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111.
Chisei Satoh Tatsuro Kondoh Hitomi Shimizu Akira Kinoshita Hiroyuki Mishima Gen Nishimura Mutsuko Miyazaki Kunihiko Okano Yoshihiko Kumai Koh-ichiro Yoshiura 《European journal of medical genetics》2021,64(2):104125
COL27A1 encodes a collagen type XXVII alpha 1 chain. It is the product of this gene that provides the structural support of connective tissue and is reported to be the causative gene of Steel syndrome (OMIM #615155). The primary symptoms of patients with this defect are consistent with systemic bone disease; however, recent reports note findings of intellectual disability and hearing loss. In this study, we identified novel COL27A1 compound heterozygous variants in two brothers with rhizomelia and congenital hip dislocation as well as dental and genital abnormalities that have not yet been reported in Steel syndrome. This variant, of maternal origin, caused an amino acid substitution of arginine for glycine, c.2026G>C or p.G676R, in the collagen helix domain, which is assumed to damage the structure of the helix. The paternally transmitted variant, c.2367G>A, is located at the 3′ end of exon 12, and cDNA analysis revealed a splicing alteration. These novel, compound heterozygous COL27A1 variants might indicate an association of the gene with tooth and genital abnormalities. 相似文献
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115.
Satoru Tanaka Masao Yoshinaga Koji Sameshima Junichiro Nishi Yukiharu Kono Yuichi Nomura Yoshifumi Kawano Mutsuko Hirata Tomoko Tachikawa Shinichiro Shimizu Katsura Arima 《Circulation journal》2005,69(2):232-236
BACKGROUND: Currently, a generalizable conclusion on the effectiveness of treatment programs for childhood obesity cannot be drawn, and how practical and effective the intervention strategies are remains a controversial subject. METHODS AND RESULTS: In the present study 36 obese elementary school children who visited an intervention program at least 4 times were followed for 12 months or more. A stepwise regression analysis was performed using the decrease in the percent relative body weight (%RBW) at 12 months after the first visit as a dependent variable, and the decrease in the %RBW and nutritional data between 2 successive visits as independent variables. The analysis revealed 4 significant predictive factors: (1) a higher ratio of energy intake from protein (20%) recommended at the first visit, (2) a greater decrease in the %RBW between the first and second visits, (3) higher age, and (4) a higher concentration of alanine aminotransferase at the first visit. CONCLUSION: Providing a strong motivation to change eating and activity behavior at the early stage of intervention and recommending diets with higher ratios of energy intake from protein are the most practical and effective strategies for treating obesity. 相似文献
116.
Takahisa Imamura Mutsuko Yamamoto-Ibusuki Aiko Sueta Tatsuko Kubo Atsushi Irie Ken Kikuchi Toru Kariu Hirotaka Iwase 《Breast cancer (Tokyo, Japan)》2016,23(6):876-885
Background
Emerging evidence has shown activation of the complement system in cancer tissues and anaphylatoxin C5a release from C5 by cancer cells, suggesting C5a as a component in the cancer microenvironment. We revealed aberrant expression of C5a receptor (C5aR) in various human cancers and C5a-elicited enhancement of C5aR-expressing cancer cell invasion.Methods
To explore an influence of the C5a–C5aR system in breast cancer (BC), we investigated BC C5aR expression in relation to clinicopathological parameters of the patients and an effect of C5a on BC cell proliferation.Results
BC cell C5aR expression was observed immunohistochemically in 22 of 171 patients (13 %) and related to larger tumor size, higher nuclear grade and Ki-67 labeling index, presence of lymph node metastasis and advanced clinical stages. Interestingly, BC cells were C5aR-negative in all patients with BC in situ and C5aR-positive rate was high (38 %) in patients with hormone receptor-negative, namely triple-negative BC. For BC cells in metastasized lymph nodes, 12 of 22 patients (55 %) were C5aR-positive and included 7 patients with C5aR-negative BC in the primary site. Survival rate of patients with C5aR-positive BC was lower than that of patients with C5aR-negative BC. C5a enhanced proliferation of C5aR-expressing triple-negative BC cells in a C5aR-dependent manner.Conclusion
Relation of BC C5aR expression to tumor development and poor prognosis of the patients and proliferation enhancing effect of C5a on C5aR-expressing BC cells suggest that the C5a–C5aR system is closely associated with BC progression. This system may be a new target to treat BC patients, particularly with triple-negative BC.117.
Ema M Hara H Matsumoto M Hirata-Koizumi M Hirose A Kamata E 《Reproductive toxicology (Elmsford, N.Y.)》2008,25(1):89-99
The developmental neurotoxicity of polysorbate 80 (PS80) was evaluated in rats. Crl:CD(SD) rats were given drinking water containing PS80 at 0, 0.018, 0.13, 1.0, or 7.5% (0, 0.035, 0.245, 1.864, or 16.783ml/kgbw/day) on day 0 of pregnancy through day 21 after delivery. Pregnant rats were allowed to deliver spontaneously. Potential adverse effects of pre- and post-natal exposure on the development and function of the nervous system in offspring of rats given PS80 were examined. Maternal body weight was lowered at 7.5%. Number of pups born was lowered at 7.5%. There were no compound-related effects on locomotor activity of offspring on postnatal days (PNDs) 14-15, 17-18, 20-21 and 33-37. No compound-related changes were found in developmental landmarks, sexual maturation, or reflex responses. Although decreased rate of avoidance responses was noted on PNDs 23-27 in male and female offspring at 7.5%, no compound-related changes were found in performance in the conditioned avoidance response on PNDs 60-67. Histopathological examinations of the brain revealed no toxicological changes. Lowered body weight was observed in male and female offspring at 7.5%. The NOAEL in this study was considered to be 1.0% (1.864ml/mg/kgbw/day). 相似文献
118.
Horiuchi I Nozawa T Fujii N Inoue H Honda M Shimizu T Taguchi M Hashimoto Y 《Biological & pharmaceutical bulletin》2008,31(5):976-980
The purpose of this study was to evaluate the pharmacokinetics of R- and S-carvedilol in routinely treated Japanese patients with heart failure. We measured peak and trough blood concentrations at steady state following repeated oral administration to 24 patients. The blood concentration of S-carvedilol with potent beta-blocking activity was lower than that of R-carvedilol. The mean oral clearance (CL/F) of R- and S-carvedilol was not altered by CYP2D6*10, UGT2B7*3, and the etiology of heart failure. In addition, the CL/F values of enantiomers were not correlated with age, creatinine clearance, and plasma concentrations of alpha1-acid glycoprotein and brain natriuretic peptide. On the other hand, the mean CL/F values of R- and S-carvedilol in patients with heart failure were 0.89 and 1.52 l/h/kg, respectively, considerably lower than those estimated previously in healthy subjects. These results suggested that the pharmacokinetics of R- and S-carvedilol was altered significantly by heart failure. 相似文献
119.
Harada T Kimura E Hirata-Koizumi M Hirose A Kamata E Ema M 《Drug and chemical toxicology》2008,31(4):473-486
Twelve male and female rats per group were given 4-aminophenol (PAP) by gavage at 0, 20, 100, or 500 mg/kg/day. Males were dosed for a total of 49 days, beginning 14 days before mating. Females were dosed for a total of 40-60 days, from 14 days before mating to Day 3 of lactation throughout the mating and gestation periods. Four males and 2 females died at 500 mg/kg/day, and all surviving males and females showed brown urine at 100 mg/kg/day and above. Body-weight gain was lower in males and females at 500 mg/kg/day, and food consumption was decreased in males at 500 mg/kg/day and in females at 100 and 500 mg/kg/day. Absolute and relative weights of the testes and epididymides were decreased at 500 mg/kg/day. Histopathological examinations revealed decreased spermatocyte and spermatid levels in the testis, debris of germ cell in the epididymis lumen, basophilic tubules in the kidney, and deposits of hemosiderin in the red pulp and extramedullary hematopoiesis in the spleen in males at 500 mg/kg/day. Longer gestation period, decreased delivery index, and lower body weight of pups on postnatal day (PND) 0 and increased number of stillborns at 500 mg/kg/day were also observed. At this dose, the viability of pups on PND 4 was decreased markedly. No adverse effects on reproduction or development were detected at 20 and 100 mg/kg/day. These findings indicate that PAP is general and reproductive/developmental toxic, but is unlikely to be teratogenic, in rats. 相似文献
120.
Hirata-Koizumi M Matsuyama T Imai T Hirose A Kamata E Ema M 《Drug and chemical toxicology》2008,31(2):275-287
In our previous toxicity studies using young rats, we showed that an ultraviolet absorber, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), principally affected the liver, and male rats had nearly 25 times higher susceptibility to the toxic effects than females. In the present study, the toxicity of HDBB was investigated in preweaning rats. HDBB was administered by gavage to male and female CD(SD) rats from postnatal days 4 to 21 at a dose of 0, 0.1, 0.5, 2.5, or 12.5 mg/kg/day. No substance-related deaths, clinical signs of toxicity, or body-weight changes were observed. Increased levels of albumin, AST and ALP in both sexes, BUN in males, and LDH in females were found at 12.5 mg/kg. Liver weights increased at 2.5 mg/kg and above in both sexes. Histopathologically, hepatocellular findings, such as nucleolar enlargement, anisokaryosis, increased mitosis, and/or hypertrophy, were observed at 2.5 mg/kg and above in both sexes. These results indicate no gender-related differences in the susceptibility to the toxic effects of HDBB in preweaning rats. 相似文献