Biomedical subjects

K Miyata

Publications and source records attributed to K Miyata.

At least 289 records · Page 16Linked to original sources

PubMed1991

Binding of viral glycoprotein with trypsin and its relation to virulency. I. Initial step of binding.

The interaction between surface proteins of some enveloped viruses and trypsin was studied by computer analysis. Prior to the cleavage of the viral protein by trypsin, hydrophobic interaction between them at the vicinity of their active sites may occur. An exposed hydrophobic portion was found there which theoretically could stimulate the interaction. This interaction would be rather non-specific: according to the analysis, trypsin could bind equally well with weakly virulent virus and virulent viruses. Following this interaction, a specific reaction between their active sites would occur. The specificity was found to be related to the virulency of the virus.

Amino Acid Sequence↗

PubMed1991

Binding of viral glycoprotein with trypsin and its relation to virulency. II. Comparison between bovine and Streptomyces griseus trypsins.

The two step nature of the binding reaction between trypsin and viral glycoproteins was further investigated using two types of trypsin, bovine trypsin and Streptomyces griseus trypsin. The experimental results were explained by the van der Waals energy operating in the second step, suggesting that the conformational aspects, in addition to the electrostatic nature, of the interacting peptides are decisive in this specific process.

Amino Acid Sequence↗

PubMed1991

Studies on the mechanism for the gastric mucosal protection by famotidine in rats.

The effect of famotidine on gastric lesions induced by the decrease in mucosal defensive resistance was investigated in rats and compared with those of cimetidine, pirenzepine and cetraxate. Famotidine (0.03, 0.1 and 0.3 mg/kg, p.o.) inhibited dose-dependently the development of gastric lesions produced by taurocholate-histamine in doses that suppressed histamine-induced acid secretion in pylorus-ligated rats. The H2-antagonist also prevented gastric mucosal lesions induced by taurocholate-serotonin, iodoacetamide, acidified aspirin and acidified ethanol. Cimetidine, pirenzepine and cetraxate showed the inhibitory effects on almost all types of the gastric lesions, but their inhibitory effects were much less potent than those of famotidine. On the other hand, famotidine inhibited the decreases of gastric mucosal blood flow induced by acidified ethanol and the mucosal contents of glycoprotein induced by water immersion restraint stress. In addition, famotidine increased the transgastric potential difference (PD) and promoted the recovery of decreased transgastric PD induced by acidified ethanol in rats. These results suggest that the preventive effect of famotidine on gastric lesions is attributable not only to suppression of acid secretion but to activation of the gastric mucosal defensive mechanisms.

Animals↗

PubMed1991

Antiemetic effects of YM060, a potent and selective serotonin (5HT)3-receptor antagonist, in ferrets and dogs.

YM060, (R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride, is a new serotonin (5HT)3-receptor antagonist. We examined the effects of YM060 on chemotherapeutic agent-, apomorphine- and copper sulfate-induced emesis. Intravenous YM060 potently prevented cisplatin (10 mg/kg, i.v.)-induced emesis with ED50 values of 0.06 (0.05-0.07) micrograms/kg, i.v. in ferrets. Based on the ED50 values, YM060 was 300, 20 and 100 times more potent than ondansetron, granisetron and the S-isomer of YM060, respectively. The relative potencies of these drugs described above were similar to those in the previously reported 5HT3-receptor antagonism. YM060 given orally also potently inhibited cisplatin (10 mg/kg, i.p.)- and cyclophosphamide (200 mg/kg, i.p.)-induced emesis in ferrets with ED50 values of 0.1 (0.09-0.11) and 0.02 (0.16-0.27) micrograms/kg, p.o., respectively. All tested 5HT3-receptor antagonists including YM060 failed to prevent apomorphine (0.1 mg/kg, s.c.)-induced emesis in dogs and copper sulfate (1%, 10 ml, p.o.)-induced emesis in ferrets. Our data indicate that YM060 is a highly potent inhibitor of chemotherapeutic agent-induced emesis and that the antiemetic effect of YM060 may be depend on 5HT3-receptor antagonism.

Administration, Oral↗

PubMed1991

Pharmacologic profile of (R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride (YM060), a potent and selective 5-hydroxytryptamine3 receptor antagonist, and its enantiomer in the isolated tissue.

(R)-5-[(1-Methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride (YM060) is a structurally novel, extremely potent, and highly selective serotonin (5HT)3 receptor antagonist. Its 5HT3 receptor blocking properties were compared with those of its enantiomer (S-form), granisetron and ondansetron, in the isolated distal colon of the guinea pig. YM060 competitively antagonized 5HT- and 2-methyl-5HT-induced contraction of the colon, with pA2 values of 8.71 +/- 0.09 (n = 12) and 8.69 +/- 0.06 (n = 9), respectively. Its antagonistic activity was approximately 200, 5 and 50 times more potent than those of the S-form (pA2 = 6.33 +/- 0.06, n = 9 against 5HT; 6.47 +/- 0.1, n = 9 against 2-methyl-5HT), granisetron (pA2 = 8.03 +/- 0.07, n = 9; 8.02 +/- 0.04, n = 9), and ondansetron (pA2 = 7.02 +/- 0.08, n = 9; 6.98 +/- 0.02, n = 9), respectively. Each pA2 value was constant and the isomeric activity ratio (R-form/S-form) was constant irrespective of the agonist used, suggesting that each drug acted on the same 5HT3 receptor. YM060 failed to antagonize contractions induced by 5HT in the saphenous vein of the dog (5HT1-like receptor) or in the aorta of the rabbit (5HT2 receptor. YM060 has a low affinity for alpha-1 (rabbit aorta; pA2 = 5.08 +/- 0.07, n = 8) and alpha-2 (guinea pig ileum; pA2 = 5.61 +/- 0.09, n = 11) adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

[A case of adult-onset nemaline myopathy (adult-onset rod disease) with distal muscular hypertrophy].

We reported a 40-year-old male with adult-onset nemaline myopathy (adult-onset rod disease) showing muscular hypertrophy of distal limbs. At the age of 25, he noticed thinness of his thighs. Difficulty in climbing stairs slowly progressed from the age of 35. On admission neurological examination revealed muscular weakness and atrophy of proximal limbs and hypertrophy of distal flexors. Normal laboratory tests included serum creatine kinase, myoglobin, aldolase and pyruvate. Electromyography revealed severe neurogenic changes in the right biceps brachial muscle and the right quadriceps muscle, and moderate changes in the right gastrocnemius. Biopsy specimen of the deltoid muscle demonstrated type 1 fiber predominance and type 1 fiber atrophy, and there was small group atrophy and type grouping. Abundant nemaline rods were found mainly in type 1 fibers (81.5%). In order to evaluate hypertrophy of calf muscles, T1-weighted MRI of lower extremity was performed. While transaxial images through mid thigh showed moderate fatty replacement, increased volume and little fatty replacement were found in the mid calf. Therefore, hypertrophy of the calf muscle seemed to be compensative hypertrophy. But in this case neurogenic factors were indicated electromyographically and histologically. These findings may advocate the notion that neurogenic factors involved not only congenital but adult-onset rod disease.

Adult↗

PubMed1991

Corneal endothelial cell damage in penetrating keratoplasty.

Fifty-eight corneal grafts were examined by specular microscopy to determine the corneal endothelial cell damage following penetrating keratoplasty. The average postoperative follow-up period was 10.1 months. The cell density decreased continuously during the observation period, and the endothelial cell loss of the central area of the cornea in all the cases averaged 10.4% at two weeks after the surgery, 16.0% at one month, 33.0% at three months, 39.4% at six months, and 48.2% at one year. However, the cell loss in the keratoconus group averaged -1.9, 1.2, 9.9, 30.6 and 33.4% for the corresponding postoperative periods. The cell loss in the bullous keratopathy eyes showed higher values compared to those in the keratoconus and the corneal leukoma eyes. It was concluded that cell loss in penetrating keratoplasty during the first postoperative year depends on the host diseases.

Adolescent↗

PubMed1991

[Prospective controlled study of elective sclerotherapy plus oral propranolol for prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage].

In a prospective, randomized controlled trial, 43 patients with cirrhosis and variceal hemorrhage were allocated after control of the bleeding to treat by elective sclerotherapy alone (n = 23) or by oral propranolol after elective sclerotherapy (n = 20). The dose of oral propranolol was based on a reduction of the resting pulse rate by 25%. The end points of the study were rebleeding or death. Both treatment groups were comparable with respect to origin and severity of liver disease, size of esophageal varices and portal pressure at entry. The mean follow up was 27 +/- 19 months for all patients. Patients treated sclerotherapy alone had more rebleeding (n = 11) did than those in the sclerotherapy plus propranolol (n = 3). The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 77 and 66% in sclerotherapy alone, and 100 and 85% in sclerotherapy plus propranolol; the difference between the two groups was significant. No statistically significant effect on mortality was seen. These data support that oral propranolol after sclerotherapy reduces the risk of recurrent bleeding in cirrhotics treated elective sclerotherapy.

Administration, Oral↗

PubMed1991

Serotonin (5-HT)3 receptor blocking activities of YM060, a novel 4,5,6,7-tetrahydrobenzimidazole derivative, and its enantiomer in anesthetized rats.

YM060 [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimida zol e hydrochloride], is structurally independent of other 5-HT3 receptor antagonists. We investigated in vivo 5-HT3 receptor blocking activity of YM060 and compared results with those of its enantiomer (S-form), ondansetron (GR38032F), granisetron (BRL43694), ICS205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], LY277359 [endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1] oct-3-yl)-7-benzofuran-carboxamide-(Z)-2-butenedioate (1:1)], Y25130 [(+-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4- dihydro-2H-1,4-benzoxazine-8-carboxamide hydrochloride] and zacopride [(R,S)4-amino-N-[1-azabicyclo (2.2.2)oct-3-yl]-5-chloro-2-methoxybenzamide(E)-2-butenedioat e]. YM060 injected i.v. dose-dependently inhibited the reduction in heart rate induced by 5-HT (30 micrograms/kg i.v.) in rats (von Bezold-Jarisch reflex) with an ED50 value of 0.036 (0.031-0.041) micrograms/kg (n = 3-5). Based on these values, YM060 was 53, 18, 23, 16, 11 and 4 times as potent as ondansetron, granisetron, ICS205-930, LY277359, Y25130 and zacopride, respectively. The S-form of YM060 also inhibited 5-HT-induced bradycardia, but with a potency approximately 250 times less than that of YM060 (R-form). YM060 dosed p.o. also inhibited 5-HT-induced bradycardia with an ED50 value of 0.59 (0.44-0.80) micrograms/kg (n = 3-5), indicating the drug to be 387, 66, 97, 6 and 16 times more potent than ondansetron, granisetron, ICS205-930, LY277359 and Y25130, respectively, but 2 times less potent than zacopride. Bioavailability of YM060 based on the p.o.-to-i.v. ED50 ratio (p.o./i.v. = 16) was lower than those of zacopride (2) and LY277359 (6), similar to that of Y25130 (22) and better than those of ondansetron (109), granisetron (60) and ICS205-930 (71).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1990

Salmonid pituitary gonadotrophs. I. Distinct cellular distributions of two gonadotropins, GTH I and GTH II.

Using antisera specific for the beta subunits of two distinct coho salmon gonadotropins, GTH I and GTH II, an immunocytochemical study of rainbow trout and Atlantic salmon pituitaries was done. Cells which immunostained with anti-GTH I beta were distributed in the periphery of the glandular cords of the proximal pars distalis (PPD), in close association with somatotrophs. On the other hand, cells immunostained with anti-GTH II beta were located in the central parts of the glandular cords of the PPD. Neither the GTH I-producing nor the GTH II-producing cells stained with antisera against chum salmon growth hormone or the beta subunit of human thyroid-stimulating hormone. Moreover, GTH I and GTH II were localized in distinctly different cells. In no case was colocalization of these GTHs in the same cell observed. Finally, it was concluded that classification of GTH cells as globular and vesicular forms does not reflect the type of hormone produced by the cell, but may reflect differences in the physiological conditions of the cells.

Animals↗

PubMed1990

Regulation of expression of carbon-assimilating enzymes by nitrogen in maize leaf.

We have utilized the cellular differentiation gradient of the developed, youngest leaf to examine the regulation by nitrogen of levels of phosphoenolpyruvate carboxylase (PEPCase), pyruvate orthophosphate dikinase (PPDK), and ribulose 1,5-bisphosphate carboxylase in maize (Zea mays L.). The protein whose level regulated most preferentially by N availability was PEPCase, followed by PPDK, and the changes in level occurred most conspicuously at the photosynthetically maturing cells. Pulse and pulse-chase experiments to analyze photosynthetic fixation of [(14)C]CO(2) indicate that maize leaf primarily exploited a C(4)-mode of photosynthetic fixation of carbon dioxide even under a selective reduction in levels of these proteins. The effects of N on the synthesis of these proteins and the accumulation of corresponding mRNAs during recovery from a deficiency were examined by pulse and pulse-chase labeling with [(35)S]Met and by hybridization, respectively. The rate of turnover of PPDK was substantially higher than that of the other proteins. Results also showed that the reduced accumulation of PEPCase, as well as PPDK, under N deficiency could largely be accounted for a reduced level of synthesis of protein with a concomitant reduction in level of their mRNAs. This indicates that the N-dependent selective accumulation of these enzymes is primarily a consequence of level of its mRNAs.

Journal Article↗

PubMed1990

A case of I-cell disease.

A case of I-cell disease is reported. The patient suffered from several episodes of pneumonia, and died of pneumonia at 12 months of age. Tissue specimens obtained at autopsy were stained with colloidal iron to demonstrate acid mucopolysaccharides. Characteristic foamy changes were observed in organs such as the heart, kidneys, liver, spleen and brain. An interesting finding in this case was that not only the interstitial cells but the alveolar epithelium in the lung showed the same foamy changes. The major causes of death of patients with I-cell disease are congestive heart failure and recurrent respiratory infections. However, there have been few reports on the histological changes in the lungs, and none have described the changes in the alveolar epithelium. Further cases must be investigated to examine the pathological relation between the histological changes in the lungs and the cause of death, because recurrent respiratory infections are the major contributor to death in patients with I-cell disease.

Female↗

PubMed1990

[A case with acute suppurative thyroiditis due to Eikenella corrodens and alpha-Streptococcus].

A 6-year-old girl with acute suppurative thyroiditis is reported. She suffered from suppurative thyroiditis twice, and E. corrodens and alpha-streptococcus were grown from the abscess each time. They were sensitive to antibiotics used, but surgical drainage was necessary to cease to inflammation each time. E. corrodens seemed to be a causative organism with or without another organism in compromised patients and/or patients with anatomical abnormalities. The presented patient was supposed to have some anatomical abnormality such as an internal fistula from the piriform sinus connecting the perithyroidal space, however, no abnormalities were detected during these episodes.

Acute Disease↗

PubMed1990

Selective and competitive histamine H2-receptor blocking effect of famotidine on the blood pressure response in dogs and the acid secretory response in rats.

Famotidine has been already demonstrated to be a competitive H2-receptor antagonist in the stomachs of dogs and cats. The present experiments were carried out to examine the effects of famotidine on changes in blood pressure induced by dimaprit and several other agonists in vagotomized, anesthetized dogs and on changes in gastric acid secretion induced by histamine in stomach-perfused, anesthetized rats. Famotidine caused a parallel displacement of the dimaprit dose-response curve to the right with a DR10 value of 0.059 mumols/kg, indicating that famotidine is 166 times more potent than cimetidine in vascular H2-blocking activity. On the contrary, famotidine did not affect the depressor responses to 2-pyridylethylamine and histamine that were antagonized by mepyramine. The histamine dose-response curve was displaced to the right more markedly after simultaneous administration of mepyramine and famotidine than after mepyramine alone. The effects of methacholine, phenylephrine and isoproterenol on blood pressure were not influenced by famotidine in doses up to 720 nmol/kg. In rats, famotidine also caused a parallel displacement of the acid dose-response curve to histamine to the right with a DR3 value of 24 mumols/kg/hr in stomach-perfused rats anesthetized with pentobarbital, exhibiting a potency 108 times greater than that of cimetidine. Analysis of the acid dose-response curve with the Edie-Hofstee transformation showed that famotidine, like cimetidine, was a competitive H2-receptor antagonist.

Anesthesia↗

PubMed1990

Fine structure of the dorsal epithelium of the mongoose tongue.

The epithelium of the lingual dorsum of the mongoose, Herpestes edwardsi, was composed of two main areas: the interpapillary area, characterised by the absence of keratinisation; and the papillary area, characterised by hard keratinisation. The number of tonofibrils in the cytoplasm gradually increased, and the volume of the individual cells also increased, from the germinal layer to the intermediate layer of the interpapillary epithelium. No keratohyalin granules were recognised in these cells. In the cells of the surface layer of the interpapillary epithelium, most of the cytoplasm was filled with tonofilaments. The germinal layer of the papillary epithelium was almost identical to that of the interpapillary epithelium. In the intermediate layer, three different types of keratohyalin granule were apparent. The first type consisted of loosely aggregated ribosomes and had moderate electron density. The second type consisted of electron-dense granules derived from granules of the first type. The third type consisted of conjugated structures made up of tonofibrils, which were embedded in electron-dense material. Free ribosomes gradually disappeared as the keratinised layer was approached and most of the cytoplasm of cells in this layer was filled with keratin fibres.

Animals↗

PubMed1990

New wound-healing model using cultured corneal endothelial cells. 1. Quantitative study of healing process.

A new in vitro model to evaluate the corneal endothelial wound-healing process was developed. Confluent monolayer cell sheets of either rabbit or bovine corneal endothelial cells were cultured on cover slips, the surface of which had been precoated with hydroxyethyl methacrylate (HEMA) except for the 8 mm-diameter area for cell culture. Wounds were made by scraping off cells in the center of the cell sheets using a rotating silicone tip. The areas of these wounds were measured by a method of computed planimetry. The average wound area was 3.00 +/- 0.21 mm2 in rabbit cell cultures and 3.18 +/- 0.28 mm2 in bovine. The healing process after the wounding was observed using an inverted phase contrast microscope and wound-healing rates (healed area per hour) were calculated. Wounded areas were recovered by 60 hours in rabbit experiments, and by 84 hours in bovine experiments. Wound-healing rates were different among the observation periods and showed differences between the two species. The healing rates in the rabbit were higher than those in the bovine in the early phase. This in vitro model can be used for quantitative evaluation of the wound-healing process of the corneal endothelium.

Animals↗

PubMed1990

New wound-healing model using cultured bovine corneal endothelial cells. 2. Role of migration and mitosis studied by immunohistochemistry.

The roles of migration and mitosis in the in vitro corneal endothelial wound-healing process were studied using an immunohistochemical method. The in vitro wound-healing model was a cultured cell sheet prepared using bovine corneal endothelium, and the wound was made at the center of the cell sheet using a rotating silicon tip. Following the wounding, specimens were incubated with bromodeoxyuridine (BrdU) for 12 hours. After the fixation with 10% phosphate-buffered formalin, the cells incorporating BrdU were stained by the avidin biotin peroxidase complex method. In 12 hours after the wounding, no stained cells were observed. In 24 hours, cell migration had started and a few cells were stained; the average number of stained cells was 14.6 +/- 4.0 cells/mm2. In 48 hours, the number of stained cells increased. The maximum number of stained cells was observed between 48 and 60 hours after the wounding. The number of stained cells decreased rapidly after 72 hours when the wound was almost closed. Stained cells were most numerous in the area within 0.8 mm of the wound edge throughout the wound-healing. The endothelial wound-healing process in this model could be divided into four phases, latent, migration, concurrence of migration and mitosis, and inhibition phases. This in vitro wound-healing model could simulate the wound-healing process in vivo and will be useful for a quantitative evaluation of drug effects on the corneal endothelial wound-healing.

Animals↗

PubMed1990

Cardiovascular and bronchial actions of famotidine in anesthetized dogs.

The effects of famotidine (Gaster; CAS 76824-35-6) and cimetidine on cardiovascular and bronchial functions were investigated in anesthetized dogs. Famotidine did not affect heart rate, blood pressure, left ventricular pressure (LVP), max. dLVP/dt, cardiac output or coronary blood flow at i.v. doses of 1 to 30 mg/kg in open-chest dogs anesthetized with pentobarbital or a combination of nitrous oxide, oxygen and halothane (GOF). No hemodynamic changes were either observed after famotidine in pentobarbital anesthetized dogs whose cardiac function was depressed by propranolol (1 mg/kg i.v.). On the contrary, cimetidine dose-dependently decreased heart rate and blood pressure at doses greater than 3 mg/kg, and left ventricular pressure, cardiac output and coronary blood flow at the dose of 30 mg/kg. Regarding the electrocardiogram (ECG), famotidine did not produce any remarkable change at doses up to 30 mg/kg with the exception of a transient increase or decrease in the T-wave amplitude at a dose of 30 mg/kg. Cimetidine prolonged Q-T intervals of ECG in addition to changing the T-wave at a dose of 30 mg/kg. Neither famotidine nor cimetidine showed any effect on resting and histamine-increased bronchoresistance at doses up to 30 mg/kg. It is concluded that famotidine is superior to cimetidine with regard to safety because famotidine has no significant effects on cardiovascular functions in anesthetized dogs.

Airway Resistance↗