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

Treatment of murine CBA splenocytes with Vibrio cholerae neuraminidase (VCN) prior to engraftment into cyclophosphamide (CY) immunosuppressed Balb/c x CBA mice reduced the incidence of acute lethal graft-versus-host disease (GvHD) and delayed mortality in the later phase of the disease. In the same model, pretreatment of donor splenocytes with VCN also reduced splenomegaly. Engraftment of F1 mice with CBA cells was clearly demonstrated at day 30 after infusion. Treatment of spleen cells with VCN did not compromise their ability to protect mice against irradiation-induced lethality. Furthermore, enzyme treatment was found to have no adverse effects on helper (TH-) and B-cell activity or on suppressor (TS-)cell function in adoptive transfer assays. Therefore, whereas the mechanism of the effect of the VCN preparation remains to be established, it is clear that the treatment provides protection against GvHD.
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PMID:Neuraminidase pretreatment of donor lymphocytes and graft-versus-host disease. 252 29

A heterogeneous group of 11 consecutive patients with leukaemia have been transplanted successfully with allogeneic marrow depleted of T lymphocytes by soy bean lectin agglutination and neuraminidase-treated sheep erythrocyte rosetting. Effective depletion was achieved, leaving less than 1% of donor T lymphocytes. Despite the small numbers of nucleated cells infused (mean 0.14 X 10(8)/kg) there was only moderately delayed recovery of peripheral blood counts and no graft failures have occurred. Standard methotrexate prophylaxis against graft-versus-host disease (GVHD) was also employed in the first four transplants. Only one case of mild grade I (skin only) acute GVHD has occurred and there has been no chronic GVHD to date. The group of patients show an actuarial cumulative survival of 55% with two early infective deaths (days 42 and 44 post-transplant) and three late deaths, two with leukaemic relapse and the third with probable viral encephalitis. The longest survivor is now 1109 days post-transplant. This series indicates that lectin fractionation of donor marrow, previously employed mainly in children, can also be effective in minimizing GVHD in adults without endangering successful engraftment.
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PMID:Allogeneic bone marrow transplantation for adult leukaemia with soy bean lectin fractionated marrow. 333 18

The major limitation of mismatched bone marrow transplantation is fatal graft versus host disease (GVHD). We processed haplotype-identical parental marrow with soybean agglutinin (SBA), sheep erythrocytes (SRBC), and neuraminidase-treated SRBC (N-SRBC) to enrich for marrow stem cells and remove mature T cells. Nine patients with severe combined immunodeficiency disease (SCID) who lacked histocompatible donors received these SBA-negative, SRBC-negative, N-SRBC-negative marrow transplants (0.5-5.0 X 10(8) cells/kg). Seven of the nine patients (78%) had documented T-lymphocyte engraftment based on HLA typing and/or chromosomal analysis. Six patients showed evidence of B-cell immunity on the basis of increased immunoglobulin levels, isohemagglutinins, and/or HLA-DR typing of non-T cells. Three patients received marrow ablative chemotherapy pretransplant for maternal-fetal GVHD; neutrophil engraftment occurred between 9 and 17 days posttransplantation, erythrocytes engrafted within 3-4 weeks of transplantation, and platelet recovery was seen between day 17 and day 49 following the transplants. No immunosuppression was given prophylactically posttransplant. Three patients had no GVHD, two had transient rash and/or fever, and two developed mild focal (stage I) chronic cutaneous GVHD. Of the seven who engrafted, five (71%) are alive and clinically well without GVHD 18-35 months posttransplant. These data demonstrate that SBA- and SRBC/N-SRBC-treated haploidentical marrow transplantation results in functional lymphocyte engraftment in SCID without significant GVHD, and can be used for some patients who otherwise would have no hope for survival.
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PMID:Haploidentical bone marrow transplantation for severe combined immunodeficiency disease using soybean agglutinin-negative, T-depleted marrow cells. 391 Jun 75

Three mAb (R2/60, S7 and 1B11) were used to study the expression of murine CD43 on peripheral T cells and intestinal intraepithelial lymphocytes (IEL) from normal mice, and from mice during acute graft versus host disease (GVHD). In the spleen, essentially all T cells expressed the R2/60 and S7 antigens, whereas the 1B11 antigen was expressed on about half of the CD8(+) cells and approximately 15% of CD4(+) T cells. Interestingly, a significant proportion of resting splenic B cells expressed the 1B11 and R2/60 antigens, but not the S7 antigen. The majority of IEL expressed R2/60 antigen; however, the S7 and 1B11 markers were differentially expressed on CD8alpha, CD8beta, TCRalphabeta and TCRgammadelta cells. Immunoprecipitation and Western blotting analyses identified characteristic 115 and 130 kDa reactive components from IEL lysates with mAb S7 and 1B11 respectively, and reactivity to both molecular entities by mAb R2/60. During acute intestinal GVHD induced by injecting CB6F(1) athymic nude mice with spleen cells from C57BL/6 enhanced-green fluorescent protein transgenic mice, 80-90% of donor T cells in the intestine epithelium expressed all CD43 isoforms; however, the level of expression of the 130 kDa CD43 antigen increased significantly and the level of the 115 kDa antigen decreased on GVHD donor T cells compared to cells at the time of transfer. Using EL4 cells, a similar shift in the expression of CD43 isoforms occurred experimentally following treatment with neuraminidase, suggesting that the type of CD43 isoform expressed on T cells is strongly influenced by conditions which affect membrane charge. The significance of these findings for intestinal immunopathology is discussed.
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PMID:Differential expression of CD43 isoforms on murine T cells and their relationship to acute intestinal graft versus host disease: studies using enhanced-green fluorescent protein transgenic mice. 1050 83

We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection <100 days posttransplantation or severe graft-versus-host disease were admitted to an intensive care unit. In-hospital mortality rate was 21.9% (7/32). The H275Y neuraminidase mutation, which confers oseltamivir resistance developed in 4 of 7 patients with PCR positive for influenza after > or = 4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised.
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PMID:Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. 2058 76