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M Shibuya

Publications and source records attributed to M Shibuya.

At least 469 records · Page 26Linked to original sources
PubMed1983

Transforming genes of avian (v-fps) and mammalian (v-fes) retroviruses correspond to a common cellular locus.

The Gardner (GA) and Snyder-Theilen (ST) isolates of feline sarcoma virus (FeSV) represent genetic recombinants between feline leukemia virus (FeLV) and transformation-specific sequences (v-fes gene) of cat cellular origin. A related transforming gene (v-fps), common to the Fujinami, PRC II, and UR 1 strains of avian sarcoma virus has also been described. Translational products of each of these recombinant virus isolates are expressed in the form of polyproteins exhibiting protein kinase activities with specificity for tyrosine residues. In the present study, v-fes and v-fps homologous sequences of GA-FeSV, ST-FeSV, and Fujinami sarcoma virus (FSV) are defined and these independently derived transforming genes are shown to correspond to a common cellular genetic locus which has remained highly conserved throughout vertebrate evolution.

Animals↗
PubMed1983

Effect of peplomycin plus carbazilquinone and mitomycin on non-small cell carcinoma of the lung.

The effects of two chemotherapeutic regimens, peplomycin (PLM) plus carbazilquinone and PLM plus mitomycin, on non-small cell carcinoma of the lung were evaluated by a randomized controlled trial. Seven partial responses were observed in 53 evaluable patients, for an overall response rate of 13.2%. There was no difference in response rate or in median survival time between PLM plus carbazilquinone (11.5% and 32 weeks) and PLM plus mitomycin (14.8% and 25 weeks). Seven patients developed interstitial pneumonitis, and four died of pulmonary fibrosis. It was concluded that the chemotherapeutic regimens that include PLM are only marginally effective against non-small cell carcinoma of the lung, with relatively frequent pulmonary fibrosis.

Adenocarcinoma↗
PubMed1983

Pulmonary toxicity induced by pepleomycin 3-[(S)-1'-phenylethylamino] propylamino-bleomycin.

Chemotherapy regimens containing pepleomycin, a derivative of bleomycin, were used for 81 patients with advanced primary lung cancer and 32 patients with metastatic pulmonary tumors. Among the patients with non-small cell carcinoma of the lung, partial responses were observed in three of 27 patients treated with pepleomycin + carbazilquinone and four of 26 patients treated with pepleomycin + mitomycin C (published in Cancer Treatment Reports, 1983). Five partial responses (primary organ: larynx, esophagus, lung, pancreas and uterus; one patient each) in 23 evaluable patients with metastatic pulmonary tumors were observed during treatment, for an overall response rate of 21.7%. In patients with primary lung cancer, no correlation between the incidence of the decrease in partial arterial oxygen tension (PaO2) during treatment and age was observed. Decrease in PaO2 during treatment was found more frequently in patients with abnormal pulmonary function before treatment than in patients with normal pulmonary function, but the mean lowest values of PaO2 in the two groups were the same. Intravenous weekly injection of pepleomycin is less likely to result in a decrease in PaO2 than two daily intramuscular injections. Definite pulmonary toxicity occurred in seven of the 113 patients (6.2%). Each of the seven received a total dose of over 60 mg and their ages were over 60 yr, although no correlation between the incidence of pulmonary fibrosis and total cumulative dose of pepleomycin was observed. Six of the seven patients died of pulmonary fibrosis in spite of prednisone treatment. Clinical, radiologic and histopathologic findings associated with pepleomycin were the same as those of bleomycin pulmonary toxicity. Further studies are needed to determine the appropriate dose schedule and route of administration of pepleomycin with regard to its benefit and toxicity.

Age Factors↗
PubMed1983

[In vitro antitumor activity of 7-N-(p-hydroxyphenyl)-mitomycin C (KW-2083) against cultured bronchogenic carcinoma cells (PC-7)].

The in vitro antitumor activity of 7-N-(p-hydroxyphenyl)-mitomycin C (KW-2083) against cultured bronchogenic carcinoma cells (PC-7) was compared with that of mitomycin C, using a 3H-thymidine uptake assay. The uptake of 3H-thymidine into PC-7 cells was well correlated with the cell concentration under 1 X 10(5)/ml. It was more strongly inhibited after incubation of the PC-7 cells with KW-2083 than with mitomycin C at the concentration of 0.5, 2.5 and 10 micrograms/ml for 20 and 60 min. The placebo of KW-2083 containing HCO-60 and propyleneglycol showed no effect on the uptake of 3H-thymidine by PC-7 cells.

Carcinoma, Bronchogenic↗
PubMed1983

[Evaluation of myocardial ischemia in acute myocardial infarct by thallium scintigraphy and radioisotope angiography].

It is very important to evaluate the size of myocardial infarction and reversibility of ischemic myocardium in order to determine the severity and prognosis of patients with acute myocardial infarction. We performed thallium-201 redistribution myocardial scintigraphy and first pass radionuclide angiography in 12 patients with acute myocardial infarction. In eight cases, left ventricular wall motion was improved after nitroglycerin infusion (improved group), but in four cases it was unchanged (non-improved group). Six of the improved group showed a positive redistribution image, while in the non-improved group, no patient showed such an image. Ejection fraction increased after nitroglycerin infusion in the improved group, but unchanged in the non-improved group. There was no significant difference in hemodynamic parameters between the two groups at the time of admission, and after treatment hemodynamic parameters changed in the same way in both groups. In coronary angiography, three collateral channels were observed in the improved group, but none in the non-improved group. The severity of coronary artery stenosis in the two groups was almost identical. In eight patients, their regional ventricular wall motion improved after nitroglycerin administration, but there were four patients whose regional ventricular wall motion was unchanged. In both groups, hemodynamic and coronary angiographic findings were not different. But there were many positive redistribution images and collateral channels in the improved group. This result shows that reversible ischemia is indispensable for the improvement of regional wall motion. There was a case which showed a positive redistribution image on acute phase Tl-201 scintigraphy and a transient defect on the chronic phase exercise Tl-201 scintigraphy. But after the improvement of ischemia by aorto-coronary bypass operation, the defect on Tl-201 scintigraphy decreased and the wall motion improved. Neither redistribution on acute phase scintigraphy nor a transient defect on chronic phase exercise scintigraphy was observed in the non-improved group. From these data we conclude that the improvement of regional wall motion depends on reversible ischemia.

Adult↗
PubMed1983

[Augmentation of the cytostatic activity of granulocytes by biological response modifiers (BRM)].

The effects of various biological response modifiers (BRM) such as Nocardia rubra cell wall skeleton (N-CWS), OK-432, muramyl dipeptide (MDP), Staphylococcal protein A, interferon, lymphokine on the cytostatic activity of granulocytes against cultured tumor cells were examined. The cytostatic activity of untreated granulocytes from 10 normal healthy volunteers ranged from 14% to 30%. Lymphokine obtained from the supernatant of lymphocytes cultured with Con A-Sepharose directly suppressed the DNA synthesis of K 562 cells in high concentration, however, other BRM showed no direct cytostatic activity. The cytostatic activity of granulocytes was augmented by low concentrations (2.5 micrograms/ml) of N-CWS, OK-432 and protein A as well as by high concentration (25 micrograms/ml) of MDP. However, the cytostatic activity was not influenced by alpha-interferon. The meanings and mechanisms of the elevation in cytostatic activity of granulocytes by BRM were discussed with regards to the clinical immunotherapy.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

[Effect of C-reactive protein on natural killer activity].

The relationship between natural killer (NK) activity of peripheral blood lymphocytes and serum C-reactive protein (CRP) concentration was analysed in patients with carcinoma of the lung and metastatic pulmonary tumors. Significant reverse correlation (r=-0.43) was found between NK activity against OAT cells or K-562 cells and serum CRP concentration. For the elucidation of the mechanism of suppressive activity of CRP against NK activity, in vitro effects of CRP on NK activity was studied. Relative NK activity compared to control decreased to 23.3 +/- 5.6% in experiment adding 1.0 mg/dl of CRP into NK assay mixture (p less than 0.001). Relative NK activity was also strongly inhibited in experiment preincubating lymphocytes with CRP. The decrease of NK activity with CRP was depending on the concentration of CRP.

Adult↗
PubMed1983

[Ototoxicity of micronomicin sulfate--audiometric assessment].

Micronomicin sulfate (MCR) is a new aminoglycoside antibiotic, and its antibacterial spectrum is similar to that of gentamicin (GM). According to the animal test, MCR has less ototoxicity than other aminoglycoside antibiotics such as GM. To check its clinical ototoxicity, MCR was given intramuscularly to 20 patients at dose of 120--240 mg/day, respectively for 2--8 days, and audiometry was carried out before and after administration of MCR. No evident change was detected between the preadministration hearing levels and the postadministration hearing levels. These data suggest that MCR is sufficiently safe in ototoxicity within dose of 120 mg/day for 4 days.

Adult↗
PubMed1983

In vivo and in vitro effects of Nocardia rubra cell wall skeleton on natural killer activity in mice.

The in vivo and in vitro effects of Nocardia rubra cell wall skeleton (N-CWS) on natural killer (NK) activity of spleen and peritoneal lymphocytes of C57BL/6 mice were studied. The NK activity of spleen and peritoneal lymphocytes against YAC-1 lymphoma cells and cultured B-16 melanoma cells peaked at 3 days after intraperitoneal or intravenous administration of N-CWS, and returned to the normal value 7 days later. The NK activity of spleen lymphocytes was augmented by in vitro incubation with N-CWS. The appropriate concentration of N-CWS for the in vitro stimulation of NK activity in spleen lymphocytes was 2-5 micrograms/ml.

Animals↗
PubMed1983

[Effect of Nocardia rubra cell wall skeleton against pleuritis carcinomatosa in adenocarcinoma of the lung].

Forty-one cases of adenocarcinoma of the lung with pleuritis carcinomatosa were randomly assigned to either chemotherapy alone or chemoimmunotherapy using Nocardia rubra cell wall skeleton as immunopotentiator. In 34 evaluable patients, the rates of volume decrease and the disappearance of tumor cells in pleural effusion were higher in chemoimmunotherapy group than in chemotherapy alone group, and median survival times from the beginning of treatment in chemotherapy alone and chemoimmunotherapy groups were 189 and 266 days, respectively. The survival times in patients with stage III and P.S. 0+1+2 were better than those in patients with stage IV and P.S. 3, respectively. Transient fever and mild elevation of GPT and GOT were tolerated without any treatment.

Adenocarcinoma↗
PubMed1983

[Phase II study of KW2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with carcinoma of the lung and metastatic pulmonary tumor].

A phase II study of KW2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C], a derivative of Mitomycin C, was carried out in 20 patients with carcinoma of the lung and in 19 patients with metastatic pulmonary tumor. KW2083 was administered by single intravenous injection at a dose of 20-30 mg/m2 weekly or a single 70 mg/m2 dose. Patients treated with a dose of 20-30 mg/m2 should be given at least 3 doses for eligibility. Of 17 evaluable patients with carcinoma of the lung (11 adenocarcinomas, 3 squamous cell carcinomas, 2 small cell carcinomas and 1 large cell carcinoma), two patients with adenocarcinoma showed a partial response (11.8%). Two patients who achieved PR had adenocarcinoma without prior therapy received KW2083 at a single dose of 70 mg/m2 Objective response rates were 18.2% for 11 patients with adenocarcinoma and 25% for 8 patients with adenocarcinoma treated with a single dose of 70 mg/m2 of 15 evaluable patients with metastatic pulmonary tumor, no patients showed any objective responses. The hematologic toxicities were thrombocytopenia (less than 5 X 10(4)/mm3, 41.6%) and leukocytopenia (less than 2000/mm3, 28.1%); it was observed in 19% of the patients, that thrombocytopenia continued for more than 6 weeks after stopping therapy. Gastrointestinal symptoms such as anorexia (81%), nausea (66%) and vomiting (16%) were severe in patients treated with a single dose of 70 mg/m2. Fever in 19%, alopecia in 13%, phlebitis in 9%, eruption in 6%, stomatitis in 6% and liver insufficiency in 13% were also observed.

Adenocarcinoma↗
PubMed1983

[Role of asialo GM 1 positive cells in the control of metastatic spread of tumor cells in mice].

The role of asialo GM1 positive cells was studied in artificial and spontaneous pulmonary metastases as well as in tumor growth by using B-16 melanoma cells in C57BL/6 mice. Single administration of 50 microliters of anti-asialo GM1 antibody resulted in the significant decrease of NK activity in the spleen cells of C57BL/6 mice lasting 13 days from the following day of administration. The anti-asialo GM1 antibody was evaluated in terms of for its effect on pulmonary metastases with regard to the timing of administration. Treatment with anti-asialo GM1 antibody 1 day before or on the day of tumor inoculation resulted in a substantial increase in the number of artificial pulmonary metastases. In the experimental system of spontaneous metastases, the anti-asialo GM1 antibody most effectively increased the number of pulmonary metastases when administered 1 to 2 weeks before the amputation of the tumor primary site. In addition, in mice treated with anti-asialo GM1 antibody, the acceleration of the growth of the transplanted tumor was observed. These results strongly suggest that asialo GM1 positive cells not only inhibit pulmonary metastases acting mainly on circulating tumor cells but also suppress the growth of transplanted tumor.

Animals↗
PubMed1982

Depside as potent inhibitor of prostaglandin biosynthesis: a new active site model for fatty acid cyclooxygenase.

Forty depsides and depsidones, the esters of phenolcarboxylic acids, were examined for their inhibitory effect against prostaglandin biosynthesis with rabbit renal microsomes. 4-0-Methylcryptochlorophaeic acid was the most active inhibitor so far tested and its IC50 value was 0.34 muM. Kinetic investigation has shown that this depside acts competitively with respect to arachidonic acid as most of the non - steroidal antiinflammatory drugs. X-Ray analysis has revealed that 4-0-methylcryptochlorophaeic acid maintains its rigid conformation by forming a strong hydrogen bond between the hydroxyl and methoxyl groups. Comparison of CPK models between 4-0-methylcryptochlorophaeic acid and non-steroidal antiinflammatory drugs revealed that the carboxyl group and the two rings of these drugs are almost superimposable to those of the depside. This finding led us to propose a new active site model based on the three dimentional structure of the depside.

Animals↗
PubMed1982

Nucleotide sequence of Fujinami sarcoma virus: evolutionary relationship of its transforming gene with transforming genes of other sarcoma viruses.

We determined the entire nucleotide sequence of the molecularly cloned DNA of Fujinami sarcoma virus (FSV). The sequence of 1182 amino acids was deduced for the FSV transforming protein P130, the product of the FSV gag-fps fused gene. The P130 sequence was highly homologous to the amino acid sequence obtained for the gag-fes protein of feline sarcoma virus, supporting the view that fps and fes were derived from a cognate cellular gene in avian and mammalian species. In addition, FSV P130 and p60src of Rous sarcoma virus were 40% homologous in the region of the carboxyterminal 280 amino acids, which includes the phosphoacceptor tyrosine residue. These results strongly suggest that the 3' region of fps/fes and src originated from a common progenitor sequence. A portion (the U3 region) of the long terminal repeat of FSV DNA appears to be unusual among avian retroviruses in its close similarity in sequence and overall organization to the same region of the endogenous viral ev1 DNA.

Amino Acid Sequence↗
PubMed1982

Synthesis and structure--activity relationship of nonyl 3-acyldithiocarbazates and related compounds for uncoupling activities.

Various nonyl 3-substituted-dithiocarbazates, methyl and dimethyl derivatives of nonyl 3-benzoyldithiocarbazate, nonyl 2-substituted-dithiocarbamates, and benzaldehyde nonyldithiocarbohydrazone were synthesized and their uncoupling activities of oxidative phosphorylation in mitochondria were examined. The results indicate that the presence of the thiocarbamoyl structure with the potential SH group is a requisite for uncoupling activity. The presence of a C=O group and a hydrophobic aromatic ring significantly increases the uncoupling activity.

Animals↗
PubMed1982

Effect of chemotherapy on natural-killer activity and antibody-dependent cell-mediated cytotoxicity in carcinoma of the lung.

The effect of chemotherapy on natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) in 15 advanced carcinomas of the lung was examined with regard to the drug, dose, route and timing of administration. The relationship between the effect of chemotherapy on the prognosis for the patients, and the changes in NK activity and ADCC, was also analysed. The NK activity and ADCC in patients with poor prognosis were significantly subnormal, even before treatment. The NK activity and ADCC began to decrease 2 weeks after the initiation of treatment and reached the lowest level during the 3rd or 4th week in all patients. Thereafter, they returned to the pretreatment level in 8 patients with stabilized disease. In contrast, they were not restored in 7 patients with progressive disease and poor prognosis. In 4 patients it was found that the effect of chemotherapy with pepleomycin and carbazilquinone on NK activity and ADCC differed according to the drug used. From this pilot study it is suggested that NK activity and ADCC are valuable prognostic factors in patients with advanced carcinoma of the lung, and that detailed analysis of the effect of each anticancer agent on NK activity and ADCC is desirable for the establishment of better treatment regimens for advanced carcinoma of the lung.

Aged↗