Analysis of germline mutation spectra at the Huntington's disease locus supports a mitotic [correction of amitotic] mutation mechanism [published erratum appears in Hum Mol Genet 1999 Apr;8(4):717]

Trinucleotide repeat disease alleles can undergo 'dynamic' mutations in which repeat number may change when a gene is transmitted from parent to offspring. By typing >3500 sperm, we determined the size distribution of Huntington's disease (HD) germline mutations produced by 26 individuals from the Venezuelan cohort with CAG/CTG repeat numbers ranging from 37 to 62. Both the mutation frequency and mean change in allele size increased with increasing somatic repeat number. The mutation frequencies averaged 82% and, for individuals with at least 50 repeats, 98%. The extraordinarily high mutation frequency levels are most consistent with a mutation process that occurs throughout germline mitotic divisions, rather than resulting from a single meiotic event. In several cases, the mean change in repeat number differed significantly among individuals with similar somatic allele sizes. This individual variation could not be attributed to age in a simple way or to ' cis ' sequences, suggesting the influence of genetic background or other factors. A familial effect is suggested in one family where both the father and son gave highly unusual spectra compared with other individuals matched for age and repeat number. A statistical model based on incomplete processing of Okazaki fragments during DNA replication was found to provide an excellent fit to the data but variation in parameter values among individuals suggests that the molecular mechanism might be more complex.      

圆二色谱在单萜和木脂体化合物结构分析中的应用

报道了10个化合物的CD谱,其中栀子酮(1)、栀二醇(2)和木脂体(3～7)均为新化合物。应用5种规则,确定了它们的绝对构型。     

小檗碱对局灶性脑缺血大鼠血小板聚集及血浆TXB2和6－keto－PGF1a水平的影响

以大鼠可逆性大脑中动脉梗塞（ＭＣＡＯ）致局灶性脑缺血为模型，观察小檗碱对大鼠ＭＣＡＯ２４ｈ后血小板粘附、聚集、血栓形成及血浆ＴＸＢ２和ＰＧＩ２生成的影响。结果表明，小檗碱２０ｍｇ·ｋｇ－１·ｄ－１ｉｐｌ，３或５ｄ，明显降低ＭＣＡｏ２４ｈ后血小板粘附性及ＡＤＰ、胶原和花生四烯酸诱导的血小板聚集率，抑制血浆ＴＸＢ２水平。同剂量ｉｐ３或５ｄ，则抑制血栓形成。提示小檗碱可能通过其抗血小板粘附和聚集及影响花生四烯酸代谢而发挥抗脑缺血作用。     

靶向给药-药剂学研究的热点

0 引言 常规剂型的药物经静脉、口服或局部注射后,药物分布于全身,真正到达治疗靶区的药物量仅为给药量的小部分,而大部分药物在非靶区的分布不仅无治疗作用,还会带来毒副作用.     

冠状动脉旁路移植术97例

1临床资料2004-03/12行冠状动脉旁路移植术(CABG)97(男76,女21)例,年龄38～81岁,其中不稳定心绞痛者46例,陈旧性心肌梗死11例,合并室壁瘤6例,合并高血压78例,合并糖尿病39例,合并主动脉瓣关闭不全4例,二尖瓣关闭不全5例.冠脉造影示:单支病变(心肌桥)7例,3支及3支以上病变90例,心功能Ⅱ级36例,心功能Ⅲ级45例,Ⅳ级16例.心脏超声检查:EF＜20%者10例,EF 20%～40%者36例,EF 40%～50%以上者51例,属二次冠状动脉旁路移植术5例,其余均为首次搭桥.     

Dyspnea and 8-year mortality among elderly men and women: The PAQUID cohort study

PAQUID is an epidemiological cohort which aims to study cerebral and functional factors of ageing. We have examined the relationship between dyspnea level at entrance into this cohort and mortality occurring during the subsequent 8 years. Dyspnea was evaluated by a questionnaire derived from a Fletcher's five-degree scale. Mortality was recorded during follow-up according to its date and cause. Of 2762 subjects (98.9%) initially giving their dyspnea level, 935 (33.5%) had died 8 years later including 444 (40%) men and 491 (29.4%) women. Mortality was closely related to dyspnea level (p < 0.0001) both in men and women, especially for grade 3 and over, even after adjusting on age, sex, smoking history and former occupation. These results show that dyspnea grade 3 or higher is an important predictive symptom of mortality, thus suggesting that this is a threshold defining the dyspneic subject.     

Deep veins of the calf: assessment with color Doppler flow imaging

The authors studied the ability of real-time ultrasound aided by color Doppler flow imaging to demonstrate the deep veins of the calf in ten healthy subjects and 49 patients (91 limbs) with suspected deep venous thrombosis. Posterior tibial and peroneal veins demonstrated flow accentuation in 98% (74 of 75) and 96% (72 of 75), respectively, of the limbs without thrombosis and in all 20 normal limbs. Sixteen legs were involved with deep venous thrombosis. Peroneal veins could not be seen in three legs with marked calf swelling due to proximal thrombosis. There were two cases of thrombosis limited to the calf, nine of popliteal thrombosis (seven with contiguous spread of thrombus), and five of thrombosis limited to above the knee (four with sparing of the deep veins of the calf). Visualization of anterior tibial veins, achieved in 65% of all legs, did not correlate with thrombosis. The authors conclude that color Doppler flow imaging can demonstrate patency of posterior tibial and peroneal veins in most patients without deep venous thrombosis and aid in detection of below-the-knee thrombosis.     

Long-term neuropsychological sequelae of early-treated congenital hypothyroidism: effects in adolescence

A cohort of over 100 children with congenital hypothyroidism (CH) detected via newborn screening was followed regularly throughout childhood and into adolescence. They were studied using a variety of different tests as part of three consecutive research components: semiannual/ annual psychological assessments using age-appropriate intelligence tests (phase I), detailed psychoeducational evaluations in grades 3 and 6 (phase II) and a thorough neuropsychological evaluation during adolescence (phase III). Controls for phase I were siblings and for phase II, classmates and siblings. Phase III controls were drawn from a larger control pool and were individually matched with each CH case for age and gender. The results showed that although the CH group was intellectually functioning well within the normal range by adolescence, the children were performing significantly below expectation. Longitudinal analyses showed significant declines in IQ with age, signifying that the CH group was failing to make the same age-related gains as controls. Children with CH showed significantly poorer performance in visuospatial, language and fine motor areas as well as selective attention and memory deficits. At school, they were initially below par in arithmetic but were able to catch up by grade 6; however, their teachers reported that they were not performing as well as controls in the classroom and they demonstrated more difficulty with more complex school subjects such as science and social studies. Correlational analyses indicated different manifestations of early hypothyroidism versus later treatment factors, suggesting that while some effects can be improved by better treatment and management approaches, others caused by prenatal and perinatal thyroid hormone insufficiency may persist.     

Challenges of Francisella classification exemplified by an atypical clinical isolate

The accumulation of sequenced Francisella strains has made it increasingly apparent that the 16S rRNA gene alone is not enough to stratify the Francisella genus into precise and clinically useful classifications. Continued whole-genome sequencing of isolates will provide a larger base of knowledge for targeted approaches with broad applicability. Additionally, examination of genomic information on a case-by-case basis will help resolve outstanding questions regarding strain stratification. We report the complete genome sequence of a clinical isolate, designated here as F. novicida-like strain TCH2015, acquired from the lymph node of a 6-year-old male. Two features were atypical for F. novicida: exhibition of functional oxidase activity and additional gene content, including proposed virulence determinants. These differences, which could potentially impact virulence and clinical diagnosis, emphasize the need for more comprehensive methods to profile Francisella isolates. This study highlights the value of whole-genome sequencing, which will lead to a more robust database of environmental and clinical genomes and inform strategies to improve detection and classification of Francisella strains.     

Evaluation of three psychologic interventions to reduce anxiety during MR imaging

The authors compared the effectiveness of three anxiety-reducing interventions for patients undergoing magnetic resonance imaging. Each of 50 subjects was randomly assigned to one of the interventions. Intervention 1 involved provision of information about the imager and nature of the examination. Intervention 2 included information and counseling. Intervention 3 included information and a 12-minute relaxation exercise. Anxiety levels were measured by means of a 20-item questionnaire before and after imaging. The latter provided a retrospective report of anxiety experienced during imaging. Patients in intervention group 3 showed significantly less increase in anxiety compared with those in groups 1 and 2. Overall, only patients who participated in intervention 1 showed a significant increase in anxiety during imaging. When anxiety levels experienced before and during the examination were compared, with the focus on each questionnaire item for each group, those in group 1 showed a significant increase in anxiety on eight of 20 items; those in group 2, three items; and those in group 3, none. Psychologic preparation that includes relaxation strategies is more effective than provision of information alone.