Cardiovascular risk factors in people with different genotypes in the insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme (ACE)

The deletion (D) allele of an insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme (ACE) has been reported to be an independent risk factor for myocardial infarction (MI), particularly in people lacking traditional risk factors. Furthermore, a borderline association between Lp(a) lipoprotein level and the I/D polymorphism at the ACE locus was reported in one study. We have searched for possible "level gene" or "variability gene" effects of ACE genes on Lp(a) lipoprotein, total cholesterol (TC), high density lipoprotein (HDL) cholesterol (HDLC), low density lipoprotein (LDL) cholesterol (LDLC), triglycerides (TG), apolipoprotein B (apoB), apolipoprotein A-I (apoA-I), and body mass index (BMI). None of these variables differed significantly between genotypes in the I/D polymorphism in any of three population samples. A single population sample created by combining the three series, exhibited an insignificant trend towards individuals carrying the D-allele having a higher level of Lp(a) lipoprotein than those lacking it, and DD homozygotes had a significantly higher Lp(a) lipoprotein level than the combined group of ID/II individuals (p = 0.03). These results may indicate that the D-allele of the I/D polymorphism at the ACE locus could influence the level of Lp(a) lipoprotein.     

High levels of Lp(a) lipoprotein in a family ith cases of severe pre-eclampsia

We report a family with two cases of severe pre-eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre-eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre-eclampsia that is genetically determined.     

Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus

A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3' to the last kringle IV structure of the gene. The "1" gene (presence of the restriction site) has a frequency of 0.316 and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1-1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.     

Representation of heading direction in far and near head space

Manipulation of objects around the head requires an accurate and stable internal representation of their locations in space, also during movements such as that of the eye or head. For far space, the representation of visual stimuli for goal-directed arm movements relies on retinal updating, if eye movements are involved. Recent neurophysiological studies led us to infer that a transformation of visual space from retinocentric to a head-centric representation may be involved for visual objects in close proximity to the head. The first aim of this study was to investigate if there is indeed such a representation for remembered visual targets of goal-directed arm movements. Participants had to point toward an initially foveated central target after an intervening saccade. Participants made errors that reflect a bias in the visuomotor transformation that depends on eye displacement rather than any head-centred variable. The second issue addressed was if pointing toward the centre of a wide-field expanding motion pattern involves a retinal updating mechanism or a transformation to a head-centric map and if that process is distance dependent. The same pattern of pointing errors in relation to gaze displacement was found independent of depth. We conclude that for goal-directed arm movements, representation of the remembered visual targets is updated in a retinal frame, a mechanism that is actively used regardless of target distance, stimulus characteristics or the requirements of the task.     

Translational repressor bruno plays multiple roles in development and is widely conserved

oskar (osk) mRNA is tightly localized to the posterior pole of the Drosophila oocyte, where the subsequent expression of Osk protein directs abdomen and germ-line formation in the developing embryo. Misplaced expression of Osk protein leads to lethal body patterning defects. The Osk message is translationally repressed before and during the localization process, ensuring that Osk protein is only expressed after the mRNA has reached the posterior. An ovarian protein, Bruno (Bru), has been implicated as a translational repressor of osk mRNA. Here we report the isolation of a cDNA encoding Bru using a novel approach to the expression cloning of an RNA-binding protein, and the identification of previously described mutants in the arrest (aret)-locus as mutants in Bru. The mutant phenotype, along with the binding properties of the protein and its pattern of accumulation within the oocyte, indicate that Bru regulates multiple mRNAs involved in female and male gametogenesis as well as early in embryogenesis. Genetic experiments provide further evidence that Bru functions in the translational repression of osk. Intriguingly, we find that Bru interacts physically with Vasa (Vas), an RNA helicase that is a positive regulator of osk translation. Bru belongs to an evolutionarily conserved family of genes, suggesting that Bru-mediated translational regulation may be widespread. Models for the molecular mechanism of Bru function are discussed.     

Tissue repair processes in healing chronic pressure ulcers treated with recombinant platelet-derived growth factor BB.

Cellular and molecular mechanisms responsible for the observed vulnerary effects of recombinant human platelet-derived growth factor BB (rP-DGF-BB) in man have not been elucidated. In a double-blinded trial, patients having chronic pressure ulcers were treated topically with either rPDGF-BB or placebo for 28 days. To explore how rPDGF-BB may induce chronic wounds to heal, biopsies were taken from the ulcers of a cohort of 20 patients from the trial and evaluated in a blinded fashion by light microscopy for 1), fibroblast content, 2) neovessel formation, and 3), collagen deposition. Electron microscopy also was used to assess fibroblast activation and collagen deposition. Before initiation of therapy most wounds had few fibroblasts and most of those present were not activated. When mean scores for the total active treatment phase (days 8, 15, and 29) for rPDGF-BB-treated ulcers were compared with the scores for placebo-treated ulcers, fibroblast content was significantly higher for the rPDGF-BB-treated ulcers (P = 0.03, Kruskal-Wallis test). More significant differences in fibroblast and neovessel content were observed when six nonhealing wounds were eliminated from the analysis (three placebo, three treatment). Thus, in all healing wounds, rPDGF-BB therapy significantly increased fibroblast (P = 0.0007) and neovessel (P = 0.02) content. These results were correlated with increased collagen fibrillogenesis by fibroblasts from healing rPDGF-BB-treated wounds, as assessed by intracellular procollagen type I immunostaining, and by electron microscopy, and were concordant with clinical measurements (eg, area of ulcer opening and ulcer volume) which showed greater healing in rPDGF-BB-treated wounds. These results suggest induction of fibroblast proliferation and differentiation is one mechanism by which rPDGF-BB can accelerate wound healing and that rPDGF-BB can augment healing responses within a majority of, but not all, nonhealing chronic pressure ulcers in man.     

Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene

Marfan Syndrome is a genetic disorder of the connective tissue. Individuals from one large family with this disorder were genotyped for COL1A2 gene associated RFLPs. Our results demonstrated that the COL1A2 gene, encoding the proa2(I) collagen chain, segregated independently of the phenotype and it is therefore excluded as the mutant locus in this family.     

Increase in the ratio of serum levels of apolipoproteins A-I and A-II during prolonged physical strain and calorie deficiency

Summary Effects of four days of intense physical activity on serum concentrations of total triglycerides, total cholesterol and apolipoproteins A-I, A-II, and B were studied in 35 well-trained young men. Serum total triglyceride levels decreased to 70% of baseline levels after 24 h, and fell further to 50% of baseline levels after 4 days. Serum levels of total cholesterol fell steadily to about 80% of baseline levels on the 4th day. Apo-B levels fell to 85% of baseline levels after 24 h, and remained at that level. Apo A-I fell to about 90%, and apo A-II to about 80% of baseline levels, causing a significant increase in the ratio of apo A-I to apo A-II. The intraindividual changes in apo B were positively correlated to changes in cholesterol during the first day (r=0.60). The changes in apo A-I and apo A-II had no significant correlation with changes in total cholesterol or triglycerides, or with one another, suggesting that apo A-I and apo A-II are metabolized independently during conditions of hard physical exercise.     

Effects of age, sex and genes on sister chromatid exchange

Sister chromatid exchange (SCE) was studied in cultured lymphocytes from a limited series of 21 like-sexed twin pairs; 11 monozygotic (MZ) and 10 dizygotic (DZ) pairs. The 18 subjects, who were between 57 and 61 years old, had an SCE mean value () of 8.0 whereas the 24 subjects between 33 and 39 years of age had a mean of 6.8. The difference was statistically significant ( P <0.001). The effect of age appeared to be present in both sexes. No significant difference was found between females (%7.3) and males (%7.5), nor between smokers (%7.3) and non-smokers (%7.4). Drug users had a slightly higher mean (%7.9) than non-users (= 7.0) ( P < 0.05). This trend was found in each age group. The within-pair variance was slightly higher in DZ than in MZ pairs. The difference was not significant. We conclude that genetic factors are probably not a major source of subject variation in SCE mean value.