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Biomedical subjects

H Sano

Publications and source records attributed to H Sano.

At least 505 records · Page 28Linked to original sources

Effect of elastase on aortic smooth muscle cell proliferation.

We studied the effects of elastase on [3H]thymidine incorporation into aortic smooth muscle cells. When elastase was added to cultured aortic smooth muscle cells, [3H]thymidine incorporation was inhibited in a dose-dependent manner in the presence of fetal bovine serum. Elastase also inhibited this incorporation in cells treated with epidermal growth factor. Epidermal growth factor (50 ng/ml) stimulated thymidine incorporation, without elastase, but with the addition of 20 units/ml of elastase the incorporation was inhibited 70%. The incorporation of thymidine into cells treated with 50 ng/ml epidermal growth factor was also inhibited 50% by a low concentration of elastase (5 units/ml). These inhibitory effects on thymidine incorporation were also observed in cells stimulated with platelet-derived growth factor. Platelet-derived growth factor (20 units/ml) markedly stimulated thymidine incorporation into cells, and elastase inhibited its activity in a dose-dependent manner. These results suggest that elastase has the potential to prevent the development of atherosclerosis by inhibiting smooth muscle proliferation.

Animals↗

Insulin responsiveness to glucose and tissue responsiveness to insulin in lactating, pregnant, and nonpregnant, nonlactating beef cows.

Insulin responsiveness to glucose and tissue responsiveness to insulin, using the hyperglycemic clamp and the hyperinsulinemic euglycemic clamp techniques, were measured in lactating, late pregnant, and nonpregnant, nonlactating (NPNL) beef cows. The glucose infusion rate (GIR) in the hyperglycemic clamp technique was higher (P less than .05). in lactating cows than in NPNL cows. The plateau in plasma insulin concentration (insulin responsiveness) was higher (P less than .05) in lactating cows than in late pregnant and NPNL cows. Pregnant cows tended to have higher GIR and lower plateau in plasma insulin concentration than NPNL cows. In the hyperinsulinemic euglycemic clamp technique, GIR (tissue responsiveness to insulin) was higher (P less than .05) in lactating cows than in late pregnant cows; values for NPNL cows were intermediate. We conclude that insulin responsiveness to glucose and tissue responsiveness to insulin were enhanced during lactation but tended to be decreased during late pregnancy in beef cows.

Animals↗

Pharmacokinetics of nizatidine in dogs and rats.

1. Plasma levels of nizatidine and two metabolites (N-desmethyl nizatidine and nizatidine S-oxide) were studied in dogs and rats. 2. The time-courses of plasma concentration of nizatidine after i.v. and oral administration to dogs well fitted a two-compartment model. Absorption after oral administration was rapid, and the peak plasma level (Cmax) and area under the plasma concentration-time curve (AUC) were proportional to doses. Absolute bioavailability was close to 100%, indicating that nizatidine has a negligible first-pass effect. 3. Nizatidine was eliminated by apparent first-order kinetics after i.v. administration to rats, and the elimination in rats was faster than in dogs. Bioavailability in rats was 72.4%, indicating a slight first-pass effect in rats. 4. When plasma clearance (Clp), or volume of distribution (Vd.beta), of nizatidine were plotted against animal body weight on a log-log scale, good correlations were obtained for rats, dogs and humans. 5. Peak levels (Cmax) of two metabolites were reached at 0.5-1.0 h after oral and i.v. administration of nizatidine to dogs. The elimination curves of the two metabolites were similar to that of nizatidine. Significant relationships were found between doses of nizatidine and Cmax or AUC of both metabolites.

Administration, Oral↗

[A comparative study between the clinical and autoptic findings in cases with malignant tumor in the head and neck].

In 106 autopsies of patients in Kitasato University Hospital from 1974 to 1989, who had died of malignant tumor in the head and neck, the relationship between the clinical diagnosis and its autoptic finding was retrospectively investigated. The result was summarized as follows. 1. Characteristics in 98 cases other than malignant lymphoma: 1) Local recurrence was detected by autopsy in 60 cases (61%) among 98. Discrepancy between clinical diagnosis and autoptic findings was recognized in 10 cases (10%), in whom 4 false positive cases by clinical diagnosis were included and it was considered that the rate was relatively high. 2) The metastatic lymph nodes were demonstrated by autopsy in 50 cases (51%). Discrepancy between clinical diagnosis and autoptic findings was found in 37 (38%), 35 of them were clinically diagnosed to be negative. However, in 35 of them it was considered that the discrepancy had not influenced their fatal courses. 3) Metastases to distant organs were demonstrated by autopsy in 49 (50%). Discrepancy between clinical diagnosis and autoptic findings was found in 39 (40%). 33 of them were clinically diagnosed to be negative. The discrepancy concerned with the causes of death was shown in 5 cases. 2. Characteristics in 8 cases of malignant lymphoma: Discrepancy between clinical diagnosis and autoptic findings of distant metastases was frequently observed but the discrepancy concerned with the causes of death was not shown. There were 2 cases in which side effect of chemotherapy may cause poor prognosis.

Adolescent↗

Inhibition of adsorption of oral streptococci to saliva treated hydroxyapatite by chitin derivatives.

This study estimated the effects of five chitin derivatives low molecular chitosan (LMCS), ethyleneglycol chitin (PEGT), carboxymethyl chitin (PCMT), sulphated chitosan (PSSS), and phosphorylated chitin (PPPT) on the adsorption of three oral streptococci to saliva-treated hydroxyapatite (S-HA). The adsorption was evaluated by measuring the optical density of the bacterial cell suspensions released from saliva-treated hydroxyapatite by 0.5 N HCl. The adsorption of test strains to S-HA progressively decreased in proportion to each additional volume of PEGT, PPPT, or PSSS. PPPT and PSSS quite effectively inhibited the adsorption of S. mutans onto S-HA, but were less effective against S. sanguis and S. mitis. PPPT, PSSS, and PCMT all markedly promoted the desorption of S. mutans cells pre-adsorbed onto S-HA. Pretreatment of S-HA with PPPT, PSSS, or PCMT significantly decreased the subsequent adsorption of S. mutans and S. mitis. Pretreatment of these cells with PEGT also decreased their adsorption to S-HA. These findings suggest that these chitin derivatives may change the ionic natures of the S-HA and the bacterial cell surface, resulting in a less favorable interaction.

Adult↗

Production of platelet derived growth factor B chain (PDGF-B/c-sis) mRNA and immunoreactive PDGF B-like polypeptide by rheumatoid synovium: coexpression with heparin binding acidic fibroblast growth factor-1.

We present evidence supporting the hypothesis that locally produced platelet derived growth factor (PDGF) B-like polypeptides, as well as heparin binding growth factor-1 (HBGF-1), are involved in stimulating the pronounced hyperplasia of rheumatoid synovial stromal fibroblastlike cells. Explanted rheumatoid synovial tissues in vitro spontaneously secreted, in a time dependent manner, mitogenic activity for rheumatoid synoviocytes that was neutralizable by anti-PDGF antibody. PDGF B/c-sis mRNA transcripts were detected in synovium from patients with rheumatoid arthritis (RA) (n = 5). Spontaneous PDGF B-like synthesis was detected by immunoprecipitation of radiolabeled PDGF B-like polypeptides secreted by explanted tissues. Furthermore, rheumatoid synovial tissues, particularly macrophage-like cells, immunostained specifically with anti-PDGF B chain. The extent and intensity of staining and mononuclear cell infiltration were highly correlated. Immunostaining of osteoarthritic and normal synovial tissues was significantly less than RA synovium. PDGF-B immunostaining of synovial specimens previously characterized for expression of HBGF-1, the precursor of acidic fibroblast growth factor (aFGF), revealed that the extent and intensity of expression of HBGF-1 and PDGF-B were highly correlated.

Arthritis, Rheumatoid↗

Localization of 14C-nizatidine in the gastric wall of rats.

Nizatidine (N-[2-[[[2- [(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2) has a selective and competitive antagonism against histamine H2-receptors. The localization of 14C-nizatidine to the parietal cells of gastric mucosa which is the effective site of nizatidine, was studied. After oral administration of 14C-nizatidine to rats, the radioactivity was rapidly distributed at higher levels in the gastric mucosa than in the plasma. The mucosal level of nizatidine at 6 h after administration was still 63.3 ng/g tissue, being similar to the effective plasma concentrations in dogs and man. Nizatidine was confirmed to be retained as an unchanged drug in the gastric mucosa, supporting the duration of pharmacological effects of nizatidine. The localization of the drug in gastric wall after intraduodenal administration was examined by means of microautoradiography. The radioactivity of 14C-nizatidine absorbed as the fine developed silver granules was widely localized into the parietal cells in the mucosal layer through the gastric wall at 30 min after administration. Also at 2 h after administration, when the suppression of gastric acid secretion was strongest, the silver granules were almost uniformly localized all over the gastric wall, but the localization was generally less dense than at 30 min.

Animals↗

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 1st communication: absorption, distribution, metabolism and excretion after single administration to rats.

Studies on the absorption, distribution, metabolism and excretion of 14C-Z-103 and 65Zn-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) were performed after oral administration to rats. After oral administration of 14C-Z-103 and 65Zn-Z-103, the blood concentrations of 14C-radioactivity were 30- to 40-fold higher than those of 65Zn-radioactivity. The 14C-radioactivity showed a dose-dependent increase of Cmax and AUC values in the dose range from 13.1 mg/kg to 100 mg/kg, and remained longer in the blood. In contrast, no dose-dependent increase of AUC was observed with 65Zn-radioactivity, suggesting saturation of absorption at doses more than 30 mg/kg of 65Zn-Z-103. The major route of excretion of 14C-radioactivity was by excretion into the expired air, amounting to 38.8% of the administered dose, while the urinary and fecal excretions were low values at 4.1% and 13.3%, respectively. The radioactivity remaining in the carcass accounted for 39.3% of the dose. On the other hand, in the case of 65Zn-radioactivity, 85.0% of the administered dose was excreted into the feces and 10.5% of the dose remained in the carcass. Both 14C- and 65Zn-radioactivities were distributed to the whole body, while 14C-radioactivity showed higher concentrations in the body, and was retained longer than the 65Zn-radioactivity. When the plasma and the liver and kidney homogenates, from rats received 14C-Z-103, were treated with trichloroacetic acid (TCA), the radioactivities in the TCA-insoluble fraction increased as a function of time. Following the treatment of the homogenates with protease, the radioactivities in the TCA-insoluble fraction decreased. In vitro study was showed that L-carnosine of 14C-Z-103 added to the homogenates of liver and small intestine was metabolized to L-histidine. The results suggest that the remaining radioactivities in tissues and organs caused the incorporation of the metabolites of 14C-Z-103 into endogenous high molecular substances.

Animals↗

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 2nd communication: absorption, distribution, metabolism and excretion after repeated administration to rats.

After repeated administration of 14C-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) to rats for 21 days, the accumulation of radioactivity in the blood and tissues was proportional to the number of doses given. Following treatment of the terminal blood, plasma, liver and kidney samples with trichloroacetic acid (TCA) or protease, the radioactivity in these tissues was demonstrated to be TCA-insoluble and solubilized by the protease treatment. Thus, the accumulation of radioactivity after repeated administration of 14C-Z-103 was considered to be due to the utilization of the metabolites of L-carnosine, the constituent of Z-103, into a protein. The cumulative ratios of radioactivity excreted into the urine, feces and expired air and the radioactivity remaining in the carcass after repeated administration of 14C-Z-103 for 21 days were similar to those values obtained after a single administration, suggesting that repeated administration did not influence the excretion profile of Z-103. During the period of repeated administration of non-radioactive Z-103 to rats for 21 days, the fecal content of zinc was higher than that in nontreated rats, whereas it returned to the control level at 48 h after the final administration. There was no significant difference in the urinary concentration of zinc between treated and non-treated animals during the period of repeated administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Study on the metabolic fate of catena-(S)-[mu-N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 3rd communication: transfer into fetus and milk in rats.

Studies on the transfer into the fetus and the milk were performed after administration of 14C-Z-103 and 65Zn-Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]- zinc], CAS 107667-60-7) to rats. After oral administration of 14C-Z-103 to pregnant rats, the transfer of radioactivity to the fetus was studied by means of whole body autoradiography (ARG) and measurement of radioactivity in the fetus. The concentration of radioactivity in the fetus was approximately the same as those in the blood and the placenta of the maternal animal. The transfer of radioactivity into the milk was demonstrated after administration of 14C-Z-103 to lactating rats. Radioactivity in the fetus and milk are considered to be due to metabolites of L-carnosine of Z-103, such as amino acid or protein. The distribution of radioactivity in the fetus was also observed after administration of 65Zn-Z-103 to pregnant rats. However, after administration of non-radioactive Z-103 to pregnant rats, the zinc level in the fetus was found to be almost the same level as that in the fetus of the untreated rats. The transfer of radioactivity to the milk was studied after administration of 65Zn-Z-103 to the lactating rats, and it was seen that the concentration of radioactive zinc in the milk was much lower than the endogenous level of zinc in the milk at any of the time points investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 4th communication: disposition of zinc and amino acids in rats, dogs and monkeys.

The time course of the zinc plasma concentrations in rats, dogs and monkeys and the metabolic fate of L-carnosine were investigated after oral administration of Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7). There was no intradiurnal variation in the plasma concentrations of endogenous zinc in rats, dogs and monkeys. The plasma concentrations of endogenous zinc in dogs and monkeys were approximately the same as that in humans, whereas the plasma concentration of zinc in rats was 2.2-fold higher than that in man. After administration of Z-103 to non-fasted dogs at 100 mg/kg, the plasma concentration of zinc reached Cmax at 0.5 h after administration (1.7-fold higher than endogenous zinc level), while the plasma concentration was the lowest in comparison with other animal species. After administration to fasting rats at 50 mg/kg, the plasma concentration of zinc reached Cmax at 1 h after administration (2.5-fold higher than endogenous zinc level) and decreased thereafter, returning to the endogenous level at 8 h after administration. After oral administration to monkeys at 10 mg/kg and 50 mg/kg, the Cmax values were 4.1-fold and 6.8-fold higher than the endogenous level, respectively. The Tmax values were achieved at 4-6 h and 8 h after each administration, respectively, showing slower absorption in comparison with other animal species.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

[Interposition graft technique for the treatment of AAE (annuloaortic ectasia) with aortic regurgitation: surgical results].

Interposition graft technique had been used exclusively in 8 consecutive patients with AAE and AR. Two patients with severely dilated left ventricle (CTR 65, 80%, LVDd 93, 83 mm, LVDs 86, 68 mm), and 1 patient complicated with the postoperative mediastinitis died in the perioperative period, 10, 145 and 135 days after surgery, respectively. In the remaining 5 patients, excellent clinical improvement was observed with the reduction of CTR and echo-cardiographic findings without formation of hematoma, pseudoaneurysm, and leak from the suture lines on DSA and CT.

Adult↗

Effect of streptokinase on prostacyclin synthesis and phospholipase activity in cultured pulmonary artery endothelial cells.

In this study, we examined the effects of streptokinase on arachidonic acid release and prostacyclin biosynthesis in cultured bovine pulmonary artery endothelial cells. When intact cells were incubated with streptokinase, a significant stimulatory effect on prostacyclin biosynthetic activity in cells was evident without any cellular damage at all concentrations used (1-10,000 units/ml). Streptokinase also caused a marked release of arachidonic acid. It induced rapid phospholipid hydrolysis, resulting in the release of up to 15% of incorporated [3H]arachidonic acid into the medium. After the addition of streptokinase, degradation of phosphatidylcholine and phosphatidylethanolamine was observed and lysophosphatidylcholine and lysophosphatidylethanolamine were produced. We also observed a transient rise in diacylglycerol after the addition of streptokinase. To test for phospholipase C activity, the release of incorporated [3H]choline, [3H]inositol and [3H]ethanolamine into the culture medium was determined. The level of radioactive inositol showed an increase, but the changes in choline and ethanolamine were comparatively small. An increase in inositol was detectable within 1 min after streptokinase addition and peaked after 15 min. Inositol phosphate and inositol trisphosphate were released, and these releases were suppressed by the addition of neomycin (50 microM). These results suggest that streptokinase stimulates phospholipase A2 and C activity, and that prostacyclin biosynthesis is subsequently increased in cultured endothelial cells.

Animals↗