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61.
62.
H Nakamura Y Kishi M A Pajares R R Rando 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(24):9672-9676
Protein kinase C (PKC) is an important enzyme that helps govern cell metabolism and growth. The enzyme is physiologically activated when an (S)-diglyceride binds to its own regulatory domain. The saturable binding site of the regulatory domain can also be bound by any of a group of structurally diverse tumor promoters, including debromoaplysiatoxins (DATs), phorbol esters, ingenols, teleocidins, and bryostatins. The question of how the same binding site can be the target of these structurally diverse molecules is of considerable importance and is addressed in this article. The relatively rigid structure of DAT and the fact that it possesses a diglyceride moiety renders it an ideal starting template. Structure-activity studies with PKC reveal that the C29 but not the C30 stereocenter of DAT is critical for activity. Furthermore, 3-deoxy-DAT and DAT are equipotent as PKC activators, hence the C3 hydroxyl group of DAT is not critical for activity. Straightforward structural considerations show that the C30 hydroxyl group of DAT matches the C3 hydroxyl group of diglyceride, the C29 stereocenter of DAT matches the C2 stereocenter of (S)-diglyceride, and the C1 ester moiety of DAT matches the C2 ester moiety of diglyceride. Based on these studies and on published structure-activity observations on other tumor promoters, a structural hypothesis is developed to account for the chemical mechanism of tumor promoter action. Experimentally testable predictions are made concerning the interactions with PKC of several classes of tumor PKC activators. 相似文献
63.
Atsushi Ishii Sawa Yasumoto Yukiko Ihara Takahito Inoue Takako Fujita Noriko Nakamura Masaharu Ohfu Yushiro Yamashita Hideo Takatsuka Toshiaki Taga Rie Miyata Masahiro Ito Hiroshi Tsuchiya Taro Matsuoka Tetsuya Kitao Kiyotaka Murakami Wang-Tso Lee Sunao Kaneko Shinichi Hirose 《Brain & development》2013
Purpose: PRRT2 mutations were recently identified in benign familial infantile epilepsy (BFIE) and infantile convulsions with paroxysmal choreoathetosis (ICCA) but no abnormalities have so far been identified in their phenotypically similar seizure disorder of benign convulsions with mild gastroenteritis (CwG), while mutations in KCNQ2 and KCNQ3 have been recognized in benign familial neonatal epilepsy (BFNE). The aim of this study was to identify PRRT2 mutations in infantile convulsions in Asian families with BFIE and ICCA, CwG and BFNE. Methods: We recruited 26 unrelated Japanese affected with either BFIE or non-familial benign infantile seizures and their families, including three families with ICCA. A total of 17 Japanese and Taiwanese with CwG, 50 Japanese with BFNE and 96 healthy volunteers were also recruited. Mutations of PRRT2 were sought using direct sequencing. Results: Heterozygous truncation mutation (c.649dupC) was identified in 15 of 26 individuals with benign infantile epilepsy (52.1%). All three families of ICCA harbored the same mutation (100%). Another novel mutation (c.1012+2dupT) was found in the proband of a family with BFIE. However, no PRRT2 mutation was found in either CwG or BFNE. Conclusions: The results confirm that c.649dupC, a truncating mutation of PRRT2, is a hotspot mutation resulting in BFIE or ICCA regardless of the ethnic background. In contrast, PRRT2 mutations do not seem to be associated with CwG or BFNE. Screening for PRRT2 mutation might be useful in early-stage differentiation of BFIE from CwG. 相似文献
64.
Hyperekplexia manifests as generalized stiffness and an excessive startle reflex to stimuli. It starts in the neonatal period and is transmitted in many cases via autosomal dominant inheritance. The etiology is an abnormality of the glycinergic neurotransmission system that is involved in inhibitory neurotransmission. Aberrations of five genes related to this neurotransmission system have been identified. The patient was a 14-year-old girl with mild mental retardation. None of her family members had a neuromuscular disease. An excessive startle reflex and generalized stiffness were noted immediately after birth and she was diagnosed with epilepsy because epileptic discharges were observed. However, the disease was resistant to various antiepileptic drugs and the startle responses persisted. GLRB gene mutations (R50X/Q216fsx222) were identified, after which the patient was diagnosed with hyperekplexia. The startle reflex improved when clonazepam treatment was initiated. When patients have a persistent startle reflex, it is necessary to consider hyperekplexia, even if epileptic discharges are observed. Only four cases with GLRB mutations, including the present patient, have been reported. To make a definite diagnosis of hyperekplexia, it may be useful to screen for genes that are involved in the glycinergic neurotransmission system. 相似文献
65.
Prediction of functional outcome after stroke rehabilitation 总被引:9,自引:0,他引:9
Inouye M Kishi K Ikeda Y Takada M Katoh J Iwahashi M Hayakawa M Ishihara K Sawamura S Kazumi T 《American journal of physical medicine & rehabilitation / Association of Academic Physiatrists》2000,79(6):513-518
OBJECTIVE: The purpose of this study is to identify predictors of functional outcome after acute stroke inpatient rehabilitation using raw Functional Independence Measure (FIM) total scores. DESIGN: Multivariate analysis was performed on data collected retrospectively from stroke rehabilitation patients. Six independent variables were obtained from patients' medical records. RESULTS: The FIM total scores at the time of discharge from the hospital correlated strongly with FIM total scores at the time of admission to the hospital and correlated negatively with age and OAI using the Spearman's rank correlation method. The FIM total scores at the time of hospital admission were the best predictor of FIM total scores at the time of discharge from the hospital. However, the nature of the stroke, gender, and LOHS did not correlate with FIM total scores at the time of discharge from the hospital. CONCLUSIONS: Because FIM total scores at the time of hospital admission and discharge are highly correlated, FIM total scores at the time of hospital admission can be used to establish a rehabilitation program, to inform the patient and family about the possibility of recovery, and to assess the amount and quality of care given in the home or discharge placement. 相似文献
66.
Takaki Maeda Keisuke Takahata Taro Muramatsu Tsukasa Okimura Akihiro Koreki Satoru Iwashita Masaru Mimura Motoichiro Kato 《Psychiatry research》2013
Self-disturbances in schizophrenia have been regarded as a fundamental vulnerability marker for this disease, and have begun to be studied from the standpoint of an abnormal “sense of agency (SoA)” in cognitive neuroscience. To clarify the nature of aberrant SoA in schizophrenia, it needs to be investigated in various clinical subtypes and stages. The residual type of chronic schizophrenia with predominant negative symptoms (NS) has never been investigated for SoA. Accordingly, we investigated SoA by an original agency attribution task in NS-predominant schizophrenia, and evaluated the dynamic interplay between the predictive and postdictive components of SoA in the optimal cue integration framework. We studied 20 patients with NS-predominant schizophrenia, and compared with 30 patients with paranoid-type schizophrenia and 35 normal volunteers. NS-predominant schizophrenia showed markedly diminished SoA compared to normal controls and paranoid-type schizophrenia, indicating a completely opposite direction in agency attribution compared with excessive SoA demonstrated in paranoid-type schizophrenia. Reduced SoA was detected in experimental studies of schizophrenia for the first time. According to the optimal cue integration framework, these results indicate that there was no increase in compensatory contributions of the postdictive processes despite the existence of inadequate predictions, contrary to the exaggerated postdictive component in paranoid-type schizophrenia. 相似文献
67.
Taro Tezuka Nathanael D. Heckmann Russell J. Bodner Lawrence D. Dorr 《The Journal of arthroplasty》2019,34(1):3-8
Background
The Lewinnek “safe zone” is not always predictive of stability after total hip arthroplasty (THA). Recent studies have focused on functional hip motion as observed on lateral spine-pelvis-hip x-rays. The purpose of this study was to assess the correlation between the Lewinnek safe zone and the functional safe zone based on hip and pelvic motion in the sagittal plane.Methods
Three hundred twenty hips (291 patients) underwent primary THA using computer navigation. Two hundred ninety-six of these hips (92.5%) were within the Lewinnek safe zone as determined by inclination of 40° ± 10° and anteversion of 15° ± 10°. All patients had preoperative and postoperative standing and sitting lateral spinopelvic x-rays. The combined sagittal index (CSI), a combination of sagittal acetabular and femoral position, was measured for each patient and used to assess the functional safe zone. Data analysis was performed to identify hips in the Lewinnek safe zone inside and outside the sagittal functional safe zone. Predictive factors for hips outside the functional safe zone were identified.Results
Of the 296 hips within the Lewinnek safe zone, 254 (85.8%) were also in the functional safe zone. Forty-two patients were outside the functional safe zone based on CSI; 19 had an increased standing CSI and 23 had a decreased sitting CSI, all were considered at risk for dislocation. Predictive factors for falling outside the functional safe zone were increased femoral mobility (P < .001, r = 0.632), decreased spinopelvic mobility (P < .001, r = 0.455), and pelvic incidence (P < .001, r = 0.400).Conclusion
In this study, 14.2% of hips within the Lewinnek safe zone were outside the functional safe zone, identifying a potential reason hips dislocate despite having “normal” cup angles. The best predictor for falling outside the functional safe zone, both preoperatively and postoperatively, was femoral mobility, not the sagittal cup position (ie, cup anteinclination).Level of Evidence
Level III, retrospective review. 相似文献68.
4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol)‐induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress 下载免费PDF全文
Noriko Goto Mariko Tsujimoto Hiroshi Nagai Taro Masaki Shosuke Ito Kazumasa Wakamatsu Chikako Nishigori 《Experimental dermatology》2018,27(7):754-762
4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD), a skin‐whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity‐dependent manner. We examined the effect of UV radiation (UVR) on RD‐induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD‐induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N‐acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress‐induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl‐RD‐catechol and RD‐pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS‐generating substances and that the tendency to produce RD‐pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD‐induced leukoderma and provide information for innovation of safe skin‐whitening compounds. 相似文献
69.
Yohjiroh Makino Katsuhiro Ishida Keita Kishi Hiroki Kodama Takeshi Miyawaki 《Journal of plastic surgery and hand surgery》2018,52(3):153-157
The Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) is widely used to predict surgical complications affecting various organs. However, there are few reports about objective evaluation methods for head and neck surgery. In this study, we retrospectively examined the association between POSSUM score and actual surgical complications of head and neck reconstruction surgery. In total, 711 patients who underwent head and neck reconstruction after cancer extirpation between January 2007 and January 2015 were studied. The predicted risk of complications was calculated using the POSSUM score and compared with the actual rate of perioperative complications. Perioperative complications occurred in 178 (25%) patients, comprising systemic complications in 52 (7%) patients, surgical site infection of the head and neck area in 78 (11%) patients and failure of the free flap in 55 (8.8%) patients. When patients were divided into a perioperative complication group and a no-complication group, a significant difference between the two groups was observed in the predicted postoperative rate calculated from the POSSUM score (p?.0001, odds ratio 1.03, 95% confidence interval?=?1.02–1.04). Furthermore, the cutoff value of the POSSUM score calculated from the receiver operating characteristic curve using Youden’s index was 43.0%. POSSUM is a useful risk indicator for head and neck reconstruction surgery. It is possible to objectively calculate the prediction level using a standard assessment method without adding burden to any medical facility. Therefore, patients may be considered at high risk for perioperative complications when the POSSUM score is 43.0% or higher. 相似文献
70.
Continuation of antithrombotic therapy may be associated with a high incidence of colonic post‐polypectomy bleeding 下载免费PDF全文
Tomoyoshi Shibuya Osamu Nomura Tomohiro Kodani Takashi Murakami Hirofumi Fukushima Yuzuru Tajima Kohei Matsumoto Hideaki Ritsuno Hiroya Ueyama Yoshihiro Inami Dai Ishikawa Kenshi Matsumoto Naoto Sakamoto Taro Osada Akihito Nagahara Tatsuo Ogihara Sumio Watanabe 《Digestive endoscopy》2017,29(3):314-321