Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BMT was carried out on a patient with DiGeorge syndrome who suffered recurrent infections after birth. At 13 months of age, 8.0 x 10(8)/kg of bone marrow nuclear cells were infused from an HLA-identical sibling using only anti-thymocyte globulin to prevent rejection. Donor DNA was not detected on microsatellite polymorphism by PCR. At 19 months of age, a second BMT from the same donor was carried out using busulfan and cyclophosphamide as conditioning. DNA examination of bone marrow showed chimerism at day 18 and complete donor origin at day 28. Seven months post-BMT, the numbers of CD3-, CD4- and CD8-positive cells were in the normal range. BMT is thus an effective therapy for DiGeorge syndrome.
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PMID:Complete-type DiGeorge syndrome treated by bone marrow transplantation. 982 24

After allogeneic bone marrow transplantation (allo-BMT), recipient alveolar macrophages (AM) are gradually replaced by AM of the donor origin. An influx of mononuclear phagocytes of donor origin to the lung is responsible for the repopulation, but the detailed kinetics remain unclear. We therefore studied 24 BMT recipients who underwent bronchoalveolar lavage (BAL) from 24 to 83 days after BMT. AM cell number, size, morphology, proliferating ability, and genotype of AM were measured. Before day 50, the number and size of AM in BAL fluid were similar to those of normal nonsmokers. However, after day 50, the mean number of AM increased threefold and the mean cell size decreased due to the increase of small AM. These small cells are presumably of donor origin based on DNA fingerprinting analysis and based on fluorescence in situ hybridization for the Y chromosome in a sex-mismatched case. Immunohistochemistry and cell cycle analysis demonstrated that the increase in AM number coincided with a remarkable increase of AM expressing proliferating cell nuclear antigen, suggesting that small AM are proliferating. This is the first report representing that augmented proliferation of donor AM in situ may contribute to the reconstitution of AM population after BMT.
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PMID:Augmented proliferation of human alveolar macrophages after allogeneic bone marrow transplantation. 988 29

Twenty eight Hungarian patients lacking a compatible related donor and their 61 HLA-A,B,DR serologically identical potential unrelated donors (selected from BMDW) were investigated in this study. Out of the 61 donor-recipient pairs only 7 (11,5%) proved to be HLA-identical at DNA level. Thirty one pairs (50,8%) differed in DP alleles, 1 pair (1,6%) has a DQ mismatch only and 22 (36,1%) pairs differed in more alleles. More than one potential donor was found for 26 patients and 5 of them have several donors with DP mismatches only. Among the 31 donor-recipient pairs differing only in DP alleles, 0, 1 and 2 mismatches were observed in GvH direction in 7, 10 and 14 cases, respectively. In the MLC assay no proliferative response was observed when no DP mismatch has been found. Among the 1 and 2 DP mismatched cases 11 (35,5%) gave negative and 13 (41,9%) gave positive MLR results. We have found a large scatter in RR values. On the basis of the DNA typing and MLR results we have found that HLA-DPB1*0101-0201 stimulator-responder combination always gave negative MLR in both direction. HLA-DPB1*0201-0301 and DPB1*0301-0401 allele combinations were reactive in all cases. In conclusion MLC assay might indicate the low immunogeneicity in certain DP allele combinations as well as the avoidable positive combinations, which may help to select the best fitting donor for BMT.
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PMID:Influence of HLA-DPB1 mismatches on MLR responses: the role of high resolution HLA class II typing and MLC in unrelated donor selection for BMT. 991 30

We isolated six clones of weakly tumorigenic fibrosarcoma (QR) from the tumorigenic clone BMT-11 cl-9. The QR clones were unable to grow in normal C57BL/6 mice when injected s.c. (1x10(5) cells). However, they formed aggressive tumours upon co-implantation with a 'foreign body', i.e. a gelatin sponge, and the rate of tumour take ranged from 8% to 58% among QR clones. The enhanced tumorigenicity was due to host cell-mediated reaction to the gelatin sponge (inflammation). Immunoblot analysis and enzyme activity assay revealed a significant inverse correlation between the frequencies of tumour formation by QR clones and the levels of manganese superoxide dismutase (Mn-SOD, P<0.005) and glutathione peroxidase (GPchi, P<0.01) in the respective tumour clones. Electron spin resonance (ESR) revealed that superoxide-scavenging ability of cell lysates of the QR clone with high level of Mn-SOD was significantly higher than that with low level of the antioxidative enzyme in the presence of potassium cyanide, an inhibitor for copper-zinc superoxide dismutase (CuZn-SOD) (P<0.001). Minisatellite mutation (MSM) induced by the inflammatory cells in tumour cells were investigated by DNA fingerprint analysis after QR clones had been co-cultured with gelatin-sponge-reactive cells. The MSM rate was significantly higher in the subclones with low levels of Mn-SOD and GPchi (P<0.05) than in the subclones with high levels of both enzymes. The MSM of the subclones with low levels of both enzymes was inhibited in the presence of mannitol, a hydroxyl radical scavenger. The content of 8-hydroxydeoxyguanosine (8-OHdG) by which the cellular DNA damage caused by active oxygen species can be assessed was significantly low in the tumours arising from the QR clone with high levels of Mn-SOD and GPchi even if the clone had been co-implanted with gelatin sponge, compared with the arising tumour from the QR clone with low levels of those antioxidative enzymes (P<0.001). In contrast, CuZn-SOD and catalase levels in the six QR clones did not have any correlation with tumour progression parameters. These results suggest that tumour progression is accelerated by inflammation-induced active oxygen species particularly accompanied with declined levels of intracellular antioxidative enzymes in tumour cells.
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PMID:Inflammatory cell-mediated tumour progression and minisatellite mutation correlate with the decrease of antioxidative enzymes in murine fibrosarcoma cells. 1002 2

We conducted a double retroviral vector (RV) gene marking trial to test for the possible contribution to relapse of follicular non-Hodgkin's lymphoma (FNHL) cells present in bone marrow (BM) and peripheral blood (PB) grafts used for hematopoietic reconstitution of patients undergoing myelaoblative chemotherapy and autologous transplant. CD34 positive selection using the CellPro Ceprate CD34 column was performed on PB mononuclear cells obtained after cyclophosphamide/G-CSF mobilization. CD34 positive cells were exposed for 4-6 hours to the LNL6 or G1 Na RV in the absence of growth factors or stromal monolayers. One week later, BM mononuclear cells were similarly processed. Patients then received total body irradiation (TBI), cyclophosphamide, and etoposide followed by infusion of both PB and BM CD34 positive cells. Semiquantitative Southern blot analysis of DNA t(14;18) amplification products showed approximately a three log reduction in t(14;18) positive cells after CD34 positive selection. The first patient showed evidence of engraftment with RV positive BM and PB cells for 9 months. He relapsed one year after transplant. At relapse, one year after transplant, he had lost evidence of RV positive cells in ficolled mononuclear BM and PB cells as well as in CD19 positive cells. The second and third patients showed evidence of engraftment with RV positive cells up to 9 and 6 months post BMT respectively. The second and third patients are still in clinical remission. Our results demonstrate engraftment of RV transduced hematopoietic cells in the PB and BM for up to 9 months.
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PMID:Hematopoietic retroviral gene marking in patients with follicular non-Hodgkin's lymphoma. 1003 25

Current guidelines for the treatment of catheter-related bacteraemia (CRB) advise against central venous catheter (CVC) exchange because of the potential risk of prolonging infection. However, there are no consistent data proving this recommendation. We evaluated prospectively the usefulness of CVC exchange by guidewire for the treatment of CRB in patients undergoing BMT or intensive chemotherapy. CVC exchange was considered when fever and positive blood cultures persisted after 2 days of adequate antimicrobial therapy and no potential source of bacteraemia other than CVC could be identified. The guidewire exchange was preceded and followed by a slow infusion of adequate antimicrobial therapy. Bacteraemia was confirmed as catheter-related by demonstrating concordance between isolates from the tip and blood cultures by pulsed-field electrophoresis of genomic DNA. This procedure was performed in 19 episodes of bacteraemia during a 1-year period. Fourteen episodes (74%) were catheter-related and 71% of these were due to coagulase-negative staphylococci. Guidewire replacement was accomplished uneventfully 4 days after development of sepsis (range 3-6). In all cases, clinical signs of sepsis disappeared in less than 24 h after replacement. Definitive catheter withdrawal was carried out a median of 16 days (range 3-42) after guidewire exchange; in all cases, the tip culture was negative. We conclude that CVC replacement by guidewire under adequate antimicrobial therapy may be a reasonable option for the treatment of CRB when antimicrobial therapy alone has been unsuccessful.
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PMID:Central venous catheter exchange by guidewire for treatment of catheter-related bacteraemia in patients undergoing BMT or intensive chemotherapy. 1003 49

Although progress has been made in the diagnosis and management of respiratory complications after BMT, such complications are still frequent and are a major cause of morbidity and mortality. The use of CMV-negative marrow and blood products, surveillance bronchoscopies, and prophylactic use of antivirals have significantly reduced the incidence of CMV pneumonia. DNA amplification techniques have allowed earlier detection of viral respiratory infections, and early detection of localized invasive aspergillosis can improve survival with lung resection and antifungal therapy. Finally, consideration for open lung biopsy should include the patient's degree of preoperative respiratory impairment, because this may relate to early postoperative survival.
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PMID:Thoracic complications related to bone marrow transplantation. 1007 85

The spectrum of pediatric bone marrow transplantation has changed in recent years. Mismatched and unrelated donor transplants are common, demanding an increased vigilance to detect incipient graft failure, secondary lymphoma as well as relapse and other problems, which now are potentially treatable. To diagnose these complications it may be important to know whether blood and marrow cells are of recipient or donor origin. To evaluate the role of mixed donor-recipient chimerism in relation to clinical problems we adapted a polymerase chain-reaction technique, using fluorescent primers analyzing DNA fragment length polymorphisms, to follow prospectively 17 bone marrow grafted children. To increase the precision of chimerism analysis, immunomagnetically isolated leukocyte populations were assayed in selected cases. Five patients encountered clinical problems related to chimerism. One infant with adenosine deaminase deficiency failed to engraft stem cells, yet succumbed to graft-versus-host disease, mediated by mature donor T-cells. Three children developed significant mixed chimerism. One of these three patients died in relapse of leukemia, while the two other patients who had received T-cell depleted grafts had persistent recipient T-cells, in spite of engraftment. After 5 months, these were displaced by donor T-cells in one of the patients. In the fifth patient, also after T-cell depleted BMT, a fatal donor cell lymphoma occurred. Twelve children had stable full chimerism or in one case a low grade mixed chimerism and remain disease-free throughout follow up (median 9 months). In conclusion, the analysis of chimerism, particularly of separated leukocyte populations, offers an almost indispensable insight and a basis for therapeutic decisions in complicated situations such as grafting involving unrelated or mismatched donors, graft manipulation, adoptive immunotherapy and in immunodeficiency patients.
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PMID:Engraftment and chimerism, particularly of T- and B-cells, in children undergoing allogeneic bone marrow transplantation. 1008 48

Despite the therapeutic efficacy of allogeneic bone marrow transplantation (allo-BMT), circulating hematopoietic progenitor cells after bone marrow transplantation have not been well characterized. In the present study, we focused on these 'post-transplant circulating progenitor cells (PTCPC)' which may be on their way to bone marrow. We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just before transplantation), 1 (8-15 h after the completion of transplantation), 2, 3, 5, 7, 10, 14, 17, 21, 28 and 35 after allo-BMT in five transplant patients using a standard methylcellulose assay. In addition, high proliferative potential colony-forming cells (HPP-CFC) of the harvested donor bone marrow (BM) and day 1 PB of recipients were assayed in five patients. The origin of HPP-CFC from day 1 PB was analyzed by polymerase chain reaction of a DNA region containing a variable number of tandem repeats. The replating potential of these HPP-CFC was evaluated by a secondary colony assay. The proportion of CD38negative cells among CD34+ cells in the harvested BM and day 1 PB was evaluated by two-color flow cytometric analysis. The number of CFU-GM on day 1 ranged from 6 to 73/10 ml PB, and became undetectable on day 5. The reappearance of PTCPC was observed on day 14, along with hematopoietic recovery. The proportion of HPP-CFC among myeloid colonies from day 1 PB was significantly higher than that from harvested BM (44.3+/-10.4% vs 11.3+/-2.1%, respectively, n=5, P=0.0030). These HPP-CFC from day 1 PB were confirmed to be of donor origin. More than 90% of these HPP-CFC had replating potential. Two-color flow cytometric analysis revealed that the proportion of CD34+CD38negative cells was significantly higher in day 1 PB than in the harvested BM (61.0+/-16.5% vs 9.3+/-3.5%, respectively, n=7, P=0.0002). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following allo-BMT.
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PMID:Hematopoietic progenitor cells from allogeneic bone marrow transplant donors circulate in the very early post-transplant period. 1021 41

To characterize the process of the establishment of complete chimerism after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), we determined the origin of leukocytes in peripheral blood (PB) obtained from 23 patients in the very early period after allo-PBSCT using amplification of mini- or microsatellite regions of genomic DNA. Donor-specific alleles were amplified from the PB obtained at day 8 post-transplant for 19 allo-PBSCT patients. Among the 19 patients, 12 showed only donor-specific alleles (complete chimerism) while 7 did both donor and host-specific alleles (mixed chimerism). Although donor specific alleles were amplified in 10 of 12 patients who received allogeneic bone marrow transplantation (allo-BMT) similarly to allo-PBSCT, all of these ten showed mixed chimerism. When the chimeric state was examined in PB samples obtained serially at 2-3-day intervals post-transplant, host-specific alleles in allo-PBSCT patients were not detectable in the PB much earlier than those in allo-BMT patients. These findings indicate that the appearance of donor-derived cells associated with the disappearance of host-derived cells in the circulation occurs earlier after allo-PBSCT as compared with allo-BMT, leading to the rapid establishment of complete chimerism.
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PMID:Early establishment of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantation. 1022 60


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