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Revisiones-Clínica-Etiología & Patología *** Reviews-Clinical-Etiology & Pathology

 

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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Enlace / Link

 

[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

 

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[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

 

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[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

 

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[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

 

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[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

 

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[6]

TÍTULO / TITLE:  - Dendritic cells: emerging pharmacological targets of immunosuppressive drugs.

REVISTA / JOURNAL:  - Nat Rev Immunol 2004 Jan;4(1):24-34.

      ●● Enlace al texto completo (gratuito o de pago) 1038/nri1256

AUTORES / AUTHORS:  - Hackstein H; Thomson AW

INSTITUCIÓN / INSTITUTION:  - Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University Giessen, Langhansstr. 7, D-35392 Giessen, Germany. holger.hackstein@immunologie.med.uni-giessen.de

RESUMEN / SUMMARY:  - Immunosuppressive drugs have revolutionized organ transplantation and improved the therapeutic management of autoimmune diseases. The development of immunosuppressive drugs and understanding of their action traditionally has been focused on lymphocytes, but recent evidence indicates that these agents interfere with immune responses at the earliest stage, targeting key functions of dendritic cells (DCs). Here, we review our present understanding of how classical and new immunosuppressive agents interfere with DC development and function. This knowledge might provide a rational basis for the selection of immunosuppressive drugs in different clinical settings and for the generation of tolerogenic DCs in the laboratory.  N. Ref:: 116

 

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[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.

 

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[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

 

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[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

 

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[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

 

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[11]

TÍTULO / TITLE:  - Skin cancers after organ transplantation.

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): <> 2003 Apr 24;348(17):1681-91.

      ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMra022137

AUTORES / AUTHORS:  - Euvrard S; Kanitakis J; Claudy A

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Edouard Herriot Hospital, Lyons, France. sylvie.euvrard@numericable.fr  N. Ref:: 100

 

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[12]

TÍTULO / TITLE:  - Haematopoietic cell transplantation as immunotherapy.

REVISTA / JOURNAL:  - Nature 2001 May 17;411(6835):385-9.

      ●● Enlace al texto completo (gratuito o de pago) 1038/35077251

AUTORES / AUTHORS:  - Appelbaum FR

INSTITUCIÓN / INSTITUTION:  - Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D5-310, PO Box 19024, Seattle, Washington 98109-1024, USA.

RESUMEN / SUMMARY:  - The graft-versus-tumour effect seen after allogeneic (genetically different) haematopoietic cell transplantation for human malignancies represents the clearest example of the power of the human immune system to eradicate cancer. Recent advances in our understanding of the immunobiology of stem-cell engraftment, tolerance and tumour eradication are allowing clinicians to better harness this powerful effect.  N. Ref:: 60

 

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[13]

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.

 

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[14]

TÍTULO / TITLE:  - Chronic graft-vs-host disease.

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl 

      ●● Cita: JAMA: <> 2003 Nov 19;290(19):2599-603.

      ●● Enlace al texto completo (gratuito o de pago) 1001/jama.290.19.2599

AUTORES / AUTHORS:  - Bhushan V; Collins RH Jr

INSTITUCIÓN / INSTITUTION:  - Hematopoietic Cell Transplantation Program, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390-8852, USA.  N. Ref:: 26

 

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[15]

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

 

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[16]

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

 

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[17]

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

 

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[18]

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

 

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[19]

- 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

 

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[20]

TÍTULO / TITLE:  - Regulating the immune response to transplants. a role for CD4+ regulatory cells?

REVISTA / JOURNAL:  - Immunity 2001 Apr;14(4):399-406.

AUTORES / AUTHORS:  - Waldmann H; Cobbold S

INSTITUCIÓN / INSTITUTION:  - Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom. herman.waldmann@path.ox.ac.uk  N. Ref:: 50

 

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[21]

TÍTULO / TITLE:  - Dendritic cells in transplantation—friend or foe?

REVISTA / JOURNAL:  - Immunity 2001 Apr;14(4):357-68.

AUTORES / AUTHORS:  - Lechler R; Ng WF; Steinman RM

INSTITUCIÓN / INSTITUTION:  - Department of Immunology, Division of Medicine, Hammersmith Hospital, Imperial College School of Medicine, Du Cane Road, London W12 ONN, United Kingdom. r.lechler@ic.ac.uk  N. Ref:: 80

 

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[22]

TÍTULO / TITLE:  - Nystatin prophylaxis and treatment in severely immunodepressed patients.

REVISTA / JOURNAL:  - Cochrane Database Syst Rev 2002;(4):CD002033.

AUTORES / AUTHORS:  - Gotzsche PC; Johansen HK

INSTITUCIÓN / INSTITUTION:  - The Nordic Cochrane Centre, Rigshospitalet, Dept. 7112, Blegdamsvej 9, Copenhagen O, Denmark, 2100. p.c.gotzsche@cochrane.dk

RESUMEN / SUMMARY:  - BACKGROUND: Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal. OBJECTIVES: To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency. SEARCH STRATEGY: MEDLINE and The Cochrane Library using a comprehensive search strategy, date of last search November 2001. Contacted industry and scanned reference lists. SELECTION CRITERIA: Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B. DATA COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently. A random effects model was used unless p>0.10 for the test of heterogeneity. MAIN RESULTS: We included 12 trials (1,464 patients). The drugs were given prophylactically in ten trials and as treatment in two. Seven trials were in acute leukaemia, two in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients. Nystatin had been compared with placebo in three trials and with fluconazole in nine; the dose varied from 1.5 MIE to 72 MIE daily. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70). The results were very similar if the three studies which were not performed in cancer patients were excluded. REVIEWER’S CONCLUSIONS: Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.  N. Ref:: 22

 

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[23]

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

 

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[24]

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.

 

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[25]

TÍTULO / TITLE:  - Regulatory T cells in transplantation tolerance.

REVISTA / JOURNAL:  - Nat Rev Immunol 2003 Mar;3(3):199-210.

      ●● Enlace al texto completo (gratuito o de pago) 1038/nri1027

AUTORES / AUTHORS:  - Wood KJ; Sakaguchi S

INSTITUCIÓN / INSTITUTION:  - Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. kathryn.wood@nds.ox.ac.uk

RESUMEN / SUMMARY:  - The identification and characterization of regulatory T (T(Reg)) cells that can control immune responsiveness to alloantigens have opened up exciting opportunities for new therapies in transplantation. After exposure to alloantigens in vivo, alloantigen-specific immunoregulatory activity is enriched in a population of CD4+ T cells that express high levels of CD25. In vivo, common mechanisms seem to underpin the activity of CD4+CD25+ T(Reg) cells in both naive and manipulated hosts. However, the origin, allorecognition properties and molecular basis for the suppressive activity of CD4+CD25+ T(Reg) cells, as well as their relationship to other populations of regulatory cells that exist after transplantation, remain a matter of debate.  N. Ref:: 138

 

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[26]

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.

 

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[27]

TÍTULO / TITLE:  - Tolerance and autoimmunity.

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): <> 2001 Mar 1;344(9):655-64.

AUTORES / AUTHORS:  - Kamradt T; Mitchison NA

INSTITUCIÓN / INSTITUTION:  - Deutsches Rheumaforschungszentrum Berlin and Universitatsklinikum Charite, Medizinische Klinik mit Schwerpunkt Rheumatologie and Klinische Immunologie, Germany. kamradt@drfz.de  N. Ref:: 151

 

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[28]

TÍTULO / TITLE:  - Organ-specific autoimmune disease: a deficiency of tolerogenic stimulation.

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: <> 2001 Sep 3;194(5):F31-6.

AUTORES / AUTHORS:  - Lesage S; Goodnow CC

INSTITUCIÓN / INSTITUTION:  - Australian Cancer Research Foundation Genetics Lab, Medical Genome Centre, John Curtin School of Medical Research, Canberra, ACT 2601, Australia.  N. Ref:: 35

 

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[29]

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

 

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[30]

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

 

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[31]

TÍTULO / TITLE:  - Strategies to improve long-term outcomes after renal transplantation.

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 Feb 21;346(8):580-90.

      ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMra011295

AUTORES / AUTHORS:  - Pascual M; Theruvath T; Kawai T; Tolkoff-Rubin N; Cosimi AB

INSTITUCIÓN / INSTITUTION:  - Renal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. mpascual@partners.org  N. Ref:: 99

 

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[32]

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

 

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[33]

TÍTULO / TITLE:  - T cell death and transplantation tolerance.

REVISTA / JOURNAL:  - Immunity 2001 Apr;14(4):407-16.

AUTORES / AUTHORS:  - Li XC; Strom TB; Turka LA; Wells AD

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.  N. Ref:: 50

 

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[34]

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

 

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[35]

TÍTULO / TITLE:  - A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 27;77(2):252-8.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000101495.22734.07

AUTORES / AUTHORS:  - Ciancio G; Burke GW; Gaynor JJ; Mattiazzi A; Roth D; Kupin W; Nicolas M; Ruiz P; Rosen A; Miller J

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu

RESUMEN / SUMMARY:  - BACKGROUND: In an attempt to reduce chronic calcineurin inhibitor induced allograft nephropathy in first cadaver and human leukocyte antigen non-identical living-donor renal transplantation, sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive therapy, with planned dose reductions of tacrolimus (Tacro) over the first year postoperatively. Adjunctive Siro therapy with a similar dose reduction algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and Siro, group C) is described in our companion report in this issue of Transplantation. The present report documents function, patient and graft survival, protocol compliance, and adverse events. RESULTS: As mentioned (in companion report), group demographics were similar. The present study shows no significant differences in 1-year patient and graft survival but does show a trend that points to more difficulties in group C by way of a rising slope of serum creatinine concentration (P=0.02) and decreasing creatinine clearance (P=0.04). There were more patients who discontinued the protocol plan in group C. Thus far, no posttransplant lymphomas have appeared, and infectious complications have not differed among the groups. However, a greater percentage of patients in group C were placed on antihyperlipidemia therapy, with an (unexpected) trend toward a higher incidence of posttransplant diabetes mellitus in this group. Group A required fewer, and group B the fewest, antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This 1-year interim analysis of a long-term, prospective, randomized renal-transplant study indicates that decreasing maintenance dosage of Tacro with adjunctive Siro or MMF appears to point to improved long-term function, with reasonably few adverse events.

 

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[36]

TÍTULO / TITLE:  - Depletion of host reactive T cells by photodynamic cell purging and prevention of graft versus host disease.

REVISTA / JOURNAL:  - Leuk Lymphoma 2003 Nov;44(11):1871-9.

AUTORES / AUTHORS:  - Goggins TF; Chao N

INSTITUCIÓN / INSTITUTION:  - Hematology-Oncology, Duke University Medical Center, 2400 Pratt Street, Ste. 1100, Durham, NC 27710, USA. goggi002@mc.duke.edu

RESUMEN / SUMMARY:  - Graft versus Host Disease (GVHD) is the principal cause of morbidity and mortality in patients undergoing allogeneic stem cell transplant. T cell depletion has been recognized as a method of reducing the incidence of GVHD in allogeneic transplants. Until recently, most T cell depletion methods were non-selective in reducing lymphocytes. Rhodamine purging is one method, which selectively reduces alloreactive T cells preventing GVHD. We review here the methods of non-selective and selective T cell depletion, particularly the newer method of photodynamic purging utilizing rhodamine.  N. Ref:: 129

 

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[37]

- 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

 

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[38]

TÍTULO / TITLE:  - Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis.

REVISTA / JOURNAL:  - J Clin Oncol 2001 Aug 15;19(16):3685-91.

AUTORES / AUTHORS:  - Cutler C; Giri S; Jeyapalan S; Paniagua D; Viswanathan A; Antin JH

INSTITUCIÓN / INSTITUTION:  - Division of Hematologic Oncology, Dana-Farber Cancer Institute, and Harvard School of Public Health, Boston, MA 02115, USA. corey_cutler@dfci.harvard.edu

RESUMEN / SUMMARY:  - PURPOSE: Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures. METHODS: An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed. RESULTS: Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P=.006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P <.001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P <.001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05). CONCLUSION: Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.

 

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[39]

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

 

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[40]

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

 

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[41]

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

 

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[42]

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

 

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[43]

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

 

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[44]

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

 

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[45]

TÍTULO / TITLE:  - Mixed chimerism and transplant tolerance.

REVISTA / JOURNAL:  - Immunity 2001 Apr;14(4):417-24.

AUTORES / AUTHORS:  - Sykes M

INSTITUCIÓN / INSTITUTION:  - Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.  N. Ref:: 80

 

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[46]

TÍTULO / TITLE:  - Chronic rejection.

REVISTA / JOURNAL:  - Immunity 2001 Apr;14(4):387-97.

AUTORES / AUTHORS:  - Libby P; Pober JS

INSTITUCIÓN / INSTITUTION:  - Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA. plibby@rics.bwh.harvard.edu  N. Ref:: 60

 

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[47]

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

 

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[48]

TÍTULO / TITLE:  - Treatment and outcome of invasive bladder cancer in patients after renal transplantation.

REVISTA / JOURNAL:  - J Urol 2004 Mar;171(3):1085-8.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000110612.42382.0a

AUTORES / AUTHORS:  - Master VA; Meng MV; Grossfeld GD; Koppie TM; Hirose R; Carroll PR

INSTITUCIÓN / INSTITUTION:  - Departments of Urology and Surgery, University of California, San Francisco, California 94143, USA. vmaster@urol.ucsf.edu

RESUMEN / SUMMARY:  - PURPOSE: Optimal management and clinical outcome of bladder cancer in renal transplant recipients are not well-defined. We analyzed single institution treatment strategies and outcomes of these patients. MATERIALS AND METHODS: We retrospectively reviewed the University of California, San Francisco transplant database which contains information on 6,288 renal transplants performed between 1964 and 2002. The United Network for Organ Sharing database and Israel Penn International Transplant Tumor Registry were also queried to characterize the global nature of bladder cancer in renal transplant recipients. RESULTS: The United Network for Organ Sharing database (1986 to 2001) contained information on 31 patients who were found to have bladder cancer (0.024% prevalence) and the Israel Penn International Transplant Tumor Registry (1967 to 2001) contained information on 135 patients representing 0.84% of all reported malignancies. We identified 7 renal transplant recipients with bladder cancer at our institution. Invasive transitional cell carcinoma developed in 5 patients at a median of 2.8 years after transplant. Three patients underwent uncomplicated radical cystectomy and preservation of the renal allograft. Overall survival at 48 months was 60%. CONCLUSIONS: Bladder cancer after renal transplantation is not common. For patients who present with invasive disease, traditional extirpative surgery should be considered. Moreover, the allograft is rarely the source of transitional cell carcinoma and can be preserved. In our experience the cancer and urinary outcomes compare favorably with nontransplant patient outcomes after treatment.  N. Ref:: 21

 

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[49]

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

 

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[50]

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

 

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[51]

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

 

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[52]

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

 

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[53]

TÍTULO / TITLE:  - Patient and graft survival following liver transplantation for hepatitis C: much ado about something.

REVISTA / JOURNAL:  - Gastroenterology 2002 Apr;122(4):1162-5.

AUTORES / AUTHORS:  - Charlton M  N. Ref:: 20

 

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[54]

TÍTULO / TITLE:  - The immunological barrier to xenotransplantation.

REVISTA / JOURNAL:  - Immunity 2001 Apr;14(4):437-46.

AUTORES / AUTHORS:  - Cascalho M; Platt JL

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.  N. Ref:: 55

 

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[55]

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

 

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[56]

TÍTULO / TITLE:  - Suppression of graft-versus-host disease by naturally occurring regulatory T cells.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 15;77(1 Suppl):S9-S11.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106475.38978.11

AUTORES / AUTHORS:  - Zeng D; Lan F; Hoffmann P; Strober S

INSTITUCIÓN / INSTITUTION:  - Division of Rheumatology and Immunology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

RESUMEN / SUMMARY:  - Studies of graft-versus-host disease after allogeneic bone marrow transplantation have shown that there are subsets of freshly isolated donor T cells that induce the disease and subsets that suppress the disease. The balance of subsets in the graft determines disease severity. The authors’ work on the nature of the regulatory-suppressor T cells and their mechanisms of action is summarized in this article.  N. Ref:: 24

 

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[57]

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

 

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[58]

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

 

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[59]

TÍTULO / TITLE:  - Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance.

REVISTA / JOURNAL:  - J Clin Oncol 2004 Mar 15;22(6):1136-51.

      ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2004.10.041

AUTORES / AUTHORS:  - Mapara MY; Sykes M

INSTITUCIÓN / INSTITUTION:  - Department of Hematology and Oncology, University Medical Center Charite, Campus Virchow Klinikum, Humboldt University Berlin, Germany.

RESUMEN / SUMMARY:  - The development of malignant disease might be seen as a failure of immune surveillance. However, not all tumors are naturally immunogenic, and even among those that are immunogenic, the uncontrolled rapid growth of a tumor may sometimes out-run a robust immune response. Nevertheless, recent evidence suggests that mechanisms of tolerance that normally exist to prevent autoimmune disease may also preclude the development of an adequate antitumor response and that tumors themselves have the ability to thwart the development of effective immune responses against their antigens. A major challenge has been to develop approaches to breaking this tolerance in tumor-bearing hosts, and recent advances in our understanding of antigen presentation and tolerance have led to some promising strategies. An alternative approach is to use T cells from nontumor-bearing, allogeneic hosts in the form of lymphocyte infusions, with or without hematopoietic cell transplantation. Immunotherapy may occur in this setting via the response of nontolerant, tumor antigen-specific T cells from nontumor-bearing hosts or via the powerful destructive effect of an alloresponse directed against antigens shared by malignant cells in the recipient. Approaches to exploiting this beneficial effect without the deleterious consequence of graft-versus-host disease in allogeneic hematopoietic cell recipients are discussed.  N. Ref:: 100

 

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[60]

TÍTULO / TITLE:  - Routes to allograft survival.

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):797-8.

AUTORES / AUTHORS:  - Bromberg JS; Murphy B

INSTITUCIÓN / INSTITUTION:  - Recanati/Miller Transplant Institute, Mount Sinai School of Medicine, New York, New York 10029, USA. jon.bromberg@mountsinai.org  N. Ref:: 21

 

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[61]

TÍTULO / TITLE:  - Cytolytic pathways in haematopoietic stem-cell transplantation.

REVISTA / JOURNAL:  - Nat Rev Immunol 2002 Apr;2(4):273-81.

      ●● Enlace al texto completo (gratuito o de pago) 1038/nri775

AUTORES / AUTHORS:  - van den Brink MR; Burakoff SJ

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. vandenbm@mskcc.org

RESUMEN / SUMMARY:  - The remarkable activity of donor T cells against malignant cells in the context of an allogeneic haematopoietic stem-cell transplantation (HSCT) is arguably, at present, the most potent clinical immunotherapy for cancer. However, alloreactive donor T cells are also important effector cells in the development of graft-versus-host disease (GVHD), which is a potentially lethal complication for recipients of an allogeneic HSCT. Therefore, the separation of the GVHD and graft-versus-tumour (GVT) activity of donor T cells has become a topic of great interest for many investigators. Recent studies have shown that donor T cells make differential use of their cytolytic pathways in mediating GVHD and GVT effects. Therefore, the selective blockade or enhancement of cytolytic pathways provides an intriguing therapeutic opportunity to separate the desired GVT effect from the potentially devastating GVHD.  N. Ref:: 96

 

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[62]

TÍTULO / TITLE:  - Preliminary guidelines for diagnosing and treating tuberculosis in patients with rheumatoid arthritis in immunosuppressive trials or being treated with biological agents.

REVISTA / JOURNAL:  - Ann Rheum Dis 2002 Nov;61 Suppl 2:ii62-3.

AUTORES / AUTHORS:  - Furst DE; Cush J; Kaufmann S; Siegel J; Kurth R

INSTITUCIÓN / INSTITUTION:  - UCLA Medical School, Los Angeles, USA Presbyterian Hospital, Dallas, USA.

 

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[63]

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

 

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[64]

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

 

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[65]

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

 

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[66]

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

 

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[67]

TÍTULO / TITLE:  - The influence of environment and experience on neural grafts.

REVISTA / JOURNAL:  - Nat Rev Neurosci 2001 Dec;2(12):871-9.

      ●● Enlace al texto completo (gratuito o de pago) 1038/35104055

AUTORES / AUTHORS:  - Dobrossy MD; Dunnett SB

INSTITUCIÓN / INSTITUTION:  - School of Biosciences, Cardiff University, Museum Avenue Box 911, Cardiff CF10 3US, Wales, UK. dobrossymd@cardiff.ac.uk  N. Ref:: 106

 

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[68]

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

 

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[69]

TÍTULO / TITLE:  - Diagnosis and therapy of coronary artery disease in renal failure, end-stage renal disease, and renal transplant populations.

REVISTA / JOURNAL:  - Am J Med Sci 2003 Apr;325(4):214-27.

AUTORES / AUTHORS:  - Logar CM; Herzog CA; Beddhu S

INSTITUCIÓN / INSTITUTION:  - Renal Section, Salt Lake VA Healthcare System, Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.

RESUMEN / SUMMARY:  - Even though cardiovascular disease is the leading cause of death in patients with CRF and end-stage renal disease (ESRD), ill-conceived notions have led to therapeutic nihilism as the predominant strategy in the management of cardiovascular disease in these populations. The recent data clearly support the application of proven interventions in the general population, such as angiotensin-converting enzyme inhibitors and statins to patients with CRF and ESRD. The advances in coronary stents and intracoronary irradiation have decreased the restenosis rates in renal failure patients. Coronary artery bypass with internal mammary graft might be the procedure of choice for coronary revascularization in these patients. The role of screening for asymptomatic coronary disease is established as a pretransplant procedure, but it is unclear whether this will be applicable to all patients with ESRD. Future studies need to focus on unraveling the mechanisms by which uremia leads to increased cardiovascular events to design optimal therapies targeted toward these mechanisms and improve cardiovascular outcomes.  N. Ref:: 125

 

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[70]

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

 

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[71]

TÍTULO / TITLE:  - Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 27;77(2):238-43.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000107285.86939.37

AUTORES / AUTHORS:  - Karras A; Thervet E; Legendre C

INSTITUCIÓN / INSTITUTION:  - Service de Nephrologie et Transplantation Renale, Hopital Saint-Louis, Paris, France.

RESUMEN / SUMMARY:  - BACKGROUND: Hemophagocytic syndrome (HPS) combines febrile hepatosplenomegaly, pancytopenia, hypofibrinemia, and liver dysfunction. It is defined by bone marrow and organ infiltration by activated, nonmalignant macrophages phagocytizing blood cells. HPS is often caused by an infectious or neoplastic disease and has rarely been described in renal transplant recipients. METHODS: We retrospectively analyzed 17 cases of HPS after cadaveric renal transplantation (13 men and 4 women, age 41+/-8 years). The median time between transplantation and hemophagocytosis was 52 days. Eleven patients (64%) had received antilymphocyte globulins during the 3 months before presentation. RESULTS: Fever was present in all patients, and hepatosplenomegaly was present in 9 of 17 patients. Other nonspecific clinical findings included abdominal, neurologic, and respiratory symptoms. Laboratory tests showed anemia (hemoglobin 6.1+/-1.3 g/dL), thrombocytopenia (34,000+/-32,000/mm3), and leukopenia (1,700+/-1,400/mm3). Elevated liver enzymes were present in 12 of 17 patients, and cholestasis was present in 10 of 17 patients. Elevated triglycerides and ferritin were noted in 75% and 86% of cases, respectively. HPS was related to viral infection in nine patients (cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8), bacterial infection in three patients (tuberculosis and Bartonella henselae), and other infections in two patients (toxoplasmosis and Pneumocystis carinii pneumoniae). Posttransplant lymphoproliferative disease was present in two patients. Despite large-spectrum anti-infectious treatment and dramatic tapering of immunosuppression, death occurred in eight patients (47%). Graft nephrectomy was performed in four of the nine surviving patients. CONCLUSIONS: We report here the largest series of HPS after renal transplantation. This rare disease is usually secondary to herpes viridae infections, mostly cytomegalovirus and Epstein-Barr virus in severely immunocompromised patients. Despite aggressive treatment, the prognosis remains poor.  N. Ref:: 22

 

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[72]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.1. Cancer risk after renal transplantation. Post-transplant lymphoproliferative disease (PTLD): prevention and treatment.

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: <> 2002;17 Suppl 4:31-3, 35-6.

RESUMEN / SUMMARY:  - GUIDELINES: A. In the first year after organ transplantation, recipients are at the greatest risk of developing lymphoproliferative diseases (PTLDs), which are induced most often by Epstein-Barr virus (EBV) infection, and patients should therefore be screened prior to or at the time of transplantation for EBV antibodies. B. In the rare cases (<5%) where the recipient is EBV seronegative, he or she has a 95% likelihood of receiving an organ from an EBV-seropositive donor, which translates into a high risk of primary EBV infection with seroconversion soon after transplantation. In such cases, the recipient should receive a prophylactic antiviral treatment with acyclovir, valacyclovir or ganciclovir, starting at the time of transplant and lasting for at least 3 months. The specific recommendations given for CMV prophylaxis could be applicable in this situation. C. The treatment of PTLD should be based on accurate pathology with extensive cell markers and phenotyping. The treatment modalities are as follows. Reduction of basal immunosuppression in all cases (either maintain only steroids, or decrease by at least 50% the anti-calcineurin drugs and stop other immunosuppressive drugs). In the case of EBV-positive B-cell lymphoma, antiviral treatment with acyclovir, valacyclovir or ganciclovir may be initiated for at least 1 month or according to the blood level of EBV replication when available. In the case of rare lymphomas from the mucosal-associated lymphoid tissue (MALT) with positive Helicobacter pylori, full eradication of H. pylori should be carried out with a validated protocol. Subsequent H. pylori prophylaxis should be implemented to avoid relapse. In the case of CD20-positive lymphomas, treatment with rituximab, a chimeric monoclonal antibody directed against CD20, should be carried out with one i.v. injection per week for 4 weeks. In the case of diffuse lymphomas or improper response to previous treatment, CHOP chemotherapy should be used alone or in combination with rituximab. The CHOP regimen is cyclophosphamide, doxorubicine, vincristine and prednisone. Complete cessation of immunosuppression with or without graft nephrectomy should also be considered.

 

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[73]

TÍTULO / TITLE:  - Individuality: the barrier to optimal immunosuppression.

REVISTA / JOURNAL:  - Nat Rev Immunol 2003 Oct;3(10):831-8.

      ●● Enlace al texto completo (gratuito o de pago) 1038/nri1204

AUTORES / AUTHORS:  - Kahan BD

INSTITUCIÓN / INSTITUTION:  - Division of Immunology and Organ Transplantation, Department of Surgery, University of Texas Medical School at Houston, Suite 6.240, 6431 Fannin, Houston, Texas 77030, USA. Barry.D.Kahan@uth.tmc.edu.

RESUMEN / SUMMARY:  - Immunosuppressive therapy aims to protect transplanted organs from host responses. Individuals have unique repertoires of responses to foreign antigens and toxic reactions to immunosuppressants; the former determining the type or intensity of rejection reactions and the latter influencing the severity of iatrogenic effects. Because existing agents target molecules that are widely distributed in tissues, new strategies must selectively block lymphoid cells only, disrupt alloresponses but not innate immune responses, interact synergistically with other agents, facilitate the homeostatic process that naturally leads to graft acceptance and ideally only interrupt donor-specific responses. Approaches presently under investigation aim to alter cell trafficking, or selectively deviate the maturation of antigen-presenting cells or inhibit lymphocyte-activation cascades - events that are crucial to rejection responses.  N. Ref:: 92

 

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[74]

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

 

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[75]

TÍTULO / TITLE:  - Regulatory (suppressor) T cells in peripheral allograft tolerance and graft-versus-host reaction.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 15;77(1 Suppl):S5.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000107184.18562.FC

AUTORES / AUTHORS:  - Rifle G; Herve P

INSTITUCIÓN / INSTITUTION:  - UPRES EA563, Faculte de Medecine, Universite de Bourgogne and Department of Nephrology-Intensive Care-Transplantation, Hopital du Bocage, Dijon, France. gerard.rifle@chu-dijon.fr.

RESUMEN / SUMMARY:  - Among the mechanisms capable of inducing peripheral tolerance, regulatory (suppressor) T cells (Treg) probably play a key role in the control of both reactivity to self-antigens and alloimmune response. Augmentation or manipulation of Treg could improve organ allograft survival or control graft-versus-host disease, thus resulting in operational tolerance. The role of this immunomanipulation as one method of inducing tolerance has yet to be clearly defined.  N. Ref:: 14

 

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[76]

TÍTULO / TITLE:  - The complementary roles of deletion and regulation in transplantation tolerance.

REVISTA / JOURNAL:  - Nat Rev Immunol 2003 Feb;3(2):147-58.

      ●● Enlace al texto completo (gratuito o de pago) 1038/nri1002

AUTORES / AUTHORS:  - Lechler RI; Garden OA; Turka LA

INSTITUCIÓN / INSTITUTION:  - Department of Immunology, Division of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Campus, Commonwealth Building, Du Cane Road, London W12 0NN, UK. r.lechler@ic.ac.uk

RESUMEN / SUMMARY:  - Neonatal tolerance of alloantigens was described in mice nearly half a century ago, but unfortunately, the translation of these early findings into the clinical arena proved to be much more challenging than was first anticipated. However, the past decade has seen considerable progress in our understanding of the mechanisms that contribute to transplantation tolerance in experimental models. This review outlines our current understanding of the mechanisms of allograft tolerance, emphasizing the complementary roles of deletion and regulation of alloreactive T cells.  N. Ref:: 145

 

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[77]

TÍTULO / TITLE:  - “Rebooting” the immune system with cyclophosphamide: taking risks for a “cure”?

REVISTA / JOURNAL:  - Ann Neurol 2003 Jan;53(1):7-9.

      ●● Enlace al texto completo (gratuito o de pago) 1002/ana.10449

AUTORES / AUTHORS:  - Lewis RA; Lisak RP  N. Ref:: 11

 

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[78]

TÍTULO / TITLE:  - Organ transplantation: what is the state of the art?

REVISTA / JOURNAL:  - Ann Surg 2003 Dec;238(6 Suppl):S72-89.

AUTORES / AUTHORS:  - Collins BH

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Division of Transplantation, Duke University Medical Center, Durham, NC 27710, USA. colli005@mc.duke.edu  N. Ref:: 130

 

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[79]

TÍTULO / TITLE:  - Nystatin prophylaxis and treatment in severely immunodepressed patients.

REVISTA / JOURNAL:  - Cochrane Database Syst Rev 2002;(2):CD002033.

AUTORES / AUTHORS:  - Gotzsche PC; Johansen HK

INSTITUCIÓN / INSTITUTION:  - The Nordic Cochrane Centre, Rigshospitalet, Dept. 7112, Blegdamsvej 9, Copenhagen O, Denmark, 2100. p.c.gotzsche@cochrane.dk

RESUMEN / SUMMARY:  - BACKGROUND: Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal. OBJECTIVES: To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency. SEARCH STRATEGY: MEDLINE and The Cochrane Library using a comprehensive search strategy, date of last search November 2001. Contacted industry and scanned reference lists. SELECTION CRITERIA: Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B. DATA COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently. The outcomes were weighted by the inverse variance. A random effects model was used unless p>0.10 for the test of heterogeneity. MAIN RESULTS: We included 12 trials (1,464 patients). The drugs were given prophylactically in ten trials and as treatment in two. Seven trials were in acute leukaemia, two in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients. Nystatin had been compared with placebo in three trials and with fluconazole in nine; the dose varied from 1.5 MIE to 72 MIE daily. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70). The results were very similar if the three studies which were not performed in cancer patients were excluded. REVIEWER’S CONCLUSIONS: Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.  N. Ref:: 21

 

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[80]

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

 

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[81]

TÍTULO / TITLE:  - Challenges to achieving clinical transplantation tolerance.

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 Oct;108(7):943-8.

AUTORES / AUTHORS:  - Salama AD; Remuzzi G; Harmon WE; Sayegh MH

INSTITUCIÓN / INSTITUTION:  - Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA.  N. Ref:: 50

 

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[82]

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

 

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[83]

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

 

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[84]

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.

 

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[85]

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

 

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[86]

TÍTULO / TITLE:  - Fatal Scopulariopsis brevicaulis infection in a paediatric stem-cell transplant patient treated with voriconazole and caspofungin and a review of Scopulariopsis infections in immunocompromised patients.

REVISTA / JOURNAL:  - J Infect 2004 Jan;48(1):112-6.

AUTORES / AUTHORS:  - Steinbach WJ; Schell WA; Miller JL; Perfect JR; Martin PL

INSTITUCIÓN / INSTITUTION:  - Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Box 3499, Durham, NC, USA. stein022@mc.duke.edu  N. Ref:: 33

 

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[87]

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

 

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[88]

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

 

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[89]

TÍTULO / TITLE:  - Drug immunosuppression therapy for adult heart transplantation. Part 2: clinical applications and results.

REVISTA / JOURNAL:  - Ann Thorac Surg 2004 Jan;77(1):363-71.

AUTORES / AUTHORS:  - Mueller XM

INSTITUCIÓN / INSTITUTION:  - Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca

RESUMEN / SUMMARY:  - This review describes the clinical application of classical immunosuppressive drugs as well as that of more recent drugs. All current immunosuppressive drugs target T-cell activation, and cytokine production and clonal expansion, or both. Immunosuppressive protocols can be broadly divided into induction therapy, maintenance immunosuppression, and treatment of acute rejection episodes.  N. Ref:: 82

 

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[90]

TÍTULO / TITLE:  - Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin’s lymphoma: a comparison with allogeneic and autologous transplantation—The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation.

REVISTA / JOURNAL:  - J Clin Oncol 2003 Oct 15;21(20):3744-53. Epub 2003 Sep 8.

      ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2003.08.054

AUTORES / AUTHORS:  - Bierman PJ; Sweetenham JW; Loberiza FR Jr; Taghipour G; Lazarus HM; Rizzo JD; Schmitz N; van Besien K; Vose JM; Horowitz M; Goldstone A

INSTITUCIÓN / INSTITUTION:  - University of Nebraska Medical Center, Omaha, NE 68198-7680, USA. pjbierman@unmc.edu

RESUMEN / SUMMARY:  - PURPOSE: To compare results of syngeneic, allogeneic, and autologous hematopoietic stem-cell transplantation for non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: The databases of the International Bone Marrow Transplant Registry (IBMTR) and the European Group for Blood and Marrow Transplantation were used to identify 89 NHL patients who received syngeneic transplants. These patients were compared with NHL patients identified from the IBMTR and the Autologous Blood and Marrow Transplant Registry who received allogeneic (T-cell depleted and T-cell replete) and autologous (purged and unpurged) transplants. RESULTS: No significant differences in relapse rates were observed when results of allogeneic transplantation were compared with syngeneic transplantation for any histology. T-cell depletion of allografts was not associated with a higher relapse risk, but was associated with improved overall survival for patients with low-grade and intermediate-grade histology. Patients who received unpurged autografts for low-grade NHL had a five-fold (P =.008) greater risk of relapse than recipients of syngeneic transplants, and recipients of unpurged autografts had a two-fold (P =.0009) greater relapse risk than patients who received purged autografts. Among low-grade NHL patients, the use of purging was associated with significantly better disease-free survival (P =.003) and overall survival (P =.04) when compared with patients who received unpurged autografts. CONCLUSION: These analyses failed to find evidence of a graft-versus-lymphoma effect, but do provide indirect evidence to support the hypothesis that tumor contamination may contribute to lymphoma relapse, and that purging may be beneficial for patients undergoing autologous hematopoietic stem-cell transplantation for low-grade NHL.

 

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[91]

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

 

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[92]

TÍTULO / TITLE:  - B cell-ablative therapy for the treatment of autoimmune diseases.

REVISTA / JOURNAL:  - Arthritis Rheum 2002 Aug;46(8):1984-5.

      ●● Enlace al texto completo (gratuito o de pago) 1002/art.10476

AUTORES / AUTHORS:  - Patel DD  N. Ref:: 18

 

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[93]

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

 

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[94]

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.

 

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[95]

TÍTULO / TITLE:  - Intestinal transplantation for gut failure.

REVISTA / JOURNAL:  - Gastroenterology 2003 May;124(6):1615-28.

AUTORES / AUTHORS:  - Fishbein TM; Gondolesi GE; Kaufman SS

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA. Thomas.Fishbein@MSNYUhealth.org  N. Ref:: 95

 

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[96]

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

 

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[97]

TÍTULO / TITLE:  - Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?

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 Feb 1;99(3):768-84.

AUTORES / AUTHORS:  - Burt RK; Slavin S; Burns WH; Marmont AM

INSTITUCIÓN / INSTITUTION:  - Division of Immune Therapy and Autoimmune Disease, Northwestern University Medical Center, 320 E. Superior, Searle Bldg. Rm 3-489, Chicago, IL 60611, USA. rburt@nwu.edu

RESUMEN / SUMMARY:  - Hematopoietic stem cells (HSCs) are the earliest cells of the immune system, giving rise to B and T lymphocytes, monocytes, tissue macrophages, and dendritic cells. In animal models, adoptive transfer of HSCs, depending on circumstances, may cause, prevent, or cure autoimmune diseases. Clinical trials have reported early remission of otherwise refractory autoimmune disorders after either autologous or allogeneic hematopoietic stem cell transplantation (HSCT). By percentage of transplantations performed, autoimmune diseases are the most rapidly expanding indication for stem cell transplantation. Although numerous editorials or commentaries have been previously published, no prior review has focused on the immunology of transplantation tolerance or development of phase 3 autoimmune HSCT trials. Results from current trials suggest that mobilization of HSCs, conditioning regimen, eligibility and exclusion criteria, toxicity, outcome, source of stem cells, and posttransplantation follow-up need to be disease specific. HSCT-induced remission of an autoimmune disease allows for a prospective analysis of events involved in immune tolerance not available in cross-sectional studies.  N. Ref:: 358

 

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[98]

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

 

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[99]

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

 

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[100]

TÍTULO / TITLE:  - Penicillin-resistant Streptococcus pneumoniae septic shock and meningitis complicating chronic graft versus host disease: a case report and review of the literature.

REVISTA / JOURNAL:  - Am J Med 2002 Aug 1;113(2):152-5.

AUTORES / AUTHORS:  - Haddad PA; Repka TL; Weisdorf DJ

INSTITUCIÓN / INSTITUTION:  - Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, USA.  N. Ref:: 34

 

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[101]

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

 

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[102]

TÍTULO / TITLE:  - Pretransplant blood transfusions revisited: a role for CD(4+) regulatory T cells?

REVISTA / JOURNAL:  - Transplantation 2004 Jan 15;77(1 Suppl):S26-8.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106469.12073.01

AUTORES / AUTHORS:  - Roelen D; Brand A; Claas FH

INSTITUCIÓN / INSTITUTION:  - Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands. d.l.roelen@lumc.nl.

RESUMEN / SUMMARY:  - Pretransplant blood transfusions have been shown to improve organ allograft survival. However, the immunologic mechanism leading to this beneficial effect of blood transfusions is still unknown. The observation that transfusions sharing at least one HLA-DR antigen (human leukocyte antigen) with the recipient are more effective than HLA-mismatched transfusions has led to the hypothesis that CD(4+) regulatory T cells are induced that recognize allopeptides of the blood transfusion donor in the context of the self-HLA-DR molecule on the donor cells. In vitro studies showed that CD(4+) T cells recognizing an allopeptide in the context of self-HLA-DR are indeed able to decrease the alloimmune response of autologous T cells by affecting the activated T cells directly or indirectly by their modulatory effect on dendritic cells. The first studies in a patient with a well-functioning kidney graft after receiving an HLA-DR-matched pretransplant blood transfusion showed that the low organ donor-specific cytotoxic T-lymphocyte response after transplantation was indeed attributable to the activity of regulatory CD(4+) T cells.  N. Ref:: 24

 

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[103]

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

 

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[104]

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

 

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[105]

TÍTULO / TITLE:  - How I treat chronic graft-versus-host disease.

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: <> 2001 Mar 1;97(5):1196-201.

AUTORES / AUTHORS:  - Vogelsang GB

INSTITUCIÓN / INSTITUTION:  - Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA. vogelge@jhmi.edu

RESUMEN / SUMMARY:  - Allogeneic stem cell transplantation (SCT) is now a commonplace procedure. Clinicians who care for patients with hematologic malignancies and aplastic anemia are almost certain to follow up patients after SCT. This review is intended to help clinicians observe patients for probably the most important late complication of SCT, chronic graft-versus-host disease (GVHD). It reviews the pathophysiology, risk factors, clinical manifestations, evaluation, treatment, and supportive care of chronic GVHD.  N. Ref:: 34

 

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[106]

TÍTULO / TITLE:  - Dendritic cells and the mode of action of anticalcineurinic drugs: an integrating hypothesis.

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 Mar;18(3):467-8; discussion 469-70.

AUTORES / AUTHORS:  - Fierro A; Mora JR; Bono MR; Morales J; Buckel E; Sauma D; Rosemblatt M

INSTITUCIÓN / INSTITUTION:  - Clinica las Condes, Transplantation Unit, Santiago, Chile. afierro@vtr.net  N. Ref:: 16

 

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[107]

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

 

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[108]

TÍTULO / TITLE:  - Therapeutic management of extrahepatic manifestations in patients with chronic hepatitis C virus infection.

REVISTA / JOURNAL:  - Rheumatology (Oxford). Acceso gratuito al texto completo a partir de los 2 años de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://rheumatology.oupjournals.org/ 

      ●● Cita: Rheumatology (Oxford): <> 2003 Jul;42(7):818-28. Epub 2003 Apr 16.

      ●● Enlace al texto completo (gratuito o de pago) 1093/rheumatology/keg299

AUTORES / AUTHORS:  - Ramos-Casals M; Trejo O; Garcia-Carrasco M; Font J

INSTITUCIÓN / INSTITUTION:  - Department of Autoimmune Diseases, Clinical Institutes of Infection and Immunology, Insitut d’Investigacions Biomediques August Pi i Sunyer, Hospital Clinic, Department of Medicine, School of Medicine, University of Barcelona, España. mramos@clinic.ub.es  N. Ref:: 123

 

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[109]

TÍTULO / TITLE:  - Manipulation of dendritic cells for tolerance induction in transplantation and autoimmune disease.

REVISTA / JOURNAL:  - Transplantation 2002 Jan 15;73(1 Suppl):S19-22.

AUTORES / AUTHORS:  - Lu L; Thomson AW

INSTITUCIÓN / INSTITUTION:  - Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. Lul@msx.upmc.edu

RESUMEN / SUMMARY:  - Dendritic cells (DC) constitute a complex system of uniquely well-equipped antigen-presenting cells that initiate and regulate immune responses. Extensive recent studies have improved our understanding of DC development, differentiation, activation, and function. DC exist as distinct subsets that differ in their lineage affiliation, surface molecule expression, and biological function. These factors seem to determine the T-cell polarizing signals and type of T cell response-T helper 1, T helper 2, or T regulatory- induced by DC (1). Evidence has accumulated that DC play an important role in both central and peripheral tolerance via various mechanisms, including induction of T-cell anergy, immune deviation, T regulatory cell activity, and promotion of activated T-cell apoptosis. Although many of the details of the molecular basis of DC tolerogenicity have yet to be elucidated, emerging information suggests that costimulatory molecule deficiency, expression of death-inducing ligands (in particular Fas [CD95] ligand), microenvironmental factors (in particular anti-inflammatory/immunosuppressive cytokines), and inhibition of gene transcription regulatory proteins (e.g., nuclear factor-kappaB) can impart tolerogenic potential to DC (2). Manipulation of DC by control of their maturation and differentiation, or genetic engineering of these cells to express immunosuppressive molecules, offers potential for therapy of allograft rejection and autoimmune disease. In this brief overview, we outline principles and methods for generation of “tolerogenic” DC and outcomes that have been reported in experimental models. Space constraints limit literature citations.  N. Ref:: 18

 

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[110]

TÍTULO / TITLE:  - Risk for myopathy with statin therapy in high-risk patients.

REVISTA / JOURNAL:  - Arch Intern Med 2003 Mar 10;163(5):553-64.

AUTORES / AUTHORS:  - Ballantyne CM; Corsini A; Davidson MH; Holdaas H; Jacobson TA; Leitersdorf E; Marz W; Reckless JP; Stein EA

INSTITUCIÓN / INSTITUTION:  - Center for Cardiovascular Disease Prevention, Baylor College of Medicine, 6565 Fannin, Mail Station A601, Suite A656, Houston, TX 77030, USA. cmb@bcm.tmc.edu

RESUMEN / SUMMARY:  - Emerging data suggest that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) offer important benefits for the large population of individuals at high risk for coronary heart disease. This population encompasses a sizable portion of individuals who are also at high risk for drug-drug interactions due to their need for multiple medications. In general, statins are associated with a very small risk for myopathy (which may progress to fatal or nonfatal rhabdomyolysis); however, the potential for drug-drug interactions is known to increase this risk in specific high-risk groups. The incidence of myopathy associated with statin therapy is dose related and is increased when statins are used in combination with agents that share common metabolic pathways. Of particular concern is the potential for interactions with other lipid-lowering agents such as fibrates and niacin (nicotinic acid), which may be used in patients with mixed lipidemia, and with immunosuppressive agents, such as cyclosporine, which are commonly used in patients after transplantation. Clinicians should be alert to the potential for drug-drug interactions to minimize the risk of myopathy during long-term statin therapy in patients at high risk for coronary heart disease.  N. Ref:: 128

 

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[111]

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.

 

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[112]

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.

 

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[113]

TÍTULO / TITLE:  - Drug immunosuppression therapy for adult heart transplantation. Part 1: immune response to allograft and mechanism of action of immunosuppressants.

REVISTA / JOURNAL:  - Ann Thorac Surg 2004 Jan;77(1):354-62.

AUTORES / AUTHORS:  - Mueller XM

INSTITUCIÓN / INSTITUTION:  - Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca

RESUMEN / SUMMARY:  - In the early days of transplantation, immunosuppression therapy was rather broad and nonspecific, mainly using high-dose corticosteroids and azathioprine. Thereafter we progressively narrowed the target of immunosuppressive strategy starting with polyclonal antibodies. The introduction of cyclosporine, OKT3, and tacrolimus further narrowed the target on the T-cell pathways. More recently mycophenolate mofetil progressively took the place of azathioprine with its higher lymphocyte specificity and sirolimus and interleukin-2 receptor antibodies were introduced. In this field in constant movement the aim is to find a drug or a regimen that provides optimal immunosuppression therapy with minimal side effects, in other words to find the right balance between overimmunosuppression and underimmunosuppression therapy. This review is divided into two parts. The first part will provide a basic understanding of the immunologic response to allograft and explain how conventional and recently introduced immunosuppressive agents work. The second part will describe the clinical application of immunosuppressive drugs to provide practical information for those in charge of heart transplant recipients.  N. Ref:: 68

 

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[114]

TÍTULO / TITLE:  - Longstanding obliterative panarteritis in Kawasaki disease: lack of cyclosporin A effect.

REVISTA / JOURNAL:  - Pediatrics 2003 Oct;112(4):986-92.

AUTORES / AUTHORS:  - Kuijpers TW; Biezeveld M; Achterhuis A; Kuipers I; Lam J; Hack CE; Becker AE; van der Wal AC

INSTITUCIÓN / INSTITUTION:  - Emma Children’s Hospital, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.w.kuijpers@amc.uva.nl

RESUMEN / SUMMARY:  - Kawasaki disease is a childhood vasculitis of medium-sized vessels, affecting the coronary arteries in particular. We have treated a therapy-resistant child who met all diagnostic criteria for Kawasaki disease. After the boy was given intravenous immunoglobulins and salicylates, as well as several courses of pulsed methylprednisolone, disease recurred and coronary artery lesions became progressively detectable. Cyclosporin A was started and seemed clinically effective. In contrast to the positive effect on inflammatory parameters, ie, C-reactive protein and white blood cell counts, a novel plasma marker for cytotoxicity (granzyme B) remained elevated. Coronary disease progressed to fatal obstruction and myocardial infarction. Echocardiography, electrocardiograms, and myocardial creatine phosphokinase did not predict impending death. At autopsy an obliterative panarteritis was observed resulting from massive fibrointimal proliferation, affecting the aorta and several large and medium-sized arteries. Immunophenotypic analysis of the inflammatory infiltrates in arteries revealed mainly granzyme-positive cytotoxic T cells and macrophages in the intima and media, as well as nodular aggregates of T cells, B cells, and plasma cells in the adventitia of affected arteries. These findings further endorse the role of specific cellular and humoral immunity in Kawasaki disease. Unremitting coronary arteritis and excessive smooth muscle hyperplasia resulted in coronary occlusion despite the use of cyclosporin A.  N. Ref:: 37

 

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[115]

TÍTULO / TITLE:  - The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation.

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: <> 2001 Dec 1;98(12):3192-204.

AUTORES / AUTHORS:  - Ho VT; Soiffer RJ

INSTITUCIÓN / INSTITUTION:  - Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.  N. Ref:: 244

 

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[116]

TÍTULO / TITLE:  - Ultraviolet light-induced regulatory (suppressor) T cells: an approach for promoting induction of operational allograft tolerance?

REVISTA / JOURNAL:  - Transplantation 2004 Jan 15;77(1 Suppl):S29-31.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000112969.24120.64

AUTORES / AUTHORS:  - Aubin F; Mousson C

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology and EA3181, University Hospital, Besancon, France. francois.aubin@ufc-chu.univ-fcomte.fr.

RESUMEN / SUMMARY:  - Ultraviolet (UV) light is known to induce skin cancers by causing DNA gene mutations and inducing immunosuppression. Taking advantage of these immunosuppressive capacities, UV light has been used, with different modalities, as an immunosuppressive therapy in a variety of diseases including allograft rejection and graft-versus-host disease. Phototherapy includes UVB irradiation, UVA irradiation, oral psoralen (+)UVA irradiation (PUVA), photodynamic therapy, and extracorporeal photopheresis, which consists of infusion of UVA-irradiated autologous leukocytes collected by apheresis and incubated with 8-methoxypsoralen. According to numerous experimental models and human data, there is increasing evidence that UVB irradiation and extracorporeal photopheresis can induce regulatory T cells and anticlonotypic activity. These therapies induce apoptosis of activated T cells or of extracorporally treated mononuclear cells, and up-regulate the expression of costimulary molecules and adhesion molecules on antigen presenting cells. UVB- or UVA-induced apoptotic cells could secrete immune suppressive cytokines (interleukin (IL)-4, IL-10). The processing and presentation of apoptotic T cell antigens from clones of pathogenic T cells by activated antigen presenting cells might explain the induction of systemic anticlonotypic activity by photopheresis. This induction of cell-mediated suppressive activity opens up future prospects with the aim of expanding regulatory T cells and/or anticlonotypic activity, especially by photopheresis in organ and cell transplantation.  N. Ref:: 40

 

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[117]

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

 

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[118]

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

 

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[119]

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

 

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[120]

TÍTULO / TITLE:  - Advances in transplantation tolerance.

REVISTA / JOURNAL:  - Lancet 2001 Jun 16;357(9272):1959-63.

AUTORES / AUTHORS:  - Yu X; Carpenter P; Anasetti C

INSTITUCIÓN / INSTITUTION:  - Human Immunogenetics Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

RESUMEN / SUMMARY:  - Immunosuppressive drugs developed in the past two decades have improved the short-term survival of organ allografts, but tolerance has not been achieved and almost all transplant recipients continue to require drugs throughout life. Graft rejection arises from the cognate interaction of T cells with antigen-presenting cells, the recognition of alloantigen through the T-cell receptor, and the delivery of accessory stimulation signals. Once activated by the specific antigen, replicating T cells die if they are re-exposed to the same antigen. Since depletion of antigen-activated T cells is one critical mechanism of transplantation tolerance, drugs such as ciclosporin that interfere with activation-induced T-cell death could inhibit tolerance, whereas drugs such as mycophenolate mofetil, that induce the death of activated T cells, could facilitate tolerance. Other tolerance mechanisms depend on inactivation rather than elimination of allograft reactive T cells. When antigen recognition occurs without costimulation through the CD28 and CD154 accessory receptors, or in absence of cell division, T cells become unresponsive. Thus, inhibitors of CD28 and CD154, and inhibition of T-cell division by rapamycin promotes transplantation tolerance.  N. Ref:: 54

 

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[121]

TÍTULO / TITLE:  - Immunisations in solid-organ transplant recipients.

REVISTA / JOURNAL:  - Lancet 2002 Mar 16;359(9310):957-65.

AUTORES / AUTHORS:  - Stark K; Gunther M; Schonfeld C; Tullius SG; Bienzle U

INSTITUCIÓN / INSTITUTION:  - Institute of Tropical Medicine, Charite, Humboldt University, Berlin, Germany. starkk@rki.de

RESUMEN / SUMMARY:  - Solid-organ transplant recipients are at increased risk of various infectious diseases, some of which are vaccine preventable mmunisations are among the most efficient interventions available. Solid-organ tranplant recipients would greatly benefit from effective immunisations, provided the recommendations are based on a careful risk-benefit analysis in which the effectiveness of the vaccine is weighed against possible adverse reactions, including graft rejection. In this review, we summarise the data from studies on relevant immunisations in solid-organ transplant recipients. The major issues are the immunogenicity and safety of immunisations, the factors associated with poor immune response, and recommendations for immunisation schemes.  N. Ref:: 94

 

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[122]

TÍTULO / TITLE:  - Xenotransplantation and other means of organ replacement.

REVISTA / JOURNAL:  - Nat Rev Immunol 2001 Nov;1(2):154-60.

      ●● Enlace al texto completo (gratuito o de pago) 1038/35100578

AUTORES / AUTHORS:  - Cascalho M; Platt JL

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.

RESUMEN / SUMMARY:  - Exciting new technologies, such as cellular transplantation, organogenesis and xenotransplantation, are thought to be promising approaches for the treatment of human disease. The feasibility of applying these technologies, however, might be limited by biological and immunological hurdles. Here, we consider whether, and how, xenotransplantation and various other technologies might be applied in future efforts to replace or supplement the function of human organs and tissues.  N. Ref:: 73

 

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[123]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.3. Cancer risk after renal transplantation. Solid organ cancers: prevention and treatment.

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: <> 2002;17 Suppl 4:32, 34-6.

RESUMEN / SUMMARY:  - GUIDELINES: J. All renal transplant recipients should have regular ultrasonography of their native kidneys (when applicable) for screening of renal cell carcinomas, which are observed at much higher incidence in both dialysed and transplant patients. K. Guidelines published for screening and prevention of solid organ cancers in the general population should be strictly applied to transplant recipients, who are in general at higher cancer risk, but would benefit equally or even greater. L. All male renal transplant recipients aged 50 and over should have a yearly prostate specific antigen (PSA) test prior to a regular digital rectal examination. M. All female renal transplant recipients should have a yearly cervical (PAP) smear together with regular pelvic examination and regular mammography, according to national recommendations where available. N. All renal transplant recipients should undergo a faecal occult-blood testing as a screening for colorectal cancer and other (pre-malignant) lesions, according to national recommendations where available. O. In all these conditions, it is recommended to reduce immunosuppression whenever possible.

 

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[124]

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

 

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[125]

TÍTULO / TITLE:  - Severe Ehrlichia chaffeensis infection in a lung transplant recipient: a review of ehrlichiosis in the immunocompromised patient.

REVISTA / JOURNAL:  - Emerg Infect Dis. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://www.cdc.gov/ 

      ●● Cita: Emerging Infectious Diseases: <> 2002 Mar;8(3):320-3.

AUTORES / AUTHORS:  - Safdar N; Love RB; Maki DG

INSTITUCIÓN / INSTITUTION:  - Section of Infectious Diseases, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA.

RESUMEN / SUMMARY:  - We describe a case of human ehrlichiosis in a lung transplant recipient and review published reports on ehrlichiosis in immunocompromised patients. Despite early therapy with doxycycline, our patient had unusually severe illness with features of thrombotic thrombocytopenic purpura. Of 23 reported cases of ehrlichiosis in immunocompromised patients, organ failure occurred in all patients and 6 (25%) died.  N. Ref:: 32

 

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[126]

TÍTULO / TITLE:  - Survival after HLA-identical allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials.

REVISTA / JOURNAL:  - Bone Marrow Transplant 2003 Aug;32(3):293-8.

      ●● Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1704112

AUTORES / AUTHORS:  - Horan JT; Liesveld JL; Fernandez ID; Lyman GH; Phillips GL; Lerner NB; Fisher SG

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

RESUMEN / SUMMARY:  - The impact of peripheral blood stem cell transplantation (PBSCT) on survival relative to bone marrow transplantation (BMT) remains poorly defined. Several randomized controlled trials (RCTs) comparing HLA-matched related PBSC- and BMT for patients with hematologic malignancies have been published, yielding differing results. We conducted a meta-analysis of published RCTs to more precisely estimate the effect of PBSCT on survival. Seven trials that assessed survival were identified and included in our analysis. Using a fixed effects model, and combining the results of all seven trials, the summary odds ratio for mortality after PBSCT was 0.81 (95% CI, 0.62-1.05) when compared to BMT. Subgroup analysis revealed no association between the median PBSCT 34+ cell dose and relative risk for morality after PBSCT. However, there was an association between the proportion of patients enrolled with advanced-stage disease and the summary odds ratio for mortality. The pooled estimate was 0.64 for studies where patients with intermediate/advanced disease comprised at least 25% of enrollment, and was 1.07 for the studies enrolling a smaller proportion. This finding substantiates results from previously published studies that have demonstrated a survival advantage with PBSCT limited to patients with advanced disease.

 

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[127]

TÍTULO / TITLE:  - One-year survival in patients with acute myocardial infarction and a saphenous vein graft culprit treated with primary angioplasty.

REVISTA / JOURNAL:  - Am J Cardiol 2003 May 15;91(10):1250-4.

AUTORES / AUTHORS:  - Nguyen TT; O’Neill WW; Grines CL; Stone GW; Brodie BR; Cox DA; Grines LL; Boura JA; Dixon SR

INSTITUCIÓN / INSTITUTION:  - William Beaumont Hospital, Royal Oak, Michigan 48073, USA.

 

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[128]

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

 

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[129]

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

 

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[130]

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.

 

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[131]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.5.1. Cardiovascular risks. Cardiovascular disease after renal transplantation.

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: <> 2002;17 Suppl 4:24-5.

RESUMEN / SUMMARY:  - GUIDELINES: A. Post-transplant cardiovascular disease is very common, an important cause of morbidity and the first cause of mortality in renal transplant recipients. Therefore, detection and early treatment of post-transplant cardiovascular disease are mandatory. B. Specific risk factors for developing post-transplant cardiovascular disease include pre-transplant cardiovascular disease, arterial hypertension, uraemia (graft dysfunction), hyperlipidaemia, diabetes mellitus, smoking and immunosuppressive treatment. These factors should be targeted for intervention. C. Pre-transplant cardiovascular disease is a major risk factor for post-transplant cardiovascular disease. Therefore, prior to transplantation, it is mandatory to detect and treat symptomatic coronary artery disease, heart failure due to valvular failure or cardiomyopathy, and pericardial constriction. This policy should also be followed in asymptomatic diabetic patients.

 

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[132]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.2. Cancer risk after renal transplantation. Skin cancers: prevention and treatment.

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: <> 2002;17 Suppl 4:31-6.

RESUMEN / SUMMARY:  - GUIDELINES: D. Due to the high prevalence of skin cancers after organ transplantation, it is highly recommended to inform patients about self-awareness. E. Primary prevention should include the avoidance of sun exposure, use of protective clothing and use of an effective sunscreen (protection factor >15) for unclothed body parts (head, neck, hands and arms) in order to prevent the occurrence of squamous-cell carcinoma. This is the most frequent skin tumour in transplant recipients, and its preferential location is the head. F. Recipients with pre-malignant skin lesions (warts, epidermodysplasia verruciformis or actinic keratoses) should be referred early to a dermatologist for active treatment and close follow-up. G. All skin cancers should be completely removed by a dermatologist with appropriate techniques, such as electro-desiccation with curettage, cryotherapy or surgical excision. H. Secondary prevention for recipients should include close follow-up by a dermatologist (at least every 6 months), the use of topical retinoids to control actinic keratoses and to diminish squamous-cell carcinoma recurrence, and reduction of immunosuppression whenever possible. I. In recipients with multiple and/or recurrent skin cancers, the use of systemic retinoids, such as low-dose acitretin, could be recommended for months/years, if well tolerated, in addition to further reduction in immunosuppression whenever possible.

 

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[133]

TÍTULO / TITLE:  - Imiquimod 5% cream for the treatment of cutaneous lesions in immunocompromised patients.

REVISTA / JOURNAL:  - Acta Derm Venereol Suppl (Stockh) 2003 Sep;(214):23-7.

AUTORES / AUTHORS:  - Johnson R; Stockfleth E

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Massachusetts General Hospital, 55 Fruit Street, Bartlett Hall, Boston, MA 02114, USA. RAJOHNSON@PARTNERS.ORG  N. Ref:: 43

 

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[134]

TÍTULO / TITLE:  - Induction of immune tolerance by dendritic cells: implications for preventative and therapeutic immunotherapy of autoimmune disease.

REVISTA / JOURNAL:  - Immunol Cell Biol 2002 Dec;80(6):509-19.

AUTORES / AUTHORS:  - Thompson AG; Thomas R

INSTITUCIÓN / INSTITUTION:  - Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia.

RESUMEN / SUMMARY:  - Dendritic cells (DC) have a key role in controlling the immune response, by determining the outcome of antigen presentation to T cells. Through costimulatory molecules and other factors, DC are involved in the maintenance of peripheral tolerance through modulation of the immune response. This modulation occurs both constitutively, and in inflammation, in order to prevent autoimmunity and to control established immune responses. Dendritic cell control of immune responses may be mediated through cytokine or cell-contact dependent mechanisms. The molecular and cellular basis of these controls is being understood at an increasingly more complex level. This understanding is reaching a level at which DC-based therapies for the induction of immune regulation in autoimmunity can be tested in vivo. This review outlines the current state of knowledge of DC in immune tolerance, and proposes how DC might control both T cell responses, and themselves, to prevent autoimmunity and maintain peripheral tolerance.  N. Ref:: 135

 

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[135]

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

 

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[136]

TÍTULO / TITLE:  - Plasticity of hematopoietic stem cells: enough to induce tolerance and repair tissue?

REVISTA / JOURNAL:  - Arthritis Rheum 2002 Apr;46(4):855-8.

      ●● Enlace al texto completo (gratuito o de pago) 1002/art.10201 [pii]

AUTORES / AUTHORS:  - Burt RK; Traynor AE; Oyama Y; Barr WG  N. Ref:: 28

 

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[137]

TÍTULO / TITLE:  - Effects of immunosuppressive drugs on dendritic cells and tolerance induction.

REVISTA / JOURNAL:  - Transplantation 2003 May 15;75(9 Suppl):37S-42S.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000067950.90241.1D

AUTORES / AUTHORS:  - Lagaraine C; Lebranchu Y

INSTITUCIÓN / INSTITUTION:  - EA 3249, Cellules hematopoietiques, hemostase et greffe, Laboratoire d’immunologie, Faculte de medecine, Tours, France.

RESUMEN / SUMMARY:  - Dendritic cells, the most effective antigen-presenting cells for priming naive T cells and initiating immune responses, are also able to induce tolerance. This balance between immunity and tolerance depends on the functional stage of dendritic cells (DC). Activation of naive T cells by immature DC can induce tolerance. It is therefore of interest to summarize the effects of immunosuppressive agents on DC maturation and functions. In contrast to glucocorticosteroids, mycophenolate mofetil, and vitamin D(3) analogs, calcineurin inhibitors do not seem to inhibit DC maturation in in vitro culture systems. However, these molecules all appear to interfere with DC functions.  N. Ref:: 44

 

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[138]

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

 

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[139]

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

 

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[140]

TÍTULO / TITLE:  - Administration of donor apoptotic cells: an alternative cell-based therapy to induce tolerance?

REVISTA / JOURNAL:  - Transplantation 2003 May 15;75(9 Suppl):43S-45S.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000067951.90241.54

AUTORES / AUTHORS:  - Kleinclauss F; Perruche S; Cahn JY; Tiberghien P; Saas P

INSTITUCIÓN / INSTITUTION:  - INSERM E0119/UPRES EA2284, Etablissement Francais du Sang Bourgogne Franche-Comte, Universite de Franche-Comte, Besancon, France.

RESUMEN / SUMMARY:  - Apoptotic cells are endowed with immunomodulatory properties. The authors propose infusing apoptotic cells as a cell-based therapy product to facilitate allogeneic hematopoietic engraftment after a nonmyeloablative conditioning regimen. Such an approach may be used to obtain macrochimerism in combined hematopoietic cells and solid organ transplantation. In this article, the authors describe the mechanisms of combined hematopoietic and organ allograft transplantation and the potential difficulties. The authors discuss how intravenous apoptotic cell infusion may influence the outcome of combined transplantation. This may prove to be an interesting approach for future development in cell therapy.  N. Ref:: 29

 

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[141]

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

 

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[142]

TÍTULO / TITLE:  - Immunosuppression and xenotransplantation of cells for cardiac repair.

REVISTA / JOURNAL:  - Ann Thorac Surg 2004 Feb;77(2):737-44.

      ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2003.08.036

AUTORES / AUTHORS:  - Xiao YF; Min JY; Morgan JP

INSTITUCIÓN / INSTITUTION:  - Stem Cell Research Laboratory, The Charles A. Dana Research Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. yxiao@bidmc.harvard.edu

RESUMEN / SUMMARY:  - The death of highly vulnerable cardiomyocytes during ischemia leads to cardiac dysfunction, including heart failure. Due to limited proliferation of adult mammalian cardiomyocytes, the dead myocardium is replaced by noncontractile fibrotic tissue. Introducing exogenous cells to participate in the regeneration of infarcted myocardium has thus been proposed as a novel therapeutic approach. In view of the availability of various xenogeneic cells and fewer ethical and political concerns that surround human embryonic stem cells and fetal cardiomyocytes, cellular xenotransplantation may be a potential alternative approach for cardiac repair in humans. However, one of the most daunting challenges of xenotransplantation is immunorejection. This article summarizes the progress in cellular xenotransplantation for cardiac repair in experimental settings and the current understanding of possible immune responses following the engraftment of xenogeneic cells. The public attitude towards xenotransplantation is reportedly more favorable to receiving cells or tissues than a whole organ, but many scientific obstacles need to be overcome before the utilization of xenogeneic cells for cardiac repair in patients with heart disease becomes applicable to clinical practice.  N. Ref:: 82

 

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[143]

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

 

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[144]

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.

 

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[145]

TÍTULO / TITLE:  - Gastroduodenal Crohn’s disease: medical management.

REVISTA / JOURNAL:  - Inflamm Bowel Dis 2003 Mar;9(2):127-8; discussion 131.

AUTORES / AUTHORS:  - Tremaine WJ

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. tremaine.william@mayo.edu  N. Ref:: 9

 

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[146]

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

 

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[147]

TÍTULO / TITLE:  - Evaluation of thalidomide for treatment or prevention of chronic graft-versus-host disease.

REVISTA / JOURNAL:  - Leuk Lymphoma 2003 Jul;44(7):1141-6.

AUTORES / AUTHORS:  - Flowers ME; Martin PJ

INSTITUCIÓN / INSTITUTION:  - Division of Clinical Research, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., DS-290, PO Box 19024, Seattle, WA 98109-1024, USA. mflowers@fhcrc.org

RESUMEN / SUMMARY:  - During the past 5 years, better understanding of immunomodulatory and anti-angiogenesis properties of thalidomide has increased interest in the use of this agent for a wider variety of clinical applications. This article reviews the clinical evaluation of thalidomide for treatment or prevention of chronic graft-versus-host-disease.  N. Ref:: 38

 

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[148]

TÍTULO / TITLE:  - Dry eye as a major complication associated with chronic graft-versus-host disease after hematopoietic stem cell transplantation.

REVISTA / JOURNAL:  - Cornea 2003 Oct;22(7 Suppl):S19-27.

AUTORES / AUTHORS:  - Ogawa Y; Kuwana M

INSTITUCIÓN / INSTITUTION:  - Institute for Advanced Medical Research, and Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. yoko@sc.itc.keio.ac.jp

RESUMEN / SUMMARY:  - PURPOSE: To review the condition of dry eye associated with chronic graft-versus-host disease (GVHD). METHODS: The immunopathogenic processes and therapeutic options for lacrimal gland chronic GVHD are discussed. RESULTS: Dry eye is the most frequent ocular complication after hematopoietic stem cell transplantation. The condition typically occurs around 6 months post-operation and is recognized as a complication of chronic GVHD. Lacrimal gland specimens from patients with dry eye show prominent fibrosis and an increase in CD34+ stromal fibroblasts in the glandular interstitium in addition to infiltration of T cells into the periductal areas. In periductal areas, CD4+ and CD8+ T cells colocalize with stromal fibroblasts that express the full component of surface molecules necessary for antigen presentation. These findings strongly suggest that periductal fibroblasts are involved in fibrogenic and immune processes by interacting with T cells in the lacrimal gland of patients with chronic GVHD, resulting in rapidly progressive dry eye. Current therapies for dry eye related to chronic GVHD include tear supplements and nonspecific immunosuppressants. CONCLUSION: We report a significant role for stromal fibroblasts in the pathogenic processes of dry eye related to chronic GVHD. Although several supportive therapies can reduce the symptoms, specific therapies that suppress fibrotic and immune processes in the lacrimal glands are necessary to control dry eye associated with chronic GVHD.  N. Ref:: 49

 

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[149]

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

 

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[150]

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.

 

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[151]

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

 

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[152]

TÍTULO / TITLE:  - Immunomodulatory effects of statins: mechanisms and potential impact on arteriosclerosis.

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: <> 2002 Jun;13(6):1673-81.

AUTORES / AUTHORS:  - Palinski W; Tsimikas S

INSTITUCIÓN / INSTITUTION:  - Department of Medicine 0682, University of California San Diego, La Jolla, California 92093-0682, USA. wpalinski@ucsd.edu

RESUMEN / SUMMARY:  - Clinical trials with statins have demonstrated a marked reduction of cardiovascular mortality. However, it remains controversial whether these clinical benefits stem from powerful cholesterol-lowering effects of statins or whether they are due in part to their cholesterol-independent effects on vascular function, plaque growth, plaque rupture, or thrombosis. The identification of several mechanisms through which statins decrease the recruitment of monocytes and T cells into the arterial wall and inhibit T cell activation and proliferation in vitro have prompted speculations that immunomodulatory effects of statins may be beneficial in recipients of organ transplants. Hypercholesterolemia is frequent in these patients, and delayed-type hypersensitivity reactions in the arterial walls of the graft may be compounded by chronic inflammation associated with conventional atherogenesis. To assess the potential clinical relevance of immunomodulatory effects of statins, the role of the immune system in atherogenesis and the effects of statins in vitro in experimental models and in clinical trials will be reviewed. It is concluded that despite solid in vitro evidence, clinical evidence for an independent immunosuppressive effect of statins in organ transplant patients is presently insufficient; however, further investigation of their in vivo occurrence and clinical relevance is warranted.  N. Ref:: 106

 

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[153]

TÍTULO / TITLE:  - Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.

REVISTA / JOURNAL:  - Pediatrics 2002 Jul;110(1 Pt 1):e9.

AUTORES / AUTHORS:  - Gavin PJ; Katz BZ

INSTITUCIÓN / INSTITUTION:  - Division of Infectious Diseases, Department of Pediatrics, Children’s Memorial Hospital and Northwestern University Medical School, Chicago, Illinois 60614, USA. pgavin@childrensmemorial.org

RESUMEN / SUMMARY:  - BACKGROUND: Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. OBJECTIVE: We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. DESIGN/METHODS: We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. RESULTS: Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia. DISCUSSION: Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response. CONCLUSIONS: Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy.  N. Ref:: 45

 

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[154]

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

 

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[155]

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

 

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[156]

TÍTULO / TITLE:  - Vascular disease in mixed connective tissue disease (MCTD).

REVISTA / JOURNAL:  - Intern Med 2001 Dec;40(12):1176.

AUTORES / AUTHORS:  - Kondo H  N. Ref:: 13

 

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[157]

TÍTULO / TITLE:  - Subcutaneous black fungus (phaeohyphomycosis) infection in renal transplant recipients:three cases.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 15;77(1):140-2.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000107287.70512.E7

AUTORES / AUTHORS:  - Yehia M; Thomas M; Pilmore H; Van Der Merwe W; Dittmer I

INSTITUCIÓN / INSTITUTION:  - Auckland Renal Transplant Group, Auckland Hospital, Auckland, New Zealand. mahay@adhb.govt.nz

RESUMEN / SUMMARY:  - We describe three cases of subcutaneous phaeohyphomycosis developing in the lower limbs of renal transplant recipients shortly after transplantation. Each case presented with dark-colored nodules that subsequently ulcerated. Histopathologic examination revealed dematiaceous fungal hyphae with a surrounding granulomatous reaction. The fungi were subsequently identified as Alternaria alternatum in two cases and Phialophora richardsiae in one case. In one case, the lesions resolved during a prolonged (6-month) course of itraconazole without the requirement for surgical excision. In the other two cases, combined medical and surgical treatment resulted in cure. A review of the literature on phaeohyphomycosis is presented.  N. Ref:: 11

 

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[158]

TÍTULO / TITLE:  - Prevention of transfusion-associated graft-versus-host disease by inactivation of T cells in platelet components.

REVISTA / JOURNAL:  - Semin Hematol 2001 Oct;38(4 Suppl 11):34-45.

AUTORES / AUTHORS:  - Luban NL

INSTITUCIÓN / INSTITUTION:  - Department of Laboratory Medicine and Pathology and the Transfusion Medicine/Donor Center, Children’s National Medical Center, Washington, DC 20010, USA.

RESUMEN / SUMMARY:  - Patients with hematological malignancies and infants with congenital immunodeficiencies who received blood are two of many populations at risk for transfusion-associated graft-versus-host disease (TA-GVHD). Of the methodologies (eg, photoinactivation, peglyation, ultraviolet light, and irradiation) that can be used to prevent TA-GVHD, only irradiation of whole blood and cellular components is currently accepted practice of the US Food and Drug Administration (FDA). Among the newer methods that have been developed to reduce the risks of bacterial and viral contaminants of platelet transfusions, photochemical treatment (PCT) using psoralens and long-wavelength ultraviolet (UVA) irradiation modifies bacterial and viral genomes sufficiently to inhibit replication. Among a broad group of compounds, the synthetic psoralen compound amotosalen hydrochloride (HCl) (S-59) has been shown to be particularly effective in inactivating bacteria and viruses, without adversely affecting in vitro and in vivo platelet function.  N. Ref:: 92

 

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[159]

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

 

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[160]

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

 

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[161]

TÍTULO / TITLE:  - Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood?

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 Jun 1;101(11):4233-44. Epub 2003 Jan 9.

      ●● Enlace al texto completo (gratuito o de pago) 1182/blood-2002-08-2510

AUTORES / AUTHORS:  - Grewal SS; Barker JN; Davies SM; Wagner JE

INSTITUCIÓN / INSTITUTION:  - University of Minnesota, 420 Delaware St SE, MMC 477, Minneapolis, MN 55455, USA. grewa002@umn.edu  N. Ref:: 165

 

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[162]

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

 

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[163]

TÍTULO / TITLE:  - Vascular thrombosis and acute cytomegalovirus infection in immunocompetent patients: report of 2 cases and literature review.

REVISTA / JOURNAL:  - Clin Infect Dis 2003 Jun 1;36(11):E134-9. Epub 2003 May 19.

AUTORES / AUTHORS:  - Abgueguen P; Delbos V; Chennebault JM; Payan C; Pichard E

INSTITUCIÓN / INSTITUTION:  - Department of Infectious Diseases, Centre Hospitalo-Universitaire, Angers, France. piabgueguen@chu-angers.fr

RESUMEN / SUMMARY:  - Acute cytomegalovirus (CMV) infection in immunocompetent patients is common worldwide, with seroprevalence rates of 40%-100%, depending on the country, socioeconomic conditions, and the patient’s age. Infection is most often asymptomatic, but acute cytomegalovirus infection is occasionally revealed by prolonged fever, cervical lymphadenitis, and arthralgia, and it is more rarely revealed by pneumonia, myocarditis, pericarditis, colitis, and hemolytic anemia. Here, we report 2 cases of acute CMV infection in nonimmunocompromised adults that were complicated by venous thrombosis with pulmonary embolism. We also review previously reported cases of vascular thrombosis and discuss the propensity of CMV to induce vascular damage with associated thrombosis.  N. Ref:: 55

 

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[164]

TÍTULO / TITLE:  - Protocol core needle biopsy and histologic Chronic Allograft Damage Index (CADI) as surrogate end point for long-term graft survival in multicenter studies.

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):773-9.

AUTORES / AUTHORS:  - Yilmaz S; Tomlanovich S; Mathew T; Taskinen E; Paavonen T; Navarro M; Ramos E; Hooftman L; Hayry P

INSTITUCIÓN / INSTITUTION:  - Data Analysis Center, Division of Transplantation, Department of Surgery, University of Calgary, Alberta, Canada.

RESUMEN / SUMMARY:  - This study is an investigation of whether a protocol biopsy may be used as surrogate to late graft survival in multicenter renal transplantation trials. During two mycophenolate mofetil trials, 621 representative protocol biopsies were obtained at baseline, 1 yr, and 3 yr. The samples were coded and evaluated blindly by two pathologists, and Chronic Allograft Damage Index (CADI) score was constructed. At 1 yr, only 20% of patients had elevated (>l.5 mg/100 ml) serum creatinine, whereas 60% of the biopsies demonstrated an elevated (>2.0) CADI score. The mean CADI score at baseline, 1.3 +/- 1.1, increased to 3.3 +/- 1.8 at 1 yr and to 4.1 +/- 2.2 at 3 yr. The patients at 1 yr were divided into three groups, those with CADI <2, between 2 and 3.9, and >4.0, the first two groups having normal (1.4 +/- 0.3 and 1.5 +/- 0.6 mg/dl) and the third group pathologic (1.9 +/- 0.8 mg/dl) serum creatinine. At 3 yr, there were no lost grafts in the low CADI group, six lost grafts (4.6%) in the in the elevated CADI group, and 17 lost grafts (16.7%) in the high CADI group (P < 0.001). One-year histologic CADI score predicts graft survival even when the graft function is still normal. This observation makes it possible to use CADI as a surrogate end point in prevention trials and to identify the patients at risk for intervention trials.

 

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[165]

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

 

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[166]

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

 

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[167]

TÍTULO / TITLE:  - Pulmonary infiltrates in the non-HIV-infected immunocompromised patient: etiologies, diagnostic strategies, and outcomes.

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: <> 2004 Jan;125(1):260-71.

AUTORES / AUTHORS:  - Shorr AF; Susla GM; O’Grady NP

INSTITUCIÓN / INSTITUTION:  - Pulmonary and Critical Care Medicine Service, Walter Reed Army Medical Center, Washington, DC 20307, USA. afshorr@dnamail.com

RESUMEN / SUMMARY:  - Pulmonary complications remain a major cause of both morbidity and mortality in immunocompromised patients. When such individuals present with radiographic infiltrates, the clinician faces a diagnostic challenge. The differential diagnosis in this setting is broad and includes both infectious and noninfectious processes. Rarely are the radiographic findings classic for one disease, and most potential etiologies have overlapping clinical and radiographic appearances. In recent years, several themes have emerged in the literature on this topic. First, an aggressive approach to identifying a specific etiology is necessary; as a corollary, diagnostic delay increases the risk for mortality. Second, the evaluation of these infiltrates nearly always entails bronchoscopy. Bronchoscopy allows identification of some etiologies with certainty, and often allows for the exclusion of infectious agents even if the procedure is otherwise unrevealing. Third, early use of CT scanning regularly demonstrates lesions missed by plain radiography. Despite these advances, initial therapeutic interventions include the use of broad-spectrum antibiotics and other anti-infectives in order to ensure that the patients is receiving appropriate therapy. With the results of invasive testing, these treatments are then narrowed. Frustratingly, outcomes for immunocompromised patients with infiltrates remain poor.  N. Ref:: 58

 

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[168]

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

 

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[169]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.13 Analysis of patient and graft survival.

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: <> 2002;17 Suppl 4:60-7.

RESUMEN / SUMMARY:  - GUIDELINES: A. It is important for a transplant unit to follow-up on the results of their transplant activities. In order to achieve correct reports on graft and patient outcome in all patients, it is necessary to have sufficient resources, such as a computerized database, and continuous updates of patient information. All data collected should be subjected to validation procedures to ensure completeness and accuracy. B. Improved outcomes following implementation of new protocols, based on evaluation of clinical multi-centre trials, should be verified at local transplant centres since centres often include a range of patients different from those selected for the trial. C. The most widely accepted descriptor of outcome is the Kaplan-Meier probability estimate of patient and graft survival. Survival estimates should be calculated at intervals of time after transplantation and should always be expressed with their 95% confidence intervals. D. Kaplan-Meier survival estimates may be calculated in three ways. (i) ‘Patient survival’ should be calculated from the date of transplantation to the date of death or the date of the last follow-up. (ii) ‘Graft survival’ (non-censored for death) should be calculated from the date of transplantation to the date of irreversible graft failure signified by return to long-term dialysis (or retransplantation) or the date of the last follow-up during the period when the transplant was still functioning or to the date of death. Here, death with graft function is treated as graft failure. (iii) ‘Graft survival censored for death with a functioning graft’ (death-censored graft survival) should be calculated from the date of transplantation to the date of irreversible graft failure signified by return to long-term dialysis (or retransplantation) or the date of last follow-up during the period when the transplant was still functioning. In the event of death with a functioning graft, the follow-up period is censored at the date of death. E. The outcome of transplants carried out at a centre should be compared with those achieved across a range of data from centres collated by national and international multi-centre registries. Interpretation of a centre’s performance should take into account the number of transplants performed and the prevalence of major risk factors. F. Major risk factors that influence transplant outcome are identifiable by applying multivariate analytical methods to large multi-centre follow-up databases. Although these major risk factors may not be identifiable in individual centre data, they should nonetheless be taken into account in patient management. G. When designing a clinical trial or evaluating data from a recent trial, the expected improvement in graft survival resulting from a reduction in acute rejection may be estimated from a knowledge of the rejection and graft survival rates that existed prior to the introduction of the new therapeutic regimen. H. When designing or evaluating a clinical trial, it is important to analyse the power of the study to verify statistically the difference (in graft survival) that might be expected and its statistical significance. A study resulting in absence of statistically significant differences between two treatment groups with insufficient statistical power to verify a difference at the expected level should not be taken as evidence of absence of a true difference.

 

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[170]

TÍTULO / TITLE:  - Posttransplantation diabetes: a systematic review of the literature.

REVISTA / JOURNAL:  - Diabetes Care. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://care.diabetesjournals.org/ 

      ●● Cita: Diabetes Care: <> 2002 Mar;25(3):583-92.

AUTORES / AUTHORS:  - Montori VM; Basu A; Erwin PJ; Velosa JA; Gabriel SE; Kudva YC

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Diabetes, Metabolism, Nutrition, and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

RESUMEN / SUMMARY:  - OBJECTIVES: To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS: We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS: Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (<10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P = 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS: Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs.  N. Ref:: 79

 

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[171]

TÍTULO / TITLE:  - Calcineurin inhibition and cardiac hypertrophy: a matter of balance.

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 Mar 13;98(6):2947-9.

      ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.051033698

AUTORES / AUTHORS:  - Leinwand LA

INSTITUCIÓN / INSTITUTION:  - Department of Molecular, Cellular, and Developmental Biology, Porter Addition, Room A3B40, University of Colorado, Boulder, CO 80309-0347, USA. leinwand@stripe.colorado.edu  N. Ref:: 18

 

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[172]

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

 

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[173]

TÍTULO / TITLE:  - Renal function as a predictor of long-term graft survival in renal transplant patients.

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 May;18 Suppl 1:i3-6.

AUTORES / AUTHORS:  - First MR

INSTITUCIÓN / INSTITUTION:  - Research and Development, Fujisawa Healthcare, Inc., Deerfield, IL 60015, USA. roy_first@fujisawa.com

RESUMEN / SUMMARY:  - Acute rejection is a major risk factor for kidney graft failure. However, as acute rejection has been progressively reduced by recent immunosuppressive regimens, other risk factors are becoming increasingly important. Evidence is accumulating that early renal function predicts long-term outcome. A recent registry survey of more than 100 000 kidney transplants found that 6- and 12-month serum creatinine levels, as well as the change between 6 and 12 months, are strongly associated with long-term graft survival. A survey of paediatric renal transplant recipients showed that poor creatinine clearance (<50 ml/min) as early as 30 days post-transplant predicted an annual rate of graft loss of 13% compared with <3% in patients with 30-day clearance >50 ml/min. This association between early renal function and long-term outcome was confirmed in multicentre studies. Renal transplant recipients (n=572) with 6-month serum creatinine levels >1.5 mg/dl suffered 3-year graft loss of 19.3% compared with only 8.5% in patients with levels <1.6 mg/dl (P<0.001). Significantly fewer patients receiving tacrolimus had 12-month serum creatinine levels >1.5 mg/dl compared with cyclosporin (42 versus 54%, P<0.05). Interestingly, a single-centre study (n=436) found that while glomerular filtration rate (GFR) at 6 months post-transplant had remained stable over the last decade, the rate of loss of renal function had decreased. A lower rate of GFR loss was associated with absence of rejection, use of mycophenolate mofetil rather than azathioprine and use of tacrolimus rather than cyclosporin (P<0.01). In conclusion, early measures of renal function allow identification of those patients at highest risk of graft failure and provide an invaluable tool for improving outcomes by tailored immunosuppression. The choice of such immunosuppression should be guided not only by its ability to prevent rejection, but also by its impact on renal function.  N. Ref:: 11

 

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[174]

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

 

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[175]

TÍTULO / TITLE:  - Mycophenolate mofetil for the prevention and treatment of graft-versus-host disease following stem cell transplantation: preliminary findings.

REVISTA / JOURNAL:  - Bone Marrow Transplant 2001 Jun;27(12):1255-62.

AUTORES / AUTHORS:  - Vogelsang GB; Arai S

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Johns Hopkins Oncology Center, Baltimore, MD 21287-8943, USA.

RESUMEN / SUMMARY:  - The therapeutic benefits of allogeneic stem cell transplantation in patients with hematologic disorders are limited by the significant morbidity and mortality of graft-versus-host disease (GVHD). Current agents for the prevention and treatment of GVHD have limited efficacy and often result in toxic side-effects. Mycophenolate mofetil (MMF) is a new immunosuppressant with a selective mechanism of action. When employed following solid organ transplantation, MMF reduces the incidence and severity of acute rejection episodes. By selectively targeting activated lymphocytes, the active metabolite of MMF, mycophenolic acid (MPA), appears to augment the actions of standard immunosuppressant agents without adding overlapping toxicities. Studies of combination regimens that include MMF report that this agent permits a dose reduction of cyclosporine, tacrolimus, or corticosteroid, without increasing the incidence of acute rejection in solid organ transplants. Reports on the efficacy of MMF following stem cell transplantation in animal studies were mixed. However, the use of a non-myeloablative conditioning regimen with a post-graft immunosuppressive regimen of MMF and cyclosporine was able to sustain stable mixed chimeras in 60% to 80% of dogs who received hematopoietic grafts from DLA-identical littermates. MMF has demonstrated activity in preliminary clinical trials for GVHD prophylaxis, and treatment of acute or chronic GVHD. Larger clinical trials are warranted to determine the optimum dose and route of MMF administration for GVHD, as well as the comparative safety and efficacy of MMF-containing regimens.  N. Ref:: 36

 

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[176]

TÍTULO / TITLE:  - Postmenopausal tubo-ovarian abscess due to Pseudomonas aeruginosa in a renal transplant patient: a case report and review of the literature.

REVISTA / JOURNAL:  - Transplantation 2001 Oct 15;72(7):1241-4.

AUTORES / AUTHORS:  - El Khoury J; Stikkelbroeck MM; Goodman A; Rubin RH; Cosimi AB; Fishman JA

INSTITUCIÓN / INSTITUTION:  - Infectious Disease Division, GRJ 504, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Pseudomonas aeruginosa is an uncommon cause of infection in the female genital tract. We report a case of postmenopausal tubo-ovarian abscess (TOA) due to P. aeruginosa in a renal transplant recipient. The presentation included mild abdominal symptoms with rapid progression of peritonitis and surgical abscess drainage. This is the first such case in an organ transplant recipient described in the English literature. METHODS AND RESULTS: Published reports of 1040 cases of TOA were reviewed. The most common features were a history of sexually transmitted disease or pelvic inflammatory disease, and symptoms including abdominal pain and fever. Escherichia coli, Bacteroides spp., and Klebsiella pneumoniae were the most frequently encountered pathogens. Neisseria gonorrhoeae and Chlamydia trachomatis, which are frequently isolated from cervical cultures, are uncommonly isolated from tubo-ovarian abscesses. Forty percent of patients were treated with antibiotics alone, 18.8% with abdominal surgery, and 32% with surgery and antimicrobial therapy. CONCLUSION: This report illustrates the muted presentation and atypical microbiology of gynecologic infection in an organ transplant recipient.  N. Ref:: 59

 

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[177]

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

 

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[178]

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.

 

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[179]

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.

 

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[180]

TÍTULO / TITLE:  - Tacrolimus ointment for the treatment of atopic dermatitis: clinical and pharmacologic effects.

REVISTA / JOURNAL:  - Allergy Asthma Proc 2002 May-Jun;23(3):191-7.

AUTORES / AUTHORS:  - Rico MJ; Lawrence I

INSTITUCIÓN / INSTITUTION:  - Fujisawa Healthcare, Inc, 3 Pookway North Deerfeild, IL 60022, USA.

RESUMEN / SUMMARY:  - The topical immunomodulator tacrolimus ointment has been shown to be safe and effective in the treatment of atopic dermatitis in clinical trials involving over 16,000 patients. Clinical trial results focusing on tacrolimus’ safety and efficacy are summarized. Minimal systemic absorption results from topical application in patients with atopic dermatitis. Although the exact mechanism of action of tacrolimus ointment in atopic dermatitis is unknown, tacrolimus is known to inhibit up-regulation of cytokine production following T cell activation and to decrease Fc epsilon RI expression on dendritic antigen-presenting cells in skin. Additional mechanisms of action of tacrolimus relevant in the pathogenesis of inflammatory skin disorders are discussed.  N. Ref:: 27

 

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[181]

- 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

 

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[182]

TÍTULO / TITLE:  - The immune tolerance network and rheumatic disease: immune tolerance comes to the clinic.

REVISTA / JOURNAL:  - Arthritis Rheum 2001 Aug;44(8):1730-5.

AUTORES / AUTHORS:  - Diamond B; Bluestone J; Wofsy D

INSTITUCIÓN / INSTITUTION:  - Albert Einstein College of Medicine, Department of Microbiology & Immunology and Medicine, Bronx, New York 10461, USA.

RESUMEN / SUMMARY:  - The development of effective, new, biologically based therapies for RA has created real excitement and justifiable optimism in recent years among rheumatologists and among patients with rheumatic diseases. Recent advances in our understanding of the mechanisms of immune activation and immune tolerance provide further cause for optimism. Against this background, the establishment of the ITN is an important step. However, significant hurdles remain to be cleared. First, despite dramatic scientific progress, restoration of immune tolerance in the face of an established autoimmune response is still an elusive goal, even in the laboratory. Not only does the ITN face this fundamental scientific challenge, but it also faces daunting practical and political challenges. For example, can the ITN influence the research agenda of the pharmaceutical and biotechnology industries? This question and other important questions will only be answered as the ITN matures. Autoimmune disease, although individually uncommon, affects more than 2% of Americans. The rheumatologist is especially aware of the devastating potential of autoimmune diseases. If the ITN succeeds in linking basic research into the mechanisms of autoimmunity with clinical trials of promising new therapies, it can be expected to play a critical role in advancing the practice of clinical rheumatology.  N. Ref:: 58

 

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[183]

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

 

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[184]

TÍTULO / TITLE:  - Cardiac allograft vasculopathy: central role of endothelial injury leading to transplant “atheroma”.

REVISTA / JOURNAL:  - Transplantation 2003 Sep 27;76(6):891-9.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000080981.90718.EB

AUTORES / AUTHORS:  - Valantine HA

INSTITUCIÓN / INSTITUTION:  - Falk Cardiovascular Research Center, Stanford University, California 94305-5406, USA. hvalantine@stanford.edu

RESUMEN / SUMMARY:  - Endothelial injury plays a central role in the pathophysiologic mechanisms underlying cardiac allograft vasculopathy (CAV). Although the accelerated course of CAV and its localization to the allograft support an important role for the alloimmune response, there is considerable evidence implicating lipoprotein abnormalities, metabolic disturbances, viral infections, and systemic inflammation in the process. This multifactorial basis for CAV may be put into a pathophysiologic context in which endothelial cell injury is the triggering event that initiates and drives the proliferative and fibrotic processes characteristic of CAV. In the transplant setting, endothelial cell injury is induced by multiple factors, including brain death, ischemia-reperfusion, alloimmune responses, and viral infections. Once initiated, propagation of the proliferative processes that ultimately lead to vascular occlusion is enhanced by the abnormal metabolic environment of elevated lipoproteins and insulin resistance encountered in most patients. This review examines the evidence for the role of potential triggers of endothelial injury in the pathophysiology of CAV and discusses the central role of the nitric oxide pathway in the disease process.  N. Ref:: 89

 

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[185]

TÍTULO / TITLE:  - Treatment of myelopathy in Sjogren syndrome with a combination of prednisone and cyclophosphamide.

REVISTA / JOURNAL:  - Arch Neurol 2001 May;58(5):815-9.

AUTORES / AUTHORS:  - Williams CS; Butler E; Roman GC

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Wilford Hall Medical Center, Lackland Air Force Base, Texas, USA. christopher.williams@59MDW.WHMC.af.mil

RESUMEN / SUMMARY:  - BACKGROUND: Peripheral neuropathy is a common complication of primary Sjogren syndrome, but central nervous system involvement also occurs and may be the only extraglandular manifestation. Sicca symptoms may also be minimal. Combinations of lesions along with relapses and remissions can suggest multiple sclerosis in the proper clinical setting, making the correct diagnosis elusive. OBJECTIVES: To report a case of progressive transverse myelopathy with previous optic neuropathy in primary central nervous system Sjogren syndrome (CNS-SS), and to review 17 previously reported cases and the patient’s responses to various therapies. DESIGN: Case report and literature review. SETTING: University hospital. PATIENT: A 63-year-old Hispanic woman with a 10-month history of progressive spastic paraparesis associated with optic neuropathy and a T10 sensory level. Magnetic resonance imaging demonstrated multifocal, contrast-enhancing lesions in the spinal cord. The patient was diagnosed as having CNS-SS because of the presence of sicca symptoms, abnormal serological test results, and salivary gland biopsy results, which fulfilled San Diego criteria for “definite” Sjogren syndrome. She responded to treatment with a combination of prednisone and cyclophosphamide. CONCLUSIONS: Diagnosis of primary CNS-SS requires a high index of suspicion and specialized clinical testing. Treatment with pulse doses of corticosteroids alone may be suboptimal, but results of treatment with a combination of corticosteroids and either cyclophosphamide or chlorambucil have been encouraging.  N. Ref:: 24

 

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[186]

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

 

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[187]

TÍTULO / TITLE:  - ‘GVHD’: graft-versus-host disease or graft-versus-Hodgkin’s disease? An old acronym with new meaning.

REVISTA / JOURNAL:  - Bone Marrow Transplant 2003 May;31(9):739-46.

      ●● Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703895

AUTORES / AUTHORS:  - Porter DL; Stadtmauer EA; Lazarus HM

INSTITUCIÓN / INSTITUTION:  - Bone Marrow and Stem Cell Transplant Program, Division of Hematology-Oncology, University of Pennsylvania Medical Center, Philadelphia 19104, USA.

RESUMEN / SUMMARY:  - The majority of patients with relapsed or refractory Hodgkin’s lymphoma (HL) will not be cured with standard therapy. Relapse rates remain high even after autologous stem cell transplantation (SCT), particularly for patients with high-risk disease. Allogeneic SCT offers several potential advantages for patients with HL. It is feasible when autologous stem cells are not available and stem cell grafts will be tumor free. Perhaps a more important advantage is the potential to generate a graft-versus-Hodgkin’s lymphoma (GVHL) effect. Unfortunately, although allogeneic SCT may cure some HL patients, treatment-related mortality has been unusually high, and superior survival, when compared to autologous SCT, has not been demonstrated. Nonmyeloablative conditioning and allogeneic SCT may induce a direct GVHL reaction with less conditioning regimen-related toxicity and ultimately may have the potential to improve cure rates and survival for advanced HL patients.  N. Ref:: 81

 

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[188]

TÍTULO / TITLE:  - Review of the antiproliferative properties of mycophenolate mofetil in non-immune cells.

REVISTA / JOURNAL:  - Int J Clin Pharmacol Ther 2003 Oct;41(10):465-9.

AUTORES / AUTHORS:  - Morath C; Zeier M

INSTITUCIÓN / INSTITUTION:  - Department of Nephrology, University of Heidelberg, Germany. christian_morath@med.uni-heidelberg.de

RESUMEN / SUMMARY:  - Mycophenolate mofetil (MMF), the prodrug ofmycophenolic acid (MPA), is a selective, non-competitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) and of the type II isoform in particular. IMPDH is the rate-limiting enzyme in the de novo biosynthesis of guanosine nucleotides. MMF strongly inhibits both T- and B lymphocyte proliferation and has been used in the prevention of acute and chronic allograft rejection since the mid 1990s. Recent evidence, however, suggests that MMF is also capable of inhibiting the proliferation of non-immune cells. In various cell lines, i.e. smooth muscle cells, renal tubular cells and mesangial cells, MPA reduced or even abrogated proliferation in response to proliferative stimuli. Furthermore, data from our own laboratory demonstrate a dose-dependent inhibition of dermal fibroblast proliferation by MPA. In animal studies, MMF ameliorated renal lesions in immune-mediated disease, i.e. in the anti-thy 1.1 model and experimental lupus nephritis, but was also effective in non-immune-mediated renal damage in the rat remnant-kidney model. These observations prompted several investigators to study the effects of MMF in proliferating (renal) disease of non-immune origin in humans. MMF significantly reduced proteinuria in minimal-change disease and focal segmental glomerulosclerosis. In addition, MMF showed beneficial effects in the treatment of chronic allograft nephropathy and calcineurin inhibitor toxicity through reduction of immune- and non-immune-mediated renal damage. MMF is well tolerated and has proven to be a relatively safe drug causing only minor bone marrow suppression. Taken together, there is a growing body of evidence pointing to therapeutic applications of MMF other than immunosuppression, in particular the prevention of fibrosis.  N. Ref:: 39

 

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[189]

TÍTULO / TITLE:  - Role of immunocompetent cells in nonimmune renal diseases.

REVISTA / JOURNAL:  - Kidney Int 2001 May;59(5):1626-40.

AUTORES / AUTHORS:  - Rodriguez-Iturbe B; Pons H; Herrera-Acosta J; Johnson RJ

INSTITUCIÓN / INSTITUTION:  - Renal Service Hospital Universitario de Maracaibo, Venezuela. bri@iamnet.com

RESUMEN / SUMMARY:  - Renal infiltration with macrophages and monocytes is a well-recognized feature of not only immune, but also nonimmune kidney disease. This review focuses on the investigations that have shown accumulation of immunocompetent cells in experimental models of acute and chronic ischemia, protein overload, hypercholesterolemia, renal ablation, obstructive uropathy, polycystic kidney disease, diabetes, aging, murine hypertension, and nephrotoxicity. We examine the mechanisms of infiltration of immunocompetent cells and their participation in the self-perpetuating cycle of activation of the angiotensin system, generation of reactive oxygen species, and further recruitment of monocytes and lymphocytes. We also discuss the possibility of antigen-dependent and antigen-independent mechanisms of immune cell activation in these animal models. Finally, we review the recent studies in which suppression of cellular immunity with mycophenolate mofetil has proven beneficial in attenuating or preventing the progression of renal functional and histologic damage in experimental conditions of nonimmune nature.  N. Ref:: 219

 

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[190]

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.

 

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[191]

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

 

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[192]

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

 

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[193]

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

 

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[194]

TÍTULO / TITLE:  - Post-transplant Burkitt’s leukemia or lymphoma. Study of five cases treated with specific intensive therapy (PETHEMA ALL-3/97 trial).

REVISTA / JOURNAL:  - Leuk Lymphoma 2003 Sep;44(9):1541-3.

AUTORES / AUTHORS:  - Xicoy B; Ribera JM; Esteve J; Brunet S; Sanz MA; Fernandez-Abellan P; Feliu E

INSTITUCIÓN / INSTITUTION:  - Services of Hematology, Hospital Universitari Germans Trias i Pujol, Badalona, España.

RESUMEN / SUMMARY:  - Burkitt’s lymphoma (BL) and Burkitt-like acute lymphoblastic leukemia (ALL) are uncommon lymphoproliferative disorders after solid organ or stem cell transplantation. Although their prognosis is considered to be poor, there are scarce data on the clinical characteristics and the response to specific therapies. We report the main clinical characteristics and the results of a specific intensive chemotherapy in 5 adult patients with postransplant BL/ALL3 included in the PETHEMA ALL3/97 protocol. Two patients died in induction, another died in consolidation phase and the remaining 2 patients are in continuous complete remission 6 and 18 months from the diagnosis.  N. Ref:: 6

 

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[195]

TÍTULO / TITLE:  - Review article: does the use of immunosuppressive therapy in inflammatory bowel disease increase the risk of developing lymphoma?

REVISTA / JOURNAL:  - Aliment Pharmacol Ther 2001 Dec;15(12):1843-9.

AUTORES / AUTHORS:  - Bebb JR; Logan RP

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology, University Hospital, Nottingham, UK.

RESUMEN / SUMMARY:  - Recent case reports have raised concerns regarding the risks of non-Hodgkin’s lymphoma in patients with inflammatory bowel disease treated with immunosuppressive agents. This evidence-based review examines this issue from data derived from the use of immunosuppression in other conditions (and inflammatory bowel disease). We conclude that, in transplant (cardiac and renal) recipients, immunosuppression increases the risk of non-Hodgkin’s lymphoma. For non-transplant patients (with psoriasis and rheumatoid arthritis), debate remains as to whether the observed increase in the incidence of non-Hodgkin’s lymphoma is due to drug or disease. For inflammatory bowel disease per se, population studies show no significant increase in the risk of non-Hodgkin’s lymphoma, with a relative risk of 1.3 (95% confidence interval, 0.9-1.7) compared to expected rates, and several studies of immuno- suppression in inflammatory bowel disease do not appear to confirm a significant rate of lymphoma incidence. Reported cases of lymphoma from single centres should be viewed with caution as evidence of increased risk. If any association exists, it is likely to be of minimal clinical significance compared to the established and more frequent risks of myelosuppression and infection, and is unlikely to outweigh the benefit of immunosuppression in inflammatory bowel disease.  N. Ref:: 43

 

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[196]

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

 

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[197]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.5.8. Cardiovascular risks. Immunosuppressive therapy.

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: <> 2002;17 Suppl 4:30-1.

RESUMEN / SUMMARY:  - GUIDELINE: Immunosuppressive therapies, especially corticosteroids and anticalcineurin inhibitors; contribute to the prevalence of cardiovascular risk factors, such as arterial hypertension, hyperlipidaemia and hyperglycaemia, and this effect is dose dependent. Reduction of the dose, withdrawal and/or switching to another drug could be useful to control these risk factors.

 

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[198]

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.

 

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[199]

TÍTULO / TITLE:  - Mechanisms of tolerance induction through the transplantation of donor hematopoietic stem cells: central versus peripheral tolerance.

REVISTA / JOURNAL:  - Transplantation 2003 May 15;75(9 Suppl):21S-25S.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000067947.90241.66

AUTORES / AUTHORS:  - Wekerle T; Blaha P; Koporc Z; Bigenzahn S; Pusch M; Muehlbacher F

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Vienna General Hospital, Waehringer Guertel 18, A 1090 Vienna, Austria. thomas.wekerle@akh-wien.ac.at

RESUMEN / SUMMARY:  - The transplantation of donor hematopoietic stem cells has been used successfully in numerous experimental settings to induce donor-specific tolerance. After appropriate host conditioning, hematopoietic stem-cell transplantation leads to a lasting state of donor macrochimerism that is associated with a robust form of tolerance. One of the key factors in the success of this approach is its reliance on intrathymic clonal deletion to ensure lifelong tolerization of newly developing T cells. Evidence for ongoing central deletion comes from studies following superantigen-reactive T cells and from experiments using mice transgenic for an alloreactive T-cell receptor. In protocols inducing tolerance through macrochimerism, the preexisting mature T-cell repertoire is controlled by either globally destroying all T cells before the hematopoietic cell transplantation or, in more recent models, by tolerizing it through co-stimulation blockade. The peripheral mechanisms induced by hematopoietic stem-cell transplantation and co-stimulation blockade include both extrathymic clonal deletion and the nondeletional mechanisms anergy, suppression, or both. In addition to these immunologic hurdles, a physiologic engraftment barrier has to be surmounted for the successful induction of mixed chimerism. This can be achieved by cytoreductive host treatment or by the infusion of high numbers of donor hematopoietic cells. A detailed delineation of the mechanisms responsible for tolerance induction after hematopoietic stem-cell transplantation is expected to help in the translation of these experimental protocols to clinical organ transplantation.  N. Ref:: 31

 

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[200]

TÍTULO / TITLE:  - Introduction to the Immunocompromised Host Society consensus conference on epidemiology, prevention, diagnosis, and management of infections in solid-organ transplant patients.

REVISTA / JOURNAL:  - Clin Infect Dis 2001 Jul 1;33 Suppl 1:S1-4.

AUTORES / AUTHORS:  - Rubin RH; Schaffner A; Speich R

INSTITUCIÓN / INSTITUTION:  - Center for Experimental Pharmacology and Therapeutics, Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02142-1308, USA. rhrubin@mit.edu

RESUMEN / SUMMARY:  - Infectious complications are still a significant cause of morbidity and death in solid-organ transplant patients, with significant infection being found in up to two-thirds of these individuals. The risk of infection in the organ transplant patient, particularly of opportunistic infection, is largely determined by 3 factors: the net state of immunosuppression, the epidemiologic exposures the patient encounters, and the consequences of the invasive procedures to which the patient is subjected. The most important principles of patient treatment are prevention, early diagnosis, and specific therapy. This issue is designed as a position paper by a group of experts on epidemiology, prevention, diagnosis, and management of infections in solid-organ transplant patients. We feel that our efforts may serve as an important first step in the development of guidelines in this area.  N. Ref:: 25

 

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