肥胖可能与病毒感染有关

随着生活水平的提高,肥胖已呈现为全球性问题.当今已将肥胖与艾滋病、癌症并称为21世纪威胁人类健康的三大疾病.而其中肥胖症则是人类健康的最大威胁.当前人们普遍认为肥胖是由于遗传、过食、运动不足、代谢异常、内分泌异常、脑疾患等因素引起.但是这些均不能完满地解释肥胖的成因.为此,美国科学家Dhurandhar等提出了一种新的解释.他们认为,肥胖可能与病毒感染有关[1].并已研究发现了第1株可引起动物肥胖的人腺病毒血清36型(adenouirus Ad-36),这是迄今所发现的第1株与肥胖有关的人腺病毒[2].证据表明,该病毒感染在动物肥胖发病中起着重要作用[2~5].是否能导致人类肥胖尚不得而知.但是,有关肥胖的病毒发现使肥胖成因的研究有了新的思考,为人类进一步了解肥胖问题的根源,以及肥胖的防治开辟了新的领域,展现出新的希望.至于病毒导致动物肥胖的具体机理以及人类肥胖是否与病毒感染有关至今尚不明确,有待深入研究.     

Possible Novel Therapy for Malignant Gliomas with Secretable Trimeric TRAIL

Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL) and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL) delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI). Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas.     

膜联蛋白A2与恶性肿瘤发展进程的关系

膜联蛋白A2 (annexin A2, ANXA2)是一种钙离子介导的磷脂结合特性的蛋白质, 属于膜联蛋白家族成员, 广泛分布于胞核、胞浆及细胞质膜外表面.它主要表达在人体内皮细胞、单核/巨噬细胞、骨髓细胞和某些肿瘤细胞中.ANXA2在细胞内参与膜形成、膜转运、胞吞、胞吐、细胞增殖、信号转导、分化及凋亡等一系列重要的生命过程.近年来的研究表明其表达水平在肿瘤组织中有显著变化, 并与肿瘤的发生、发展、浸润及转移密切相关.现着重就ANXA2与肿瘤发展、浸润、转移等进程的相关研究进展进行综述.     

Antiarrhythmic Agents and the Risk of Malignant Neoplasm of Liver and Intrahepatic Bile Ducts

BackgroundThe objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD).MethodsWe used the research database of the Taiwan National Health Insurance Program to conduct a population-based, case-control study. We identified 9944 patients with antiarrhythmic history who were first diagnosed as having MNLIHD between 2005 and 2010. We identified an additional 19,497 patients with antiarrhythmic history in the same period who did not develop MNLIHD and were frequency-matched using age, sex, and index year to form a control group. Five commercially available antiarrhythmic agents, amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed.ResultsThe adjusted odds ratio (OR) of MNLIHD was 1.60 (95% confidence interval [CI], 1.45–1.77) for amiodarone users versus nonamiodarone users. In subgroup analysis, amiodarone use was significantly associated with an increased risk of MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7–20.5) for patients with comorbidities compared to an OR of 2.43 (95% CI, 1.92–3.06) for those without comorbidities. After adjustment for age, sex, statins, anti-diabetes medications, non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with annual mean defined daily doses of ≤30, 31–145, and >145, respectively.ConclusionsThe results of the present study indicated that amiodarone might be associated with the development of MNLIHD in a dose-dependent manner, particularly among patients with comorbidities.     

Possible Association of APOE Genotype with Working Memory in Young Adults

Background

Possession of the ε4 allele of the Apolipoprotein E (APOE) gene is associated with an increased risk of Alzheimer’s disease. Early adult life effects of ε4 are less well understood. Working memory has been relatively little studied (compared to episodic memory) in relation to APOE genotype despite its importance in cognitive functioning. Our hypothesis was that ε4 would lead to an impairment in working memory in young adults.

Methods

We studied working memory using a computerised n-back task in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18. Data was available for 1049–1927 participants and for the 2- and 3-back versions of the task. Using multiple and multi-level regression controlling for important confounders we examined the association between APOE genotype on accuracy and reaction times.

Results

There was no evidence of a genotype effect on accuracy when the two difficulty levels were examined separately. There was some evidence to support a deleterious effect of the ε4 allele on n-back accuracy in the multi-level regression. There was weak evidence that the ε22 group were less accurate but the numbers were very low in this group. The ε34 group had faster reaction times than the reference ε33 group in all adjusted analyses but the ε44 group were only faster in the 3-back condition in multi-level analyses.

Conclusions

There was no evidence of benefit in ε4 carriers, but there was some evidence of a detrimental effect on working memory in this large study.     

卵巢恶性肿瘤患者血清CA72-4和SIL-2R水平的检测及其临床意义

目的:探讨良、恶性卵巢肿瘤患者血清中SIL-2R和卵巢癌相关抗原CA72-4的临床应用价值.方法:采用酶联免疫吸附测定法检测正常对照组,卵巢肿瘤良、恶性患者组的血清CA72-4及SIL-2R的值,观测其在恶性卵巢肿瘤诊断中的敏感性.结果:在恶性卵巢肿瘤患者中,CA72-4及SIL-2R的值均显著高于良性卵巢肿瘤组及正常对照组,两者联合检测恶性卵巢肿瘤的敏感性为83.3%.结论:血清CA72-4及SIL-2R的联合检测在恶性卵巢肿瘤的诊断及预后判断方面有较好的临床应用价值.     

Association of Increased Circulating Catecholamine and Glucocorticoid Levels with Risk of Psychological Problems in Oral Neoplasm Patients

Background

Noradrenergic pathways and glucocorticoid-mediated signal pathways have been implicated in the growth and progression of oral cancer. Patients with oral neoplasms can have high psychological distress levels, but the effects of stress-related hormones on oral neoplasm growth are unknown.

Methods

We have investigated the relationships between pre-surgical measurements of psychological problems with Symptom Checklist-90-revised Inventory (SCL90-R), tumor histology, circulating blood catecholamine and glucocorticoid levels among 75 oral neoplasm patients, including 40 oral cancer patients and 35 benign oral tumor patients.

Results

The results showed that most dimension scores of SCL90-R did not show a significant difference between the two groups except depression (p = 0.0201) and obsessive-compulsion (p = 0.0093), with the scores for these symptoms being higher among oral cancer group versus the benign oral tumor group. The differences of total score, average score and other monomial factor scores were not statistically significant. The mean concentrations of catecholamine and glucocorticoid in peripheral blood of the oral cancer group were higher than those in benign oral tumor group (p<0.01). We also examined whether associations observed between biobehavioral measures and circulating blood catecholamine and glucocorticoid levels extended to other compartments in the oral cancer group.

Conclusions

These findings suggest that stress hormones may affect oral cancer behavior by influencing the tumor micro-environment though the circulating blood.     

Possible Association of GroES and Antigen 85 Proteins with Heat Resistance of Mycobacterium paratuberculosis

Conflicting reports on the heat resistance of Mycobacterium paratuberculosis prompted an examination of the effect of culture medium on this property of the organism. M. paratuberculosis was cultured in three types of media (fatty acid-containing medium 7H9-OADC (oleic acid-albumin-dextrose-catalase supplement) and glycerol-containing media WR-GD and 7H9-GD [glycerol-dextrose supplement]) at pH 6.0. M. paratuberculosis grown under these three culture conditions was then tested for heat resistance in distilled water at 65°C. Soluble proteins and mycolic acids of M. paratuberculosis were evaluated by two-dimensional electrophoresis (2-DE) and thin-layer chromatography (TLC), respectively. The type of culture medium used significantly affected the heat resistance of M. paratuberculosis. The decimal reduction times at 65°C (D_65°C values; times required to reduce the concentration of bacteria by a factor of 10 at 65°C) for M. paratuberculosis strains grown in 7H9-OADC were significantly higher than those for the organisms grown in WR-GD medium (P < 0.01). When the glycerol-dextrose supplement of WR was substituted for the fatty acid supplement (OADC) in 7H9 medium (resulting in 7H9-GD), the D_65°C value was significantly lower than that for the organism grown in 7H9-OADC medium (P = 0.022) but higher than that when it was cultured in WR-GD medium (P = 0.005). Proteomic analysis by 2-DE of soluble proteins extracted from M. paratuberculosis grown without heat stress in the three media (7H9-OADC, 7H9-GD, and WR-GD) revealed that seven proteins were more highly expressed in 7H9-OADC medium than in the other two media. When the seven proteins were subjected to matrix-assisted laser desorption ionization-mass spectrometric analysis, four of the seven protein spots were unidentifiable. The other three proteins were identified as GroES heat shock protein, alpha antigen, and antigen 85 complex B (Ag85B; fibronectin-binding protein). These proteins may be associated with the heat resistance of M. paratuberculosis. Alpha antigen and Ag85B are both trehalose mycolyltransferases involved in mycobacterial cell wall assembly. TLC revealed that 7H9-OADC medium supported production of more trehalose dimycolates and cell wall-bound mycolic acids than did WR-GD medium. The present study shows that in vitro culture conditions significantly affect heat resistance, cell wall synthesis, and protein expression of M. paratuberculosis and emphasize the importance of culture conditions on in vitro and ex vivo studies to estimate heat resistance.     

The L-Phase of Erwinia carotovora var. atroseptica and its Possible Association with Plant Tissue

S ummary . The growth and recognition of the L-phase of Erwinia carotovora var. atroseptica in vitro and in vivo is described. Evidence is offered for its existence in nature. It is postulated that the bacterium may be present in the potato plant in such a form, closely associated with the plant tissue cells, and as such may be the means of transmitting the disease from one plant to another without the disease being apparent. Under certain circumstances, as yet undetermined, changes in the environment may lead to the reversion of the L-phase to the bacterial phase with the consequent development of the characteristic disease syndrome.     

Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors.To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia.Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2–3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14).Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52–95.28).These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.     

Association between Malignant Disease in Children and Maternal Virus Infections

The possibility of an association between virus infections during pregnancy and subsequent malignant disease in the child has been investigated using retrospective data from the Oxford Survey of Childhood Cancers. Such an association appears to exist for influenza, chickenpox, and possibly rubella. For influenza and rubella the estimated risk is small; the data do not permit an estimate to be made directly in the case of chickenpox. It is suggested that there may be a specific association between maternal chickenpox and tumours of the nervous system.It is important to emphasize that, even if the relative risk associated with these viruses is fairly large, the number of cases of childhood cancer and leukaemia actually attributable to them is probably very small.