Biomedical subjects

K Miyata

Publications and source records attributed to K Miyata.

At least 235 records · Page 13Linked to original sources

PubMed1994

Serotonin (5-HT)3-receptor antagonism of 4,5,6,7-tetrahydrobenzimidazole derivatives against 5-HT-induced bradycardia in anesthetized rats.

We investigated the mode of the 5-HT3-receptor antagonism of 4,5,6,7-tetrahydrobenzimidazole derivatives, YM060, YM114 (KAE-393), YM-26103-2 and YM-26308-2, against 5-HT-induced transient bradycardia in anesthetized rats. Results were compared with those of ondansetron and granisetron. YM060 (0.03-0.1 microgram/kg, i.v.), YM114 (0.03-0.3 microgram/kg, i.v.), YM-26103-2 (0.01-0.03 microgram/kg, i.v.), YM-26308-2 (0.01-0.03 microgram/kg, i.v.) and granisetron (0.3-3 micrograms/kg, i.v.) displaced the 5-HT dose-response curve to the right, with apparent DR2 values of 0.068, 0.068, 0.019, 0.011 and 0.69 microgram/kg, i.v., respectively. Higher doses of these compounds inhibited 5-HT-induced bradycardia with a reduced maximal response. In contrast, ondansetron displaced the 5-HT dose-response curve to the right without affecting the maximal response. Judged by the apparent DR2 values, YM060, YM114, YM-26103-2 and YM-26308-2 were approximately 13, 13, 50 and 79 times more potent than ondansetron, respectively, whereas granisetron was equipotent to ondansetron. Single i.v. doses of YM060 and granisetron inhibited 5-HT-induced bradycardia significantly longer than ondansetron. Moreover, inhibitory effects of p.o. doses of YM060 (3 micrograms/kg), YM114 (80 micrograms/kg), YM-26103-2 (12 micrograms/kg), YM-26308-2 (5 micrograms/kg) and granisetron (250 micrograms/kg) on the von Bezold-Jarisch reflex lasted for 3-6 hr, whereas ondansetron (700 micrograms/kg, p.o.) antagonized 5-HT3 receptors for only 1 hr. In isolated guinea pig colon, the inhibitory effect of YM-compounds on 5-HT-induced contraction persisted significantly longer than those of ondansetron and granisetron after washout of the bath containing compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[Production of transgenic mice from in vitro fertilized eggs cryopreserved by ultrarapid freezing].

In vitro fertilized mouse eggs (C57BL/6N), followed by ultrarapid freezing were used for production of transgenic mice by microinjection of the chicken beta-actin promoter-driven the firefly luciferase cDNA (beta act-Luc). Following micromanipulation, the survival rates of the cryopreserved eggs and of the fresh in vitro fertilized eggs (control) were 70.8% (131/185) and 71.9% (159/221), respectively. After transferring them into oviducts of psudopregnant recipients on Day 1, 13.6% (17/125) of the cryopreserved eggs developed to live offspring and 14.1% (21/149) of fresh eggs did so. It was confirmed by Southern blotting analysis that each two transgenic mice were produced from the cryopreserved eggs (12%, 2/17) and the fresh eggs (10%, 2/21). All of transgenic mice produced from both eggs showed the expression of the luciferase gene. These results indicate that the in vitro fertilized eggs cryopreserved by ultrarapid freezing, can be, easily and conveniently, used for generation of transgenic mice.

Animals↗

PubMed1994

[Clinical features of infantile patient with juvenile rheumatoid arthritis].

Little is known about clinical features of infantile juvenile rheumatoid arthritis (JRA) because it is very rare for the patients to develop JRA within one year of age. In the past 20 years, we experienced three JRA patients whose onset was under 1 year of age. The incidence of infantile JRA was 3.2% of all JRA patients in our facility. They are 9 month-old male with systemic onset, 6-month-old female with polyarticular onset and 8 month-old female with systemic onset. It was difficult to evaluate subjective symptoms such as arthralgia or morning stiffness since the patients could not complain precisely. Therefore, careful observation on their behaviors, such as the delayed development of their motor function and bad humor and/or loss of activity in the morning, was important for evaluating joint symptoms. In case 1, measuring the serum level of hyaluronic acid was specifically useful to evaluate the arthritis. Drug therapy was not successful especially in infantile JRA. One of the reason for this ineffectiveness of drug therapy might be explained by poor adsorption of drugs in infants; the serum acetyl salicylic acid level was lower in infantile patients than the other patients with JRA even though they received enough dose of aspirin. Infantile JRA was revealed to have specific difficulties in early diagnosis and adequate treatment. Therefore, accumulated case studies about clinical features of infantile JRA is essential for their better prognosis.

Arthritis, Juvenile↗

PubMed1994

[Quantitative analysis of glycosaminoglycans in tear fluids during corneal epithelial wound healing in rabbits].

We performed quantitative analyses of glycosaminoglycans in the tear fluids in a rabbit wound healing model. We ablated rabbit corneal epithelium with trephine and spatula, and sampled tear fluids before the epithelial ablation, and at 3, 24, 48, and 72 hours after it. After an instillation of 200 microliters saline solution in the conjunctival sac, as much tear fluid as possible was collected from the lower cul-del-sac. The glycosaminoglycans in the tears were then treated with chondoroitinase ABC to make fractions of disaccharides. The quantities of disaccharides were determined with high-performance liquid chromatography as weight per unit protein in the tears. The concentrations of delta Di-HA in the tear fluids at 3 and 24 hours were significantly higher than those before the treatment and returned to the initial value at 72 hours after making the epithelial wound. Among the disaccharides of chondroitin sulfate, delta Di-0S and delta Di-6S showed a significant increase at 3 hours after the treatment but delta Di-4S did not show any significant variation. The results suggest that the glycosaminoglycans in the rabbit tear fluids may play an important role in the corneal epithelial wound healing process.

Animals↗

PubMed1994

[Multivariate analysis of risk factors of rejection in penetrating keratoplasty].

In order to evaluate preoperative risk factors that affect the incidence of endothelial rejection after penetrating keratoplasty, we performed statistical analysis on 571 consecutive cases who had been followed at the University of Tokyo Hospital for at least one year. We applied a logistic regression model (multiple variate analysis) to determine the significance of the association between the preoperative factors and the incidence of rejection. We identified four preoperative risk factors of endothelial rejection in a year as follows: the extent of corneal vascularization, failed previous graft continuous sutures, and preoperative corneal endothelial damage. When the rejection cases were divided into an early group that suffered rejection within 3 months and a late group that suffered rejection after 6 to 12 months, young patients were likely to suffer rejection in the early postoperative period.

Adolescent↗

PubMed1994

[Molecular typing of the methicillin resistance determinant (mec) of clinical strains of Staphylococcus based on mec hypervariable region length polymorphisms].

We used a method for molecular typing of the methicillin resistance determinant (mec) based on the size of the mec-associated hypervariable region amplified by the polymerase chain reaction (PCR) to examine 106 methicillin-resistant Staphylococcus aureus (MRSA), 9 methicillin-resistant (Mcr) S. epidermidis and 5 Mcr S. haemolyticus clinical isolates. In the 106 MRSA isolates, 5 sizes of PCR products were observed. The MRSA isolates were grouped into five hypervariable region (HVR) genotypes on the basis of the size of the PCR product. The PCR products amplified from 8 of 9 Mcr S. epidermidis isolates were the same as products amplified from MRSA isolates, which was confirmed by the PCR-SSCP (single-strand conformation polymorphism) method. In 32 methicillin-susceptible isolates, the target gene was not amplified. This method is thought to be useful in epidemiological investigations of nosocomial infections caused by MRSA. This is the first typing method capable of comparing the mec determinants of MRSA isolates and Mcr CNS isolates to establish the origin of the mec determinant.

Base Sequence↗

PubMed1994

Pharmacological profile of (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo- 5-phenyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), a new potent and selective gastrin/cholecystokinin-B receptor antagonist, in vitro and in vivo.

(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022) is an extremely potent and highly selective gastrin/cholecystokinin (CCK)-B receptor antagonist. We compared the gastrin/CCK-B receptor-blocking properties of this compound with those of the racemate (mixture of YM022 and its S-form), its enantiomer (S-form), L-365, 260 and Cl-988 in vitro and in vivo. YM022 replaced specific binding of [125I]CCK-8 to rat brain gastrin/CCK-B receptors in a stereoselective and competitive manner. The Ki value of YM022 for gastrin/CCK-B receptors in brain were estimated to be 0.068 nM. The racemate, the S-form of YM022, L-365,260 and Cl-988 also replaced gastrin/CCK-B receptor binding, with Ki values of 0.11, 140, 19 and 6.3 nM, respectively. The affinity of YM022 for gastrin/CCK-B receptor was more than 2 orders of magnitude higher than that for rat pancreatic CCK-A receptor and various other receptors, such as benzodiazepine. In vivo, intravenous (i.v.) administration of YM022 inhibited pentagastrin-induced gastric acid secretion in anesthetized rats, with an ED50 value of 0.0078 mumol/kg. Inhibition by the S-form of YM022 was only 33.8% even at the relatively high dose of 1 mumol/kg i.v. L-365,260 (1-10 mumol/kg i.v.) and Cl-988 (0.3-3 mumol/kg i.v.) also antagonized acid secretion induced by pentagastrin, with ED50 values of 4.23 and 1.01 mumol/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

YM022 [(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl- 1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea], a potent and selective gastrin/cholecystokinin-B receptor antagonist, prevents gastric and duodenal lesions in rats.

We evaluated the effect of YM022 [(R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl)urea], a potent and selective gastrin/cholecystokinin-B receptor antagonist, on gastric acid secretion and gastric and duodenal lesions in rats. Oral YM022 (0.1-10 mumol/kg), famotidine (0.3-30 mumol/kg) and omeprazole (3-100 mumol/kg) dose-dependently suppressed acid secretion in pylorusligated rats with ED50 values of 0.83, 1.63 and 10.9 mumol/kg, respectively. YM022 (1-10 mumol/kg p.o.), famotidine (1-10 mumol/kg p.o.) and omeprazole (10-100 mumol/kg p.o.) prevented indomethacin-induced gastric lesions in a dose-related manner. The potency of YM022 was comparable to that of famotidine and was 8 times greater than that of omeprazole. YM022 and famotidine partially inhibited gastric damage induced by water-immersion and restraint stress, whereas omeprazole abolished these lesions. In an acidified ethanol-induced gastric injury model, all three drugs inhibited the formation of erosions. The YM022 dosage required in this model was much greater than that required in the inhibition of gastric acid. The inhibitory effect of YM022 was partially reversed by indomethacin, indicating the involvement of a prostaglandin-mediated pathway. YM022 (3-100 mumol/kg p.o.), famotidine (1-30 mumol/kg p.o.) and omeprazole (3-100 mumol/kg p.o.) inhibited mepirizole-induced duodenal ulcers. On the basis of ED50 values, YM022 was 5 times less potent than famotidine and as potent as omeprazole against mepirizole-induced duodenal ulcers. These results suggest that YM022 possesses antisecretory and antiulcer activities that are as potent as those of famotidine in rats and that YM022 represents a useful therapeutic agent in the treatment of peptic ulcer disease.

Animals↗

PubMed1994

[Histopathological study of the meibomian glands in 72 autopsy cases].

We investigated histopathological changes in human meibomian glands and analyzed the incidence of histopathological parameters and the relationship between parameters and age or sex of patients. Human meibomian glands, measuring 3 x 3 mm in size, were excised from both upper eyelids of 72 autopsy cases (mean age 63 +/- 12 years; 44 males, 28 females). The specimens were stained with hematoxylin and eosin and examined in detail with the light microscope. The following histopathological changes were investigated as parameters: (1) cystic dilatation of the duct and/or the acini, (2) atrophy of the acini, and (3) granulomatous inflammation. The incidences of the parameters were (1) 34.7% (25 cases), (2) 19.4% (14 cases), and (3) 18.6% (13 cases). There was statistically significant correlation between age and atrophy of the acini, which was found in the older patients. No sex difference was found in any of the parameters. These results suggest that the decrease in the meibomian gland secretion with aging is related to atrophy of the acini. These results further suggest that cystic dilatation, which has been described as a histopathological finding in meibomian gland dysfunction, may be caused by factors other than aging.

Adolescent↗

PubMed1994

[Statistic evaluation of prognostic risk factors in penetrating keratoplasty using Cox multiple regression model].

Preoperative risk factors that may influence the prognosis in penetrating keratoplasty were statistically analyzed on 698 consecutive eye that had been operated on at the University of Tokyo Hospital. A Cox multiple regression model (proportional hazards models) was constructed with simultaneous consideration of follow-up periods and prognostic factors. Six preoperative risk factors were identified: corneal endothelial damage, the presence of anterior synechiae, glaucoma, older donor age, the area of vascularization, and aphakia or pseudophakia. Simulations of the prognosis were attempted using the significant factors.

Adult↗

PubMed1994

[Inhibition of liver metastases in rabbits by arterial infusion of angiogenesis inhibitor, TNP-470].

We examined the prevention of liver metastases by arterial infusion of the angiogenesis inhibitor, TNP-470, in Japanese White Rabbits; 1.0 x 10(6) of VX2 carcinoma cells were injected into the mesenteric vein for tumor inoculation. Then the rabbits were divided into the following two groups. Group 1: 2 ml of distilled water was continuously injected into the common hepatic artery of control for 7 days. Group 2: 50 mg of TNP-470 solved in 2 ml of distilled water was continuously administered into the common hepatic artery for 7 days. On day 14, the number of metastases on each liver surface was counted. The mean number of metastases were 237.0 +/- 133.26 and 24.4 +/- 15.05 in Group 1 and 2, respectively. There was a significant difference between the two groups (p < 0.05). We found no side effects of TNP-470 such as body weight loss or liver disfunction. Microphil was injected into the common hepatic artery to observe the neovasculature. The proliferation of tumor vessels was suppressed in Group 2. We considered that arterial infusion of TNP-470 is effective to prevent liver metastases, because the blood supply to liver metastases is well developed from the hepatic artery, and TNP-470 is directly effective on the endothelium itself, and inhibits neovascularization.

Animals↗

PubMed1994

[Recurrence and survival rate of advanced gastric cancer after preoperative EAP-II intra-arterial infusion therapy].

Ninety-eight patients with advanced gastric cancers underwent gastrectomy from Jan. 1989 to Dec. 1991. For these patients, preoperative intra-arterial injection therapy using EAP-II (etoposide 100 mg, epirubicin 20 mg, carboplatin 100 mg) was given to 24 patients. In this report, the recurrence and survival rate of these patients were investigated. After curative resection, the survival rate of patients with EAP-II 36 months after operation was 76.9%, while that of patients without EAP-II was 78.6%. There were no significant differences between these two groups. Two peritoneal carcinomatoses and two liver metastases were seen in patients with EAP-II (recurrence rate, 30.7%). Eight recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination, 4; local recurrence, 3; lymph node recurrence, 1). Previously, we reported that drugs were remarkably accumulated in gastric cancer tissue and regional lymph nodes after EAP-II intra-arterial injection therapy. This high accumulation might cause no local or lymph node recurrence was seen in patient with EAP-II. Thus, it was concluded that preoperative EAP-II intra-arterial injection may prevent local and lymph node recurrences, and that further study of the combination and dose of anti-cancer drug needed to improve the postoperative survival rate in advanced gastric cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

[Survey of activities of daily living in non-institutionalized elderly residents].

To investigate the states of activities of daily living (ADLs) in the elderly, non-institutionalized residents-aged 65 and over living in Azuchi (population of approximately 12,000) were interviewed. Data was collected from 1,287 subjects (509 men and 778 women; 92.1%) for the 3 years, 1990 to 1992. Differences in difficulties with the 6 basic ADLs (BADLs) and the 7 instrumental ADLs (IADLs) were analyzed according to gender and age. For the BADLs (eating, dressing, bathing, using the toilet, mobility, and incontinence), only the percentage of incontinence was significantly higher in women than in men (p < 0.01). The percentage of those fully independent in the 6 BADLs in men was 87%, which was higher than that in women (77%), but except for incontinence there were no significant differences between the sexes. The percentages of disability in the BADLs for women and for both sexes combined were higher according to age (p < 0.01), but for men, only those of dressing (p < 0.05) and of incontinence (p < 0.01) were related with age. The disability percentage for cooking was the only activity among the IADLs (cooking, using the telephone, cleaning house, walking, shopping, going up and down steps, and using transportation) which was significantly higher in men (p < 0.01), but those for walking, going up and down steps, and using transportation were higher in women (p < 0.01). The percentage of those who were fully independent was 74% in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

PubMed1994

Occipital roof development in the Japanese musk shrew, Suncus murinus.

The occipital squama of the Japanese musk shrew, Suncus murinus, consists only of membrane bone which arises from the periosteal bony band of the supraoccipital cartilage. No cartilaginous tectum posterius, generally forming the dorsal border to the foramen magnum, was found in the developing chondrocranium. Also additional intramembranous ossification centres were occasionally observed, and could be interpreted as being the primordium of the interparietal bone. These observations indicate that the membrane bone is homologous not with the interparietal bone but with the tectum posterius, i.e. the membranous supraoccipital bone. This is an instance of interchangeability between cartilage and membrane bone in a mammal.

Animals↗

PubMed1994

[Cryopreservation of in vitro fertilized embryos from transgenic rat by ultrarapid freezing].

We cryopreserved pronuclear stage-embryos from the Transgenic rats produced by introducing the rat GH antisense transgene, by ultrarapid freezing. The embryos were obtained by fertilization in vitro with the sperm of homozygous males for the transgene. After thawing of a part of cryopreserved embryos (97 embryos), the 40 embryos (41%) were morphologically normal, and were transferred to oviducts of recipients. All four live young (10%) obtained (one male and three females) preserved the transgene and exhibited dwarfism. We also produced the homozygous transgenic rats after brother-sister mating of those young. These results demonstrated the possibility of the cryopreservation of embryos by ultrarapid freezing for sustaining transgenic rat line.

Animals↗

PubMed1993

Comparison of the effects of trimebutine and YM114 (KAE-393), a novel 5-HT3 receptor antagonist, on stress-induced defecation.

YM114 (KAE-393), (R)-5-[(2,3-dihydro-1-indolyl)carbonyl]-4,5,6,7- tetrahydro-1H-benzimidazole hydrochloride, is a derivative of YM060, a potent 5-HT3 receptor antagonist. We investigated the effects of YM114 on 5-HT3 receptors, both in vitro and in vivo, and on bowel dysfunction induced by restraint stress, 5-HT and thyrotropin-releasing hormone (TRH), and compared them with the effect of trimebutine. YM114 dose dependently inhibited the reduction in heart rate induced by 5-HT (30 micrograms/kg i.v.) in rats (ED50 = 0.31 micrograms/kg i.v.), and the potency of YM114 was almost the same as that of the racemate. The S-form of YM114 also inhibited 5-HT-induced bradycardia, but 1350 times less potent than the R-form. YM114 and its S-form inhibited [3H]GR65630 binding to N1E-115 cell membranes in a concentration-dependent manner with Ki values of 0.341 and 616 nM, respectively, showing the isomeric activity ratio (R-/S-form) of YM114 to be much greater (1800). YM114 antagonized 5-HT-induced depolarization of the nodose ganglion (EC50 = 1.39 nM). Trimebutine (1 mg/kg i.v.) failed to inhibit 5-HT-induced bradycardia, implying that it does not possess 5-HT3 receptor antagonistic activity. YM114 significantly and dose dependently prevented restraint stress-, 5-HT- and TRH-induced increases in fecal pellet output, and restraint stress- and 5-HT-induced diarrhea in rats and mice (ED50 = 6.9, 72.5, 154.6, 9.7 and 52.4 micrograms/kg p.o., respectively). Trimebutine significantly prevented stress- and 5-HT-induced diarrhea (ED50 = 29.4 and 87.3 mg/kg p.o., respectively), but only partially affected stress-, 5-HT- and TRH-induced increases in fecal pellet output. Thus, YM114 is a potent and stereoselective 5-HT3 receptor antagonist with much greater protective effects against stress-induced defecation than trimebutine.

Animals↗

PubMed1993

Sexual dimorphism in the trigeminal motor neurons innervating the mouse masseter muscle.

The extrafusal and intrafusal muscle fibers in the masseter muscle are innervated by motoneurons in the trigeminal motor nucleus (Mo 5). In the present study, we found that the number of trigeminal motor neurons in the male mouse was significantly larger than that in the female. However, we could not detect any significant difference between male and female mice in the number of sensory neurons in the trigeminal mesencephalic nucleus (Me 5). This is the first report on sexual dimorphism in masticatory motoneurons of mammals.

Animals↗

PubMed1993

Mechanisms of cisplatin- and m-chlorophenylbiguanide-induced emesis in ferrets.

We investigated the involvement of peripheral and central serotonin (5-HT)3 receptors in cisplatin- and 5-HT3 receptor agonist-induced emesis in ferrets. Cisplatin (10 mg/kg i.v.)-induced emesis was inhibited by intravenous YM060 (0.003-0.1 microgram/kg). A highly selective and potent 5-HT3 receptor agonist, m-chlorophenylbiguanide (1-10 mg/kg i.p.), dose dependently elicited emesis an effect which was inhibited by YM060 (0.003-0.3 microgram/kg i.v.). Vagotomy markedly reduced this emesis, and the combination of abdominal vagotomy and greater splanchnicectomy abolished emesis. Lesion of greater splanchnic nerves alone did not markedly inhibit emesis. Intracerebroventricularly (4th ventricle) administered YM060 inhibited cisplatin- and m-chlorophenylbiguanide-induced emesis only at higher doses (0.01-0.1 and 0.01-0.03 microgram, respectively). Intracerebroventricularly (4th ventricle) administered m-chlorophenylbiguanide (30-100 micrograms) produced only a weak retching response. These results indicate that stimulation of abdominal vagal afferent nerves via peripheral 5-HT3 receptors is important for triggering cisplatin- and m-chlorophenylbiguanide-induced emesis in ferrets.

Animals↗