Evidence for localisation of a Theileria parasite AT hook DNA-binding protein to the nucleus of immortalised bovine host cells.

Immortalisation of bovine leukocytes by the macroschizont stage of the tick transmitted protozoan parasite, Theileria annulata, results in the clonal expansion of infected cells and dissemination throughout the bovine host. The parasite-encoded factors which induce this unique transformation event have not been defined to date. In this study, a gene family (TashAT) has been characterised that encodes polypeptides with homology to known DNA-binding proteins. Expression of TashAT genes occurs at the intracellular macroschizont stage of the parasite life cycle and during differentiation to the merozoite, negative regulation of TashAT genes is detected early relative to other macroschizont genes. Interestingly, the early reduction in TashAT expression coincides with the initial decrease in host cell proliferation. One member of the family, TashAT2, was characterised in detail and the predicted polypeptide sequence was found to harbor three AT hook DNA-binding domains. Antisera generated against two distinct regions of TashAT2 both located the antigen to the host cell nucleus and, combined with protein translation inhibition and immunoprecipitation studies, provide evidence that this polypeptide could be transported from the parasite to this location. Further evidence for this postulation was provided by transfection studies which demonstrated that TashAT2 does encode the structural information required for localisation to the nucleus of a mammalian cell. Thus, TashAT2 is a potential candidate for a parasite-encoded factor that modulates host cell gene expression and may be involved in the control of host cell proliferation.     

Dundee step test: a simple method of measuring the blood pressure response to exercise.

The exercise systolic blood pressure (BP) response provides prognostic information over and above that of resting clinic BP in both normotensive and hypertensive individuals. We have developed a 3-min step test as a method of measuring the exercise systolic BP. Healthy volunteers and patients referred for assessment of hypertension took part in validating this exercise test. We assessed the reproducibility of the exercise systolic BP response, and this was compared with that obtained using the cycle ergometry at an equivalent workload. We also compared the baseline characteristics, BP profiles and exercise systolic BP responses in different subject groups. The intra-observer coefficient of variation assessed in 25 subjects was 5.9% with a mean difference of 1.8 mm Hg. The values for between observer were 8.3% and 2.5 mm Hg respectively. Exercise systolic BP measured with the step test correlated with that of cycle ergometer (n = 37, r = 0.93, P < 0.01). Exercise systolic BP data from healthy volunteers (n = 107) showed a normal distribution. An exercise systolic BP of >/=180 mm Hg was greater than 2 standard deviations from the mean and was taken as an abnormally high BP during exercise. There was a positive correlation between exercise BP and increasing age in healthy volunteers (r = 0.57, P < 0.01). This was also present in hypertensive subjects (n = 46, r = 0.48, P = 0.001), however the slope of this relationship was twice as steep as in the normal subjects. Hypertensive subjects with high exercise systolic BP had significantly higher clinic BP, ABPM and a greater BP rise during exercise. The Dundee step test is quick, reproducible and may be prognostically useful.     

抑制差减杂交筛选严重烫伤大鼠免疫细胞差异基因

目的 探索严重烧伤早期免疫细胞基因表达变化与烧伤后免疫功能紊乱的关系。方法 分离严重烫伤F344雌性大鼠的外周血免疫细胞并提取mRNA，以烫伤前为对照进行抑制差减杂交筛选差异表达基因，将差异基因克隆后测序，与Genbank进行同源性比较。结果 分离的免疫细胞经检测基本为单核细胞及淋巴细胞，抑制差减杂交得到多个位于200－400bp的条带，将它们克隆到pGEM-T质粒载体，构建了差异表达基因库。随机测序20个克隆，得到的基因与烧伤后机体改变相符，部分新基因序列在Genbank登录。结论 严重烧伤早期外周血免疫细胞的基因表达就有改变。构建了F344雌性大鼠的差异表达基因库，从中检出的部分基因可能对严重烧伤后的免疫功能紊乱有诱发作用。     

A community-based study of cigarette smoking behavior in relation to variation in three genes involved in dopamine metabolism: Catechol-O-methyltransferase (COMT), dopamine beta-hydroxylase (DBH) and monoamine oxidase-A (MAO-A)

OBJECTIVE: Cigarette smoking behavior may be influenced by catechol-O-methlyltransferase (COMT), dopamine beta-hydroxylase (DBH), and monamine oxidase-A (MAO-A), genes that play roles in dopamine metabolism. The association between common polymorphisms of these genes and smoking behavior was assessed among 10,059 Caucasian volunteers in Washington County, MD in 1989. METHODS: Age-adjusted logistic regression was used to measure the association between variants of these single nucleotide polymorphisms and smoking initiation and persistent smoking. RESULTS: Overall, no association was seen between each genotype and smoking behavior. However, among younger (<54 years) women, the COMT GG genotype was positively associated with smoking initiation (OR=1.3; 95% CI: 1.0 1.5), and the MAO-A TT genotype was inversely associated with persistent smoking (OR=0.7; 95% CI: 0.4, 1.0). Men who smoked fewer than 10 cigarettes per day were more likely to be persistent smokers if they had the COMT GG (OR=1.7; 95% CI: 1.0, 2.9) or the DBH GG (OR=1.6; 95% CI: 1.0, 2.5) genotypes. CONCLUSION: Overall the results of this large community-based study do not provide evidence to support the presence of important associations between variants of COMT, DBH, or MAO-A and smoking initiation or persistent smoking.     

彩色多普勒超声评价肾外肾动静脉瘘所致复杂血流动力学改变

目的 应用彩色多普勒超声主人肾外肾动静肪 所致血流动力学改变。方法 采用Ｇａｔｅｗａｙ ＦＸ彩色多普勒超声仪进行检查,对腹部受累血管进行观察、测量和分析,并与ＤＳＡ和手术结果进行对照。结果 彩超能够显示肾外肾动静脉瘘的瘘口和血流动力学改变,受累脏器的缺血性改变,以及心脏的结构和功能的改变。结论 彩超可较好地评价发生于腹部大血管的动静脉瘘的血流动力学改变,并很好地与动脉瘤、囊性病变和管道扩张等进行鉴     

Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial

CONTEXT: In patients with primary hypothyroidism, anecdotal evidence suggests that well-being is optimized by fine adjustment of T(4) dosage, aiming for a serum TSH concentration in the lower reference range. This has not been tested in a clinical trial. OBJECTIVE: Our objective was to test whether adjustment of T(4) dosage aiming for a serum TSH concentration less than 2 mU/liter improves well-being compared with a serum TSH concentration in the upper reference range. DESIGN: We conducted a double-blind, randomized clinical trial with a crossover design. PARTICIPANTS: Fifty-six subjects (52 females) with primary hypothyroidism taking T(4) (>/=100 microg/d) with baseline serum TSH 0.1-4.8 mU/liter participated. INTERVENTIONS: Each subject received three T(4) doses (low, middle, and high in 25-microg increments) in random order. OUTCOME MEASURES: Outcome measures included visual analog scales assessing well-being (the primary endpoint) and hypothyroid symptoms, quality of life instruments (General Health Questionnaire 28, Short Form 36, and Thyroid Symptom Questionnaire), cognitive function tests, and treatment preference. RESULTS: Mean (+/- sem) serum TSH concentrations were 2.8 +/- 0.4, 1.0 +/- 0.2, and 0.3 +/- 0.1 mU/liter for the three treatments. There were no significant treatment effects on any of the instruments assessing well-being, symptoms, quality of life, or cognitive function and no significant treatment preference. CONCLUSIONS: Small changes in T(4) dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life, despite the expected changes in serum TSH and markers of thyroid hormone action. These data do not support the suggestion that the target TSH range for the treatment of primary hypothyroidism should differ from the general laboratory range.