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951.
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major hepatic autoimmune conditions. Patient morbidity and mortality remain high across these three diseases, and an unmet need for rational therapy exists. Disease understanding has focused on combining clinical and laboratory based science to provide better insights into the joint host and environmental factors necessary for the initiation, and perpetuation, of hepato-biliary inflammation. Twin studies, family studies, population studies and an inter-relationship with other autoimmune phenomena suggest a genetic component to risk for each disease. Until recently, understanding of this genetic risk has been limited to HLA haplotypes. Associations with risk-conferring and protective HLA haplotypes are present in all three diseases. Over the last few years, genome-wide association studies (GWAS), and related genetic association studies, have greatly increased understanding of the genetic risk signature of these three diseases and autoimmunity in general. Here we consider the rationale for GWAS in general and with specific reference to hepatic autoimmunity. We consider the process of GWAS, and highlight major findings to date. Potential functional implications of key findings are discussed including the IL-12/STAT4 pathway in PBC and the CD28/IL-2 pathway in PSC. We describe the marked pleiotropy demonstrated by PBC and PSC, which is consistent with other autoimmune diseases. Further, we focus on specific gene associations including SH2B3, which is common to all three diseases, and FUT2 in PSC, which represents a link between environment and genetics. We review attempts to translate GWAS findings into basic laboratory models including in vivo systems and highlight where clinical observations relate to genetics. Finally we describe deficiencies in GWAS to date and consider future study of genetics in hepatic autoimmunity. 相似文献
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953.
Kohta Fujiwara Jun Hata Yuji Oshima Sawako Hashimoto Takeshi Yoshitomi 《Seminars in ophthalmology》2018,33(6):813-819
Purpose: To estimate the prevalence and risk factors for polypoidal choroidal vasculopathy (PCV) in a general Japanese population. Methods: This population-based, cross-sectional study was conducted in 2007 with subjects from the Hisayama Study. Of the 3,648 residents in Hisayama, Japan, 2,663 who were ≥ 50 years old were enrolled in this study. The characteristics of PCV were determined by fundus examination or based on indocyanine green and fluorescein angiographic findings. We evaluated the contributions of the risk factors for PCV. Results: Among the 207 participants with age-related macular degeneration (AMD), 174 (6.5%) had early AMD, and 33 (1.2%) had late AMD, including 10 participants with PCV (0.4%). Male and smoking habit were significant risk factors for the development of PCV. Conclusions: The prevalence of PCV is higher among Japanese subjects than Caucasians in Western countries. Male gender and smoking habit were significant risk factors for PCV in a general Japanese population. 相似文献
954.
Mohemmed Faraz Khan Mohammad Mumtaz Alam Garima Verma Wasim Akhtar Moshahid Alam Rizvi Asif Ali 《Toxicology mechanisms and methods》2017,27(2):151-163
Dioxins and dioxin-like compounds (DLCs) are the ones with poor water solubility and low volatility, resistant to physical, chemical and biological processes, persistent in the environment even under extreme conditions. Due to lipophilic nature, they get adhered to the fatty material and concentrate through biomagnification and bioaccumulation, thereby easily getting incorporated into food chains, paving the way to endocrine disruption via modulation of various human receptors. This in turn leads to certain adverse health effects. In the present study, a total of 100 dioxins and DLCs were taken and their binding pattern was assessed with the ketosteroid receptors, i.e. androgen (hAR), glucocorticoid (hGR), progesterone (hPR) and mineralocorticoid (hMR) in comparison to the corresponding natural steroids and a known endocrine disrupting xenobiotic, Bisphenol A (BPA). Most of the DLCs, particularly those bearing hydroxyl (-OH) group showed considerable affinities with ketosteroid receptors. On comparing D scores of all the dioxins and DLCs against all four receptors, compound 8-hydroxy-3,4-dichlorodibenzofuran(8-OH-DCDF) exhibited least D score of -9.549?kcal mol?1 against hAR. 3,8-Dihydroxy-2-chlorodibenzofuran(3,8-DiOH-CDF), 4′-hydroxy-2,3,4,5-tetrachlorobiphenyl (4′-OH-TCB) and 4-hydroxy-2,2′,5′-trichlorobiphenyl(4-OH-TCB) also showed comparable molecular interactions with the ketosteroid receptors. These interactions mainly include H-bonding, π–π stacking, hydrophobic, polar and van der Waals’ interactions. In contrast, BPA and some natural ligands tested in this study showed lower binding affinities with these receptors than certain DLCs reported herein, i.e. certain DLCs might be more toxic than the proven toxic agent, BPA. Such studies play a pivotal role in the risk assessment of exposure to dioxins and DLCs on human health. 相似文献
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956.
Simona Zaami Francesco Paolo Busardò Fabrizio Signore Nicola Felici Vito Briganti Giovanni Baglio 《The journal of maternal-fetal & neonatal medicine》2018,31(11):1412-1417
Aims: The aim of this study was to examine 24 cases of obstetric brachial plexus palsy (OBPP) in 41,002 deliveries occurred at San Camillo–Forlanini Hospital in Rome, during the period 2000–2012.Materials and methods: A population-based retrospective case-control study was designed and the database of the hospital was searched; for each case, maternal and fetal records were examined and some risk factors were evaluated.Results: A statistically significant association between the 24 cases OBPP and the following risk factors: primiparity (p?.014), birth weight (p?.002), maternal age (p?.02), diabetes (p?.03) and shoulder dystocia (p?.003) was found, moreover all the OBPP cases were recorded only in vaginal deliveries.Conclusions: The absence of OBPP cases in cesarean deliveries highlighted in this study supports the option of proposing an elective cesarean in the presence of known risk factors after a full disclosure with the mother of risks and benefits in order to obtain a valid consent. Furthermore, when cases of OBPP occur, communication between the physician and the parents of newborns is crucial and it may represent a valid risk-management tool to reduce malpractice lawsuits. 相似文献
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960.
目的:比较卡贝缩宫素和缩宫素治疗剖宫产高危产妇的效果。方法:选取122例剖宫产高危产妇为研究对象,按照随机数字表法分为观察组与对照组各61例。两组均行剖宫产手术,胎儿娩出后,对照组给予缩宫素治疗,观察组给予卡贝缩宫素治疗,比较两组术中、产后2、24 h出血量,产后加用前列素氨丁三醇率,凝血功能指标[纤维蛋白原(FIB)、D-二聚体(D-D)、凝血酶原时间(PT)、部分凝血活酶时间(APTT)]水平,心率,血压,血红蛋白水平和不良反应发生率。结果:观察组术中、产后2、24 h出血量均低于对照组,差异有统计学意义(P<0.05);观察组加用卡前列素氨丁三醇率为4.92%(3/61),明显低于对照组的16.39%(10/61),差异有统计学意义(P<0.05);术后,两组FIB、D-D水平均高于术前,且观察组高于对照组,两组PT、APTT均短于术前,且观察组短于对照组,差异有统计学意义(P<0.05);术后,两组血红蛋白水平均低于术前,但观察组高于对照组,差异有统计学意义(P<0.05);手术前后,两组心率、血压和不良反应发生率比较,差异均无统计学意义(P>0.05)。结论:卡贝缩宫素治疗剖宫产高危产妇可减少出血量和加用卡前列素氨丁三醇率,提高其术后血红蛋白水平,以及改善凝血功能指标,效果优于缩宫素。 相似文献