Identification of A(2A) adenosine receptors as “natural”
brakes of inflammation provided a useful framework for understanding how
tissues regulate inflammation and how to enhance or decrease (engineer)
inflammation by targeting this endogenous anti-inflammatory pathway. These
findings point to the need of more detailed testing of anti-inflammatory
agonists of A(2A) receptors and create a previously unrecognized strategy to
enhance inflammation and targeted tissue damage by using antagonists of A(2A)
receptors. It is important to further identify the contributions of different
types of immune cells at different stages of the inflammatory processes in
different tissues to enable the “tailored” treatments with drugs that modulate
the signaling through A(2A) purinergic receptors. N. Ref:: 113
----------------------------------------------------
[159]
TÍTULO / TITLE: - Mechanisms of
corticosteroid resistance in rheumatoid arthritis: a putative role for the
corticosteroid receptor beta isoform.
REVISTA
/ JOURNAL: - Ann N Y Acad Sci 2002 Jun;966:39-48.
AUTORES
/ AUTHORS: - Chikanza IC
INSTITUCIÓN
/ INSTITUTION: - Bone and Joint Research Unit, John Vane
Building, St. Bartholomew’s and Royal London School of Medicine, Charterhouse
Square, London, United Kingdom. i.c.chikanza@gmul.uk
RESUMEN
/ SUMMARY: - Corticosteroids (CSs) have potent
immunosuppressive effects and are commonly used to treat a range of
immunological and inflammatory diseases such as rheumatoid arthritis (RA).
These effects are mediated by the ability of CSs to modulate gene expression.
CSs act by binding to the CS receptor (CR), which exists as alpha and beta
isoforms. Only CRalpha binds CS. CRbeta functions as an endogenous inhibitor of
CS and is expressed in several tissues. The CS/CRalpha complex binds to the
glucocorticosteroid response element in the nucleus and also interferes with
AP-1 and NF-kappaB binding. Thus, CSs inhibit the transcription of AP-1 and
NF-kappaB inducible genes, such as interleukin (IL)-2, IL-6, IL-8, IL-1beta,
and tumor necrosis factor (TNF) alpha, as well as T-cell proliferation. In
clinical practice, a proportion of RA patients do not respond adequately to CS
therapy. On this basis, RA patients can be divided on clinical grounds and on
the ability of CSs to inhibit concanavalin A (conA)-induced peripheral blood
T-cell proliferation in vitro into CS-sensitive (SS) and CS-resistant (SR)
subgroups. The in vitro defined SS and SR subgroups correlate with the clinical
responses to CS therapy. The mechanisms of the SR in RA patients remain unknown
but may include the following: dysregulation of CRalpha function, alterations
in the intracellular signaling mechanisms and/or utilization of various other
cellular activation pathways, perturbations of the cytokine milieu, and inhibition
of lipocortin. In SR subjects, CSs fail to significantly inhibit conA-induced
IL-2 and IL-4 secretion and LPS-induced IL-8, IL-1beta secretion in vitro. CS
therapy fails to reduce the circulating levels of IL-8, IL-1beta, and TNFalpha
in SR RA patients. Peripheral blood mononuclear cells (PBMCs) from SR
significantly overexpress activated NF-kappaB and IkappaBalpha. In vitro CSs
fail to significantly inhibit conA-induced NF-kappaB activation in PBMCs from
SR RA patients. Our preliminary observations show enhanced CRbeta expression by
PBMCs from SR RA patients. It is most likely that other molecular mechanisms
such as enhanced AP-1 expression are involved, and we currently are
investigating such possibilities. N.
Ref:: 60
----------------------------------------------------
[160]
TÍTULO / TITLE: - The role of monoclonal
antibodies in stem cell transplantation.
REVISTA
/ JOURNAL: - Semin Oncol 2004 Feb;31(1):83-9.
AUTORES
/ AUTHORS: - Wasil T; Rai KR; Mehrotra B
INSTITUCIÓN
/ INSTITUTION: - Long Island Jewish Medical Center,
Division of Hematology-Oncology, New Hyde Park, NY 11040, USA.
RESUMEN
/ SUMMARY: - Monoclonal antibodies directed at the
lymphoid antigens have become established treatments for hematological
malignancies either alone or in combination with chemotherapy. However, their
incorporation in the transplant setting remains investigational. This review
focuses on the currently available data for in vitro and in vivo purging with
these antibodies as well as their role in modulating graft-versus-host disease
(GVHD). N. Ref:: 44
----------------------------------------------------
[161]
TÍTULO / TITLE: - Weakness of respiratory
and skeletal muscles after a short course of steroids in patients with acute
lung rejection.
REVISTA
/ JOURNAL: - Eur Respir J 2002 Aug;20(2):497-9.
AUTORES
/ AUTHORS: - Nava S; Fracchia C; Callegari G; Ambrosino
N; Barbarito N; Felicetti G
INSTITUCIÓN
/ INSTITUTION: - Respiratory Unit, Istituto Scientifico di
Montescano, Pavia, Italy. snava@fsm.it
RESUMEN
/ SUMMARY: - There have been occasional reports of
acute respiratory and skeletal muscle weakness in intensive care unit patients
treated with massive doses of corticosteroids. However, in this setting the
concomitant use of other drugs may have influenced the finding. In this study
the effects of 5 days of treatment with high doses of steroids in consecutive
patients with acute lung rejection after transplantation were systematically
evaluated. Maximal inspiratory pressure during phrenic nerve stimulation and
peak torque of isokinetic contraction of the quadriceps and hamstring muscles
were measured objectively. Compared to the pretreatment condition,
approximately 45% of patients showed acute generalised muscle weakness that recovered
after approximately 2 months. This demonstrates muscle weakness induced by
steroids within patients. N.
Ref:: 6
----------------------------------------------------
[162]
TÍTULO / TITLE: - Calcineurin
inhibitor-free CD28 blockade-based protocol protects allogeneic islets in
nonhuman primates.
REVISTA
/ JOURNAL: - Diabetes. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://diabetes.diabetesjournals.org/
●●
Cita: Diabetes: <> 2002 Feb;51(2):265-70.
AUTORES
/ AUTHORS: - Adams AB; Shirasugi N; Durham MM; Strobert
E; Anderson D; Rees P; Cowan S; Xu H; Blinder Y; Cheung M; Hollenbaugh D;
Kenyon NS; Pearson TC; Larsen CP
INSTITUCIÓN
/ INSTITUTION: - Emory Transplant Center, Department of
Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
RESUMEN
/ SUMMARY: - Recent success using a steroid-free
immunosuppressive regimen has renewed enthusiasm for the use of islet
transplantation to treat diabetes. Toxicities associated with the continued use
of a calcineurin inhibitor may limit the wide-spread application of this
therapy. Biological agents that block key T-cell costimulatory signals, in
particular the CD28 pathway, have demonstrated extraordinary promise in animal
models. LEA29Y (BMS-224818), a mutant CTLA4-Ig molecule with increased binding
activity, was evaluated for its potential to replace tacrolimus and protect
allogeneic islets in a preclinical primate model. Animals received either the
base immunosuppression regimen (rapamycin and anti-IL-2R monoclonal antibody
[mAb]) or the base immunosuppression and LEA29Y. Animals receiving the
LEA29Y/rapamycin/anti-IL-2R regimen (n = 5) had significantly prolonged islet
allograft survival (204, 190, 216, 56, and >220 days). In contrast, those
animals receiving the base regimen alone (n = 2) quickly rejected the transplanted
islets at 1 week (both at 7 days). The LEA29Y-based regimen prevented the
priming of anti-donor T- and B-cell responses, as detected by interferon-gamma
enzyme-linked immunospot and allo-antibody production, respectively. The
results of this study suggest that LEA29Y is a potent immunosuppressant that
can effectively prevent rejection in a steroid-free immunosuppressive protocol
and produce marked prolongation of islet allograft survival in a preclinical
model.
----------------------------------------------------
[163]
TÍTULO / TITLE: - Nutrient signaling
through TOR kinases controls gene expression and cellular differentiation in
fungi.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:53-72.
AUTORES
/ AUTHORS: - Rohde JR; Cardenas ME
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Genetics and
Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
RESUMEN
/ SUMMARY: - The TOR kinases were first identified in
Saccharomyces cerevisiae as the targets of the immunosuppressive drug
rapamycin. Subsequent studies employing rapamycin as a tool in yeast have given
us insight into the structure and function of the TOR kinases, as well as the
biological role of the TOR signaling program in transmitting nutrient signals
to promote cell growth. One of the major advances from this area has been in
defining an unexpected role for TOR signaling in the regulation of
transcription. The identification of target genes subject to regulation by TOR
has provided a platform for the dissection of the signaling events downstream
of the TOR kinases. Studies aimed at understanding TOR-regulated transcription
have begun to shed light on how TOR signaling cooperates with other signaling
programs. In addition, the TOR pathway regulates the developmental program of
pseudohyphal differentiation in concert with highly conserved MAP kinase and
PKA signaling programs. Remarkably, rapamycin also blocks filamentation in a
number of important human and plant pathogens and the mechanism of rapamycin
action is conserved in Candida albicans and Cryptococcus neoformans. The
antimicrobial properties of less immunosuppressive analogs of rapamycin hold
promise for the development of an effective antifungal therapy. N. Ref:: 65
----------------------------------------------------
[164]
TÍTULO / TITLE: - Signaling pathways
involved in translational control of protein synthesis in skeletal muscle by
leucine.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Mar;131(3):856S-860S.
AUTORES
/ AUTHORS: - Anthony JC; Anthony TG; Kimball SR;
Jefferson LS
INSTITUCIÓN
/ INSTITUTION: - Department of Cellular and Molecular
Physiology, P.O. Box 850, The Pennsylvania State University College of
Medicine, Hershey, PA 17033, USA.
RESUMEN
/ SUMMARY: - Numerous reports established that in
skeletal muscle the indispensable branched-chain amino acid leucine is unique
in its ability to initiate signal transduction pathways that modulate
translation initiation. Oral administration of leucine stimulates protein
synthesis in association with hyperphosphorylation of the translational repressor,
eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1), resulting in
enhanced availability of the mRNA cap-binding protein eIF4E, for binding eIF4G
and forming the active eIF4F complex. In addition, leucine enhances
phosphorylation of the 70-kDa ribosomal protein S6 kinase (S6K1). These results
suggest that leucine upregulates protein synthesis in skeletal muscle by
enhancing both the activity and synthesis of proteins involved in mRNA
translation. The stimulatory effects of leucine on translation initiation are
mediated in part through the protein kinase mammalian target of rapamycin
(mTOR), where both insulin signaling and leucine signaling converge to promote
a maximal response. N.
Ref:: 34
----------------------------------------------------
[165]
TÍTULO / TITLE: - The HCMV gene products
US2 and US11 target MHC class I molecules for degradation in the cytosol.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2002;269:37-55.
AUTORES
/ AUTHORS: - van der Wal FJ; Kikkert M; Wiertz E
INSTITUCIÓN
/ INSTITUTION: - Department of Medical Microbiology, Leiden
University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
RESUMEN
/ SUMMARY: - Over millions of years of coevolution with
their hosts, viruses have developed highly effective strategies to elude the
host immune system. The degradation of major histocompatibility complex (MHC)
class I heavy chains by human cytomegalovirus (HCMV) is an example of this. Two
HCMV proteins, US2 and US11, target newly synthesized MHC class I heavy chains
for destruction via a pathway that involves ubiquitin-dependent retrograde
transport, or “dislocation”, of the heavy chains from the ER to the cytosol,
where the proteins are degraded by proteasomes. In this review, US2- and
US11-mediated degradation of MHC class I heavy chains is discussed in relation
to data concerning the degradation of other ER luminal proteins. A new, unified
model for translocon-facilitated dislocation and degradation of MHC class I
heavy chains is presented. N.
Ref:: 115
----------------------------------------------------
[166]
TÍTULO / TITLE: - Beta-herpesvirus
challenges in the transplant recipient.
REVISTA
/ JOURNAL: - J Infect Dis. Acceso gratuito al texto
completo a partir de los 2 años de la publicación; - http://www.journals.uchicago.edu/
●●
Cita: J. of Infectious Diseases: <> 2002 Oct 15;186 Suppl 1:S99-S109.
AUTORES
/ AUTHORS: - Ljungman P
INSTITUCIÓN
/ INSTITUTION: - Karolinska Institutet, SE-14186 Stockholm,
Sweden. per.ljungman@medhs.ki.se
RESUMEN
/ SUMMARY: - Cytomegalovirus (CMV) has major
consequences after allogeneic stem cell and solid organ transplantation. CMV
may cause significant morbidity and mortality, and monitoring to detect
reactivation to reduce disease or management of end organ disease is associated
with increased resource utilization. Two other members of the beta-herpesvirus
family, human herpesvirus (HHV) type 6 and HHV-7, are increasingly recognized
as important pathogens in transplant recipients, either by direct infection
(e.g., encephalitis, hepatitis, or pneumonitis) or via interaction with CMV. In
addition to direct effects of CMV infection, such indirect effects as an
increased risk for bacterial and fungal infections or impaired graft acceptance
and function are important research topics. Diagnosis and treatment of CMV
infection is currently more advanced than for HHV-6 and HHV-7. N. Ref:: 109
----------------------------------------------------
[167]
TÍTULO / TITLE: - A benefit-risk
assessment of basiliximab in renal transplantation.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2004;27(2):91-106.
AUTORES
/ AUTHORS: - Boggi U; Danesi R; Vistoli F; Del Chiaro
M; Signori S; Marchetti P; Del Tacca M; Mosca F
INSTITUCIÓN
/ INSTITUTION: - Division of General Surgery and
Transplants, Department of Oncology, Transplants and Advanced Technologies in
Medicine, University of Pisa, Pisa, Italy. uboggi@med.unipi.it
RESUMEN
/ SUMMARY: - Interleukin-2 (IL-2) and its receptor
(IL-2R) play a central role in T lymphocyte activation and immune response
after transplantation. Research on the biology of IL-2R allowed the
identification of key signal transduction pathways involved in the generation
of proliferative and antiapoptotic signals in T cells. The alpha-chain of the
IL-2R is a specific peptide against which monoclonal antibodies have been
raised, with the aim of blunting the immune response by means of inhibiting
proliferation and inducing apoptosis in primed lymphocytes. Indeed,
basiliximab, one of such antibodies, has proved to be effective in reducing the
episodes of acute rejection after kidney and pancreas transplantation. The use
of basiliximab was associated with a significant reduction in the incidence of
any treated rejection episodes after kidney transplantation in the two major
randomised studies (placebo 52.2% vs basiliximab 34.2% at 6 months, European
study; placebo 54.9% vs basiliximab 37.6% at 1 year, US trial). Basiliximab and
equine antithymocyte globulin (ATG) administration resulted in a similar rate
of biopsy-proven acute rejection at 6 months (19% for both) and at 12 months
(19% and 20%, respectively). The use of basiliximab appears not to be
associated with an increased incidence of adverse events as compared with
placebo in immunosuppressive regimens, including calcineurin inhibitors,
mycophenolate mofetil or azathioprine and corticosteroids, and its safety
profile is superior to ATG. Moreover, a similar occurrence of infections is
noted in selected studies (65.5% after basiliximab vs 65.7% of controls),
including cytomegalovirus infection (17.3% vs 14.5%), and cytokine-release
syndrome is not observed. Finally, economic analysis demonstrated lower costs
of overall treatment in patients treated with basiliximab. Therefore, the use
of basiliximab entails a very low risk, allows safe reduction of corticosteroid
dosage and reduces the short- and mid-term rejection rates. However, the
improvement in the long-term survival of kidney grafts in patients treated
according to modern immunosuppressive protocols is still to be demonstrated.
These conclusions are based on a systematic review of the scientific
literature, indexed on Medline database, concerning the mechanism of action,
therapeutic activity, safety and pharmacoeconomic evaluation of basiliximab in
renal transplantation. N.
Ref:: 62
----------------------------------------------------
[168]
TÍTULO / TITLE: - Cardiac allograft
vasculopathy and dysregulation of the NO synthase pathway.
REVISTA
/ JOURNAL: - Arterioscler Thromb Vasc Biol. Acceso
gratuito al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://atvb.ahajournals.org/
●●
Cita: Arteriosclerosis & Thrombosis :
A J. Vasc Biol: <> 2003 Apr 1;23(4):567-75. Epub 2003 Mar 20.
●●
Enlace al texto completo (gratuito o de pago) 1161/01.ATV.0000067060.31369.F9
AUTORES
/ AUTHORS: - Weis M; Cooke JP
INSTITUCIÓN
/ INSTITUTION: - Division of Cardiovascular Medicine,
Stanford University School of Medicine, Stanford, Calif 94305-5406, USA.
RESUMEN
/ SUMMARY: - Cardiac allograft vasculopathy is the most
aggressive form of atherosclerosis in humans and is the leading cause of death
after the first year of heart transplantation. Endothelial dysfunction is a
major contributing factor to the acceleration of coronary vascular disease in
these individuals. A reflection of this endothelial dysfunction is the severe
impairment in endothelium-dependent vasodilation that occurs early after
transplantation. The etiology of this allograft endothelial alteration is
multifactorial and may include preexisting atherosclerosis of the graft
vessels, reperfusion injury during transplantation, denervation, disruption of
the lymphatic system, and acute and chronic immune injury, as well as
traditional risk factors for coronary artery disease (hyperlipidemia, diabetes,
hypertension, or hyperhomocysteinemia) and pathogens, such as cytomegalovirus.
The alteration in endothelial function affects vasomotor tone of the coronary arteries.
Evidence indicates that there may be an impairment of endothelial production
and/or activity of NO. Because NO is a potent vasodilator, its deficiency would
explain the abnormal vasomotor tone in these individuals. In addition, because
NO inhibits key processes in vascular inflammation and atherosclerosis, its
absence may contribute to the acceleration of transplant vascular disease.
Recent studies from our group and others have shed light on the mechanisms of
endothelial dysfunction and its importance in cardiac allograft vasculopathy.
In addition, the alteration in endothelial function contributes to vascular
inflammation and progression of the disease.
N. Ref:: 148
----------------------------------------------------
[169]
TÍTULO / TITLE: - The effect of
hematopoietic growth factors on the risk of graft-vs-host disease after
allogeneic hematopoietic stem cell transplantation: a meta-analysis.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2003
Oct;32(8):771-5.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1704228
AUTORES
/ AUTHORS: - Ho VT; Mirza NQ; Junco Dd D; Okamura T;
Przepiorka D
INSTITUCIÓN
/ INSTITUTION: - Baylor College of Medicine, Center for
Cell and Gene Therapy, Houston, TX, USA.
RESUMEN
/ SUMMARY: - The effect of hematopoietic growth factors
on neutrophil recovery after allogeneic transplantation is well-recognized.
Recent laboratory studies demonstrated that these cytokines may also modify
T-cell and dendritic cell function, but whether the effect is strong enough to
alter the risk of GVHD is unclear. We performed a meta-analysis to determine
the effect of G-CSF or GM-CSF on the risk of nonhematopoietic outcomes after
allogeneic transplantation. A search of the literature from 1986 to present
yielded 18 publications in which data were provided for cohorts receiving
growth factor vs either placebo or no therapy. These included nine prospective
randomized studies, eight retrospective cohort studies, and one case-control
study comprising a total of 1198 patients. The publication types were
heterogeneous with regard to demographic and treatment characteristics,
although within publications, comparative groups were generally balanced. The
pooled risk ratio estimates with use of growth factor was 1.08 (95% CI
0.87-1.33, P=0.48) for grades 2-4 acute GVHD, 1.22 (95% CI 0.80-1.86, P=0.99)
for grades 3-4 acute GVHD, and 1.02 (95% CI 0.82-1.26, P=0.87) for chronic
GVHD. This analysis did not detect a significant change in the risk of acute or
chronic GVHD after allogeneic hematopoietic stem cell transplantation when
hematopoietic growth factors were used to shorten the initial period of
neutropenia.
----------------------------------------------------
[170]
TÍTULO / TITLE: - Self major
histocompatibility complex class-II-specific regulatory CD4 T cells prevent
both Th1- and Th2-mediated autoimmune diseases in the rat.
REVISTA
/ JOURNAL: - Microbes Infect 2001 Sep;3(11):955-60.
AUTORES
/ AUTHORS: - Pelletier L; Savignac M; Xystrakis E;
Duplan V; Druet P; Abdelhadi S
INSTITUCIÓN
/ INSTITUTION: - Inserm U28, Hopital Purpan, place du D
Baylac, 31059, Toulouse, France. Lucette.Pelletier@purpan.inserm.fr
RESUMEN
/ SUMMARY: - It is clear that functional heterogeneity
of T cells may be explained by differential cytokine production. The aim of
this paper was to review evidence for regulatory cells, generated after
HgCl(2)-exposure. They differ from classical Th1 and Th2 cells, produce
transforming growth factor-beta and interleukin-10 and exert their regulatory
functions in a Th1/Th2-unrestricted fashion.
N. Ref:: 46
----------------------------------------------------
[171]
TÍTULO / TITLE: - Role of leucine in the
regulation of mTOR by amino acids: revelations from structure-activity studies.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Mar;131(3):861S-865S.
AUTORES
/ AUTHORS: - Lynch CJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cellular and Molecular
Physiology, The Pennsylvania State University College of Medicine, 500
University Drive, Hershey, PA 17033, USA. clynch@psu.edu
RESUMEN
/ SUMMARY: - In this study an overview is presented of
the mTOR signaling pathway and its regulation by amino acids, particularly
L-leucine. Our laboratory is studying amino acid regulation of mTOR in
adipocytes. Potential roles for mTOR in adipocytes that were previously posited
include hypertrophic growth, leptin secretion, protein synthesis and adipose
tissue morphogenesis. A current area of interest in the field is how amino
acids regulate mTOR and which amino acids are regulatory. Revelations
concerning mechanism and recognition are emerging from different laboratories
that examined the structural requirements for stimulation and inhibition of the
mTOR signaling pathway by leucine and amino acid analogs. In adipocytes and
some other cell types, leucine appears to be the main regulatory amino acid.
However, this is not uniformly the case. In those cells where mTOR is regulated
by several amino acids, there is evidence that the mechanism of mTOR activation
may be different from cells where mainly leucine is regulatory. Furthermore, in
tissues where leucine regulates mTOR, the possible existence of different
tissue-specific leucine recognition sites may be indicated. N. Ref:: 47
----------------------------------------------------
[172]
TÍTULO / TITLE: - Drug-eluting stents and
glycoprotein IIb/IIIa inhibitors: combination therapy for the future.
REVISTA
/ JOURNAL: - Am Heart J 2003 Oct;146(4 Suppl):S13-7.
●●
Enlace al texto completo (gratuito o de pago) 1016/j.ahj.2003.09.004
AUTORES
/ AUTHORS: - Leon MB; Bakhai A
RESUMEN
/ SUMMARY: - BACKGROUND: Although coronary stenting has
improved the results of coronary interventions compared to coronary angioplasty
alone, in-stent restenosis remains a significant limitation of this procedure.
Drug-eluting stents with or without glycoprotein IIb/IIIa inhibitor therapy
represent an additional advance in the evolution of this strategy. METHODS: We
review the currently available trials comparing studies of non-drug-eluting and
drug-eluting stents using sirolimus and paclitaxel agents and their
derivatives. RESULTS: Ten studies are available that compare drug-eluting to
traditional non-drug-eluting stents. A variety of antiplatelet regimes have
been used. The majority of these studies are in the process of being published.
No head-to-head studies comparing different drug-eluting stents are available.
CONCLUSIONS: Drug-eluting stents using sirolimus and paclitaxel in combination
with enhanced antiplatelet strategies represent an important advantage over
non-drug-eluting stents for the reduction of in-stent restenosis. The rate at
which drug-eluting stents are adapted into widespread practice depends heavily
on whether they are safe, efficacious, and cost-effective in various clinical
settings. N. Ref:: 28
----------------------------------------------------
[173]
TÍTULO / TITLE: - Targeted therapy of
solid malignancies via HLA class II antigens: a new biotherapeutic approach?
REVISTA
/ JOURNAL: - Oncogene 2003 Sep 29;22(42):6564-9.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.onc.1206960
AUTORES
/ AUTHORS: - Altomonte M; Fonsatti E; Visintin A; Maio
M
INSTITUCIÓN
/ INSTITUTION: - Cancer Bioimmunotherapy Unit, Department
of Medical Oncology, Centro di Riferimento Oncologico, Istituto di Ricovero e
Cura a Carattere Scientifico, via Pedemontana Occ. le, 12, Aviano 33081, Italy.
maltomonte@cro.it
RESUMEN
/ SUMMARY: - Intracellular signals, delivered in
professional antigen-presenting cells following the engagement of major
histocompatibility complex (MHC) class II molecules, activate a variety of
cellular functions that also contribute to efficient antigen presentation. As far
as human malignancies, the signaling ability of human leukocyte antigens (HLA)
class II molecules is a rather well-characterized event in hematologic tumors;
in contrast, very limited evidences are available in solid neoplasias of
different histotypes that may constitutively express HLA class II antigens.
Among solid malignancies, a significant proportion of human cutaneous melanomas
have been shown to express HLA class II molecules, and cutaneous melanoma
undoubtedly represents a ‘model disease’ to investigate tumor immunobiology, to
unveil the molecular basis underlying the interactions between neoplastic cells
and host’s immune system, and ultimately to set up new bio-immunotherapeutic
approaches. Upcoming preclinical evidences unveil a signaling potential of
HLA-DR antigens expressed on melanoma cells, and suggest for the clinical
implication of HLA class II molecules as novel therapeutic targets. Therefore,
in this review, we will focus on the emerging role of HLA class II antigens as
intracellular signal transducing elements in neoplastic cells of the
melanocytic lineage, emphasizing their foreseeable role in targeted therapy of
human melanoma and potentially of HLA class II antigens-positive tumors of
different histology. N.
Ref:: 94
----------------------------------------------------
[174]
TÍTULO / TITLE: - Cellular engineering of
HSV-tk transduced, expanded T lymphocytes for graft-versus-host disease
management.
REVISTA
/ JOURNAL: - Acta Haematol 2003;110(2-3):121-31.
●●
Enlace al texto completo (gratuito o de pago) 1159/000072461
AUTORES
/ AUTHORS: - Burger SR; Kadidlo DM; Basso L; Bostrom N;
Orchard PJ
INSTITUCIÓN
/ INSTITUTION: - Advanced Cell and Gene Therapy, Chapel
Hill, NC 27516, USA. sburger@ac-gt.com
RESUMEN
/ SUMMARY: - Engineering donor T lymphocytes with
inducible ‘suicide genes’, such as herpes simplex virus thymidine kinase, has
potential to improve safety and efficacy in allogeneic transplantation by
facilitating management of graft-versus-host disease. Elective administration
of a relatively nontoxic pro-drug would induce in vivo negative selection of
engineered lymphocytes specifically, sparing other donor hematopoietic cells.
The engineered cells must retain immunologic function, and undergo negative
selection in response to clinically attainable plasma concentrations of
pro-drug. The cell engineering process itself, typically involving activation,
transduction, ex vivo expansion, and selection, must produce clinically useful
numbers of genetically modified cells at high purity. We discuss development of
a cellular engineering manufacturing process that yields transduced, expanded T
lymphocytes meeting these requirements.
N. Ref:: 37
----------------------------------------------------
[175]
TÍTULO / TITLE: - Hereditary
hemochromatosis: perspectives of public health, medical genetics, and primary
care.
REVISTA
/ JOURNAL: - Genet Med 2003 Jan-Feb;5(1):1-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.GIM.0000047946.94270.34
AUTORES
/ AUTHORS: - Imperatore G; Pinsky LE; Motulsky A; Reyes
M; Bradley LA; Burke W
INSTITUCIÓN
/ INSTITUTION: - National Canter for Chronic Disease
Prevention and Health Promotion, Centers for Disease Control and Prevention,
Atlanta, Georgia 30341, USA.
RESUMEN
/ SUMMARY: - Hereditary hemochromatosis (HHC) is a
condition characterized by excess iron in body tissues, resulting in
complications such as cirrhosis, cardiomyopathy, diabetes, and arthritis. These
complications usually manifest during adulthood. Two methods of screening for
the detection of early stage of HHC are available: serum iron measures and
molecular testing to detect mutations in the gene. These phenotypic and
genotypic screening tests are of particular interest because a simple
treatment-periodic phlebotomy-can be used to prevent iron accumulation and
clinical complications. HHC might represent the first adult-onset genetic
disorder for which universal population-based screening would be appropriate.
Therefore, HHC has been proposed as a paradigm for the introduction of adult
genetic diseases into clinical and public health practice. However, universal
screening for HHC has not been recommended because of the uncertainty about the
natural history of the iron overload or HHC and, in particular, uncertainty
about the prevalence of asymptomatic iron overload and the likelihood that it
will progress to clinical complications. If universal screening is not
appropriate based on current data, what other measures might reduce the disease
burden of iron overload? New studies provide more systematic information about
the penetrance of the C282Y mutation and shed further light on the natural
history of the disorder. The authors review these data and consider their
implications for public health, medical genetics, and primary care. N. Ref:: 64
----------------------------------------------------
[176]
TÍTULO / TITLE: - B-cell activation and
lymphoma in patients with HIV.
REVISTA
/ JOURNAL: - Curr Opin Oncol 2002 Sep;14(5):528-32.
AUTORES
/ AUTHORS: - Martinez-Maza O; Breen EC
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology, David Geffen School
of Medicine, University of California-Los Angeles, 90095, USA. omartinez@mednet.ucla.edu
RESUMEN
/ SUMMARY: - The risk of developing non-Hodgkin
lymphoma (AIDS lymphoma) is greatly increased in HIV infection. Disruption of
immune function by HIV infection may contribute to lymphomagenesis by inducing
(1) loss of immunoregulation of Epstein-Barr virus-infected B cells
[immunoblastic and central nervous system (CNS) lymphoma] caused by loss of
T-cell function, and (2) chronic B-cell hyperactivation enhancing the
generation of genetic lesions (c- :immunoglobulin gene translocation, -6
overexpression) associated with some forms of AIDS lymphoma (Burkitt
lymphoma-like small noncleaved cell lymphoma and large noncleaved cell
lymphoma). Also, the overproduction of B-cell-stimulatory cytokines
(interleukin 10 and 6) has the potential to contribute to tumor development by
supporting the growth and viability of nascent lymphoma cell clones. Therefore,
HIV infection-associated B-cell hyperactivation, including direct activation of
B cells by various mechanisms, and chronic overproduction of B-cell-stimulatory
cytokines have the potential to contribute to the development and growth of
AIDS lymphoma. Several recent reports are discussed in this review, including
recent work relevant to understanding the potential of a virus-encoded
cytokine-like molecule, HHV8 vIL6, to induce B-cell hyperactivation in
HIV-infected people, work pointing to the potential role of a chemokine
(stromal cell-derived factor 1) in lymphomagenesis, and studies on phenotypic
changes in circulating B cells in HIV infection. N. Ref:: 38
----------------------------------------------------
[177]
TÍTULO / TITLE: - New therapies for
ankylosing spondylitis: etanercept, thalidomide, and pamidronate.
REVISTA
/ JOURNAL: - Rheum Dis Clin North Am 2003
Aug;29(3):481-94, viii.
AUTORES
/ AUTHORS: - Davis JC Jr; Huang F; Maksymowych W
INSTITUCIÓN
/ INSTITUTION: - Division of Rheumatology, Department of Medicine,
University of California-San Francisco, 533 Parnassus Avenue, Box 0633, San
Francisco, CA 94143, USA. jdavis@medicine.ucsf.edu
RESUMEN
/ SUMMARY: - Ankylosing spondylitis (AS) is the most
common of a group of diseases called seronegative spondyloarthropathies. This
group of diseases shares common demographic, clinical, and genetic features.
This article reviews the rationale, clinical efficacy, and safety reports of
etanercept, thalidomide, and pamidronate in the treatment of patients who have
AS. N. Ref:: 48
----------------------------------------------------
[178]
TÍTULO / TITLE: - Signal transduction via
MHC class I molecules in endothelial and smooth muscle cells.
REVISTA
/ JOURNAL: - Crit Rev Immunol 2003;23(1-2):109-28.
AUTORES
/ AUTHORS: - Reed EF
INSTITUCIÓN
/ INSTITUTION: - UCLA Immunogenetics Center, Department of
Pathology and Laboratory Medicine, David Geffen School of Medicine, University
of California, Los Angeles, CA 90095, USA. ereed@mednet.ucla.edu
RESUMEN
/ SUMMARY: - MHC class I molecules have long been
recognized for their ability to stimulate intracellular signals in T and B
lymphocytes. More recently, it has become clear that MHC class I molecules can
also initiate intracellular signals in endothelial and smooth muscle cells,
which synergize with growth factor receptors to elicit cell proliferation. This
review describes our current knowledge of class I-mediated signaling pathways
in human endothelial and smooth muscle cells. The role of the class I signaling
pathway in modulating cell growth and the clinical significance of this pathway
in chronic allograft rejection are discussed.
N. Ref:: 190
----------------------------------------------------
[179]
TÍTULO / TITLE: - Targeting proximal T
cell receptor signaling in transplantation.
REVISTA
/ JOURNAL: - Transplantation 2003 Jun 27;75(12):1921-7.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000070168.42915.47
AUTORES
/ AUTHORS: - Hamawy MM
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Wisconsin, Madison, 53792, USA. hamawy@surgery.wisc.edu
RESUMEN
/ SUMMARY: - In the past two decades, an immense amount
of information has been generated on the mechanism of T cell receptor (TCR)
signaling (also called signal 1). This overview describes the major signalling
pathways in the TCR signal transduction cascade and focuses on proximal events
in TCR signaling. The review also discusses some of the strategies that target
proximal TCR signaling, which are used for preventing graft rejection. N. Ref:: 61
----------------------------------------------------
[180]
TÍTULO / TITLE: - Alemtuzumab
(Campath-1H) for treatment of lymphoid malignancies in the age of
nonmyeloablative conditioning?
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2002
Dec;30(12):797-804.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703733
AUTORES
/ AUTHORS: - Hale G; Slavin S; Goldman JM; Mackinnon S;
Giralt S; Waldmann H
INSTITUCIÓN
/ INSTITUTION: - Sir William Dunn School of Pathology,
University of Oxford, Oxford, UK.
RESUMEN
/ SUMMARY: - The anti-CD52 (Campath-1) monoclonal
antibodies (Mabs) have a substantial history of use for controlling
graft-versus-host disease in allogeneic bone marrow transplantation. Now, with
the availability of a humanised form, alemtuzumab (Campath-1H), and the
demonstration that this agent can reduce the tumour burden in B-CLL, a new
niche may be found - as a potentially curative agent in which its tumour
purging ability in vivo combines with its role as a conditioning agent in
nonmyeloablative transplantation. Review of the literature shows that
alemtuzumab has unique advantages as a method of depleting malignant
lymphocytes, including those in patients resistant to conventional chemotherapy.
Alemtuzumab can also be used in BMT for depletion of normal T and B lymphocytes
of both the recipient and donor for prevention of graft rejection and GVHD. It
allows good stem cell recovery with resultant rapid engraftment, has a low risk
of EBV-triggered secondary malignancy and does not interfere with blood stem
cell mobilisation. As a method of eliminating the malignant clone in B-CLL,
alemtuzumab has shown remarkable efficacy in heavily pre-treated patients, a
number of whom have progressed to autologous or allogeneic transplantation.
Efficacy data are shown within the context of other transplantation data for
B-CLL. These results indicate that the combination of tumour-depleting and
immunosuppressive properties of alemtuzumab should be explored, with the hope
of providing improved treatment options for elderly patients with advanced
B-CLL or indolent lymphoma whose prognosis is too poor currently to allow
treatment with traditional regimens of high-dose myeloablative chemotherapy. N. Ref:: 74
----------------------------------------------------
[181]
TÍTULO / TITLE: - Modulation of T cell
immunity by TCR/pMHC dwell time and activating/inhibitory receptor pairs on the
antigen-presenting cell.
REVISTA
/ JOURNAL: - Curr Pharm Des 2003;9(3):233-44.
AUTORES
/ AUTHORS: - Kalergis AM
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Genetics and
Immunology, The Rockefeller University. Departmento de Genetica Molecular y
Microbiologia, Pontificia Universidad Catolica de Chile. kalergi@rockefeller.edu
RESUMEN
/ SUMMARY: - The molecular interactions occurring at
the interface between the antigen presenting cell (APC) and the T lymphocyte
play an important role in the immune surveillance against infectious agents and
tumors, as well as in autoimmunity and transplant rejection. The significance
of the APC-T cell interaction in immunity is underscored by the observation
that deficiencies in the function of either one of these two cell types cause
extreme susceptibility to infections and tumor growth. Furthermore, a
disregulated APC-T cell interaction can initiate autoimmunity. Thus, antigen
recognition by T cells must be tightly regulated in order to ensure protection
against pathogens and tumors, avoiding activation of self-reactive T cells.
Efficient T cell activation requires two simultaneous signals provided by the
APC: Antigen (or signal 1) and co-stimulation (or signal 2). The specificity of
antigen recognition by T cells (signal 1) is controlled exclusively by the T
cell receptor (TCR), an extremely diverse heterodimeric protein composed of
disulfide-bonded alpha and beta chains. While it is clear that the TCR
recognizes antigens as small peptides bound to molecules of the Major
Histocompatibility Complex (MHC), the molecular explanation for the specificity
of antigen recognition by the betaalphaTCR is just beginning to be elucidated.
In this review are described some of the advances made in the understanding of
the molecular interactions that define the antigen-specificity of the TCR, and
the current models for T cell activation by antigen on APCs are discussed. N. Ref:: 128
----------------------------------------------------
[182]
TÍTULO / TITLE: - Monoclonal antibodies
for the prevention and treatment of graft-versus-host disease.
REVISTA
/ JOURNAL: - Semin Oncol 2003 Aug;30(4):509-19.
AUTORES
/ AUTHORS: - Bruner RJ; Farag SS
INSTITUCIÓN
/ INSTITUTION: - Bone Marrow Transplantation Program, The
Ohio State University Comprehensive Cancer Center, Columbus, USA.
RESUMEN
/ SUMMARY: - Acute and chronic graft-versus-host
disease (GvHD) remain major obstacles to successful allogeneic hematopoietic
stem cell transplantation, contributing substantially to morbidity and
non-relapse mortality. Better understanding of the immunopathophysiology of
GvHD has identified a number of targets for intervention. Among newly developed
agents suitable for the prevention and treatment of GvHD, monoclonal antibodies
hold much promise. Monoclonal antibodies currently available, such as
infliximab and anti-interferon-gamma (anti-IFN-gamma), are capable of blocking
of the action of initiating and effector cytokines. Antibodies directed against
activated T cells, including daclizumab, visilizumab and ABX-CBL, may offer more
specificity than the more broadly acting pan-T-cell-depleting agents. Finally,
the clinical investigation of antibodies to adhesion molecules (such as LFA-1),
or distal effector mechanisms (such as FasL) may offer another level of
specificity. Many of these monoclonal antibodies have already undergone
clinical testing. Campath-1H has been used for the prevention of acute GvHD
with success. Daclizumab, infliximab, visilizumab, and ABX-CBL have shown
promising activity in steroid-resistant acute GvHD in early clinical testing.
This review summarizes current experience with monoclonal antibodies in the
management of acute and chronic GvHD. Over the next decade, however, the
challenge will be to define the relative place of these antibodies in the
therapeutic armamentarium for GvHD and their impact on long-term survival. N. Ref:: 101
----------------------------------------------------
[183]
TÍTULO / TITLE: - Genetic predisposition
to infectious pathogens: a review of less familiar variants.
REVISTA
/ JOURNAL: - Pediatr Infect Dis J 2003
May;22(5):457-61.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.inf.0000068205.82627.55
AUTORES
/ AUTHORS: - Somech R; Amariglio N; Spirer Z; Rechavi G
INSTITUCIÓN
/ INSTITUTION: - Pediatric Hemato-Oncology, Chaim Sheba
Medical Center, Tel Hashomer, Israel.
RESUMEN
/ SUMMARY: - The susceptibility and clinical
manifestations of infectious diseases in human populations are influenced by a
variety of factors, among them host genetics. Obvious examples for the effect
of host genetics on predisposition to unique infections are the primary
immunodeficiency diseases. Minor gene variants that influence the host immune
system are much more common. The iceberg model can be used to illustrate the
epidemiology of immunodeficiency states. Accordingly only a few individuals
have known and severe recognized primary immunodeficiencies, whereas many more
patients have mild immunodeficiencies that may remain undiagnosed and are
predisposed to a unique infectious disease. We review some of the less common
variants that influence the host defense and predispose to certain infectious
agents or change their outcome. N.
Ref:: 43
----------------------------------------------------
[184]
TÍTULO / TITLE: - Tissue factor and
coronary artery disease.
REVISTA
/ JOURNAL: - Cardiovasc Res 2002 Feb 1;53(2):313-25.
AUTORES
/ AUTHORS: - Moons AH; Levi M; Peters RJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiology, Academic Medical
Center, Room F3-236, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
RESUMEN
/ SUMMARY: - Plaque disruption with superimposed
thrombosis is the main cause of acute coronary events such as acute myocardial
infarction and unstable angina. Among other factors, tissue factor seems to
play an important role determining plaque thrombogenicity. Tissue factor is a
potent initiator of the coagulation cascade situated within the vessel wall and
is highly exposed to the blood after plaque rupture. Several mediators involved
in the process of atherosclerotic plaque formation are capable of inducing
tissue factor expression in cells such as monocytes, macrophages and
endothelial cells, which under normal conditions do not express tissue factor
or to a limited extent only. The increased expression of tissue factor is not
limited to the plaque but is also found in circulating monocytes in patients
with acute coronary syndromes. In addition, studies have shown an important
contribution of tissue factor in the pathogenesis of thrombosis and restenosis
after balloon angioplasty. Recent basic studies focus on the therapeutic
inhibition of tissue factor. Specific and non-specific inhibitors of tissue
factor or the tissue factor/factor VIIa complex have been developed or
identified, and have been tested in experimental studies. Clinical studies are
currently being initiated. In this review, we present the current knowledge on
the role of tissue factor in atherosclerosis, arterial intervention and
potential pharmacological approaches, with focus on acute coronary
syndromes. N. Ref:: 162
----------------------------------------------------
[185]
TÍTULO / TITLE: - HFE gene and hereditary
hemochromatosis: a HuGE review. Human Genome Epidemiology.
REVISTA
/ JOURNAL: - Am J Epidemiol 2001 Aug 1;154(3):193-206.
AUTORES
/ AUTHORS: - Hanson EH; Imperatore G; Burke W
INSTITUCIÓN
/ INSTITUTION: - United States Air Force School of
Aerospace Medicine, Brooks Air Force Base, San Antonio, TX, USA. erichansonmdmph@yahoo.com
RESUMEN
/ SUMMARY: - Hereditary hemochromatosis (HHC) is an
autosomal recessive disorder of iron metabolism characterized by increased iron
absorption and deposition in the liver, pancreas, heart, joints, and pituitary
gland. Without treatment, death may occur from cirrhosis, primary liver cancer,
diabetes, or cardiomyopathy. In 1996, HFE, the gene for HHC, was mapped on the
short arm of chromosome 6 (6p21.3). Two of the 37 allelic variants of HFE
described to date (C282Y and H63D) are significantly correlated with HHC.
Homozygosity for the C282Y mutation was found in 52-100% of previous studies on
clinically diagnosed probands. In this review, 5% of HHC probands were found to
be compound heterozygotes (C282Y/H63D), and 1.5% were homozygous for the H63D
mutation; 3.6% were C282Y heterozygotes, and 5.2% were H63D heterozygotes. In
7% of cases, C282Y and H63D mutations were not present. In the general
population, the frequency of the C282Y/C282Y genotype is 0.4%. C282Y
heterozygosity ranges from 9.2% in Europeans to nil in Asian, Indian
subcontinent, African/Middle Eastern, and Australasian populations. The H63D
carrier frequency is 22% in European populations. Accurate data on the
penetrance of the different HFE genotypes are not available. Extrapolating from
limited clinical observations in screening studies, an estimated 40--70% of
persons with the C282Y homozygous genotype will develop clinical evidence of
iron overload. A smaller proportion will die from complications of iron
overload. To date, population screening for HHC is not recommended because of
uncertainties about optimal screening strategies, optimal care for susceptible
persons, laboratory standardization, and the potential for stigmatization or discrimination. N. Ref:: 103
----------------------------------------------------
[186]
TÍTULO / TITLE: - Ethical considerations
on preimplantation genetic diagnosis for HLA typing to match a future child as
a donor of haematopoietic stem cells to a sibling.
REVISTA
/ JOURNAL: - Hum Reprod 2002 Mar;17(3):534-8.
AUTORES
/ AUTHORS: - Pennings G; Schots R; Liebaers I
INSTITUCIÓN
/ INSTITUTION: - Department of Philosophy, Lok. 5 C 442,
Academic Hospital, Free University Brussels, Pleinlaan 2, B-1050 Brussels,
Belgium. gpenning@vub.ac.be
RESUMEN
/ SUMMARY: - Recently, several requests were made by
couples with an affected child who wanted preimplantation genetic diagnosis
(PGD) to select embryos in the hope of conceiving an HLA identical donor
sibling. This article considers the ethical arguments for and against the
application of PGD for this goal. Only embryos HLA matched with an existing
sibling in need of a compatible donor of haematopoietic stem cells would be transferred.
The main arguments are the instrumentalization of the child, the best-interests
standard, the postnatal test for acceptability and the experience of the donor
child. It is argued that conceiving a child to save a child is a morally
defensible decision on the condition that the operation that will be performed
on the future child is acceptable to perform on an existing child. The
instrumentalization of the donor child does not demonstrate disrespect for its
autonomy or its intrinsic worth. N.
Ref:: 29
----------------------------------------------------
[187]
TÍTULO / TITLE: - Host and viral genetics
and risk of cervical cancer: a review.
REVISTA
/ JOURNAL: - Virus Res 2002 Nov;89(2):229-40.
AUTORES
/ AUTHORS: - Hildesheim A; Wang SS
INSTITUCIÓN
/ INSTITUTION: - Division of Cancer Epidemiology and
Genetics, National Cancer Institute, 6120 Executive Blvd, Room 7062, EPS/MSC#
7234, Rockville, MD 20852, USA. hildesha@exchange.nih.gov
RESUMEN
/ SUMMARY: - Infection with human papillomaviruses
(HPV) is known to play a central role in the development of cervical cancer.
Both host and viral genetic factors have been postulated to be important
determinants of risk of HPV progression to neoplasia among infected
individuals. In this report, we review epidemiological studies that have
evaluated the role in cervical cancer pathogenesis of genetic variation in
human leukocyte antigen (HLA) genes and in the HPV genome itself. A protective
effect of HLA Class II DRB1*13/DBQ1*0603 alleles is the most consistent HLA
finding in the published literature. A consistent association between HPV16
non-European variants and risk of disease is also evident from published work.
These findings are discussed. Gaps in our understanding and future research
needs are also discussed. N.
Ref:: 90
----------------------------------------------------
[188]
TÍTULO / TITLE: - Preventing saphenous
vein graft failure: does gene therapy have a role?
REVISTA
/ JOURNAL: - Ann Thorac Surg 2003 Sep;76(3):959-66.
AUTORES
/ AUTHORS: - Akowuah EF; Sheridan PJ; Cooper GJ; Newman
C
INSTITUCIÓN
/ INSTITUTION: - Cardiovascular Research Group, The
University of Sheffield, Sheffield, United Kingdom. akowuah@yahoo.com
RESUMEN
/ SUMMARY: - Gene therapy potentially allows local
delivery and expression of cytokines, growth factors, and other mediators. In
spite of increasing knowledge of the human genome, applications in clinical
practice are only just beginning. The main limitations of effective clinical
gene therapy are safety and low transfection efficiency. Saphenous vein grafts
permit the transfection of the conduit ex vivo. This allows a variety of
transfection techniques to be used, enhancing the transfection efficiency while
limiting the risk of systemic complications. This review examines the potential
mechanisms of gene delivery and genetic targets that may be applied to
saphenous vein graft failure. N.
Ref:: 68
----------------------------------------------------
[189]
- Castellano -
TÍTULO / TITLE:Las inmunofilinas: agentes
neuroprotectores y promotores de la regeneracion neural. Immunophilins:
neuroprotective agents and promoters of neural regeneration.
REVISTA
/ JOURNAL: - Neurologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.stmeditores.com/Revistas/ffasciculo.php?Mw==&MTk=&MjUy
●●
Cita: Neurologia: <> 2002 Apr;17(4):200-13.
AUTORES
/ AUTHORS: - Udina E; Navarro X
INSTITUCIÓN
/ INSTITUTION: - Grupo de Neuroplasticidad y Regeneracion,
Departamento de Biologia Celular, Fisiologia e Inmunologia, Universitat
Autonoma de Barcelona, Bellaterra, España.
RESUMEN
/ SUMMARY: - Immunophilins are a family of proteins
mainly known because they act as receptors of the immunosuppressant drugs
cyclosporin A (CsA) and FK506. Immunophilins serve several general functions,
including regulation of mitochondrial permeability, modulation of ion channels
stability and acting as chaperones for a variety of proteins. However,
immunophilins are also present at high density in the nervous system. CsA,
FK506 and other derivatives inhibit the function of immunophilins and, through
bloking or activating several intracellular pathways, it has been shown that
they exert neuroprotective effects in different experimental models of
ischemia, Parkinson’s disease and excitotoxic insults. Moreover, FK506 also has
neuroregenerative effects, by enhancing the axonal regeneration rate after
lesions of the peripheral nervous system. The development of new agents that
selectively bind to immunophilins opens new interesting perspectives for the
therapy of degenerative diseases and injuries of the nervous system. N. Ref:: 100
----------------------------------------------------
[190]
TÍTULO / TITLE: - Protein phosphatase 2A
on track for nutrient-induced signalling in yeast.
REVISTA
/ JOURNAL: - Mol Microbiol. Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.blackwell-synergy.com/
●●
Cita: Molecular Microbiology: <> 2002 Feb;43(4):835-42.
AUTORES
/ AUTHORS: - Zabrocki P; Van Hoof C; Goris J; Thevelein
JM; Winderickx J; Wera S
INSTITUCIÓN
/ INSTITUTION: - Laboratorium voor Moleculaire Celbiologie,
K.U.Leuven, Kasteelpark Arenberg 31, B-3001 Leuven-Heverlee, Flanders, Belgium.
RESUMEN
/ SUMMARY: - Early studies identified two bona fide
protein phosphatase 2A (PP2A)-encoding genes in Saccharomyces cerevisiae,
designated PPH21 and PPH22. In addition, three PP2A-related phosphatases,
encoded by PPH3, SIT4 and PPG1, have been identified. All share as much as 86%
sequence similarity at the amino acid level. This review will focus primarily
on Pph21 and Pph22, but some aspects of Sit4 regulation will also be discussed.
Whereas a role for PP2A in yeast morphology and cell cycle has been readily
recognized, uncovering its function in yeast signal transduction is a more
recent breakthrough. Via their interaction with phosphorylated Tap42, PP2A and
Sit4 play a pivotal role in target of rapamycin (TOR) signalling. PPH22
overexpression mimics overactive cAMP-PKA (protein kinase A) signalling and
PP2A and Sit4 might represent ceramide signalling targets. The methylation of
its catalytic subunit stabilizes the heterotrimeric form of PP2A and might
counteract TOR signalling. We will show how these new elements could lead us to
understand the role and regulation of PP2A in nutrient-induced signalling in
baker’s yeast. N.
Ref:: 41
----------------------------------------------------
[191]
TÍTULO / TITLE: - Acremonium strictum
pulmonary infection in a leukemic patient successfully treated with
posaconazole after failure of amphotericin B.
REVISTA
/ JOURNAL: - Eur J Clin Microbiol Infect Dis 2002
Nov;21(11):814-7. Epub 2002 Oct 31.
●●
Enlace al texto completo (gratuito o de pago) 1007/s10096-002-0828-8
AUTORES
/ AUTHORS: - Herbrecht R; Letscher-Bru V; Fohrer C;
Campos F; Natarajan-Ame S; Zamfir A; Waller J
INSTITUCIÓN
/ INSTITUTION: - Departement d’Hematologie et d’Oncologie,
Hopital de Hautepierre, Avenue Moliere, 67098 Strasbourg, France. raoul.herbrecht@chru-strasbourg.fr
RESUMEN
/ SUMMARY: - A severely neutropenic patient with
chronic lymphocytic leukemia developed a diffuse bilateral pulmonary infection
while receiving a therapeutic daily dosage of intravenous amphotericin B for
Candida glabrata esophagitis. Computed tomography of the chest showed numerous
lung nodules, ground glass areas and a pleural effusion. Biopsy of one nodule
demonstrated hyaline septate hyphae. Multiple sputum cultures grew Acremonium
strictum. Increasing the dose of amphotericin B and the addition of
itraconazole did not resolve the infection. Change of treatment to posaconazole
given orally at 200 mg four times/d resulted in progressive improvement leading
finally to cure after 24 weeks of therapy. Treatment with posaconazole was
clinically and biologically well tolerated.
N. Ref:: 15
----------------------------------------------------
[192]
TÍTULO / TITLE: - mTOR as a target for
cancer therapy.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:339-59.
AUTORES
/ AUTHORS: - Houghton PJ; Huang S
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Pharmacology, St.
Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794,
USA. peter.houghton@stjude.org
RESUMEN
/ SUMMARY: - The target of rapamycin, mTOR, acts as a
sensor for mitogenic stimuli, such as insulin-like growth factors and cellular
nutritional status, regulating cellular growth and division. As many tumors are
driven by autocrine or paracrine growth through the type-I insulin-like growth
factor receptor, mTOR is potentially an attractive target for
molecular-targeted treatment. Further, a rationale for anticipating
tumor-selective activity based on transforming events frequently identified in
malignant disease is becoming established.
N. Ref:: 73
----------------------------------------------------
[193]
TÍTULO / TITLE: - Hepatitis B core
antibody-positive grafts: recipient’s risk.
REVISTA
/ JOURNAL: - Transplantation 2003 Feb 15;75(3
Suppl):S49-53.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000047006.96782.64
AUTORES
/ AUTHORS: - de Villa VH; Chen YS; Chen CL
INSTITUCIÓN
/ INSTITUTION: - Liver Transplant Program, Department of
Surgery, Chang Gung University, Chang Gung Memorial Hospital, Kaohsiung Medical
Center, Kaohsiung, Taiwan.
RESUMEN
/ SUMMARY: - The transmission of hepatitis B virus
infection through hepatitis B core antibody (anti-HBc)-positive liver grafts in
hepatitis B surface antigen (HBsAg)-negative recipients has been established.
The mandatory use of immunosuppression in transplant patients favors
reactivation of latent virus that may be present in grafts from HBsAg-negative
anti-HBc-positive donors. With the persistent organ donor scarcity, the use of
these grafts cannot be avoided, especially in urgent cases and in areas where
the prevalence of the hepatitis B virus is high, as in Asia. The recognition of
posttransplant de novo hepatitis B from core antibody-positive liver donors
has, therefore, led to modifications in graft allocation policies and the
introduction of strategies for prophylaxis. The risk of developing this type of
new-onset hepatitis B virus infection in liver transplant recipients and the
various approaches to minimize this risk are reviewed. The peculiar
implications of using core antibody-positive grafts in the context of living
donor liver transplantation in Asia are discussed. N. Ref:: 30
----------------------------------------------------
[194]
TÍTULO / TITLE: - Commentary. Major
breakthrough in the HLA-G debate: occurrence of pregnancy in human depends on
the HLA-G status of preimplantation embryos.
REVISTA
/ JOURNAL: - Eur J Immunol 2002 Feb;32(2):309-10.
●●
Enlace al texto completo (gratuito o de pago) 1002/1521-4141(200202)32:2<309::AID-IMMU309>3.0.CO;2-H
[pii]
AUTORES
/ AUTHORS: - Bouteiller PL
INSTITUCIÓN
/ INSTITUTION: - INSERM U395, CHU Purpan, BP 3028, 31024
Toulouse Cedex 3, France. phil.lb@toulouse.inserm.fr N. Ref:: 16
----------------------------------------------------
[195]
TÍTULO / TITLE: - Serine-threonine
protein phosphatase inhibitors: development of potential therapeutic
strategies.
REVISTA
/ JOURNAL: - J Med Chem 2002 Mar 14;45(6):1151-75.
AUTORES
/ AUTHORS: - McCluskey A; Sim AT; Sakoff JA
INSTITUCIÓN
/ INSTITUTION: - School of Biological & Chemical
Science, Medicinal Chemistry Group, The University of Newcastle, Callaghan, NSW
2308, Australia. amcclusk@mail.newcastle.edu.au N. Ref:: 329
----------------------------------------------------
[196]
TÍTULO / TITLE: - Filgrastim treatment of
acute myelogenous leukemia (M7) relapse after allogeneic peripheral stem cell
transplantation resulting in both graft-versus-leukemia effect with cytogenetic
remission and chronic graft-versus-host disease manifesting as polyserositis
and subsequent bronchiolitis obliterans with organizing pneumonia.
REVISTA
/ JOURNAL: - Int J Hematol 2002 Nov;76(4):360-4.
AUTORES
/ AUTHORS: - Law L; Tuscano J; Wun T; Ahlberg K;
Richman C
INSTITUCIÓN
/ INSTITUTION: - Division of Hematology/Oncology,
Department of Internal Medicine, University of California, Davis, California,
USA.
RESUMEN
/ SUMMARY: - Filgrastim (granulocyte colony-stimulating
factor) has recently been reported to successfully treat patients with leukemic
relapse after allogeneic peripheral stem cell transplantation (PSCT). However,
the majority of the patients who responded also developed graft-versus-host
disease (GVHD). Polyserositis as a manifestation of GVHD is a rare phenomenon.
We report the first case of polyserositis following the use of filgrastim to
treat a patient with acute myelogenous leukemia (M7), who had relapsed after an
initially successful allogeneic PSCT. The polyserositis manifested with
effusions and was initially controlled with high doses of steroids and
pericardial stripping; however, after a quiescent period the patient eventually
developed bronchiolitis obliterans with organizing pneumonia that required
additional immunosuppressive therapy. We review the literature on GVHD-associated
polyserositis and offer potential explanations for its pathogenesis. N. Ref:: 20
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[197]
TÍTULO / TITLE: - Inflammatory
myopathies: clinical, diagnostic and therapeutic aspects.
REVISTA
/ JOURNAL: - Muscle Nerve 2003 Apr;27(4):407-25.
●●
Enlace al texto completo (gratuito o de pago) 1002/mus.10313
AUTORES
/ AUTHORS: - Mastaglia FL; Garlepp MJ; Phillips BA;
Zilko PJ
INSTITUCIÓN
/ INSTITUTION: - Centre for Neuromuscular and Neurological
Disorders, University of Western Australia, Queen Elizabeth II Medical Centre,
Nedlands, Australia. flmast@cyllene.uwa.edu.au
RESUMEN
/ SUMMARY: - The three major forms of immune-mediated
inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and
inclusion-body myositis (IBM). They each have distinctive clinical and
histopathologic features that allow the clinician to reach a specific diagnosis
in most cases. Magnetic resonance imaging is sometimes helpful, particularly if
the diagnosis of IBM is suspected but has not been formally evaluated.
Myositis-specific antibodies are not helpful diagnostically but may be of
prognostic value; most antibodies have low sensitivity. Muscle biopsy is
mandatory to confirm the diagnosis of an inflammatory myopathy and to allow
unusual varieties such as eosinophilic, granulomatous, and parasitic myositis,
and macrophagic myofasciitis, to be recognized. The treatment of the
inflammatory myopathies remains largely empirical and relies upon the use of
corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all
of which have nonselective effects on the immune system. Further controlled
clinical trials are required to evaluate the relative efficacy of the available
therapeutic modalities particularly in combinations, and of newer
immunosuppressive agents (mycophenolate mofetil and tacrolimus) and
cytokine-based therapies for the treatment of resistant cases of DM, PM, and
IBM. Improved understanding of the molecular mechanisms of muscle injury in the
inflammatory myopathies should lead to the development of more specific forms
of immunotherapy for these conditions. N.
Ref:: 256
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[198]
TÍTULO / TITLE: - MHC class I antigen
processing regulated by cytosolic proteolysis-short cuts that alter peptide
generation.
REVISTA
/ JOURNAL: - Mol Immunol 2002 Oct;39(3-4):171-9.
AUTORES
/ AUTHORS: - Kessler BM; Glas R; Ploegh HL
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, Harvard Medical
School, Room 137, Building D2, 200 Longwood Avenue, Boston, MA 02115, USA.
RESUMEN
/ SUMMARY: - Cytotoxic T lymphocyte (CTL)-mediated
immune responses rely on the efficiency of MHC class I ligand generation and
presentation by antigen presenting cells (APCs). Whereas the abnormal
expression of MHC molecules and transporters associated with antigen processing
(TAPs) are commonly discussed as factors that modulate antigen presentation,
much less is known about possible regulatory mechanisms at the level of
proteolysis responsible for the generation of antigenic peptides. The
ubiquitin-proteasome system is recognized as the major component responsible
for this process in the cytosol and its activity can be regulated by cytokines,
such as IFN-gamma. However, new evidence suggests the involvement of other
proteases that can contribute to cytosolic proteolysis and therefore, to the
quality and quantity of antigen production. Here, we review recent findings on
an increasing number of proteolytic enzymes linked to antigen presentation, and
we discuss how regulation of cytosolic protease activities might have
implications for immune escape mechanisms that could be used by tumor cells and
pathogens. N. Ref:: 99
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[199]
TÍTULO / TITLE: - MHC class I receptors
on natural killer cells: on with the old and in with the new.
REVISTA
/ JOURNAL: - Clin Sci (Lond) 2003 Aug;105(2):127-40.
●●
Enlace al texto completo (gratuito o de pago) 1042/CS20030095
AUTORES
/ AUTHORS: - Khakoo SI; Brooks CR
INSTITUCIÓN
/ INSTITUTION: - Division of Infection Inflammation and
Repair, School of Medicine, University of Southampton, Mailpoint 811,
Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. sik@soton.ac.uk
RESUMEN
/ SUMMARY: - The functions of natural killer (NK) cells
are controlled by an abundance of activating and inhibitory receptors. Many of
these interact with MHC class I molecules. The MHC system also interacts with
cytotoxic T-lymphocytes and has been shown to comprise a rapidly evolving
family of molecules. This challenges the functional relationship of NK cell
receptors with their ligands. Although individual receptors have become subject
to species-specific expansions over evolutionary time, the main themes of the
NK cell interaction with MHC class I have been preserved. This review details
the interaction of NK cell receptors with MHC class I and discusses their
unexpectedly rapid evolution. N.
Ref:: 122
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[200]
TÍTULO / TITLE: - Mitochondrial
permeability transition in acute neurodegeneration.
REVISTA
/ JOURNAL: - Biochimie 2002 Feb-Mar;84(2-3):241-50.
AUTORES
/ AUTHORS: - Friberg H; Wieloch T
INSTITUCIÓN
/ INSTITUTION: - Laboratory for Experimental Brain
Research, Wallenberg Neuroscience Center, BMC A13, 221 84 Lund, Sweden.
RESUMEN
/ SUMMARY: - Acute neurodegeneration in man is
encountered during and following stroke, transient cardiac arrest, brain
trauma, insulin-induced hypoglycemia and status epilepticus. All these severe
clinical conditions are characterized by neuronal calcium overload, aberrant
cell signaling, generation of free radicals and elevation of cellular free
fatty acids, conditions that favor activation of the mitochondrial permeability
transition pore (mtPTP). Cyclosporin A (CsA) and its analog N-methyl-valine-4-cyclosporin
A (MeValCsA) are potent blockers of the mtPTP and protect against neuronal
death following excitotoxicity and oxygen glucose deprivation. Also, CsA and
MeValCsA diminish cell death following cerebral ischemia, trauma, and
hypoglycemia. Here we present data that strongly imply the mtPT in acute
neurodegeneration in vivo. Compounds that readily pass the blood-brain-barrier
(BBB) and block the mtPT may be neuroprotective in stroke. N. Ref:: 100
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