Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses

Cytokines and their receptors represent key targets for therapeutic intervention. Ligands are being used to supplement cell numbers that become depleted as a result of disease (organ failure, infection) or subsequent disease treatments (i.e. chemotherapy). Conversely, the inhibition of target cell binding by cytokines is an established strategy for abrogating pathologic cellular activities common to many immunological diseases. Considerable effort in biomedical research is being focused on the cytokine families that play a dominant role in regulating immunity and then prioritizing each member for its therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is widely recognized for its central involvement in controlling lymphocyte function and is the most explored for medical utility. Collectively, these proteins (or their antagonists) are either marketed drugs or have received advanced testing for an impressive array of indications including cancer, infectious disease, transplantation, inflammation and allergic asthma. Here we review the current understanding of IL-21, the most recent member of this cytokine family to be discovered. As will be discussed, IL-21 shares many of the same attributes as its relatives in that it has broad immunoregulatory activity and can modulate both humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour responses in mice defines one therapeutic indication that merits clinical development.     

T cell reactivity in neonates from an East and a West German city--results of the LISA study

BACKGROUND: Within an ongoing birth cohort study (LISA) the cytokine production of cord blood T cells was compared between neonates from Leipzig (East Germany) and Munich (West Germany). The aim of this study was to analyse regional differences and influencing factors of the immune status. METHODS: Cytokine production was measured in a randomly selected subgroup of 158 children from the LISA (Life style - Immune system - Allergy) cohort by intracellular cytokine staining. Information on family "atopy" history (FAH) and home characteristics was obtained from questionnaires. RESULTS: Reduced numbers of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) producing T cells were found in association with biparental FAH and housing renovation during pregnancy. In addition, cytokine production was influenced by season. In Munich, the frequency of biparental FAH and of renovation measures during pregnancy was significantly higher as compared to Leipzig. Neonates from Munich showed significantly decreased amounts of IFN-gamma and TNF-alpha and elevated levels of interleukin-4 (IL-4) producing T cells. Differences in cytokine production between Munich and Leipzig were influenced by season (IL-4) and housing renovation (IFN-gamma, TNF-alpha). CONCLUSIONS: Since differences in the T cell cytokine production of neonates in Munich and Leipzig are independent from FAH our findings may provide evidence for the impact of environmental factors upon the fetal immune system.     

Comprehensive Assessment of Pain in Juvenile Rheumatoid Arthritis: An Empirical Model

A comprehensive assessment model of variables hypothesized toinfluence pediatric pain perception was empirically investigatedin 23 families who had a child with juvenile rheumatoid arthritis.To determine the effects of family environment, child psychologicaladjustment, and disease parameters on child pain perception,a developmentally appropriate model was developed. Childrenbetween the ages of 5 and 15 were found to be reliable judgesof their pain intensity. Several family environmental and childpsychological factors were found to interact with specific diseaseparameters in determining pediatric pain perception and report.A multidimensional age-appropriate assessment model is suggestedfor use in the further examination of pediatric chronic andrecurrent pain.     

Accumulation of atopic disorders within families: a sibling effect only in the offspring of atopic fathers

BACKGROUND: Several studies have reported an association between a child's risk of atopic disorders and family size. However, the inverse association might not be the same in populations with a different genetic disposition for atopic disorders. OBJECTIVE: This longitudinal study was designed to assess risk factors of atopy. METHODS: Lifetime prevalence of asthma, hay fever and eczema of 1440 families including 3165 offspring was ascertained by means of standardized questionnaires. RESULTS: After possible confounders had been controlled for, an inverse association between atopic disorders and the number of older siblings was found only in the offspring of atopic fathers (trend for older siblings: chi2 = 13.38, degrees of freedom [d.f.] = 1, P= 0.0002; odds ratio 'no older sibling'= 2.87 (95% confidence interval 2.18-3.78); '1 older sibling' = 2.11 [1.52-2.92], '2 older siblings' = 1.29 [0.74-2.23]; '3 or more older siblings' = 0. 15 [0.02-0.981). No such relationship was found for children without a history of paternal atopy (trend for older siblings: chi2 = 1.5 1, d.f. = 1, P = 0.22; odds ratio 'no older sibling' = 1 [reference]; '1 older sibling' =0.82 [0.63-1.06]; '2 older siblings' = 0.97 [0.67-1.40]; '3 or more older siblings' = 0.64 [0.31-1.33]). The trend for older siblings in the case of paternal atopy was significantly different from the trend for older siblings without a history of paternal atopy (chi2 = 8.68, d.f. = 1, P = 0.003). The number of younger siblings was not related to child's risk of atopy (trend for younger siblings: chi2 = 0.001, d.f. = 1, P = 0.97). CONCLUSIONS: Data from this study suggest a protective effect of sibship size only in children with a history of paternal atopy and if older siblings are present. The reason for this combined effect remains unclear. Thus, further investigations are needed to interpret the biological cause of the so called 'sibling effect'.     

Routine mortality monitoring for detecting mass murder in UK general practice: test of effectiveness using modelling.

BACKGROUND: The Shipman Inquiry recommended mortality rate monitoring if it could be 'shown to be workable' in detecting a future mass murderer in general practice. AIM: To examine the effectiveness of cumulative sum (CUSUM) charts, cross-sectional Shewhart charts, and exponentially-weighted, moving-average control charts in mortality monitoring at practice level. DESIGN OF STUDY: Analysis of Scottish routine general practice data combined with estimation of control chart effectiveness in detecting a 'murderer' in a simulated dataset. METHOD: Practice stability was calculated from routine data to determine feasible lengths of monitoring. A simulated dataset of 405,000 'patients' was created, registered with 75 'practices' whose underlying mortality rates varied with the same distribution as case-mix-adjusted mortality in all Scottish practices. The sensitivity of each chart to detect five and 10 excess deaths was examined in repeated simulations. The sensitivity of control charts to excess deaths in simulated data, and the number of alarm signals when control charts were applied to routine data were estimated. RESULTS: Practice instability limited the length of monitoring and modelling was consequently restricted to a 3-year period. Monitoring mortality over 3 years, CUSUM charts were most sensitive but only reliably achieved >50% successful detection for 10 excess deaths per year and generated multiple false alarms (>15%). CONCLUSION: At best, mortality monitoring can act as a backstop to detect a particularly prolific serial killer when other means of detection have failed. Policy should focus on changes likely to improve detection of individual murders, such as reform of death certification and the coroner system.     

TCRVβ基因谱系分析在AIDS疾病T细胞克隆性研究中的应用

对于T淋巴细胞TCRVB基因家族以及T细胞的克隆性的研究是近年的热点问题.通过对艾滋病人(模型)的TCRVβ基因谱系分析,测定特定CDR3长度及序列出现的频率能反映T细胞克隆扩增的程度和功能状态,进而有助于对MDS的临床诊断、免疫机制、药物或疫苗的治疗效果等的理解.     

Heredity in personality disorders — an overview

The concept of personality disorders is based on deviant personality traits in both the DSM-III-R and ICD-10 classifications. A diagnosis of personality disorder can be made reliably with structured interviews. Many individuals are diagnosed with more than one personality disorder, and other mental disorders are often found at the same time. Among the 11 personality disorders in DSM-III-R, only the schizotypal, borderline, and antisocial have been examined to any considerable extent for gene effects. The problems of studying heredity are here demonstrated for borderline and antisocial personality disorders. Recommendations are given as to strategies for further study of heredity in personality disorders.     

行为问题儿童的生活质量及其影响因素调查

目的:探讨行为问题儿童的生活质量及影响因素.方法:采用Conners量表和儿少主观生活质量问卷调查2087例少年儿童的行为问题和生活质量,然后将问题儿童与正常儿童的结果做比较.结果:行为问题儿童的生活质量明显低于正常儿童,相关分析显示儿少主观生活质量问卷与Conners量表父母问卷和教师评定量表的部分因子存在不同程度的相关.逐步回归显示儿童的学业、行为问题、家庭经济、父亲性格、年龄、父母对不良行为的处理方式、独生共7个变量影响着儿童的生活质量.结论:行为问题儿童生活质量下降,需要得到学校、家庭、同伴、社会等多方面的关怀帮助.     

The risk for congenital heart defects in offspring of individuals with congenital heart defects

BACKGROUND: Congenital heart defects (CHDs) occur in approximately 1% of all live births. Although most CHDs are of unknown etiology, a family history of CHDs is a known risk factor, and offspring of individuals with CHDs are at a higher risk of having CHDs. The aim of this study was to investigate the relative risk for CHDs to offspring of individuals with CHDs. METHODS: The prevalence rates of CHDs in offspring of 203 individuals with CHDs and 282 individuals without CHDs were investigated. The study participants completed a questionnaire that included information on medical and reproductive history, lifestyle indicators, and family history of CHDs and other congenital malformations. The prevalence rates of CHDs in offspring were calculated. RESULTS: The prevalence of CHDs was 3.1% (18/575) in offspring of individuals with CHDs and 1.3% (8/589) in offspring of individuals without CHDs. The adjusted odds ratio for CHDs to offspring of parents with CHDs was 1.73 (95% confidence interval [95% CI] 0.89-2.44, p=0.02). The estimated relative risk for offspring to females with CHD was higher than for males [2.3 (95% CI 1.1-4.7, p=0.03) versus 1.31 (95% CI 0.48-4.30, p=0.66), respectively]. There was no suggestion of association between CHDs and maternal smoking, alcohol consumption, and use of medication during pregnancy. CONCLUSIONS: Offspring of parents with CHDs are at a higher risk for CHDs compared with the general population. Couples where one member is affected with CHD should receive pre-conceptional or pre-natal genetic counseling and should be informed about the magnitude of the potential risk of CHDs to the offspring.