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1.
Kouroku Y Fujita E Jimbo A Kikuchi T Yamagata T Momoi MY Kominami E Kuida K Sakamaki K Yonehara S Momoi T 《Human molecular genetics》2002,11(13):1505-1515
Accumulation of unfolded and malfolded proteins causes endoplasmic reticulum (ER) stress, stimulating unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) activation and activating caspase-12 located on the ER. Little is known about the relationship between the ER stress and polyglutamine [poly(Q)] aggregates. Poly(Q)72 repeats [poly(Q)(72)] induced the stimulation of ER stress signals such as JNK activation, upregulation of Grp78/Bip and caspase-12 activation in C2C5 cells. We prepared antiserum against the cleavage site of mouse caspase-12 at D(318) (anti-m12D318), and showed that poly(Q)(72) with perinuclear aggregates, cytoplasmic inclusions and nuclear inclusions stimulated JNK activation and anti-m12D318 immunoreactivity, but poly(Q)(72) with dispersed aggregates and small nuclear aggregates showed a significantly less effect. Poly(Q)(72) and poly(Q)(11) dispersed in cytoplasm did not. Anti-m12D318-positive cells showed apoptotic features. Unlike anti-m8D387 immunoreactivity, the anti-m12D318 immunoreactivity was not coaggregated with poly(Q). Ac-IETD-fmk (caspase-8 inhibitor) and Ac-DEVD-CHO (caspase-3 inhibitor) did not prevent the anti-m12D318 immunoreactivity induced by poly(Q)(72) aggregates. Anti-m12D318 immunoreactivity was detected in caspase-8(-/-) and caspase-3(-/-) mouse embryonic fibroblasts expressing poly(Q)(72) aggregates. Thus, caspase-12 was activated by poly(Q)(72) aggregates via a pathway independent of caspase-8 and caspase-3 activation, and caspase-12 activation was closely associated with poly(Q) aggregate-mediated cell death. Stimulation of ER stress signals may be involved in the pathogenesis of neurodegenerative disorders with poly(Q) expansion. 相似文献
2.
Recent studies have suggested that the basal ganglia are related to motivational control of behavior. To study how motivational signals modulate motor signals in the basal ganglia, we examined activity of midbrain dopamine (DA) neurons and caudate (CD) projection neurons while monkeys were performing a one-direction-rewarded version (1DR) of memory-guided saccade task. The cue stimulus indicated the goal position for an upcoming saccade and the presence or absence of reward after the trial. Among four monkeys we studied, three were sensitive to reward such that saccade velocity was significantly higher in the rewarded trials than in the nonrewarded trials; one monkey was insensitive to reward. In the reward-sensitive monkeys, both DA and CD neurons responded differentially to reward-indicating and no-reward-indicating cues. Thus DA neurons responded with excitation to a reward-indicating cue and with inhibition to a no-reward-indicating cue. A group of CD neurons responded to the cue in their response fields (mostly contralateral) and the cue response was usually enhanced when it indicated reward. In the reward-insensitive monkey, DA neurons showed no response to the cue, while the cue responses of CD neurons were not modulated by reward. Many CD neurons in the reward-sensitive monkeys, but not the reward-insensitive monkey, showed precue activity. These results suggest that DA neurons, with their connection to CD neurons, modulate the spatially selective signals in CD neurons in the reward-predicting manner and CD neurons in turn modulate saccade parameters with their polysynaptic connections to the oculomotor brain stem. 相似文献
3.
Simple self‐reported behavioral or psychological characteristics as risk factors for future type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 14 下载免费PDF全文
Yoriko Heianza Yasuji Arase Satoru Kodama Hiroshi Tsuji Kazuya Fujihara Kazumi Saito Shigeko Hara Hirohito Sone 《Journal of diabetes investigation.》2015,6(2):236-241
Aims/Introduction
Depression, anger, sleep disorders and cognitive impairment are regarded as presenting a high risk for diabetes. We investigated whether responses to single statements on a self-report questionnaire on the presence of each of these four factors were associated with the development of type 2 diabetes.Materials and Methods
We investigated 3,211 Japanese individuals without diabetes. Cumulative incidence rate and hazard ratios (HRs) for future type 2 diabetes over 7–13 years were evaluated according to the presence of lack of perseverance, anger, memory loss or sleep disorders.Results
Results of Cox regression analysis showed that lack of perseverance (age- and sex-adjusted HR 1.41, 95% confidence interval 1.07–1.84), anger, (HR 1.51, 95% confidence interval 1.07–2.12) or memory loss (HR 1.47, 95% confidence interval 1.14–1.90) was predictive of the development of diabetes. Even after adjustment for metabolic factors including glycemic measurements, anger was significantly associated with an increased risk of future diabetes. Individuals with both anger and memory loss had a 1.94-fold (95% confidence interval 1.19–3.15) increased risk of type 2 diabetes than those without those two symptoms.Conclusions
Responses to a simple self-report questionnaire as to whether individuals were aware of anger or memory loss were associated with the development of type 2 diabetes independent of traditional risk factors for diabetes in this cohort of Japanese individuals. 相似文献4.
5.
Comparison of clinical characteristics in patients with type 2 diabetes among whom different antihyperglycemic agents were prescribed as monotherapy or combination therapy by diabetes specialists 下载免费PDF全文
6.
Ma Hao Zhou Tao Li Xiang Maraganore Demetrius Heianza Yoriko Qi Lu 《Age (Dordrecht, Netherlands)》2022,44(3):1479-1488
GeroScience - We examined the interactions between educational attainment and genetic susceptibility on dementia risk among adults over 60 years old. A total of 174,161 participants were... 相似文献
7.
Yoshiyuki Okano Miki Okamoto Masahide Yazaki Ayano Inui Toshihiro Ohura Kei Murayama Yoriko Watanabe Daisuke Tokuhara Yasuhiro Takeshima 《Molecular genetics and metabolism》2021,132(1):63-70
Patients with citrin deficiency during the adaptation/compensation period exhibit diverse clinical features and have characteristic diet of high protein, high fat, and low carbohydrate. Japanese cuisine typically contains high carbohydrate but evaluation of diet of citrin-deficient patients in 2008 showed a low energy intake and a protein:fat:carbohydrate (PFC) ratio of 19:44:37, which indicates low carbohydrate consumption rate. These findings prompted the need for diet intervention to prevent the adult onset of type II citrullinemia (CTLN2). Since the publication of the report about 10 years ago, patients are generally advised to eat what they wish under active dietary consultation and intervention. In this study, citrin-deficient patients and control subjects living in the same household provided answers to a questionnaire, filled-up a maximum 6-day food diary, and supplied physical data and information on medications if any. To study the effects of the current diet, the survey collected data from 62 patients and 45 controls comparing daily intakes of energy, protein, fat, and carbohydrate. Food analysis showed that patient's energy intake was 115% compared to the Japanese standard. The confidence interval of the PFC ratio of patients was 20–22:47–51:28–32, indicating higher protein, higher fat and lower carbohydrate relative to previous reports. The mean PFC ratio of female patients (22:53:25) was significantly different from that of male patients (20:46:34), which may explain the lower frequency of CTLN2 in females. Comparison of the present data to those published 10 years ago, energy, protein, and fat intakes were significantly higher but the amount of carbohydrate consumption remained the same. Regardless of age, most patients (except for adolescents) consumed 100–200 g/day of carbohydrates, which met the estimated average requirement of 100 g/day for healthy individuals. Finally, patients were generally not overweight and some CTLN2 patients were underweight although their energy intake was higher compared with the control subjects. We speculate that high-energy of a low carbohydrate diet under dietary intervention may help citrin-deficient patients attain normal growth and prevent the onset of CTLN2. 相似文献
8.
Ken Higashimoto Toshiyuki Maeda Junichiro Okada Yasufumi Ohtsuka Kensaku Sasaki Akiko Hirose Makoto Nomiyama Toshimitsu Takayanagi Ryuji Fukuzawa Hitomi Yatsuki Kayoko Koide Kenichi Nishioka Keiichiro Joh Yoriko Watanabe Koh-ichiro Yoshiura Hidenobu Soejima 《European journal of human genetics : EJHG》2013,21(11):1316-1319
Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR. 相似文献
9.
Predictors for typical asthma onset from cough variant asthma. 总被引:6,自引:0,他引:6
Masaki Fujimura Yoriko Nishizawa Masaru Nishitsuji Satoshi Nomura Miki Abo Haruhiko Ogawa 《The Journal of asthma》2005,42(2):107-111
Cough variant asthma is recognized to be a precursor of asthma or preasthmatic state because nearly 30% patients with cough variant asthma develop typical asthma within several years. However, predictors for risk of typical asthma onset from cough variant asthma are unknown. Forty-one patients with cough variant asthma (median age 50 years, 13 men and 28 women), who had undertaken spirometry, bronchial reversibility test, methacholine provocation test, measurements of peripheral blood eosinophil count, serum total IgE, and specific IgE to common allergens, and induced sputum eosinophil count at presentation, were followed up with special emphasis on typical asthma onset during 1 year or more (median 4 years, range 1-12.4). Long-term inhaled corticosteroids (ICS) were taken in 27 patients. Univariate and multivariate logistic analyses were performed to determine the predictors for typical asthma onset. Asthma onset was recognized in 7 patients. Bronchial hyperresponsiveness, peripheral blood eosinophil count, and no use of ICS were significant predictors for the typical asthma onset by univariate analysis. However, only bronchial hyperresponsiveness was the significant predictor when multivariate analysis was used (adjusted OR 0.028, 95% CI 0.001-0.783, p = 0.0355). Bronchial hyperresponsiveness may be the most important predictor for risk of typical asthma onset from cough variant asthma. 相似文献