The BCR gene recombines preferentially with Alu elements in complex BCR- ABL translocations of chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR- ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.      

吸入性急性氯气中毒71例

1临床资料1994-08/2004-07两次氯气泄漏事故造成吸入性急性氯气中毒123例,其中资料完整的71(男34,女37)例,年龄15～84(平均35.4)岁.临床表现有:鼻咽不适、流涕、喉中灼热、声哑、呛咳、咯痰、胸闷、气急、呼吸喘促及窒息窘迫感;眼酸流泪、睁眼困难;吞咽不畅、恶心呕吐、食欲不振;头晕、心悸、全身无力及睡眠不安;结膜充血、咽部红肿、呼吸增速和心跳加快.肺部可闻及一过性干罗音和一侧或双侧肺底湿鸣等.以急性中毒性呼吸炎症为主要表现57例,急性中毒性肺炎14例.WBC升高16例.患者肺部X线普遍透光性降低,肺纹理增粗增多模糊15例,肺底湿鸣患者肺野中下部偏外侧有斑片密度增高的模糊阴影14例.     

Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfusion and reperfusion in isolated rabbit hearts perfused with erythrocyte suspensions

Current therapy of myocardial infarction may include early reperfusion. We simulated myocardial perfusion conditions during evolving myocardial infarction in isolated, normothermic, isovolumic rabbit hearts perfused with buffer containing bovine red blood cells (hematocrit of 40%), and we assessed the effects of high levels of glucose and insulin as "therapy" during prolonged (150-minute) severe underperfusion and reperfusion. Protocol 1 consisted of underperfusion at a constant coronary perfusion pressure of 8 mm Hg. The control group (n = 8) received 5.5 mmol/l glucose and 15 microunits/ml insulin; the group treated with high levels of glucose and insulin (G + I) (n = 8) received 19.5 mmol/l glucose and 250 microunits/ml insulin during both underperfusion and reperfusion. Relative to the control group, the G + I group experienced 1) greater developed pressure during underperfusion and increased recovery during reperfusion, 2) preserved diastolic function during underperfusion and reperfusion, 3) lower coronary resistance and greater coronary flow during the underperfusion period, 4) increased glycolytic flux and preserved glycogen stores and high energy phosphate levels, and 5) less loss of myocyte enzymes (creatine kinase and alanine aminotransferase). In protocol 2, coronary flow was kept identical in control (n = 8) and G + I hearts (n = 8) during the underperfusion period, and left ventricular end-diastolic pressure was kept below 10 mm Hg in both groups to minimize subendocardial damage and vascular compression. In this protocol, the effect of the G + I intervention in the prevention of an increase in coronary resistance during the underperfusion period was distinguished from its myocellular metabolic effects; the high G + I substrate had protective effects on mechanical and metabolic function that were less marked than, but similar to, those in protocol 1, indicating that its mechanisms of protection during underperfusion affected both cardiac function and coronary resistance. We conclude that the G + I intervention, in clinically relevant concentrations, markedly protected severely underperfused myocardium for 150 minutes and may be a beneficial intervention in combination with reperfusion therapy in acute myocardial infarction.     

The association between health risk behaviors and sexual orientation among a school-based sample of adolescents

OBJECTIVE: This study is one of the first to examine the association between sexual orientation and health risk behaviors among a representative, school-based sample of adolescents. DESIGN: This study was conducted on an anonymous, representative sample of 4159 9th- to 12th-grade students in public high schools from Massachusetts' expanded Centers for Disease Control and Prevention 1995 Youth Risk Behavior Survey. Sexual orientation was determined by the following question: "Which of the following best describes you?" A total of 104 students self-identified as gay, lesbian, or bisexual (GLB), representing 2.5% of the overall population. Of GLB youth, 66.7% were male and 70% were white (not Hispanic). Health risk and problem behaviors were analyzed comparing GLB youth and their peers. Those variables found to be significantly associated with GLB youth were then analyzed by multiple logistic regression models. RESULTS: GLB youth were more likely than their peers to have been victimized and threatened and to have been engaged in a variety of risk behaviors including suicidal ideation and attempts, multiple substance use, and sexual risk behaviors. Four separate logistic regression models were constructed. Model I, Onset of Behaviors Before Age 13, showed use of cocaine before age 13 years as strongly associated with GLB orientation (odds ratio [OR]: 6.10; 95% confidence interval [CI] = 2.45-15.20). Early initiation of sexual intercourse (2.15; 10.6-4.38), marijuana use (1.98; 1.04-4.09), and alcohol use (1.82; 1.03-3.23) also was associated with GLB orientation. Model II, Lifetime Frequencies of Behaviors, showed that frequency of crack cocaine use (1.38; 1.06-1.79), inhalant use (1.30; 1.05-1.61), and number of sexual partners (1.27; 1.06-1.43) was associated with GLB orientation. Model III, Frequency of Recent Behaviors, showed smokeless tobacco use in the past 30 days (1.38; 1. 20-1.59) and number of sexual partners in the previous 3 months (1. 47; 1.31-1.65) were associated with GLB orientation. Model IV, Frequency of Behaviors at School, showed having one's property stolen or deliberately damaged (1.23; 1.08-1.40) and using marijuana (1.29; 1.05-1.59) and smokeless tobacco (1.53; 1.30-1.81) were associated with GLB orientation. Overall, GLB respondents engaged disproportionately in multiple risk behaviors, reporting an increased mean number of risk behaviors (mean = 6.81 +/- 4.49) compared with the overall student population (mean = 3.45 +/- 3.15). CONCLUSION: GLB youth who self-identify during high school report disproportionate risk for a variety of health risk and problem behaviors, including suicide, victimization, sexual risk behaviors, and multiple substance use. In addition, these youth are more likely to report engaging in multiple risk behaviors and initiating risk behaviors at an earlier age than are their peers. These findings suggest that educational efforts, prevention programs, and health services must be designed to address the unique needs of GLB youth.     

电针丰隆及足三里穴对非酒精性脂肪性肝炎大鼠的干预效应

目的:近年来,中医药在防治非酒精性脂肪性肝病方面显示了优势和发展前景。观察电针丰隆、足三里对非酒精性脂肪性肝炎大鼠模型血脂、肝功及肝组织形态学的影响。方法:实验于2003-11/2004-05在广州中医药大学实验动物中心及暨南大学医学院病理生理教研室、中心实验室完成。实验材料:选择SPF级SD大鼠30只,由广州中医药大学实验动物中心提供,雌雄各半,体质量(200±20)g,按随机数字表法分为正常对照组、模型组和电针组,每组10只。实验方法:正常对照组喂养基础饲料,其他两组喂养高脂高糖饲料。高脂高糖饮食造模第3天开始对电针组大鼠进行电针丰隆、足三里干预。10周后测定大鼠血脂四项、肝功能三项,光镜、电镜下行肝组织形态学观察。实验过程中对动物处置符合动物伦理学标准。结果:30只大鼠均进入结果分析。①模型组大鼠低密度脂蛋白胆固醇、总胆固醇均较正常对照组升高(P<0.01)。电针组大鼠血清胆固醇、低密度脂蛋白胆固醇、总胆红素、丙氨酸氨基转移酶含量均较模型组下降(P<0.01,P<0.05)。②模型组大鼠肝细胞增大,胞浆内脂肪滴大小不一,呈中重度脂肪变性,且100%存在汇管区炎症和小叶内炎症,未发现碎屑样坏死,大多出现灶性纤维增生,但其中2只出现桥接坏死;与模型组比较,电针组脂肪变性程度和炎症活动度均明显减轻(P<0.01,P<0.05),但仍有2只出现桥接坏死。③模型组大鼠肝细胞内出现大量脂肪滴,可见散在糖原颗粒,线粒体肿胀,嵴排列紊乱,内织网肿胀。电针组肝细胞内均可见多少不等的脂肪滴,其超微结构改变介于模型组和正常对照组之间。结论:①电针具有保护肝细胞、减轻炎症反应、改善肝功能作用。②血脂和血清酶学检查结果与肝组织病理形态学检测结果并不完全一致,检测肝组织活检更有意义。。     

Giving birth and returning to work: the impact of work-family conflict on women's health after childbirth

PURPOSE: Since 1970, women of childbearing age have increasingly participated in the workforce. However, literature on work-family conflict has not specifically addressed the health of postpartum women. This study examined the relationship between work-family conflict and mental and physical health of employed mothers 11 weeks after childbirth. METHODS: Employed women, 18 years and older, were recruited while in the hospital for childbirth (N = 817; 71% response rate). Mental and physical health at 11 weeks postpartum was measured using SF-12 version 2. General linear models estimated the associations between the independent variables and health. A priori causal models and directed acyclic graphs guided selection of confounding variables. RESULTS: Analyses revealed that high levels of work interference with family were associated with significantly lower mental health scores. Medium and high levels of family interference with work revealed a dose-response relationship resulting in significantly worse mental health scores. Coworker support was strongly and positively associated with better physical health. CONCLUSIONS: Work-family conflict was negatively associated with mental health but not significantly associated with physical health. Availability of social support may relieve the burden women can experience when balancing work roles and family obligations.     

Specificity of the helper T cell for the cytolytic T lymphocyte response to influenza viruses

We have described a model system in which helper T cells are required to mount a primary antiviral cytolytic T lymphocyte response. The radioresistant helper cell can be found in the spleens of mice that have been immunized subcutaneously with influenza viruses 6-8 d previously. These helper cells appear to be type specific but cross-reactive among the subtypes of influenza A viruses. The phenotypes of the interacting cell populations were determined.     

Anti-i causing acute hemolysis following a negative immediate-spin crossmatch

A unique case of acute hemolysis following transfusion of red cells (RBCs) that were found compatible by immediate-spin (IS) crossmatch technique is reported. Screening tests for unexpected antibodies, using low-ionic-strength saline (LISS), 10 minutes' incubation at 37 degrees C, and anti-IgG, were nonreactive; however, 1 transfused unit was found crossmatch incompatible by indirect antiglobulin technique (IAT). An anti-i (titer 512 at 4 degrees C) that was not an autoantibody was identified in the patient's serum. Unlike the incriminated donor RBCs, most I+ RBCs did not react by LISS-IAT. Variable reactivity was seen with ficin-treated I+ RBCs, and there was marked hemolysis of iadult and icord RBCs. In marked contrast, dominant Lu(a-b-) RBCs, with reduced expression of i, did not react by any test method; nor did autologous I+, Lu(b+) RBCs. The in vivo clinical significance of this anti-i was confirmed by monocyte monolayer assay and RBC survival studies. The patient's i antigen may have been altered, by either chemotherapy or disease, and lacked part of the i antigen-mosaic. Her antibody was directed at epitopes of i that were absent from her RBCs. Those i epitopes missing from her RBCs are also absent on dominant Lu(a-b-) RBCs. This anti-i represents a unique cause of an acute hemolytic transfusion reaction. It also represents a case of acute immune-mediated hemolysis following transfusion of IS crossmatch-compatible blood when screening tests for unexpected antibodies are nonreactive. Because of the rarity of such cases (less than 1/200,000 RBC units transfused), modifications to pretransfusion testing protocols are not proposed.