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Biomedical subjects

I Kato

Publications and source records attributed to I Kato.

At least 19 recordsLinked to original sources

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗

Improved search for nu(mu) --> nu(e) oscillation in a long-baseline accelerator experiment.

We performed an improved search for nu(mu) --> nu(e) oscillation with the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment, using the full data sample of 9.2 x 10(19) protons on target. No evidence for a nu(e) appearance signal was found, and we set bounds on the nu(mu) --> nu(e) oscillation parameters. At Deltam(2)=2.8 x 10(-3) eV(2), the best-fit value of the K2Knu(mu) disappearance analysis, we set an upper limit of sin(2)2theta(mue) < 0.13 at a 90% confidence level.

Journal Article↗

Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice.

Galectin-3, a beta-galactoside-binding animal lectin, is a multifunctional protein. Previous studies have suggested that galectin-3 may play an important role in inflammatory responses. Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a liver condition that may progress to end-stage liver disease and based on the known functions of galectin-3, it was hypothesized that galectin-3 might play a role in the development of NAFLD. Thus, this study investigated the role of galectin-3 in NAFLD by comparing galectin-3 knockout (gal3(-/-)) mice and wild-type (gal3(+/+)) mice. The livers of gal3(-/-) male mice at 6 months of age histologically displayed mild to severe fatty change. The liver weight per body weight ratio, serum alanine aminotransferase levels, liver triglyceride levels, and liver lipid peroxide in gal3(-/-) mice were significantly increased compared with those in gal3(+/+) mice. Furthermore, the hepatic protein levels of advanced glycation end-products (AGE), receptor for AGE (RAGE), and peroxisome proliferator-activated receptor gamma (PPARgamma) were increased in gal3(-/-) mice relative to gal3(+/+) mice. In conclusion, this study suggests that the absence of gal3 can cause clinico-pathological features in male mice similar to those of NAFLD.

Alanine Transaminase↗

Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats.

UNLABELLED: Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R), stimulates a release of growth hormone, prolactin and adrenocorticotropic hormone. Also, ghrelin increases food intake in adult rats and humans and exhibits gastroprotective effect against experimental ulcers induced by ethanol or stress. The aim of present study was to examine the influence of ghrelin administration on gastric and duodenal growth and expression of pepsin and enterokinase in young mature rats with intact or removed pituitary. METHODS: Two week after sham operation or hypophysectomy, eight week old Wistar male rats were treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a day for 4 days. Expression of pepsin in the stomach and enterokinase in the duodenum was evaluated by real-time PCR. RESULTS: In animals with intact pituitary, treatment with ghrelin increased food intake, body weight gain and serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These effects were accompanied with stimulation of gastric and duodenal growth. It was recognized as the significant increase in gastric and duodenal weight and mucosal DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg caused maximal growth-promoting effect. In contrast to these growth-promoting effects, administration of ghrelin reduced expression of mRNA for pepsin in the stomach and was without effect on expression of mRNA for enterokinase in the duodenum. Hypophysectomy alone lowered serum concentration of growth hormone under the detection limit and reduced serum level of IGF-1 by 90%. These effects were associated with reduction in daily food intake, body weight gain and gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was without significant effect on food intake, body weight gain or growth of gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was not affected by ghrelin administration in rats with removed pituitary. CONCLUSION: Administration of ghrelin stimulates gastric and duodenal growth in young mature rats with intact pituitary, but inhibits expression of mRNA for pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an essential role in growth-promoting effects of ghrelin in the stomach and duodenum.

Analysis of Variance↗

Central and local (enteric) action of orexins.

Orexin-A (OXA, hypocretin-1) and orexin-B (OXB, hypocretin-2) are peptides derived from the same 130 amino acid long precursor (prepro-orexin) that bind and activate two closely related orphan G protein-coupled receptors. Orexins and their receptors were first discovered in the rat brain, and soon after that in peripheral neural structures, including the vagal nerve and enteric nervous system, and in other structures involving the gastrointestinal tract diffuse neuroendocrine system, pancreas tissue, stomach and intestinal mucosa. Orexins and their receptors were also demonstrated in the testes, adrenals, kidneys, and placenta. This review is focused on central and enteric actions. Originally, orexins were considered to be neurotransmitters that centrally stimulate food intake in animals and humans, but it soon became evident that their action is broader due to activation of a large number of neuronal pathways involved in energy homeostasis, sleep-awake behavior, nociception reward seeking, food and drug addiction, as well as reproduction, cardiovascular and adrenal function. In the gastrointestinal tract, orexins have been found so far to affect gastrointestinal motility and gastric, intestinal and pancreatic secretions. The effects were observed following central (intraventricular) or local (intraluminal, intraarterial), but not peripheral (intravenous), administrations of orexins. Since the expression of orexins in the gastrointestinal tract is enhanced during fasting, and fasting reveals many of the orexin gastrointestinal effects, it seems probable that on the local level, orexins keep the gastrointestinal tract functions ready during fasting and play role in brain-gut axis control.

Amino Acid Sequence↗

The effect of orexins on intestinal motility in vitro in fed and fasted rats.

Orexin-A and -B (OXA, OXB) are peptides involved in many gastrointestinal (GI) functions, including motility. Orexins, their precursors and receptors are present in the GI tract. The expression of orexins increases in the hypothalamus and gastrointestinal tract in response to fasting. We have examined the effect of OXA and OXB on GI motility in vitro in fed and fasted rats. The intestinal segments were mounted in chambers filled with Krebs solution. Isotonic contractions were measured in response to acetylcholine (10(-5) M), electric field stimulation (EFS), and orexins (10(-9)-10(-7) M) alone or in the presence of orexin-1 type receptor antagonist, SB- 334867 (10(-5) M), tetrodotoxin (TTX) 10(-6) M, or atropine (10(-5) M). Orexins caused a dose-dependent increase of intestinal segment contractions with a more pronounced effect of OXB over OXA. Fasting did not influence orexin-induced responses. Incubation with SB-334867 led to a marked decrease in orexin-induced contractions in OXA-treated segments, while those of OXB were not affected. Atropine diminished contractions only in fasted animals, while TTX led to a decreased response to orexins in both groups. The results show that OXB is predominant in inducing gut motility response, that the effect of orexins is not fully dependent on cholinergic and Na(+) transmissions, and that involvement of other transmitters is possible.

Animals↗

Search for coherent charged pion production in neutrino-carbon interactions.

We report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed, and an upper limit of is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.

Journal Article↗

Apnea, glial apoptosis and neuronal plasticity in the arousal pathway of victims of SIDS.

Of 27,000 infants whose sleep-wake characteristics were studied under the age of 6 months, 38 died unexpectedly 2-12 weeks after the sleep recording in a pediatric sleep laboratory. Of these infants, 26 died of sudden infant death syndrome (SIDS), and 12 of definitely identified causes. The frequency and duration of sleep apneas were analysed. Sleep recordings and brainstem histopathology were studied to elucidate the possible relationship between sleep apnea and neuropathological changes within the arousal system. Immunohistochemical analyses were conducted using tryptophan hydroxylase (TrypH), a serotonin synthesizing enzyme, and growth-associated phosphoprotein 43 (GAP43), a marker of synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis. The pathological and physiological data were correlated for each infant. In the SIDS victims, statistically significant positive correlations were seen between the number of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apneas (p = 0.03), between the number of TUNEL-positive glial cells in the pedunculopontine tegmental nucleus (PPTN) and the average number of spines in GAP43-positive neurons in the PPTN (p = 0.04). These findings in the dorsal raphe nucleus of the midbrain and PPTN, that play important roles in the arousal pathway suggest a possible link between changes in arousal and SIDS.

Apoptosis↗

Evidence for muon neutrino oscillation in an accelerator-based experiment.

We present results for nu(mu) oscillation in the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment. K2K uses an accelerator-produced nu(mu) beam with a mean energy of 1.3 GeV directed at the Super-Kamiokande detector. We observed the energy-dependent disappearance of nu(mu), which we presume have oscillated to nu(tau). The probability that we would observe these results if there is no neutrino oscillation is 0.0050% (4.0 sigma).

Journal Article↗

Distribution of urocortin 2 in various tissues of the rat.

Urocortin (Ucn) 2 is a new member of the corticotrophin-releasing hormone (CRH) neuropeptide family that is expressed in the central nervous system and peripheral tissues. However, the expression levels of Ucn 2 in various tissues of the rat remains unclear. Thus, the aim of the present study was to characterise the expression of Ucn 2 in the various tissues of the rat. Reverse transcriptase-polymerase chain reaction analysis demonstrated that Ucn 2 mRNA is expressed in the hypothalamus, pituitary, adrenal, stomach, skin, ovary, uterus and skeletal muscle. Histologically, Ucn 2 mRNA and Ucn 2-like immunoreactivity (LI) were demonstrated in both the anterior and intermediate lobes of the pituitary, but not detected in the posterior lobe. Furthermore, all Ucn 2-positive cells in the anterior and intermediate lobes were also positive for beta-endorphin. Ucn 2 mRNA was detected in the adrenal cortex and medulla although Ucn 2-LI was only found in the adrenal medulla. High-performance liquid chromatography analysis of hypothalamic, pituitary, and adrenal extracts showed that the main Ucn 2-LI peak occurred at the same molecular size as that of synthetic Ucn 2. These results suggest that Ucn 2 is synthesised in various tissues, including the anterior and intermediate lobes of the pituitary and the adrenal.

Adrenal Glands↗

Relationship between obesity, glucose tolerance, and periodontal disease in Japanese women: the Hisayama study.

BACKGROUND: Recent studies have reported a relationship between obesity and periodontal disease. Obesity is the strongest risk factor for type 2 diabetes, which is, in turn, a risk factor for periodontal disease. An oral glucose tolerance test is necessary to diagnose diabetes; however, no study has examined the relationship between obesity and periodontal disease by taking oral glucose tolerance test results into consideration. METHODS: In all, 584 Japanese women aged between 40 and 79 years old, with at least 10 teeth, underwent health examinations. Body mass index, waist-hip ratio, body fat, and oral glucose tolerance test results were used as independent variables with known risk factors for periodontal disease. Mean probing pocket depth and mean attachment loss were used as the dependent variables. RESULTS: In all of the analyses, body mass index, body fat, and waist--hip ratio were significantly associated with the highest quintile of mean probing pocket depth, even when adjusted for oral glucose tolerance test results. In the multivariate analysis, the subjects with the highest quartile of body mass index had a significantly higher odds ratio (OR) for the highest quintile of mean probing pocket depth [OR, 4.3; 95% confidence interval (CI), 2.1--8.9; p<0.001], whereas neither impaired glucose tolerance nor diabetes were significantly associated with deep pockets. The relationships between the obesity indexes and mean attachment loss did not reach statistical significance. CONCLUSION: Obesity was associated with deep pockets in Japanese women, even after adjusting for oral glucose tolerance test.

Adult↗

Ten year recurrence after first ever stroke in a Japanese community: the Hisayama study.

BACKGROUND: Very few population based cohort studies have focused on the long term recurrence of stroke. OBJECTIVE: To examine 10 year cumulative recurrence rates for stroke in a Japanese cohort according to pathological type and clinical subtype of brain infarction. METHODS: During a 32 year follow up of 1621 subjects >/=40 years of age, 410 developed first ever stroke. These were followed up prospectively for 10 years after stroke onset. RESULTS: During follow up, 108 (26%) experienced recurrent stroke. The cumulative recurrence rates were 35.3% at five years and 51.3% at 10 years. The 10 year recurrence rates of subarachnoid haemorrhage (SAH), brain haemorrhage, and brain infarction were 70.0%, 55.6%, and 49.7%, respectively; the difference between SAH and brain infarction was significant (p = 0.004). Most recurrent episodes after SAH or brain haemorrhage happened within a year after the index stroke, whereas recurrence of brain infarction increased consistently throughout the observation period. Cardioembolic stroke had a higher recurrence rate (75.2%) than lacunar infarction (46.8%) (p = 0.049). The 10 year risk of stroke recurrence increased with age after lacunar or atherothrombotic brain infarction, but not after the other types or subtypes. After atherothrombotic brain infarction, cardioembolic stroke, or SAH, the type and subtype of most recurrent strokes were the same as for the index stroke, but recurrence after lacunar infarction or brain haemorrhage showed divergent patterns. CONCLUSIONS: Japanese people have higher recurrence rates of stroke than other populations. Recurrence rate after a first brain infarct increases consistently through the next 10 years.

Adult↗

Variable effect of ghrelin administration on pancreatic development in young rats. Role of insulin-like growth factor-1.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been primarily isolated from the human and rat stomach. Ghrelin has been shown to stimulate appetite and fat deposition in adult rats and humans. The aim of this study was to investigate the effect of ghrelin administration on pancreatic growth in suckling, weaned and peripubertal seven week old rats. Rats were treated with saline or ghrelin (4, 8 or 16 nmol/kg/dose) intraperitoneally twice a day: suckling rats were treated for 7 or 14 days starting from the first postnatal day, three week old weaned rats and seven weeks old rats were treated for 5 days. Treatment with ghrelin did not affect animal weight in suckling or weaned rats, whereas in young seven week old rats, ghrelin caused a significant increase in body weight. Ghrelin decreased food intake in weaned rats; whereas in seven week old rats, food intake was enhanced. In suckling rats, ghrelin decreased the pancreatic weight, pancreatic amylase content, DNA synthesis and DNA content. In contrast, ghrelin increased pancreatic weight, DNA synthesis, DNA content and amylase content in weaned or young seven week old rats. Pancreatic blood flow was not affected by ghrelin in any group of rats tested. Ghrelin increased serum level of growth hormone in all rats. This effect was weak in suckling rats, higher in weaned and the highest in seven week old animals. Ghrelin did not affect serum level of insulin-like growth factor-1 (IGF-1) in suckling rats. In weaned and in seven week old rats, treatment with ghrelin caused increase in serum level of IGF-1. We conclude that ghrelin reduces pancreatic growth in suckling rats; whereas in weaned and young seven week old animals, treatment with ghrelin increases pancreatic growth. This biphasic effect of ghrelin in young animals on pancreatic growth seems to be related to age-dependent changes of the release of anabolic IGF-1.

Amylases↗

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗

Search for electron neutrino appearance in a 250 km long-baseline experiment.

We present a search for electron neutrino appearance from accelerator-produced muon neutrinos in the K2K long-baseline neutrino experiment. One candidate event is found in the data corresponding to an exposure of 4.8 x 10(19) protons on target. The expected background in the absence of neutrino oscillations is estimated to be 2.4+/-0.6 events and is dominated by misidentification of events from neutral current pi(0) production. We exclude the nu(micro) to nu(e) oscillations at 90% C.L. for the effective mixing angle in the 2-flavor approximation of sin((2)2theta(microe)( approximately 1/2sin((2)2theta(13))>0.15 at Deltam(2)(microe)=2.8 x 10(-3) eV(2), the best-fit value of the nu(micro) disappearance analysis in K2K. The most stringent limit of sin((2)2theta(microe)<0.09 is obtained at Deltam(2)(microe)=6 x 10(-3) eV(2).

Journal Article↗

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.

Journal Article↗

Circulating enterolactone and risk of breast cancer: a prospective study in New York.

It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.

4-Butyrolactone↗

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study.

We assessed the association of sex hormone levels with breast cancer risk in a case-control study nested within the cohort of 7054 New York University (NYU) Women's Health Study participants who were postmenopausal at entry. The study includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and 563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for breast cancer for the highest quintile of each hormone and sex-hormone binding globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47-4.21), P(trend)=0.003 for oestradiol; 3.24 (1.87-5.58), P(trend)<0.001 for oestrone; 2.37 (1.39-4.04), P(trend)=0.002 for testosterone; 2.07 (1.28-3.33), P(trend)<0.001 for androstenedione; 1.74 (1.05-2.89), P(trend)<0.001 for dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31-0.82), P(trend)<0.001 for SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years prior to diagnosis showed results in the same direction as overall analyses, although the tests for trend did not reach statistical significance for DHEAS and SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95 cases and their matched controls who had given a second blood donation within 5 years of diagnosis, were of small magnitude and overall not different in cases and controls. The association of androgens with risk did not persist after adjustment for oestrone (1.08, 95% CI=0.92-1.26 for testosterone; 1.15, 95% CI=0.95-1.39 for androstenedione and 1.06, 95% CI=0.90-1.26 for DHEAS), the oestrogen most strongly associated with risk in our study. Our results support the hypothesis that the associations of circulating oestrogens with breast cancer risk are more likely due to an effect of circulating hormones on the development of cancer than to elevations induced by the tumour. They also suggest that the contribution of androgens to risk is largely through their role as substrates for oestrogen production.

Aged↗