Entactin and laminin gamma 1-chain gene expression in the early chick embryo.

The expression patterns of entactin and laminin gamma1 chain genes were examined by in situ hybridization of their mRNAs in the early chick embryo from stage X (morula) to stage HH10-11 (10-somites). The entactin and laminin gamma1 transcripts were found in abundance in the embryo at stage X. Entactin polypeptides were detected in embryos at stage X by immunoprecipitation. The expression of the laminin transcripts was intense and of entactin milder in the epiblast and in the hypoblast of embryos at stage XIII (blastula). During gastrulation (stage HH3-4), the laminin gamma1 and entactin cRNAs gave strong signals in the cells ingressing through the primitive streak, in the migrating mesenchymal cells and the cells of the lower layer. At the neurula stage (stage HH5-6), punctate groups of cells expressed laminin gamma1 strongly in the neural ectoderm, while the signal of expression was milder and more uniform in chordamesoderm. The entactin cRNAs gave a strong punctate pattern of mRNA expression in the neural ectoderm, in mesoderm and in endoderm in embryos at the late gastrula stage (HH4), but mRNA expression was mild in the neural plate and in mesoderm and gave no signal in endoderm and lateral ectoderm in embryos at stage HH6 (neurula). At the 10-somite stage, the laminin gamma1 cRNAs gave strong signals in the neural tube and in neural crest cells migrating along the neural tube ventrally and low signals in ectoderm, intense signals in the myotome and milder signals in the dermatome and sclerotome of somites and intense signals in the mesonephric tubules. The punctate pattern of entactin expression was notable in cells at all stages studied. Ubiquitous expression of laminin gamma1 and entactin genes during the morula and blastula stages becomes restricted to specific cell populations as the first cell commitments start.

Morphofunctional studies of the glomerular wall in mice lacking entactin-1.

The architecture of the basement membranes is essential for proper function. This architecture is based on interactions among its components, which assemble in a complex network. Entactin-1 appears to be the mastermind of this assembling. In entactin-1-null transgenic mice, immunocytochemistry established the absence of entactin-1 in the glomerular basement membrane, and morphological thickening of this membrane was demonstrated. This prompted us to investigate the organization of other components of the glomerular basement membrane in the transgenic animals. The distribution of type IV collagen and laminin remained unchanged, whereas that of anionic charges was significantly altered. We also evaluated the impact of the absence of entactin-1 on cell relays by studying the alpha(3)- and the alpha(v)-integrins along the endothelial and epithelial glomerular cell plasma membranes. Only the density of alpha(v) was found to be increased. Finally, the filtration properties of the glomerular wall were evaluated by revealing endogenous albumin distribution across the basement membrane. This was altered in transgenic animals, suggesting changes in permselectivity properties. Entactin-1 appears to be an essential component in basement membranes because its absence appears to modify the molecular organization leading to alterations in functional properties.

Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1.

Entactin-1 (nidogen-1) is an ubiquitous component of basement membranes. From in vitro experiments, entactin-1 was assigned a role in maintaining the structural integrity of the basement membrane because of its binding affinity to other components, such as type IV collagen and laminin. Entactin-1 also interacts with integrin receptors on the cell surface to mediate cell adhesion, spreading, and motility. Targeted disruption of the entactin-1 gene in the mouse presented in this study revealed a duplication of the entacin-1 locus. Homozygous mutants for the functional locus lacked entactin-1 mRNA and protein and often displayed seizure-like symptoms and loss of muscle control in the hind legs. The behavior patterns suggested the presence of neurologic deficits in the central nervous system, thus providing genetic evidence linking entactin-1 to proper functions of the neuromuscular system. In homozygous mutants, structural alterations in the basement membranes were found only in selected locations including brain capillaries and the lens capsule. The morphology of the basement membranes in other tissues examined superficially appeared to be normal. These observations suggest that the lost functions of entactin-1 result in pathologic changes that are highly tissue specific.

The Jamaican childhood cardiovascular risk status study; blood pressure in Jamaican school children, relationship to body size and composition - abstract

Hypertension is one of the most prevalent chronic cardiovascular diseases and is the leading cause of death in the Caribbean as well as in the developed countries. Childhood blood pressure is predictive of hypertension in adulthood. Risk factors for hypertension, including body composition, are often present in childhood when they may be modified in order to contribute to primary prevention of hypertension. As part of a study of risk factors for cardiovascular disease, we measured blood pressure (BP) and anthropometry in Jamaican schoolchildren. Anthropometric and demographic variables were analysed to explain the variance of blood pressure in the children. A total of 2332 children (1046 males; 1286 females) were studied. Their ages ranged from 6 to 16 years. Boys and girls were similar in age. Mean diastolic and systolic blood pressures were similar in boys and girls' pulse rate was significantly higher than in boys. Boys had significantly greater Waist-Hip Ratio (0.82 vs 0.76; p<0.0001) and Lean Body Mass (34.2 vs 33.20 kg; p=0.006). Girls had significantly greater weight (42.3 vs 39.5; p<0.0001); Height (150.6 vs 148.9; p=0.005); BMI (18.2 vs 17.3; p<0.0001); MUAC (21.5 vs 20.8; p<0.0001); Hip Circumference (79.5 vs 73.9; p<0.0001); Triceps Skinfold (11.6 vs 8.3; p<0.0001); Per cent Body Fat (19.5 vs 11.6; p<0.0001); Fat Weight (9.1 vs 5.2; p<0.0001). Systolic BP increased steadily with age from 101 ñ 9.9 mm Hg at 6 years to 112 ñ 8.5 mm Hg at 16 years. Systolic BP was significantly correlated with weight, height, BMI, MUAC, WH Ratio, fat mass and lean body mass on univariate analysis but only weight and lean body mass were independently correlated (p<0.0001 for both variables). There was a significant age-sex interaction on Systolic BP (p<0.0001) but only at age 15 years were the mean BPs significantly different (boys vs girls = 119 ñ 15.2 vs 107.8 ñ 10.8; p<0.001). Diastolic BP increased less steeply with age. Significant predictors were MUAC and hip circumference (p<0.0001 and p<0.002, respectively). The data reveal significant correlation between anthropometric variables and blood pressure. This could provide an opportunity for intervention and primary prevention of hypertension (AU)

Studies on the effect of diet on hepatic lipogenesis

This thesis is an account of investigation in which special diets were fed to rats and the resulting effects on hepatic lipogenesis studied. The carbohydrate and fat contents of the diets were varied and groups of rats on the different diets compared. It was shown in a test system consisting of liver slices that rats, which were previously fed for two days on a relatively high carbohydrate diet, incorporated the carbon of 14C labelled glucose into fatty acids and carbon dioxide at an increased rate when compared with rats fed a relatively low and a control diet. Hepatic glucose - 6 - phosphatase activity was not altered by feeding the different diets. Liver glycogen concentrations was also unaltered. The ratio of this concentrations of oxidised to reduced diphosphopyridine nucleotide in liver was higher for rats on the "high" carbohydrate diet than for rats on the "low" carbohydrate and the control diets. The concentration of reduced triphosphopyridine nucleotide in liver was decreased by feeding the "high" carbohydrate diet. The plasma "insulin activity" of the rats on the "high" carbohydrate diet was less than that of rats on the "low" carbohydrate diet. There was no significant difference between the "insulin binding" capacity of the livers of rats fed the "high" and "low" carbohydrate diets. It was not possible to offer any explanation, from the experimental results, of how the "high" carbohydrate diet caused an increase in hepatic lipogenesis (AU)

The effects of small changes of diet on liver metabolism (abstract only)

The livers of rats fed on slightly different diets synthesise fat at different rates. The levels of Glucose-6-Phosphatase, oxidised and reduced diphosphopyridine nucleotide and reduced triphosphopyridine nucleotide were determined in these livers (AU)