Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure

BACKGROUND: The benefits of angiotensin-converting-enzyme inhibitors and beta-blockers may be smaller in black patients than in patients of other races, but it is unknown whether race influences the response to carvedilol in patients with chronic heart failure. METHODS: In the U.S. Carvedilol Heart Failure Trials Program, 217 black and 877 nonblack patients (in New York Heart Association class II, III, or IV and with a left ventricular ejection fraction of no more than 0.35) were randomly assigned to receive placebo or carvedilol (at doses of 6.25 to 50 mg twice daily) for up to 15 months. The effects of carvedilol on ejection fraction, clinical status, and major clinical events were retrospectively compared between black and nonblack patients. RESULTS: As compared with placebo, carvedilol lowered the risk of death from any cause or hospitalization for any reason by 48 percent in black patients and by 30 percent in nonblack patients. Carvedilol reduced the risk of worsening heart failure (heart failure leading to death, hospitalization, or a sustained increase in medication) by 54 percent in black patients and by 51 percent in nonblack patients. The ratios of the relative risks associated with carvedilol for these two outcome variables in black as compared with nonblack patients were 0.74 (95 percent confidence interval, 0.42 to 1.34) and 0.94 (95 percent confidence interval, 0.43 to 2.05), respectively. Carvedilol also improved functional class, ejection fraction, and the patients' and physicians' global assessments in both the black patients and the nonblack patients. For all these measures of outcome and clinical status, carvedilol was superior to placebo within each racial cohort (P<0.05 in all analyses), and there was no significant interaction between race and treatment (P> 0.05 in all analyses). CONCLUSIONS: The benefit of carvedilol was apparent and of similar magnitude in both black and nonblack patients with heart failure.     

Comparison of the unlabeled and labeled pre-mRNA splicing assays in vitro

Pre-mRNA splicing is a fundamental process required for the expression of most metazoan genes. It is carried out by the spliceosome that catalyzes the removal of non-coding intron sequences to ligate exons into mature mRNA prior to transport and translation. The purpose of our study is to explore whether the in vitro unlabeled pre-mRNA splicing assay could be performed as an alternative method of splicing reaction other than the radiolabeled one. Two different splicing methods in vitro , P labeled and unlabeled pre-mRNA as the substrates in the reaction, were investigated. The radiolabeled products were visualized by autoradiography while the unlabeled products were observed by Ethidium Bromide (EB) staining. As a result, although there are more unspecific bands in the EB staining assay than 32P labeled one, the RNA products of in vitro splicing could be observed clearly. This suggests that the unlabeled pre-mRNA splicing assay can be an optional substitution for the isotope-labeled assay.     

Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. METHODS: We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. RESULTS: One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). CONCLUSIONS: At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.     

Evolution of age at menarche and at onset of regular cycling in a large cohort of French women

BACKGROUND: Early exposure to ovarian hormones is considered to increase breast cancer incidence. The age at which the ovaries become functional is thus important. METHODS: We explored the evolution of age at first menstruation and at onset of regular cycling in 86 031 women participating in the E3N-EPIC cohort study, part of the European Prospective Investigation into Cancer. RESULTS: We observed an increase in mean age at menarche among women born between 1925 and 1930, followed by a steady decrease in the youngest birth cohorts. In contrast, age at onset of regular cycling increased gradually from 1925 onwards. There was thus a steady increase in the interval between age at menarche and at onset of regular cycling, mainly due to an increase in the percentage of women in whom regular cycling started at least 5 years after menarche (from 9.0% among women born in 1925-1929 to 20.8% in those born in 1945-1950). The increase in the interval between menarche and onset of regular cycling was even greater among women with a late menarche. CONCLUSIONS: This increase might be due to a change in dietary intake and/or physical exercise aimed at achieving the slim silhouette desired by the younger generations.     

大鼠新生期皮下注射谷氨酸单钠对成年后下丘脑ACTH神经元和正中隆起CRF神经纤维免疫反应性的影响

本文采用过氧化酶—抗过氧化酶(PAP)的免疫组织化学和荧光免疫组织化学的方法,研究了新生期大鼠皮下注射谷氨酸单纳(MSG)对成年后下丘脑弓状核促肾上腺皮质激素(ACTH)神经元和正中隆起内促肾上腺皮质激素释放因子(CRF)神经纤维免疫反应的影响。新生期MSG处理后,弓状核中ACTH神经元的数目明显减少,正中隆起CRF样免疫反应末稍也大大减少,减少程度随MSG剂量增大而增加。提示MSG通过损伤前阿黑皮素(POMC)衍生的神经多肽,从而影响下丘脑—垂体—肾上腺皮质轴的功能。     

大鼠单克隆抗体——Ⅶ.用降植烷和福氏佐剂预处理大鼠后腹水产生及单克隆抗体产量的增加

作者研究了腹腔注射降植烷、福氏不完全佐剂(IFA)以及上述两种佐剂的混合物(V/V)(称PIFA)对Louvain大鼠腹水产生及单克隆抗体(McAb)产量的影响。当腹腔注射杂交瘤或免疫细胞瘤细胞的同时注射2ml PIFA可获得最佳结果。若与未经处理的对照大鼠相比,腹水产生增加4.7倍,单克隆抗体产量增加6倍多。 大鼠-大鼠杂交瘤系统有以下优点:①在小鼠系统不适宜的情况下,可用大鼠代     

不同型Kaposi肉瘤的免疫表型观察

对Kaposi肉瘤(KS)的免疫表型特征，仍有不同观点，多数学者认为是一恶性肿瘤，也有学者认为是一增生性病变。我们对30例地方性和AIDS相关KS做了观察。     

The Effects of Extracellular Matrix on Tissue Engineering Construction of Cartilage in Vitro

In the study of bone and cartilage diseases in our laboratory, chondrocyte stereo-differentiation mod-el was cultured into cartilage tissue. The cultured cartilage tissue was closely similar to natural tissue inboth histological condition and biochemical metabolism. The model mimicked the chondrocyte differenti-ation and metabolism in vivo completely〔1〕. We studied some essential extracellular matrices, includingcollagen, proteoglycan(PG) and hyaluronic acid(HA) on the construction of grow…     

HIV-1感染引起组蛋白乙酰化和增加p21WAF1表达

目的：DNA甲基化和组蛋白乙酰化是基因表达调控的主要形式。人类免疫缺陷病毒（HIV-1）可引起T淋巴细胞DNA甲基化酶上调。本文旨在明确HIV-1对细胞周期依赖刺激酶抑制剂p21^WAF1表达的影响。方法：建立HIV-1感染的Hut78细胞系；以RT-PCR和Westem blotting 分析p21^WAF1表达情况；以亚硫酸氢钠修饰DNA和基因测序，研究p21^WAF1基因启动子甲基化，以Western blot-ting 和染色体免疫测定探究总组蛋白和与p21^WAF1基因启动子相关的组蛋白乙酰化水平。并以GST pull-down和免疫沉淀分析HIV-1导致乙酰化及乙酰化引起p21^WAF1过表达的可能机理。结果：HIV-1感染后，其反式激活蛋白Tat与辅助转录因子P/CAF、hGCN5结合，共同刺激组蛋白H3乙酰化。尽管p21^WAF1启动子部分区域有甲基化发生，但p21^WAF1表达仍上调。这可能与E2A对p21^WAF1的作用有关。结论：HIV-1感染可引起T淋巴细胞p21^WAF1基因的甲基化和乙酰化紊乱，导致p21^WAF1表达增强。     

生理参数及药物注射方式对球形实体肿瘤中药物输运的影响

目的　研究球形实体肿瘤中生理参数对药物输运的影响，以及探讨有较好效果的药物注射方式。方法　设肿瘤中毛细血管网成球对称分布，肿瘤中的毛细血管表面积和肿瘤体积之比为半径的函数。肿瘤间质为多孔介质，化学药物透过毛细血管壁进入肿瘤间质，在肿瘤间质中输运满足扩散方程。肿瘤外正常组织富含血管和淋巴，药物能被淋巴管吸收，药物输运采用改进的药代动力学模型。用肿瘤中各部位药物浓度维持在最小药物浓度MEC水平以上的时间曲线面积(AUC)来衡量药物的效果。结果　增大肿瘤间质中毛细血管对药物的通透性P，提高药物在肿瘤间质的扩散系数D，AUC的值均增大。在给出的六种给药方式中，分时段连续滴注和等时间间隔一次性注射的给药方式，它们的AUC值最大。结论　增大肿瘤间质中毛细血管对药物的通透性，提高药物在肿瘤间质的扩散系数，以及采用分时段连续滴注和等时间间隔一次性注射的给药方式，有利于肿瘤的治疗。