A MYLK variant regulates asthmatic inflammation via alterations in mRNA secondary structure

Myosin light-chain kinase (MYLK) is a gene known to be significantly associated with severe asthma in African Americans. Here we further examine the molecular function of a single-nucleotide polymorphism (SNP), located in the non-muscle myosin light-chain kinase isoform (nmMLCK), in asthma susceptibility and pathobiology. We identified nmMLCK variant (reference SNP: rs9840993, {"type":"entrez-nucleotide","attrs":{"text":"NM_053025","term_id":"116008191","term_text":"NM_053025"}}NM_053025: 721C>T, c.439C>T) with a distinct mRNA secondary structure from the other variants. The nmMLCK variant (721C) secondary structure exhibits increased stability with an elongated half-life in the human endothelial cell, and greater efficiency in protein translation initiation owing to an increased accessibility to translation start site. Finally, nmMLCK expression of 721C- and 721T-containing MYLK transgenes were compared in nmMLCK^−/− mice and confirmed deleterious effects of nmMLCK expression on asthmatic indices and implicated the augmented influence of MYLK 721C>T (c.439C>T) SNP on asthma severity. The confirmation of the novel mechanism of the regulation of asthmatic inflammation by a MYLK advances knowledge of the genetic basis for asthma disparities, and further suggests the potential of nmMLCK as a therapeutic target. Our study suggests that in addition to altering protein structure and function, non-synonymous SNPs may also lead to phenotypic disparity by altering protein expression.     

Propranolol in acute migraine: a controlled study

Propranolol is an established agent in migraine prophylaxis. Uncontrolled studies have suggested an action in the acute attack. We present the first double-blind placebo controlled study of propranolol in 27 unselected patients with common (migraine without aura) and classical (migraine with aura) migraine. There were 23 pairs of headaches in the 14 patients who completed the study. No difference was found, when the data were analysed by headache pair or by patient, in severity duration and subjective assessment of efficacy between those treated in an attack with propranolol 40 mg and placebo.     

Characterization of the cholesterol crystallization-promoting low- density particle isolated from human bile

BACKGROUND & AIMS: Biliary concanavalin A-binding glycoprotein (CABG) contains cholesterol crystallization-promoting activity that is not accounted for by the pronucleators that have been characterized in this fraction. The aim of this study was to isolate and characterize the missing activity. METHODS: Biliary glycoprotein was isolated using concanavalin A-Sepharose. Promoting activity in CABG was purified using density gradient ultracentrifugation. RESULTS: Activity in CABG separated into two fractions at low (1.08) and high (1.29) density, which showed different crystallization kinetics in a model bile. The high-density fraction had a late onset time (49.2 +/- 17.8 hours) but a high crystal growth rate (13.4 +/- 5.2 micrograms. mL-1.h-1). The low- density fraction had a rapid onset time (33.9 +/- 20.9 hours) but a slower growth rate (6.5 +/- 3.8 micrograms.mL-1 .h-1). The high-density fraction was not further characterized in this study. The low-density fraction contained solid particles consisting of lipid and very little protein, and the activity was fully pronase resistant. Delipidation of the low-density fraction removed all activity. CONCLUSIONS: A potent pronase-resistant nucleation-promoting activity was activated from human bile and characterized. The low-density fraction may be responsible for the rapid nucleation in bile from typical patients with fast-nucleating gallstones. (Gastroenterology 1996 Jun;110(6):1936-44)     

功能磁共振成像与弥散张量成像联合监测视觉通路异常在高压氧治疗前后的结构及功能变化

目的:联合应用血氧依赖功能磁共振成像(BOLD-fMRI)和弥散张量成像技术评价视觉通路异常高压氧患者在康复过程中脑功能和解剖结构的重组特点。方法:①临床资料:选择2006-01/2007-05解放军南京军区福州总医院收治的因视觉通路病变致单侧或双侧视觉障碍的16例患者为病变组,均接受2个标准大气压高压氧治疗3个疗程。以性别、年龄与病变组大致匹配的正常视力者12例作为正常对照组。②磁共振扫描及分析:两组以相同条件,采用黑白棋盘格变化刺激双眼,应用Signa xcite HD 1.5T双梯度16通道磁共振成像系统进行测试。BOLD-fMRI数据处理采用AFNI软件包进行,弥散张量成像应用日本东京大学影像计算和分析实验室开发的Volume-one 1.64下的dTV.II.R1软件进行数据处理。③观察指标:病变组高压氧干预前后BOLD-fMRI激活体数和弥散张量成像表现,并与正常对照组比较。结果:28例受试者均进入结果分析。①BOLD-fMRI激活体数值:病变组高压氧治疗前视皮质激活体数低于正常对照组(P<0.01),高压氧治疗后视皮质激活体数与正常对照组比较差异不显著(P>0.05),但高于高压氧治疗前(P<0.05)。②弥散张量成像示视放射部分各向异性值:病变组高压氧治疗前部分各向异性值低于正常对照组(P<0.05),高压氧治疗后与正常对照组比较差异不显著(P>0.05),且显著高于高压氧治疗前(P<0.05)。病变组中的6例视神经病变患者视放射显示完整,康复前后的视放射部分各向异性值与正常对照组比较无显著性差异(P>0.05),10例枕叶视中枢病变患者视放射纤维部分中断,视放射各向异性值低于视神经病变患者(P<0.05)。结论:BOLD-fMRI联合弥散张量成像能从功能和结构方面探讨视觉通路病变的发生、发展及康复过程,为脑功能的康复提供较为可靠的治疗依据。     

A simple monthly means chart system for monitoring sperm concentration

A simple, robust monthly means chart system for monitoring sperm concentration was developed and used in our andrology laboratory. The system relied on the central limit theorem to allow estimation of chart limits without resorting to data transformation procedures. Once the chart was drawn up, the arithmetic mean of sperm concentration was determined monthly and plotted. Monthly means which fell outside 2 SE from the baseline mean were investigated. Initial experience with this chart system suggests that it provides a simple and useful quality assurance method which should be applicable to other semen variables such as motility and sperm morphology.