#10#
Revisiones-Ciencias
Básicas-Molecular, Bioquímica, Metabolismo & Genética *** Reviews-Basic
Sciences-Molecular, Biochemistry, Metabolism & Genetics
INMUNOSUPRESIÓN
*** IMMUNOSUPPRESSION
(Conceptos
/ Keywords: Immunosuppression; Immunosuppressive ag.; Transpl. immunol.; GVH;
Antirejection therapy; Lymphocyte depletion; Transpl. conditioning; etc).
Enero /
January 2001 --- Marzo / March 2004
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Only articles written in Spanish and/or English are included.
[1]
TÍTULO / TITLE: - Hepcidin: a putative
iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia
of chronic disease.
REVISTA
/ JOURNAL: - Proc Natl Acad Sci U S A. Acceso gratuito
al texto completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.pnas.org/
●●
Cita: Proc Natl Acad Sci USA (PNAS): <> 2001 Jul 17;98(15):8160-2.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.161296298
AUTORES
/ AUTHORS: - Fleming RE; Sly WS
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Saint Louis
University School of Medicine, St. Louis, MO 63014, USA. N. Ref:: 30
----------------------------------------------------
[2]
TÍTULO / TITLE: - Beta lactam monotherapy
versus beta lactam-aminoglycoside combination therapy for sepsis in
immunocompetent patients: systematic review and meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2004 Mar 20;328(7441):668. Epub 2004
Mar 2.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.38028.520995.63
AUTORES
/ AUTHORS: - Paul M; Benuri-Silbiger I; Soares-Weiser
K; Leibovici L
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine E and Infectious
Diseases Unit, Rabin Medical Centre, Beilinson Campus, Petah-Tikva 49100,
Israel. mica@zahav.net.il
RESUMEN
/ SUMMARY: - OBJECTIVE: To compare beta lactam
monotherapy with beta lactam-aminoglycoside combination therapy for severe
infections. DATA SOURCES: Medline, Embase, Lilacs, Cochrane Library, and
conference proceedings, to 2003; references of included studies; contact with
all authors. No restrictions, such as language, year of publication, or
publication status. STUDY SELECTION: All randomised trials of beta lactam
monotherapy compared with beta lactam-aminoglycoside combination therapy for
patients without neutropenia who fulfilled criteria for sepsis. DATA SELECTION:
Two reviewers independently applied selection criteria, performed quality
assessment, and extracted the data. The primary outcome assessed was all cause
fatality by intention to treat. Relative risks were pooled with the random
effect model (relative risk < 1 favours monotherapy). RESULTS: 64 trials
with 7586 patients were included. There was no difference in all cause fatality
(relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared
the same beta lactam (1.02, 0.76 to 1.38), and 31 studies compared different
beta lactams (0.85, 0.69 to 1.05). Clinical failure was more common with
combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing
different beta lactams (0.76, 0.68 to 0.86). There was no advantage to combination
therapy among patients with Gram negative infections (1835 patients) or
Pseudomonas aeruginosa infections (426 patients). There was no difference in
the rate of development of resistance. Nephrotoxicity was significantly more
common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not
significant for these comparisons. CONCLUSIONS: In the treatment of sepsis the
addition of an aminoglycoside to beta lactams should be discouraged. Fatality
remains unchanged, while the risk for adverse events is increased. N. Ref:: 26
----------------------------------------------------
[3]
TÍTULO / TITLE: - Immunopathogenesis and
immunotherapy in AIDS virus infections.
REVISTA
/ JOURNAL: - Nat Med 2003 Jul;9(7):861-6.
●●
Enlace al texto completo (gratuito o de pago) 1038/nm0703-861
AUTORES
/ AUTHORS: - Letvin NL; Walker BD
INSTITUCIÓN
/ INSTITUTION: - Division of Viral Pathogenesis, Beth
Israel Deaconess Medical Center, Massachusetts General Hospital, Harvard
Medical School, Boston, Massachusetts 02114, USA.
RESUMEN
/ SUMMARY: - The heterogeneity of HIV and the different
human leukocyte antigen (HLA) backgrounds of infected individuals have posed
challenges to understanding the pathogenesis of HIV infection. But continuing
advances in our knowledge of the role of immune responses in controlling HIV
viremia should help to define goals for immune-based therapies and vaccine
strategies against AIDS. N.
Ref:: 106
----------------------------------------------------
[4]
TÍTULO / TITLE: - Integration of growth
factor and nutrient signaling: implications for cancer biology.
REVISTA
/ JOURNAL: - Mol Cell 2003 Aug;12(2):271-80.
AUTORES
/ AUTHORS: - Shamji AF; Nghiem P; Schreiber SL
INSTITUCIÓN
/ INSTITUTION: - Harvard Biophysics Program, Harvard
University, 12 Oxford Street, Cambridge, MA 02138, USA.
RESUMEN
/ SUMMARY: - Signaling networks that promote cell
growth are frequently dysregulated in cancer. One regulatory network, which
converges on effectors such as 4EBP1 and S6K1, leads to growth by promoting
protein synthesis. Here, we discuss how this network is regulated by both
extracellular signals, such as growth factors, and intracellular signals, such
as nutrients. We discuss how mutations amplifying either type of signal can
lead to tumor formation. In particular, we focus on the recent discovery that a
tumor suppressor complex whose function is lost in tuberous sclerosis patients
regulates the nutrient signal carried by the critical signaling protein TOR to
the effectors 4EBP1 and S6K1. Finally, we describe how the small molecule
rapamycin, which inhibits TOR and thereby the activation of these effectors,
could be useful to treat tumors that have become dependent upon this pathway
for growth. N. Ref:: 80
----------------------------------------------------
[5]
TÍTULO / TITLE: - Defying death—HIV
mutation to evade cytotoxic T lymphocytes.
REVISTA
/ JOURNAL: - N Engl J Med. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://content.nejm.org/
●●
Cita: New England J Medicine (NEJM): <> 2002 Oct 10;347(15):1203-4.
●●
Enlace al texto completo (gratuito o de pago) 1056/NEJMcibr022067
AUTORES
/ AUTHORS: - Lieberman J
INSTITUCIÓN
/ INSTITUTION: - Center for Blood Research, Boston, MA
02115, USA. N. Ref:: 5
----------------------------------------------------
[6]
TÍTULO / TITLE: - Genetic and functional
relationships between MHC and NK receptor genes.
REVISTA
/ JOURNAL: - Immunity 2001 Sep;15(3):363-74.
AUTORES
/ AUTHORS: - Trowsdale J
INSTITUCIÓN
/ INSTITUTION: - Immunology Division, Pathology Department,
University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
RESUMEN
/ SUMMARY: - HLA class I and NK receptors are encoded
within dense clusters of immune loci. The MHC, at 6p21.3, and the complex
containing the KIR loci, at 19q13.4, both feature variation in the number of
genes, as well as sequence polymorphism. In addition to T cell receptors,
several variable class I-related molecules interact with polymorphic NK
receptors. Some of the lectin-related NK receptor genes, at 12p13.1, also have
ligands belonging to the extended class I family. The expanding clusters of
class I-related sequences and their receptors, some of which evolved recently,
reveal further complexity in immune recognition of disease. N. Ref:: 85
----------------------------------------------------
[7]
TÍTULO / TITLE: - Impact of shared
epitope genotype and ethnicity on erosive disease: a meta-analysis of 3,240
rheumatoid arthritis patients.
REVISTA
/ JOURNAL: - Arthritis Rheum 2004 Feb;50(2):400-12.
●●
Enlace al texto completo (gratuito o de pago) 1002/art.20006
AUTORES
/ AUTHORS: - Gorman JD; Lum RF; Chen JJ; Suarez-Almazor
ME; Thomson G; Criswell LA
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
CA 94143-0500, USA. lac@itsa.ucsf.edu
RESUMEN
/ SUMMARY: - OBJECTIVE: The strongest known genetic
association in rheumatoid arthritis (RA) is with HLA-DRB1 alleles that share a
similar amino acid sequence, termed the shared epitope (SE). Although many
studies have examined the association of the SE with disease severity, the
results have been inconsistent, which may reflect the relatively small sample
sizes or ethnic differences. The aim of this study was to assess the
association of HLA-DRB1 SE alleles and genotype with the development of bony
erosions in RA by meta-analysis. METHODS: We identified English-language
articles published between January 1, 1987 and June 1, 1999 through Medline,
EMBase, and manual searches of 6 relevant journals. Included were studies in
which molecular typing of HLA-DRB1 alleles was performed and in which the
presence or absence of bony erosions was reported. Data were extracted from the
studies, and erosions were coded as present or absent. Authors were contacted
for missing information and data on individual patients. RESULTS: A total of 29
studies and 3,240 patients were available for analysis. The summary odds ratios
(ORs), when all patients were evaluated as a single group, demonstrated a
significant association of the presence of the SE (2 or 1 versus 0 SE alleles)
with erosions (OR 2.0; 95% confidence interval [95% CI] 1.8-2.2), although
significant heterogeneity was present (P = 0.002). Subgroup analyses demonstrated
the important influence of ethnic background. For example, no association of
the SE with erosions was demonstrated in Greeks (OR 0.8 [95% CI 0.2-1.5]). In
contrast, there was a striking dose-dependent relationship in southern European
Caucasians and Asians, with ORs as high as 6.2 and 5.4, respectively, in
patients with 2 SE alleles. Although our ability to assess the relationship
between SE genotype and erosions was limited, particular importance of the
DRB1*0401 SE allele was suggested in an analysis restricted to northern
European Caucasians. CONCLUSION: The SE is associated with the development of
erosive disease in many ethnic groups; however, striking exceptions exist.
These variations may be due to allele differences between populations, such as
the frequency of DRB1*0401 among different ethnic groups. Further study to
better understand the genetic and environmental differences between these
populations may provide insight into mechanisms that influence the clinical
expression of RA.
----------------------------------------------------
[8]
TÍTULO / TITLE: - Routes to transplant
tolerance versus rejection; the role of cytokines.
REVISTA
/ JOURNAL: - Immunity 2004 Feb;20(2):121-31.
AUTORES
/ AUTHORS: - Walsh PT; Strom TB; Turka LA
INSTITUCIÓN
/ INSTITUTION: - University of Pennsylvania, 700 Clinical
Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
RESUMEN
/ SUMMARY: - The alloimmune response can be divided
into specific junctures where critical decisions between tolerance and immunity
are made which define the outcome of the transplant. At these “decision nodes”
various cytokines direct alloresponsive T cells to develop either a
proinflammatory response aimed at graft destruction or an immunoregulatory
response facilitating graft acceptance. This review will focus on the role of
these cytokines in influencing the progression of an alloimmune response
leading ultimately to either allograft survival or rejection. N. Ref:: 97
----------------------------------------------------
[9]
TÍTULO / TITLE: - Microchimerism: an
investigative frontier in autoimmunity and transplantation.
REVISTA
/ JOURNAL: - JAMA. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl
●●
Cita: JAMA: <> 2004 Mar 3;291(9):1127-31.
●●
Enlace al texto completo (gratuito o de pago) 1001/jama.291.9.1127
AUTORES
/ AUTHORS: - Adams KM; Nelson JL
INSTITUCIÓN
/ INSTITUTION: - Program in Human Immunogenetics, Clinical
Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
98109-1024, USA.
RESUMEN
/ SUMMARY: - Recent studies indicate cells transfer
between fetus and mother during pregnancy and can persist in both decades
later. The presence within one individual of a small population of cells from
another genetically distinct individual is referred to as microchimerism.
Naturally acquired microchimerism has recently been investigated in autoimmune
diseases, including scleroderma, thyroiditis, primary biliary cirrhosis,
Sjogren syndrome, systemic lupus, dermatomyositis, and neonatal lupus.
Iatrogenic chimerism has been investigated in transplantation and following
blood transfusion. Considering findings of naturally acquired microchimerism
along with iatrogenic microchimerism suggests microchimerism can have
detrimental and/or beneficial effects in both settings. Recent identification
of tissue-specific microchimerism either from naturally acquired or iatrogenic
microchimerism (eg, cardiac myocytes) raises the possibility that
microchimerism can be a target of autoimmunity or alternatively contribute to
tissue repair. Advances in this new frontier of research with varied and numerous
implications for human health are summarized.
N. Ref:: 26
----------------------------------------------------
[10]
TÍTULO / TITLE: - The allogeneic response
and tumor immunity.
REVISTA
/ JOURNAL: - Nat Med 2001 Jun;7(6):649-52.
●●
Enlace al texto completo (gratuito o de pago) 1038/89008
AUTORES
/ AUTHORS: - Fabre JW
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Sciences, Institute
of Liver Studies Guy’s, King’s and St Thomas’ School of Medicine, London, UK. john.fabre@kcl.ac.uk
RESUMEN
/ SUMMARY: - The strong allogeneic response to donor
MHC molecules in transplantation and the weak response to tumor antigens
represent two important and divergent but potentially interactive immune
responses. A patient’s response to allogeneic MHC molecules might promote an
effective T-cell response to self MHC-restricted tumor peptides and the
possibilities for this are discussed here. These allogeneic responses might
successfully be harnessed to promote the immune eradication of metastatic
cancer. N. Ref:: 45
----------------------------------------------------
[11]
TÍTULO / TITLE: - Lack of association of
the HLA-DRB1 shared epitope with rheumatoid nodules: an individual patient data
meta-analysis of 3,272 Caucasian patients with rheumatoid arthritis.
REVISTA
/ JOURNAL: - Arthritis Rheum 2004 Mar;50(3):753-62.
●●
Enlace al texto completo (gratuito o de pago) 1002/art.20119
AUTORES
/ AUTHORS: - Gorman JD; David-Vaudey E; Pai M; Lum RF;
Criswell LA
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
and School of Public Health, University of California, Berkeley.
RESUMEN
/ SUMMARY: - OBJECTIVE: The objective of this
individual patient data (IPD) meta-analysis was to examine the relationship of
rheumatoid nodules to the HLA-DRB1 shared epitope (SE) and to individual SE
genotypes. METHODS: English-language studies that enrolled adult non-Hispanic
Caucasian patients with rheumatoid arthritis (RA) were identified by searches
of Medline and Embase, and by manual searches of medical journals. All authors
were contacted for IPD. Meta-analysis was performed to assess the association
of SE presence, dose, and genotype with rheumatoid nodules. Meta-analyses
adjusted for disease duration and cumulative meta-analyses were also performed
to assess the influence of RA duration and year of study publication on the
results. RESULTS: A total of 24 studies and 3,272 patients were available for
analysis. IPD were obtained for 22 of the studies. There was a nonsignificant
association between the presence of the SE (i.e., 1 or 2 alleles versus 0
alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence
interval [95% CI] 0.97-1.6). Analysis by SE genotype, however, demonstrated a
weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95%
CI 1.1-1.8). No other genotypes achieved statistical significance in the
adjusted or unadjusted analyses. CONCLUSION: The presence of the HLA-DRB1 SE
does not appear to significantly increase the risk of rheumatoid nodules among
Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative,
suggesting only a potential (and at most modest) role of the DRB1*0401 SE
allele. Results from this IPD meta-analysis implicate other genetic,
stochastic, and/or environmental factors in the susceptibility to rheumatoid
nodules.
----------------------------------------------------
[12]
TÍTULO / TITLE: - Genetic control of MHC
class II expression.
REVISTA
/ JOURNAL: - Cell 2002 Apr;109 Suppl:S21-33.
AUTORES
/ AUTHORS: - Ting JP; Trowsdale J
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology and Immunology
and The Lineberger Comprehensive Cancer Center, University of North Carolina,
Chapel Hill, NC 27599, USA. panyun@med.unc.edu
RESUMEN
/ SUMMARY: - The presentation of peptides to T cells by
MHC class II molecules is of critical importance in specific recognition by the
immune system. Expression of class II molecules is exquisitely controlled at
the transcriptional level. A large set of proteins interact with the promoters
of class II genes. The most important of these is CIITA, a master controller
that orchestrates expression but does not bind directly to the promoter. The
transcriptosome complex formed at class II promoters is a model for induction
of gene expression. N.
Ref:: 108
----------------------------------------------------
[13]
TÍTULO / TITLE: - Interferon-gamma
reduces interleukin-4- and interleukin-13-augmented transforming growth
factor-beta2 production in human bronchial epithelial cells by targeting Smads.
REVISTA
/ JOURNAL: - Chest. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.chestjournal.org/
●●
Cita: Chest: <> 2003 Mar;123(3 Suppl):372S-3S.
AUTORES
/ AUTHORS: - Wen FQ; Liu XD; Terasaki Y; Fang QH;
Kobayashi T; Abe S; Rennard SI
INSTITUCIÓN
/ INSTITUTION: - Pulmonary and Critical Care Medicine
Section, University of Nebraska Medical Center, Omaha, NE 68198-5125, USA. N. Ref:: 0
----------------------------------------------------
[14]
TÍTULO / TITLE: - When the lymphocyte
loses its clothes.
REVISTA
/ JOURNAL: - Immunity 2003 Apr;18(4):453-7.
AUTORES
/ AUTHORS: - Nekrep N; Fontes JD; Geyer M; Peterlin BM
INSTITUCIÓN
/ INSTITUTION: - Institute of Biochemistry, Medical Faculty
of the University of Ljubljana, Slovenia.
RESUMEN
/ SUMMARY: - The type II bare lymphocyte syndrome (BLS)
or major histocompatibility complex class II (MHCII) deficiency is a severe
combined immunodeficiency (SCID) that is characterized by the absence of
constitutive and inducible expression of MHCII determinants on immune cells.
Four complementation groups of BLS have been defined, and they result from
mutations in DNA-bound activators and the coactivator for MHCII transcription.
Recently, all complementation groups of BLS patients have been accounted for.
Studies of the syndrome and specific mutations reveal important lessons for the
genetics of the immune response. N.
Ref:: 35
----------------------------------------------------
[15]
TÍTULO / TITLE: - Ex vivo selection of
recipient-type alloantigen-specific CD4(+)CD25(+) immunoregulatory T cells for
the control of graft-versus-host disease after allogeneic hematopoietic
stem-cell transplantation.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1
Suppl):S32-4.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106470.07410.CA
AUTORES
/ AUTHORS: - Trenado A; Fisson S; Braunberger E;
Klatzmann D; Salomon BL; Cohen JL
INSTITUCIÓN
/ INSTITUTION: - Biologie et Therapeutique des Pathologies
Immunitaires, Hopital Pitie-Salpetriere, Paris, France.
RESUMEN
/ SUMMARY: - Allogeneic hematopoietic stem-cell
transplantation (HSCT) is the treatment of choice for many malignant and
nonmalignant hematologic disorders. Donor T cells present in the hematopoietic
stem-cell transplant improve engraftment and immune reconstitution and
contribute to the graft-versus-leukemia effect, but are also responsible for
the life-threatening graft-versus-host disease (GVHD). CD4(+)CD25(+)
immunoregulatory T cells, which play a pivotal role in preventing
organ-specific diseases, can also modulate GVHD if administered in equal
numbers of T cells at the time of grafting. In this article, the authors
describe a procedure of ex vivo selection and expansion of regulatory T cells
specific for recipient-type alloantigens. These expanded regulatory T cells
controlled GVHD. Their therapeutic use in HSCT should allow specific
suppression of the activation of donor alloreactive T cells involved in GVHD
while preserving the beneficial effects of other T cells. N. Ref:: 27
----------------------------------------------------
[16]
TÍTULO / TITLE: - Hemochromatosis gene
modifies course of hepatitis C viral infection.
REVISTA
/ JOURNAL: - Gastroenterology 2003 May;124(5):1509-23.
AUTORES
/ AUTHORS: - Pietrangelo A
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Centre
for Hemochromatosis and Metabolic Liver Diseases, University of Modena and
Reggio Emilia, Modeno, Italy. antonello@unimore.it N. Ref:: 161
----------------------------------------------------
[17]
TÍTULO / TITLE: - T cell receptor-MHC
interactions up close.
REVISTA
/ JOURNAL: - Cell 2001 Jan 12;104(1):1-4.
AUTORES
/ AUTHORS: - Hennecke J; Wiley DC
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular and Cellular
Biology, Harvard University and Howard Hughes Medical Institute, Cambridge, MA
02138, USA. hennecke@crystal.harvard.edu N. Ref:: 18
----------------------------------------------------
[18]
- Castellano -
TÍTULO / TITLE:La ruta de senalizacion CA++/calcineurina/NFAT
en activacion endotelial y angiogenesis: efectos de la ciclosporina A. CA++/
calcineurin/NFAT signaling in endothelial activation and angiogenesis: effects
od cyclosporin A .
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 3:44-8.
AUTORES
/ AUTHORS: - Quesada AJ; Redondo JM
INSTITUCIÓN
/ INSTITUTION: - Centro de Biologia Molecular Severo Ochoa,
Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid
y Centro Nacional de Investigaciones Cardiovasculares (CNIC), Sinesio Delgado,
4 28049 Cantoblanco, Madrid. jmredondo@cbm.uam.es N. Ref:: 31
----------------------------------------------------
[19]
TÍTULO / TITLE: - Disease modifying
therapies in multiple sclerosis: report of the Therapeutics and Technology
Assessment Subcommittee of the American Academy of Neurology and the MS Council
for Clinical Practice Guidelines.
REVISTA
/ JOURNAL: - Neurology 2002 Jan 22;58(2):169-78.
AUTORES
/ AUTHORS: - Goodin DS; Frohman EM; Garmany GP Jr;
Halper J; Likosky WH; Lublin FD; Silberberg DH; Stuart WH; van den Noort S
----------------------------------------------------
[20]
TÍTULO / TITLE: - Identification of TOR
signaling complexes: more TORC for the cell growth engine.
REVISTA
/ JOURNAL: - Cell 2002 Oct 4;111(1):9-12.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road,
La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - The Target of Rapamycin (TOR) proteins
function in signaling pathways that promote protein synthesis and cell growth.
In yeast, TOR signaling is regulated by nutrient availability, whereas in
metazoan cells TOR activities may be controlled by both nutrients and growth
factors. The recent identification of novel TOR-interacting proteins has
provided crucial insights into TOR regulation and function. N. Ref:: 20
----------------------------------------------------
[21]
TÍTULO / TITLE: - Immune tolerance after
long-term enzyme-replacement therapy among patients who have
mucopolysaccharidosis I.
REVISTA
/ JOURNAL: - Lancet 2003 May 10;361(9369):1608-13.
AUTORES
/ AUTHORS: - Kakavanos R; Turner CT; Hopwood JJ; Kakkis
ED; Brooks DA
INSTITUCIÓN
/ INSTITUTION: - Lysosomal Diseases Research Unit,
Department of Chemical Pathology, Women’s and Children’s Hospital, North
Adelaide, South Australia, Australia
RESUMEN
/ SUMMARY: - BACKGROUND: Enzyme-replacement therapy has
been assessed as a treatment for patients who have mucopolysaccharidosis I
(alpha-L-iduronidase deficiency). We aimed to investigate the humoral immune
response to recombinant human alpha-L-iduronidase among these patients.
METHODS: We characterised the antibody titres and specific linear sequence
epitope reactivity of serum antibodies to alpha-L-iduronidase for ten patients
with mucopolysaccharidosis I, at the start of treatment and after 6, 12, 26,
52, and 104 weeks. We compared the values for patients’ samples with those for
samples from normal human controls. FINDINGS: Before enzyme-replacement
therapy, all patients had low serum antibody titres to recombinant human
alpha-L-iduronidase that were within the control range. Five of the ten
patients produced higher-than-normal titres of antibody to the replacement
protein during the treatment course (serum antibody titres 130000-500000 and
high-affinity epitope reactivity). However, by week 26, antibody reactivity was
reduced, and by week 104 all patients had low antibody titres and only
low-affinity epitope reactivity. Patients who had mucopolysaccharidosis I with
antibody titres within the normal range at 6-12 weeks did not subsequently
develop immune responses. INTERPRETATION: After 2 years of treatment, patients
who initially had an immune reaction developed immune tolerance to
alpha-L-iduronidase. This finding has positive implications for long-term
enzyme-replacement therapy in patients who have mucopolysaccharidosis I. N. Ref:: 32
----------------------------------------------------
[22]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[23]
TÍTULO / TITLE: - Stress management: MHC
class I and class I-like molecules as reporters of cellular stress.
REVISTA
/ JOURNAL: - Immunity 2003 Oct;19(4):469-77.
AUTORES
/ AUTHORS: - Gleimer M; Parham P
INSTITUCIÓN
/ INSTITUTION: - Program in Immunology, Stanford University
School of Medicine, Stanford, CA 94305, USA.
RESUMEN
/ SUMMARY: - The evolutionarily ancient intracellular
stress response protects cells from the effects of external and internal forces
which perturb cellular metabolism. Members of the major histocompatibility
complex (MHC) class I-like superfamily act as cell surface indicators of the
intracellular stress response. Cellular immunity employs these indicators as a
cue for elimination of damaged, infected, and malignant cells, promoting the
health of the individual and the evolutionary success of the species. N. Ref:: 77
----------------------------------------------------
[24]
TÍTULO / TITLE: - Interleukin 2 receptor
antagonists for renal transplant recipients: a meta-analysis of randomized trials.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):166-76.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000109643.32659.C4
AUTORES
/ AUTHORS: - Webster AC; Playford EG; Higgins G;
Chapman JR; Craig JC
INSTITUCIÓN
/ INSTITUTION: - Cochrane Renal Group, Centre for Kidney
Research, Children’s Hospital at Westmead, Westmead, NSW, Australia.
RESUMEN
/ SUMMARY: - BACKGROUND: Interleukin 2 receptor
antagonists (IL-2Ra) are increasingly used to treat renal transplant
recipients. This study aims to systematically identify and summarize the
effects of using IL-2Ra as induction immunosuppression, as an addition to
standard therapy, or as an alternative to other antibody therapy. METHODS:
Databases, reference lists, and abstracts of conference proceedings were
searched extensively to identify relevant randomized controlled trials in all
languages. Data were synthesized using the random effects model. Results are
expressed as relative risk (RR), with 95% confidence intervals (CI). RESULTS: A
total of 117 reports from 38 trials involving 4,893 participants were included.
When IL-2Ra were compared with placebo (17 trials; 2,786 patients), graft loss
was not significantly different at 1 year (14 trials: RR 0.84; CI 0.64-1.10) or
3 years (4 trials: RR 1.08; CI 0.71-1.64). Acute rejection was significantly
reduced at 6 months (12 trials: RR 0.66; CI 0.59-0.74) and at 1 year (10
trials: RR 0.67; CI 0.60-0.75). At 1 year, cytomegalovirus infection (7 trials:
RR 0.82; CI 0.65-1.03) and malignancy (9 trials: RR 0.67; CI 0.33-1.36) were
not significantly different. When IL-2Ra were compared with other antibody
therapy, no significant differences in treatment effects were demonstrated, but
IL-2Ra had significantly fewer side effects. CONCLUSIONS: Given a 40% risk of
rejection, seven patients would need treatment with IL-2Ra in addition to
standard therapy, to prevent one patient from undergoing rejection, with no
definite improvement in graft or patient survival. There is no apparent
difference between basiliximab and daclizumab.
----------------------------------------------------
[25]
TÍTULO / TITLE: - Genetic interaction of
CTLA-4 with HLA-DR15 in multiple sclerosis patients.
REVISTA
/ JOURNAL: - Ann Neurol 2003 Jul;54(1):119-22.
●●
Enlace al texto completo (gratuito o de pago) 1002/ana.10617
AUTORES
/ AUTHORS: - Alizadeh M; Babron MC; Birebent B; Matsuda
F; Quelvennec E; Liblau R; Cournu-Rebeix I; Momigliano-Richiardi P; Sequeiros
J; Yaouanq J; Genin E; Vasilescu A; Bougerie H; Trojano M; Martins Silva B;
Maciel P; Clerget-Darpoux F; Clanet M; Edan G; Fontaine B; Semana G
INSTITUCIÓN
/ INSTITUTION: - Laboratoire Universitaire d’Immunologie
(UPRES EA 1257, IFR 97) and Etablissement Francais du Sang Bretagne, Faculte de
Medecine, Rennes, France.
RESUMEN
/ SUMMARY: - Multiple sclerosis is a chronic
inflammatory disease of the central nervous system with a genetic component.
Until now, the more consistent association with the disease is found with the
major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype.
In this report, we demonstrate the interaction of Cytotoxic T
Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in
multiple sclerosis genetic susceptibility. Our data were obtained from two
European independent family-based studies including 610 multiple sclerosis
family trios. Ann Neurol 2003;54:119-122
N. Ref:: 20
----------------------------------------------------
[26]
TÍTULO / TITLE: - Novel therapeutic
molecular targets for prostate cancer: the mTOR signaling pathway and epidermal
growth factor receptor.
REVISTA
/ JOURNAL: - J Urol 2004 Feb;171(2 Pt 2):S41-3;
discussion S44.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7
AUTORES
/ AUTHORS: - Tolcher AW
INSTITUCIÓN
/ INSTITUTION: - Director Clinical Research, Institute for
Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.
RESUMEN
/ SUMMARY: - PURPOSE: The scientific rationale and
existing evidence for the use of novel molecular targets in the chemoprevention
of cancer are reviewed, with special attention to prostate cancer. MATERIALS
AND METHODS: A search for relevant literature on basic science and clinical
trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of
molecularly targeted therapies for advanced malignancies creates an important
opportunity to examine these agents for the chemoprevention of prostate cancer.
Two critical targets in the proliferation and malignant transformation of
normal cells, the PI3/Akt signal transduction pathway and the epidermal growth
factor receptor, are currently the focus of several novel investigational
therapies that are in late stage phase II and phase III studies. CONCLUSIONS:
Research to date supports consideration of these novel molecular targets as
future agents in the chemoprevention of prostate cancer. N. Ref:: 28
----------------------------------------------------
[27]
TÍTULO / TITLE: - Tolerogenic dendritic
cells induced by vitamin D receptor ligands enhance regulatory T cells
inhibiting allograft rejection and autoimmune diseases.
REVISTA
/ JOURNAL: - J Cell Biochem 2003 Feb 1;88(2):227-33.
●●
Enlace al texto completo (gratuito o de pago) 1002/jcb.10340
AUTORES
/ AUTHORS: - Adorini L; Penna G; Giarratana N;
Uskokovic M
INSTITUCIÓN
/ INSTITUTION: - BioXell, SpA, 20132 Milano, Italy. luciano.adorini@bioxell.com
RESUMEN
/ SUMMARY: - Dendritic cells (DCs) not only induce but
also modulate T cell activation. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]
induces DCs with a tolerogenic phenotype, characterized by decreased expression
of CD40, CD80, and CD86 costimulatory molecules, low IL-12 and enhanced IL-10
secretion. We have found that a short treatment with 1,25(OH)(2)D(3) induces
tolerance to fully mismatched mouse islet allografts that is stable to
challenge with donor-type spleen cells and allows acceptance of donor-type
vascularized heart grafts. This effect is enhanced by co-administration of
mycophenolate mofetil (MMF), a selective inhibitor of T and B cell
proliferation that has also effects similar to 1,25(OH)(2)D(3) on DCs. Graft
acceptance is associated with an increased percentage of CD4(+)CD25(+)
regulatory cells in the spleen and in the draining lymph node that can protect
100% of syngeneic recipients from islet allograft rejection. CD4(+)CD25(+)
cells, able to inhibit the T cell response to a pancreatic autoantigen and to
significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells, are
also induced by treatment of adult nonobese diabetic (NOD) mice with 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor
vitamin D(3) (BXL-698). This treatment arrests progression of insulitis and Th1
cell infiltration, and inhibits diabetes development at non-hypercalcemic
doses. The enhancement of CD4(+)CD25(+) regulatory T cells, able to mediate
transplantation tolerance and to arrest type 1 diabetes development by a short
oral treatment with VDR ligands, suggests possible clinical applications of
this approach. N.
Ref:: 41
----------------------------------------------------
[28]
TÍTULO / TITLE: - Immune activation:
death, danger and dendritic cells.
REVISTA
/ JOURNAL: - Curr Biol 2004 Jan 6;14(1):R30-2.
AUTORES
/ AUTHORS: - Pulendran B
INSTITUCIÓN
/ INSTITUTION: - Emory Vaccine Center, 954 Gatewood Road,
Atlanta, Georgia 30329, USA. bpulend@rmy.emory.edu
RESUMEN
/ SUMMARY: - Dendritic cells are critical for host
immunity, and sense microbes with pathogen recognition receptors. New evidence
indicates that these cells also sense uric acid crystals in dead cells,
suggesting that the immune system is conscious not only of pathogens, but also
of death and danger. N.
Ref:: 20
----------------------------------------------------
[29]
TÍTULO / TITLE: - Pathways for
self-tolerance and the treatment of autoimmune diseases.
REVISTA
/ JOURNAL: - Lancet 2001 Jun 30;357(9274):2115-21.
AUTORES
/ AUTHORS: - Goodnow CC
INSTITUCIÓN
/ INSTITUTION: - Australian Cancer Research Foundation,
Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical
Research, Australian National University, Canberra, Australia.
RESUMEN
/ SUMMARY: - Antigen delivers both immunogenic and
tolerogenic signals to lymphocytes. The outcome of antigen exposure represents
a complex integration of the timing of antigen binding with signals from many
other immunogenic and tolerogenic costimulatory pathways. A road map of these
signalling pathways is only beginning to be charted, revealing the mechansim of
action and limitations of current immunotherapeutic agents and the points of
attack for new agents. Ciclosporin and tacrolimus interfere with tolerogenic
signals from antigen in addition to blocking immunogenic signals, thus
preventing active establishment of tolerance. Corticosteroids inhibit a key
immunogenic pathway, NFkappaB, and more specific inhibitors of this pathway may
allow tolerance to be actively established while immune responses are blocked.
New experimental therapies aim to mimic tolerogenic antigen signals by
chronically stimulating antigen receptors with antigen or antibodies to the
receptor, or aim to block costimulatory pathways involving CD40 ligand, B7, or
interleukin 2. Obtaining the desired response with these strategies is
unpredictable because many of these signals have both tolerogenic and
immunogenic roles. The cause of autoimune diseases has been determined for
several rare monogenic disorders, revealing inherited deficiencies in
tolerogenic costimulatory pathways such as FAS. Common autoimmune disorders may
have a biochemically related pathogenesis.
N. Ref:: 52