Lipid lowering in a multidisciplinary clinic compared with primary physician management

OBJECTIVE: This study analyzed questionnaire items that address complaints about sleep from the National Vietnam Veterans Readjustment Study, a nationally representative sample of the 3.1 million men and women who served in Vietnam. This study compared the frequency of nightmares and difficulties with sleep onset and sleep maintenance in male Vietnam theater veterans with male Vietnam era veteran and male civilian comparison subjects. It focused on the role of combat exposure, nonsleep posttraumatic stress disorder (PTSD) symptoms, comorbid psychiatric and medical disorder, and substance abuse in accounting for different domains of sleep disturbance. METHOD: The authors undertook an archival analysis of the National Vietnam Veterans Readjustment Study database using correlations and linear statistical models. RESULTS: Frequent nightmares were found exclusively in subjects diagnosed with current PTSD at the time of the survey (15.0%). In the sample of veterans who served in Vietnam (N = 1,167), combat exposure was strongly correlated with frequency of nightmares, moderately correlated with sleep onset insomnia, and weakly correlated with disrupted sleep maintenance. A hierarchical multiple regression analysis showed that in Vietnam theater veterans, 57% of the variance in the frequency of nightmares was accounted for by war zone exposure and non-sleep-related PTSD symptoms. Alcohol abuse, chronic medical illnesses, panic disorder, major depression, and mania did not predict the frequency of nightmares after control for nonsleep PTSD symptoms. CONCLUSIONS: Frequent nightmares appear to be virtually specific for PTSD. The nightmare is the domain of sleep disturbance most related to exposure to war zone traumatic stress.     

Factor structure of a measure of anxiety sensitivity in children

Anxiety sensitivity (i.e., the disposition to react to autonomic arousal with fear) has taken a central role in recent conceptualizations of anxiety. However, questions regarding the dimensional nature of anxiety sensitivity remain. In particular, the factor structure of anxiety sensitivity is unexplored in nonadult populations. The factor structure of the Anxiety Sensitivity Index for Children (ASIC) was examined in three studies. Study 1 (N = 95) used a sample of school children in Grades 4-8 to investigate the reliability of items and factor structure. Items with weak psychometric properties were eliminated, and subsequent analyses revealed that the ASIC was best viewed as a hierarchical scale with a higher order factor (Anxiety Sensitivity) and two first-order factors (Fear of Physiological Arousal and Fear of Mental Catastrophe). Study 2 (N = 112) and Study 3 (N = 144) used more distressed samples of youngsters, and they also found the ASIC to be a hierarchical scale. These findings add a developmental perspective to the Anxiety Sensitivity Index factor analytic discussion and are highly consistent with emergent thinking in the adult anxiety sensitivity literature.     

Spontaneous and induced mutagenesis in a culture of Chinese hamster cells

Spontaneous and nitrosoguanidine (NG)-induced rate of reversions to glutamine independence was studied in cultured temperature-sensitive glutamine auxotrophs of Chinese hamster cells. In 3 experiments the spontaneous rate of reversions varied from 0.8-10(-6) to 3.84-10(-6) per cell per generation. A dependence of the yield of NG-induced back mutations upon the time interval between the mutagenic treatment and the transfer to selective conditions (glutamine deficient medium, 40 degrees C) was established. No induced revertants were detected when cells were transferred to selective conditions immediately after the treatment with NG. After 2--3 days cultivation in glutamine containing medium at 36 degrees C and the sunsequent transfer to selective conditions the frequency of induced reversions varied from 0.56-10(-4) to 10.55-10(-4) in different experiments; after 6 days -- from 0.05-10(-4) to 4.0-10(-4). In all cases where induction was detected, the difference, between the frequency of glutamine prototrophs in treated and control plates was significant. Glutamine independence proved to be stable after prolonged cultivation under non-selective conditions, the degree of prototrophy being greatly unequal in different clones. No differnce in this respect was detected between spontaneous and NG-induced revertants. The proposed system of reverse mutations can be used for studying diverse problems of somatic cell genetics.     

Insulin-stimulated phosphatidylinositol 3-kinase. Association with a 185-kDa tyrosine-phosphorylated protein (IRS-1) and localization in a low density membrane vesicle

Insulin stimulates the appearance of anti-tyrosine(P)-immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipocytes, predominantly in an intracellular membrane fraction (Kelly, K. L., Ruderman, N. B., and Chen, K. S. (1992) J. Biol. Chem. 267, 3423-3428). Neither the mechanism underlying this activation nor the precise subcellular compartment in which it occurs is known. To address these questions, studies were performed using isolated rat adipocytes and subcellular fractions of these cells. In intact cells, insulin stimulated the rapid appearance of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate in 32P-labeled adipocytes without changing the labeling of phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, or phosphatidylinositol 4,5-bisphosphate. This effect was accompanied by the tyrosyl phosphorylation of a 185-kDa protein, tentatively identified as IRS-1, with which PI 3-kinase became associated. The majority of the p85, the regulatory subunit of PI 3-kinase, in untreated adipocytes was present in the cytosol; however, neither the activity of PI 3-kinase nor the total amount of p85 in this fraction was modified in response to insulin. In contrast, insulin increased the association of p85 with IRS-1, the tyrosyl phosphorylation of the IRS-1 associated with p85, and the total activity of PI 3-kinase in the plasma membranes and low density membranes. After insulin treatment, similar amounts of p85 were bound to IRS-1 in the low density and plasma membrane fractions; however, tyrosyl-phosphorylated IRS-1 and PI 3-kinase activity were an order of magnitude greater in the low density membranes. The complex of tyrosyl-phosphorylated IRS-1.p85 that formed in response to insulin was localized to a very low density vesicle subpopulation that could be distinguished from vesicles containing the GLUT-4 glucose transporter and the insulin receptor. These data suggest that the activation of PI 3-kinase by insulin in the adipocyte involves the formation of a complex between IRS-1 and PI 3-kinase in a very low density membrane fraction that is not enriched in GLUT-4 or insulin receptors. They also suggest that PI 3-kinase activation correlates more closely with the extent of tyrosyl phosphorylation of the IRS-1 complexed to PI 3-kinase than it does to the amount of p85 bound to IRS-1.     

Cellular pathways acting along the germband and in the amnioserosa may participate in germband retraction of the Drosophila melanogaster embryo

Germband retraction in Drosophila melanogaster, like most embryonic morphogenetic events in this organism and in higher eukaryotes, is not well understood. We have taken several approaches to study the relationships between previously identified mutations (u-shaped, serpent, hindsight and tailup) that selectively cause germband retraction defects in homozygous embryos, and a more pleiotropically acting locus, DER/faint little ball. Our observations from genetic, immunohistochemical, and embryo culture experiments suggest that the former four loci are elements of at least two parallel and partially redundant cellular pathways that affect germband retraction by acting in amnioserosal development or maintenance. An additional discrete and unique pathway, represented by DER/faint little ball, is likely to function in the germband itself. While the role of the amnioserosa during germband retraction appears to be permissive, the action of DER in the germband may be mediated by the cytoskeleton.     

A comparison of the effect of benzopyrones and other drugs with anti-inflammatory properties on acid and neutral protease activity levels in various tissues after thermal injury

Generally, the benzopyrones enhanced acid protease activity levels in the oedema fluid and the extracellular compartment of the skin. This is the region where thermal injury has its greatest impact. The proteolysis induced by the drugs in this region represents a means of rapidly reducing some of the derangements which the thermal injury has caused. Levamisole also enhanced acid protease activity levels in the serum and extracellular compartment of the skin 6 hours after thermal injury, while Reparil had the same effect at 24 hours. Generally the benzopyrones had little or no effect on neutral protease levels, while levamisole and Reparil caused their depression. The later effects could possibly be attributed to serum deactivation or to inhibition of their release. The enzyme enhancing activity of these drugs has been shown to correlate remarkably well with their oedema reducing ability. Generally, those which increased enzyme activity levels the most were the most effective in reducing the oedema. The cells upon which the drugs exert their effects in thermal oedema mainly seem to be the macrophages; the fibroblasts seem to be of secondary importance. This is to be contrasted with their action in the initial stages of lymphoedema where they are believed to stimulate the neutrophils. The net result of the proteolysis is many small fragments which can rapidly leave the injured tissue thus releasing the oedema fluid.