癌症基因组图集数据库及其应用

癌症多是由DNA变异引起的细胞恶性增生,在基因组水平上研究这些变异及变异间相互作用引起的癌变分子机制,将有助于提高我们对癌症的预防、诊断及治疗能力。基于此,美国国家癌症研究所（NCI）和国家人类基因组研究所（NHGRI）联合发起了癌症基因组图集计划（TCGA）,获得了海量数据。这些数据加速了人们对癌变分子机制的认识,为精准治疗和个性化治疗奠定了坚实的基础。此计划完成后国内鲜有对其详实的介绍,本文将对该基因组数据的产生、数据的类型、数据的获取与应用等进行描述,促进这些数据运用于癌症的预防、早期诊断和治疗中。     

浙江省实验动物中心长爪沙鼠群体遗传状况分析

目的 探讨浙江实验动物中心长爪沙鼠群体的遗传状况。方法 应用生化基因位点遗传检测方法，测定初始和生物净化长爪沙鼠群体27个生化位点等位基因的分布。结果 2个长爪沙鼠群体均具有丰富的遗传多样性；生物净化群体与初始群体比较有17．86％的基因丢失率，但尚未出现明显的遗传分化现象（FST〈0．05）。结论 群体均偏离了哈迪-温伯格平衡（P〈0．05）。     

人原始生殖细胞分离培养的初步研究

[目的]探讨分离培养人原始生殖细胞的最佳条件。[方法]用胰蛋白酶消化5～9周人流组织中的人胚生殖嵴,获取人原始生殖细胞。以小鼠胚胎成纤维细胞作饲养层,在高糖DMEM培养基中添加10μmol/L福司克林(forskolin)和5～μg/L碱性成纤维细胞生长因子(bFGF)的培养液中培养、传代,并对子代细胞进行碱性磷酸酶活性检测和体外分化实验。[结果]原代培养时形成许多大小不等,形态各异的由人原始生殖细胞组成的集落,约5～7d传代。传代后,集落生长,变大。细胞培养到第七代,检测碱性磷酸酶染色为强阳性,体外分化实验有拟胚体形成。[结论]人原始生殖细胞可以用胰蛋白酶消化分离培养。用高糖DMEM培养基,添加forskolin和bFGF有利于人原始生殖细胞增殖。体外分化实验初步证实人原始生殖细胞具有多向分化潜能。     

Long-Term Comparison of Tacrolimus- and Cyclosporine-Induced Nephrotoxicity in Pediatric Heart-Transplant Recipients

Nephrotoxicity is an adverse effect of cyclosporine and tacrolimus. Studies comparing their long-term nephrotoxicities are lacking. This study evaluates the nephrotoxicity of these agents over a 7-year period following heart transplantation. Pediatric heart-transplant recipients receiving cyclosporine or tacrolimus as primary immunosuppression were evaluated at two centers from 1982 to 1998. Data collected included serum creatinine, height and weight prior to transplantation, at 1 and 6 months and 1 years post transplantation, and at yearly intervals thereafter. Creatinine clearance was calculated and compared between the two groups. Glomerular filtration rate was measured using Tc-99m diethylenetriaminepentacetic acid. In total, 123 patients were evaluated. Demographic data of the two groups were comparable. Creatinine clearance demonstrated a steady decline. This decline did not differ statistically between the two groups: tacrolimus 98.9 and 90.7mL/min/1.73 m2 at 1 month and 5 years, respectively; cyclosporine 110.7 and 81.7 mL/min/ 1.73 m2 at 1 month and 5 years, respectively. Four patients developed end-stage renal failure. Calculated creatinine clearance consistently overestimated glomerular filtration rate, the latter being greater than 2 standard deviations below the mean normal in 38% of patients. We conclude that the nephrotoxicities of tacrolimus and cyclosporine are comparable over the medium- to long-term in pediatric heart-transplant recipients.     

Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin

Hyaluronic acid (HA) is a naturally occurring polyanionic, polysaccharide that consists of N-acetyl-D-glucosamine and beta-glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock-absorbing role. The unique viscoelastic nature of HA along with its biocompatibility and non-immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, HA has been investigated as a drug delivery agent for various routes of administration, including ophthalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% HA gel, Solaraze, for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost-effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5-fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of HA together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.     

Heritability of psychosis in Alzheimer disease.

OBJECTIVE: The authors have previously demonstrated familial clustering of psychotic symptoms in late-onset Alzheimer disease (LOAD+P) and sought to estimate and explore the nature of the heritability of LOAD+P. METHODS: The heritability of LOAD+P, defined by single and multiple psychotic symptoms, was estimated with data from the National Institute of Mental Health AD Genetics Initiative. RESULTS: The estimated heritability for LOAD+P defined by multiple psychotic symptoms was 61%; for LOAD+P defined by any occurrence of psychotic symptoms, it was 30%. CONCLUSION: Multiplicity of symptoms may represent a useful means for defining a genetically determined LOAD+P phenotype.     

Chronic encapsulated mediastinal abscess presenting with remote cutaneous fistulization 12 years after redo aortic valve replacement for prosthetic valve endocarditis

Chronic encapsulated mediastinal abscess is an unusual complication of previous open heart surgery. We report on the case of a 79 year old male who presented with epigastric fistulization of an encapsulated anterior mediastinal abscess 12 years after a redo aortic valve replacement for prosthetic valve endocarditis. The encapsulated abscess and its complex branching tracts and the cutaneous fistula were excised completely except the thin longitudinal strip of the ascending aorta which formed part of the posterior wall of the infected tract. This was covered with transposed greater omentum based on right gastroepiploic artery pedicle. Patient remains fit and well 2 years after his operation.     

Heritability of fearful-anxious endophenotypes in infant rhesus macaques: a preliminary report.

BACKGROUND: Research efforts to discover the genetic underpinnings of anxiety and depression is challenging because of the etiologic heterogeneity inherent to these disorders. These efforts might be aided by the study of related behavioral phenotypes in model organisms, such as monkeys. METHODS: Eighty-five rhesus monkeys (Macaca mulatta) from the Oregon National Primate Research Center were drawn from a standard matriarchal colony and tested for behavioral response in four testing paradigms designed to elicit fearful-anxious reactions. Heritabilities were estimated using variance component-based quantitative genetic analyses with much of the genetic information arising from paternal half-sibs. RESULTS: Individual behaviors reflecting increased distress responses (e.g., vocalizations and teeth grinding) and behavioral inhibition (e.g., latency to leave mother, latency to inspect novel fruit) showed significant heritability, even though a small number of monkeys were assessed. Exploratory factor analyses identified seven clusters of behaviors across tests, some of which were found to be heritable. CONCLUSIONS: These results indicate that several specific fearful-anxious behaviors in infant rhesus monkeys are heritable within this colony. Accordingly, these phenotypes, which are believed to represent the genetic liability for anxiety and depression, are good candidates for further genetic investigation in this population.     

Bone-ingrowth hip prostheses in asymptomatic patients: radiographic features

The radiographic changes of 85 bone-ingrowth femoral prostheses in 77 asymptomatic patients were reviewed. The average postoperative follow-up time was 21.8 months. In decreasing order of frequency, the alterations included (a) remodeling of the proximal medial edge of the cut femoral neck (stress shielding) (98%), (b) linear lucency with a thin sclerotic margin at the prosthesis-bone interface (that may increase in width or length with time) (79%), (c) endosteal sclerosis at the prosthesis tip (36%), (d) heterotopic bone (24%), (e) cortical thickening at the tip of the prosthesis (12%), (f) prosthetic subsidence (7%), (g) intraoperative fracture (7%), and (h) periosteal reaction (4%). In this study, radiographic evidence of these findings was not associated with clinical failure. This is in distinction to the findings in cemented prostheses, in which many of these phenomena (especially the development of increasing width of the lucent line adjacent to the cement or prosthesis) have been associated with failure. Long-term investigations of porous-coated prostheses are necessary. Currently, however, an awareness of the radiographic alterations that occur with asymptomatic bone-ingrowth prostheses can prevent their misinterpretation as abnormal.