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Martin and Wilson (1982) describe two forms of sampling bias in twin studies. One is "hard selection," where individuals above a threshold participate, and those below do not. The second is "soft selection," where the probability of including a pair of relatives varies over the range of the character. We present an alternative model of soft selection which has strikingly different consequences for the resemblance between relatives. In general, the softer the threshold, the more the correlation resembles that in the underlying population. Results are presented where the probability of selection equals the cumulative distribution function of a normal distribution with 10% of the variance of the selected variable. In these circumstances, soft selection usually leads to less severely attenuated correlations than truncate selection.
The unique nature of the hepatic extracellular matrix (ECM) is predicated by the special configuration of the space of Disse. Whereas other epithelial organs have two basement membranes (BM) and a substantial ECM interposed between endothelial and epithelial cells, the liver lobule has no BM and only an attenuated ECM, consisting mostly of fibronectin, some collagen type I, and minor quantities of types III, IV, V, and VI. This configuration, together with the abundant fenestrations and gaps of the sinusoidal endothelial cells, seems ideally suited to facilitate the rapid bidirectional exchange of macromolecules normally taking place between plasma and hepatocytes. During organogenesis, the liver anlage is vascularized by continuous capillaries with BM, but by day 13.5 of development (in the rat) the vessels in the immediate proximity of hepatocytes become fenestrated, lacking specialized junctions and BM, suggesting that the hepatocytes produce signals capable of modulating the endothelial phenotype. In regeneration, hepatocyte proliferation precedes vascular proliferation resulting in the formation of hepatocyte clusters that, temporarily, lack sinusoids. Eventually, vascular proliferation follows and the normal hepatocyte-vascular relationships are restored. During this period laminin synthesis by Ito cells is prominent. As soon as hepatocytes become stable, secretion of the sinusoid phenotype-maintaining factors resumes and laminin synthesis and secretion terminates. The interplay between extracellular matrix and liver cells is essential for normal homeostasis and its modification results in deranged hepatic function.
From 354 visual fields of 137 normal subjects, various components of variance were calculated separately for each test location of the Octopus automated-perimetry program J0. The method of component analysis of variance was used. The following components were analyzed: interindividual variation (variation of visual-field measurements in different subjects), long-term fluctuation (variation of different visual-field measurements in the same subject), differences between the right and left eyes and fluctuation within one visual field test in one subject, i.e., short-term fluctuation. The results show increased variations at the center relative to the paracentral area and a slight increase with eccentricity.
We present numerical results concerning the accuracy of approximate maximum-likelihood estimators of variance components for several models of univariate human twin data. The approximations are obtained via a spectral decomposition of the twin model covariance matrix. The results apply to likelihood functions for univariate twin data based on either the Wishart distribution or the bivariate normal distribution. For sample sizes of 100 twin pairs for each zygosity group, if the difference of the traces of the sample covariance matrices is 10% or less of the sum of the traces, the approximate solutions can be used as the maximum-likelihood estimators for some models.
The macroanatomy of the clinically important lumbar muscles has recently been investigated in detail, whereas the information about their microscopic structure in healthy persons is still scanty. In this study we have analysed lumbar multifidus and erector spinae muscles from 21 previously healthy persons who died suddenly and were of working age (range 23-65 years, mean 44.7 years). The microscopic structure of myofibers within the lumbar muscles was found to be regionally uniform, which renders in vivo biopsies representative of the whole muscle bulk. Somewhat surprisingly, age did not significantly influence fiber type composition, fiber size, or proportion of nonmuscular tissue. There was a slight predominance of type 1 fibers. The size of type 1 fibers (mean lesser diameter 54.0 microns) corresponded to that in other skeletal muscles, with no significant sex difference (55.1/51.6 microns male/female). Selective type 2 fiber atrophy was a common finding in both sexes, but significantly less so in men (mean diameter 38.8/28.4 microns male/female). We suggest that the values of fiber type proportions and fiber size in the deep multifidus presented in this study can be used as reference values for healthy adults in the present society with limited physical activity.
AIMS/HYPOTHESIS: Oxidative stress is associated with diabetes, hypertension and atherosclerosis. Insulin resistance is implicated in the development of these disorders. We tested the hypothesis that oxidative stress induces insulin resistance in rats, and endeavoured to identify mechanisms linking the two. METHODS: Buthionine sulfoximine (BSO), an inhibitor of glutathione synthase, was administered to Sprague-Dawley rats and 3T3-L1 adipocytes. Glucose metabolism and insulin signalling both in vivo and in 3T3-L1 adipocytes were examined. In 3T3-L1 adipocytes, the effects of overexpression of a dominant negative mutant of inhibitory kappa B (I kappa B), one role of which is to block oxidative-stress-induced nuclear factor (NF)-kappa B activation, were investigated. RESULTS: In rats given BSO for 2 weeks, the plasma lipid hydroperoxide level doubled, indicating increased oxidative stress. A hyperinsulinaemic-euglycaemic clamp study and a glucose transport assay using isolated muscle and adipocytes revealed insulin resistance in BSO-treated rats. BSO treatment also impaired insulin-induced glucose uptake and GLUT4 translocation in 3T3-L1 adipocytes. In BSO-treated rat muscle, adipose tissue and 3T3-L1 adipocytes, insulin-induced IRS-1 phosphorylation in the low-density microsome (LDM) fraction was specifically decreased, while that in whole cell lysates was not altered, and subsequent translocation of phosphatidylinositol (PI) 3-kinase from the cytosol and the LDM fraction was disrupted. BSO-induced impairments of insulin action and insulin signalling were reversed by overexpressing the dominant negative mutant of I kappa B, thereby suppressing NF-kappa B activation. CONCLUSIONS/INTERPRETATION: Oxidative stress induces insulin resistance by impairing IRS-1 phosphorylation and PI 3-kinase activation in the LDM fraction, and NF-kappa B activation is likely to be involved in this process.
Our purpose was to quantify the intracranial cerebrospinal fluid (CSF) volume components using an original MRI-based segmentation technique and to investigate whether a CSF volume index is useful for diagnosis of normal pressure hydrocephalus (NPH). We studied 59 subjects: 16 patients with NPH, 14 young and 13 elderly normal volunteers, and 16 patients with cerebrovascular disease. Images were acquired on a 1.5-T system, using a 3D-fast asymmetrical spin-echo (FASE) method. A region-growing method (RGM) was used to extract the CSF spaces from the FASE images. Ventricular volume (VV) and intracranial CSF volume (ICV) were measured, and a VV/ICV ratio was calculated. Mean VV and VV/ICV ratio were higher in the NPH group than in the other groups, and the differences were statistically significant, whereas the mean ICV value in the NPH group was not significantly increased. Of the 16 patients in the NPH group, 13 had VV/ICV ratios above 30%. In contrast, no subject in the other groups had a VV/ICV ratios higher than 30%. We conclude that these CSF volume parameters, especially the VV/ICV ratio, are useful for the diagnosis of NPH.
We have isolated the arpA gene from Aspergillus oryzae as a homologue of the Neurospora crassa ro-4 gene. In N. crassa, mutations in the ro-4 gene, which encodes a major component of the dynactin complex Arp1, causes curling of hyphae and abnormalities in nuclear distribution. The arpA gene contains two introns and encodes a polypeptide of 381 amino acids, with a 78% sequence identity to the N. crassa Arp1. Overexpression of the arpA gene causes a defect in nuclear migration into elongating hyphae of germlings in A. oryzae. We constructed arpA disruptant strains of A. oryzae. The arpA null mutants showed poor growth and hyper-branched mycelia, as well as a nuclear distribution defect. Scanning electron microscopy revealed that the arpA null mutant has an aberrant conidiophore morphology with irregular phialides.
With the use of a B-scan phase-locked tracking system, 108 observations of fetal breathing were performed on 97 normal antenatal patients at term. One hundred thirty-three recorded segments of fetal breathing movements were obtained. Breath-to-breath variability was analyzed in 79 segments and expressed as a coefficient of variability. The mean coefficient of variability was 28.6% +/- 13.2%, and a histogram plot revealed a normal distribution. All fetuses had normal antepartum testing and all Apgar scores and neonatal courses were normal. The potential application of human fetal breathing variability as a test for fetal health is discussed.
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Earlier studies with two-dimensional measurement techniques consistently found higher frontal flow in normal subjects during resting wakefulness. However, this finding could not be confirmed by several laboratories with the more modern and technologically more sophisticated three-dimensional measurement techniques. This discrepancy can have strong implications for psychiatric research in which both types of techniques are frequently used. This article reviews the existing literature, discusses possible reasons for the discrepancy, and evaluates evidence from other sources on the activity of the frontal lobe during wakefulness.
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The present study measured the concentration of monoamines, metabolites and estimates of turnover rate in eighteen separate brain regions from controls and a rat model of Korsakoff's disease induced by a two week bout of pyrithiamine and thiamine deficient diet (PTD). A behaviorally tested control (n = 12) and PTD (n = 17) group, and a non-behaviorally tested PTD group (n = 8) were sacrificed 7 months after recovery from treatment. The brains were dissected into nine cortical areas and nine subcortical regions. In behaviorally tested PTD animals, a significant reduction of NE was observed in entorhinal cortex. Diminished norepinephrine (NE) concentration was also observed in entorhinal, hippocampal, septal and olfactory areas of the non-behaviorally tested PTD group. Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased in several brain areas, particularly midbrain-thalamus, striatum, of both groups of recovered PTD animals. These findings are discussed with respect to results and hypotheses presented in our previous study of this animal model. Significant differences in monoamine, metabolite and turnover estimates were also observed among cortical areas of the control animals. Entorhinal cortex contained the highest concentration of NE and 5-hydroxytryptamine (5-HT), while DA was highest in somatosensory cortex. The distribution of 5-HT and 5-HIAA were more homogeneous and displayed a rostral-caudal decline in concentration.