Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With a prevalence of approximatively 50%, diarrhoea is a frequent event in immune deficiency of any cause. Because this condition is permanent in AIDS, the main characteristic of diarrhoea is chronicity. Non infectious causes are more common in conditions other than AIDS with, for exemple, intestinal injuries related to graft versus host disease or to chemotherapy toxicity. Among infectious causes, enteric parasitic diseases such as cryptosporidiosis or microsporidiosis are more commonly observed in the immunodeficiency related to HIV while viral infections due to cytomegalovirus or adenovirus seem possible in any case of severe troubles of the immunity. Gram-negative infections and Clostridium difficile colitis have to be diagnosed because efficient treatment is available. In these patients usually in bad general condition, because diarrhoea is often of unknown aetiology or non curable, the diagnostic and therapeutic strategy has to be pragmatic in order to control the symptoms without an excess of invasive procedures.
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PMID:[Diarrhea in immune deficiency status]. 874 35

Mice expressing the severe combined immunodeficiency trait (SCID) lack functional T and B lymphocytes and have been widely used for the study of B- cell development and for cancer and HIV research. The purpose of this study was to evaluate the SCID mouse as a potential model for T-cell maturation and transplantation studies. C3H/HEN SCID mice screened by fluorescence-activated cell sorting (FACS) and radial immunodiffusion assay (RID) were verified homozygous recessive if CD3-, CD22-, and serum (IgG) <5 mg/liter. C3H/HEN SCID mice pretreated with 250 R total-body gamma irradiation were reconstituted with 2.5 to 4 x 10(7) donor bone marrow cells derived from [syngeneic (syn): male wild-type C3H/HEN, allogeneic (allo): male BALB/c or C57BL/6) mice by intravenous injection. Four weeks post-transplant, engraftment was determined by FACS; repopulation of blood, thymus, and spleen; RID; and histologic evaluation. Immune function against donor, recipient, and third-party antigen was assayed in vitro by mixed lymphocyte response (MLR) and in vivo by full-thickness skin grafting. Greater than 90% of both syngeneic and allogeneic reconstitutions expressed CD3+, CD4+, CD8+, and CD22+ cells of donor origin in peripheral blood and spleen. FACS analyses of lymphocyte subpopulations in blood and spleen were not significantly different between reconstituted SCID mice and wild-type C3H/HEN or BALB/c controls, with engraftment stable for >4 months. No evidence of graft-versus-host disease was observed in stable, long-term (>4 months postreconstitution) chimeras. White blood cell, total thymocyte, and total splenocyte counts were significantly elevated (P < 0.05: ANOVA, Student's t) following reconstitution of homozygous SCID mice to levels found in wild-type controls. Serum (IgG) for reconstituted allo- and syn-SCID mice was consistently > 150 mg/liter (n = 22), with histologic lymphocyte engraftment of spleen, duodenum, and thymus. Histologic examination of lymphocyte engraftment in spleen, duodenum, and thymus was indistinguishable from normal controls in SCID mice after reconstitution. Prior to reconstitution, scant lymphoid cells were observed at these sites. Allo-SCID splenocyte response against third-party antigen was significantly elevated (P < 0.01: ANOVA, Student's t) when compared with donor and recipient antigen response with a proliferation index (PI) comparable to wild-type controls. Unreconstituted SCID mice were unresponsive. In vivo, allo-SCID mice demonstrated rejection of only third-party skin grafts between postoperative days 9 and 14 (controls: postoperative days 7 and 11). The SCID mouse model demonstrates in vitro and in vivo B- and T-cell immune function comparable to that of wild-type mice and provides a useful model for T-cell maturation and transplantation studies.
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PMID:SCID mouse as a model for transplantation studies. 889 4

Bone marrow transplantation (BMT) results in hematopoietic chimeras that demonstrate donor specific tolerance to tissue and cellular grafts. The clinical application of chimerism to induce tolerance is limited by the morbidity associated with human BMT: failure of engraftment, graft-versus-host disease (GVHD), and toxic host conditioning. BMT in an immunologically mature host has until recently been believed to require complete ablation of the host's immune system to allow donor engraftment. Lethal conditioning is associated with significant morbidity and mortality. Stable multilineage mixed allogeneic chimerism has more recently been achieved in mice using partial myeloablation prior to BMT. Chimeras prepared in this fashion exhibit donor specific tolerance in vitro and in vivo similar to lethally-conditioned recipients. A second factor that has limited the widespread application of BMT to nonmalignant disease, including attempts to induce tolerance, is GVHD. Although T-cell depletion of donor marrow reduces the incidence of GVHD, engraftment is often jeopardized. Although highly purified stem cells (SC) engraft at relatively low doses in syngeneic recipients, they do not durably engraft in MHC-disparate recipients. It has recently become clear that a second cell (facilitating cell) that enhances bone marrow engraftment and minimizes the occurrence of GVHD is required for SC to engraft in MHC-disparate recipients. Methods to optimize engraftment yet minimize GVHD may provide an approach to apply BMT clinically. With decreased morbidity through incomplete recipient conditioning and the ability to engineer a bone marrow graft to contain only the desired cells to optimize engraftment, BMT may provide a reasonable strategy to treat nonmalignant diseases including enzyme deficiencies, hemoglobinopathies, autoimmune diseases, and species-specific viral infections such as HIV. BMT-induced donor specific tolerance may benefit recipients of solid organ transplants by eliminating the need for nonspecific immunosuppression and by preventing chronic rejection. This review will focus on approaches to enable BMT yet minimize recipient morbidity and mortality.
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PMID:Chimerism and tolerance: from freemartin cattle and neonatal mice to humans. 907 64

The total number of blood donors in 1994 was 6.6 millions, and 200 ml whole blood donation occupied 41.8% of all donations, whereas 400 ml and apheresis donations occupied 35.6%, 22.5% of all donations respectively. From the donated blood, about 8.35 million bags of blood components were prepared and were used for blood transfusion. Besides used as blood components, 720,000 L source plasma was used to produce plasma derivatives, and therefore Japan has achieved self-sufficiency in Factor VIII by donated blood. Blood transfusion has become quite safer but there are still risks of acquiring transfusion-associated GVHD(TA-GVHD) or infecting with HIV from blood in window period. To avoid adverse reactions of blood transfusion, the strategies for reducing homologous blood transfusion has been promoting. The use of red cell substitutes will be an option of using non-human derived substitutes toward "zero" adverse reaction of transfusion, and when red cell substitutes are accepted in Japan, they will be applied as the substitution to allogeneic blood transfusion below 1200 ml hemorrhage. They will also be applied as an alternation to and/or combination with allogeneic and autologous blood transfusion and the use of erythropoietin.
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PMID:The impact of red cell substitutes on the blood service in Japan. 908 26

Two years have passed since the product liability(PL) law took effect in our country on July 1, 1995. At the start, we were uneasy about such things as an increase in lawsuits, the rise of medical care costs and the concealment of medical information. However, no-one has brought an action concerning blood products so far under the PL law. In terms of quality control of blood products, regular inspection of various instruments, reagents and manuals is the fundamental rule. Moreover, in order to ensure blood products of good quality, it is very important to select blood donors on the basis of physical examination and questionnaires on their medical condition, not to mention a range of screening tests to detect viral and bacterial infection. Since the first HIV infection through blood derived from an HIV-seronegative donor was reported in our country, it is especially desirable to improve measures for detecting HIV in window period blood for HIV antibody. There is also a problem concerning the irradiation of blood products to prevent PT-GVHD. We expect the PL law to provide a higher degree of safety of blood transfusion; however, it is also necessary to make proper use of blood products and to take the right measures in the event of adverse transfusion reaction, so as to raise the safety of blood transfusion.
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PMID:[Important points concerning quality control of blood products under the product liability law]. 930 Dec 79

Tumor necrosis factor-alpha (TNF-alpha) is a highly pleiotropic cytokine produced mainly by activated macrophages. This cytokine has been found to mediate the growth of certain tumors, the replication of HIV-1, septic shock, cachexia, graft-versus-host disease, and autoimmune diseases. The binding of TNF-alpha to the p55 tumor necrosis factor receptor type I (TNFRI) is considered one of the initial steps responsible for the multiple physiologic effects mediated by TNF-alpha. The role of TNF-alpha as an inflammatory mediator through TNFRI makes both of these genes attractive targets for intervention in both acute and chronic inflammatory diseases. We have designed antisense oligodeoxynucleotides (ODNs) containing chemically modified purine and pyrimidine bases that specifically inhibit TNFRI expression and functions. These ODNs were designed to hybridize to the 3'-polyadenylation signal region of the TNFRI gene. In cell-based assays, gene-specific antisense inhibition occurred in a dose-dependent fashion at submicromolar concentrations in the presence of cellular uptake enhancing agents. Within ODN sets with a common pattern of stabilizing backbone substitution, the inhibition of the gene expression is found to be correlated with the affinity of the ODNs for their cognate mRNA target sites, providing direct evidence for an antisense mechanism of action. In addition, events triggered by the binding of TNF-alpha to TNFRI, such as the production of IL-6 and IL-8, were significantly reduced by treatment of cells with the anti-TNFRI ODN. Therefore, antisense ODNs can be used to control biologic processes mediated by TNF-alpha and may be useful as therapeutic agents to treat conditions resulting from overproduction of TNF-alpha.
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PMID:Sequence-specific inhibition of the tumor necrosis factor-alpha receptor I gene by oligodeoxynucleotides containing N7 modified 2'-deoxyguanosine. 936 4

Oral ganciclovir is effective in preventing cytomegalovirus (CMV) disease in HIV-infected patients despite a bioavailability of only 6-9%. To determine safety, pharmacokinetics, and the influence of acute gastrointestinal graft-vs.-host disease (GI-GVHD) on the bioavailability and antiviral effect of oral ganciclovir after marrow transplantation, CMV seropositive patients received oral ganciclovir (1000 mg 3 times per day) from day 35 (+/- 7 days) until day 100 after transplantation. Single-dose (intravenous and oral) and steady-state oral pharmacokinetic profiles and weekly trough levels were performed. Twenty-one patients received oral ganciclovir (seven with GI-GVHD, 14 without); 17 had steady-state pharmacokinetic profiles and seven had single-dose profiles. The absolute bioavailability was similar in patients with or without acute GI-GVHD (7.2 vs. 6.9%). At steady state, the extent and rate of absorption of oral ganciclovir were comparable in these same patient subgroups (area under the curve [AUC] = 13.5 and 10.2 mg x hours/L, respectively; time to peak serum ganciclovir concentrations = 5.5 and 3.8 hours, respectively). Breakthrough CMV antigenemia, viremia, or plasma polymerase chain reaction positivity occurred in eight of 21 (38%) patients (four of seven with GVHD and four of 14 without). Drug discontinuation because of GI adverse effects was required in six of 21 (29%) patients. Neutropenia occurred in two of 15 (13%) patients who had received oral ganciclovir for more than 10 days. In conclusion, the bioavailability of oral ganciclovir seems similar to that reported in other settings. The presence of acute GVHD of the GI tract did not appear to adversely affect absorption of oral ganciclovir. The use of oral ganciclovir was limited by the presence of GI intolerance in the early posttransplant period. The efficacy of oral ganciclovir in preventing CMV infection in marrow transplant recipients is being assessed in a separate randomized controlled trial.
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PMID:A study of the pharmacokinetics, antiviral activity, and tolerability of oral ganciclovir for CMV prophylaxis in marrow transplantation. 970 87

4-1BB is an inducible T cell surface receptor which belongs to the tumor necrosis factor receptor superfamily, a group of cysteine-rich cell-surface molecules. Both human and mouse 4-1BB recently received HLDA nomenclature. Naive T cells lack 4-1BB, which is not only induced upon T cell activation, but also remains on activated T cells. The natural ligand for 4-1BB, 4-1BBL is also induced and is found on activated antigen-presenting cells. Cross-linking of the 4-1BB molecule by agonistic antibody transmits a distinct and potent co-stimulatory signal leading to the activation and differentiation of CD4(+) and CD8(+) cells. 4-1BB transmits signals through the TRAF2-NIK pathway and activates NF-kappaB. Signals relayed through 4-1BB inhibit activation-induced cell death and rescue the immune system during the post-CD28 phase. Antibodies to the 4-1BB molecule can increase GVHD, accelerate the rejection of cardiac allograft and skin transplants, and eradicate established tumors. Interference with the 4-1BB-4-1BBL pathway may be of therapeutic use in the treatment of HIV infection. 4-1BB-deficient mice show dysregulated immune responses and mount elevated Ig responses to T-dependent antigens.
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PMID:Role of 4-1BB in immune responses. 982 81

Human immunodeficiency virus (HIV-1) associated immune deficiency has the characteristics of chronic graft versus host disease (GVHD) caused by human leukocyte antigen (HLA) class 2 incompatibility. The envelope glycoprotein fragment TKAKRRVVEREKR mimics HLA class 1 C molecules serologically, and also mimics an immune regulatory T cell epitope, in the region of amino acids 67 to 71, within the HLA DR beta chain. This beta chain alloepitopic region (between amino acids 67 to 80) furnishes peptides predicted to bind optimally to HLA class 1 B alleles. The hypothesis predicts that viral parameters, such as viral load, and clinical parameters, such as rate of progress to acquired immune deficiency syndrome (AIDS) and severity of the associated immune deficient state, are linked to the HLA B and HLA DR beta chain haplotype in infected patients. Immune suppression is caused by HLA class 1 B restricted CD8+ T cells which normally regulate HLA class 2 DR restricted antigen specific responses. The hypothesis further predicts the severity of immune deficiency to be linked to those HLA DR beta chain allotypes which express the amino-acid glutamine (Q) in position 70.
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PMID:How HIV-1 lentivirus causes immune deficiency disease. 1034 73

Graft-versus-host disease (GvHD) is a chief complication of allogeneic bone marrow transplantation. In HLA-identical bone marrow transplantation, GvHD may be induced by disparities in minor histocompatibility antigens (mHags) between the donor and the recipient, with the antigen being present in the recipient and not in the donor. Cytotoxic T lymphocytes (CTLs) specific for mHags of the recipients can be isolated from the blood of recipients with severe GvHD (ref. 3). A retrospective study demonstrated an association between mismatch for mHags HA-1, -2, -4 and -5 and the occurrence of GvHD in adult recipients of bone marrow from HLA genotypically identical donors. Tetrameric HLA-peptide complexes have been used to visualize and quantitate antigen-specific CTLs in HIV-infected individuals and during Epstein-Barr virus and lymphocytic choriomeningitis virus infections. Here we show the direct ex vivo visualization of mHag-specific CTLs during GvHD using tetrameric HLA-class and I-mHag HA-1 and HY peptide complexes. In the peripheral blood of 17 HA-1 or HY mismatched marrow recipients, HA-1- and HY-specific CTLs were detected as early as 14 days after bone marrow transplantation. The tetrameric complexes demonstrated a significant increase in HA-1- and HY-specific CTLs during acute and chronic GvHD, which decreased after successful GvHD treatment. HLA class I-mHag peptide tetramers may serve as clinical tools for the diagnosis and monitoring of GvHD patients.
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PMID:Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease. 1039 33


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