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Biomedical subjects

T Mizushima

Publications and source records attributed to T Mizushima.

8 recordsLinked to original sources

Inhibition of Escherichia coli DNA topoisomerase I activity by phospholipids.

The DNA relaxation activity of Escherichia coli DNA topoisomerase I in vitro was greatly inhibited by cardiolipin. Inhibition also occurred to some extent with phosphatidylglycerol from egg yolk. Analysis with synthetic phospholipid revealed that phosphatidylglycerol containing unsaturated fatty acids exhibited a strong inhibitory effect, whereas inhibition by phosphatidylglycerol containing saturated fatty acids was weak. Phosphatidylethanolamine showed no inhibitory effect. Chlorpromazine, which interacts with phospholipids, suppressed the inhibitory effect of cardiolipin. Cardiolipin and phosphatidylglycerol with unsaturated fatty acid precipitated topoisomerase I even at low concentrations, whereas phosphatidylglycerol from egg yolk and a synthetic phosphatidylglycerol containing saturated fatty acids precipitated this enzyme only at high concentrations. One-third of the total topoisomerase I in E. coli was found in the membrane fraction. Treatment of E. coli cells with chlorpromazine resulted in relaxation of plasmid DNA. This DNA relaxation was not observed in a topA mutant, suggesting that this relaxation by chlorpromazine in vivo is catalysed by topoisomerase I.

Chlorpromazine

Induction by psychotropic drugs and local anesthetics of DnaK and GroEL proteins in Escherichia coli.

We examined effects of psychotropic drugs and local anesthetics on the synthesis of heat shock proteins in Escherichia coli. Chlorpromazine, a phenothiazine derivative, was shown to induce DnaK and GroEL proteins, major heat shock proteins in E. coli. The inductions of these proteins were not observed in an rpoH (= htpR) amber mutant strain, indicating that the heat shock sigma factor sigma 32 was required for their inductions. Northern blot hybridization analysis revealed that chlorpromazine induced increases of messenger RNAs for the DnaK and GroEL proteins. Thus, the induction occurred at the level of transcription. Chlorpromazine also induced non-heat shock proteins with molecular masses of 21 kDa, 20 kDa, and 17 kDa, even in the rpoH mutant strain. Other psychotropic drugs and local anesthetics, namely, dibucaine, lidocaine, imipramine, tetracaine and procaine, also induced DnaK and GroEL proteins and the small molecular weight proteins.

Anesthetics, Local

Decrease by psychotropic drugs and local anaesthetics of membrane fluidity measured by fluorescence anisotropy in Escherichia coli.

The effects of psychotropic drugs and local anaesthetics on the fluidity of Escherichia coli cell membranes were examined. Chlorpromazine was shown to increase 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, indicating that it decreased the membrane fluidity. This increase was significant at a temperature of more than 24 degrees C. Dibucaine, lignocaine, imipramine, tetracaine and procaine also increased the fluorescence anisotropy.

Anesthetics, Local

Histological changes in recurrent soft tissue sarcomas: analysis of 56 patients.

Histological changes in 56 patients with recurrent soft tissue sarcomas (STS) were analysed. The original tumors included 23 malignant fibrous histiocytomas, five liposarcomas, four leiomyosarcomas, four synovial sarcomas, four neurogenic sarcomas, four dermatofibrosarcomas and 12 other assorted tumor types. The histological features of the recurrent tumors which underwent changes included increased cellularity, an increased number of mitotic figures, extension of sclerotic areas and the appearance of a storiform pattern; these were found in 30%, 43%, 41% and 29% of cases, respectively. No case showed a histological change from one subtype to another. A follow-up study revealed increased cellularity and mitotic counts in the recurrent tumors to be signs of an unfavorable prognosis.

Adolescent

Treatment for osteosarcoma--a study of thirty-two patients treated with systemic chemotherapy and radical surgery.

Thirty-two patients with osteosarcoma of the femur and the tibia were treated with systemic chemotherapy and radical surgery between 1976 and 1984. Adriamycin (ADR) alone, ADR plus high-dose methotrexate with citrovorum factor (HD-MTX-CF) (protocol A) and ADR plus HD-MTX-CF plus cis-platinum plus bleomycin, cyclophosphamide and actinomycin-D (BCD) (protocol B) were given as chemotherapeutic regimens. Twenty-nine out of 32 patients received chemotherapy both preoperatively and postoperatively, and eleven of 29 patients had a good response. Amputation was performed on 19 patients and en bloc resection on 13 patients. No local recurrence was detected in any of the 32 patients. The disease-free survival rate was 35%. Disease-free survival rate of patients treated with protocol A and protocol B was 25% and 91% respectively. Fourteen out of 17 patients who developed pulmonary metastasis underwent thoracotomy. Survival rate after thoracotomy was 50%. The overall survival rate of 32 patients with osteosarcoma was 56%.

Adolescent

Treatment of mucopolysaccharidosis: clinical and biochemical aspects of leucocyte transfusion as compared with plasma infusion in patients with Hurler's and Scheie's syndromes.

The therapeutic effectiveness of leucocyte transfusion (LT) was compared with that of plasma infusion (PI) clinically by range of motion (ROM) of joints and biochemically from the standpoint of alpha-L-iduronidase activity and urinary excretion of acid mucopolysaccharides (AMPS) in 2 patients with Hurler's and Scheie's syndromes. Both syndromes are considered to be due to the lack of alpha-L-iduronidase activity, a congenital metabolic disorder. As a result, leukocyte transfusion surpasses plasma infusion with respect to enzyme content, the grade and duration of clinical improvement in the stiffness of joints. Clinical improvement in the stiffness of joints was correlated with the degradation of AMPS when the ratio of urinary AMPS fragments to the total large molecule AMPS has become 50% or more after the leucocyte transfusion and plasma infusion.

Adult