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Biomedical subjects

M Tsuchida

Publications and source records attributed to M Tsuchida.

At least 73 records · Page 4Linked to original sources

[Infant leukemia with t(1;22) presenting proliferation of erythroid and megakaryocytic cell lineages].

We report a case of infant leukemia with the proliferation of both erythroblast and megakaryoblast lineages. The blasts became double-positive for both erythroblastic and megakaryoblastic surface markers at the time of bone marrow relapse. A 9-month-old girl was admitted to our hospital presenting chiefly poor with weight gain and anemia. She also had splenomegaly, pleural effusion, leukocytosis, and thrombocytopenia. A bone marrow specimen showed 53.2% erythroblasts (PAS positive, alpha-NA positive, CD41 negative, MPO negative) and 20.4% megakaryoblasts with marked cytoplasmic blebs. We examined specimens by two-color flow cytometric analysis. At the onset, CD41+ glycophorin A- fraction and CD41- glycophorin A+ fraction were two major components. At the bone marrow relapse, the majority of blasts had altered to double-positive. Chromosomal analysis showed t (1; 22) (p13; q13), which has been reported to be specific for acute megakaryoblastic leukemia (M7) in infants. We reasoned that a leukemia had occurred in this patient at a progenitor cell level common to both erythroid and megakaryocytic lineages.

Bone Marrow Cells↗

[A case of thoracoscopic resection of a pulmonary infarction mimicking a metastatic lung tumor].

We report here a rare case of pulmonary infarction which was resected as a metastatic pulmonary tumor. A 57-year-old male patient referred for exhibiting an abnormal shadow on chest X-ray 8 months after the resection of invasive adrenal tumor. The patient underwent thoracoscopic resection of the lesion as a metastatic tumor. However, intraoperative pathological examination revealed that the resected specimen was pulmonary infarction. Post-operative MRI and ultrasound images showed no evidence of venous thrombus. Pulmonary infarction can exhibit an abnormal shadow in the lung fields, and it is necessary to be distinguished from true tumor.

Diagnosis, Differential↗

Clinical and biological aspects of acute lymphoblastic leukemia in 62 infants: retrospective analysis of the Tokyo Children's Cancer Study Group.

BACKGROUND: As a first step to formulate a new treatment strategy for refractory acute lymphoblastic leukemia (ALL) in infants, clinical results and immunophenotypic and cytogenetic data were analyzed and compared with those from overseas. METHODS: There were 62 infants with ALL who were treated between 1977 and 1995 at 30 institutions affiliated with the Tokyo Children's Cancer Study Group. Clinical and laboratory data obtained from these infants (all under 1 year of age) were retrospectively studied. RESULTS: The morphological diagnoses were FAB-L1 for 51 patients (82.2%) and FAB-L2 for 11 patients (17.8%). Hepatomegaly and splenomegaly were found in 40 (70.0%) and 40 patients (68.3%), respectively. The mean (+/- SEM) leukocyte count at diagnosis was 205,900 +/- 35,700/microL. The involvement of the central nervous system was evident in nine of 36 patients who were subjected to lumbar puncture, while three of these nine patients were free of neurological symptoms at diagnosis. Thirty-one patients (55.4%) were CD10 negative and 14 (25.0%) were CD10 positive. Thirty-one of 47 patients (65.9%) exhibited chromosomal abnormalities, including 28 patients (59.6%) with 11q23 abnormalities. Rearrangements in the MLL gene were found in nine of 13 infants (69.2%) examined. Translocation of 11q23 and/or MLL gene rearrangement (11q23/MLL) was significantly associated with the absence of the CD10 antigen. Hyperleukocytosis of more than 50,000/microL and 11q23/MLL gene rearrangements were related to a poor prognosis. The probability of an event-free survival in 62 infants was 13.1 +/- 4.8% at 48 months. CONCLUSIONS: New therapeutic strategies and large-scale cooperative prospective trials are needed to improve the prognosis of ALL in infants.

Chromosomes, Human, Pair 11↗

Clinical application of a fiberscope for periodontal lesions: case reports.

In dentistry, the endoscope has generally been used to visualize inaccessible areas, e.g., inside root canals or coronal surfaces of teeth; however, it has not been used in periodontally diseased lesions. In this study, a newly designed fine fiberscope (0.8- to 1.0-mm outer diameter) with an irrigation system was used to visualize root surfaces and periodontal tissues affected by periodontal disease. The fiberscope was inserted through fistulas, periodontal pockets, or root furcations in 5 patients to provide clear operational views without the obstruction of blood or soft tissues. The irrigation system of the endoscope effectively allowed differentiation of hard and soft tissues as well as restorative materials. The fiberscope system developed in this study was effective for diagnosis, for enhancing visualization for periodontal surgery, and for treating lesions such as fistulous tracts or furcation lesions.

Adult↗

Safety evaluation of Nostoc flagelliforme (nostocales, Cyanophyceae) as a potential food.

The safety of the alga genus Nostoc flagelliforme Born. etFlah. as a human food source was evaluated in an oral acute toxicity study and in a 28-day oral subacute toxicity study using rats. In the acute toxicity study, the dried powder of N. flagelliforme was orally administered to male and female rats at a dose of 1250 mg/kg and 2500 mg/kg. Neither mortality nor changes in general condition were observed in either the study groups or the control group over a 14-day observation period. In the subacute toxicity study, N. flagelliforme powder was administered orally to male and female rats at a dose of 500 mg/kg and 1000 mg/kg for a period of 28 days. Neither mortality nor changes in general condition were observed in either the treatment group or the control group throughout the 28-day administration period. No reduction in food consumption or body weight gain was observed in the experimental animals. Ophthalmological tests performed at the end of the administration period revealed no abnormalities within the ophthalmological parameters. In the haematological tests and serum biochemical tests performed at the time of completion of the administration period, no adverse effects of N. flagelliforme were observed. At autopsy, organ weight at the end of the experimental period and histopathological tests of specimens obtained from the autopsied animals revealed no significant influences of N. flagelliforme. In conclusion, considering the absence of adverse effects of N. flagelliforme in this study, findings in the oral acute toxicity study and the 28-day oral subacute toxicity study may indicate the safety of N. flagelliforme for human consumption. This study is in agreement with the novel nutraceutical idea "Phycophagism".

Animals↗

Primate renal transplants using immunotoxin.

BACKGROUND: T-lymphocyte depletion 7 days before transplantation with immunotoxin FN 18-CRM9 has resulted in tolerance to subsequent renal allografts. We tested the effect of giving immunotoxin on the day of the transplantation and evaluated its effect on rhesus monkey and allograft survival, on antibody production, and on T-cell recovery. METHODS: Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys. Immunotoxin was given starting on the day of transplantation, with and without prednisone and mycophenolate mofetil for 3 days. T-cell subsets and alloantibody levels were measured by flow cytometry. The ability of treated monkeys to develop antibody to tetanus, diphtheria, and xenoantibody was measured. Histology of renal transplants was read in a blinded manner. RESULTS: Immunotoxin started on the day of transplantation resulted in prolonged allograft survival in all treatment groups. Graft loss between days 50 and 135 was most often due to interstitial nephritis. Later graft loss was due to chronic rejection. Monkeys had intact antibody responses to alloantigen, tetanus, diphtheria, and xenoantibody. Their CD4 cells recovered gradually over 6 months. CONCLUSIONS: Immunotoxin reliably prolongs renal allograft survival when started on the day of transplantation, but interstitial nephritis and chronic rejection limit the development of long-term tolerance. T-cell-dependent B-cell responses remain intact after treatment.

Animals↗

[Results of surgical treatment in patients with T3 non-small cell lung cancer].

To investigate the prognosis of pathological proven T3N0-1M0 non-small cell lung cancer (NSCLC), 73 patients who underwent pulmonary resection between 1975 and 1993 were reviewed. The 5-year survival rate for all patients was 46.3%. The subject included chest wall invasion in 34 (parietal pleura 17, intercostal muscle or ribs 17), invasion to another lobe in 30, main bronchus involvement less than 2 cm distal to the carina in 12, invasion to pericardium in 6 and invasion to diaphragm in 3. The 5-year survival rates was as follows: chest wall invasion 46.7%, invasion to another lobe 51.7%, main bronchus involvement 41.7%, invasion to pericardium and diaphragm 33.3% respectively. The 5-year survival rate was 58.8% when invasion was limited within parietal pleura, whereas 35.3% when invasion extended outside intercostal muscle. Patients invaded within parietal pleura had better prognosis than that of outside intercostal muscle. In conclusion, good outcome would be expected in patients with T3N0-1M0 non-small cell lung cancer when the invasion limited within parietal pleura.

Adult↗

Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia.

The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) developed MDS/AML; 8 of these were within 36 months of the diagnosis of AA, much earlier than previous reports. Six of the 11 children received rhG-CSF exceeding 10 microg/kg/d, and 9 received rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no development of MDS/AML among 41 children treated with either CSA or rhG-CSF or among 48 children who underwent bone marrow transplantation. A well-controlled clinical trial is warranted to determine whether therapeutic modalities affect the development of MDS/AML in children with severe acquired AA.

Acute Disease↗

Delaying transplantation after total body irradiation is a simple and effective way to reduce acute graft-versus-host disease mortality after major H2 incompatible transplantation.

BACKGROUND: We have previously reported that delaying histoincompatible transplantation after total body irradiation (TBI) conditioning markedly decreased the mortality of acute graft-versus-host disease (GVHD) in severe combined immunodeficiency mice. However, it was not clear whether the delayed transplantation would affect the final engraftment and acute GVHD mortality in normal hosts. METHODS: BALB/c mice (H2d) were lethally irradiated with 8.5 Gy TBI and transplanted with C57BL/6 (H2d) bone marrow plus spleen cells on the same day (TBI+day 0) or 4 days after TBI conditioning (TBI+day 4). RESULTS: We again demonstrated that delaying transplantation by 4 days after TBI conditioning markedly reduced acute GVHD mortality in normal hosts after major histoincompatible transplantation. The survival rates were 66% in TBI+day 4 vs. 0% in TBI+day 0 allogeneic transplanted animals by day +60 (P<0.001). Further analysis demonstrated that the 4-day rest between the TBI and allogeneic transplantation broke the interaction of cell/inflammatory tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 cytokine reactions stimulated by TBI and incompatible transplantation. Flow cytometry revealed 97% donor cells in host marrow by 2 weeks in TBI+day 0 transplantation versus 57% in TBI+day 4 transplantation. There was no difference in percentage of donor CD3+ T-cell engraftment between the TBI+day 0 and TBI+day 4 allogeneic transplanted animals. In TBI+day 4 transplantation, the percentage of donor cells in host marrow steadily increased to 74% by day +60 and 93% by day +100. CONCLUSIONS: This 2- to 3-month early mixed chimerism in TBI+day 4 transplanted animals might be related to lower levels of tumor necrosis factor-alpha and IL-6 both of which have been shown to stimulate lymphohematopoiesis and was associated with lower acute GVHD mortality. The data again demonstrated in immunologically normal BALB/c mice that delaying allogeneic transplantation after TBI is a simple and effective way to reduce acute GVHD mortality, achieve satisfactory engraftment and significantly increase overall survival.

Animals↗

The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene.

The recurrent translocation t(11;16)(q23;p13) has been reported to be associated with therapy-related acute leukemia. The MLL gene involved in other 11q23 abnormalities was also rearranged by this translocation. We analyzed two patients with myelodysplastic syndrome with t(11;16) and showed that the MLL gene on 11q23 was fused with CREB-binding protein (CBP) gene on 16p13 in these patients. The CBP gene encodes a transcriptional adaptor/coactivator protein and it is mutated in patients with Rubinstein-Taybi syndrome. The CBP gene is also involved in acute myeloid leukemia (AML) with t(8;16)(p11;p13). In-frame MLL-CBP fusion transcripts combine the MLL AT-hook motifs and DNA methyltransferase homology region with a largely intact CBP. Our results combined with the finding of the MOZ-CBP fusion in t(8;16)-AML suggest that the CBP gene may be associated with leukemogenesis through translocations.

Amino Acid Sequence↗

Gianotti-Crosti syndrome associated with cytomegalovirus antigenemia after bone marrow transplantation.

Gianotti-Crosti syndrome (GCS) is characterized by a distinctive self-limiting acral papular or papulovesicular eruption associated with an underlying viral illness. It has not been previously reported in patients post-bone marrow transplantation. We report a 6-year-old Japanese boy who underwent allogeneic bone marrow transplantation from an unrelated donor for acute lymphoblastic leukemia (ALL) in second remission. He had clinical and histopathologic findings characteristic of GCS and evidence of subclinical infection with cytomegalovirus (CMV) detected by CMV antigenemia assay. It is likely that CMV is the causative agent for the GCS in this case.

Acrodermatitis↗

Synergistic cytotoxicity between a protein kinase C inhibitor, UCN-01, and monoclonal antibody to the epidermal growth factor receptor on MDA-468 cells.

Cytotoxic effect of the monoclonal antibody to the epidermal growth factor receptor (anti-EGFR MAb) given alone or in combination with UCN-01, a selective protein kinase C inhibitor, was investigated in vitro. MDA-468 human breast cancer cells expressing both a large amount of EGF receptors and its ligand, transforming growth factor a, were used. A given number of the cells were plated and treated with the MAb and/or UCN-01 for 48 h. These cells were replated and incubated for colony formation assay. Cytotoxicity of the anti-EGFR MAb alone was hardly detected. However, when cells were treated with both anti-EGFR MAb and UCN-01, the combined cytotoxic effect was synergistic.

Alkaloids↗

Effect of oral adsorbent AST-120 on cyclosporin absorption in rats.

The oral adsorbent AST-120 is used to inhibit the progression of renal failure by adsorbing uraemic toxins in the gastrointestinal tract. When AST-120 is administered to patients receiving immunosuppressive medicines, it is important to study the effect of AST-120 on the amount of these and other drugs absorbed. We have, therefore, studied the in-vitro adsorption of cyclosporin by AST-120 and investigated the effect of oral administration of AST-120 on the absorption of cyclosporin in rats. The in-vitro adsorption ratios of AST-120 for cyclosporin were more than 80%. When pure cyclosporin powder was administered with AST-120, blood cyclosporin concentrations were significantly higher than when cyclosporin was administered alone. When cyclosporin dissolved in medium-chain triglyceride was administered to rats by intramuscular injection there was no significant difference in the blood cyclosporin concentration of rats given combined AST-120 and cyclosporin and those given cyclosporin alone. There was no significant difference between the serum concentration of total bile acids, in rats receiving combined oral AST-120 and cyclosporin dissolved in olive oil, and those receiving orally solely a solution of cyclosporin dissolved in olive oil. These results suggest that oral administration of AST-120 accelerates the absorption of orally administered cyclosporin from the gastrointestinal tract and does not affect the metabolism of cyclosporin. When a solution of cyclosporin in olive oil is administered orally, however, oral administration of AST-120 has no influence on cyclosporin absorption and does not affect the enterohepatic circulation of bile acids.

Absorption↗

Effect of cardiopulmonary bypass on cytokine release and adhesion molecule expression in alveolar macrophages. Preliminary report in six cases.

Although recent studies have shown that adhesion molecules on alveolar macrophages are important in a variety of pulmonary diseases, there have been few studies on the phenotypic and functional changes of alveolar macrophages during cardiopulmonary bypass. To investigate the possible role of alveolar macrophages in activating pulmonary immunity during cardiopulmonary bypass, we measured the expression of adhesion molecules on alveolar macrophages and peripheral blood monocytes in patients undergoing cardiopulmonary bypass. Antigens were stained with monoclonal antibodies against adhesion molecules, and the expression of antigens was quantified by flow cytometry as the ratio of specific to nonspecific linear fluorescence. On alveolar macrophages obtained after the release of aortic cross-clamp, macrophages as compared with alveolar macrophages obtained before cardiopulmonary bypass, there was a significant enhancement of CD11a, CD11b, CD11c, and CD18. In addition, alveolar macrophages, but not peripheral monocytes, produced higher levels of TNF-alpha and IL-8 when they were cultured in vitro. A higher expression of CD11 and CD18 on alveolar macrophages and enhanced production of cytokines after release of the aortic cross-clamp may contribute to immune activation in lung by macrophage-lymphocyte interaction.

Adult↗

Morphological and flow cytofluorometrical analyses of regenerated rat thymus after irradiation.

Reconstituted rat thymuses were studied by immunohistochemistry, transmission electron microscopy (TEM) and flow cytofluorometry on days 0, 1, 2, 3, 5, and 7 after whole-body sublethal irradiation (6 Gy). One day after irradiation, numerous apoptotic cells were seen in the cortical thymus; the percentage of the sub-G1 peak representing apoptotic cells was 8.9% in the DNA content histogram of cytofluorometry. On day 3, the thymic structure had been destroyed and no distinction was drawn between the cortex and medulla. In this stage, few thymocytes but many macrophages were present, and the percentage of the sub-G1 peak reached a peak at 13.0%. Bromodeoxyuridine (BrdU) incorporated cells gradually increased after irradiation, and immunohistochemically numerous apoptotic cells were found primarily in the cortex on day 7. These thymocytes showed some levels of electron density of the nucleus as revealed by TEM. The percentage of S phase cells did not change markedly (20-30%) based on one-color DNA content histograms, but the percentage of early S and S phase cells was extremely high on day 7 (70%). These data indicate that a part of DNA synthetic cells may result in apoptosis. The combination of immunohistochemistry, TEM and flow cytofluorometry to analyze DNA content and BrdU incorporation proved a useful tool for investigating the reconstituted thymus.

Animals↗

[Surgical treatment of T4 lung cancer: combined resection of lung and heart or great vessels].

From 1980 to 1995, sixteen patients with T4 lung cancer underwent resection of left atrium (LA) or great vessels combined with pulmonary resection. For eight patients with lung cancer invading LA, LA was resected under simple clamp of LA in seven cases, and under extracorporeal circulation in one case. For three patients with lung cancer invading aorta, resection and reconstruction of aorta was performed under femoro-femoral bypass in one case, and under temporary bypass using a heparin-coated tube in two cases. For five patients with lung cancer invading superior vena cava (SVC), SVC was resected under partial clamp or simple clamp of SVC in each case. In remaining three patients, SVC was resected under internal bypass in one case, and under temporary bypass using a heparin-coated tube in two cases. Three were two operative deaths, one (SVC) died of acute heart failure, and the other (LA) died of acute respiratory distress syndrome. Four patients are alive without recurrence and three of them (one LA and two SVC) have been surviving more than five years after operation.

Aged↗