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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 703 records · Page 39Linked to original sources

Glutamate dehydrogenase deficiency in spinocerebellar degenerations.

Glutamate dehydrogenase (GDH) activity in leukocytes and platelets in spinocerebellar degenerations (SCD) was determined. In the same subject, GDH activity was higher and more reproducible in platelets than in leukocytes. GDH was decreased significantly in olivopontocerebellar atrophy (OPCA) (Ca. 30% decrease). Pyruvate dehydrogenase (PDH) in platelets showed non specific decreased activity in SCD and amyotropic lateral sclerosis. Energy metabolism in cerebellum may be diminished in some types of ataxia, and glutaminergic neurons may be more affected in OPCA than in other SCD.

Adult↗

Serological analysis of cell surface antigens of null cell acute lymphocytic leukemia by mouse monoclonal antibodies.

Nine antigens systems were defined. Two were related to HLA-A,B,C and to Ia-like antigens; the others could be grouped into three categories. (i) NL-22, NL-1: NL-22 antibody reacted with leukemia cells from 12 to 16 cases of null cell acute lymphocytic leukemia (null-ALL) but not with any other type of leukemia tested or with lymphoid cells of various origins. Among cultured cell lines tested, one (NALM-6) of three null-ALL cell lines was positive, the others were negative. Absorption analysis confirmed the restriction of NL-22 antigen to null-ALL. NL-1 antibody was reactive with leukemia cells from 10 to 16 cases of null-ALL and 3 of 6 cases of chronic myelocytic leukemia in blastic crisis (CML-BC). The antigen was present also on a minor population of normal lymphoid cells. The distribution and molecular weight (100,000; glycoprotein) of the NL-1 antigen resembled that of the previously described common ALL antigen (cALL). (ii) NL-30, NL-4: Both antibodies exhibited almost identical patterns of reactivities against cultured cell lines tested. They reacted with leukemia cells from some cases of null-ALL, adult T-cell leukemia, and CML-BC, although they showed discordance in their reactivities against a panel of leukemia cells, (iii) NL-9, NL-8, NL-25: These three antibodies detect serologically distinguishable determinants on a broad range of leukemias and normal lymphoid and hematopoietic cell types. The antibodies analyzed in this study provide evidence for the heterogeneity of null-ALL by demonstrating a variety of antigen phenotypes on leukemia cells. One of the antigens (NL-22) appears to be restricted to null-ALL.

Animals↗

[Optimal administration schedules of antineoplastic antibiotics based on their pharmacokinetics, with special reference to bleomycins and anthracyclines].

Optimal dose schedule of administration of antitumor antibiotics-bleomycin, adriamycin and aclacinomycin A-was reviewed from a point of view of pharmacokinetics. In case of bleomycin, according to its fast disappearance from blood, fast and significant excretion into urine, cell-cycle-dependent antitumor action, fast repair of potentially lethal damage, and pulmonary toxicity due to damage in endothelium of pulmonary capillary caused by high blood concentration of bleomycin, continuous intravenous administration seems to be a useful method to prevent pulmonary toxicity and to enhance antitumor effect. In case of adriamycin, according to its cardiotoxicity due to damage in cardiac muscle cell caused by high blood concentration on adriamycin, drip infusion or weekly low dose schedule is a safe, effective therapy to prevent cardiomyopathy. In case of aclacinomycin A, based on the mechanism of action of its marked inhibition in RNA synthesis compared to adriamycin, daily administration for certain days is an effective method.

Aclarubicin↗

[Pulmonary toxicity of antineoplastic agents--with special reference to current findings on pulmonary toxicity of bleomycin].

Pulmonary toxicity due to antitumor agents, chiefly bleomycin pulmonary toxicity including clinical feature, histopathology, pathophysiology, biochemical changes, common clinical settings (risk factors), and prevention was reviewed. Moreover, pulmonary toxicity from methotrexate, busulfan, cyclophosphamide, mitomycin C, 6-mercaptopurine, nitrosourea and procarbazine was reviewed.

Animals↗

[The effect of levamisole on non-resected lung cancer--the results of randomized controlled study].

The effect of levamisole in the treatment of 61 non-resected lung cancer-26 squamous cell ca., 8 adenocarcinoma, 13 large cell ca. and 14 small cell ca- was studied by a randomized controlled trial. Levamisole was given at a daily dose of 150 mg per body weight for 3 consecutive days every 2 weeks. The main therapy, combining polychemotherapy and radiotherapy of standard dose or low dose, was given to both levamisole and control groups. The survival rate of the levamisole group was superior to that of the control group, with median survival time of 52 weeks in the former and 36 weeks in the latter, and with significant difference (p less than 0.05) during 46th to 52nd weeks. Comparing between the selected cases, the levamisole group was significantly superior (p less than 0.05) to the control group in all course examined, with median survival time of 64 weeks in the former and 36 weeks in the latter. Levamisole was more effective in the group of squamous and adenocarcinoma than large and small cell carcinoma. In the group where PPD reaction was negative at the time of initiation of the treatment levamisole was more effective than in the group of PPD positive, and also more effective in non-responders to the main therapy than responders. No side effect such as agranulocytosis was observed. Summarizing the present study, an immunotherapy employing levamisole combined with chemo-radiotherapy for non-resected lung cancer could be said to be effective in prolongation of survival time.

Adenocarcinoma↗

[Adriamycin, cardiotoxicity--a case report].

In 1976, a 61-year-old female was diagnosed as malignant cystosarcoma phyllodes, and she was admitted to the hospital for chemotherapy. She was started receiving the combination chemotherapy consisting of adriamycin. 60 mg/3-week, mitomycin C, 1 mg/week, 5-Fluorouracil, 175 mg/week, and citosine arabinoside, 10 mg/week. The initial ECG revealed incomplete right bundle branch block pattern. After the first 60 mg administration of adriamycin, the ECG showed non-specific ST-T changes in addition to I.R.B.B.B. pattern. At the second 60 mg administration of adriamycin, the ECG returned to normal. After the administration of adriamycin, the ECG showed the same ST-T changes again which were seen at the first adriamycin treatment. The same phenomenon was observed at the third adriamycin treatment. In this case, there was a reproducible coincidence between the administration of adriamycin and the occurrence of non-specific changes on ECG; the fore a possibility of adriamycin cardiotoxicity was strongly suggested.

Breast Neoplasms↗

[Application of flow cytometry to clinical oncology].

The application of flow cytometry (FCM) in the field of clinical oncology is reviewed. Since the development of the instruments, it has already passed more than a decade and, these days, FCM is utilized in a variety of fields, both basic and clinical researches. FCM has been getting familiar also in Japan for these several years and now more than fifty instruments are running in many laboratories. In this issue, the application of FCM to clinical oncology is described by several authors from different fields. In this review, the definition of FCM, the principle how it works, its advantages and the history of its development are briefly introduced. Furthermore, the application of FCM by measurements of cellular DNA content for estimation of cell cycle distribution and ploidy studies or by measurements of cell surface fluorescence for detection of cell surface antigens is reviewed in hematology, immunology, cell kinetics of cancer and chemotherapy, automated cytology, chromosome analysis and other fields.

Cell Cycle↗

[Effect of levamisole hydrochloride on advanced and recurrent breast cancer--LMS randomized controlled study of a group responding to CAF (cyclophosphamide, adriamycin, and 5-FU) therapy].

The effect of levamisole HCL on advanced and recurrent breast cancer was investigated cooperatively by a randomized controlled study using envelope method. Patients with advanced and recurrent breast cancer who had showed either complete response or partial response to the previous CAF therapy (cyclophosphamide 100 mg/body/day p.o. from day 1 to 14, adriamycin 30 mg/body/day i.v. on day 1 and 8, 5-FU 500 mg/body/day i.v. on day 1 and 8) were entered in this study and divided randomly into a control group and a levamisole group. No further treatment was given to patients of the control group until they fell into progressive disease. Patients of the levamisole group were given the drug at a daily dose of 150 mg for 3 consecutive days every fortnight. Fifty-nine cases were entered in this protocol, but 9 cases of them were ruled out as exclusions or dropouts. Therefore, the number of eligible cases was 31 in the levamisole group and 19 in the control group. Both the duration of remission and the survival time were significantly (p less than 0.05) prolonged in the levamisole group compared with the control group. There was no difference in side effects between these two groups.

Antineoplastic Agents↗

[Antineoplastic action of prostaglandin D2--effect of PGD2 on proliferation of L1210 leukemic cells in culture].

Prostaglandin D2 was found to have a potent cytotoxic effect on L1210 leukemia culture cells. When Prostaglandin D2 was added to the culture medium, at the concentration of over 5 micrograms/ml growth of L1210 cells was almost completely inhibited. IC50 of Prostaglandin D2 for L1210 cell was 2.4 micrograms/ml. Cells exposed this agent showed remarkable change in its cytoplasm with many vacuoles and lysis of cells were observed at the concentration over 5 micrograms/ml.

Animals↗

[Antitumor effects of p-aminobenzoic acid-N-xyloside Na--effects of single administration and combination with radiotherapy].

Therapeutic effect of p-aminobenzoic acid-N-xyloside Na (K-247) were studied. Eleven patients with a variety of solid tumors were treated with K-247 alone. K-247 was given orally 800mg daily for 4 weeks. As for side effect of the drug, only mild gastritis was observed in a few patients. Partial response (over 25% reduction of tumor size) with a median duration of two months was observed in 3 patients. These cases were metastatic tumor of lung from the carcinoma of thyroid, metastatic tumors of lung from the carcinoma of kidney, and mediastinal tumor. In eight patients the response was classified as no change and in one patient there was progressive disease. Thus K-247 has some therapeutic activity in patients with solid tumor. Combination therapy of irradiation and administration of K-247 were also studied. In twelve patients received the combination therapy, partial response was observed in 7 patients with complete response in 3 patients. In some patients it seems that the effect of irradiation was enhanced by K-247 administration. To confirm this observation, randomized controlled trial is required.

4-Aminobenzoic Acid↗

[Phase I study of a new anticancer agent CAM--results of cooperative study].

CAM is a derivative compound of mycophenolic acid produced by Penicillium brevicompactum, and is a new oral Purine antagonistic anticancer agent. The Phase I study was carried out cooperatively in ten hospitals. The results are as follows: The administration method was single administration and the starting dose was 200 mg/m2 (1n). The dose level was escalated according to varied Fibonacci formula. The number of total cases was thirty-one: three cases at 1n level, four at 2n, six at 3.3n, six at 7n and seven at 9n. Side effects were observed in five of thirteen cases over 7n dose levels, such as nausea, vomiting, anorexia and diarrhea. Leukopenia was developed in only one case at 7n dose level. Other side effects such as anemia, thrombocytopenia, and disturbances of liver function and renal function were not observed. It was estimated from above results that a dose limiting factor of CAM is nausea and vomiting. A subtoxic dose was 7n (1,400 mg/m2) and a maximum tolerated dose was 9n (1,800 mg/m2) which corresponded to 2,200-3,000 mg as a single administration.

Animals↗

[Phase I study of a new antitumor antibiotic, neothramycin].

Phase I study of a new antitumor antibiotic, neothramycin which belongs to anthramycins was performed by a cooperative study group involving 15 major institutions. A total of 63 cases including 42 various solid tumors and 21 hematologic tumors refractory to standard treatments underwent the study during June 1979 to June 1981. Doses of single injection were escalated from an initial dose of 2 mg/m2 estimated by one twentieth of LD10 in mice up to 60 mg/m2. The most frequent and severest toxicity was nausea and vomiting seen in about the half of patients being administered dosages ranged from 24 mg/m2 to 40 mg/m2, and 3 out of 4 patients received dosages exceeding 50 mg/m2 required clinical managements; moreover, 1 out of 2 patients administered 60 mg/m2 was ranked as grade 4 of the criterion of toxicities in WHO handbook. Other clinical toxicities such as skin rash, hepatotoxicity or nephrotoxicity observed in the minority of the patients were reversible. Furthermore, hematologic toxicity was extremely mild and appeared not to be dose dependent. One patient with chronic myelogeneous leukemia had a hematological improvement and the other with esophageal cancer had a partial response. The result indicates that a dose limiting factor of neothramycin is nausea and vomiting, and a maximum tolerated dose of a single injection is 60 mg/m2. A dose schedule of 30-40 mg/m2 appears to be an optimal dose for Phase II study.

Animals↗

[Antitumor activity of macromomycin].

An antitumor activity of macromomycin, a polypeptide antitumor antibiotic, was tested in vitro and in vivo. The results obtained were as follows: 1) The cytostatic effect on L1210 cells in culture was identical to that of neocarzinostatin. 2) The effect of MCR on the survival of L1210 or P388 leukemia was as same level as NCS. 3) Effects of MCR were independent from the treatment schedules. 4) MCR was inactive on the survival of Lewis lung carcinoma.

Animals↗