Establishment of T cell lines to bovine beta-casein and beta-casein-derived epitopes in patients with type 1 diabetes

Enhanced cellular immune response to bovine beta-casein has been reported in patients with type 1 diabetes. In this study we aimed to establish beta-casein-specific T cell lines from newly diagnosed type 1 diabetic patients and to characterise these cell lines in terms of phenotype and epitope specificity. Furthermore, since sequence homologies exist between beta-casein and putative beta-cell autoantigens, reactivity to the latter was also investigated. T cell lines were generated from the peripheral blood of nine recent onset type 1 diabetic patients with different HLA-DQ and -DR genotypes, after stimulation with antigen pulsed autologous irradiated antigen presenting cells (APCs) and recombinant human interleukin-2 (rhIL-2). T cell line reactivity was evaluated in response to bovine beta-casein, to 18 overlapping peptides encompassing the whole sequence of beta-casein and to beta-cell antigens, including the human insulinoma cell line, CM, and a peptide from the beta-cell glucose transporter, GLUT-2. T cell lines specific to beta-casein could not be isolated from HLA-matched and -unmatched control subjects. beta-Casein T cell lines reacted to different sequences of the protein, however a higher frequency of T cell reactivity was observed towards the C-terminal portion (peptides B05-14, and B05-17 in 5/9 and 4/9 T cell lines respectively). Furthermore, we found that 1 out of 9 beta-casein-specific T cell lines reacted also to the homologous peptide from GLUT-2, and that 3 out of 4 of tested cell lines reacted also to extracts of the human insulinoma cell line, CM. We conclude that T cell lines specific to bovine beta-casein can be isolated from the peripheral blood of patients with type 1 diabetes; these cell lines react with multiple and different sequences of the protein particularly towards the C-terminal portion. In addition, reactivity of beta-casein T cell lines to human insulinoma extracts and GLUT-2 peptide was detected, suggesting that the potential cross-reactivity with beta-cell antigens deserves further investigation.     

激光治疗瘢痕的特征

目的:介绍国内近20年来激光治疗瘢痕的临床研究概况,以期进一步了解激光治疗瘢痕的新进展。资料来源:应用计算机检索Pubmed和中国生物医学文献数据库1983/2006的相关文章,限定文章语言种类为英文和中文,检索词为“cicatrices(瘢痕),laser(激光)”。资料选择:对资料进行初审,选择临床试验研究文献查找全文。纳入标准:①有明确诊断标准。②随机对照实验或对照试验。有无随访,是否采用盲法不限制。③治疗组干预措施为激光或激光联合药物;对照组干预措施为曲安奈德、冷冻联合曲安奈德或不采用药物措施。排除标准:①非对照研究。②治疗组或对照组的干预措施不符合纳入标准。③机制研究。④重复研究。资料提炼:共收集到相关文献120篇,按上述标准纳入31篇,其余文献均被排除。资料综合:31篇文章中11篇为随机对照研究,10篇为对照研究,各研究的研究期为1～6个月。各研究所纳入的病例数量为10～50例。其中6个研究对比了激光与传统药物治疗瘢痕的疗效及安全性,2个研究进行了激光治疗瘢痕基础研究机制比较,10个研究观察了激光结合与单纯药物或单纯激光对瘢痕的疗效,4个研究比较了激光联合西药治疗瘢痕的疗效,2个研究观察了激光治疗瘢痕的副作用。7篇介绍国内或国外瘢痕治疗的研究情况。结论:激光治疗瘢痕的疗效可靠,具有副作用少,方法简单,安全性高,易被患者接受等优势。但由于激光治疗瘢痕还存在着一定的局限性,今后还需要在激光的穿透深度方面研究。     

Mice overexpressing the mitochondrial phospholipid hydroperoxide glutathione peroxidase in male germ cells show abnormal spermatogenesis and reduced fertility

To investigate the physiological effects of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mPHGPx) overexpression during early male germ cell differentiation, we have generated transgenic mice bearing the rat mPhgpx coding sequence driven by the mouse synaptonemal complex protein 1 promoter, allowing the transgene to be specifically activated in the testis from the zygotene to diplotene stages of the first meiotic division. Northern/Western blotting and immunocytochemical analyses of endogenous mPHGPx expression during spermatogenesis showed a low enzyme level in middle-late pachytene spermatocytes, but not in earlier meiotic stages, and a significant increase in mPHGPx content in round spermatids. The histological and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis of transgenic testes revealed a number of spermatogenetic defects, including primary spermatocyte apoptosis, haploid cell loss, and seminiferous epithelium disorganization. In line with these features, adult transgenic male mice also displayed a reduction in fertility. Results obtained in this study suggest that mPHGPx expression is tightly regulated in pachytene spermatocytes, with any spatial-temporal increase in mPHGPx expression resulting in damage to spermatogenesis and eventual loss of haploid cells. Present findings in the mouse may be of interest to human male fertility.     

The quality of life of Palestinians living in chronic conflict: assessment and determinants

This study assessed the quality of life (QoL) of Palestinians living in conditions of chronic conflict and examined its determinants. An adapted World Health Organization quality of life (WHOQoL-Bref) instrument was used in a representative sample of 1,008 adults. Factor analysis and multiple regression were conducted to determine associations between demographic and socioeconomic characteristics and scores of extracted principal determinants, and estimated overall and domain-specific QoL scores. Men, older persons and those less educated reported lower QoL than their counterparts. Negative associations were also found with higher distress and fear levels, and lower financial and freedom status. The chronic and entrenched conflict over generations resulted in lower QoL for the population of the Occupied Palestinian Territory.

Smoking and alcohol use during pregnancy affects preterm infants'' docosahexaenoic acid (DHA) status

This study investigated the effect of alcohol consumption and smoking during pregnancy on the fatty acid composition of the infants. A total of 40 very-low-birth-weight (VLBW) infants, weighing between 750 and 1500 g, were enrolled in the study after being hospitalized and ventilated for respiratory distress syndrome (RDS). Maternal and infant demographic information was recorded. Questions regarding maternal smoking (none, < 10 and > or = 10 cigarettes/d) and alcohol consumption (none, occasionally, moderate and severe) were recorded. Erythrocyte membrane (EMB; n = 40) total fatty acid analyses were performed at birth (baseline) and on days 14 and 28 postnatally. During pregnancy, 42% of mothers consumed alcohol and 50% smoked. At birth, infants of mothers who smoked and consumed alcohol during pregnancy, had significantly higher blood docosahexaenoic acid (DHA; p < 0.05) than infants of mothers who abstained from both alcohol and smoking. The consequences of this finding remain unknown.     

Chromosome rearrangements in normal fibroblasts from xeroderma pigmentosum homozygotes and heterozygotes

Chromosome analysis was carried out in cultured fibroblasts from unaffected skin of five unrelated xeroderma pigmentosum (XP) patients and nine family members. Structural chromosome changes were observed in cultures from all examined individuals. Furthermore, in one XPD patient and in one XPC patient and his parents, cytogenetically abnormal clones were detected. Some of these clones were present starting from the primary explant. This cytogenetic pattern is similar to that observed in an XPC patient previously studied by us. The analysis of breakpoint distribution from clonal and non-clonal chromosome rearrangements showed that some breakpoints were more frequent and common to different families or to different family members although definite evidence of preferential involvement of chromosome bands was not obtained. This investigation indicates that there is a consistent tendency toward chromosome instability in XP mutation carriers. The instability could be related to the multiple chromosome anomalies characterizing skin tumors in XP subjects.     

Defective Calcium Increase and Inositol Phosphate Production in Anti-CD3-Stimulated Lymphocytes of Alcoholics without Progressive Liver Disease

Intracellular free calcium concentration, phosphoinositide turnover, and inositol phosphate production were analyzed in peripheral blood lymphocytes from seven well-nourished alcoholic patients without severe acute or chronic liver disease, before and after stimulation with anti-CD₃ antibody. Seven comparable nondrinkers were studied as controls. A lower increase in intracellular free calcium concentration was detected in alcoholics, after anti-CD₃ stimulation of lymphocytes, than in control subjects. Lymphocyte activation generated inositol phosphates in both controls and alcoholics, but inositol phosphate production was significantly lower in alcoholics. The agreement between these findings indicates that the reduction in inositol phosphates is one of the most important events in the early phases of lymphocyte activation in alcoholics.