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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 109 records · Page 6Linked to original sources
PubMed2000

Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions.

The SGS1 gene of Saccharomyces cerevisiae is a homologue for the Bloom's syndrome and Werner's syndrome genes. The disruption of the SGS1 gene resulted in very poor sporulation, and the majority of the cells were arrested at the mononucleated stage. The recombination frequency measured by a return-to-growth assay was reduced considerably in sgs1 disruptants. However, double-strand break formation, which is a key event in the initiation of meiotic DNA recombination, occurred; crossover and noncrossover products were observed in the disruptants, although the amounts of these products were slightly decreased compared with those in wild-type cells. The spores produced by sgs1 disruptants showed relatively high viability. The sgs1 spo13 double disruptants sporulated poorly, like the sgs1 disruptants, but spore viability was reduced much more than with either sgs1 or spo13 single disruptants. Disruption of the RED1 or RAD17 gene partially alleviated the poor-sporulation phenotype of sgs1 disruptants, indicating that portions of the population of sgs1 disruptants are blocked by the meiotic checkpoint. The poor sporulation of sgs1 disruptants was complemented with a mutated SGS1 gene encoding a protein lacking DNA helicase activity; however, the mutated gene could suppress neither the sensitivity of sgs1 disruptants to methyl methanesulfonate and hydroxyurea nor the mitotic hyperrecombination phenotype of sgs1 disruptants.

Adenosine Triphosphatases↗
PubMed2000

Foods and nutrients in relation to bladder cancer risk: a case-control study in Aichi Prefecture, Central Japan.

To elucidate the role of diet in the etiology of bladder cancer, we conducted a case-control study from 1996 to 1999 in Aichi Prefecture, Central Japan. Cases were patients newly diagnosed with bladder cancer, and one hospital control was selected for each case, matching gender, age, and hospital. A well-validated food frequency questionnaire was adopted to estimate intakes of nutrients and food groups. Odds ratios (ORs) adjusted for smoking and occupational history were computed using conditional logistic models. The analyses based on 297 cases and 295 controls revealed the following. 1) The more the intake of milk and dairy products, the lower the OR; the ORs across quartiles in all subjects were 1.02, 0.73, and 0.52. Fruit intake was negatively associated with the risk, particularly in men (ORs across quartiles = 0.76, 0.77, and 0.52). Green-yellow vegetables were associated with a decreased risk in the highest quartile of consumption in men (OR = 0.57). 2) Dietary intakes of retinol and saturated fatty acids were related to a reduced risk in all subjects (ORs across quartiles = 0.75, 0.54, and 0.66 and 0.55, 0.54, and 0.60, respectively). Monounsaturated fatty acids had an inverse association with bladder cancer risk in men.

Adult↗
PubMed2000

[Pharmacological characteristics of perospirone hydrochloride, a novel antipsychotic agent].

It is now known that the blockade of 5-HT2 receptors can ameliorate the negative symptoms of schizophrenia and extrapyramidal side effects (EPS) associated with antipsychotic treatments. Perospirone hydrochloride (perospirone), which was identified as a novel serotonin-dopamine antagonist (SDA)-type antipsychotic agent in 1987 by Sumitomo Pharmaceuticals, possesses high affinities both for dopamine 5-HT2 and D2 receptors. Perospirone, like conventional antipsychotics, significantly inhibited various behaviors induced by dopaminergic hyperactivation. Perospirone also produced a significant improvement in animal models of the negative symptoms and mood disorders, where the conventional antipsychotics were unaffected. In addition, perospirone was weaker than the conventional antipsychotics (e.g., haloperidol) in inducing EPS signs (e.g., catalepsy and bradykinesia), suggesting that the drug has an atypical antipsychotic property. A recent double-blind study with schizophrenia patients demonstrated that perospirone was comparative with haloperidol in improving the positive symptoms, but was significantly superior to haloperidol against the negative symptoms. Furthermore, the extrapyramidal score in patients with perospirone treatment was lower that those with haloperidol treatment. These findings suggested that perospirone acts as an antagonist both for 5-HT2 and D2 receptors and has broader clinical efficacy and lower EPS liability than haloperidol in schizophrenia treatment.

Animals↗
PubMed2000

Different domains of Sgs1 are required for mitotic and meiotic functions.

The SGS1 of Saccharomyces cerevisiae is a homologue for human Bloom's syndrome, Werner's syndrome, and Rothmund-Thomson's syndrome causative genes. Disruptants of SGS1 show high sensitivity to methyl methanesulfonate (MMS) and hydroxyurea, and hyper recombination phenotypes including interchromosomal homologous recombination in mitotic growth. In addition, sgs1 disruptants show poor sporulation and a reduced level of meiotic recombination as assayed by return-to-growth. We examined domains of Sgs1 required for mitotic and meiotic functions of Sgs1 by transfecting variously mutated SGS1 into sgs1 disruptants. The N-terminal 1-401 amino acid region was required for complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations of sgs1 disruptants in mitotic growth and for complementation of poor sporulation and of reduced meiotic recombination. Although the N-terminal 1-125 amino acid region was absolutely required for the complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations in mitotic growth, it was dispensable for the meiotic functions. In contrast, the highly acidic region (400-596 amino acid) was dispensable for the mitotic functions but a deletion of this region affected the meiotic functions. The C-terminal 1271-1350 amino acid region containing a HRDC (helicase and RNaseD C-terminal) domain was dispensable for the mitotic and meiotic functions. Although DNA helicase activity of Sgs1 was not required for Sgs1 to complement the meiotic functions, a deletion of helicase motifs III-IV (842-1046 amino acid) abolished the complementing activity of Sgs1, indicating that a structurally intact helicase domain is necessary for Sgs1 to fulfill its meiotic functions.

Alleles↗
PubMed2000

Insulin sensitivity and calcium homeostasis in young, lean, normotensive male subjects.

Insulin resistance is known to be closely related to essential hypertension. It has been hypothesized that abnormal calcium homeostasis both at the cellular level and in the whole body plays a substantial role in hypertension associated with insulin resistance. We attempted to determine the relationships among insulin sensitivity, blood pressure (BP), body mass index (BMI), and calcium-related parameters in young, lean, normotensive male subjects with extreme susceptibilities to hypertension, and to investigate the effects of euglycemic hyperinsulinemia on calcium-related parameters. Seven young, lean, normotensive male subjects with family histories of essential hypertension and 10 age-matched controls without any parental cardiovascular events were enrolled. Insulin sensitivity measurement by the euglycemic hyperinsulinemic clamp technique and a 75-g oral glucose tolerance test were performed. Calcium-related parameters, including intracellular Ca2+ levels in platelets, were measured simultaneously. Diastolic BP was inversely correlated with insulin sensitivity in vivo (M-value). Insulin sensitivity was inversely correlated with BMI and with intracellular Ca2+ in platelets. In the multivariate stepwise regression analysis using both diastolic BP and insulin sensitivity as dependent variables, BMI was found to be a determinant independent variable. Euglycemic hyperinsulinemia decreased intact parathyroid hormone levels and increased fractional excretion of calcium. In conclusion, BMI rather than a family history of hypertension plays a determinant role on the regulation of diastolic BP and insulin sensitivity even in young, lean, normotensive male subjects with extreme predispositions for the development of hypertension. Hyperinsulinemia decreased intact parathyroid hormone levels and increased fractional excretion of calcium.

Adult↗
PubMed2000

Mapping of four simple sequence repeat (SSR) markers on rat chromosome 4.

We previously reported that several markers on rat chromosome (Chr) 4 cosegregated with the occurrence of cerebral stroke and brain edema in stroke-prone spontaneously hypertensive rats (SHRSP). To obtain insights into the positional candidate genes for stroke susceptibility in this region, we mapped four genes, Taurine transporter (Tau), tumor necrosis factor receptor (Tnfr), GABA transporter (Gat1) and glucose transporter-3 (Glut3) genes, using newly developed simple sequence repeat (SSR) markers on rat Chr 4. We isolated the SSRs for the genes either by screening a rat genomic library or by searching the GenBank database. By linkage analysis using two sets of backcrosses, Gat1 and Tnfr were mapped in the region associated with stroke, while Taut was located distant from the region. The Glut3 locus was also assigned to rat Chr 4 using a rat x mouse hybrid clone panel. These results indicated that the Tnfr, Gat1 and Glut3 genes were good positional candidates for the stroke susceptibility in SHRSP, suggesting that further evaluation of these genes by functional studies could prove useful.

Animals↗
PubMed2000

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and adrenal insufficiency induced by rathke's cleft cyst: a case report.

We report a case of a seventy-year-old woman with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and adrenal insufficiency induced by Rathke's cleft cyst. She experienced nausea, vomiting, diarrhea, and headache and disturbance of consciousness induced by hyponatremia at a serum sodium level of 100 mEq/l. In spite of severe hyponatremia, urinary sodium excretion was not suppressed and serum osmolality (270 mOsm/kg) was lower than urine osmolality (304 mOsm/kg), and arginine vasopressin (AVP) remained within normal range. SIADH was diagnosed because she was free from other diseases known to cause hyponatremia such as dehydration, cardiac dysfunction, liver dysfunction, renal dysfunction, hypothyroidism, and adrenal insufficiency. Cranial computed tomographic (CT) scan and cranial magnetic resonance (MR) imaging showed a cystic lesion of approximately 2 cm in diameter in the pituitary gland. These images suggested that the cystic lesion was a Rathke's cleft cyst, which was the cause of SIADH. Water restriction therapy normalized her serum sodium concentration and improved her symptoms. After one year, she suffered from general fatigue, appetite loss, fever, and body weight loss (5 kg/2 months). She had neither hypotension nor hypoglycemia, but her serum sodium level was low and serum cortisol, ACTH, and urine free cortisol were very low. Therefore, secondary adrenal insufficiency was suspected and diagnosed by stimulation tests. After start of hydrocortisone replacement therapy (10 mg/day), her symptoms disappeared. In conclusion, Rathke's cleft cyst should be kept in mind as a potential cause in a patient with SIADH, hypopituitarism, and/or adrenal insufficiency.

Adrenal Insufficiency↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats--overview of the studies.

The National Institute of Health Sciences and 28 member companies of the Japan Pharmaceutical Manufacturers Association (JPMA) have conducted a validation study intended to examine whether or not lesions in the male reproductive organs noted in 4-week treatment studies can also be detected after 2-week treatment. In this study, lesions in the male reproductive organs after 2-week treatment were, therefore, compared with those after 4-week treatment. A total of 24 test substances was evaluated, these being nucleic acid modulators, cell division inhibitors, central hormonal modulators, hormonal drugs and their antagonists, other drugs and general chemicals. Among these substances, theophylline did not cause any appreciable lesions in the male reproductive organs even after 4-week treatment in the preliminary studies. With busulfan, data reported in the literature was not reproduced in the preliminary study and all animals died. Therefore, detailed examinations were not conducted for busulfan and theophylline. The remaining 22 test substances, when given to animals for 2 weeks at doses equal to or higher than for 4-week treatment, caused lesions similar to those noted after 4 weeks. It is evident from these findings that effects of pharmaceuticals on the male reproductive organs can be detected in most cases with 2-week treatment.

Animals↗
PubMed2000

Correlation between erythropoietin and lactate in humans during altitude exposure.

The plasma concentrations of both immunoreactive erythropoietin (EPO) and lactate were determined in four healthy untrained subjects at sea level and on the 2nd or 3rd day at altitudes (1,300 and 3,500 m). The mean plasma EPO (18.8 +/- 1.6 mU/ml at sea level) increased significantly on the 3rd day at 1,300 m (25.5 +/- 2.0 mU/ml, p < 0. 05) and showed an almost three-fold increase on the 2nd day at 3,500 m (53.5 +/- 3.7 mU/ml, p < 0.001). Likewise, the mean plasma lactate at 3,500 m (3.98 +/- 0.27 mmol/l) was 3.6 times as high as that at sea level (1.11 +/- 0.05 mmol/l) (p < 0.001). The plasma EPO concentrations were found to correlate well with the lactate concentrations at sea level and altitudes (r = 0.86, p < 0.01). These results are consistent with the well-known EPO/lactate response to altitudes and suggest that the circulating EPO concentration as well as blood lactate concentration can be used as an index of anaerobic condition.

Adult↗
PubMed2000

Depressive mood and suicide among middle-aged workers: findings from a prospective cohort study in Nagoya, Japan.

BACKGROUND: In Japan, mortality from suicide has peaked around 50 years old among men, with increasing trend after 65 years old, and this peak became more apparent in recent years. Beside this, "psychological autopsy" has revealed depression as one of the most important risk factors for suicide. There is, however, no cohort study which examined the relationship between depressive mood measured by simple method and suicide in middle-aged general population. METHODS: In 1989, baseline information was collected by a self-administered questionnaire, and 18,450 workers were followed up to March 31, 1995. All deaths observed during active service were identified, and when retired, its date was recorded. Among 5,352 male workers aged between 40 to 54, 11 committed suicide during follow-up period of 5 years. Analysis were carried out by Cox's proportional hazard model, controlling for age. RESULTS: Those who slept 9 hours or more per night demonstrated 12.14-fold risk of suicide compared with those who slept less than 9 hours. Smokers were more likely to commit suicide than non-smokers. Those who answered affirmatively to more than 7 out of 12 questions, which were derived from Zung self-rating depression scale, experienced an increased risk of suicide (RR 9.95; 95%CI: 1.89-52.44), even after adjusting for other confounding factors. CONCLUSION: We found an association between depressive mood and subsequent suicide in a middle-aged workers. Detailed observation and follow-up of those with depressive mood should be systematically organized with due attention and caution.

Adult↗
PubMed2000

Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan.

A nationwide epidemiologic survey of idiopathic hypoparathyroidism and pseudohypoparathyroidism was conducted in 1998 to clarify the prevalence of the two disorders in Japan. From a total of 14,100 departments of pediatrics, internal medicine, neurology, and endocrinology in whole Japan, 2952 (20.9%) study departments were selected at random. Of these departments receiving the first questionnaire, 1855 (62.8%) responded. From these departments 390 patients with idiopathic hypoparathyroidism and 203 with pseudohypoparathyroidism who visited the hospitals in 1997 were reported. The total numbers of patients were estimated to be 900 (690-1100) for idiopathic hypoparathyroidism and 430 (330-520) for pseudohypoparathyroidism (95% confidence intervals in parentheses). Using these data, the period prevalence of the diseases were 7.2 (5.5-8.8) per million population in idiopathic hypoparathyroidism, and 3.4 (2.6-4.2) in pseudohypoparathyroidism (95% confidence intervals in parentheses).

Adolescent↗
PubMed2000

Maternal active and passive smoking and fetal growth: A prospective study in Nagoya, Japan.

In order to examine the effect of maternal active and passive smoking on fetal growth, we carried out a population-based cohort study. A self-administered questionnaire was distributed to 15,207 women who notified their pregnancy from April, 1989 to March, 1991. A total of 7,411 mother-singleton infant pairs were analyzed in this study. Paternal smoking status and maternal hours exposed to environmental tobacco smoke (ETS) were used as indicators of passive smoking. Infants born to active smoking mothers were 96 g lighter, on an average, at birth than those born to non-smokers, and the relative risk for intrauterine growth retardation was 1.79 (95% confidence interval (CI) = 1.05-3.04) among active smoking mothers. Infants with smoking fathers weighted 11 g lighter, on an average, than those with non-smoking fathers, and mean birth weight of infants was reduced by 19 g among mothers exposed to ETS. The relative risk for intrauterine growth retardation in non-smoking pregnants with a smoking husband and those exposed to ETS was 0.95 (95% CI = 0.72-1.26) and 0.95 (95% CI = 0.71-1.26), respectively. Our findings indicated an adverse effect of maternal active smoking on fetal growth in Japanese pregnant population, but with small influence of maternal passive smoking.

Analysis of Variance↗
PubMed2000

Sleep patterns and total mortality: a 12-year follow-up study in Japan.

A population-based cohort study was conducted to assess the relationship between total mortality and self-reported sleep patterns as regards not only to sleep duration but also subjective sleep quality. A total of 5,322 inhabitants in Gifu Prefecture, Japan, completed a self-administered questionnaire on health status and lifestyles including habitual sleep patterns, and were followed-up for an average of 11.9 years. Relative risks were computed by using Cox proportional hazards models. Both longer and shorter sleep, compared to 7-8 hour-sleep, was related to significantly increased risk of total mortality in males (relative risk [RR] for > or = 10 hours = 1.94, and RR for < 7 hour = 1.90), but not in females. Females complaining of poor awakening state experienced a higher mortality risk compared to those who woke up normally (RR: 1.97). Males who usually fell asleep easily showed a marginally lower mortality risk compared to those who fell asleep normally (RR: 0.70). Female users of sleeping pills were at an elevated risk (RR: 1.89). These findings were almost unchanged after adjustment for sleep duration and other confounders. Poor self-reported quality of sleep seemed to be associated with an increased risk of mortality independently of sleep duration.

Adult↗
PubMed2000

(2R-trans)-2-butyl-5-heptylpyrrolidine as a potent sigma receptor ligand produced by Streptomyces longispororuber.

A potent sigma (sigma) receptor ligand was isolated from the culture broth of Streptomyces longispororuber #525. The active compound was identified to be (2R-trans)-2-butyl-5-heptylpyrrolidine by spectroscopic and chemical studies. The compound exhibited high affinity and selectivity for sigma receptors. The IC50 values toward sigma1, sigma2 and dopamine D2 receptors were 2.0, 22.7 and more than 40,000 nM, respectively. Its (2S-trans)- and (+/-)-cis-isomers, both synthesized, were also found to be high affinity sigma ligands.

Animals↗
PubMed2000

Comparative developmental toxicity study of indium in rats and mice.

The developmental toxicity of indium was examined in both rats and mice using comparable experimental protocols. Pregnant rats received a single intravenous administration of indium trichloride (InCl(3)) at 0.4 mg In/kg, on day 9, 10, or 11 of pregnancy and their fetuses were examined on day 20. Pregnant mice were treated in the same manner at 0.8 or 1.6 mg In/kg on day 7, 8, or 9 of pregnancy and their fetuses were examined on day 18. In rats, indium caused fetal weight decrease and fetal gross malformations, such as brachyury, kinked tail, cleft palate, and oligodactyly, most severely by the administration on day 10. In mice, however, indium did not cause fetal gross malformations, although it caused fetal weight decrease at 0.8 mg In/kg or more and fetal death at 1.6 mg In/kg, most severely by the administration on day 8. It was concluded from these results that rats and mice were susceptible to the embryotoxicity of indium at similar developmental stages in the early organogenetic period, but mice were less susceptible to the teratogenicity of indium than rats in terms of gross malformation. Toxicokinetic factors may be involved in this different susceptibility. Teratogenesis Carcinog. Mutagen. 20:219-227, 2000.

Abnormalities, Drug-Induced↗
PubMed2000

[Clinical quality assurance at institutions according to a patterns of care study. Japanese PCS Working Group].

The clinical quality assurance (QA) of an institution is important in any multiinstitutional prospective study. Patterns of Care Study (PCS) is a well-known study for QA activity in the United States. PCS is a nationwide retrospective study done by two-staged cluster sampling of institutions and patients and external audits. After data are accumulated, National averages on various survey items are calculated as a QA measure. In 1996, PCS was imported into the radiation oncology field in Japan with the support of the Ministry of Health and Welfare. Preliminary results showed significant differences in treatment process, structure, and preliminary outcome according to the stratification of institutions. These data can be useful in improving the structure and process at the institutional as well as the national level. PCS will also clarify the dissemination of positive clinical results into national practice.

Esophageal Neoplasms↗