Genomewide linkage scan of resting blood pressure: HERITAGE Family Study. Health,Risk Factors,Exercise Training,and Genetics

The purpose of this study was to search for genomic regions influencing resting systolic (SBP) and diastolic (DBP) blood pressure (BP) in sedentary families (baseline), and for resting BP responses (changes) resulting from a 20-week exercise training intervention (post-training-baseline) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. A genome-wide scan was conducted on 317 black individuals from 114 families and 519 white individuals from 99 families using a multipoint variance-components linkage model and a panel of 509 markers. Promising results were primarily, but not exclusively, found in the black families. Linkage evidence (P<0.0023) with baseline BP replicated other studies within a 1-logarithm of odds (LOD) interval on 2p14, 3p26.3, and 12q21.33, and provided new evidence on 3q28, 11q21, and 19p12. Results for several known hypertension genes were less compelling. For response BP, results were not very strong, although markers on 13q11 were mildly suggestive (P<0.01). In conclusion, these HERITAGE data, in conjunction with results from previous genomewide scans, provide a basis for planning future investigations. The major areas warranting further study involve fine mapping to narrow down 3 regions on 2q, 3p, and 12q that may contain "novel" hypertension genes, additional typing of some biological candidate genes to determine whether they are the sources of these and other signals, multilocus investigations to understand how and to what extent some of these candidates may interact, and multivariate studies to characterize any pleiotropy.     

Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study

We studied the effects of 20 weeks of supervised cycle-ergometer exercise on plasma lipids in 675 healthy, sedentary, normolipidemic white and black men and women aged 17 to 65 years, participating in the HERITAGE Family Study. Fasting plasma lipids were assessed twice at baseline and 24 and 72 hours after the last exercise session and adjusted for plasma volume changes. No significant differences from the mean baseline levels were observed for total, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B (Apo B). A significant reduction (P < .01) from baseline levels in plasma total and VLDL triglycerides was observed only in the 24-hour posttraining specimens, reflecting a response to the last bout of exercise. High-density lipoprotein (HDL) cholesterol increased 3.6% for the combined group, primarily due to an increase in HDL2, with an associated increase in Apo A-1 (P < .001). No significant differences were noted in the HDL response by sex, race, or age. An inverse correlation (r = -.241) was observed between the increase in HDL cholesterol and change in body fat only in men, and the increase in HDL cholesterol was unrelated to the change in maximal oxygen uptake (VO2max).     

PPARγ配体对高糖诱导大鼠腹膜间皮细胞结缔组织生长因子和纤溶酶原激活抑制因子1表达的影响

目的 研究过氧化物酶体增殖物活化受体γ（PPARγ）天然配体15d-PGJ2及人工合成配体吡格列酮（pioglitazone）对高糖诱导大鼠腹膜间皮细胞（RPMC）表达结缔组织生长因子（CTGF）和纤溶酶原激活抑制因子1（PAI-1）的影响。 方法 胰蛋白酶消化法分离培养RPMC,经鉴定分组：（1）0.1%、1.5%、2.5%、4.25%葡萄糖作用24 h组;（2）2.5%葡萄糖作用0、6、12、24、36、48、72 h组 ;（3）0.1%、1.5%、2.5%、4.25%甘露醇作用24 h组;（4）15d-PGJ2（5、15 μmol/L）及吡格列酮（5、15 μmol/L）分别预孵育2 h,加2.5%葡萄糖再作用24 h。RT-PCR检测CTGF和PAI-1 mRNA表达;Western印迹检测PPARγ、CTGF及PAI-1 蛋白表达。 结果 正常RPMC有PPARγ表达。1.5%葡萄糖使RPMC的PPARγ蛋白表达减少（P < 0.05）,而4.25%葡萄糖作用最大（P < 0.01）;2.5%葡萄糖作用6 h,RPMC的PPARγ蛋白表达减少（P < 0.05）,而72 h达高峰（P < 0.01）。各种浓度的甘露醇作用24 h,RPMC的PPARγ蛋白表达均无明显变化（P > 0.05）。2.5%葡萄糖作用后RPMC的CTGF和PAI-1 mRNA和蛋白表达均显著增加（P < 0.01）。5 μmol/L的吡格列酮显著降低CTGF和PAI-1 mRNA和蛋白表达（均P < 0.05）,而15 μmol/L作用更强（P < 0.01）。5 μmol/L的15d-PGJ2显著降低RPMC的CTGF mRNA和蛋白表达以及PAI-1 mRNA的表达（均P < 0.05）,但不影响PAI-1蛋白表达（P > 0.05）,15 μmol/L的15d-PGJ2对CTGF和PAI-1 mRNA和蛋白表达均有抑制作用（P < 0.05或P < 0.01）。 结论 葡萄糖以时间和剂量依赖方式调节RPMC PPARγ的表达,其作用与高渗透浓度无关。PPARγ配体可显著抑制高糖诱导的CTGF和PAI-1 的表达,提示激活PPARγ可能成为防治腹膜透析相关腹膜纤维化的新途径之一。     

Bronchoscopy in severe childhood asthma: Irresponsible or irreplaceable?

For children with severe asthma, guideline‐based management focuses on the escalation of anti‐inflammatory and bronchodilatory medications while addressing comorbid conditions. Bronchoscopy, in this context, has been relegated to ruling out asthma mimickers. More recently, however, there have been questions surrounding the clinical utility of bronchoscopy in severe childhood asthma. In this solicited lecture summary, we discuss the past, present, and potential future applications of bronchoscopy in severe childhood asthma.     

Detection of Chlamydia in the peripheral blood cells of normal donors using in vitro culture, immunofluorescence microscopy and flow cytometry techniques

Background

In May 2003 the Soest County Health Department was informed of an unusually large number of patients hospitalized with atypical pneumonia.

Methods

In exploratory interviews patients mentioned having visited a farmers' market where a sheep had lambed. Serologic testing confirmed the diagnosis of Q fever. We asked local health departments in Germany to identiy notified Q fever patients who had visited the farmers market. To investigate risk factors for infection we conducted a case control study (cases were Q fever patients, controls were randomly selected Soest citizens) and a cohort study among vendors at the market. The sheep exhibited at the market, the herd from which it originated as well as sheep from herds held in the vicinity of Soest were tested for Coxiella burnetii (C. burnetii).

Results

A total of 299 reported Q fever cases was linked to this outbreak. The mean incubation period was 21 days, with an interquartile range of 16–24 days. The case control study identified close proximity to and stopping for at least a few seconds at the sheep's pen as significant risk factors. Vendors within approximately 6 meters of the sheep's pen were at increased risk for disease compared to those located farther away. Wind played no significant role. The clinical attack rate of adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies.

Conclusion

Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3^rd trimester and to test animals in petting zoos regularly for C. burnetii.     

酪氨酸相关肽的合成及抗孕酮生成活性

利用固相法合成了二十个含羟基氨基酸的小肽。其中,以0.5mol·L^-1二甲二氯硅烷/1.5mol·L^-1苯酚/DCM*为脱除Boc试剂,以TFMSA为切除树脂试剂。经C-18反相柱纯化后,全部产物均通过氨基酸分析要求。体外黄体细胞分泌孕酮实验表明有八个肽化物GlyTyrAlaLys,(SarSer)₂Lys及其申酯,TyrLys,HisTyr-NH₂,ThrProTyrLys-NH₂,TyrThrProArgLys,AspHisProThr-PheLys显示较强的抑制hCG致孕酮分泌的活性,而且前三个肽还能显著抑制基础孕酮的分泌,相反,GlySerTyr能刺激基础孕酮的分泌。目前尚未建立合理的结构一活性关系。     

Effect of regular exercise on homocysteine concentrations: the HERITAGE Family Study

We investigated whether regular aerobic exercise could affect plasma total homocysteine (tHcy), and whether there were sex-related or racial differences in tHcy changes. Data were available for 816 black and white men and women, aged 17–65 years, 711 of whom completed a 20 week aerobic exercise training program. The tHcy concentration was measured in frozen plasma samples by an HPLC method. In Blacks, tHcy did not change with exercise training [men −0.5 (SD 3.7) μmol/l, women 0.0 (2.2) μmol/l) but increased significantly in Whites (men +0.3 (1.7) μmol/l, women +0.2 (1.6) μmol/l). No sex-related differences were found in either racial group. Changes in tHcy correlated negatively with baseline homocysteine (r = −0.40, P < 0.0001). Homocysteine levels of the “High” (hyperhomocysteinemia) (≥15 μmol/l) group (n = 30) decreased significantly with regular aerobic exercise from 23.1 (12.1) to 19.6 (7.6) μmol/l. Homocysteine levels of the “Normal” group increased slightly from 8.2 ± 2.2 to 8.5 ± 2.4 μmol/l. Men exhibit racial differences for tHcy responses to exercise training. Regular aerobic exercise has favorable effects on individuals with hyperhomocysteinemia, but tHcy slightly increased in individuals within the normal range.     

Fitness alters the associations of BMI and waist circumference with total and abdominal fat

OBJECTIVE: We tested the following hypotheses in black and white men and women: 1) for a given BMI or waist circumference (WC), individuals with moderate cardiorespiratory fitness (CRF) have lower amounts of total fat mass and abdominal subcutaneous and visceral fat compared with individuals with low CRF; and 2) exercise training is associated with significant reductions in total adiposity and abdominal fat independent of changes in BMI or WC. RESEARCH METHODS AND PROCEDURES: The sample included 366 sedentary male (111 blacks and 255 whites) and 462 sedentary female (203 blacks and 259 whites) participants in the HERITAGE Family Study. The relationships between BMI and WC with total fat mass (determined by underwater weighing) and abdominal subcutaneous and visceral fat (determined by computed tomography) were compared in subjects with low (lower 50%) and moderate (upper 50%) CRF. The effects of a 20-week aerobic exercise training program on changes in these adiposity variables were examined in 86% of the subjects. RESULTS: Individuals with moderate CRF had lower levels of total fat mass and abdominal subcutaneous and visceral fat than individuals with low CRF for a given BMI or WC value. The 20-week aerobic exercise program was associated with significant reductions in total adiposity and abdominal fat, even after controlling for reductions in BMI and WC. With few exceptions, these observations were true for both men and women and blacks and whites. DISCUSSION: These findings suggest that a reduction in total adiposity and abdominal fat may be a means by which CRF attenuates the health risk attributable to obesity as determined by BMI and WC.