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Anti-rods/rings autoantibody generation in hepatitis Cpatients during interferon-α/ribavirin therapy

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World Journal of Gastroenterology 2016年第6期22卷 1966-1974页

作者： Gerson Dierley Keppeke S John Calise edward kl chan Luis Eduardo C Andrade Rheumatology Division Escola Paulista de MedicinaUniversidade Federal de São PauloSP 04023-062Brazil Department of Oral Biology University of FloridaGainesvilleFL 32610-0424United States 3 Immunology DivisionFleury Medicine and Health Laboratories São PauloSP 04102-050Brazil

Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.

关键词： Rods and rings autoantibodies Hepatitis C ribavirin Interferon-α

白塞病相关自身抗原Kinectin的表达型cDNA文库筛选与鉴定

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中华风湿病学杂志 2005年第10期9卷 577-581页

作者：陆瑜叶萍陈顺乐顾越英 Eng M.Tan edward kl chan 上海第二医科大学附属仁济医院风湿科上海市风湿病研究所 200001 Scripps研究所自身免疫病中心

目的研究白塞病患者血循环中的自身抗体及其针对的细胞内靶抗原。方法应用免疫印迹-化学发光法对39例白塞病患者血清进行初步研究,以含有高滴度抗体的患者血清作为“探针”免疫筛选表达型!ZAP噬菌体cDNA文库并鉴定候选克隆,通过真核转... 详细信息

目的研究白塞病患者血循环中的自身抗体及其针对的细胞内靶抗原。方法应用免疫印迹-化学发光法对39例白塞病患者血清进行初步研究,以含有高滴度抗体的患者血清作为“探针”免疫筛选表达型!ZAP噬菌体cDNA文库并鉴定候选克隆,通过真核转录、翻译以及免疫沉淀实验分析阳性克隆表达产物的抗原性。结果文库筛选获得6个独立候选克隆,均为人Kinectin部分全长cDNA,以其中最大克隆的基因表达产物为抗原基质的免疫沉淀研究显示,23.1%(9/39)的白塞病患者血清呈阳性反应,正常人以及系统性红斑狼疮、干燥综合征患者对照阴性。结论Kinectin是白塞病相关自身靶抗原;抗Kinectin抗体与白塞病免疫发病机制的关系值得深入探索,抗体可能对疾病具有潜在血清学诊断价值。

关键词：自身抗原基因文库免疫沉淀法 Kinectin 白塞病 cDNA文库筛选自身抗原白塞病抗Kinectin抗体鉴定基因表达产物系统性红斑狼疮候选克隆全长cDNA

Expression of androgen receptor target genes in skeletal muscle

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Asian Journal of Andrology 2014年第5期16卷 675-683,I0006页

作者： Kesha Rana Nicole kl Lee Jeffrey D Zajac Helen E MacLean Department of Medicine Austin Health University of Melbourne Heidelberg Victoria Australia

We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor （AR）-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity （AR△ZF2） versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR△ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7, p57Kip2, IEf2 and calcineurin Aa, was increased in AR△ZF2 muscle, and the expression of all but p57kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

关键词： androgen receptor anabolic atrophy gene expression skeletal muscle

Prevalence and features of colorectal lesions among Hispanics: A hospital-based study

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World Journal of Gastroenterology 2015年第46期21卷 13095-13100页

作者： Hassan Ashktorab Adeyinka O Laiyemo edward Lee Marcia Cruz-Correa Amita Ghuman Mehdi Nouraie Hassan Brim Gastroenterology Division and Cancer Center Pathology DepartmentHoward University College of Medicine

AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic ***: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size,adenomas with villous histology,high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ2 statistics and ***: The median age of the patients was 54 years,64.2% were females. Polyps were observed in 489(30.0%) of patients. Adenoma prevalence was 16.8%(n = 273),advanced adenoma 2.4%(n = 39),and colorectal cancer 0.4%(n = 7). Hyperplastic polyps were seen in 6.6% of the cohort(n = 107). Adenomas predominantly exhibited a proximal colonic distribution(53.7%,n = 144); while hyperplastic polyps were mostly located in the distal colon(70%,n = 75). Among 11.7%(n = 191) patients who underwent screening colonoscopy,the prevalence of colorectal lesions was 21.4% adenoma,2.6% advanced adenoma; and 8.3% hyperplastic ***: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However,the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies.

关键词： Colon Rectum Adenoma Carcinoma Hispanics

Race and colorectal cancer screening compliance among persons with a family history of cancer

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World Journal of Gastrointestinal Endoscopy 2015年第18期7卷 1300-1305页

作者： Adeyinka O Laiyemo Nicole Thompson Carla D Williams Kolapo A Idowu Kathy Bull-Henry Zaki A Sherif edward L Lee Hassan Brim Hassan Ashktorab Elizabeth A Platz Duane T Smoot Division of Gastro-enterology Department of Medicine Howard University College of Medicine Howard University Cancer Center Department of Medicine Georgetown Univer-sity Department of Biochemistry and Molecular Biology Howard University College of Medicine Department of Pathology Howard University Department of Epidemiology Johns Hopkins Bloomberg School of Public Health the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Department of Medicine Meharry Medical Center

AIM: To determine compliance to colorectal cancer(CRC) screening guidelines among persons with a family history of any type of cancer and investigate racial differences in screening ***: We used the 2007 Health Information National Trends Survey and identified 1094(27.4%)respondents(weighted population size = 21959672) without a family history of cancer and 3138(72.6%) respondents(weighted population size = 58201479) with a family history of cancer who were 50 years and older. We defined compliance with CRC screening as the use of fecal occult blood testing within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared compliance with CRC screening among those with and without a family member with a history of cancer. RESULTS: Overall, those with a family member with cancer were more likely to be compliant with CRC screening(64.9% vs 55.1%; OR = 1.45; 95%CI: 1.20-1.74). The absolute increase in screening rates associated with family history of cancer was 8.2% among whites. Hispanics had lowest screening rates among those without family history of cancer 41.9% but had highest absolute increase(14.7%) in CRC screening rate when they have a family member with cancer. Blacks had the lowest absolute increase in CRC screening(5.3%) when a family member has a known history of cancer. However, the noted increase in screening rates among blacks and Hispanics when they have a family member with cancer were not higher than whites without a family history of cancer:(54.5% vs 58.7%; OR = 1.16; 95%CI: 0.72-1.88) for blacks and(56.7% vs 58.7%; OR = 1.25; 95%CI: 0.72-2.18) for ***: While adults with a family history of any cancer were more likely to be compliant with CRC screening guidelines irrespective of race/ethnicity, blacks and Hispanics with a family history of cancer were less likely to be compliant than whites without a family history. Increased burden from CRC among blacks may be related to poor uptake of screening

关键词： Colon cancer Health disparities Screening Fecal bl