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Biomedical subjects

H Ikegami

Publications and source records attributed to H Ikegami.

At least 127 records · Page 7Linked to original sources

Differences in regional sweating responses during exercise between athletes trained on land and in water.

We investigated whether there are any differences in regional sweating responses during exercise between athletes trained on land and in water. We measured the local sweating rates on the left forearm (mswf) and the left scapula (msws), body temperatures (mean skin temperature, and rectal temperature Tre) in eight athletes trained on land (five soccer players, one distance runner and two baseball players, L group) and seven athletes trained in water (seven swimmers, W group) during cycle ergometer exercise at 50% maximal oxygen uptake for 40 min. The heart rate and oxygen uptake in the two groups during exercise showed nearly the same pattern of change. The Tre at the end of the exercise were 38.13 (SEM 0.19) degrees C in the L group and 38.26 (SEM 0.34) degrees C in the W group. Although the mswf in the two groups were similar, msws were significantly higher in L than in W at 30, 35 and 40 min of exercise. The msws at any given mean body temperature tended to be greater in L than in W. These results showed that a difference in regional sweating rate during exercise between the athletes trained on land and in water was present on the scapula.

Adult↗

Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain.

A possible pathogenic mutation in the beta 3-adrenergic-receptor gene (Trp64Arg) has been reported to be associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and clinical features of the insulin resistance syndrome in Pima Indian, Finnish and French subjects. Since marked heterogeneity has been reported in the association of mutations of candidate genes with NIDDM between Japanese and other ethnic groups, we investigated the association of Trp64Arg with NIDDM in Japanese subjects. The allele frequency of the mutation (Arg) was slightly, but not significantly, higher in NIDDM than in control subjects (70 out of 342 alleles [20.5%] vs 40 out of 248 [16.1%], respectively, p > 0.2). When our data were combined with those of Pima Indian and Finnish subjects, however, the Arg/Arg genotype was significantly associated with NIDDM as compared with the other two genotypes (p < 0.005, relative risk [RR] 2.13, 95% confidence interval [CI] 1.28-3.55). The Arg allele was also associated with NIDDM (p < 0.05, RR 1.27, 95% CI 1.06-1.52). Japanese subjects homozygous for the mutation had a significantly higher body mass index (mean +/- SD: 25.5 +/- 3.9 kg/m2) than heterozygotes (22.6 +/- 4.1, p < 0.05) and normal homozygotes (22.8 +/- 3.8, p < 0.05). NIDDM patients homozygous for the mutation tended to have an earlier age of onset of NIDDM than those with other genotypes. These data suggest that the Trp64Arg mutation not only contributes to weight gain and age-at-onset of NIDDM but is also associated with susceptibility to NIDDM.

Age of Onset↗

Intraventricular administration of estradiol modulates rat prolactin secretion and synthesis.

The effect of estradiol (E2) on rat tuberoinfundibular dopaminergic (TIDA) neurons was examined in vivo, employing chronic intraventricular (i.c.v.) infusion technique using an osmotic mini-pump. The activity of TIDA neurons was assessed by the release and synthesis of prolactin (PRL) in the rat pituitary gland and by the changes in the 3, 4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) levels and in the DOPAC/DA ratio in the rat hypothalamus. We also examined the [3H] E2 binding in the rat hypothalamus. Ovariectomized female Wistar rats with E2 replacement were treated with daily i.c.v. infusion of 1 microM of E2 or saline vehicle for 1, 3, and 7 days using the Alzet osmotic mini-pump and brain infusion kit. At 1 day of i.c.v. infusion of E2, the serum PRL level was significantly decreased compared with that in the vehicle group. Northern blot analysis of the total RNA isolated from the pituitary glands demonstrated a decrease in the PRL gene transcript level in the E2 group. At 3 days of E2 treatment, however, the serum PRL level was significantly increased compared with that of the vehicle-injected group and Northern blot analysis also demonstrated that the PRL gene transcript level was increased in the E2 group. At 7 days of E2 administration, there were no significant differences between the E2 and vehicle groups in either serum PRL or PRL gene transcript levels. There was a significant increase in the DOPAC/DA ratio after 1 day in the E2 group. However, no significant effects of E2 on this ratio were observed at 3 and 7 days of treatment. The DOPAC concentration in the E2 group was significantly increased at day 1 and significantly decreased at day 3, compared with that of the respective time in vehicle group. At day 7 there was no significant change in DOPAC concentration in either groups. The DA concentrations in the hypothalamus was not changed on any day in either group. Specific [3H] E2 binding was observed in the rat hypothalamus. These data suggest that E2 may have a biphasic effect on the accumulation of PRL gene transcripts and on the PRL secretion in the rat pituitary by first stimulating and then inhibiting the TIDA neuronal activity.

3,4-Dihydroxyphenylacetic Acid↗

Identification of genes regulated by glucose in a pancreatic beta-cell line by a new method for subtraction of mRNA.

Various genes are differentially expressed in cells during cell differentiation, development, aging, and in pathological conditions. To identify and isolate the genes that are specifically and differentially expressed in cells, we established a ligation-mediated polymerase chain reaction (PCR)-based method for cDNA subtraction. As this method is PCR-based, when target genes are expressed at high levels relative to the driver (a control pool for subtraction), even a small amount of target genes can be amplified. By this newly developed PCR-based subtraction method, a set of genes regulated by glucose were identified in a mouse insulinoma cell line. This PCR-based and non-radioactive subtraction method will be a powerful tool for identification of novel genes, specifically and differentially expressed in cells.

Animals↗

A novel microsatellite polymorphism in the human OB gene: a highly polymorphic marker for linkage analysis.

The mouse ob gene and its human homologue OB have recently been cloned. The mutations in the ob gene are known to be associated with extreme obesity. The relationship between the human OB gene and disease, however, is largely unknown due to the lack of suitable markers within or adjacent to the OB gene. To obtain informative markers, we searched for simple tandem repeat polymorphisms in the genomic sequence of the human OB gene and identified a novel tetranucleotide repeat in the 3' flanking region. Fifteen alleles were detected in this marker with a heterozygosity of 0.85 and polymorphism information content of 0.83, indicating a highly informative nature of this marker. Two-point linkage mapping in two Centre Etude Polymorphisme Humaine (CEPH) reference families suggested that this marker is located in the interval between D7S514 and D7S530, the same interval where the OB gene is located (recombination fractions with D7S514 and D7S530 were 0.026 and 0.034, respectively). Although allele frequency distributions of this marker did not differ between 84 control subjects and 69 NIDDM patients, there was a tendency to higher body weight in control subjects with class I/class I genotype than in those without this genotype (68.8 +/- 11.1 vs 60.8 +/- 10.3 kg, p = 0.05). The highly polymorphic nature of this marker and its location in the OB gene makes this marker useful for linkage studies of the OB gene with a number of phenotypes, such as obesity, non-insulin-dependent diabetes mellitus, hypertension and the insulin resistance syndrome.

Alleles↗

Role of HLA class II alleles in Korean patients with IDDM.

MHC associations with IDDM in the Korean population were studied to investigate genetic susceptibility to this disorder. The frequencies of HLA-DR3, -DR4 and -DR9 were significantly higher in diabetic patients. However, the frequency of DR2 was significantly decreased in diabetic patients. DQA1*0301 and DQA1*0501 were positively and DQA1*0102 and DQA1*0201 negatively associated with IDDM. DQB1*0301 and DQB1*0601 were negatively associated with IDDM. Heterodimers DQA1*0301-DQB1*0201, DQA1*0501-DQB1*0201 and DQA1*0501-DQB1*0302 were positively associated with DQA1*0102-DQB1*0601 negatively associated with IDDM. The frequencies of DR3-DQA1*0301-DQB1*0201 and -DQA1*0501-DQB1*0201 were significantly higher in diabetic patients. The frequencies of DR4-DQA1*0301-DQB1*0201 and DR9-DQA1*0301-DQB1*0303 were significantly higher in diabetic patients. The presence of non-aspartic acid at position 57 of the DQ beta-chain was not associated with susceptibility to IDDM. However, the frequency of Arg 52 homozygotes was significantly higher in diabetic patients. These results suggest a role of the MHC molecule and also suggest racial differences in susceptibility to IDDM even within the Asian populations.

Adult↗

A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer. Osaka Lung Cancer Chemotherapy Study Group.

Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m-2 i.v.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-1) starting on day 8. An overall response rate of 40.4% was observed in 47 evaluable patients, which included one complete response and 18 partial responses. Responses were achieved in 61.1% of stage 3 patients and 27.6% of stage 4 patients. The median progression-free interval was 19.3 weeks, and median survival time was 41.6 weeks (47.1 weeks for patients with stage 3 disease and 38.7 weeks for those with stage 4 disease). Toxicity was well tolerated. Gastrointestinal and renal toxicities did not exceed WHO grade 2. Grade 3 or 4 leucopenia and anaemia occurred in nine (19%) and four (9%) patients respectively, but only grade 2 thrombocytopenia was observed. Phlebitis at the infusion site was observed in 24 patients (53%). This treatment programme achieved a response rate similar to other active combination regimens for the treatment of advanced NSCLC, and was less toxic.

Adenocarcinoma↗

The influence of exercise intensity on sweating efficiency of the whole body in a mild thermal condition.

To investigate whether the exercise intensity affects sweating efficiency (eta sw) during exercise under mild environmental conditions, six healthy males, aged 22 +/- 2 years, performed three bicycle ergometer exercises at varying intensities (73W: Ex-1, 103W: Ex-2 and 133W: Ex-3) for 40 min under the conditions of 25 degrees C room temperature, 50% relative humidity and 0.3-0.4 m s-1 wind velocity. Heart rate, oxygen consumption, rectal temperature (Tre), mean skin temperature (Tsk; 4 skin sites) and total sweat rate were determined intermittently throughout the experiments. Moreover, heat loss by evaporation (E), radiation (R), convection (C) and eta sw were calculated using the heat balance equations. The findings concerning thermoregulatory parameters under the three experimental conditions were summarized as follows: (1) the higher the exercise intensity, the larger the values of Tre and Tsk at the end of exercise and E, R and C during exercise (2) the mean values +/- SE of eta sw were 55.4 +/- 5.1, 63.2 +/- 5.2 and 58.5 +/- 1.9% for Ex-1, Ex-2 and Ex-3, respectively. The results suggest that exercise intensity would have no effect on eta sw in this mild thermal environment.

Adult↗

Responses of sweating and body temperature to sinusoidal exercise in physically trained men.

The effect of physical training on the dynamic responses of sweating to transient exercise is still controversial. We determined the phase response and amplitude response (delta) of sweating rate and body temperature to sinusoidal exercise in physically trained and untrained subjects. Eight trained and seven untrained male subjects exercised on a cycle ergometer with a constant load for 30 min; for the next 28 min, they exercised with a sinusoidal load. The sinusoidal load variation ranged from approximately 10 to 60% of peak O2 uptake with a 4-min period. The ambient temperature and the relative humidity during exercise were 25 degrees C and 35%, respectively. There was no difference between the groups in the phase lags of esophageal temperature (Tes) and mean skin temperature (Tsk), whereas the phase lags of sweating rates for the chest and forearm were significantly shorter in the trained group (P < 0.05). The delta of Tes and Tsk per 1 W of exercise load in the trained group was significantly smaller than that in the untrained group (both, P < 0.05), whereas there was no difference between the groups in the delta of sweating rate for the chest and forearm. We conclude that subjects who have undergone long-term physical training show prompter dynamic characteristics of sweating response compared with untrained subjects and have a higher capacity to maintain constant body temperature during exercise at transient load.

Adult↗

Tilt responses of neurons in the caudal descending nucleus of the decerebrate cat: influence of the caudal cerebellar vermis and of neck receptors.

1. In decerebrate cats with intact cerebellums, we studied the responses of neurons in the caudal areas of the vestibular nuclei to natural vestibular stimulation in vertical planes and to neck rotation. The activity of most neurons was recorded in the caudal half of the descending nucleus. 2. One goal of our experiments was to compare the dynamic and spatial properties of responses to sinusoidal vestibular stimulation with those seen in previous experiments in which the caudal cerebellar vermis, including the nodulus and uvula, was removed. This part of the cerebellum receives vestibular input and projects to the caudal areas of the vestibular nuclei, suggesting that it could influence responses to stimulation of the labyrinth. 3. As in our previous experiments, most neurons could be classified as receiving predominant input either from the otoliths or from one vertical semicircular canal. When mean gain and phase and response vector orientations were compared, there were no obvious differences between the behavior of neurons in the partially decerebellate preparation and the one with the cerebellum intact, demonstrating that in the decerebrate cat the nodulus and uvula have little or no influence on the processing of vertical vestibular input in this region of the vestibular nuclei. 4. Only 23 of 74 (31%) of neurons tested responded to neck rotation. This contrasts with the much larger fractions that respond to this stimulus in Deiters' nucleus and in the rostral descending nucleus. We also recorded from neurons near the vestibular nuclei, mainly in the external cuneate nucleus. All of them (9 of 9) responded to neck rotation. 5. Responses to neck rotation also differed in their dynamics from those found more rostrally in the vestibular nuclei. Dynamics of more rostral neurons resemble those of neck muscle spindles, as do those of external cuneate neurons. The dynamics of caudal vestibular neurons, on the other hand, have a steeper gain slope and more advanced phases than do those of neurons in the more rostral vestibular nuclei. This suggests the possibility of involvement of additional receptors in the production of these responses. 6. In the more rostral vestibular nuclei, responses to vestibular and neck rotation are most often antagonistic, so that head rotation results in little or no response. This is not the case in the caudal areas of the vestibular nuclei, where less than half the neurons tested displayed antagonistic behavior. Further experiments are required to put the neck projection to the caudal vestibular nuclei in a functional context.

Animals↗

Analysis of candidate genes for insulin resistance in essential hypertension.

To clarify the genetic basis of insulin resistance in hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Since the main site of insulin resistance in hypertension is glycogen synthesis in skeletal muscle, genes that encode molecules involved in this pathway, i.e. insulin receptor (INSR), insulin-responsive glucose transporter (GLUT4) and glycogen synthase (GSY), were studied. In addition, since recent studies suggest the contribution of beta3 adrenergic receptor to the insulin resistance syndrome, the gene encoding beta3 adrenergic receptor (ADRB3) was also studied. Frequency of homozygotes for common C allele of a microsatellite polymorphism in the INSR gene was higher in the hyperinsulinemia group, but not in the normoinsulinemia group of hypertensive patients than in normotensive control subjects. Insulin sensitivity, however, was not significantly different between hypertensive patients with C/C genotype and those without this genotype. No significant differences were observed in the distribution of alleles or genotypes of the GLUT4, GSY and ADRB3 genes between hyperinsulinemia and normoinsulinemia groups of hypertensive patients or between these groups and the control group. These data suggest that the INSR polymorphism is associated with hyperinsulinemia, but not with insulin resistance, in hypertension.

Case-Control Studies↗

Genetics of insulin-dependent diabetes mellitus.

IDDM is caused by autoimmune destruction of insulin-producing beta cells of the pancreas in genetically susceptible individuals. Although the incidence and prevalence if IDDM in Japan are much lower than those in Caucasian countries, the recurrence risk in siblings of IDDM probands is much higher than the population prevalence, indicating that IDDM is clustered in families even in Japan, where the incidence of the disease is the lowest in the world. The higher concordance rate in monozygotic twins than in dizygotic twins indicates that genetic factors contribute to the familial clustering of IDDM in Japan. Analysis of the HLA region revealed that susceptibility genes (IDDM1) consist of multiple components, those in class II DR and DQ regions and another in the class I region. Analysis in NOD mice, an animal model of IDDM, supports this observation: susceptibility genes (Idd1) are mapped to class II A and E regions, but the incidence of the disease is strongly affected by a gene or genes outside of this segment (Idd16). Studies in both humans and an animal model will clarify the genetic components of IDDM, facilitating prediction of the disease and the development of effective strategies for its prevention.

Animals↗

Exercise-induced change in beta-adrenergic receptor number in lymphocytes from trained and untrained men.

This study was undertaken to clarify whether beta-adrenergic receptor (beta-AR) translocation from intracellular sites to the cell surface contributes to an increase in the number of beta-AR in lymphocytes from trained and untrained men after exercise. Nine trained and 9 untrained subjects performed exercise on a bicycle ergometer until exhaustion. The number of beta-AR in the cell surface (beta-AR(surface)) and intracellular sites (beta-AR(intra)) was determined at rest and after maximal exercise by measuring the binding of the radioligand 125I-iodocyanopindolol in the presence or absence of hydrophilic (CGP-12177A) or lipophilic (propranolol) unlabeled ligands. The number of beta-AR(surface) increased after exercise from 1,524.4 +/- 321.4 to 3,432.6 +/- 503.3 sites/cell (p < 0.01), whereas that of beta-AR(intra) decreased from 356.2 +/- 85.7 to 190.3 +/- 60.2 sites/cell (p < 0.05). The isoproterenol-stimulated cAMP production per 1 x 10(6) lymphocytes after exercise was significantly higher than that at rest. However, the cAMP production per single beta-AR(surface) tended to be lower after exercise. No differences between the trained and untrained subjects were found in beta-AR numbers or intracellular cAMP levels. These findings demonstrate that maximal exercise induces the translocation of beta-AR from intracellular sites to the cell surface in human lymphocytes. However, this translocation accounts for only 10% of the increase in total cellular beta-AR, suggesting that other mechanisms are predominant and contribute substantially to the increase in beta-AR(surface).

Adult↗

[Effect of estriol and bone mineral density of lumbar vertebrae in elderly and postmenopausal women].

To compare the efficacy of estriol (E3) in postmenopausal and senile osteoporosis, we administered orally 1 g/day calcium lactate either alone (control groups) or with 2 mg/day estriol (estrogen groups) for 10 months to 20 postmenopausal women aged 50-65 years and to 29 elderly women aged 70-84 years, and measured their bone mineral density of the lumbar vertebrae by dual energy X-ray absorptiometry. Out of 41 subjects who completed 10 months of treatment, 8 postmenopausal women and 12 elderly women in the estrogen groups had significant (p < 0.05) increases in bone mineral density (5.59 +/- 4.79% of the respective basal values). Ten postmenopausal women and 11 elderly women in the control groups had decreases bone mineral density (-4.02 +/- 7.00% and -3.26 +/- 4.60% of the respective basal values) at the 10th month. Genital bleeding as a side effect of estriol was seen in 6 out 29 elderly subjects at this dose. Moreover, decreases in the levels of calcium, total cholesterol, and triglycerides in serum, and an increase in the level of high-density lipoprotein-cholesterol were seen only in the elderly women receiving estriol. Although a lower dosage of estriol may be recommended for elderly subjects, these observations suggest that hormone replacement therapy with estriol is effective against degenerative osteoporosis, and that low-turnover bones in elderly women are also responsive to estriol.

Aged↗