Molecular genetic analysis of autosomal dominant cerebellar ataxia with retinal degeneration (ADCA type II) caused by CAG triplet repeat expansion

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCAII) was previously mapped by linkage analysis studies to chromosome 3p12- p21.1 (SCA7). Positional cloning efforts have recently identified a novel gene, SCA7 , containing a translated CAG repeat, expanded in SCA7 patients. We cloned the SCA7 gene from a yeast artificial chromosome (YAC) clone contig spanning the SCA7 candidate region. Using a combination of genomic sequencing and cosmid-based exon trapping, two expressed sequence tags were identified. Sequencing of the corresponding cDNA clones and RT-PCR analysis identified the full- length SCA7 cDNA. Together, our sequence data defined the intron/exon boundaries of the first two coding exons of the SCA7 gene, with the first exon containing the expanded CAG repeat. Further, sequence comparison with the published SCA7 cDNA identified one additional putative exon in the 5'-UTR region of the SCA7 gene. The SCA7 gene was mapped on the YAC contig in the 2.5 cM interval between D3S1600 and D3S1287. In one extended Belgian SCA7 pedigree the expanded alleles ranged from 38 to at least 55 repeats with allele lengths being inversely correlated with onset age of ADCAII symptoms. The SCA7 repeats increased in length in successive generations. Normal alleles had from four to 18 repeats, with 10 repeats being the most common allele.      

真核表达人呼吸道合胞病毒F蛋白的纯化方法

目的 真核表达人呼吸道合胞病毒(human respiratory syncytial virus,SV)融合蛋白(fusion protein,),并完成蛋白纯化及纯度测定.方法 根据编码F蛋白的基因序列设计引物,CR方法扩增出3'端带His标签的F基因序列,克隆入pGEM-T-easy载体,经核酸序列分析后,进一步克隆到pcDNA3.1( )真核表达载体,限制性内切酶鉴定,用脂质体Lipofectamine2000转染COS-7细胞,2 h后再用Westem blot检测目的蛋白的表达.Ni柱亲和层析纯化COS-7细胞表达的F蛋白,高效毛细管电泳分析纯化后蛋白纯度.结果 核酸序列分析证实获得带His标签的RSV F基因序列,没有发生无义突变.转染COS-7细胞后,利用Western blot方法检测到F蛋白的特异性条带,纯度达99%以上.结论 初步建立了真核表达RSV F蛋白的纯化方法,为进一步优化RSV F蛋白制备条件及单克隆抗体及诊断试剂等研究奠定了基础.     

How reorganizing a general medicine clinic affected residents' and patients' satisfaction

The authors examined how satisfied patients and residents were before and after the restructuring of the general medicine clinic at a large urban teaching hospital in 1985; the change to a longitudinal care clinic was made to provide greater continuity of care, more consistent access of residents to attending physicians, and a more structured educational curriculum. Questionnaires to assess satisfaction were administered three weeks before and ten months after the change to all 80 of the second- and third-year residents. A convenience sample of 310 patients seen during a two-week period before the change and another such sample of 267 patients seen during a two-week period ten months after the change comprised the patients who completed a patients' satisfaction questionnaire. The residents were significantly more satisfied with the quality of care, functioning, and educational value of the new longitudinal care clinic. Their average overall rating of satisfaction (on a scale where 1 = completely dissatisfied and 5 = completely satisfied) increased from 2.3 to 3.7 (p less than .001). Unexpectedly, the patients were "very satisfied" with both clinic models and their overall ratings changed little (4.5 before, 4.4 after). In addition, the patients' and residents' before-and-after perceptions of the quality of care delivered in the clinic differed substantially. These findings show that the longitudinal care clinic significantly enhanced the satisfaction of the residents but not of the patients. Furthermore, the data suggest that results from standardized patients' satisfaction surveys may not accurately assess the quality of care being delivered.     

激素治疗增加绝经后健康妇女尿失禁的发病率和严重程度

问题：在绝经后健康妇女中，激素治疗（hormone therapy，HT）对尿失禁（urinary incontinence，UI）的效果如何？     

Biopsy in a patient with PMP22 exon 2 mutation recapitulates pathology of Trembler-J mouse

We describe a patient with a longstanding history of hypertrophic neuropathy of Dejerine–Sottas type, ultimately diagnosed with CMT1E disease due to a new p.Leu18Arg missense mutation in the first transmembrane domain of the PMP22 gene. The patient never walked independently and was wheelchair bound by age 18 years. Her parents and son were unaffected. Her peroneal muscular atrophy syndrome presented with scoliosis, bilateral hearing loss, pes planus, distal sensory loss and generalized areflexia. A nerve biopsy at age 26 years showed nerve hypertrophy, myelin uncompaction, defects in mesaxon formation, Schwann cells with irregular outline, axons incompletely surrounded by Schwann cell processes and very short internodes interspersed with denuded axons. Large, mostly denervated, onion bulb formations were also prominent. These findings indicate that demyelination continues undeterred in the advanced stages of the disease and is followed by remyelination attempts that recapitulate the early defects in Schwann cell/axon interaction seen in the Trembler-J mouse, which carries a mutation in the same transmembrane domain.     

Maintenance of resting energy expenditure after weight loss in premenopausal women: potential benefits of a high-protein, reduced-calorie diet

The number of contemporary diet plans promoting high protein intakes for weight management has increased dramatically. Complementing this dietary approach with increased physical activity has proven to be beneficial. Recent studies have suggested that protein intakes in excess of the current Recommended Dietary Allowance (0.8 g/kg) may be of metabolic benefit during weight loss. This investigation assessed changes in resting energy expenditure and substrate oxidation in overweight and obese premenopausal women in response to a weight loss intervention that combined a high-protein, reduced-calorie diet with increased physical activity. Thirty-nine overweight and obese premenopausal women (age, 30.9 +/- 1.5 years; body mass index, 30.2 +/- 0.5 kg/m2) participated in a 10-week weight loss program in which they ate a reduced-calorie diet for which protein provided 30% of total energy and approximated 1.4 g/kg. Subjects incrementally increased physical activity (ie, steps walking) throughout the diet intervention period. Resting energy expenditure, substrate oxidation, and body composition were assessed before (PRE) and after (POST) the 10-week weight loss program. Subjects experienced a 5% decrease in body weight, with significant decreases in both fat mass (PRE, 35.5 +/- 1.2 kg; POST, 32.4 +/- 1.1 kg; P < .0001) and fat-free mass (PRE, 44.6 +/- 0.7 kg; POST, 43.6 +/- 0.7 kg; P < .0001). Changes in body weight or body composition did not alter resting energy expenditure. Protein oxidation increased (PRE, 18% +/- 1%; POST, 20% +/- 1%; P < .05) and fat oxidation decreased (PRE, 37% +/- 3%; POST, 30% +/- 3%; P < .05) after the 10-week intervention. These findings illustrate that a weight loss intervention combining consumption of a high-protein, reduced-calorie diet with increased physical activity promotes weight loss without negatively impacting resting energy expenditure in this population of women.     

High intake of cholesterol results in less atherogenic low-density lipoprotein particles in men and women independent of response classification

The influence of a high-cholesterol diet on the atherogenicity of the low-density lipoprotein (LDL) particle was examined by measuring LDL peak diameter and composition, LDL susceptibility to oxidation, and the distribution of cholesterol between LDL subclasses. The crossover intervention randomly assigned 27 premenopausal women and 25 men (18 to 50 years) to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) diet for 30 days, followed by a 3-week washout period. Subjects were classified as either hyperresponders (>2.5 mg/dL increase in plasma cholesterol for each 100 mg additional dietary cholesterol consumed) or hyporesponders to dietary cholesterol. Sex was found to have a significant effect on 3 of the parameters examined. LDL peak diameter was significantly larger (P <.005) in females (26.78 +/- 0.59 nm, n = 27) as compared with males (26.52 +/- 0.49 nm, n = 25), regardless of response to dietary cholesterol. The LDL particles of the male participants also had a higher number of triglyceride (TG) and cholesteryl ester (CE) molecules (P <.01); however, cholesterol ester transfer protein (CETP) activity was higher in females (P <.05). Response classification also revealed significant differences in the determination of LDL subclasses. Independent of sex, the LDL-1 particle (P <.05), which is considered to be less atherogenic, was predominant in hyperresponders and this finding was associated with increased cholesterol intake (interactive effect, P <.001). In addition, CETP and lecithin: cholesterol acyltransferase (LCAT) activities were higher in hyperresponders during the egg period (interactive effect, P <.05). Sex, response to cholesterol intake, and diet were not found to affect the susceptibility of LDL to oxidation (P > 0.5). Because LDL peak diameter was not decreased and the larger LDL-1 subclass was greater in hyperresponders following egg intake, these data indicate that the consumption of a high-cholesterol diet does not negatively influence the atherogenicity of the LDL particle.     

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges

BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2^nd generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation.     

上皮样血管瘤16例临床与病理分析

 目的:探讨上皮样血管瘤（EH）的临床及组织病理学特征。 方法:回顾性分析16例已确诊患者的临床及病理资料,并对相关文献进行综述。 结果:16例患者中女8例,男8例;平均年龄（45.44±12.52）岁;病程3个月~20年;皮损主要表现为红色至暗红色丘疹、结节,可伴瘙痒和糜烂,好发于头皮、耳部,其中发生在头部10例、耳部5例、外阴1例;皮损单发者5例,多发者11例。皮损组织病理学检查均具有典型的血管增生,管壁增厚,内皮细胞呈上皮样突向管腔,管周大量淋巴细胞及嗜酸性粒细胞浸润。结论：上皮样血管瘤少见,诊断需要临床与病理密切结合。加强对该病的认识,可避免误诊误治。