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Revisiones-Ciencias Básicas-Molecular, Bioquímica, Metabolismo & Genética *** Reviews-Basic Sciences-Molecular, Biochemistry, Metabolism & Genetics

 

INMUNOSUPRESIÓN *** IMMUNOSUPPRESSION

(Conceptos / Keywords: Immunosuppression; Immunosuppressive ag.; Transpl. immunol.; GVH; Antirejection therapy; Lymphocyte depletion; Transpl. conditioning; etc).

 

Enero / January 2001 --- Marzo / March 2004

 

La biblioteca del conocimiento biomédico© es un servicio GRATUITO. Toda la información ha sido obtenida de fuentes públicas, de portales de internet que no requieren registro alguno para su uso, que no requieren estar de acuerdo con sus Términos de uso, que son de libre acceso a todo el mundo, y son a su vez gratuitos. La biblioteca (revisiones, guías, protocolos, medicina basada en la evidencia, etc...) se recopila en base a una patente que permite a Effiloop la catalogación de los artículos por campos de interés así como por el orden de su importancia (se proveen las primeras 200 revisiones). Toda la informacion se ampara en las leyes de libre pensamiento-expresión, y de uso justo. Este documento sólo contiene artículos escritos en Castellano y/o Inglés.

 

The biomedical library© is a FREE service. All the information has been obtained from public sources, from web sites that do not require registration for their use, that do not require an agreement with their Terms of use, that provide free access for all, and are free of charge. The library (reviews, guides, protocols, medicine based medicine, etc) is arranged according to a patent that warrants Effiloop to catalogue the articles by fields of interest as well as to sort articles by true relevance (the first 200 reviews are provided). All the information is provided according to the freedom of speech and fair use laws. Only articles written in Spanish and/or English are included.

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:  - Genetic and functional relationships between MHC and NK receptor genes.

REVISTA / JOURNAL:  - Immunity 2001 Sep;15(3):363-74.

AUTORES / AUTHORS:  - Trowsdale J

INSTITUCIÓN / INSTITUTION:  - Immunology Division, Pathology Department, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.

RESUMEN / SUMMARY:  - HLA class I and NK receptors are encoded within dense clusters of immune loci. The MHC, at 6p21.3, and the complex containing the KIR loci, at 19q13.4, both feature variation in the number of genes, as well as sequence polymorphism. In addition to T cell receptors, several variable class I-related molecules interact with polymorphic NK receptors. Some of the lectin-related NK receptor genes, at 12p13.1, also have ligands belonging to the extended class I family. The expanding clusters of class I-related sequences and their receptors, some of which evolved recently, reveal further complexity in immune recognition of disease.  N. Ref:: 85

 

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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:  - 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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[12]

TÍTULO / TITLE:  - Genetic control of MHC class II expression.

REVISTA / JOURNAL:  - Cell 2002 Apr;109 Suppl:S21-33.

AUTORES / AUTHORS:  - Ting JP; Trowsdale J

INSTITUCIÓN / INSTITUTION:  - Department of Microbiology and Immunology and The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. panyun@med.unc.edu

RESUMEN / SUMMARY:  - The presentation of peptides to T cells by MHC class II molecules is of critical importance in specific recognition by the immune system. Expression of class II molecules is exquisitely controlled at the transcriptional level. A large set of proteins interact with the promoters of class II genes. The most important of these is CIITA, a master controller that orchestrates expression but does not bind directly to the promoter. The transcriptosome complex formed at class II promoters is a model for induction of gene expression.  N. Ref:: 108

 

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[13]

TÍTULO / TITLE:  - Interferon-gamma reduces interleukin-4- and interleukin-13-augmented transforming growth factor-beta2 production in human bronchial epithelial cells by targeting Smads.

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

      ●● Enlace a la Editora de la Revista http://www.chestjournal.org/ 

      ●● Cita: Chest: <> 2003 Mar;123(3 Suppl):372S-3S.

AUTORES / AUTHORS:  - Wen FQ; Liu XD; Terasaki Y; Fang QH; Kobayashi T; Abe S; Rennard SI

INSTITUCIÓN / INSTITUTION:  - Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, NE 68198-5125, USA.  N. Ref:: 0

 

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[14]

TÍTULO / TITLE:  - When the lymphocyte loses its clothes.

REVISTA / JOURNAL:  - Immunity 2003 Apr;18(4):453-7.

AUTORES / AUTHORS:  - Nekrep N; Fontes JD; Geyer M; Peterlin BM

INSTITUCIÓN / INSTITUTION:  - Institute of Biochemistry, Medical Faculty of the University of Ljubljana, Slovenia.

RESUMEN / SUMMARY:  - The type II bare lymphocyte syndrome (BLS) or major histocompatibility complex class II (MHCII) deficiency is a severe combined immunodeficiency (SCID) that is characterized by the absence of constitutive and inducible expression of MHCII determinants on immune cells. Four complementation groups of BLS have been defined, and they result from mutations in DNA-bound activators and the coactivator for MHCII transcription. Recently, all complementation groups of BLS patients have been accounted for. Studies of the syndrome and specific mutations reveal important lessons for the genetics of the immune response.  N. Ref:: 35

 

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[15]

TÍTULO / TITLE:  - Ex vivo selection of recipient-type alloantigen-specific CD4(+)CD25(+) immunoregulatory T cells for the control of graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 15;77(1 Suppl):S32-4.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106470.07410.CA

AUTORES / AUTHORS:  - Trenado A; Fisson S; Braunberger E; Klatzmann D; Salomon BL; Cohen JL

INSTITUCIÓN / INSTITUTION:  - Biologie et Therapeutique des Pathologies Immunitaires, Hopital Pitie-Salpetriere, Paris, France.

RESUMEN / SUMMARY:  - Allogeneic hematopoietic stem-cell transplantation (HSCT) is the treatment of choice for many malignant and nonmalignant hematologic disorders. Donor T cells present in the hematopoietic stem-cell transplant improve engraftment and immune reconstitution and contribute to the graft-versus-leukemia effect, but are also responsible for the life-threatening graft-versus-host disease (GVHD). CD4(+)CD25(+) immunoregulatory T cells, which play a pivotal role in preventing organ-specific diseases, can also modulate GVHD if administered in equal numbers of T cells at the time of grafting. In this article, the authors describe a procedure of ex vivo selection and expansion of regulatory T cells specific for recipient-type alloantigens. These expanded regulatory T cells controlled GVHD. Their therapeutic use in HSCT should allow specific suppression of the activation of donor alloreactive T cells involved in GVHD while preserving the beneficial effects of other T cells.  N. Ref:: 27

 

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[16]

TÍTULO / TITLE:  - Hemochromatosis gene modifies course of hepatitis C viral infection.

REVISTA / JOURNAL:  - Gastroenterology 2003 May;124(5):1509-23.

AUTORES / AUTHORS:  - Pietrangelo A

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Centre for Hemochromatosis and Metabolic Liver Diseases, University of Modena and Reggio Emilia, Modeno, Italy. antonello@unimore.it  N. Ref:: 161

 

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[17]

TÍTULO / TITLE:  - T cell receptor-MHC interactions up close.

REVISTA / JOURNAL:  - Cell 2001 Jan 12;104(1):1-4.

AUTORES / AUTHORS:  - Hennecke J; Wiley DC

INSTITUCIÓN / INSTITUTION:  - Department of Molecular and Cellular Biology, Harvard University and Howard Hughes Medical Institute, Cambridge, MA 02138, USA. hennecke@crystal.harvard.edu  N. Ref:: 18

 

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[18]

- Castellano -

TÍTULO / TITLE:La ruta de senalizacion CA++/calcineurina/NFAT en activacion endotelial y angiogenesis: efectos de la ciclosporina A. CA++/ calcineurin/NFAT signaling in endothelial activation and angiogenesis: effects od cyclosporin A .

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

      ●● Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/ 

      ●● Cita: Nefrologia: <> 2003;23 Suppl 3:44-8.

AUTORES / AUTHORS:  - Quesada AJ; Redondo JM

INSTITUCIÓN / INSTITUTION:  - Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid y Centro Nacional de Investigaciones Cardiovasculares (CNIC), Sinesio Delgado, 4 28049 Cantoblanco, Madrid. jmredondo@cbm.uam.es  N. Ref:: 31

 

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[19]

TÍTULO / TITLE:  - Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.

REVISTA / JOURNAL:  - Neurology 2002 Jan 22;58(2):169-78.

AUTORES / AUTHORS:  - Goodin DS; Frohman EM; Garmany GP Jr; Halper J; Likosky WH; Lublin FD; Silberberg DH; Stuart WH; van den Noort S

 

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[20]

TÍTULO / TITLE:  - Identification of TOR signaling complexes: more TORC for the cell growth engine.

REVISTA / JOURNAL:  - Cell 2002 Oct 4;111(1):9-12.

AUTORES / AUTHORS:  - Abraham RT

INSTITUCIÓN / INSTITUTION:  - Program in Signal Transduction Research, Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. abraham@burnham.org

RESUMEN / SUMMARY:  - The Target of Rapamycin (TOR) proteins function in signaling pathways that promote protein synthesis and cell growth. In yeast, TOR signaling is regulated by nutrient availability, whereas in metazoan cells TOR activities may be controlled by both nutrients and growth factors. The recent identification of novel TOR-interacting proteins has provided crucial insights into TOR regulation and function.  N. Ref:: 20

 

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[21]

TÍTULO / TITLE:  - Immune tolerance after long-term enzyme-replacement therapy among patients who have mucopolysaccharidosis I.

REVISTA / JOURNAL:  - Lancet 2003 May 10;361(9369):1608-13.

AUTORES / AUTHORS:  - Kakavanos R; Turner CT; Hopwood JJ; Kakkis ED; Brooks DA

INSTITUCIÓN / INSTITUTION:  - Lysosomal Diseases Research Unit, Department of Chemical Pathology, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia

RESUMEN / SUMMARY:  - BACKGROUND: Enzyme-replacement therapy has been assessed as a treatment for patients who have mucopolysaccharidosis I (alpha-L-iduronidase deficiency). We aimed to investigate the humoral immune response to recombinant human alpha-L-iduronidase among these patients. METHODS: We characterised the antibody titres and specific linear sequence epitope reactivity of serum antibodies to alpha-L-iduronidase for ten patients with mucopolysaccharidosis I, at the start of treatment and after 6, 12, 26, 52, and 104 weeks. We compared the values for patients’ samples with those for samples from normal human controls. FINDINGS: Before enzyme-replacement therapy, all patients had low serum antibody titres to recombinant human alpha-L-iduronidase that were within the control range. Five of the ten patients produced higher-than-normal titres of antibody to the replacement protein during the treatment course (serum antibody titres 130000-500000 and high-affinity epitope reactivity). However, by week 26, antibody reactivity was reduced, and by week 104 all patients had low antibody titres and only low-affinity epitope reactivity. Patients who had mucopolysaccharidosis I with antibody titres within the normal range at 6-12 weeks did not subsequently develop immune responses. INTERPRETATION: After 2 years of treatment, patients who initially had an immune reaction developed immune tolerance to alpha-L-iduronidase. This finding has positive implications for long-term enzyme-replacement therapy in patients who have mucopolysaccharidosis I.  N. Ref:: 32

 

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[22]

TÍTULO / TITLE:  - Interleukin-2 receptor monoclonal antibodies in renal transplantation: meta-analysis of randomised trials.

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

      ●● Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.

      ●● Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789

AUTORES / AUTHORS:  - Adu D; Cockwell P; Ives NJ; Shaw J; Wheatley K

INSTITUCIÓN / INSTITUTION:  - Department of Nephrology, Queen Elizabeth Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk

RESUMEN / SUMMARY:  - OBJECTIVE: To study the effect of interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft loss, deaths, and rate of infection and malignancy in patients with renal transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline, Embase, and Cochrane library for years 1996-2003 plus search of medical editors’ trial amnesty and contact with manufacturers of the antibodies. SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2 receptor antibodies with placebo or no additional treatment in patients with renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight randomised controlled trials involving 1871 patients met the selection criteria (although only 1858 patients were analysed). Interleukin-2 receptor antibodies significantly reduced the risk of acute rejection (odds ratio 0.51, 95% confidence interval 0.42 to 0.63). There were no significant differences in the rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23), overall incidence of infections (0.97, 0.77 to 1.24), incidence of cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to 0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar for all ciclosporin based immunosuppression regimens (test for heterogeneity P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin based immunosuppression reduces episodes of acute rejection at six months by 49%. There is no evidence of an increased risk of infective complications. Longer follow up studies are needed to confirm whether interleukin-2 receptor antibodies improve long term graft and patient survival.

 

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[23]

TÍTULO / TITLE:  - Stress management: MHC class I and class I-like molecules as reporters of cellular stress.

REVISTA / JOURNAL:  - Immunity 2003 Oct;19(4):469-77.

AUTORES / AUTHORS:  - Gleimer M; Parham P

INSTITUCIÓN / INSTITUTION:  - Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.

RESUMEN / SUMMARY:  - The evolutionarily ancient intracellular stress response protects cells from the effects of external and internal forces which perturb cellular metabolism. Members of the major histocompatibility complex (MHC) class I-like superfamily act as cell surface indicators of the intracellular stress response. Cellular immunity employs these indicators as a cue for elimination of damaged, infected, and malignant cells, promoting the health of the individual and the evolutionary success of the species.  N. Ref:: 77

 

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[24]

TÍTULO / TITLE:  - Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 27;77(2):166-76.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000109643.32659.C4

AUTORES / AUTHORS:  - Webster AC; Playford EG; Higgins G; Chapman JR; Craig JC

INSTITUCIÓN / INSTITUTION:  - Cochrane Renal Group, Centre for Kidney Research, Children’s Hospital at Westmead, Westmead, NSW, Australia.

RESUMEN / SUMMARY:  - BACKGROUND: Interleukin 2 receptor antagonists (IL-2Ra) are increasingly used to treat renal transplant recipients. This study aims to systematically identify and summarize the effects of using IL-2Ra as induction immunosuppression, as an addition to standard therapy, or as an alternative to other antibody therapy. METHODS: Databases, reference lists, and abstracts of conference proceedings were searched extensively to identify relevant randomized controlled trials in all languages. Data were synthesized using the random effects model. Results are expressed as relative risk (RR), with 95% confidence intervals (CI). RESULTS: A total of 117 reports from 38 trials involving 4,893 participants were included. When IL-2Ra were compared with placebo (17 trials; 2,786 patients), graft loss was not significantly different at 1 year (14 trials: RR 0.84; CI 0.64-1.10) or 3 years (4 trials: RR 1.08; CI 0.71-1.64). Acute rejection was significantly reduced at 6 months (12 trials: RR 0.66; CI 0.59-0.74) and at 1 year (10 trials: RR 0.67; CI 0.60-0.75). At 1 year, cytomegalovirus infection (7 trials: RR 0.82; CI 0.65-1.03) and malignancy (9 trials: RR 0.67; CI 0.33-1.36) were not significantly different. When IL-2Ra were compared with other antibody therapy, no significant differences in treatment effects were demonstrated, but IL-2Ra had significantly fewer side effects. CONCLUSIONS: Given a 40% risk of rejection, seven patients would need treatment with IL-2Ra in addition to standard therapy, to prevent one patient from undergoing rejection, with no definite improvement in graft or patient survival. There is no apparent difference between basiliximab and daclizumab.

 

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[25]

TÍTULO / TITLE:  - Genetic interaction of CTLA-4 with HLA-DR15 in multiple sclerosis patients.

REVISTA / JOURNAL:  - Ann Neurol 2003 Jul;54(1):119-22.

      ●● Enlace al texto completo (gratuito o de pago) 1002/ana.10617

AUTORES / AUTHORS:  - Alizadeh M; Babron MC; Birebent B; Matsuda F; Quelvennec E; Liblau R; Cournu-Rebeix I; Momigliano-Richiardi P; Sequeiros J; Yaouanq J; Genin E; Vasilescu A; Bougerie H; Trojano M; Martins Silva B; Maciel P; Clerget-Darpoux F; Clanet M; Edan G; Fontaine B; Semana G

INSTITUCIÓN / INSTITUTION:  - Laboratoire Universitaire d’Immunologie (UPRES EA 1257, IFR 97) and Etablissement Francais du Sang Bretagne, Faculte de Medecine, Rennes, France.

RESUMEN / SUMMARY:  - Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a genetic component. Until now, the more consistent association with the disease is found with the major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype. In this report, we demonstrate the interaction of Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in multiple sclerosis genetic susceptibility. Our data were obtained from two European independent family-based studies including 610 multiple sclerosis family trios. Ann Neurol 2003;54:119-122  N. Ref:: 20

 

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[26]

TÍTULO / TITLE:  - Novel therapeutic molecular targets for prostate cancer: the mTOR signaling pathway and epidermal growth factor receptor.

REVISTA / JOURNAL:  - J Urol 2004 Feb;171(2 Pt 2):S41-3; discussion S44.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7

AUTORES / AUTHORS:  - Tolcher AW

INSTITUCIÓN / INSTITUTION:  - Director Clinical Research, Institute for Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.

RESUMEN / SUMMARY:  - PURPOSE: The scientific rationale and existing evidence for the use of novel molecular targets in the chemoprevention of cancer are reviewed, with special attention to prostate cancer. MATERIALS AND METHODS: A search for relevant literature on basic science and clinical trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of molecularly targeted therapies for advanced malignancies creates an important opportunity to examine these agents for the chemoprevention of prostate cancer. Two critical targets in the proliferation and malignant transformation of normal cells, the PI3/Akt signal transduction pathway and the epidermal growth factor receptor, are currently the focus of several novel investigational therapies that are in late stage phase II and phase III studies. CONCLUSIONS: Research to date supports consideration of these novel molecular targets as future agents in the chemoprevention of prostate cancer.  N. Ref:: 28

 

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[27]

TÍTULO / TITLE:  - Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases.

REVISTA / JOURNAL:  - J Cell Biochem 2003 Feb 1;88(2):227-33.

      ●● Enlace al texto completo (gratuito o de pago) 1002/jcb.10340

AUTORES / AUTHORS:  - Adorini L; Penna G; Giarratana N; Uskokovic M

INSTITUCIÓN / INSTITUTION:  - BioXell, SpA, 20132 Milano, Italy. luciano.adorini@bioxell.com

RESUMEN / SUMMARY:  - Dendritic cells (DCs) not only induce but also modulate T cell activation. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induces DCs with a tolerogenic phenotype, characterized by decreased expression of CD40, CD80, and CD86 costimulatory molecules, low IL-12 and enhanced IL-10 secretion. We have found that a short treatment with 1,25(OH)(2)D(3) induces tolerance to fully mismatched mouse islet allografts that is stable to challenge with donor-type spleen cells and allows acceptance of donor-type vascularized heart grafts. This effect is enhanced by co-administration of mycophenolate mofetil (MMF), a selective inhibitor of T and B cell proliferation that has also effects similar to 1,25(OH)(2)D(3) on DCs. Graft acceptance is associated with an increased percentage of CD4(+)CD25(+) regulatory cells in the spleen and in the draining lymph node that can protect 100% of syngeneic recipients from islet allograft rejection. CD4(+)CD25(+) cells, able to inhibit the T cell response to a pancreatic autoantigen and to significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells, are also induced by treatment of adult nonobese diabetic (NOD) mice with 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-698). This treatment arrests progression of insulitis and Th1 cell infiltration, and inhibits diabetes development at non-hypercalcemic doses. The enhancement of CD4(+)CD25(+) regulatory T cells, able to mediate transplantation tolerance and to arrest type 1 diabetes development by a short oral treatment with VDR ligands, suggests possible clinical applications of this approach.  N. Ref:: 41

 

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[28]

TÍTULO / TITLE:  - Immune activation: death, danger and dendritic cells.

REVISTA / JOURNAL:  - Curr Biol 2004 Jan 6;14(1):R30-2.

AUTORES / AUTHORS:  - Pulendran B

INSTITUCIÓN / INSTITUTION:  - Emory Vaccine Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. bpulend@rmy.emory.edu

RESUMEN / SUMMARY:  - Dendritic cells are critical for host immunity, and sense microbes with pathogen recognition receptors. New evidence indicates that these cells also sense uric acid crystals in dead cells, suggesting that the immune system is conscious not only of pathogens, but also of death and danger.  N. Ref:: 20

 

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[29]

TÍTULO / TITLE:  - Pathways for self-tolerance and the treatment of autoimmune diseases.

REVISTA / JOURNAL:  - Lancet 2001 Jun 30;357(9274):2115-21.

AUTORES / AUTHORS:  - Goodnow CC

INSTITUCIÓN / INSTITUTION:  - Australian Cancer Research Foundation, Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra, Australia.

RESUMEN / SUMMARY:  - Antigen delivers both immunogenic and tolerogenic signals to lymphocytes. The outcome of antigen exposure represents a complex integration of the timing of antigen binding with signals from many other immunogenic and tolerogenic costimulatory pathways. A road map of these signalling pathways is only beginning to be charted, revealing the mechansim of action and limitations of current immunotherapeutic agents and the points of attack for new agents. Ciclosporin and tacrolimus interfere with tolerogenic signals from antigen in addition to blocking immunogenic signals, thus preventing active establishment of tolerance. Corticosteroids inhibit a key immunogenic pathway, NFkappaB, and more specific inhibitors of this pathway may allow tolerance to be actively established while immune responses are blocked. New experimental therapies aim to mimic tolerogenic antigen signals by chronically stimulating antigen receptors with antigen or antibodies to the receptor, or aim to block costimulatory pathways involving CD40 ligand, B7, or interleukin 2. Obtaining the desired response with these strategies is unpredictable because many of these signals have both tolerogenic and immunogenic roles. The cause of autoimune diseases has been determined for several rare monogenic disorders, revealing inherited deficiencies in tolerogenic costimulatory pathways such as FAS. Common autoimmune disorders may have a biochemically related pathogenesis.  N. Ref:: 52