Effect of tetrandrine on cellular electrophysiology and calcium uptake of myocardium in guinea pigs and dogs

目的　本文旨在研究汉防已甲素对豚鼠及狗的心肌动作电位 (AP)、收缩力及肌浆网钙吸收的作用。方法　用玻璃微电极的方法 ,研究用药后心肌细胞AP、dV/dt、峰张力 (PT)及dT/dt等指标的改变 ,并用生化方法估价用药后心肌肌浆网钙吸收率及无机磷释放等指标的变化。结果　汉防已甲素起着浓度依赖性和频率依赖性负性变力性作用 ,且缩短了动作电位时程。汉防已甲素抑制心肌dT(E) /dt和dT(L) /dt,也抑制了心肌张力 ,并降低了慢动作电位的dV/dt和幅度 ,这些暗示汉防已甲素可阻止慢钙通道。另外 ,与Thapsigargin(一种特异性肌浆网Ca2 ATP酶抑制剂 )进行了比较 ,汉防已甲素较之更为明显地抑制了心肌的收缩。结论　汉防已甲素是一种植物性广谱钙离子拮抗剂。它不仅阻止电压操纵的钙通道 (象其它作者所报导的那样 ) ,而且在影响Ca2 ATP酶及肌浆网钙释放通道方面也起着重要的作用。我们的资料提示钙通道对心肌收缩似乎比肌浆网更为关键。     

Metabolic control and diet in Finnish diabetic adolescents

The effects of dietary, clinical and demographic factors on metabolic control in 105 diabetic adolescents were studied. All patients had diabetes for longer than two years and a daily insulin dose greater than 0.5 IU/kg body weight. Low body mass index, high social class, high number of daily eating occasions, high day-to-day variation in energy intake, high number of urine tests and a long interval between insulin injection and eating were associated with good metabolic control. Many of these determinants reflect also the general compliance with the diabetic regimen. The results stress the importance of good coordination between insulin injections and eating habits.     

A follow-up study of the diet of Finnish diabetic adolescents

Changes with age and time in energy-adjusted food consumption and nutrient intake of 74 diabetic subjects initially aged 12-17 years were studied. Food consumption was measured by the 48-h recall method. During the three-year follow-up (from 1985 to 1988), the proportion of carbohydrate of total energy intake decreased from 49% to 47%, that of fat increased from 33% to 36% and that of protein decreased slightly. The densities of fibre and several vitamins decreased in the diet of the diabetic adolescents. These unfavourable changes in the diet of diabetic adolescents took place with increasing age and duration of diabetes, while virtually no changes with time were detected.     

香港华人妇女产后抑郁危险因素的前瞻性研究

目的：产后抑郁是一种常见的精神障碍，对产妇、新生儿和其它家庭成员导致广泛的伤害。产后抑郁的病因学研究大多是基于西方样本，对其中的社会文化原因也缺乏实证研究。本研究从人口学、心理社会及种族文化因素等方面探讨中国妇女产后抑郁症状学的决定因素。方法：在大学附属综合医院产前门诊连续收集登记的中国孕妇959例，从她们第一次产前检查开始评估（基线），以后分别在孕期的最后3个月、产后即刻和产后3个月时评估。调查涉及的危险因素分6个方面：人口学和社会经济背景，躯体疾病及精神疾病病史，产前抑郁情绪，围生期应激源，人际关系，和种族文化环境。采用等级回归进行分析。因变量是产后3个月时的抑郁评分。结果：决定产后抑郁症状学的因素有：目前的生活事件，缺乏社会支持，婚姻不满意，既往有故意自伤史，以及产前存在抑郁情绪。婆媳关系不好和没有陪月在产后阶段也与抑郁评分高有关联。结论：西方研究所确立的产后抑郁危险因素大体适用于中国妇女。产褥期的社会文化特点同样对产妇情绪有影响。     

Chromatin conformation of the H19 epigenetic mark

Genomic imprinting in mammals is an epigenetic process that results in differential expression of the two parental alleles. The tightly linked murine H19 and Igf2 genes are reciprocally imprinted: H19 is expressed from the maternal chromosome while Igf2 is expressed from the paternal chromosome. A single regulatory region in the 5' flank of the H19 gene has been implicated in silencing both genes. On the paternal chromosome, this region is heavily methylated at CpG residues, leading to repression of the H19 gene. The mechanism by which the same region in an unmethylated state on the maternal chromosome silences Igf2 is less well understood. We have probed the chromatin structure of the region by assessing its sensitivity to nuclease digestion. Two regions of nuclease hypersensitivity that are specific to the maternal chromosome were identified. These coincide with the region that is most heavily methylated on the paternal chromosome. As is the case with paternal methylation, hypersensitivity is present in all tissues surveyed, irrespective of H19 expression. We suggest that the chromatin structure of the maternal 5' flank of the H19 gene may represent an epigenetic mark involved in the silencing of Igf2.      

A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1

We report a mutation (Y99C) in guanylate cyclase activator 1A (GUCA1A), the gene for guanylate cyclase activating protein (GCAP1), in a family with autosomal dominant cone dystrophy. Linkage analysis excluded all the known cone and cone-rod dystrophy loci, except the chromosome 6p21.1 region. This is known to contain the RDS gene, which is associated with dominant cone-rod dystrophy. Screening of the RDS gene by heteroduplex analysis and direct sequencing failed to demonstrate sequence changes in the coding region of this gene. The gene for GCAP1, a calcium binding protein which is highly expressed in photoreceptor outer segments, is also located in 6p21.1. It was screened for mutations, and all affected individuals showed a single base pair missense mutation (A-->G) at codon 99 in exon 2 of this gene generating a tyrosine-to-cysteine change in the GCAP1 protein. This change was absent from 206 unrelated normal controls. We propose that this change would at least disrupt the EF3handof GCAP1 thereby preventing calcium binding and consequently interfere with activation. The resulting effect on cGMP production would predictably modify the number of open cGMP gated cation channels, and could explain the ultimate demise of cone photoreceptor cells.      

The BCR gene recombines preferentially with Alu elements in complex BCR- ABL translocations of chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR- ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.      

The value of biochemical and ultrasound measurements in predicting pregnancy outcome in women with a history of recurrent miscarriage

In this study, the potential prognostic value of serial ultrasonographic, endocrinological and biochemical measurements in the early pregnancy of women with a history of unexplained recurrent miscarriage was examined. A total of 113 pregnancies among 93 women were studied, of which 77 (68%) resulted in live birth, whereas 36 (32%) ended in a miscarriage. The normal range (5-95th centile) of various measurements was derived from pregnancies which resulted in a live birth. Among the 36 failed pregnancies, 42% had one or more human chorionic gonadotrophin (HCG) measurements, 35% had one or more gestation-sac diameter measurements, 33% had one or more embryonic heart rate measurements, 20% had one or more crown-rump length measurements and 9% had one or more placental protein 14 measurements below the normal range, a week or more prior to the confirmation of miscarriage. Altogether, 22/36 = 61% of the failed pregnancies could have been predicted on the basis of one or more of the measurements below the normal range.