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Biomedical subjects

Kazuo Inoue

Publications and source records attributed to Kazuo Inoue.

At least 19 recordsLinked to original sources

Effects of CH-19 sweet, a non-pungent cultivar of red pepper, in decreasing the body weight and suppressing body fat accumulation by sympathetic nerve activation in humans.

'CH-19 Sweet' is a non-pungent red pepper and enhances the energy expenditure in humans in like manner to the pungent red pepper. We investigated in this study the effects of a repeated intake of CH-19 Sweet for two weeks on the body weight and body fat in humans. Changes in the autonomic nervous activity after ingesting CH-19 Sweet were also measured by a power spectral analysis. We established a new protocol which allows the precise detection of weight change in humans by using fewer subjects. These methods were used to show that the repeated intake of CH-19 Sweet reduced the body weight and suppressed body fat accumulation. Furthermore, the body weight loss due to the repeated intake of CH-19 Sweet was significantly correlated with the sympathetic nervous response after its ingestion. We propose that the repeated intake of CH-19 Sweet reduced the body weight and suppressed body fat accumulation by sympathetic nervous activation in humans.

Adipose Tissue↗

Transforming growth factor-beta in the brain regulates fat metabolism during endurance exercise.

We have previously reported that the concentration of transforming growth factor-beta (TGF-beta) increases in the cerebrospinal fluid of rats during exercise and that there is an increase in whole body fat oxidation following the intracisternal administration of TGF-beta. These results led us to postulate that TGF-beta in the brain regulates the enhancement of fatty acid oxidation during exercise. To test this hypothesis, we carried out respiratory gas analysis during treadmill running following the inhibition of TGF-beta activity in rat brain by intracisternal administration of anti-TGF-beta antibody or SB-431542, an inhibitor of the type 1 TGF-beta receptor. We found that each reagent partially blocked the increase in the fatty acid oxidation. We also compared the plasma concentrations of energy substrates in the group administered anti-TGF-beta antibody and the control group during running. We found that the plasma concentrations of nonesterified fatty acids and ketone bodies in the group administered anti-TGF-beta antibody were lower than in the control group at the end of running. In the same way, we carried out respiratory gas analysis during treadmill running after depressing corticotropin-releasing factor activity in the brain using intracisternal administration of astressin, an inhibitor of the corticotropin-releasing factor receptor. However, there were no significant differences in respiratory exchange ratio or oxygen consumption in moderate running (60% maximum oxygen consumption). These results suggest that brain TGF-beta has a role in enhancing fatty acid oxidation during endurance exercise and that this regulation is executed at least partly via the type 1 TGF-beta receptor signal transduction system.

Animals↗

Body mass index as a predictor of mortality in community-dwelling seniors.

BACKGROUND AND AIMS: The relationship between body mass index (BMI) and mortality remains inconclusive in seniors. This study aimed at assessing this relationship in a community-dwelling elderly population in Japan. METHODS: The subjects were 371 Japanese elders, 65 years old and older, who lived in a geographically well-defined rural community and had participated in a general health screening program in 1995. Both height and weight of subjects were measured directly by medical staff. Subjects were classified into three groups according to their BMI values: low, <18.5; normal, 18.5-25.0; and high, >25.0. Univariate analysis was applied to explore potential associations between mortality and possible confounders. Multivariate Cox proportional hazards models were used to analyze the association between mortality and BMI, after adjusting for other risk factors. RESULTS: At baseline, 54 subjects (14.6%) had BMI values in the low range, 280 (75.5%) in the normal range, and 37 (10.0%) in the high range. All 371 subjects were followed prospectively for mortality. Over the next five years, 37 subjects had died. In univariate analysis, male sex, age, BMI and serum creatinine were associated with mortality. The mortality rate in the low BMI group was about twice that in the normal BMI group. No deaths were observed in the higher BMI group. In multivariate analysis, age and low BMI were associated with mortality. CONCLUSIONS: BMI may be a useful predictor of mortality among seniors living in the general, non-institutionalized population.

Age Factors↗

POMC and orexin mRNA expressions induced by anticipation of a corn-oil emulsion feeding are maintained at the high levels until oil ingestion.

We investigated the gene expression dynamics of several hypothalamic neuropeptides associated with appetite regulation when rats are anticipating being fed a corn-oil emulsion. For 5 days at the same hour each day, rats were fed 5% corn oil emulsified with 0.3% xanthan gum or the vehicle for 20 min. On Day 6, the 5% corn oil emulsion or the vehicle (Vehicle) was presented to the rats, some of which (Oil-intake) were allowed to eat it and some of which (Oil-anticipation) were kept from eating it. Despite waiting a corn-oil, the mRNA levels of proopiomelanocortin (POMC), a beta-endorphin precursor, and orexin showed increases, and high levels of mRNAs of POMC and orexin were maintained for 30 min after the corn-oil was placed before the rats, and only gradually decreased through 150 min. However, the mRNA levels of POMC and orexin in the hypothalamus were decreased within 30 min after starting to ingest the corn-oil emulsion. These results suggest that POMC and orexin mRNA expression was induced by the anticipation in rats after learning the palatability of 5% corn oil emulsion, and the induced mRNA expression based on the anticipation was maintained for at least for 30 min as the rats eagerly waited for ingestion.

Animal Feed↗

Daily increase of fat ingestion mediated via mu-opioid receptor signaling pathway.

We investigated the involvement of opioid receptors such as the mu and delta receptors in the predominant elevation of corn oil appetite just after 5-day repeated treatment of corn oil ingestion. Rats were given 5% corn oil emulsified with 0.3% xanthan gum for 20 min at the same hour for 5 consecutive days. A strong appetite for fat was formed after the 5 days presentation, and it was inhibited by naloxonazine, a selective antagonist of the mu-1 receptor, at doses of 3 mg/kg, but not by antagonists of the opioid delta receptor. In days 6, after the formation of a strong appetite for corn oil, an additional injection of naloxonazine suppressed fat intake 0-30, 30-60, 60-90 and 90-150 min after the presentation of the corn oil, but antagonists of the opioid delta receptor did not. These data suggested that the opioid mu receptor is involved in the sharp elevation of corn oil appetite during repeated presentation of corn oil to rats.

Animals↗

The physiological and behavioral effects of subchronic intracisternal administration of TGF-beta in rats: comparison with the effects of CRF.

We studied the physiological and behavioral effects of subchronic intracisternal administration of transforming growth factor-beta (TGF-beta) for 7 days. Subchronic intracisternal administration of TGF-beta significantly inhibited the increase in body weight of rats but did not affect food intake. In the measurement of locomotor activity after the final intracisternal administration on day 7, the total count for 1.5 h increased significantly in the TGF-beta group compared with the vehicle group. However, that for 10 h was not different between both groups. Furthermore, significant elevations in oxygen consumption were observed in the TGF-beta group during both light and dark phase. Subchronic TGF-beta treatment induced a significant decrease in the number of total leukocytes and lymphocytes and the relative weight of the thymus, and a significant increase in brown adipose tissue weight. Corticotropin-releasing factor (CRF) is the primary neuroendocrine factor released in response to stress. Subchronic treatment with CRF, as a positive control, significantly affected body weight, food intake, oxygen consumption, total leukocyte and lymphocyte counts, and thymus and adrenal weight. Subchronic TGF-beta administration partially mimicked the stress responses, implicating a role for TGF-beta in the brain in stress.

Adaptation, Ocular↗

Face-selective and auditory neurons in the primate orbitofrontal cortex.

Neurons with responses selective for faces are described in the macaque orbitofrontal cortex. The neurons typically respond 2-13 times more to the best face than to the best non-face stimulus, and have response latencies which are typically in the range of 130-220 ms. Some of these face-selective neurons respond to identity, and others to facial expression. Some of the neurons do not have different responses to different views of a face, which is a useful property of neurons responding to face identity. Other neurons have view-dependent responses, and some respond to moving but not still heads. The neurons with face expression, face movement, or face view-dependent responses would all be useful as part of a system decoding and representing signals important in social interactions. The representation of face identity is also important in social interactions, for it provides some of the information needed in order to make different responses to different individuals. In addition, some orbitofrontal cortex neurons were shown to be tuned to auditory stimuli, including for some neurons, the sound of vocalizations. The findings are relevant to understanding the functions of the primate including human orbitofrontal cortex in normal behaviour, and to understanding the effects of damage to this region in humans.

Acoustic Stimulation↗

Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase.

In adipocytes, hydrolysis of triglycerides results in the release of free fatty acids and glycerol. Aquaporin 7 (AQP7), a member of aquaglyceroporins, is known to permeabilize glycerol and water. We recently generated Aqp7-knockout (KO) mice and demonstrated that such mice have low plasma glycerol levels and impaired glycerol release in response to beta3-adrenergic agonist, suggesting that AQP7 acts as a glycerol gateway molecule in adipocytes for the efficient release of glycerol in vivo. Although there was no difference in body weight between WT and KO mice until 10 weeks of age, here we found that KO mice developed adult-onset obesity. The body weight and fat mass increased significantly in KO mice compared with WT mice after 12 weeks of age. Adipocytes of KO mice were large and exhibited accumulation of triglycerides compared with WT mice. The KO mice developed obesity and insulin resistance even at a young age after consumption of high-fat/high-sucrose diet. We demonstrated the enhanced glycerol kinase enzymatic activity in Aqp7-KO and -knockdown adipocytes. A series of our results indicate that AQP7 disruption elevates adipose glycerol kinase activity, accelerates triglycerides synthesis in adipocytes, and, finally, develops obesity.

3T3-L1 Cells↗

Novel visual stimuli activate a population of neurons in the primate orbitofrontal cortex.

Neurons were found in the rhesus macaque anterior orbitofrontal cortex that respond to novel but not to familiar visual stimuli. Some of these neurons responded to all novel stimuli, and others to only a subset (e.g., to novel faces). The neurons have no responses to familiar reward- or punishment-associated visual stimuli, nor to taste, olfactory or somatosensory inputs. The responses of the neurons typically habituated with repeated presentations of a novel stimulus, and five presentations each 1s was the median number for the response to reach half-maximal. The neurons did not respond to stimuli which had been novel and shown a few times on the previous day, indicating that the neurons were involved in long-term memory. The median latency of the neuronal responses was 120 ms. The median spontaneous firing rate was 1.3 spikes/s, and the median response to novel visual stimuli was 6.0 spikes/s. These findings indicate that the long-term memory for visual stimuli is information that is represented in a region of the primate anterior orbitofrontal cortex.

Analysis of Variance↗

Association of periodontitis with increased white blood cell count and blood pressure.

This study was aimed to examine the association of periodontitis with white blood cell (WBC) count and blood pressure (BP). In 2002, 424 subjects (manufacturing workers) were investigated for periodontitis by a general dentist. All were Japanese. Among them, 364 subjects (269 men and 95 women) who also attended the next year's (2003) screening were enrolled for this study. Of the 364 subjects, 55 (15.1%) had periodontitis. We also measured the BP and WBC count in periodontitis and non-periodontitis subjects at baseline and 1-year later follow-up. The WBC count higher in subjects with periodontitis than in subjects without periodontitis, both at baseline [mean +/- standard error (SE) 6.6 x 10(3) +/- 0.2 x 10(3)/ml vs 5.8 +/- 0.3 x 10(3)/ml; p < 0.001] and follow-up (7.0 +/- 0.3(3)/ml vs 6.5 +/- 0.1(3)/ml; p = 0.003). The systolic BP was higher in subjects with periodontitis than in subjects without periodontitis, both at the baseline (128 +/- 2.1 mmHg vs 120.8 +/- 0.8 mmHg; p < 0.001) and follow-up (129.2 +/- 2.3 mmHg vs 123.0 +/- 0.8 mmHg; p = 0.011), and so was the diastolic BP both at baseline (76 +/- 1.5 mmHg vs 71.2 +/- 0.6 mmHg; p = 0.003) and follow-up (80.5 +/- 1.7 mmHg vs 75.4 +/- 0.7 mmHg; p = 0.004). Periodontitis is associated with increased BP and WBC count. This finding may provide one underlying pathway linking periodontitis and cardiovascular disease.

Adult↗

Factors associated with rural doctors' intention to continue a rural career: a survey of 3072 doctors in Japan.

OBJECTIVE: To show the relationship between the personal and educational backgrounds of rural doctors and their intention to continue a rural career. DESIGN: Nationwide postal survey. SETTING: Public clinics or hospitals in municipalities that are classified as 'rural' by the national government. SUBJECTS: A total of 4896 doctors working for 828 public clinics and hospitals. MEASUREMENTS: A questionnaire was mailed. The questionnaire inquired about the subject's age, sex, hometown, exposure to rural practice in undergraduate education, postgraduate training, continuing medical education, current position and affiliation status with a medical school, as well as his or her intention to continue a rural career. RESULTS: Response rate was 64%; 26% answered that they intended to continue a rural career. Postgraduate training in general internal medicine, general surgery, anaesthesiology, paediatrics and gastroenterology were positively related with the intention to continue a rural career (odds ratio = 2.045, 1.59, 1.30, 1.48, 1.38). Rural background, undergraduate exposure to rural practice, multispecialty-rotation in postgraduate training and current administrative position had positive correlations with the intention to continue in logistic regression analysis (odds ratio = 1.80, 2.47, 1.54, 2.17). Affiliation with a medical school department was negatively related with the intention to continue (odds ratio = 0.45). CONCLUSION: In addition to the rural background of physicians, some undergraduate and postgraduate factors were independently associated with the intention to continue a rural career.

Adult↗

Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice.

Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enhanced insulin sensitivity with induced phosphorylation of Akt in adipose tissue. AdipoPten-KO mice also showed marked hyperthermia and increased energy expenditure with induced mitochondriagenesis in adipose tissue, associated with marked reduction of p53, inactivation of Rb, phosphorylation of cyclic AMP response element binding protein (CREB) and increased expression of Ppargc1a, the gene that encodes peroxisome proliferative activated receptor gamma coactivator 1 alpha. Physiologically, adipose Pten mRNA decreased with exposure to cold and increased with obesity, which were linked to the mRNA alterations of mitochondriagenesis. Our results suggest that altered expression of adipose Pten could regulate insulin sensitivity and energy expenditure. Suppression of adipose Pten may become a beneficial strategy to treat type 2 diabetes and obesity.

Adiponectin↗

High-tech rural clinics and hospitals in Japan: a comparison to the Japanese average.

CONTEXT: Japanese medical facilities are noted for being heavily equipped with high-tech equipment compared to other industrialised countries. Rural facilities are anecdotally said to be better equipped than facilities in other areas due to egalitarian health resource diffusion policies by public sectors whose goal is to secure fair access to modern medical technologies among the entire population. OBJECTIVES: To show the technology status of rural practice and compare it to the national level. DESIGN: Nationwide postal survey. SETTING, SUBJECTS & INTERVENTIONS: Questionnaires were sent to the directors of 1362 public hospitals and clinics (of the 1723 municipalities defined as 'rural' by four national laws). Information was collected about the technologies they possessed. The data were compared with figures from a national census of all hospitals and clinics. RESULTS: A total of 766 facilities responded (an effective response rate of 56%). Rural facilities showed higher possession rates in most comparable technologies than the national level. It is noted that almost all rural hospitals had gastroscopes and colonoscopes and their possession rates of bronchoscopes and dialysis equipment were twice as high as the national level. The discrepancy in possession rates between rural and national was even more remarkable in clinics than in hospitals. Rural clinics owned twice as many abdominal ultrasonographs, and three times as many gastroscopes, colonoscopes, defibrillators and computed tomography scanners as the national level. CONCLUSIONS: Rural facilities are equipped with more technology than urban ones. Government-led, tax based, technology diffusion in the entire country seems to have attained its goal. What is already known on this subject: As a general tendency in both developing and developed countries, rural medical facilities are technologically less equipped than their urban counterparts. What does this paper add?: In Japan, rural medical facilities are technologically better equipped than urban facilities.

Ambulatory Care Facilities↗

Neoadjuvant chemotherapy with S-1 for scirrhous gastric cancer: a pilot study.

We conducted a pilot study using S-1 (TS-1), a novel oral derivative of 5-fluorouracil, as neoadjuvant chemotherapy for potentially resectable scirrhous gastric cancer. The neoadjuvant chemotherapy consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 at 100-120 mg/body per day. Five patients were enrolled in this pilot study and underwent resection. The response rate for the neoadjuvant chemotherapy was 60% (three partial response [PR]; two stable disease [SD]). Three of the five patients received curative resection; the other two patients received noncurative resection because of localized peritoneal dissemination and positive results on cytological examination of the abdominal washing. No toxicity of grade 3 or more was exhibited during the two courses of chemotherapy. Pathological examination of the resected specimens revealed a marked reduction in the distribution of viable cancer cells in the stomach in the three patients with PR. In one of these patients, pathological findings suggestive of the possibility of disappearance of the cancer cells in the perigastric and paraaortic lymph nodes were noted. Because of the unexpectedly high response to S-1, we consider that the efficacy of S-1 as neoadjuvant chemotherapy for scirrhous gastric cancer should be verified by phase II and III trials.

Adenocarcinoma, Scirrhous↗

Activity of primate subgenual cingulate cortex neurons is related to sleep.

The most frequent type of neuronal response found in the subgenual cingulate cortex (area 25) of the rhesus macaque was a highly significant increase of firing rate when the monkey fell asleep (median rate = 1.6 spikes/s) compared with the awake state (median rate = 0.1 spikes/s). On average, the firing rate of the neurons when awake was 23% of that when the monkeys were asleep. Neurons were not found in this region with responses related to taste, olfactory, and visual stimuli including faces or related to movement. These results are relevant to understanding the function of this region in humans, in which it has been suggested that activation may be related to disengagement from tasks and to induced sadness, both of which we note lead to a more passive or resting behavior. A decrease in the activation of this area in humans has been observed during the recovery from depression, which we note leads to a more active state of behavior.

Action Potentials↗

Effects of intracranial injection of transforming growth factor-beta relevant to central fatigue on the waking electroencephalogram of rats: comparison with effects of exercise.

To investigate the detailed actions of transforming growth factor-beta (TGF-beta) in the brain, which increase accompanied with continuity of exercise, the authors performed electroencephalogram (EEG) spectral analysis for 2 h after intracranial injection of TGF-beta in rats and compared with the effects of swimming exercise. Relative power values (power percent) of the theta frequency band (4-7 Hz) increased and power percent of the alpha frequency band (7-13 Hz) decreased after intracranial injection of TGF-beta. The directions of these changes of EEG after intracranial injection of TGF-beta were consistent with those after exercise. The EEG pattern produced by leucine-enkephalin (Leu-enk), a typical brain peptide related to exercise, was completely different from that after exercise. The results suggested that the increase in TGF-beta concentration in the brain is, at least partly, relevant to the change of neuronal activity after exercise.

Animals↗