Activation-induced cytidine deaminase induces DNA break repair events more frequently in the Ig switch region than other sites in the mammalian genome

Activation-induced cytidine deaminase (AID) produces DNA breaks in immunoglobulin genes during antibody diversification. Double-stranded breaks (DSB) in the switch region mediate class switch recombination, and contribute to gene conversion and somatic hypermutation in the variable regions. However, the relative extent to which AID induces DSB in these regions or between these and other actively expressed sequences is unknown. Here, we exploited an enhancer-trap plasmid that identifies DSB in actively expressed loci to investigate the frequency and position of AID-induced vector integration events in mouse hybridoma cells. Compared to control cells, wild-type AID stimulates plasmid integration into the genome by as much as 29-fold. Southern and digestion-circularization PCR analysis revealed non-uniformity in the integration sites, with biases of 30- and 116-fold for the immunoglobulin kappa light chain and mu heavy chain genes, respectively. Further, within the immunoglobulin mu gene, 73% of vector integrations map to the mu switch region, an enhancement of five- and 12-fold compared to the adjacent heavy chain variable and mu gene constant regions, respectively. Thus, among potential highly transcribed genes in mouse hybridoma cells, the immunoglobulin heavy and light chain genes are important AID targets, with the immunoglobulin mu switch region being preferred compared to other genomic sites.     

Current understandings and perspectives on non-cancer health effects of benzene: A global concern

Objective

Benzene, as a volatile organic compound, is known as one of the main air pollutants in the environment. The aim of this review is to summarize all available evidences on non-cancerous health effects of benzene providing an overview of possible association of exposure to benzene with human chronic diseases, specially, in those regions of the world where benzene concentration is being poorly monitored.

Methodology

A bibliographic search of scientific databases including PubMed, Google Scholar, and Scirus was conducted with key words of “benzene toxic health effects”, “environmental volatile organic compounds”, “diabetes mellitus and environmental pollutants”, “breast cancer and environmental pollution”, “prevalence of lung cancer”, and “diabetes prevalence”. More than 300 peer reviewed papers were examined. Experimental and epidemiologic studies reporting health effects of benzene and volatile organic compounds were included in the study.

Results

Epidemiologic and experimental studies suggest that benzene exposure can lead to numerous non-cancerous health effects associated with functional aberration of vital systems in the body like reproductive, immune, nervous, endocrine, cardiovascular, and respiratory.

Conclusion

Chronic diseases have become a health burden of global dimension with special emphasis in regions with poor monitoring over contents of benzene in petrochemicals. Benzene is a well known carcinogen of blood and its components, but the concern of benzene exposure is more than carcinogenicity of blood components and should be evaluated in both epidemiologic and experimental studies. Aspect of interactions and mechanism of toxicity in relation to human general health problems especially endocrine disturbances with particular reference to diabetes, breast and lung cancers should be followed up.     

血清谷氨酰转肽酶、碱性磷酸酶、腺苷脱氨酶联合糖类抗原 CA19-9在黄疸鉴别中的意义

目的：探讨血清谷氨酰转肽酶（ GGT）、碱性磷酸酶（ ALP）、腺苷脱氨酶（ ADA）、糖类抗原CA19-9升高程度在黄疸类型鉴别中的价值。方法选取本院2011年1月-2013年10月收治的黄疸患者614例,根据黄疸类型将614位患者分为肝细胞性黄疸组和梗阻性黄疸组,后者又分为良性梗阻性黄疸和恶性梗阻性黄疸两组,分析 GGT、ALP、ADA、CA19-9水平在各组间分布差异。结果 GGT、ALP 值在梗阻性黄疸组中较肝细胞性黄疸组高,差异有统计学意义（P ＜0.05）;ADA 值在肝细胞性黄疸组较对照组与梗阻性黄疸组增高,差异有统计学意义（P＜0.05）;GGT、ALP、CA19-9值在恶性梗阻性黄疸组中较良性梗阻性黄疸组高,差异有统计学意义（ P ＜0.05）。结论 GGT、ALP 显著升高,而 ADA 无明显升高的黄疸考虑梗阻性黄疸;GGT、ALP 轻中度升高,而 ADA 显著升高的黄疸考虑肝细胞性性黄疸;GGT、ALP、CA19-9均显著升高者考虑恶性梗阻性黄疸。     

高三尖杉酯碱联合阿糖胞苷治疗老年急性髓系白血病的效果

目的 分析高三尖杉酯碱联合阿糖胞苷治疗老年急性髓系白血病的临床效果.方法 将本院收治的42例急性髓系白血病患者随机分为观察组21例和对照组21例,对照组采用柔红霉素＋阿糖胞苷联合化疗,观察组采用高三尖杉酯碱＋阿糖胞苷联合化疗,评价两组的临床疗效、不良反应发生率、3年内复发率、3年内累计生存率及中位生存时间.结果 观察组的总有效率为85.71％,高于对照组的66.67％,差异有统计学意义（P＜0.05）.观察组的Ⅲ～Ⅳ级感染、Ⅲ～Ⅳ级出血、肝肾毒性发生率低于对照组,差异有统计学意义（P＜0.05）.观察组的3年内复发率低于对照组,3年内累计生存率高于对照组,中位生存时间长于对照组,差异有统计学意义（P＜0.05）.结论 高三尖杉酯碱联合阿糖胞苷治疗老年急性髓系白血病能有效提高临床效果,降低药物毒副反应,并提高患者的远期疗效,值得临床推广应用.     

A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

胞嘧啶转氨酶基因联合5-氟胞嘧啶对喉癌细胞的抑制作用

目的 研究腺病毒载体（Ad）介导的胞嘧啶转氨酶（CD）基因转移联合5-氟胞嘧啶（5-FC）对喉鳞状细胞癌（简称喉癌）细胞株Hep-2的体外作用.方法 将构建的含CD基因的重组腺病毒载体在293细胞中扩增,体外感染喉癌细胞株Hep-2,并给予不同浓度前药5-FC进行肿瘤细胞体外杀伤效果观察.结果 用制备的Ad-CD液感染Hep-2细胞,加入不同浓度的前药5-FC,肿瘤细胞生长受到不同程度的抑制.结论 Ad介导的CD基因转染效果强,可直接杀伤喉癌细胞Hep-2.     

Livedo racemosa in neurological diseases: an update on the differential diagnoses

Livedo is a net‐like violaceous skin pattern. It can be classified as physiological or pathological. The physiological livedo reticularis usually appears in cold conditions, whereas the pathological and irregular livedo, which persists in warm temperatures, is often labeled as ‘livedo racemosa’. Some neurological pathologies are associated with livedo, most commonly those with an inflammatory component or those derived from systemic disorders. The present review summarizes the most important central and peripheral neurological diseases in pediatric and adult age groups associated with livedo, providing physicians with an overview of the clinical presentation, etiology, diagnosis and management of these conditions.     

阿糖胞苷分别联合拓扑替康及阿克拉霉素双诱导治疗难治性急性单核细胞白血病疗效观察

目的：探讨阿糖胞苷分别联合拓扑替康及阿克拉霉素双诱导治疗复发难治性急性单核细胞白血病疗效。方法14例病人先用“AA”方案（阿克拉霉素20～40mgdl-3,阿糖胞苷150—200mg d1-5）诱导治疗．诱导化疗结束后10d,无论血象、骨髓是否恢复而强行实施第二疗程化疗。采用“TA”方案（拓扑替康2mgd1-5,阿糖胞苷10（hng／m2,d1-5）化疗。结果：14例患者中6例1次双诱导即获CR,2例PR,CR率为42．86％。总有效率57．14％。结论：阿糖胞苷分别联合阿克拉霉素及拓扑替康双诱导治疗复发难治性急性单核细胞白血病疗效明显。     

Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

Deficiency of adenosine deaminase 2; special focus on central nervous system imaging

Purpose

To increase the knowledge of central nervous system (CNS) imaging features in deficiency of adenosine deaminase 2 (DADA2) by examining magnetic resonance imaging (MRI) studies of a relatively large number of patients.