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Biomedical subjects

A Asanuma

Publications and source records attributed to A Asanuma.

At least 19 recordsLinked to original sources
PubMed1999

Molecular analysis of Japanese patients with steroid 21-hydroxylase deficiency.

We have designed a rapid and convenient strategy to determine nine of the most common mutations in the 21-hydroxylase gene (CYP21). The frequency of the mutations was investigated in 34 Japanese patients affected with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency. We characterized 82% of the CAH chromosomes. The most frequent mutations were a C/A to G substitution in intron 2 in the salt-wasting form of the disease and an I172N in the simple virilizing form. Three de novo mutations were found. Two homozygous mutations (S268T and N493S) were detected by direct sequencing of all exons of CYP21 in two siblings, who had a normal genotype at all positions screened. We successfully applied these methods for prenatal diagnosis in one family. These procedures proved to be sensitive and rapid for the detection of the most common known mutations in the CYP21 gene and may be useful for genetic screening.

Adrenal Hyperplasia, Congenital↗
PubMed1999

In vivo and in vitro toxicodynamic analyses of new quinolone-and nonsteroidal anti-inflammatory drug-induced effects on the central nervous system.

We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the gamma-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 microM) > FRP (0. 3 microM) > FLB (0.2 microM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

Animals↗
PubMed1999

Growth of two children after six months interruption of GH therapy.

We describe two short boys with normal GH responses to the stimuli in whom GH therapy was interrupted for 6 months. Their growth rates before and after the interruption, and after re-administration of GH were evaluated. Height velocity (HV) in case 1 before and after the interruption was 6.6 cm/y and 5.0 cm/y, respectively. HV was not increased (5.0 cm/y) by re-initiation of GH therapy despite the high serum IGF-1 level. Height velocity (HV) in case 2 before and after the interruption was 5.6 cm/y and 3.6 cm/y, respectively. HV was slightly increased to 4.1 cm/y by re-administration of GH, but it was far below the pretreatment value. Serum IGF-1 was increased by GH in this case as well. We conclude that re-acceleration of growth by re-administration of GH after interruption of therapy, as seen in classical GHD patients, may not be expected in normal short children.

Body Height↗
PubMed1998

28-day repeated oral toxicity study of a hypolipidemic agent, NK-104 in rats.

NK-104, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, was administered orally to Wistar rats at a dose of 2, 10, 50 or 100 mg/kg for 28 days consecutively, and the toxicity of NK-104 and its recovery with 2 weeks cessation of drug treatment were examined. As major clinical signs, loose stool, diarrhea, crouching and emaciation were observed in both sexes at 50 or 100 mg/kg, and all females at 100 mg/kg died or became moribund due to severe emaciation before the completion of treatment. The suppression of body weight gain or decrease in body weight was observed in the female dose group at 50 mg/kg and both sexes at 100 mg/kg. Decreased food intake was observed in both sexes at 100 mg/kg. Moreover, an increase in cholinesterase (Ch.E) in the male dose groups at 50 and 100 mg/kg and an increase in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the female dose group at 50 mg/kg were observed in blood chemistry testing. Macroscopic examination showed thickening of the forestomach mucosa in the groups of 10 mg/kg or more. Microscopic examination revealed hyperkeratosis and hypertrophy of the spinous layer associated with both cell infiltration of the mucosal propria and submucosal edema. In addition, skeletal muscle lesions including atrophy, vacuolation and focal necrosis were observed in the female dose groups at 50 and 100 mg/kg. The above-mentioned microscopic changes were not observed on cessation of drug treatment. The non-toxic dose level of NK-104 in the 28-day repeated oral toxicity study using rats was determined to be 2 mg/kg.

Administration, Oral↗
PubMed1998

Six-month repeated oral toxicity study of NK-104 in rats.

NK-104 is a novel potent inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and has been shown to be a highly effective agent in lowering blood cholesterol. In the present study, NK-104 was orally administered to Wistar rats at a dose of 0.3, 1, 3 or 010 mg/kg for 6 months for examination of toxicity. Additional recovery groups of 8 rats each of both sexes receiving 0 and 10 mg/kg were maintained without treatment for 1 month in order to assess recovery. As a result, no toxicological changes were observed in general signs, body weight, food intake, ophthalmological examination, urinalysis, hematological and blood chemical examinations for organ weights. An autopsy revealed thickening of the forestomach mucosa in both sexes at a dose of 1 mg/kg or more. This change was microscopically recognized as hyperkeratosis and hypertrophy of the spinous layer associated with both cell infiltration of the mucosal propria and edema of sub-mucosa in the forestomach in both sexes at doses of 3 and 10 mg/kg. Forestomach changes were not observed in any cases after 1 month cessation of drug treatment. The non-toxic dose of NK-104 in the 6-month repeated oral toxicity study in rats is estimated to be 1 mg/kg/day.

Administration, Oral↗
PubMed1998

Primary cutaneous T-cell lymphoma involving the cheek: an infant case with a unique clinicopathologic feature.

We report a clinicopathologic feature of primary cutaneous T-cell lymphoma (CTCL) in a five-year-old boy with increasing swelling of his cheek since two years of age. Histologically, an infiltrate of atypical lymphoid cells with mature T-cell phenotype and clonality was prominent from the dermis to the subcutaneous tissue of the cheek. Although little effect was seen with aggressive multidrug-combined chemotherapy, therapy with interferon-alpha and steroids achieved a prolonged remission. This patient may provide important clues to understanding the clinicopathologic feature of rare primary CTCL in young children.

Cheek↗
PubMed1997

Inhibitory effect of new quinolones on GABA(A) receptor-mediated response and its potentiation with felbinac in Xenopus oocytes injected with mouse-brain mRNA: correlation with convulsive potency in vivo.

Convulsions induced by the interaction of new quinolone antimicrobial agents (NQs) and nonsteroidal anti-inflammatory drugs (NSAIDs) were previously reported, and blockade of GABA(A) receptor by NQs and its potentiation with NSAIDs were considered as one of its possible mechanisms. However, useful methodology for prediction of convulsive potencies of NQs with or without NSAIDs in vivo based on in vitro screening was not established. Therefore, we applied the Xenopus oocytes translation system of exogenous messenger RNA (mRNA) to examine the mechanism of convulsion induced by interaction of NQs and NSAIDs, and the relationship between convulsive potencies in vivo and inhibitory effect on GABA-induced current response in vitro was investigated. This system also has alternative possibility for the in vivo toxicological studies sacrificing innumerous animals. Glutamic acid, kainic acid, quisqualic acid, NMDA, and serotonin-induced currents were not modified by ENX of NQs and/or FLB of NSAIDs, while glycine- and ACh-induced currents were slightly inhibited. GABA (10 microM)-induced current was inhibited by norfloxacin (NFLX), ciprofloxacin, ENX, and ofloxacin (OFLX) with IC50 of 17, 33, 58, and 280 microM, respectively. IC50 of NQs decreased to 1/3 (OFLX)-1/165 (NFLX) in the presence of 10 microM FLB, while FLB did not modulate the GABA response in the absence of NQs. CSF concentration of ENX at the time of convulsion in clinical situation approximated the IC50 of ENX for the GABA response. The increase of incidence for NQs-induced convulsion by concomitant NSAIDs in vivo could also be explained by the potentiation of inhibitory effects of NQs with FLB in the normal range of CSF concentration of these drugs. We also examined convulsive potency (threshold dose for convulsion) in CNS by intracerebral infusion of NQs to mice with or without FLB pretreatment, and significant correlations between the convulsive potencies and IC50 of NQs for the GABA response were observed. These findings suggested that the blockade of GABA-ersic neurotransmission in CNS is a dominant mechanism of convulsion induced by NQs and that the convulsant-adverse reaction of NQs in vivo may be predicted from the inhibitory effect on the GABA(A) receptor in vitro using the Xenopus oocytes translation system of exogenous mRNA.

Animals↗
PubMed1997

Neurotoxic study of H2 antagonists using Xenopus oocytes injected with mouse-brain mRNA.

To clarify the dominant mechanism for the convulsant activity of H2 antagonists, the effects of an H2 antagonist, cimetidine, on membrane currents induced by various agonists were investigated. In Xenopus oocytes injected with mouse-brain mRNA, acetylcholine (ACh), serotonin (5-HT), gamma-aminobutyric acid (GABA), glycine (Gly), glutamic acid (Glu), kainic acid (KA), quisqualic acid (QA) and N-methyl-D-aspartic acid (NMDA)-induced current responses were recorded under a voltage-clamp condition. Cimetidine inhibited GABA-induced currents in a concentration-dependent manner; however, the current responses induced by the other agonists were not modified. The IC50 of various H2 antagonists, famotidine, nizatidine, cimetidine and ranitidine, for GABA (10 microM)-induced current response were 66, 260, 450 and 980 microM, respectively. However, these values of cimetidine and ranitidine were 40-400 times higher than the reported brain and cerebrospinal fluid (CSF) concentration of H2 antagonists at the occurrence of a clonic convulsion in vivo. In conclusion, we observed an inhibitory effect of H2 antagonists on the GABA response; however, this inhibition of GABA-mediated neurotransmission may not be the dominant mechanism for H2 antagonist-induced clonic convulsion in vivo.

Animals↗
PubMed1995

Suppression of age-related changes in mouse hippocampal CA3 nerve cells by a free radical scavenger.

This study was designed to evaluate the relationship between oxygen free radicals and age-related morphological changes in hippocampal nerve cells using K-7259 (N,N' bis[4-(3,4,5-trimethoxyphenyl)butyl] homopiperazine dihydrochloride), a known neuro-protective agent. A chemiluminescence assay has shown that this agent is a potent free radical scavenger with an IC50 of 1.6 x 10(-5)M. Mice fed diets containing 10, 20, 40 mg/kg/day of K-7259, for periods ranging from 25 to 40 or 50 weeks of age were used as test groups, and 10-, 20-, 30-, 40-, and 50-week-old mice fed a standard diet were used as controls. We measured the number and area of pyramidal nerve cells within a defined frame in the hippocampal CA3 field using an image analyzer and the density of nerve cells by the disector method. These values decreased gradually in controls as expected, and the number and area yielded a significant difference between control mice at the ages of 10 and 30 weeks. As compared with the corresponding controls, all test groups had greater cell numbers (statistical significance at 40 weeks in the 40 mg/kg/day group) and density, while cell areas were greater in all but a 10 mg/kg/day group (statistical significance at 50 weeks). In summary, the free radical scavenger K-7259 forestalled an age-related decrease in the number and size of hippocampal CA3 nerve cells, thus suggesting that free radicals play an important role in the cellular morphological changes which appear with age.

Aging↗
PubMed1995

Experimental myocardial infarction with cartilaginous and osseous metaplasia in SHR and WKY rats.

Myocardial infarction was induced by ligation of the coronary artery in fifteen 32-week-old male spontaneously hypertensive rats (SHR) and fifteen 32-week-old male normotensive Wistar-Kyoto rats (WKY). Age-matched male SHR (n = 6) and WKY (n = 7) without the operation were used as non-infarcted control rats. Four weeks after the operation, cartilaginous metaplasia and osseous metaplasia were observed histopathologically in all SHR and 13 of the 15 WKY with myocardial infarction, but not in the control rats. The mean rates of infarction to the heart and the mean areas of metaplasia per rat showing metaplasia were greater in SHR than in WKY. The metaplastic areas were well correlated with the infarct percentage in SHR. It is therefore considered that extensive myocardial infarction is associated with the pathogenesis of cartilaginous and osseous metaplasia.

Animals↗
PubMed1995

[Morphological study on the gastric mucosa in diabetes mellitus rats induced by streptozotocin].

To clarify the pathogenesis of vulnerability to acute gastric mucosal lesion (AGML) in diabetes mellitus (DM), we investigated histopathologically the gastric mucosa of the fundic gland in streptozotocin-induced DM rats. The length of the mucosa and the thickness of the surface epithelial cell (SEC) layer were measured, and the number of proliferating cell nuclear antigen (PCNA) positive cells was counted. As results, compared with control rats, the ratio of the length of SEC layer to that of mucosa, and the number of PCNA positive cells were significantly decreased in DM rats, whereas the length of the mucosa tended to extend in DM rats. Consequently, it is considered that attenuation of mucosal barrier in the SEC layer can be closely associated with susceptibility to occurrence of AGML in DM.

Animals↗
PubMed1995

[Age-related memory impairment and hippocampal damage in ddY male mice].

The relationship between behavioral change and hippocampal lesion was studied in ddY male mice, at 4.5, 20, 40 and 60 weeks of age. In passive avoidance response, the aging mice (40 and 60 weeks of age) showed shorter latency than young mice (4.5 weeks of age). The degenerated pyramidal cells were more numerous after 40 weeks of age in the CA3 than CA1. The mean incidence of the degenerated pyramidal cells in the CA3 was 20.8% at 60 weeks of age. In 71.9% of mice, impairment of passive avoidance response was associated well with hippocampal lesions. These results indicate that the hippocampus plays some role in the memory in mice. The ddY mice may be possible to use as models for reversible hippocampal lesion.

Aging↗
PubMed1994

New interpretation and management of dry lung syndrome: a case report.

A premature female infant with life-threatening respiratory distress which was diagnosed as 'dry lung syndrome' is reported. The mother had 4 weeks of large volume leakage of the amniotic fluid due to premature rupture of the fetal membranes (PROM) at 23 weeks' gestation. The infant was born after 27 weeks' gestation (birthweight, 1016 g) and was suffering severe respiratory distress. Although a chest radiogram and gastric juice microbubble test did not improve the possibility of respiratory distress syndrome (RDS), very high ventilator settings did not improve her respiratory disorders. Considering the infant's deteriorating respiratory status and the prolonged leakage of the amniotic fluid, we suspected the presence of pulmonary hypoplasia. Although an attempt at high frequency oscillation (HFO) to rescue this infant had no effect, intratracheal instillation of epinephrine (EP) showed dramatic improvement of her respiratory status. This clinical course showed that the patient did not have pulmonary hypoplasia but might have severe airway obstruction and this airway obstruction may be the major cause of 'dry lung syndrome'. We postulate that when a newborn with suspected pulmonary hypoplasia is unresponsive to respiratory support. HFO should be administered. If HFO is ineffective in relieving the respiratory distress, one should suspect the presence of airway collapse and administer a bronchodilator such as EP. If the infant improves, a diagnosis of 'dry lung syndrome' may be assumed.

Adult↗
PubMed1993

Inhibition of GABAA receptor-mediated current responses by enoxacin (new quinolone) and felbinac (non-steroidal anti-inflammatory drug) in Xenopus oocytes injected with mouse-brain messenger RNA.

The convulsant interaction between enoxacin (ENX), a new quinolone antibacterial agent (NQ), and felbinac (FLB), a non-steroidal anti-inflammatory drug (NSAID), in vivo was reproduced as the change of GABA-induced current response in Xenopus oocytes injected with mouse brain mRNA. GABA (10 microM) response was inhibited by ENX in a dose-dependent manner, and IC50 of ENX was 96 microM. Moreover, the inhibitory effect of ENX was 80-fold potentiated in the presence of 10 microM FLB. The GABAA-antagonistic interaction between these two drugs in vitro was considered a possible mechanism of convulsant reaction after concomitant administration of NQs and NSAIDs in vivo.

Animals↗
PubMed1993

[Study on the glomerular foam cells in stroke-prone SHR].

Recent evidence suggests focal glomerulosclerosis may be analogous to atherosclerosis. To investigate the role of hypertension and hypercholesterolemia in the appearance of glomerular foam cells, 2, 6 or 9-month-old stroke-prone SHR (SHRSP) were fed the high fat cholesterol diet (2% cholesterol, 0.5% cholic acid, 7% lard, 0.2% methylthiouracil; HFC) for 4 weeks. Serum total cholesterol was significantly elevated in HFC. Form cells were observed in glomeruli of 6- and 9-month-old, but not 2-month-old SHRSP with dietary-induced hypercholesterolemia. The glomerular foam cells varied in quantity almost in parallel with the duration of severe hypertension. Glomeruli with foam cells prominently situated in juxtamedullary region. Foam cells were frequently seen in glomerular sclerotic area. These results suggest that hypertension rather than hyperlipidemia may be more important for glomerular deposition of lipid, especially in early lesions, and hyperlipidemia may play a role in the foam cells accumulation.

Animals↗
PubMed1990

Gradual increases in marginal leakage of resin composite restorations with thermal stress.

The effects of thermal stress on the marginal leakage of resin composite restorations in bovine teeth were investigated by a method that preserved the specimens. The changes in marginal leakage of specimens with increasing numbers of thermal cycles were measured by an electrical conductivity method. Four brands of posterior resin composites were used to fill cylindrical cavities (2.0 mm in diameter and 1.5 mm in depth) on the labial surfaces of bovine incisors, according to the manufacturer's instructions. Thermal cycling stress was applied to the specimens for up to about seven weeks (9000 cycles). During this time, the electrical conductance between the pulp and a drop of physiological saline solution covering the resin restoration was measured periodically by application of an electrical potential (60 Hz, 10 Vp-p). Thermal stress increased the marginal leakage gradually, rather than step-wise. Even before application of any thermal stress, wide variations of marginal leakage were found among different specimens restored with the same brand of resin. Specimens with less initial leakage showed less increase in leakage, and vice versa, throughout the experimental period.

Animals↗
PubMed1990

[Spontaneous bone marrow granulomas in rats--effect of ovariectomy on granulomas formation].

Spontaneous granulomas developed frequently in the bone marrow of Slc: Wistar female rats over 19 weeks of age, whereas none did in JCL: SD and Slc: SD rats of either sex. These granulomas were composed histologically of epithelioid cells and macrophages clustered mostly in the center and lymphocytes and plasma cells located in the periphery, and they contained neither microorganisms nor foreign bodies. Ovariectomy of Slc: Wistar rats at 6 weeks of age resulted in a significant decrease in the incidence and size of bone marrow granulomas at 20 and 24 weeks of age. It is concluded that two factors, the strain of rats and female sex hormone, contribute to the pathogenesis of bone marrow granulomas--the former as a hereditary disposition and the latter as a promoter.

Animals↗