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S Mochizuki

Publications and source records attributed to S Mochizuki.

At least 145 records · Page 8Linked to original sources
PubMed1990

Effects of topical application of KT1-32 on transmucosal potential difference and acid secretion in the rat stomach.

Effects of intragastric application of azuletil sodium (KT1-32), a novel antiulcer drug, on transmucosal potential difference (PD) and acid secretion were investigated in the rat stomach. The stomach was mounted on a Lucite chamber and perfused with saline before and after exposure to KT1-32 for 10 min. KT1-32 (3-30 mg/kg) produced an elevation of PD in a dose-dependent manner with a rise of the luminal pH. The increased PD response caused by KT1-32 (10 mg/kg) persisted after removal of the agent from the stomach, but this PD generating effect was significantly mitigated by pretreatment with omeprazole (60 mg/kg, i.p.). KT1-32 raised PD under basal conditions, but did not significantly affect the reduced PD response caused by 30% ethanol. In addition, topical application of KT1-32 significantly reduced acid secretion caused by histamine (4 mg/kg/hr, i.v.) and carbachol (20 micrograms/kg/hr, i.v.). In the in vitro study, KT1-32 at 3.9 x 10(-4) M showed 50% inhibition of the H/K ATPase activity prepared from the hog gastric mucosa. These results suggest that KT1-32 exerts locally antisecretory and PD generating effects. The latter may be accounted for by the antisecretory action, which is probably related to the H/K ATPase inhibition.

Administration, Topical↗
PubMed1990

Effects of KT-362, a new calcium release blocker, on vascular selectivity and hemodynamic actions in anesthetized dogs.

Pharmacological properties of 5-(3-((2-(3,4-dimethoxyphenyl)ethyl)-amino)-1- oxopropyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate (KT-362), a newly synthesized calcium release blocker, were studied by comparing its vascular selectivity and cardiovascular actions with those of verapamil, a calcium entry blocker. The relaxing effect of KT-362 in rabbit femoral and basilar artery strips contracted with norepinephrine was greater than that in aortic and coronary artery strips. In anesthetized mongrel dogs, KT-362 (0.1-3.0 mg/kg, i.v.) decreased the mean blood pressure, heart rate and total peripheral resistance in a dose-dependent manner, while cardiac output increased slightly despite a decrease in left ventricular pressure. This is consistent with the data on verapamil. Both i.a. and i.v. injections of KT-362 produced a marked dose-dependent increase in vertebral and femoral blood flow. Pretreatment of atropine, propranolol or diphenhydramine exerted no significant effect on the KT-362-induced vasodilation. Verapamil caused a marked increase in the vertebral and coronary blood flows after the injections, but only a slight increase in femoral blood flow. KT-362 at the dose of 10 mg/kg, i.v., had no significant effect on the PQ interval on the electrocardiogram in anesthetized dogs, but 0.1 mg/kg of verapamil increased this interval significantly. These results suggest that KT-362 has properties similar to calcium entry blockers such as verapamil on systemic hemodynamic actions except for the reactivity of vasculatures.

Anesthesia, Intravenous↗
PubMed1990

[Study of blood flow in hyperthermia using human renal cell carcinoma heterotransplanted in nude mice--differences in histological tumour pattern upon the effects of hyperthermia].

Utilizing two types of human renal cell carcinoma heterotransplanted in nude mice (JRC 1; papillary, avascular pattern, grade III, JRC 11; anaplastic and alveolar, hypervascular pattern, grade IV), we investigated the influence of tumor blood flow upon the effects of local hyperthermia (42.5 degrees C), induced by 915 MHz microwave. Blood flow was determined from the rate of thermal clearance by use of the bio-heat transfer equation. The rate of thermal clearance was measured at intervals of approximately 10 minutes throughout the treatment session after turning off the microwave for 50 seconds. With both strains it was necessary to increase the microwave power until the constant steady-state temperature of 42.5 degrees C was reached. The JRC 11 strain needed more power for the constant temperature than JRC 1, but it needed a greater decrease in power level during the heating session to maintain a constant steady-state temperature. This was an indication that the tumour blood flow decreased more markedly in the JRC 11 strain. In both tumours, a decrease of blood flow was observed during the heating session. In the case of the JRC 1 strain, it was observed that the mean value of blood flow was 1.87 times higher than that of JRC 11. This indicated a sharp reduction in blood flow in JRC 11 strain. This reduction was confirmed by the thermal clearance measurement at the end of the treatment session. A sharp reduction in blood flow in hypervascular tumour (JRC 11 strain) is caused by a stasis of intra-tumoural blood circulation during the heating.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Clinical evaluation of high dose rate intra-cavitary irradiation in the treatment of uterine cervical cancer, combined with pepleomycin suppository in uterine cavity].

By means of re-irradiation using pepleomycin suppository in uterine cavity, we attained local control for one patient who had local recurrence in uterine cavity and suffered from uterine fluor in which viable cancer cells were confirmed. We were enlightened by this therapeutic experience, so we attempted combination therapy using pepleomycin suppositories to supplement intra-cavitary irradiation, for the 11 selected patients who were suffering from uterine fluor. We investigated the treatment results in 7 patients of stage III out of 11 patients (of all stages), in comparison with 13 patients of stage III who were treated by irradiation alone. Consequently, these treatment results were approximately equivalent, and the incidence of sigmoid complications could be decreased. Side effects which were followed by the combination therapy were not serious, and so we believe that pepleomycin suppository is a simple method and valuable to supplement radiation therapy of uterine cervical cancer.

Administration, Intravaginal↗
PubMed1990

[Immunohistological demonstration of developmental protein GP68 in human tumor and embryonic tissues].

A developmental protein GP68 is known to appear stage-specifically in the developmental mouse brain. The expression of GP68 in tissues of 265 various human tumors and of 2 human embryos was examined immunohistologically using specific anti-GP68 rabbit antisera. Generally, endodermal, neural, and germ cell tumors were most frequently positive, while mesenchymal tumors were mostly and ectodermal tumors were intermediate. Anti-GP68 also gave positive reactions with some of non-neoplastic cells of cancer patients generally to lesser extents than neoplastic cells. Muscle and bone tissues of a 4-week-old embryo were weakly positive. Some tumors that were negative for CEA and AFP were strongly positive for GP68. The expression of GP68 in human tumor cells may represent an abnormal cellular gene-expression associated with the neoplastic change of the cell.

Carcinoembryonic Antigen↗
PubMed1990

Phosphonylmethoxyalkyl derivatives of purine as inhibitors of human hepatitis B virus DNA synthesis.

A selected number of antiviral compounds which have been previously shown to inhibit the replication of DNA viruses or retroviruses were examined for their inhibitory effects on human hepatitis B virus (HBV) DNA synthesis. The assay system was based on the use of a human hepatoblastoma cell line (HB611) that continuously synthesizes HBV DNA. The following phosphonylmethoxyalkyl-purine derivatives were found to inhibit HBV DNA synthesis: 9-(2-phosphonyl-methoxyethyl)-2',6'-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA). PMEDAP, HPMPA and PMEA not only inhibit HBV DNA synthesis in HB611 cells but also duck hepatitis B virus (DHBV) DNA and core antigen synthesis in primary duck hepatocytes.

Adenine↗
PubMed1990

[Mitogenic activity of lipopolysaccharide from Bacteroides intermedius against C3H/HeJ mice spleen cells].

Bacteroides intermedius is one of the periodontal disease generative bacteria. Lipopolysaccharide preparation obtained from B. intermedius ATCC 25611 and ATCC 33563 strains was investigated as to Limulus activity observed with Pyrodic (endotoxin specific) reagent, and mitogenic activity in both normal and tolerant mice induced by Escherichia coli. Limulus activities of all LPS's were nearly similar to that of E. coli. LPS's preparation from B. intermedius were found to be strongly mitogenic for C3H/HeN mice spleen cells, whereas no LPS preparations were mitogenic for thymocytes of BALB/c mice. LPS-nonresponsive C3H/HeJ mice spleen cells were found to good mitogenic responses to LPS's from B. intermedius, as well as LPS from B. gingivalis 381 strain. Polymyxin B had remarkable inhibitory effect on the mitogenicity of LPS's from B. intermedius for C3H/HeN and C3H/HeJ mice spleen cells, also that activity of B. gingivalis LPS was inhibited by polymyxin B. The mitogenicity of the LPS from B. intermedius, as measured in C3H/HeJ mice spleen cells, was considerably resistant to the proteolytic effects of proteinase K.

Animals↗
PubMed1990

Increasing effect of sodium 3-ethyl-7-isopropyl-1-azulenesulfonate 1/3 hydrate (KT1-32), a novel antiulcer agent, on gastric mucosal blood flow in anesthetized.

Effect of a novel azulene derivative KT1-32 on gastric mucosal blood flow (GMBF) was studied to elucidate its mucosal defensive mechanisms underlying the antiulcer action. The GMBF was measured by two methods which were based on heat clearance and laser Doppler velocimetry in the rat. Intravenous administration of KT1-32 produced a dose-dependent increase in GMBF at doses of 0.3-10 mg/kg; significant increases in GMBF were observed at doses not less than 1 or 3 mg/kg by the laser Doppler or heat clearance method, respectively. The duration of action was about 10 min at 10 mg/kg of KT1-32. A good parallelism in these GMBF changes was noted between both methods. Cetraxate, an antiulcer agent, elicited an increase in GMBF at 30 mg/kg, i.v., when GMBF was measured by the heat clearance method. Sodium guaiazulene 3-sulfonate, another azulene antiulcer agent, showed no increase in GMBF. It is suggested that the increasing effect of KT1-32 on GMBF contributes to its antiulcer activity through strengthening mucosal defensive mechanisms.

Anesthesia↗
PubMed1990

[An early clinical study of Z-100 in leukopenia caused by radiotherapy].

The clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated in an early clinical study using three doses, 2, 10 and 20 micrograms. According to the evaluation by investigators and time-course of WBC, the highest effective rate was achieved by 20 micrograms. Adverse reactions occurred in all groups, but there were no serious or clinically relevant reactions. These results suggested that Z-100 is clinically useful for the treatment of leukopenia caused by radiotherapy.

Adult↗
PubMed1989

Cross-reactive antibodies to BLV and HTLV in bovine and human hosts with retrovirus infection.

Sera of 22 cattle naturally infected with bovine leukemia virus (BLV), of 2 calves vaccinated with BLV, and of 22 patients with human T cell leukemia virus type I (HTLV-I) infection were tested to BLV and HTLV-I by enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB). Sera of 22 healthy cattle and from 22 healthy persons, and mouse monoclonal antibody to BLV-gp51, to HTLV-I-p24, or to HTLV-I-p19 were also tested. Sera of virus-infected hosts gave significantly higher ELISA values than sera of healthy donors to both BLV and HTLV-I. The correlation between ELISA values of bovine sera to BLV and those to HTLV-I was r = 0.76, whereas that of human sera was r = 0.35. By WB and competitive WB assays, bovine sera that were ELISA-positive to BLV reacted with one or more of p12, p15, and p24 of BLV, and with only p24 of HTLV-I. Human sera that were ELISA-positive to HTLV-I reacted with p12 and p24 of BLV, and with one or more of p12, p15, p19, and p24 of HTLV-I. These results demonstrate that BLV and HTLV-I are capable of evoking cross-reactive immune response in at least some hosts under natural infection as well as by virus vaccination.

Animals↗
PubMed1989

Hyperthermia with simultaneous administration of interferon using established human renal carcinoma heterotransplanted in nude mice.

Using human renal carcinoma heterotransplanted in nude mice, the effects of the combined use of hyperthermia and interferon (natural human interferon-alpha; IFN-alpha, and recombinant interferon-gamma; IFN-gamma) were examined. The hyperthermic device used was the Clini-Therm, Mark VII, 915 MHz, microwave. The administration of interferon was started immediately before hyperthermia and carried out on consecutive days. The combined use of hyperthermia and IFN was compared with hyperthermia and with IFN alone. The combined use of hyperthermia and IFN-alpha was shown to have significant anti-tumour effects compared with the former or latter alone. Of 10 nude mice (10 implanted tumours) used for the experiment, 5 showed complete disappearance of the implanted tumours and the others showed prolongation of survival. Combined treatment with IFN-gamma and hyperthermia showed no significant effect when compared with other treatment groups. Combined treatment with local hyperthermia and IFN-alpha may have some application to the clinical management of renal carcinoma.

Animals↗
PubMed1989

Effects of KT-362, a new Na and Ca influx and Ca release inhibitor, on canine ventricular arrhythmias.

Antiarrhythmic effects of the new drug KT-362, which was reported to suppress Na and Ca currents of cardiac cells and also to suppress intracellular Ca release in isolated smooth muscle preparations, were examined using two-stage coronary ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in the dog. Intravenous KT-362 at 10 mg/kg suppressed coronary ligation arrhythmia both at 24 and 48 hr after ligation, and the minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation and 48 hr coronary ligation were 6.1 +/- 1.7 and 8.6 +/- 2.7 micrograms/ml, respectively. Antiarrhythmic effects were accompanied by transient hypotension. Oral administration of 70-100 mg/kg was also effective on 24 hr coronary ligation arrhythmia. However, there was no prominent hypotension in these experiments. Intravenous KT-362 at 3 mg/kg suppressed digitalis arrhythmia; and the minimum effective plasma concentration was 3.3 +/- 1.2 micrograms/ml, which was lower than the effective plasma concentrations for coronary ligation arrhythmias. Intravenous KT-362 at 1 mg/kg also suppressed adrenaline arrhythmia; and the minimum effective plasma concentration was 1.0 +/- 0.1 microgram/ml, the lowest among the effective plasma concentrations. These pharmacological profiles of KT-362 are quite different from those of class 4 Ca antagonists, but similar to those of class 1 drugs such as propafenone. Though KT-362 has a hypotensive effect, it is effective on canine ventricular arrhythmias; thus its clinical usefulness for supraventricular and ventricular arrhythmias is expected.

Animals↗
PubMed1989

Thromboxane A2 antagonistic action of a new anti-ulcer agent, azuletil sodium (KT1-32).

The TXA2/PGH2 receptor antagonistic activity of azuletil sodium (KT1-32), a new anti-ulcer agent, was examined. KT1-32 competitively antagonized the contraction of canine gastric arteries induced by U-46619, PGF2 alpha, and PGE2, whereas it had no effect on the PGF2 alpha-, PGE2- and LTD4-induced contraction of guinea-pig ileum, which was not affected by U-46619. In anesthetized dogs, KT1-32 significantly reduced the U-46619-induced decrease in gastric arterial blood flow. Gastric contraction induced by U-46619 in anesthetized rats was markedly inhibited by KT1-32. KT1-32 showed no influence on TXA2 synthetase and cyclooxygenase activities. These results indicate that KT1-32 is a competitive TXA2/PGH2 receptor antagonist, which may be important as to the effectiveness of KT1-32 against gastric ulcer.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Effects of dietary ethanol on ascorbic acid and lipid metabolism, and liver drug-metabolizing enzymes in rats.

Effects of dietary ethanol on ascorbic acid and lipid metabolism, and liver drug-metabolizing enzymes in rats fed a semi-purified diet containing a powdered ethanol preparation (30 cal% in the diet) were studied. Administration of ethanol increased urinary ascorbic acid excretion (p less than 0.001) and ascorbic acid level in the liver (p less than 0.001) and the spleen (p less than 0.01). The activity of hepatic aniline hydroxylase was increased (p less than 0.05) by ethanol feeding but that of aminopyrine N-demethylase was not. Increases of serum total and high-density-lipoprotein (HDL) cholesterol level, commonly observed by the administration of xenobiotics, were not observed. These results showed ethanol possessed rather similar properties to xenobiotics such as polychlorinated biphenyls (PCB) or 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT) in some metabolic changes. In this study, no accumulation of lipid in the liver was observed.

Aminopyrine N-Demethylase↗
PubMed1989

[Prognostic factors of common epithelial ovarian cancer treated by surgery and cisplatin based combination chemotherapy].

Retrospective analysis of prognostic factors in 171 patients who had common epithelial ovarian cancer (WHO) and treated by surgeries and cisplatin based combination chemotherapies were performed by survival assay and multivariate analysis. In FIGO stage 3, the estimated parameter values were in following order: residual tumour age grade performance status histological type. On analysing Stage patients, histological grading and histological typing had an effect on prognosis. Patients with grade 2 or tumours had a worse prognosis than did those with grade 1 tumours, and patients with clear-cell carcinoma or undifferentiated adenocarcinoma showed a poor prognosis.

Adult↗
PubMed1989

Antigenic variations of retrovirus in Japanese cancer patients.

Previously we demonstrated the prevalence of human T lymphotropic virus type I (HTVL-I) infection among cancer patients in Japan. This study was carried out to examine antigenic properties of retroviruses prevalent among Japanese cancer patients. Sera of 126 Japanese patients with cancer of different organs and with no history of blood transfusion, 94 in adult T cell leukemia (ATL)-endemic area and 32 in ATL-nonendemic area, were surveyed for antibodies to HTLV-I and HTLV-II by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunogold electron microscopy. Among patients who were seropositive to HTLV-I, 39 of 56 (69.6%) in ATL-endemic area and 9 of 9 (100%) in ATL-nonendemic area were seropositive also to HTLV-II. Of 48 sera positive to both HTLV-I and HTLV-II, 34 (70.8%) showed stronger reactivities to HTLV-I than to HTLV-II. Among patients who were seronegative to HTLV-I, 3 of 38 (7.9%) in ATL-endemic area and 5 of 23 (21.7%) in ATL-nonendemic area were seropositive to HTLV-II. Antibodies appearing and disappearing in sera of patients examined during the clinical course reacted with peptide species of HTLV-I and/or HTLV-II not always consistent with peptide species cross-reactive between HTLV-I and HTLV-II. These results indicate the antigenic diversity of retroviruses prevalent among Japanese cancer patients.

Antigenic Variation↗
PubMed1988

Acid-base changes in ischemic myocardium and intervention with hypothermia or bicarbonate.

Effects of ischemia and reperfusion on acid-base changes in relation to myocardial contractility, and the effects of correcting H+ were studied by lowering PCO2 or increasing HCO3- levels. The hearts were perfused by working heart mode and whole heart ischemia was induced by use of a one way valve followed by myocardial warming (37 degrees C, normothermia), cooling (18 degrees C, hypothermia) or warming plus 2.1 mM NaHCO3 for 15 min. The hearts were then reperfused for 20 min. Coronary effluent was collected through pulmonary artery cannulation and used for the measurement of acid-base changes. There were close correlations between the decrease in coronary flow and LV pressure, LV dP/dt. Close correlations were also observed between the decline in LV pressure and the rise in PCO2, H+, and the decline in HCO3-. A highly significant correlation was seen between H+ and lactate production. Myocardial contractility decreased to the same extent in 3 groups during ischemia, whereas its recovery rate in both the hypothermia and HCO3- -treated groups were significantly higher than in the normothermia group. The increment of H+ was significantly less in both the hypothermia and HCO3- -treated groups than in normothermia. These results indicate that lactate production is the major H+ producing source and the correction of H+ could minimize the ischemic insult and at the same time contribute to the reperfusion injury.

Acid-Base Imbalance↗