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Biomedical subjects

T Shibuya

Publications and source records attributed to T Shibuya.

At least 253 records · Page 14Linked to original sources

Treatment of myelodysplastic syndrome and atypical leukemia with low-dose aclarubicin.

To study the therapeutic effect of low-dose aclarubicin (ACR), we carried out comparative treatment of 15 patients with myelodysplastic syndrome (MDS) and atypical leukemia using this drug. Complete remission (CR) was achieved in three patients with RAEB-t and one patient with AML, partial remission was obtained in one patient with RAEB and hematological improvement in one patient with refractory anemia (RA). Interestingly, prolonged CR for more than 26 months with persistent chromosomal abnormalities was observed in a case of AML, which progressed from RA. Myelosuppression caused by low-dose ACR was milder than that caused by low-dose Ara-C. Furthermore, in vitro studies indicated that ACR induced differentiation of bone marrow cells from one patient with MDS. From these observations, it is suggested that low-dose ACR may be an alternative to low-dose Ara-C for treatment of MDS, and that the in vivo effect of ACR may be mediated by the differentiation of abnormal hemopoietic clones.

Aclarubicin↗

Brain synaptosomal Ca2+ uptake: comparison of Sprague-Dawley, Wistar-Kyoto and spontaneously hypertensive rats.

1. K(+)-stimulated 45Ca2+ uptake by synaptosomes was measured with respect to the strain differences between Sprague-Dawley (SD), Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. 45Ca2+ uptake by synaptosomes isolated from cerebral cortex of SD, WKY and SHR was measured at 15, 30, 60, 120 and 240 sec time periods. 3. The sequence of both the magnitude and rate of resting and depolarization-dependent 45Ca2+ uptake was SHR greater than WKY greater than SD. 4. The fastest rates of resting and depolarization-dependent 45Ca2+ uptake occurred in each rat during the first 15 sec and uptake rates dropped off quickly in both resting and depolarization states. 5. At 15 sec, there were significant differences between SHR and WKY, while there were no significant differences between WKY and SD. 6. The results suggest that an important alteration in Ca2+ channel characteristics may occur in SHR brain synaptosomes.

Animals↗

Acute 'bilineal-biphenotypic' leukaemia.

We describe a unique case of hybrid leukaemia with bilineal and biphenotypic features. The coexistence of lymphoblasts and monoblasts was determined morphologically and cytochemically. Immunofluorescence and immunohistochemical analysis revealed that each blast population had both T lymphoid (CD2, cytoplasmic CD3) and myeloid (CD11, CD13, CD15) markers. Southern blot analysis of DNA extracted from the lymph node biopsy demonstrated the presence of monoclonal rearrangement of the TcR-C beta gene. Cytogenetic analysis of the bone marrow cells showed a karyotype of 48, XY, 7q+ in all of the metaphases examined. These observations are suggestive of a monoclonal origin for these two distinct blast populations.

Acute Disease↗

Effect of N-methionine-free, bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in a primate model.

We demonstrate the in vivo effects of bacterially synthesized, N-methionine-free recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) using a crab-eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM-CSF (30 micrograms/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (greater than 15.0 x 10(9)/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (greater than 8 x 10(9)/l) on d 10. Readministration of rh GM-CSF (30 micrograms/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two-fold increase of granulocyte/macrophage colony-forming units was also seen in the bone marrow, while the number of burst-forming units-erythroid was not affected. These data indicate that rh GM-CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.

Animals↗

[A neurochemical study on brain cholinergic neuron; a newly improved pyrolysis gas chromatography/mass spectrometry (PY/GC/MS) method and its application].

A new method for measuring the endogenous acetylcholine (ACh) and choline (Ch) levels using a PY/GC/MS was established, and then the alteration of cholinergic neurons in the iminodipropionitrile (IDPN) induced dyskinesia model rat brain was studied. In performing the determinations of small amounts of brain ACh and Ch levels using a curie point PY/GC/MS, the following points were improved upon in the present study: 1) We shortened the distance between the sample tube and injection port allowing the rapid transformation to an analytical system without sub-reaction and re-synthesis of demethylated products. 2) The suitable pyrolytic temperature (curie point) was adjusted to 333 degrees C. 3) Then the aqueous sample (2 microliters) was wrapped in a pyrofoil with a curie point of 333 degrees C followed by drying at 80 degrees C. Subsequently, the pyrofoil was formed by a 200 kgf/cm2 press. 4) A fused silica capillary column (DB-5) was used instead of a pre-packed column (Jenden Phase). By these improvements, both calibration curves of ACh and Ch have high linearities (r = 0.988) between 1 pmol and 2 pmol, and the apparent peak of quasi-molecular ion and less fragment ion of each Ch analog was obtained. In the globus pallidus, caudate nucleus, hippocampus and cerebellum of IDPN induced dyskinesia model rats, remarkable reductions of ACh levels were observed using our newly improved PY/GC/MS method. Thus, our improved method can be utilized for measuring ACh levels in small discrete brain regions.

Acetylcholine↗

[The correlation between the activity of tissue plasminogen activator (TPA), levels of tissue plasminogen activator inhibitor (PAI-1) antigen and serum lipids in healthy subjects].

It is well known that abnormality of the coagulation-fibrinolytic system and serum lipids plays an important role in the development of thrombi and atherosclerotic disease. In the present study, the correlation between the activity of tissue plasminogen activator (TPA), the levels of tissue plasminogen activator inhibitor (PAI-1) and serum lipids (TC, TG, beta-Lp, HDLC, LDLC and apolipoproteins) were studied in 102 healthy subjects. The activity of TPA showed negative correlation with the obesity rate (r = 0.21, p less than 0.05) but levels of PAI-1 antigen showed a positive correlation with the obesity rate (r = 0.182, p less than 0.1). The activity of TPA showed no correlation with serum lipids including apolipoproteins, while the levels of PAI-1 antigen showed a positive correlation between TG and beta-Lp (r = 0.292, p less than 0.01, r = 0.211, p less than 0.05). The levels of PAI-1 antigen showed a negative correlation with HDLC (r = -0.286, p less than 0.01). These results indicate that TPA and PAI-1 play an important role in the development of thrombotic disease and atherosclerotic disease.

Adult↗

Epithelial cyst of the fourth ventricle. Case report.

A case of epithelial cyst in the fourth ventricle of a 4-year-old child is described. A single epithelial layer with a clear basement membrane lining the cyst wall was observed. There were no prominent histological findings to suggest a pathogenesis for this cyst based on immunohistochemical or ultrastructural studies; however, the cyst fluid contained significant amounts of carcinoembryonic antigen. It is considered that the epithelial layer lining the cyst wall was possibly of endodermal origin.

Brain Diseases↗

Granulocyte-macrophage colony-stimulating factor suppresses induction of neutrophil alkaline phosphatase synthesis by granulocyte colony-stimulating factor.

We evaluated the in vitro effects of recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) and rh granulocyte-macrophage CSF (GM-CSF) on neutrophil alkaline phosphatase (NAP) activity and the incorporation of amino acids into polymorphonuclear leukocytes (PMN) from normal individuals and patients with chronic myelogenous leukemia (CML). Both the NAP activity and incorporation of amino acids into PMN were enhanced by the addition of G-CSF in a dose-dependent manner. NAP activity induced by G-CSF in PMN from CML patients showed a greater increase than that in PMN from normal controls. In contrast to G-CSF, GM-CSF did not affect the NAP activity in PMN in spite of the enhanced incorporation of amino acids into PMN by GM-CSF. Interestingly, both the NAP-inducing ability of G-CSF and its enhancing ability for amino acid incorporation were suppressed by GM-CSF in a dose-dependent manner when PMN were incubated with various concentrations of GM-CSF in addition to 100 ng/ml of G-CSF. These observations suggest that G-CSF and GM-CSF act differently: G-CSF induces NAP synthesis in PMN, whereas GM-CSF negatively modulates the effect of G-CSF. Further, it is suggested that protein synthesis induced by G-CSF is negatively modulated by GM-CSF in a general fashion.

Alkaline Phosphatase↗

[Adult T-cell leukemia/lymphoma associated with unusual positivity of anti-ATLA (adult T-cell leukemia-cell-associated antigen) antibodies].

A 56-year-old female was admitted because of generalized lymphadenopathy. Based upon histological findings of biopsied lymph node, malignant lymphoma, diffuse large cell type was diagnosed. The surface marker analysis showed that malignant cells were positive for CD4 and CD2 but negative for CD8. Although anti-ATLA (adult T-cell leukemia associated antigen) antibody was negative with the use of a gelatin particle agglutination method (P.A.), other methods such as an indirect immunofluorescence assay (I.F.), an enzyme-linked immunosorbent assay (E.I.A.) and a Western blotting assay revealed the positivity for anti-ATLA antibody. Adult T-cell leukemia/lymphoma (ATL/L) was confirmed by the presence of monoclonal integration of HTLV-I proviral DNA in biopsied specimen. This case, showing a pattern of P.A. (-) and I.F. (+), is extremely unusual, because I.F. and P.A. show highly close correlation. Thus, it is important to employ different methods for screening of anti-ATLA antibodies in the diagnosis of ATL/L.

Agglutination Tests↗

Drug sensitivity test for acute myeloblastic leukemia by an efficient leukemic blast colony assay using 5637-conditioned medium as a stimulator.

Drug sensitivity of clonogenic leukemic blast cells was measured using the leukemic blast colony formation technique. Each of three chemotherapeutic agents, cytosine arabinoside, daunorubicin and aclarubicin, was added at the start of culture, and sensitivity was measured in terms of numbers of surviving leukemic blast colonies formed under continuous exposure to the drug. A substantial number of colonies was observed in all cases examined when the conditioned medium of human bladder carcinoma cell line 5637 was used as the leukemic blast colony stimulator. Although drug sensitivity varied considerably among the cases examined, sensitivity to administered drugs in clinical non-responders was significantly poorer than that in clinical responders (p less than 0.05).

Aclarubicin↗

Sonographic diagnosis of venocclusive disease of the liver and danazol therapy for autoimmune thrombocytopenia in an autologous marrow transplant patient.

A 16-Year-old boy with lymphoblastic lymphoma underwent an autologous bone marrow transplantation (ABMT) after conditioning with high-dose busulfan and cyclophosphamide. On day 39 post-transplant, right upper quadrant pain occurred with an increase in the size of the liver. Liver function tests showed a subsequent deterioration. Ultrasonographic studies of the abdomen disclosed hepatosplenomegaly, ascites, thickening of the gall bladder wall and a failure to visualize the major hepatic veins. The venocclusive disease of the liver (VOD) diagnosis was confirmed from these findings. Ultrasonographic monitoring reflected the disease status well and demonstrated a complete recovery from the VOD. We emphasize, thus, that abdominal ultrasonography can be applied easily, being a non-invasive procedure, and is useful in diagnosing VOD. Furthermore, the procedure can be repeated serially for evaluating the severity of VOD. Although engraftment was confirmed with granulocytes exceeding 500/microliters, platelet recovery was delayed; the megakaryocytes had not decreased in bone marrow aspirates and platelet-associated IgG was significantly elevated. Since autoimmune thrombocytopenia was highly suspected, to prevent immunosuppression danazol was given as an immune modulator instead of prednisolone, and a complete recovery was obtained. Accordingly, danazol can be used as an alternative to prednisolone for the treatment of autoimmune thrombocytopenia after bone marrow transplantation.

Adolescent↗

[Prevention of progression of coronary atherosclerosis by drug and diet therapy].

In 102 patients with ischemic heart disease the severity of stenosis was classified into 7 grades (0, 25, 50, 75, 90, 99, 100%) in accordance with the AHA reporting system. The coronary angiograms were compared at first and second catheterization (intervals 2-84 months) and progression was considered present if the stenosis in the second study showed more than one grade increase in comparison with the first study. Fifty six patients met criteria for progression. Risk factors were obtained within the first second catheterization. Drug and diet therapy were evaluated by interview. No significant difference could be found between the progression (P) group and the nonprogression (N) group in relation to family history and obesity. A history of hypertension was more common in the P group. In respect to blood sampling, the values of total cholesterol, Apo B, CII, E and Apo B/AI were significantly higher in the P group than those in the N group at first and second catheterization. The percentage of patients showing abnormal levels of blood sugar and lipid were higher in the P group than the N group although the percentage of patients with drug and diet therapy were higher in the P group than in the N group. The percentage of patients with diet therapy for hyperglycemia and hyperlipidemia were higher in the P group, however weight increase was more common in the P group. These data suggest that sufficient diet and drug therapy is necessary for patients with risk factors.

Adult↗

[Transient dysfibrinogenemia and cerebral thrombosis following remission induction therapy for acute lymphoblastic leukemia].

A 38-year-old female with acute lymphoblastic leukemia developed monoplegia of the left upper extremity following chemotherapy for remission induction consisting of vincristine, prednisolone, cyclophosphamide, adriamycin and methotrexate. Hemorrhagic infarction due to thrombosis of the right cortical vein was diagnosed by brain images using computed tomography and magnetic resonance imaging in addition to the clinical course. At this time, a plasma level of fibrinogen measured by the thrombin time method had decreased to 84 mg/dl, while its antigenicity was 276 mg/dl. There was no evidence of activation of the blood coagulation and fibrinolysis system nor of abnormal liver function. A mixing test with normal plasma disclosed the absence of an inhibitory factor against fibrin polymerization in her plasma. Fibrinogen levels as assessed by the thrombin time method recovered to the antigenicity level one and half months later. The discrepancy between the activity and antigenicity of fibrinogen indicated the occurrence of acquired dysfibrinogenemia, probably induced by antileukemic agents. Thus, it is suggested that dysfibrinogenemia is a possible cause of cerebral thrombosis in this patient.

Adult↗

[Effect of topical injections of native alpha-interferon (HLBI) in the treatment of skin lesions of adult T cell leukemia: report of a case].

A case of adult T cell leukemia associated with prominent skin infiltrations was treated with native alpha-interferon (Human lymphoblastoid interferon; HLBI). Although previous therapy with intramuscular injections of HLBI showed no effect on the skin lesions, this time topical injections of HLBI induced regression and disappearance of skin lesions within one month. Cellular immunity in this patient evaluated by PPD reaction and PHA blastoid transformation had been depressed at the time of systemic administrations of HLBI, but at the beginning of the topical injections of HLBI, they were within normal range. CD4/CD8 ratio reversed to 0.86 after topical injections of HLBI, suggesting the effect of HLBI on cytotoxic T lymphocyte activation. Thus, topical subcutaneous injections of HLBI may be an alternative form of therapy for ATL skin infiltrations when systemic HLBI administration is not effective, especially for the patient with normal cellular immunity.

Aged↗