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Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 37 records · Page 2Linked to original sources
PubMed1995

Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit.

The NMDA (N-methyl-D-aspartate) receptor channel is important for synaptic plasticity, which is thought to underlie learning, memory and development. The NMDA receptor channel is formed by at least two members of the glutamate receptor (GluR) channel subunit families, the GluR epsilon (NR2) and GluR zeta (NR1) subunit families. The four epsilon subunits are distinct in distribution, properties and regulation. On the basis of the Mg2+ sensitivity and expression patterns, we have proposed that the epsilon 1 (NR2A) and epsilon 2 (NR2B) subunits play a role in synaptic plasticity. Here we show that targeted disruption of the mouse epsilon 1 subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation at the hippocampal CA1 synapses. The mutant mice also showed a moderate deficiency in spatial learning. These results support the notion that the NMDA receptor channel-dependent synaptic plasticity is the cellular basis of certain forms of learning.

Animals↗
PubMed1995

Two-dimensional electrophoretic analysis of down-regulated proteins in human fibroblasts immortalized by treatment with either 4-nitroquinoline 1-oxide or 60Co gamma rays.

Cellular proteins were examined by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) in order to determine the mechanisms of cellular aging and immortalization of human fibroblasts. A total of 10 cell lines were studied, four of which were immortalized. OUMS-24F and SUSM-1 cells were immortalized by repeated treatment with 4-nitroquinoline 1-oxide (4NQO), KMST-6 cells were immortalized by intermittent exposure to 60Co-gamma rays, and IMR-90/SV40 cells were immortalized with simian virus 40 (SV40). None of these immortalized cells were tumorigenic. Four normal human fibroblast cell lines, OUMS-24, AD 387, KMS-6 and IMR-90, and two human cervical cancer cell lines, HeLa and A-431, were also studied. Applying 2-D PAGE, the down-regulation of the identical proteins was observed in the four immortalized cell lines and in the two human cancer cell lines. Their molecular masses were about 80 kDa and the isoelectric points ranged between 5.5 and 6.3. We could not find any information on our proteins from the recent protein data bases. Further characterization of the proteins indicated that they might be phosphorylated cytoskeletal proteins.

4-Nitroquinoline-1-oxide↗
PubMed1995

Isolation of porcine adenovirus as a candidate of 5th serotype.

A strain of cytopathic virus, named strain TG/K79, was isolated from the brain of a newborn piglet, pure Hampshire breed, which died shortly after birth. The physicochemical property of virus was considered to be that of the family Adenoviridae. A significant difference between our isolated and 4 reference porcine adenoviruses was demonstrated by cross-seroneutralization test. Differences between TG/K79 and other porcine adenoviruses were also seen in electrophoretic patterns of viral DNA in agarose gel after digested by restriction endonucleases. Two SPF pigs, 2-month-old, experimentally infected via intranasal showed a fever and a hemorrhagic enteritis. A serological survey indicates that at least swine in the farm where the virus was isolated have been highly contaminated.

Adenoviridae Infections↗
PubMed1995

Prevalence of focal dystonias in the western area of Tottori Prefecture in Japan.

We evaluated the prevalence of focal dystonias in the western area of Tottori Prefecture in Japan. The population of the area was 244,935 on October 1, 1992. Because four patients with blepharospasm and three patients with writer's cramp did not visit any hospitals or clinics in 1993 and did not reply to our question letter, we could not confirm their present condition: with or without focal dystonia in 1993. Four patients with facial dystonia including blepharospasm and oromandibular dystonia, seven with spasmodic torticollis, and four with writer's cramp were observed. The prevalence of focal dystonias was 6.12 per 100,000 persons, which may be lower than that in western countries. Although the reasons for this difference are still unclear, a genetic factor may be one implication.

Adult↗
PubMed1995

Attenuation of the endotoxin-stimulated increase in hepatic amino acid transport with a glucocorticoid receptor antagonist.

The role of the glucocorticoid hormones in mediating the accelerated hepatic amino acid transport that is characteristic of endotoxemia was investigated. To determine the role of these steroid hormones, rats that received endotoxin (LPS) were pretreated with the glucocorticoid receptor antagonist RU38486. The activities of the Na(+)-dependent amino acid transport systems A, ASC, and N and the Na(+)-independent systems L, y+, n, b0,+, and asc in hepatic plasma membrane vesicles were measured 4 hr after exposure to LPS. Endotoxin treatment resulted in time- and dose-dependent 5-fold (System A), 2.5-fold (System N), 2.6-fold (System ASC), and 2-fold (System y+ and b0,+) increases in transport activity attributable to an increase in carrier Vmax. The activities of L, asc, and n were unchanged by LPS administration. Pretreatment of endotoxemic animals with RU38486 attenuated the LPS-induced enhancement in transport activity by 20-60% by diminishing carrier Vmax, with no effect on transport Km. We conclude that the marked increase in hepatic amino acid transport activity that occurs during endotoxemia requires participation of the glucocorticoid hormones.

Amino Acids↗
PubMed1995

Rapid turnover proteins as a prognostic indicator in cancer patients.

We investigated the relation between the plasma levels of various proteins, especially rapid turnover proteins (RTPs), and the prognosis in advanced cancer patients receiving total parenteral nutrition (TPN). In the patients with benign disease (n = 40), RTPs increased abruptly following TPN, but in patients with malignant disease, they rose slowly. Patients with malignant disease were divided into two different groups according to the outcome; group A, surviving 3 months or more after TPN and group B, who died within 3 months after TPN initiation. Whereas the RTP levels were elevated significantly in group A, they did not show any noticeable increase in group B. There was a close correlation between the plasma protein levels at 2 weeks and the survival time after TPN initiation. Thus, using the estimated critical values of RTPs with prognostic significance, the correct prognosis rate in 37 newly treated cases was: transferrin 75.7%, prealbumin: 91.9%, retinol-binding protein: 86.5%. These results clearly indicate that the TPN-induced changes in RTPs, notably in the PA value, can be a good prognostic indicator of survival in advanced cancer patients.

Adult↗
PubMed1995

Seasonal variation in sweating responses of older and younger men.

Eight older (60-65 years) and six younger (20-25 years) men were exposed to a standard heat stress for 60 min in summer, autumn, winter, and spring. The test consisted of placing the lower legs and feet in a 42 degrees C water bath while sitting in constant environmental conditions (30 degrees C and 45% relative humidity). The increase of rectal temperature (delta Tre) was significantly greater (P < 0.05) in autumn, winter, and spring than in summer for the older group, but significantly greater only in winter than in summer for the younger group (P < 0.05). The delta Tre was greater for the older group in all seasons, but of significance only in autumn and spring (P < 0.01). There were no significant season-related differences for metabolic heat production (M) and mean skin temperature (Tsk) during the heat test in the respective groups, although the M and Tsk were lower for the older group in all seasons (P < 0.01). In the older group total body sweating rate (msw) divided by delta Tre (total msw/delta Tre) decreased from summer to winter (P < 0.02) and did not differ between winter and spring, whereas total msw/delta Tre in the younger group increased in spring after decreasing from autumn to winter (P < 0.03). The variations of the value, local sweating rate on the back and thigh divided by delta Tre (back msw/delta Tre and thigh msw/delta Tre), were similar to those of the total msw/delta Tre in each group, except for back msw/delta Tre in the younger group, which did not increase from winter to spring.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMed1995

Longitudinal study of the effect of high intensity weight training on aerobic capacity.

To investigate the effect of a long-term weight lifting programme characterized by high intensity, low repetition and long rest period between sets on maximal oxygen consumption (VO2max) and to determine the advantage of this programme combined with jogging, 26 male untrained students were involved in weight training for a period of 3 years. The VO2max and body composition of the subjects were examined at beginning, 1 year, 2 years (T2), and 3 years after (T3) training. Of the group, 19 subjects performed the weight lifting programme 5 days each week for 3 years (W-group), 4 subjects performed the same weight lifting programme for 3 years with an additional running programme consisting of 2 miles of jogging once a week during the 3rd year (R1-group), and 3 subjects performed the weight lifting programme during the 1st year and the same combined jogging and weight lifting programme as the R1-group during the 2nd and 3rd years (R2-group). The average VO2max relative to their body mass of the W-group decreased significantly during the 1st year, followed by an insignificant decrease in the 2nd year and a levelling off in the 3rd year. The average VO2max of the W-group at T2 and T3 was 44.2 and 44.1 ml.kg-1.min-1, respectively. The tendency of VO2max changes in the R1- and R2-groups was similar to the W-group until they started the jogging programme, after which they recovered significantly to the initial level within a year of including that programme, and they then levelled off during the next year. Lean body mass estimated from skinfold thicknesses had increased by about 8% after 3 years of weight lifting. The maximal muscle strength, defined by total olympic lifts (snatch, and clean and jerk), of these three groups increased significantly and there was no significant difference among the amounts of the increase in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Age predicts cardiovascular, but not thermoregulatory, responses to humid heat stress.

Cross-section comparisons of the effect of age on physiological responses to heat stress have yielded conflicting results, in part because of the inability to separate chronological age from factors which change in concert with the biological aging process. The present study was designed to examine the relative influence of age on cardiovascular and thermoregulatory responses to low intensity cycle exercise (60 W for 1 h) in a warm humid environment (35 degrees C, 80% relative humidity). Specifically, the relative importance of age compared to other individual characteristics [maximal oxygen uptake (VO2max), physical activity level, anthropometry, and adiposity] was determined by multiple regression analysis in a heterogeneous sample of 56 subjects in which age (20-73 years) and VO2max (1.86-4.44 l.min-1) were not interrelated. Dependent variables (with ranges) included final values of thermoregulatory responses [rectal temperature (Tre, 37.8-39.2 degrees C), calculated heat storage (S, 3.4-8.1 J.g-1), sweat loss (238-847 g.m-2)] and cardiovascular responses [heart rate (HR, 94-176 beats.min-1), forearm blood flow (FBF, 5.3-31.3 ml.100 ml-1.min-1), mean arterial blood pressure (MAP, 68-122 mmHg), and forearm vascular conductance (FVC = FBF.MAP-1, 0.06-0.44 ml.100 ml-1.min-1.mmHg-1). Age had no significant influence on Tre, S, or sweat loss, all of which were closely related to VO2max. On the other hand, HR, MAP, FBF, and FVC were related to both age and VO2max. Anthropometric variables and adiposity had secondary, but statistically significant, effects on MAP, FBF, FVC, and sweat loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Seasonal variation in physiological responses to mild cold air in young and older men.

Eight men aged 60-65 years and six men aged 20-25 years, wearing only swimming trunks, were exposed to an air temperature of 17 degrees C and 45% R.H. in each of the four seasons. The increase in the rate of metabolic heat production (% delta M) for the older group in the cold test was significantly higher in summer and autumn than in winter and spring (P < 0.05), but did not differ in the young group between seasons. Compared to the young group the % delta M was significantly greater for the older group (due to a marked increase in four individuals) in summer and autumn (P < 0.04). At the end of the period of cold exposure, the decrements of rectal temperature (delta Tre), mean skin temperature (Tsk; due to a marked decrease in four individuals) and foot skin temperature (Tfoot) were significantly greater for the older group compared to the young group at all times of the year (P < 0.003). Seasonal variations in the two groups were similar, e.g., the delta Tre gradually became smaller from summer to winter (P < 0.05) and then increased slightly in the spring (P = 0.07). Tfoot for both groups decreased from summer to autumn (P < 0.01) and remained unchanged subsequently. No seasonal variations were observed for Tsk in either group. The increase in diastolic blood pressure (BPd) during the test was significantly smaller in winter in both groups (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMed1995

The in vivo-in vitro replicative DNA synthesis (RDS) test with hepatocytes prepared from male B6C3F1 mice as an early prediction assay for putative nongenotoxic (Ames-negative) mouse hepatocarcinogens.

To assess the efficacy of the in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test as a short-term assay, 41 putative nongenotoxic (Ames-negative) mouse hepatocarcinogens, as well as 31 noncarcinogens, were examined using male 8-week-old B6C3F1 mice and an in vitro [methyl-3]thymidine-incorporation technique. Animals were exposed to the maximum tolerated dose (MTD) and 1/2 MTD of each chemical by gavage and after 24, 39 or 48 h, hepatocytes were prepared with a collagenase-perfusion technique. Assessment of the distribution of spontaneous RDS in a total of 337 control mice gave an average incidence of 0.15 +/- 0.08% within the range of 0 to 0.39% (mean +/- 3 x SE) with a 99.7% probability. Values of 0.4% or more for RDS incidences induced by test samples were therefore judged as indicating a positive response in our RDS test. Under the experimental conditions applied, 32 of 41 putative nongenotoxic hepatocarcinogens gave clear positive responses (positive sensitivity: 78%), and of 31 noncarcinogens 25 samples gave negative responses (negative specificity: 81%), thus giving an overall concordance for the RDS test with long-term findings of 79%.

Administration, Oral↗
PubMed1995

Cerebellum of the adult reeler mutant mouse contains two Purkinje cell populations with respect to gene expression for the N-methyl-D-aspartate receptor channel.

Recent studies have identified five NMDA receptor subunits, which exhibit distinct cellular expressions in the normal rodent brain. The purpose of this investigation is to clarify the molecular-anatomical organization in the cerebellum of the reeler mutant mouse, in which various categories of the Purkinje cells are present as to the cell position and synaptic connectivity. In comparison with the distribution of the inositol 1,4,5-trisphosphate receptor mRNA, a molecular marker specific to the Purkinje cells, the epsilon 1 subunit mRNA of the NMDA receptor channel was found in the adjacent sections to be expressed in a subset of the Purkinje cells. In the rostrocaudal extent, the Purkinje cells expressing the epsilon 1 subunit mRNA were distributed preferentially in the rostral cerebellum, irrespective of the normal and heterotopic positions. In the mediolateral extent, they formed segregated cell clusters, interposed by epsilon 1 subunit mRNA-negative clusters. Hybridizing signals for the zeta 1 subunit mRNA were found in all the Purkinje cell population, whereas those for the epsilon 2, epsilon 3, and epsilon 4 subunit mRNAs were not detected in the cells. These findings suggest that the reeler cerebellum is topographically compartmentalized by two subpopulations of the Purkinje cells, one expressing the epsilon 1 and zeta 1 subunit mRNAs, and the other expressing the zeta 1 subunit mRNA alone.

Animals↗
PubMed1995

Effect of chronic vanadate administration in partially depancreatized rats.

The effects of vanadate on B-cell function and replication in rats after 90% partial pancreatectomy (Px) were compared with insulin therapy. At the age of 4 weeks, male Wistar rats were subjected to sham operation or Px. Vanadate (0.2 mg/ml) was given in drinking water for 3 weeks starting at 2 weeks after surgery. Regular insulin (2.4 units/day) was administered as a continuous subcutaneous infusion through an osmotic pump. Plasma glucose levels were significantly higher in the Px rats than in the sham rats from 1 week after surgery. Vanadate lowered plasma glucose levels to near normal values in the Px rats as early as 2 days. The effect was sustained throughout the experiment. The hypoglycemic effect of insulin was less than that of vanadate. During an i.p. glucose tolerance test, plasma glucose levels were decreased in the Px rats treated with vanadate or insulin, while plasma insulin levels were not affected. The insulin content in the Px rats treated with vanadate was significantly (P < 0.01) greater than in the insulin-treated Px rats. Histological examination showed fibrotic degeneration in the enlarged islets of Px rats, whereas the normal structure was retained in most islets of the Px rats treated with vanadate and insulin. In addition, B-cell areas within the islet were restored to normal levels not only in the insulin-treated Px rats but in the vanadate-treated Px rats. However, both vanadate and insulin failed to stimulate proliferative activity of the B-cells. These data suggest that vanadate is a new therapeutic option to ameliorate the diabetic state after Px.

Analysis of Variance↗
PubMed1995

Lack of effect of CS-045, a new antidiabetic agent, on insulin secretion in the remnant pancreas after 90% pancreatectomy in rats.

We assessed the effect of CS-045, a new hypoglycemic agent, on B-cell function in partially pancreatectomized rats. At the age of 4 weeks, male Wistar rats were subjected to 90% pancreatectomy (Px). For 2 weeks starting at 6 weeks after surgery the Px rats were treated with CS-045 (CS rats) mixed with chow pellets in a proportion of 0.2% (w/w). To compare the efficacy of CS-045 with that of insulin therapy, an osmotic pump was implanted to release insulin (1.2 units/day) into the intraperitoneal cavity of the Px rats (Is rats). Plasma glucose levels in the CS and Is rats were significantly lower than in the control Px rats; however, no marked improvement in plasma glucose or insulin levels was observed in glucose tolerance test (2 g/kg, i.p.) in the CS rats. Insulin secretion by the isolated perfused pancreas in response to 16.7 mM glucose showed a biphasic pattern, but was slightly reduced in the Px and CS rats compared with the Is rats. Insulin secretion induced by 19 mM arginine was unaffected by the treatment. The insulin content of the CS rats was significantly greater than in the Px and Is rats. Histological observations suggested regranulation of the pancreatic islets of the CS rats. B-cell areas within the islet were restored to normal levels in the Cs and Is rats. These findings indicate that the hypoglycemic effect of CS-045, which is not mediated by insulin secretion from the residual pancreas, prevents destruction of the islet.

Animals↗
PubMed1995

Dietary regulation of the hepatic system n glutamine transporter in tumor-bearing rats.

BACKGROUND: Hepatocytes possess a novel, plasma-membrane, sodium ion (Na+)-independent, glutamine transporter (system n), which functions to transport glutamine out of the cell into the blood. In the tumor-bearing rat, the activity of system n increases but its regulation is unknown. We hypothesized that the increase in system n that occurs in rats with cancer was related to a fall in the circulating glutamine concentration. METHODS: Ten male rats underwent flank implantation with a cube of methylcholanthrene-induced fibrosarcoma cells and 10 rats underwent a sham operation. After 9 days of standard diet, all rats were randomized to receive either a glutamine-enriched oral diet or an isonitrogenous diet without supplemental glutamine, for 1 week. Tumors and livers were harvested 16 days postimplantation. Arterial blood samples were obtained from all animals. Hepatic plasma membrane vesicles were prepared and the carrier-mediated, Na(+)-independent transport of glutamine was assayed. RESULTS: When compared to nontumor-bearing animals, tumor-bearing rats that were fed a control diet exhibited hypoglutaminemia and a 2.3-fold increase in the activity of system n. Glutamine dietary supplementation produced blood glutamine levels that were similar in both tumor-bearing and nontumor-bearing rats, apparently abrogating the increase in system n activity that was observed in tumor-bearing rats that were not fed supplemental glutamine. Tumor-bearing animals receiving supplemental glutamine had a decreased number of system n carriers (Vmax) in the hepatic plasma membrane compared to that of tumor-bearing animals receiving a control diet; this apparently abrogated the glutamine efflux rate. Glutamine feeding did not alter system n activity in nontumor-bearing controls. CONCLUSIONS: In the tumor-bearing animal model, system n is modulated by the circulating glutamine concentration. This is the first study that demonstrates the ability of specialized nutrition to "downregulate" transport activity in vivo. Provision of glutamine-enriched diets to the host with cancer may maintain hepatic glutamine levels and prevent host glutamine depletion.

Animals↗
PubMed1995

Evaluation of serum KL-6 levels in patients with pulmonary tuberculosis.

SETTING: KL-6, a human MUC-1 mucin preferentially expressed on type II pneumocytes, is a sensitive serum marker for evaluating alveolar damage of interstitial pneumonia and pulmonary fibrosis. Some patients with pulmonary tuberculosis develop severe respiratory dysfunction caused by extensive pulmonary fibrosis, compensatory emphysema and fibrous pleural thickening. OBJECTIVE: To evaluate the clinico-pathological significance of KL-6 in pulmonary tuberculosis. DESIGN: Serum KL-6 levels were measured in sera from 57 patients with active pulmonary tuberculosis and 38 healthy controls by a sandwich-type enzyme-linked immunosorbent assay. Immunohistochemistry was performed by an avidin-biotin-peroxidase complex method. RESULTS: KL-6 levels were significantly higher in the patients than in the healthy controls (518 +/- 693 [SD] vs 227 +/- 91 U/ml, P < 0.001) and increased significantly according to the extent of pulmonary lesions evaluated by chest X-ray (P < 0.001). There was a significant negative correlation between serum KL-6 levels and % vital capacity (VC) (r = 0.642, P < 0.05). KL-6 was strongly expressed on proliferated type II pneumocytes and cuboidal epithelial cells adjacent to thickened intralobular septa and pleura. CONCLUSIONS: In pulmonary tuberculosis, serum KL-6 originates from proliferated type II pneumocytes and cuboidal epithelial cells, and is a useful marker presenting the degree and extent of pulmonary fibroproductive lesions.

Aged↗
PubMed1995

Biomechanical behavior of the periodontium before and after orthodontic tooth movement.

This study was designed to investigate the biomechanical behavior of the periodontium including the periodontal ligament (PDL) in terms of tooth mobility. Tooth mobility was measured in the canines of 10 adolescent patients before and after distal movement. Distal movement of the canines was carried out by use of a calibrated sectional archwire exerting an initial retraction force of 200 g. Tooth mobility was measured immediately before and after canine retraction by use of a noncontact displacement sensor when varying distal forces of 0 to 500 g were applied to the mesial of the canine. Before tooth movement, tooth mobility exhibited a substantial increase in loading with forces ranging from 50 to 150 g. The rate of increase gradually decreased up to 500 g. A nonlinear change in tooth mobility was similarly observed at the end of tooth movement or 24 days after the initiation of movement. Tooth mobility, however, was significantly greater when forces above 200 g were loaded. The periodontal tissues--the PDL and alveolar bone in particular--become more flexible at the end of tooth movement, indicating reduced support by the periodontal tissues. These findings suggest that the elastic nature of the PDL and alveolar bone may decrease substantially at the end of tooth movement.

Adolescent↗