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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 919 records · Page 51Linked to original sources
PubMed1994

Increased calcium-channel currents of pancreatic beta cells in neonatally streptozocin-induced diabetic rats.

Using a whole-cell patch-clamp technique, voltage-dependent Ca(2+)-channel activities were found to be increased in cultured single beta cells isolated from neonatally streptozocin-induced diabetic rats (NSZ rats). The current-voltage relationship and inactivation time course of Ba2+ currents via L-type Ca2+ channels were indistinguishable between NSZ and control rats. However, the current density observed in NSZ rats was significantly greater than that in control rats. Ba2+ currents via T-type Ca2+ channels were also found to be enhanced in NSZ beta cells. The insulin-secretory capacity of cultured pancreatic islets in response to a depolarizing stimulus (20 mmol/L arginine or 30 mmol/L KCl) in the presence of 11.1 mmol/L glucose was augmented in NSZ rats, whereas that in response to 11.1 and 16.7 mmol/L glucose alone was significantly reduced. It is concluded that the impaired insulinotropic action of glucose in beta cells in NSZ rats is not due to reduced activity of voltage-dependent Ca2+ channels. The fact that insulin secretion induced by a depolarizing stimulus was enhanced in NSZ rats may be related to the augmented activity of the voltage-dependent calcium current found in NSZ beta cells.

Animals↗
PubMed1994

Effects of intravenous infusions of cholecystokinin-8 and pentagastrin on plasma concentrations of insulin and glucagon in sheep.

The effects of cholecystokinin-8 (CCK-8) and pentagastrin on insulin and glucagon secretion were studied in conscious sheep. Intravenous infusions of CCK-8 (3 to 1000 pmol kg-1 min-1 for 30 minutes) induced a dose-dependent increase in plasma insulin, but did not alter plasma glucagon concentration. The threshold dose of CCK-8 for stimulation of insulin secretion was 10 to 30 pmol kg-1 min-1. Pentagastrin was infused intravenously at doses of 10 to 3000 pmol kg-1 min-1. The maximal dose of pentagastrin slightly stimulated insulin, but not glucagon, secretion. The insulin secretory activity of pentagastrin was only 1/300 that of CCK-8 on a molar basis. The threshold dose of CCK-8 for stimulation of insulin secretion was similar to that for exocrine pancreatic secretion obtained in earlier studies. In conclusion, CCK is a potential candidate as a physiological factor regulating insulin secretion in sheep.

Animals↗
PubMed1994

Plasma secretin fluctuates in phase with periodic pancreatic secretion and the duodenal migrating myoelectric complex in calves.

Plasma secretin and cholecystokinin (CCK) levels and the periodic secretions of the exocrine pancreas were studied simultaneously with the duodenal migrating myoelectric complexes (MMC) in six milk-fed calves which had been starved overnight. The experiments were performed first when the calves were 10 to 16 days old and subsequently when they were 36 to 45 days old. Plasma secretin and the secretion of pancreatic juice fluctuated periodically in phase with the duodenal MMC: plasma secretin, and the pancreatic secretion of water and protein were significantly higher during the phase of irregular spiking activity than during the phase of no spiking activity in both investigations. Plasma CCK did not change throughout the MMC. The intravenous infusion of secretin at 120 pmol kg-1 bodyweight for one hour markedly stimulated pancreatic secretion and prolonged the duodenal MMC cycle, but it did not abolish pancreatic and duodenal periodic activity.

Aging↗
PubMed1994

Effects of hyaluronic acid on the development of 1- and 2-cell porcine embryos to the blastocyst stage in vitro.

The purpose of this study was to evaluate the ability of hyaluronic acid to improve the development of 1- and 2-cell porcine embryos to the blastocyst stage in a simple medium. In Experiment 1, we confirmed the ability of Whitten's medium supplemented with 15 mg/ml BSA to support the development of porcine embryos to the blastocyst stage under our experimental conditions. Embryos collected from oviducts were cultured at 38.5 degrees C in an atmosphere of 5% CO(2) in humidified air up to 6 d. After 2 d of culture, 82 and 78% of embryos reached the 4-cell stage or beyond in TCM199 supplemented with 10% fetal calf serum (FCS) and in Whitten's medium with BSA, respectively. However, no embryo developed to the morula stage in TCM199 after 6 d of culture. On the other hand, 26 and 15% of embryos developed to the morula and the blastocyst stage in Whitten's medium, respectively. In Experiment 2, we determined whether supplementation of hyaluronic acid in Whitten's medium would improve the development of porcine embryos to the blastocyst stage. After 6 d of culture, development of the embryos to the blastocyst stage was best supported in Whitten's medium with 4 mg/ml BSA and 0.5 mg/ml hyaluronic acid (70%). The proportion of degenerated embryos was lower in the presence than in the absence of hyaluronic acid. These results indicate that the supplementation of Whitten's medium with hyaluronic acid improves the development of 1- and 2-cell porcine embryos to the blastocyst stage.

Journal Article↗
PubMed1994

Mu opioid receptor: expression and vagotomy-induced depletion of the mRNA in medullary preganglionic neurons.

By in situ hybridization with digoxigenin-labeled RNA probes, distinct expression of mu opioid receptor mRNA was found in rat medullary preganglionic neurons for vagal parasympathetic outflow. Two days or more following unilateral vagotomy, the expression was almost completely abolished on the operated side. The results, taken together with previous findings indicating proximodistal axonal transport of radioligand-labeled opioid receptors, suggest that the medullary preganglionic neurons thus identified are the source for mu opioid receptor acting in cardiorespiratory and gastrointestinal tissues.

Animals↗
PubMed1994

Late relapse of small cell lung cancer treated with radiation therapy alone--case report.

This report describes an unusual case of a long-term survivor with small cell lung cancer (SCLC), treated with radiation therapy alone having a late relapse with solitary brain metastasis 6.5 years after the initial treatment. He received radiation therapy and died of the brain metastasis 8.5 years after the initial treatment. Autopsy revealed no tumor recurrence at the primary site and no distant metastases except for the brain. The histology of the brain tumor was small cell carcinoma.

Brain Neoplasms↗
PubMed1994

Effect of minoxidil sulfate and pinacidil on single potassium channel current in cultured human outer root sheath cells and dermal papilla cells.

Minoxidil sulfate and pinacidil are K channel openers and are considered to promote hair growth. However, there have been no studies on the single channel current of isolated cells from hair follicles. Therefore, we characterized the single K channel current of outer root sheath cells and dermal papilla cells and the effect of K channel openers on K currents by patch clamp. We also carried out 86Rb efflux studies to observe macroscopic K channel currents. In physiological saline, these two cells showed two types of K channels, large and small conductance Ca(2+)-activated K channels, both intact cell-attached and excised inside-out patches. In symmetrical 150 mM K solution, unitary conductances were 246 and 70 pS, respectively. Intracellular ATP (up to 5 mM) or glibenclamide (20 nM), a specific ATP-sensitive K channel blocker, did not block these channels. Minoxidil sulfate (5 micrograms/ml) or pinacidil (10 microM) did not open these two types of K channels or increase 86Rb efflux. These results suggest that minoxidil sulfate or pinacidil did not activate K channel current in hair follicles, and that the drug effect on hair growth might be mediated by other mechanisms such as increased blood flow.

Calcium↗
PubMed1994

Temperature change of the ripple structure in fully hydrated dimyristoylphosphatidylcholine/cholesterol multibilayers.

The ripple structure was studied as a function of temperature in fully hydrated dimyristoylphosphatidylcholine (DMPC)/cholesterol multibilayers using synchrotron x-ray small-angle diffraction and freeze-fracture electron microscopy. In the presence of cholesterol, the ripple structure appears below the pretransition temperature of pure DMPC multibilayers. In this temperature range the ripple periodicity is relatively large (25-30 nm) and rapidly decreases with increasing temperature. In this region, defined as region I, we observed coexistence of the P beta' phase and the L beta' phase. The large ripple periodicity is caused by the formation of the P beta' phase region in which cholesterol is concentrated and the L beta' phase region from which cholesterol is excluded. An increase in ripple periodicity also takes place in the narrow temperature range just below the main transition temperature. We define this temperature region as region III, where the ripple periodicity increases dramatically toward the main transition temperature. In region II, between regions I and III, the ripple periodicity decreases gradually with temperature. This behavior is quite similar to that of pure DMPC. Temperature-versus-ripple periodicity curves are parallel among pure DMPC and DMPCs with various cholesterol contents. We explain this behavior in terms of a model proposed by other workers.

Cholesterol↗
PubMed1994

Characterization of multiple molecular forms of Mg(2+)-dependent protein phosphatase from Saccharomyces cerevisiae.

Three molecular species of Mg(2+)-dependent protein phosphatase (MPPs-1, -2, and -3) were isolated by DEAE cellulose column chromatography and gel filtration from an extract of Saccharomyces cerevisiae. MPP-1 was further purified 150-fold by chromatography using thio-phosphorylated myosin light chain-agarose. MPPs-1, -2, and -3 were distinct from the major acid and alkaline phosphatases, and their activities were not affected by okadaic acid, microcystin-LR or Ca2+, and calmodulin, resembling the enzymatic properties of type 2C protein phosphatase of mammalian cells. The apparent molecular masses of MPPs-1, -2, and -3 on gel filtration were 53, 112, and 128 kDa, respectively. It was demonstrated that MPP-1 is a globular protein of 53-55 kDa and that MPPs-2 and -3 are oligomeric proteins that dissociate upon sucrose density gradient centrifugation, generating catalytic proteins of about 50 kDa. Since the substrate specificities of MPPs-1, -2, and -3 differed from each other both before and after sucrose density gradient centrifugation, it was suggested that the catalytic proteins of these three enzymes are distinct molecular species.

Chromatography, DEAE-Cellulose↗
PubMed1994

Efficacy of twice-daily cimetidine in pediatric peptic ulcer.

The clinical efficacy of twice-daily cimetidine (20 mg/kg/day) was retrospectively studied in 19 children with gastric ulcer (GU) and 23 with duodenal ulcer (DU) in the active stage. Endoscopically confirmed cumulative healing rates at 2, 4, and 8 weeks of treatment were 53.5, 73.7, and 94.7% in the GU group and 15.4, 50.0, and 87.0% in the DU group, respectively. There was no significant difference between the groups at each time point. The mean period of time until complete disappearance of symptoms in the GU and DU groups was 3.5 +/- 2.6 and 4.2 +/- 3.3 days, respectively (NS). With regard to symptoms, abdominal tenderness rather than spontaneous pain appeared to be a better indicator of ulcer healing. Ulcer recurrence was found endoscopically during follow-up in 2 of 13 GU patients (15.4%) and 11 of 19 DU patients (57.9%); thus, the cumulative recurrence rate of the DU group was higher than that of the GU group (p < 0.05). No adverse effects related to cimetidine were demonstrated during treatment or short-term follow-up. We conclude that twice-daily cimetidine at a dosage of 20 mg/kg/day is as effective for the symptomatic improvement and healing of peptic ulcer as the conventional three- or four-times-daily regimens. The optimal dosage of cimetidine requires further study.

Adolescent↗
PubMed1994

The effects of omeprazole on the ultrastructure of gastric parietal cells.

This study was designed to investigate ultrastructural changes in parietal cells during treatment with omeprazole. Endoscopic biopsies were performed in patients treated with omeprazole (n = 2) and cimetidine (n = 4) and in normal controls (n = 3). In the patients who received omeprazole, many parietal cells (90.9 and 66.6%) were in the "stimulated" or "partially stimulated" stage. As reported previously, our results suggest that omeprazole fails to prevent the morphological transition of parietal cells to an actively secreting phase, although it strongly inhibits acid secretion. The altered cells frequently demonstrated more marked dilation of the secretory canaliculi, compared with those of normal controls and cimetidine-treated patients. Vacuolation was found in one patient given omeprazole and one given cimetidine. In the former patient, initial famotidine treatment also led to the vacuolation of parietal cells. However, this change does not seem to imply serious parietal cell degeneration. There were no adverse morphological changes in mitochondria and nuclei in any of the groups. In conclusion, vacuolation is not specific to omeprazole. Moreover, if omeprazole is administered at a pharmacologically effective dosage for a short period of time, it may not have serious effects on the ultrastructure of human parietal cells.

Child↗
PubMed1994

Changes in hypothalamic-pituitary function following bone marrow transplantation in children.

Patients who undergo bone marrow transplantation (BMT) frequently experience impaired pituitary function, but precise assessment using repeated provocative tests has not been described. We studied 32 children (16 boys) who had BMT after receiving preparative irradiation. Assessment of pituitary function was performed by infusing insulin, luteinizing hormone-releasing hormone (LHRH), and thyrotropin-releasing hormone (TRH) on several occasions at various intervals during the follow-up period. Serum free thyroxine (FT4) and thyrotropin (TSH) levels tended to be low during the early period following BMT. Serum FT4 concentrations reverted to the low-normal range 1 year after transplant, and eight of 29 patients had subnormal and delayed TSH response to TRH consecutively. No children showed overt hypothyroidism. Basal and peak serum gonadotropin levels in response to LHRH were elevated in the patients who had received transplant around the time of puberty. Leydig cell function assessed by human chorionic gonadotropin test was normal. Three girls experienced menarche, and one male patient fathered a normal boy 7 years after BMT. Pituitary-adrenal function and prolactin secretion were not affected. A high incidence of transient hypothyroidism which did not require replacement therapy and gonadal failure among pubertal children were observed. Shielding of gonads should be attempted, if possible, at the time of preparative irradiation to prevent resultant hypogonadism.

Adolescent↗
PubMed1994

Local versus peripheral blood administration of cholecystokinin-8 and secretin on pancreatic secretion in calves.

The effects of local and peripheral administration of cholecystokinin-8 (CCK-8) and secretin on the interdigestive pancreatic secretion were examined in conscious preruminating calves. Six calves were surgically fitted with a pancreatic catheter and duodenal cannula, duodenal electrodes and strain gauges, and cooling devices on the cervical vagi. Local intra-arterial (I.A.) infusions were made into the duodenal branch of the right gastroepiploic artery, and peripheral infusions (I.V.) into the external jugular vein. CCK-8 and secretin were infused I.A. and I.V. for 5 min (0, 10, 30 and 100 pmol (kg body weight)-1) during the asecretory phase of the pancreatic interdigestive cycle. CCK-8 and secretin at 100 pmol kg-1 were administered concomitant with reversible cold vagal blockade. Local infusion of CCK-8 without vagal blockade resulted in a significantly faster and stronger pancreatic response than the respective peripheral infusion, although CCK in peripheral blood plasma was paradoxically only minimally increased after I.A. CCK-8 in comparison with a marked increase after I.V. CCK-8. Vagal blockade noticeably decreased the pancreatic response for I.A. CCK-8, but not for I.V. CCK-8. Secretin produced similar pancreatic responses after I.V. and I.A. administration, but the plasma secretin concentration in peripheral blood was markedly lower after I.A. than after I.V. infusions. Cold vagal blockade uniformly reduced the stimulatory effect of I.A. and I.V. secretin infusion on the exocrine pancreas. In calves, CCK-8 apparently stimulates the exocrine pancreas by two different mechanisms: by a direct effect that is vagally independent as well as by an indirect effect in the duodenum that is vagally dependent. The indirect effect of secretin in the duodenum is less clear, but both direct and indirect effects of secretin depend on vagal integrity.

Animals↗
PubMed1994

Chemical specificity of short-chain fatty acids in stimulating insulin and glucagon secretion in sheep.

The chemical specificity and structural requirements of short-chain fatty acids (SCFAs) in stimulating pancreatic endocrine responses was investigated in conscious sheep. Normal SCFAs with one to eight carbons were injected intravenously at seven doses of 39-2,500 mumol/kg body wt. The isomers or derivatives of SCFAs were administered at 625 mumol/kg body wt. Analysis of dose-response curves showed that n-butyric acid (4 carbons in the molecule) was most effective for both insulin and glucagon secretion among the normal SCFAs tested. In addition, one carboxylic group was absolutely required, since hormone secretion was significantly reduced or abolished with compounds in which the carboxylic element was replaced by other groups and with dicarboxylic acids. The form of the hydrocarbon chain (branched, cyclic, or benzoic ring) also affected hormone secretory activity. Most of the compounds that replaced hydrogen in the hydrocarbon chain by other groups at various positions reduced or abolished the hormone secretory effect obtained by n-butyric acid. In conclusion, a monocarboxylic acid with several numbers of hydrocarbons was required for insulin or glucagon secretion. These results suggest that the pancreatic endocrine system can recognize the chemical structure of SCFAs in detail and induce hormone secretion in sheep.

Animals↗
PubMed1994

Prostaglandin E1 abrogates early reductive stress and zone-specific paradoxical oxidative injury in hypoperfused rat liver.

This study was designed to investigate the effects of prostaglandin E1 on reductive stress and the subsequent oxidative cell injury in hypoperfused rat liver. The intralobular heterogeneity of hepatocellular redox state, mitochondrial dysfunction, and intracellular hydroperoxide formation were visually monitored by digital microfluorography of pyridine nucleotide autofluorescence, rhodamine 123, and dichlorofluorescein fluorescence, respectively. Under the 25% low flow perfusion, pyridine nucleotide autofluorescence increased time-dependently and reached a steady state at 10 min among the entire lobules. The decrease in mitochondrial membrane potential was > 20 mV in all portions of the lobules at 60 min. The onset of hydroperoxide formation was observed at 40 min in the marginally oxygenated proximal portion of anoxic pericentral regions and the oxidative impact reached a maximum level at 60 min. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazo [1,5-a]-1,3,5-triazine-4-olate monohydrate (BOF 4272), a novel xanthine oxidase inhibitor, suppressed the zone-specific oxidative changes without attenuating the increase in pyridine nucleotide autofluorescence and mitochondrial dysfunction. Pretreatment with prostaglandin E1 not only abrogated an early increase in pyridine nucleotide fluorescence and mitochondrial dysfunction induced by hypoperfusion but also diminished the subsequent midzonal oxidative injury. Since prostaglandin E1 has no oxyradical-scavenging action, the preventive effect of this reagent on the hypoxia-induced oxidative cell injury is attributable to the attenuation of mitochondrial dysfunction. These results suggest that, in low flow hypoxia, early reductive stress plays a key role in the initiation of xanthine oxidase-mediated midzonal oxidative changes, which may lead to subsequent centrilobular necrosis.

Alprostadil↗
PubMed1994

Pulmonary haemodynamics in awake rats following treatment with endotracheal pancreatic elastase.

The purpose of this paper was to study pulmonary haemodynamics in an elastase-induced emphysema model in awake rats (Group-EL, n = 9) in comparison with saline-treated controls (Group-C, n = 12). Four weeks before haemodynamic study, porcine pancreatic elastase and normal saline were intratracheally instilled in Group-EL and Group-C, respectively. Indwelling pulmonary artery and abdominal aortic catheters were positioned two days before the haemodynamic study. Breathing room air, mean pulmonary artery pressure (Ppa) tended to be higher in Group-EL than in Group-C, although the difference was not statistically significant. Systemic pressure, total systemic vascular resistance and cardiac index did not differ between groups. When exposed to 10% O2, Ppa and pulmonary vascular resistance (PVR) of both groups rose significantly. The increase of Ppa, (but not PVR) in Group-EL during hypoxia was significantly higher than that in Group-C. The magnitude of hypoxic pulmonary vasoconstriction (HPV) tended to be larger in Group-EL than in Group-C. Right ventricles of Group-EL were more hypertrophic than those of Group-C, suggesting a period of higher pulmonary artery pressure than for Group-C. The present results imply that the pressor response of pulmonary vasculature to acute alveolar hypoxia is possibly enhanced in awake rats upon examination four weeks after elastase treatment.

Animals↗