Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency

While the presence of a lipoyl-containing protein (protein X) separate from lipoyl transacetylase in the pyruvate dehydrogenase complex (PDC) has been known for some time, until recently only the cDNA for the yeast enzyme has been cloned. We have cloned, sequenced and characterized the cDNA encoding the human protein X and localized the protein X gene to chromosome 11p13. We also report here a new case of protein X deficiency identified immunologically, with decreased activity of PDC and without mutations in the E1alpha subunit or E1beta subunit. We report that the cDNA and gene of this patient for protein X has a homozygous 4 bp deletion, specifically in the putative mitochondrial targeting signal sequence which results in a premature stop codon. This is the first documented case of a molecular defect in pyruvate dehydrogenase protein X.      

Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease)

Vitelliform macular dystrophy (Best's disease) is an autosomal dominant, early-onset form of macular degeneration in which the primary defect is thought to occur at the level of the retinal pigment epithelium. Genetic linkage has mapped the disease locus to chromosome 11q12-q13.1 within a 980 kb interval flanked by markers at loci D11S4076 and uteroglobin. To identify the disease gene, we systematically characterized genes from within the critical region and analysed the coding regions for mutations in 12 patients from large multigeneration Best's disease families. Following this approach, we identified a novel gene of unknown function carrying heterozygous mutations in all 12 probands. Of these, 10 result in distinct missense mutations of amino acids that are highly conserved throughout evolution, spanning a phylogenetic distance from Caenorhabditis elegans to human, and include V9M, A10T, W24C, R25Q, R218Q, Y227N, Y227C, V235M, P297A and F305S. One deletion mutation, DeltaI295, was found in two families and segregates with the disease in both cases. Northern blot analysis reveals tissue-specific expression for this gene, exclusively in the retinal pigment epithelium. In conclusion, our data provide strong evidence that mutations in the gene that we have identified cause Best's disease.      

电脑终端视疲劳原因及防治

0引言 操作电脑终端(video display terminal, VDT)过久有时会头昏、头胀、颈和腰背酸痛、四肢酸麻、食欲减退、便秘和视疲劳,称为VDT综合征(video display terminal syndrome,VDTS)[1]. 因操作电脑而引起的视疲劳(眼干、胀、酸、痛、视力下降)在学校日益增多.现将70例电脑终端操作者出现的视疲劳眼部表现分析如下.     

Follow-up and management of serologically active clinically quiescent cases in pediatric systemic lupus erythematosus

ObjectivesOur aim is to identify the presence of serologically active clinically quiescent (SACQ) episodes in pediatric systemic lupus erythematosus (SLE) patients. We aim to identify serologic biomarkers associated with SACQ episodes and discuss risks and benefits of escalating treatments.Material and methodsWe evaluated 25 pediatric SLE patients, 13 of whom experienced SACQ episodes. Serologically active clinically quiescent was defined as two consecutive clinic visits without any clinical symptoms or clinical examination findings of a lupus flare with a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of zero, but either elevated anti-ds-DNA antibodies or low complement (C3 and/or C4) levels.ResultsAmong the 13 patients who experienced a SACQ episode, there were a total of 24 episodes, with each patient experiencing 1–4 SACQ episodes. Erythrocyte sedimentation rate (ESR) was the most commonly elevated laboratory marker in a SACQ episode, followed by low hemoglobin levels, and then elevated anti-dsDNA antibodies. Of the 17 episodes treated during a SACQ episode, 15 (88%) did not progress to a clinical flare within six months, while two did. Furthermore, of the 7 patients who were not treated during their SACQ episode, 2 (29%) continued to be SACQ without flare, whereas 5 led to a clinical flare within six months.ConclusionsSerologically active clinically quiescent episodes were identified in pediatric SLE patients, suggesting that the presence of SACQ is not limited to adults with SLE. Serologic markers such as increased ESR, hemoglobin, and elevated anti-dsDNA antibodies are preliminarily associated with pediatric SACQ episodes. Treating these SACQ episodes in pediatric SLE patients was less likely to lead to a clinical flare within six months when compared to not treating (p < 0.05). More research with a larger sample size is needed to define SACQ episodes, determine the prevalence in pediatric SLE patients, and establish SACQ treatment guidelines.     

Centre credentialing for Trans Tasman Radiation Oncology Group trial 06.02: multicentre feasibility study of accelerated partial breast irradiation

Introduction: Inconsistencies in contouring target volumes for partial breast irradiation (PBI) may result in geographical misses and compromise treatment outcomes. The present study aimed to (1) determine the variability of the target volumes contoured and treatment plans generated by participating centres in credentialing for participation in a multicentre PBI trial; and (2) assess dosimetric changes when standardized target volumes were used. Methods: The CT image sets of two de‐identified patients post‐breast conserving surgery were used. Contouring of the target volumes for the two cases was performed and a treatment plan as per protocol specifications was generated for each case by the seven participating centres. Planning of both cases was repeated by five centres using a set of standardized target volumes to evaluate resulting dosimetric changes in the treatment plans. Results: The surgical cavity, the part of the planning target volume used for dose evaluation and ipsilateral whole breast volumes contoured by the centres varied by 25%, 16% and 21% (1 standard deviation), respectively. The dosimetric variations found when the standardized target volumes were used were smaller than those noted when centre‐specific volumes were used. The volumes of the ipsilateral lungs receiving 30% of the prescribed dose and the volumes of the ipsilateral whole breasts receiving 95% and 50% of the prescribed dose were reduced in the treatment plans developed using the standardized target volumes. Conclusions: Given the impact of contouring on dose distributions, quality assurance procedures in clinical trials of PBI need to take into account both the technical approaches and the contouring.     

Gestational weight gain and risk of overweight in the offspring at age 7 y in a multicenter, multiethnic cohort study

BACKGROUND: The earliest determinants of obesity may operate during intrauterine life, and gestational weight gain may influence the intrauterine environment in a way that may affect the risk of overweight in the offspring. OBJECTIVE: The purpose of this study was to examine the association of gestational weight gain with offspring overweight. DESIGN: This was a retrospective cohort study of 10,226 participants from the Collaborative Perinatal Project (1959-1972). Anthropometric and sociodemographic variables were assessed during gestation, at birth, and at age 7 y. The association between gestational weight gain and offspring overweight at 7 y was examined after adjustment for important confounding factors. RESULTS: The odds of overweight in offspring at age 7 y increased by 3% for every 1 kg of gestational weight gain (adjusted odds ratio: 1.03; 95% CI: 1.02, 1.05). When gestational weight gain was examined using Institute of Medicine guidelines, the odds of overweight was 48% greater for children of mothers who gained more than the weight gain recommendations than for children of mothers who met the weight gain guidelines (adjusted OR: 1.48; 95% CI: 1.06, 2.06). The association remained significant after additional adjustment for birth weight. The association between gestational weight gain and overweight in the offspring was strongest for women who were underweight before pregnancy (P for interaction < 0.01). CONCLUSION: Helping pregnant women to meet the recommended weight gain during pregnancy may be an important and novel strategy for preventing pediatric obesity.     

呋喃二氢吡啶Ⅰ对离体兔心局部缺血的保护作用

呋喃二氢吡啶Ⅰ20μmol╱L能使离体兔心局部缺血心肌肌酸磷酸激酶(CPK)和α-羟丁酸脱氢酶(HBD)的释放量明显减少;冠脉阻力下降,流量增加;并能降低血浆及心肌中钙、钠含量,预防缺血性心律失常的发生。提示该药对离体兔心缺血心肌的保护作用,与降低缺血心肌细胞钙、钠含量有关。     

尼可地尔对缺血再灌注心肌线粒体功能的保护作用

近年来,许多资料表明,心肌缺血再灌注损伤与氧自由基有关,后者的主要细胞毒性反应是膜的脂质过氧化。尼可地尔(nicorandil,NICO)又名N-(2-羟乙基)硝酸烟酰胺,为烟酰胺与硝酸酯的结合物,是临床治疗心绞痛的新药。前文发现它对心肌缺血再灌注损伤有保护作用,其作用可能与抗脂质过氧化有关。本文用血液灌注离体兔心模型,观察缺血再灌注损伤时心肌线粒体呼吸功能的变化,及尼可地尔的保护作用。     

Physical activity before and after exercise in women with chronic fatigue syndrome

We measured physical activity after strenuous exercise in 20 women with chronic fatigue syndrome (CFS), compared to 20 sedentary healthy volunteers who exercised no more than once per week. Activity was measured for 2 weeks using a portable waist-worn vertical accelerometer. After the first week of activity monitoring, all participants returned for a maximal treadmill test, followed by continued activity monitoring for the second week. Five activity measures were derived from the data: (i) average activity; (ii) total activity; (iii) duration of waking day; (iv) duration; and (v) number of daily rests. A repeated measures ANCOVA was used to determine post- treadmill group differences accounting for pre-treadmill differences. There was a significant reduction in overall average activity after the treadmill test, with the greatest decrease on days 12 through 14. This reduction was accompanied by a significant increase in the duration of the waking day and number of daily rests. Thus, marked exertion does produce changes in activity, but later than self-report would suggest, and are apparently not so severe that CFS patients cannot compensate.      

三七中人参三醇甙抗心律失常作用的研究

三七三醇甙(PTS)为三七的组分之一,能明显对抗乌头碱、BaCl₂和肾上腺素诱发的实验性心律失常。PTS减慢大鼠心率,延长P-R和Q-Tc间期;减慢离体豚鼠右房自发频率;使异丙肾上腺素加速右房自发频率的量效-曲线右移并抑制最大效应。PTS与胺碘达隆作用相似,使离体豚鼠乳头状肌细胞电位APD和ERP显著延长,2相复极化斜率降低。PTS对上述动作电位的影响呈剂量依赖性关系。