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Biomedical subjects

T Hashida

Publications and source records attributed to T Hashida.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Antagonism of diazepam-induced sedative effects by flumazenil in patients after surgery under lumbar spinal or epidural anesthesia].

The efficacy and general safety of flumazenil (YM684), a specific benzodiazepine antagonist, have been evaluated. Forty-seven patients scheduled for surgery under lumbar spinal or epidural anesthesia with diazepam sedation received flumazenil at the end of the procedure. Criteria of efficacy were the degree of sedation and antegrade amnesia. Before injection all patients were heavily sedated with the mean dose of 27 mg of diazepam (range 10-50 mg). After the mean dose of 0.21 mg of flumazenil (range 0.2-0.4 mg), all patients were awake or drowsy within 1-6 min but sedation recurred in one patient 1 hour later. The amnesia was eliminated by flumazenil in 34 patients (72%). No serious side-effects or hemodynamic changes were observed after flumazenil. It is concluded that flumazenil is an effective antagonist of sedation induced by diazepam.

Adult↗
PubMed1989

Effect of cyclosporine on oxidative phosphorylation and adenylate energy charge of regenerating rat liver.

The effect of cyclosporin A (CyA) on regenerating liver was investigated in subtotal hepatectomized rats treated with CyA in terms of mitochondrial phosphorylative activity, hepatic energy charge, and serum bilirubin levels. In the CyA-treated hepatectomized group, the energy charge decreased from normal control value of 0.857 to 0.782 at 6 h after hepatectomy. The decreased energy charge, however, gradually increased and returned to 0.842 at 48 h after hepatectomy with no significant changes being observed between CyA-treated and untreated hepatectomized groups. Phosphorylation rate in the CyA-untreated group increased to 142% of the normal control at 24 h and then decreased to 114% at 48 h after hepatectomy. By contrast, phosphorylation rate in the CyA-treated group increased to 144% of the normal control at 24 h, but remained at the high value of 132% (P less than 0.01; compared to the CyA-untreated group) even at 48 h after hepatectomy. Serum total bilirubin levels in the CyA-treated group were significantly higher than those in the CyA-untreated group during all experimental periods. We conclude that CyA does not exert a direct detrimental effect on mitochondrial function and that, despite the marked hyperbilirubinemia induced by CyA, the mitochondrial phosphorylative activity increases adaptively to provide sufficient energy for enhanced ATP-utilizing reactions in an early process of liver regeneration.

Adenine Nucleotides↗
PubMed1989

Immunological treatment with low dosage ciclosporin in rat liver allotransplantation.

Ciclosporin (CsA) was administered subcutaneously at a dose of 3 mg/kg body weight/day from the day of operation to 14 days of liver allotransplantation in ACI rat (RT1a) to LEW rat (RT1(l) strain combination. All LEW recipients of ACI liver transplants without immunosuppressive treatment had severe rejection and expired within 12 days. In contrast, 7 out of 9 recipients in the same strain combination with temporary CsA treatment survived indefinitely. Histologically, widespread cellular infiltration and massive hepatocyte necrosis were evident upon autopsy of the recipients without CsA treatment. In contrast, in the surviving rats of the CsA-treated group, mononuclear cell infiltration was restricted to the periportal field and hepatocytes appeared to be normal at 14 days posttransplant. CsA concentrations in whole blood were determined by high-performance liquid chromatography. The trough levels were 788 +/- 48, 621 +/- 76 and 546 +/- 52 ng/ml, at 5, 10 and 14 days posttransplant, respectively. We concluded that this relatively low-dose subcutaneous administration of CsA offered adequate immunosuppression in rat liver allotransplantation in this strain combination.

Animals↗
PubMed1989

[Appearance of Philadelphia chromosome at relapse of erythroleukemia in a 12-year-old boy].

A 12-year-old boy was referred to our hospital because of anemia and jaundice. On admission bone marrow smears were compatible with M6 classification of the FAB, revealing 74.5% erythroblasts of all nucleated cells and 40% blasts of nonerythroid cells. Karyotype analysis revealed 46, XY. Gene rearrangement within the breakpoint cluster region (bcr) on chromosome 22 was negative at this time. Complete remission was attained by a combination chemotherapy. However, at 10 months of remission, cytogenetic studies of the bone marrow demonstrated Ph1 positive (10%). One month later, the patient fully relapsed with a 75% Ph1 positive karyotype associated with positive bcr. Subsequently, the patient died of refractory leukemia.

Child↗
PubMed1988

Role of adenosine 3'5'-cyclic monophosphate in antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1) on human neuroblastoma cells.

To determine the role of adenosine 3'5'-cyclic monophosphate (cAMP) in the antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1), we studied 2 cell lines of human neuroblastoma; i.e. GOTO and SK-N-DZ. PGE1 or E2 at 30 micrograms/ml and PGD2 or PGA1 at 5 micrograms/ml were cytotoxic to these neuroblastoma cells. In both cell lines, increase of intracellular cAMP was closely associated with E-type PGs cytotoxicity, however, in PGD2, or PGA1 cytotoxicity, cAMP increase was observed only in GOTO cells. Pretreatment of GOTO cells with 5 micrograms/ml PGE2 for 24 hr caused a desensitization of cAMP responses to PGE1, PGD2 or PGA1 only in association with a reduced cytotoxicity of PGE1. On the other hand, PGE2-pretreated SK-N-DZ cells resulted in a desensitization in response to PGE1, but not to other PGs, without affecting the cytotoxicity of these PGs. A decreased [3H]PGE1 binding similarly occurred in either the PGE2-pretreated GOTO or SK-N-DZ cells. However, cholera toxin- or forskolin-induced cAMP production was suppressed only in the pretreated GOTO cells. cAMP response by forskolin rather increased in the pretreated SK-N-DZ cells. These results indicate that antineoplastic effect of E type PGs mediates through cAMP, but not that of PGD2 and PGA1 and that PGE2 pretreatment may cause a down regulation of PGE1 receptor site in both cell lines. It is also suggested that PGE2 pretreatment results in a heterologous desensitization in GOTO and a homologous desensitization in SK-N-DZ cells.

Alprostadil↗
PubMed1987

[Clinical features and therapeutic results in 14 cases of malignant histiocytosis in childhood].

Fourteen children, 4 males and 10 females, with malignant histiocytosis (MH) were treated between July 1980 and June 1986. None of them had an affected sibling with a similar disorder. Septic-type fever was the most prominent symptom in all cases. Hepatosplenomegaly was present in 13 cases, lymphadenopathy, skin rash and jaundice in 8, pulmonary infiltration or pleural effusion on chest X-ray in 8, convulsion in 6, and renal involvement in 5 out of the 14 cases. Disseminated intravascular coagulation (DIC) was seen in 13 cases and this occurred within two weeks from onset in 6 cases. Pancytopenia, abnormal results of liver function tests, hypofibrinogenemia and hypocholesterolemia were common. The diagnosis was made for all 14 cases by characteristic clinical symptoms, signs, and bone marrow findings. In 8 cases, biopsy or autopsy specimens confirmed the diagnosis. Two patients died prior to chemotherapy. Twelve patients were treated with adriamycin, cyclophosphamide, vincristine and prednisone (ACOP). Complete response (CR) was achieved in five patients, and another two patients attained CR after subsequent treatment with other combinations including VP 16-213. These 7 complete responders are now alive and free of disease 11+ to 70+ months (median, 50+ months) from the onset of disease. All partial and non-responders died within 6 months with a median survival of 20 days. Among several clinical features as prognostic indicators, renal involvement, convulsion, and DIC occurring within 2 weeks were significantly related to poor outcome. Although MH is an aggressive disease with a poor prognosis, prompt diagnosis and early treatment with intensive systemic combination chemotherapy should further improve the outcome.

Adolescent↗
PubMed1986

Plasma membranes purified from myeloid leukemia cells before and after differentiation. I. Characterization of spectrin-like proteins and increased association of actin.

Two-step sucrose density gradient centrifugation was used to isolate the plasma membrane of a myeloid leukemia cell line (Ml). Calspectin (or fodrin) was identified in the Triton-insoluble fraction from the plasma membrane, and the molecular size and actin- and calmodulin-binding activity were studied. During differentiation of this cell line, which accompanied the induction of cell motility and phagocytic activity, the membrane-bound actin increased dramatically, whereas calspectin increased only slightly. Therefore, calspectin does not appear to have a major function in the increased binding of actin filaments to the plasma membrane, a requirement for the induction of cell motility.

Acid Phosphatase↗
PubMed1986

Cell kinetic studies of PGD2 cytotoxicity on the in vitro growth of human neuroblastoma.

To determine the mechanism of the antineoplastic effect of PGD2, we studied the intracellular adenosine 3',5'-cyclic monophosphate (cAMP), cell growth and the kinetics of a human neuroblastoma (NCG line) in culture. Cells were maintained in RPMI 1640 with 10% FCS. cAMP level was determined for the cells, which were incubated for 10 min. with and without PGD2 (1 microgram/ml) in the presence of 100 microM papaverine. Growth inhibition was examined by counting viable cells after treatment with PGD2 (0-100 micrograms/ml) for 4 consecutive days starting at Day 4 after subculture. Effects on cell kinetics were examined for similarly treated cells by DNA cytofluorometry combined with 3H-thymidine autoradiography. In response to PGD2, the NCG line failed to increase its cAMP; however, cell growth was inhibited (IC50 13 micrograms/ml), accompanied by the marked decrease of S phase cells. The results indicate that PGD2 exerts its cytotoxic effect by a probable G1 block of the cell cycle and not through cAMP action.

Antineoplastic Agents↗
PubMed1986

Malignant histiocytosis in childhood. Clinical features and therapeutic results by combination chemotherapy.

Ten children, four males and six females, with malignant histiocytosis were treated from July 1980 to July 1984. None of them had an affected sibling with a similar disorder. Septic-type fever, hepatosplenomegaly, lymphadenopathy, pulmonary infiltration, and disseminated intravascular coagulation were common signs and symptoms, and convulsion occurred in four cases. The diagnosis was made from bone marrow smears in all cases. In five cases, biopsy or autopsy specimens confirmed the diagnosis. In five cases studied, proliferating histiocytes in lymph nodes were demonstrated to be S100 protein-positive. All patients were treated with adriamycin, cyclophosphamide, vincristine, and prednisone (ACOP). Complete response was achieved in four patients after two to three courses of ACOP, and another case attained complete remission after further drug treatment. The five complete responders are now alive without evidence of disease after 23-48 months from the onset. Among partial and no responders, four died within 3 months and one has been alive with disease for 2 months. Bone marrow aspiration is useful for prompt diagnosis, and early treatment with intensive combination chemotherapy improves the prognosis of malignant histiocytosis in childhood.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

[Improved results of treatment in 30 cases of acute nonlymphocytic leukemia in childhood].

Thirty cases of childhood acute nonlymphocytic leukemia (ANLL) have been treated with intermittent, intensive multi-drug combinations during the past 5 years. Three patients never attained complete remission (CR) and 3 died of complications after less than one month of treatment. Twenty-four (86.7 %) attained CR with a median CCR of 26 months. The median for disease-free survival (DFS) among the total 30 cases was 15 months. Twelve out of the 24 CR patients have been disease-free for longer than 16 months, indicating significantly improved therapeutic results. Among the factors affecting prognosis, we found that patients with certain clonal abnormalities of leukemic cells and initial leukocytosis (greater than 40,000/microliter) had poor prognosis. Further revision of treatment should be considered for patients with high-risk ANLL.

Acute Disease↗
PubMed1985

Characterization of meiosis-deficient mutants by electron microscopy and mapping of four essential genes in the fission yeast Schizosaccharomyces pombe.

Meiosis-deficient mutants of the fission yeast Schizosaccharomyces pombe carrying mei1, mei2, mei3, mei4 and mes1 mutant alleles were characterized by electron microscopy and staining of the nucleus with 4', 6-diamidino-2-phenylindole. Zygotes of either mei1, mei2 or mei3 mutants contained one round nucleus with a single spindle pole body (SPB). These mutants were arrested before premeiotic DNA synthesis. Zygotes of mei4 mutants had one elongated nucleus containing thick electron-dense filaments (linear elements). In the mes1 mutant, the first meiotic division was completed but the SBPs did not duplicate. Modification of the SPB (outer plaque formation) was also blocked and the forespore membrane was not assembled. By haploidization, random spore and tetrad analyses, four essential genes for meiosis (mei2, mei3, mei4 and mes1) were mapped. Gene mei2 was located on chromosome I 14.2 cM distant from ura2. Gene mei3 was linked to ade7 (45.4 cM) on chromosome II. Gene mei4 was linked to cdc2 (0.6 cM) on chromosome II. Gene mes1 was linked to ura3 (25.3 cM) on chromosome I.

Ascomycota↗
PubMed1985

Therapeutic effects of human leukocyte interferon on chronic active hepatitis B in children.

Seven children with chronic active hepatitis (CAH) and one child with persistently abnormal results of liver function test due to hepatitis B virus (HBV) infection were treated with human leukocyte interferon (Hu-alpha-IFN). Five of them were positive for eAg and two of the three who were measured for DNA polymerase (DNAP) activity in sera showed moderate elevations of its levels. Hu-alpha-IFN was injected intramuscularly daily or once weekly at doses of 0.05-1 X 10(6) IU. The total dose per patient varied from 10.5-54 X 10(6) IU. After administration of Hu-alpha-IFN, rapid loss of eAg was observed in two of the five eAg patients, and DNAP activity reverted to normal ranges in the two patients with moderate elevations of its levels. One of the patients who lost eAg has retained normal serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels for more than 2 years after therapy with Hu-alpha-IFN. Serial hepatic biopsies were performed in only one patient. In the second biopsy, 3 months after therapy with Hu-alpha-IFN, infiltration of inflammatory cells in the portal region was improved compared with earlier findings. Immediate and/or prolonged adverse side effects were not observed during or after administration of Hu-alpha-IFN. For the present, we propose these six conditions for use of Hu-alpha-IFN in children with HBV infection. Children should: (a) be more than 1 year old; (b) have abnormal liver function for more than 6 months; (c) have a liver biopsy demonstrating CAH; (d) have moderate elevation of DNAP activity; (e) be eAg positive; and (f) be unresponsive to other treatments.

Child↗
PubMed1985

A monovalent cation-sensitive actin-binding factor in a myeloid leukemia cell line.

Cell extracts of a murine leukemia cell line, M1, apparently contain three kinds of actin-gelation factors; a filamin-like protein, and 38K-dimer and 105K-dimer proteins. Unlike gelation by the filamin-like protein, gelation by the latter two proteins is inhibited by low concentrations of KCl. Our study of the 38K protein has been reported elsewhere (Takagi, K. et al., J. Biochem. Tokyo 97, 605-616, 1985). We here describe the purification and characterization of the 105K protein. The 105K protein differs from the alpha-actinin group of proteins in its antigenicity, peptide components and Ca2+-insensitivity. The saturated binding ratio of the protein to purified skeletal muscle actin is 1:8; when this ratio exceeds 1:20, gelation takes place. This gelation is inhibited completely by the presence of 25 mM KCl. Electron microscopy revealed that, in the absence of KCl, the 105K protein/actin mixture forms short actin bundles that are accompanied by a meshwork of short single filaments. The presence of 25 mM KCl did not prevent actin-bundling, but the bundles became longer and the meshwork of short filaments was no longer present.

Actins↗