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Biomedical subjects

A Takami

Publications and source records attributed to A Takami.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cytotoxicity against lymphoblastoid cells mediated by a T-cell clone from an aplastic anaemia patient: role of CD59 on target cells.

In an attempt to elucidate the pathogenic role of a CD4+ cytotoxic T-cell clone NT4.2 isolated from the bone marrow of a patient with cyclosporine-dependent aplastic anaemia, we characterized the T-cell clone as well as its cytotoxicity against an autologous Epstein-Barr (EB) virus-transformed B-lymphoblastoid cell line (LCL). NT4.2 expressed BV21+ BJ2.7+ with a complementarity-determining region (CDR) 3 motif of SQGQGEVEQY which was homologous to that of a T-cell clone isolated from a patient with connective tissue disease. NT4.2 started to lyse LCL cells within 2 h and exerted maximal cytotoxicity within 3 h of incubation. The cytotoxicity required the presence of divalent cations and was not associated with DNA fragmentation of the target cells. Anti-CD59 monoclonal antibodies (MoAb) blocked the cytotoxicity to the same degree as anti-CD3, HLA-DR or CD2 mAb. Flow cytometric analysis of the peripheral blood of this patient during remission after cyclosporine therapy revealed 1.7% of granulocytes to be deficient in CD59. These findings indicate that NT4.2 exerts its cytotoxicity through a perforin-mediated pathway, not a Fas/Fas ligand-dependent pathway, and that haemopoietic stem cells lacking CD59 may evade cytotoxic T lymphocytes, leading to the in vivo expansion of a paroxysmal nocturnal haemoglobinuria clone.

Aged↗
PubMed1999

Early establishment of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantation.

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.

Adolescent↗
PubMed1999

Cone-beam CT angiography of the thorax: an experimental study.

The authors recently developed a cone-beam computed tomography (CT) scanner and this report presents their evaluation of its potential for thoracic vascular imaging. An X-ray tube and a video-fluoroscopic system were rotated around the objects and 360 projected images were collected in a 12-s scan. Each image was digitized and a 3 dimensional (D) image (256x256x256 voxel volume with a voxel dimension of 0.9x0.9x0.9 mm) was reconstructed. Two different 3D-CT angiographies were investigated in 2 pigs: right atriography and thoracic aortography. Each pig was anesthetized, mechanically ventilated and positioned within the scanner. Contrast agent was infused through the right atrium or the aortic root at a rate of 3 ml/s during the scan. The right atriography scan clearly delineated the anatomy of the pulmonary artery, heart chambers and thoracic aorta. The thoracic aortography scan also clearly delineated the aortic anatomy including the internal thoracic and intercostal arteries. In conclusion, cone-beam CT angiography is potentially useful for thoracic vascular imaging.

Angiography↗
PubMed1999

Successful therapy of myelodysplastic syndrome with menatetrenone, a vitamin K2 analog.

Although vitamin K2 is an inducer of the in vitro differentiation of myeloid leukemic cell lines, its clinical efficacy in the treatment of myelodysplastic syndrome (MDS) is unclear. We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to an 80-year-old woman with MDS (refractory anemia) heavily dependent on red-cell transfusions. The patient's pancytopenia gradually improved, and she became transfusion-independent after 14 months. Pancytopenia recurred when menatetrenone was discontinued but recovered again with readministration. Administration of menatetrenone at a dose effective in improving osteoporosis may also be useful in restoring hematopoiesis in MDS patients, possibly by way of inducing differentiation.

Aged↗
PubMed1998

Successful treatment of Epstein-Barr virus-associated natural killer cell large granular lymphocytic leukaemia using allogeneic peripheral blood stem cell transplantation.

We report a case of natural killer cell large granular lymphocytic (NK-LGL) leukaemia successfully treated with allogeneic peripheral blood stem cell transplantation (allo-PBSCT). The peripheral blood (PB) revealed an abnormal expansion of LGL that were CD3-, CD16- and CD56+, and had natural killer activity. In situ EBER-1 hybridization of the PB mononuclear cells showed the presence of Epstein-Barr virus (EBV) in the LGL as well as in lymphocytes infiltrating the tonsils and colon. Southern blotting with an EBV-terminal repetitive sequence probe demonstrated clonal proliferation of EBV+ cells. The patient received allo-PBSCT from his HLA-matched sister with a conditioning regimen involving the use of cyclophosphamide and fractionated total body irradiation. The patient promptly recovered trilineage haematopoiesis without graft-versus-host disease, and has been in complete remission without therapy for 10 months since allo-PBSCT, suggesting that allo-PBSCT could eradicate the NK-LGL leukaemic cells.

Adolescent↗
PubMed1998

Castability of a commercial castable glass ceramics.

This study was carried out to determine the design and thickness of the cervical margin of a castable ceramic restoration from the point of view of its castability. Castability of castable ceramics was lower compared to Ag-Pd-Au and Co-Cr alloy with the use of the mesh pattern and rod pattern test (p < 0.05). It was more dependent on the pattern thickness than alloys (p < 0.05), and perfect reproducibility with non-measurable variability could be estimated to reach 1.0 mm thickness of the original pattern (p < 0.001). Marginal shape was certainly more reproducible in a right angle shoulder than in 30, or 45 degree bevels (p < 0.05). From these results, it is suggested that a right angle shoulder margin with 1.0 mm thickness is more suitable to castable glass ceramic restoration than any other design.

Analysis of Variance↗
PubMed1998

Simple and Patlak models for myocardial blood flow measurements with nitrogen-13-ammonia and PET in humans.

UNLABELLED: The Simple and Patlak models for estimating myocardial blood flow with 13N-ammonia have become attractive for clinical applications with PET because of their simplicity and ease of implementation. However, these models are sensitive to factors such as the data acquisition times and data integration times, which can cause errors in the estimation of myocardial blood flow, as demonstrated in this study. Limiting the application of these models to specific conditions can minimize the errors. METHODS: Dynamic PET images of the uptake of 13N-ammonia in the heart were obtained in seven humans under rest and dipyridamole stress. Myocardial blood flow was estimated using the Simple and Patlak models for different data acquisition times and data integration times. Blood flow values were compared to flow values computed with the two-compartment model as a reference. RESULTS: Blood flow values calculated with the Simple and Patlak models during the first 2 min of data acquisition were closely correlated to the two-compartment model values. Longer acquisition times resulted in significant underestimation of blood flow for the Simple model. Long integration times of greater than 60 sec also resulted in significant underestimation of blood flow for both models. CONCLUSION: The Simple and Patlak models produce estimates of myocardial blood flow that are well correlated with the two-compartment model estimated blood flows for the integration time of 60 sec from 60 to 120 sec postinjection. Because of the errors associated with longer data acquisition times and longer integration times, use of these models should be limited to a well-documented data acquisition paradigm.

Ammonia↗
PubMed1998

CD20-positive T-cell chronic lymphocytic leukaemia.

Although CD20 is considered to be a representative marker for B lymphocytes, the antigen is weakly expressed on a small subset of normal T lymphocytes. A 60-year-old man developed pancytopenia and hepatosplenomegaly due to clonal proliferation of atypical lymphocytes that were weakly positive for CD20. The leukaemic cells were also positive for T-cell antigens such as CD2, CD3, CD5, CD7, CD8 and T-cell receptor (TCR) Vbeta8 and for activation antigens such as CD38 and HLA-DR, but were negative for CD19, CD21, CD22, CD25. Southern blot analysis revealed rearrangement of the TCR-beta gene and a germline configuration of the immunoglobulin heavy chain gene. This is the first report of a case of clonal expansion of CD20dim T lymphocytes.

Antigens, CD20↗
PubMed1998

High-resolution cardiac PET in rabbits: imaging and quantitation of myocardial blood flow.

UNLABELLED: A high-resolution PET system for small animals was tested for its applicability to the investigation of regional myocardial blood flow (MBF) in rabbits. METHODS: Nineteen measurements were performed in 10 closed-chest anesthetized rabbits at baseline and during infusions of adenosine (0.2 mg/kg/min) and propranolol (0.20-1.20 mg slow infusion) to obtain a wide range of MBF. Myocardial blood flow was assessed both by dynamic 13N-ammonia PET and by colored microspheres. Blood was withdrawn directly from the femoral artery, and arterial 13N activity was measured by coincidence type gamma detection system for the input function. Nitrogen-13 myocardial uptake was calculated by dividing the myocardial 13N activity by the integral value of the input function. RESULTS: Three or four contiguous cross-sectional myocardial images were obtained after 13N-ammonia injection. The left ventricular wall and cardiac cavity were clearly visualized. Moreover, initial passage of the tracer through the heart was obtained with serial 10-sec PET images. Nitrogen-13 myocardial uptake correlated well with flow measured with microspheres (r = 0.88). CONCLUSION: Our cardiac PET system can be used for in vivo imaging and quantitation of MBF in small animals and may play an important role in the future study of animal models of cardiovascular diseases.

Adenosine↗
PubMed1997

Inhibition of immature erythroid progenitor cell proliferation by macrophage inflammatory protein-1alpha by interacting mainly with a C-C chemokine receptor, CCR1.

Several lines of evidence indicate that macrophage inflammatory protein-1alpha (MIP-1alpha) modulates the proliferation of hematopoietic progenitor cells, depending on their maturational stages. To clarify the mechanisms for the modulation of hematopoiesis by this chemokine, we examined the expression of a receptor for MIP-1alpha, CCR1, on bone marrow cells of normal individuals using a specific antibody and explored the effects of MIP-1alpha on in vitro erythropoiesis driven by stem cell factor (SCF) and erythropoietin (Epo). CCR1 was expressed on glycophorin A-positive erythroblasts in addition to lymphocytes and granulocytes. CCR1+ cells, isolated from bone marrow mononuclear cells (BMMNCs) using a cell sorter, comprised virtually all erythroid progenitor cells in the BMMNCs. Moreover, MIP-1alpha inhibited, in a dose-dependent manner, colony formation by burst-forming unit-erythroid (BFU-E), but not by colony forming unit-erythroid (CFU-E), in a methylcellulose culture of purified human CD34+ bone marrow cells. Although reverse-transcription polymerase chain reaction (RT-PCR) showed the presence of CCR1, CCR4, and CCR5 transcripts in CD34+ cells in BM, anti-CCR1 antibodies significantly abrogated the inhibitory effects of MIP-1alpha on BFU-E formation both in a methylcellulose culture and in a single cell proliferation assay of purified CD34+ cells. Although the contribution of CCR4 or CCR5 cannot be completely excluded, these results suggest that MIP-1alpha-mediated suppression of the proliferation of immature, but not mature erythroid progenitor cells, is largely mediated by CCR1 expressed on these progenitor cells.

Analysis of Variance↗
PubMed1997

Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia.

The existence of T cells capable of inhibiting in vitro hematopoiesis has been shown in aplastic anemia (AA), although whether such inhibition is mediated by a specific immune reaction involving an HLA allele remained unknown. We isolated a CD4+ Vbeta21+ T-cell clone that was most dominant among Vbeta21+ T cells in the bone marrow (BM) of an AA patient whose HLA-DRB1 alleles included 1501 and 0405. The T-cell clone named NT4.2 lysed an autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) and phytohemagglutinin-stimulated lymphocytes (PHA-blasts) as well as allogeneic LCLs sharing HLA-DRB1*0405. Cytotoxicity against LCL cells and PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody (MoAb) or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells enriched with CD34+ cells that had been cultured for one week in the presence of colony-stimulating factors as well as allogeneic CD34+ cells of a normal individual carrying HLA-DRB1*0405, cultured in the same way. Moreover, NT4.2 strongly inhibited colony formation by hematopoietic progenitor cells derived from cultured CD34+ cells sharing HLA-DRB1*0405. These results indicate that the AA patient has T cells capable of killing hematopoietic cells in an HLA-DRB1*0405-restricted manner and that such cytotoxic T cells may contribute to the pathogenesis of AA.

Aged↗
PubMed1997

Induction of autocytotoxic T cells with cyclosporine and interferon-gamma for patients with non-Hodgkin's lymphoma after transplantation of peripheral blood stem cells.

BACKGROUND: Autologous graft-versus-host disease is inducible after autologous bone marrow transplantation by means of administration of cyclosporine. OBJECTIVE: This study was performed to investigate the inducibility of autologous graft-versus-host disease after transplantation of peripheral blood stem cells (PBSCs). METHODS: Two patients with non-Hodgkin's lymphoma in remission underwent PBSC transplantation followed by administration of cyclosporine and low-dose interferon-gamma. RESULTS: Although autologous graft-versus-host disease did not develop in either patient, T lymphocytes with cytotoxic activity against autologous lymphocytes appeared transiently in the early posttransplant period. Such autocytotoxic lymphocytes were not detectable in another patient who underwent PBSC transplantation who did not receive cyclosporine and interferon-gamma. When CD4+ and CD8+ cells were sorted from the peripheral blood mononuclear cells of one of the two patients and tested for cytotoxicity against autologous lymphocytes, only CD8+ cells exhibited cytotoxic activity. CONCLUSIONS: The results indicate that administration of cyclosporine and interferon-gamma after PBSC transplantation can induce autocytotoxic CD8+ T cells, even though it may not produce autologous graft-versus-host disease. It is unclear whether induction of such autocytotoxic T cells among patients with non-Hodgkin's lymphoma who undergo PBSC transplantation has any antilymphoma effect.

Adult↗
PubMed1997

Induction of two UDP-glucuronosyltransferase isoforms sensitive to phenobarbital that are involved in morphine glucuronidation: production of isoform-selective antipeptide antibodies toward UGT1.1r and UGT2B1.

We document here in that two UDP-glucuronosyltransferase (UGT) isoforms sensitive to phenobarbital are involved in morphine glucuronidation in Wistar and Sprague-Dawley rats. The hepatic microsomal morphine UGT activity in untreated Gunn rats was significantly less than that of untreated Wistar rats. Although the morphine UGT activity in the liver of Gunn rats was increased by phenobarbital (PB) treatment, this was significantly less than that in the liver of PB-treated Wistar rats. UGT1.1r is an isoform of morphine UGT in rat, and UGT2B1 is also considered an isoform of morphine UGT, because UGT2B1 (stably expressed in V79 cells) exhibited morphine UGT activity. We prepared specific antipeptide antibodies against UGT1.1r and UGT2B1. Using isoform-specific antipeptide antibodies, both UGT1.1r and UGT2B1 in Wistar and Sprague-Dawley rats were inducible by PB treatment. However, UGT1.1r is not present in the liver from Gunn rats. This study is the first demonstration that protein levels of two morphine UGT isoforms, UGT1.1r and UGT2B1, in the liver of Wistar and Sprague-Dawley rats are inducible by PB treatment.

Animals↗
PubMed1997

[Sudden cardiac tamponade due to hemorrhagic myocarditis after preconditioning marrow transplantation with cyclophosphamide in a patient with aplastic anemia].

A 28-year-old male was diagnosed as aplastic anemia in 1983. He maintained on corticosterone with a large transfusion requirement for being resistant to other therapies, and combined with hemochromatosis at 20-year-old. In February 1994, he was admitted to the hospital for consideration of BMT. Echocardiogram was normal on admission. He was transplanted with bone marrow from his HLA-matched MLC negative sister following contained of TLI (7.5 Gy) and CY 50 mg/kg for four days on March 10 1994. Disturbance of consciousness appeared, an echocardiogram showed severe pericardial effusion on day 1 after BMT. He was diagnosed cardiac tamponade, pericardiocentesis was done immediately and 100 ml pericardial effusion was removed. Transiently he became alert, however, irreversible cardiac arrest occurred on day 2. Postmortem examination revealed thickened left ventricles with intramyocardial hemorrhage. It seems necessary to reduce CY, or substitute it with anti-thymocyte globulin (ATG) or TBI etc. for BMT in aplastic anemia accompanied by hemochromatosis.

Adult↗
PubMed1996

Response to immunosuppressive therapy and an HLA-DRB1 allele in patients with aplastic anaemia: HLA-DRB1*1501 does not predict response to antithymocyte globulin.

HLA-DRB1*1501, a subtype of HLA-DR2, has been shown to be closely associated with a good response to cyclosporine (CyA) therapy in patients with aplastic anaemia (AA). To determine whether this DRB1 allele can also predict a response to antithymocyte globulin (ATG) therapy in AA patients, we analysed the results of HLA-DRB1 typing in 59 Japanese patients who received ATG within 2 years after diagnosis of AA and also in 52 patients treated with CyA. All patients were divided into three groups: those with DRB1*1501, those with DRB1*1502, and those without either of these two alleles (DR2-). The response rate to ATG in DRB1*1501+ patients (56%) was not significantly higher than that in DRB1*1502+ patients (47%) and in the other DR2- patients (54%). In contrast, the response rate to CyA therapy in DRB1*1501+ patients (92%) was significantly higher than that in the DRB1*1502+ (41%) and in DR2- patients (57%). Multivariate analysis revealed that possessing DRB1*1501 was an independent factor significantly predictive of a good response to CyA. These results indicate that although identifying the DRB1*1501 allele in AA patients prior to therapy is predictive of a good response to CyA therapy, it does not have a predictive value for ATG therapy.

Adolescent↗
PubMed1996

Relative erythroid hyperplasia in the bone marrow at diagnosis of aplastic anaemia: a predictive marker for a favourable response to cyclosporine therapy.

Predicting the treatment response of aplastic anaemia (AA) is essential when considering cyclosporine (CyA) therapy among several treatment options, because it requires at least 2 months determine whether the therapy is beneficial to a patient with AA. To identify the characteristics of patients with AA who are likely to respond to CyA therapy we retrospectively reviewed the clinical records and bone marrow smears of patients treated with CyA. Among 30 patients who received the therapy for at least 3 months within 1 year after diagnosis of AA, and who had not been exposed to antilymphocyte or antithymocyte globulin, 16 (53%) responded with disease remission. CyA-responsive patients had a significantly higher ratio of erythroblasts to granulocytes (E/G ratio) in the bone marrow at the time of diagnosis as compared with patients refractory to therapy (P = 0.004). Multivariate analysis revealed that a high E/G ratio ( > 0.6) was significantly associated with a good response to CyA (P = 0.03): 15 (83%) of the 18 patients with an E/G ratio > 0.6 responded, but only one (8%) of the 12 with an E/G ratio > or = 0.6 did. Although the presence of subclinical paroxysmal nocturnal haemoglobinuria was suspected from the relative erythroblastosis observed in the bone marrow of these patients, flow cytometric analysis of neutrophils in the peripheral blood failed to reveal neutrophils deficient for glycosyl-phosphatidylinositol (GPI) anchored membrane proteins in all but one case. Identification of the presence of relative erythroid hyperplasia in he bone marrow when AA is diagnosed may help to predict a favourable response to CyA therapy, and therefore facilitate the selection of optimal therapy for AA.

Adolescent↗
PubMed1996

-Rejection of an allogeneic bone marrow graft following successful treatment of severe graft-versus-host disease (GVHD).

A 38-year-old female with acute myelogenous leukemia (M2) received an allogeneic bone marrow graft from an HLA-DR one locus-mismatched sister during the first remission. The conditioning regimen consisted of busulfan and cyclophosphamide. Acute graft-versus-host disease (GVHD) developed on day 11 after transplantation. Although the GVHD was successfully treated with methylprednisolone, peripheral blood neutrophils that had begun to increase disappeared in association with improvement of the GVHD and graft rejection was eventually diagnosed. The second bone marrow transplantation from the same donor ended up with engraftment failure. She died of sepsis due to Candida albicans following the development of Epstein-Barr virus-associated B-lymphoproliferative disorder. The clinical course of this patient indicates that successful therapy of severe GVHD with methylprednisolone may lead to marrow graft rejection.

Acute Disease↗