Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin and rectal biopsy tissue from 34 allogeneic and 23 autologous BMT recipients was prospectively analysed for CMV using immunohistochemistry and PCR to investigate the hypothesis that target organ infection with CMV initiates and/or exacerbates GVHD. Biopsies were obtained prior to and at 3, 8 and 26 weeks after BMT and whenever GVHD was suspected. Surveillance specimens of peripheral blood leucocytes (PBL), urine and throat swabs were obtained every 2 weeks until 12 weeks after BMT, and whenever CMV was suspected. Cryostat sections were analysed immunohistochemically for CMV antigens and PBL and biopsies for CMV DNA by PCR. Of the 31 patients who engrafted, 28 (90%) developed GVHD clinically, confirmed histologically in 56 biopsies. GVHD proved clinically severe in 14 patients, 4 of whom had treatment-resistant GVHD. CMV was detected in PBL more frequently in patients with severe GVHD than in those with mild/moderate GVHD (29% vs. 7%). However, in all but one patient the onset of GVHD preceded detection of CMV. In biopsy specimens, CMV was detected in only 2 patients, 1 of whom had an exacerbation of GVHD temporally associated with CMV. Thus, despite a high incidence of GVHD in this series, with 56 episodes of GVHD in 28 patients, only 1 patient had CMV in biopsy tissue temporally associated with GVHD. This suggests that biopsy infection with CMV is not a major factor in initiating or exacerbating GVHD in this cohort. This study thus does not support a role for target organ infection with CMV in the pathogenesis of GVHD.
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PMID:Role of target organ infection with cytomegalovirus in the pathogenesis of graft-versus-host disease. 765 81

Intestinal biopsy samples derived from 22 consecutive patients with severe diarrhoea (> 1.5 1/day for 3 or more consecutive days) following allogeneic BMT were analysed for the local presence of cytomegalovirus (CMV) and histological and immunohistological alterations described as typical for acute graft-versus-host disease (GVHD). Seventeen patients showed extensive histopathological lesions typical for acute intestinal GVHD grade > I, 14 marked GVHD-related immunohistological alterations. In intestinal biopsies from 10 of these 22 patients CMV-DNA was detected using PCR- and in situ hybridisation techniques. In 7 of these 10 CMV-DNA positive samples CMV protein expression and in 5 cytomegalic cells were demonstrated. CMV could predominantly be shown in biopsies obtained from the ascending colon and/or the terminal ileum. All 10 patients with local CMV infection showed severe histopathological and immunohistological alterations described as typical for acute intestinal GVHD. Five of seven patients with a CMV-positive intestinal biopsy showed marked improvement of lower gastrointestinal tract disease on antiviral therapy. Five of seven patients lacking local presence of CMV but with severe histopathological lesions responded to therapy with high-dose steroids. Thus, PCR screening for CMV and histopathological analysis may help to treat lower intestinal disease in the marrow transplant recipient early and effectively.
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PMID:Incidence of local CMV infection and acute intestinal GVHD in marrow transplant recipients with severe diarrhoea. 771 74

Between May 1989 and February 1994, we performed 48 volunteer unrelated donor BMTs for first chronic phase chronic myeloid leukemia using in vivo T cell depletion for acute graft-versus-host disease (aGvHD) prophylaxis. In 40 cases, adequate material was available to measure the frequency of antirecipient MHC cytotoxic T lymphocyte precursor (CTLp) cells in the blood of potential donors. This supplemented standard serological typing, one-dimensional isoelectric focusing for class I proteins, and allogenotyping for DR and DQ alleles using DNA RFLP analysis in the donor selection process. All recipients were conditioned with cyclophosphamide 120 mg/kg, TBI 1320 cGy, and intravenous Campath 1G. GvHD prophylaxis consisted of CsA, short-course methotrexate, and intravenous Campath 1G. Minimum follow-up in all surviving recipients was 100 days. The development of aGvHD and the probability of leukemia-free survival were compared between the high frequency group (CTLp > 1 in 100,000) (n = 15) and the low frequency group (CTLp < 1 in 100,000) (n = 25). There was a trend for increasing grade of aGvHD, which was statistically significant in the high frequency group when compared with the low frequency group (P = 0.003). Both a high frequency of CTLp (relative risk [RR] = 9.0, P = 0.016) and HLA mismatch (RR = 6.7, P = 0.023) were predictors of severe aGvHD (grade III or IV). Multivariate analysis showed that CTLp group (RR = 3.4, P = 0.015) and CMV status (RR = 3.9, P = 0.008) were predictors of leukemia-free survival. Further investigation showed an interaction between the two, such that CMV seropositive recipients in the high frequency group had a relative risk of 9.4 (P = 0.0001) of treatment failure (death or relapse) when compared with other combinations. We conclude that with our present GvHD prophylaxis regimen, CTLp frequency analysis predicts post-BMT outcome and is a valuable aid in donor selection.
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PMID:Cytotoxic T lymphocyte precursor frequency analyses in bone marrow transplantation with volunteer unrelated donors. Value in donor selection. 776 66

The (NZW x BXSB)F1 (W/BF1) mouse is known to be an animal model of systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP). These mice produce not only anti-DNA antibodies but also anti-platelet antibodies, resulting in decreased platelet counts. They show a high level of proteinuria, increased white blood cell (WBC) counts, hypertension, and myocardial infarction due to the high levels of anti-cardiolipin antibodies. When W/BF1 mice (4-5 months) were lethally irradiated and then reconstituted with T cell-depleted bone marrow cells of normal BALB/c mice (8 weeks), 60% of the mice survived more than one year. The WBC and platelet counts in the mice were normalized, and the levels of anti-DNA and anti-platelet antibodies decreased. The renal dysfunction was also ameliorated as indicated by a lower level of proteinuria, lower levels of serum creatinine (S-CRTN) and blood urea nitrogen (BUN), and by improved histology. The blood pressure (BP) of the treated W/BF1 mice decreased due to the improved renal functions. In contrast to the non-treated W/BF1 mice which died of myocardial infarction or renal failure by the age of 7 months, the treated W/BF1 mice showed no evidence of myocardial infarction even one year after BMT. This was due to the lower cardiolipin levels.
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PMID:Effect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice. 778 96

Materno-fetal GVHD is commonly a fatal condition occurring in patients with severe combined immunodeficiency (SCID). Definitive diagnosis is often difficult. We describe a patient with clinical features suggestive of materno-fetal GVHD but in whom histology was atypical. Y chromosome-specific PCR amplification analysis of DNA extracted from the skin biopsy was performed to detect chimeric evidence of infiltrating maternal T cells. This revealed strong positivity for the Y chromosome, indicating lack of maternal T cell engraftment and thus confirming a diagnosis of Omenn's syndrome, a variant of SCID in which atypical lymphocyte clones give rise to a similar picture. In contrast, Y chromosome-specific PCR analysis of skin biopsy DNA from a male patient with a rash clinically and histologically typical of materno-fetal GVHD revealed absence of the Y chromosome, indicating infiltration of maternal cells and thus confirming the diagnosis of materno-fetal GVHD. Y chromosome-specific PCR analysis is thus a useful investigation for the differentiation of materno-fetal GVHD from Omenn's syndrome in pre-BMT SCID patients presenting with unexplained rash.
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PMID:Differentiation of materno-fetal GVHD from Omenn's syndrome in pre-BMT patients with severe combined immunodeficiency. 795 Nov 6

We assessed the origin of peripheral blood cells and bone marrow cells of 92 samples obtained from 19 patients after allo BMT by two-step polymerase chain reaction (PCR) amplification of MCT118, one of the variable number of tandem repeat regions (VNTR) which has a different length in 19 of 32 sibling pairs examined, that can detect the DNA pattern of a minor cell population of only 1% without using radioisotopes. Mixed chimerism (MC) was detected in the hematopoietic cells of four patients. Two patients who showed progressive MC developed relapse of leukemia 3 months and 4 months after the detection of MC, and two patients died with bone marrow hypoplasia 61 days and 7 months after BMT. These data suggest the clinical importance of analyzing the correlation of MC and clinical complications after BMT by this method, which can be used to monitor MC in about two thirds of allo BMT patients with an adequate sensitivity.
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PMID:Evaluation of mixed chimerism by two-step polymerase chain reaction amplification of hypervariable region MCT118 after allogeneic bone marrow transplantation. 800 60

We report a study of CMV detection by a nonradioactive in situ hybridization (ISH) technique using a biotinylated CMV-DNA probe. The method was applied to blood and bone marrow cells and its results were compared with those of other currently used techniques. First, we analysed peripheral leucocytes on blood donors, and, after comparison with PCR, we obtained 75% sensitivity and 87% specificity rates. We then studied four BMT recipients during the first 105 d post-transplant. A positive signal was detected as a predominantly nuclear staining. The detection of an ISH-positive signal occurred at least 8 d before CMV isolation from viral culture. The number of positive cells was variable according to the patients' clinical evolution, showing a dramatic increase of labelled cells in viraemic patients and then a decrease until complete disappearance of labelled cells when an efficient anti-viral treatment was initiated. This study suggests that the detection of CMV-DNA by ISH performed on peripheral leucocytes is a valuable tool for the early diagnosis of CMV infection and could lead to the initiation of optimal ganciclovir treatment.
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PMID:In situ hybridization for the detection of cytomegalovirus in blood or bone marrow leucocytes after allogeneic bone marrow transplantation. 804 44

Current practice for the selection of unrelated donors involves serological typing of HLA-A, -B and -DR antigens, DNA analysis of the class II region and the MLR. However, even after matching for the class II loci at the DNA level, a significant proportion of matched unrelated pairs remain MLR reactive. Ideal matching for BMT would be a match for the whole MHC haplotype rather than individual HLA loci. In the present study, we have evaluated the complementary role of class III typing in determining MHC identity. A group of 86 donor/recipient pairs, of which 14 were unrelated, was investigated using C4, Bf, HSP70 and TNF DNA probes. Phenotypically HLA-matched siblings were always identical at the C4 locus which is the most polymorphic of all the loci examined. Nine of the 14 HLA serologically matched MLR non-reactive (RRI < 20%) unrelated pairs had class III mismatching. Four of these pairs with class III mismatching were matched at the DRB and DQB loci by RFLP analysis. These results demonstrate that serological identity, DRB/DQB RFLP-matching and a negative MLR do not always match the whole haplotype in unrelated pairs. It can be concluded that the linkage of the class III loci to both HLA regions makes this region a reliable marker of the whole MHC haplotype.
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PMID:MHC class III polymorphisms in selection of donors for BMT. 809 7

Since both donor/recipient origin of hematopoietic cells and the proportion of residual host cells influence the outcome of BMT, we performed this study to design a rapid and efficient strategy for chimerism analysis. Using the polymerase chain reaction, we analyzed the informativity and sensitivity of two kinds of polymorphism in 35 HLA-identical sibling pairs: four variable number of tandem repeats (VNTR) systems and the frameworks (FW) of the beta-globin gene. The latter polymorphisms were analyzed by means of denaturing gradient gel electrophoresis, a method that identifies heterozygosity by the presence of heteroduplexes. All the siblings were found to be informative for at least one polymorphic system. In addition, 34 of the 35 sibling pairs (97%) bore at least one VNTR or FW system which permitted the detection of the minor population (i.e., the first sibling's DNA contained an allele that was absent from the second sibling's DNA). The VNTR- and FW-based methods were highly sensitive, being able to reveal minor populations representing as little as 1% and 5% of total DNA, respectively. The value of the beta-globin gene FW analysis lies in the detection of additional heteroduplexes, which reflect genotypic differences between siblings' DNA. We describe the experimental conditions required to detect the minor DNA population in virtually all cases. As direct evidence of mixed chimerism can be obtained from denaturing gradient gel electrophoresis analysis of any highly informative polymorphic system, this method can be applied to chimerism analysis.
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PMID:Molecular analysis of polymorphic loci to study chimerism after allogeneic bone marrow transplantation. Heteroduplex analysis in denaturing gradient gel electrophoresis: a new approach to detecting residual host cells. 810 82

We assessed the origin of peripheral blood cells and bone marrow cells obtained from 15 patients after allogeneic bone marrow transplantation (allo BMT) by sensitive two-step polymerase chain reaction (PCR) amplification of MCT118, a variable number of tandem repeats regions (VNTR), that can be used to detect the DNA pattern of a minor cell population of only 1% without using radioisotopes. Mixed chimerism(MC) was detected in the haematopoietic cells of 3 patients. Two patients developed relapse of leukaemia after the detection of MC and one patient died of bone marrow hypoplasia 7 months after BMT. These findings indicate the clinical usefulness of this method to monitor patients with MC. Also, we analyzed cytokine gene expression in peripheral blood mononuclear cells during the development of graft-versus-host disease (GVHD) in patients who underwent allo BMT using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of interleukin(IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA was increased during the development of GVHD and the degree of this increment depended on the severity of the disease. These findings suggest that IL-1 beta, IL-6, and TNF-alpha produced by peripheral blood mononuclear cells play an important role in the development of GVHD. Therefore, analysis of MC and cytokine mRNA expression using the PCR technique after allogeneic bone marrow transplantation provide important information for treatment and monitoring of marrow transplant patients.
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PMID:[Clinical application of gene technology to monitor bone marrow transplantation]. 815 60


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