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Biomedical subjects

L H Cohen

Publications and source records attributed to L H Cohen.

At least 55 records · Page 3Linked to original sources
PubMed1989

Regulation of squalene synthetase in human hepatoma cell line Hep G2 by sterols, and not by mevalonate-derived non-sterols.

Incubations of Hep G2 cells for 18 h with human low-density lipoprotein (LDL) resulted in a decrease of squalene synthetase activity, whereas heavy high-density lipoprotein (hHDL) stimulated the activity. Simultaneous addition of LDL abolished the hHDL-induced stimulation, indicating that manipulating the regulatory sterol pool within the cells influenced the enzyme activity. Blocking the endogenous cholesterol synthesis either at the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase site with compactin or at the 2,3-oxidosqualene cyclase site with the inhibitor U18666A gave rise to an elevation of the squalene synthetase activity. Simultaneous addition of mevalonate abolished the compactin-induced increase. However, at total blockade of sterol synthesis by 30 microM U18666A, added compactin and/or mevalonate did not change the enzyme activity further. It was concluded that sterols regulate the squalene synthetase activity, whereas, in contrast with the regulation of the HMG-CoA reductase activity in Hep G2 cells, mevalonate-derived non-sterols did not influence this enzyme.

Androstenes↗
PubMed1989

Coping strategies and psychological distress: prospective analyses of early and middle adolescents.

Administered measures of coping, life events, and anxiety and depression to junior high and senior high school samples on two occasions, separated by a 5-month interval. Factor analyses supported the creation of coping subscales for problem solving, cognitive coping, social entertainment, physical exercise, and peer support. A one-item index of parental support was also included in the analyses. The coping subscales showed moderate temporal stability. Mothers' reports of their children's coping provided only marginal support for the validity of the adolescents' self-reports. Prospective regression analyses of the early adolescent data revealed that problem-solving coping was negatively related to depression, and that social entertainment coping was negatively related to anxiety. The prospective effects for the middle adolescents' coping were nonsignificant. The findings are discussed in terms of their implications for the measurement of adolescent coping strategies and research on the relation between these strategies and psychological functioning.

Adaptation, Psychological↗
PubMed1989

Instrumentality as a life-stress moderator for early versus middle adolescents.

Used a longitudinal design to test the main and stress-buffering effects of instrumentality of measures of trait anxiety, depression, and self-esteem. Ss were early (junior high school) and middle (senior high school) adolescent boys and girls. The hypothesis that instrumentality would be negatively related to psychological distress was supported by the cross-sectional and longitudinal regression analyses of every subgroup of Ss. The hypothesized stress-buffering effect of instrumentality was found in the cross-sectional and longitudinal analyses of senior high girls, specifically in the context of interpersonal negative events (relationship stress). The analyses for junior high girls revealed that instrumentality was beneficial only at a low level of relationship stress. There were no significant interaction effects in the regression analyses of boys. The findings suggest that, when experiencing relationship stress, instrumentality is helpful for middle adolescent girls but not for early adolescent girls. Therefore, future research on adolescents' life-stress adjustment should consider the roles of gender, age, personality, and type of life stress.

Adaptation, Psychological↗
PubMed1989

Relationships among life stress, perceived family environment, and the psychological distress of spina bifida adolescents.

Fifty-three teen-agers with spina bifida participated in a mail survey and completed measures of recent life events, perceived family environment, and psychological distress. Low levels of perceived family conflict and control served as life stress buffers in the prediction of distress, whereas a high level of perceived independence served as a life stress exacerbator. These interaction effects differ from those obtained for a normal sample of adolescents in the lone previous study (Burt, Cohen, & Bjorck, 1988) that reported comparable analyses. The results suggest that the process by which family environments moderate stress adjustment differs for able-bodied vs. spina bifida adolescents.

Adaptation, Psychological↗
PubMed1988

Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA contents in human hepatoma cell line Hep G2 by distinct classes of mevalonate-derived metabolites.

Hep G2 cells were incubated under conditions known to influence the HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase activity, e.g. in the presence of compactin (a competitive inhibitor of HMG-CoA reductase itself) and U18666A (a squalene-2,3-epoxide cyclase inhibitor). We studied the effects of these conditions both on the HMG-CoA reductase activity and on the reductase mRNA content. In the presence of compactin the mRNA content increased, but less than the enzyme activity, as determined after removal of the inhibitor. The increase in mRNA could be prevented by addition of mevalonate or by a combination of low-density lipoprotein (LDL) plus a low concentration of mevalonate. LDL alone prevented the compactin-induced increases in mRNA and activity only partially. The effect of U18666A on reductase mRNA content and activity was biphasic, i.e. a slight decrease at low (0.3-0.5 microM) concentrations, with a concomitant formation of polar sterols [Boogaard, Griffioen & Cohen (1987) Biochem. J. 241, 345-351], and an increase at high (20-30 microM) concentrations, with complete blockage of sterol formation. At these high concentrations of U18666A, additional compactin (2 microM) increased the reductase activity, but not the mRNA content. We conclude that non-sterol metabolites of mevalonate regulate exclusively at the enzyme level, whereas sterol metabolites regulate at the reductase mRNA level. In the latter group of regulators we distinguish mevalonate metabolites which can, and metabolites which cannot, be replaced by exogenous LDL.

Androstenes↗
PubMed1988

Perceived family environment as a moderator of young adolescents' life stress adjustment.

A longitudinal design was employed to test the main and stress-moderating effects of young adolescents' perceived family environment (Family Environment Scales; FES; Moos & Moos, 1981) on their depression, anxiety, and self-esteem. This study was part of a larger longitudinal project (L. Cohen, Burt, & Bjorck, 1987) that demonstrated the significant cross-sectional effects of the young adolescents' controllable and uncontrollable negative events, and the significant longitudinal effects of the former. The present cross-sectional analyses demonstrated the hypothesized main effects of the FES scores; families perceived as cohesive, organized, and expressive were related to positive psychological functioning, whereas families perceived as conflict-ridden and controlling were related to negative functioning. However, in general these effects were nonsignificant in the longitudinal analyses. Although there were a number of significant Negative Events x FES interactions, in no instance did the pattern support the hypothesized stress-buffering role of positive family climate.

Adolescent↗
PubMed1988

Effects of induced mood on self-reported life events and perceived and received social support.

This study tested the relation between mood (depressed [D], elated [E], or neutral [N]), induced by the Velten (1968) procedure, and college students' responses on a subjectively scored life events questionnaire and measures of perceived and received social support. A manipulation check showed that the mood manipulation was successful. There was a significant mood effect on the number of self-reported negative life events, with E subjects reporting the fewest. However, mood had no significant effect on the number of self-reported positive life events or the rated intensity of negative and positive events. Mood had a significant effect on perceived social support, with D subjects scoring the lowest. Self-report of received social support, however, was not affected by the mood manipulation. The findings challenge the widespread use of life event and perceived social support questionnaires whose independence from a mood-related response bias has not been adequately demonstrated. The findings also challenge causal interpretation of significant effects for self-reported life stress and perceived social support obtained in cross-sectional prediction studies of concurrent psychological distress.

Depression↗
PubMed1988

The production of tissue-specific histone complements during development.

At least two mechanisms generate tissue differences in the histone subtype composition during development: subtype dilution and subtype replacement. Subtype dilution, which occurs when cells continue dividing after having ceased to synthesize one more histone subtypes, allows the elimination of stable subtypes. It is the major mechanism generating cell differences in histone composition in sea urchin embryogenesis. Subtype replacement has been observed in mammalian tissues, both in the intact animal and in cultured cells. It is most evident in nondividing cells but occurs to some extent in dividing cells as well. Examples of the two mechanisms are presented and their possible biological significance, as well as that of the differences they produce, is discussed.

Animals↗
PubMed1987

Effect of ketoconazole on cholesterol synthesis and on HMG-CoA reductase and LDL-receptor activities in Hep G2 cells.

Ketoconazole, an imidazole derivative, is a member of a class of metabolic inhibitors acting specifically at cytochrome-P450 mediated reactions. We studied the effects of this compound on cholesterol synthesis, and on HMG-CoA reductase and LDL receptor activities, in cultures of human hepatoma cell line Hep G2. Ketoconazole, added in concentrations of 2-100 microM, inhibited cholesterol synthesis, and caused accumulation of lanosterol and dihydrolanosterol. Total mass formation of sterols was depressed. After 20 hr preincubation of the cells with the drug in these concentrations, activity of HMG-CoA reductase was markedly decreased, while the receptor-mediated binding, uptake and degradation of human LDL were increased. This increase is at least partly due to a higher affinity of LDL for its receptor. Ketoconazole prevented the fall in LDL-receptor activity caused by preincubation with LDL, whereas it did not affect the suppression caused by preincubation with exogenous mevalonate. These findings are discussed with respect to the involvement of endogenous sterol and non-sterol effectors of reductase and receptor activities.

Carcinoma, Hepatocellular↗
PubMed1987

Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in human hepatoma cell line Hep G2. Effects of inhibitors of cholesterol synthesis on enzyme activity.

Incubating Hep G2 cells for 18 h with triparanol, buthiobate and low concentrations (less than 0.5 microM) of U18666A, inhibitors of desmosterol delta 24-reductase, of lanosterol 14 alpha-demethylase and of squalene-2,3-epoxide cyclase (EC 5.4.99.7) respectively, resulted in a decrease of the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activity. However, U18666A at concentrations higher than 3 microM increased the HMG-CoA reductase activity in a concentration-dependent manner. None of these inhibitors influenced directly the reductase activity in Hep G2 cell homogenates. Analysis by t.l.c. of 14C-labelled non-saponifiable lipids formed from either [14C]acetate or [14C]mevalonate during the cell incubations confirmed the sites of action of the drugs used. Beside the 14C-labelled substrates of the blocked enzymes and 14C-labelled cholesterol, another non-saponifiable lipid fraction was observed, which behaves as polar sterols on t.l.c. This was the case with triparanol and at those concentrations of U18666A that decreased the reductase activity, suggesting that polar sterols may play a role in suppressing the reductase activity. In the presence of 30 microM-U18666A (sterol formation blocked) the increase produced by simultaneously added compactin could be prevented by addition of mevalonate. This indicates the existence of a non-sterol mevalonate-derived effector in addition to a sterol-dependent regulation. LDL (low-density lipoprotein), which was shown to be able to decrease the compactin-induced increase in reductase activity, could not prevent the U18666A-induced increase. On the contrary, LDL enhanced the U18666A effect, showing that the LDL regulation is not merely the result of introducing cholesterol to the cells.

Androstenes↗
PubMed1987

Sex roles and social support as moderators of life stress adjustment.

In this study we used a longitudinal design to test the stress-buffering effects of sex role orientation in combination with perceived social support on measures of trait anxiety and depression. College undergraduates served as subjects. The cross-sectional analyses provided strong support for the hypothesis that masculinity would function as a life stress buffer. The hypothesis that social support would serve as a stress buffer when coupled with high masculinity was supported by one of the cross-sectional analyses as well as the longitudinal analysis. This pattern was found primarily for perceptions of tangible social support. The longitudinal analysis also revealed a significant interaction involving negative life events and masculinity and femininity. This interaction effect provided unexpected support for a balance model of androgyny, in that non-sex-typed subjects showed greater resilience to recent life stress than did sex-typed subjects. The findings are discussed in terms of their implications for the study of life stress adjustment.

Adolescent↗
PubMed1986

Regulation of squalene synthetase activity in rat liver: elevation by cholestyramine, but no diurnal variation.

Squalene synthetase activity in liver microsomes from rats sacrificed at three different times of the diurnal cycle showed no significant differences. Addition of 4% cholestyramine to the food resulted in a marked increase in activity (280% of control), independent of the time of killing. 3-Hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase activity, determined as positive controls, were also found to be elevated by cholestyramine and additionally showed a diurnal variation. On the other hand, five control enzyme activities, not directly related to cholesterol metabolism, i.e. glutamate dehydrogenase, NADPH cytochrome-c reductase, beta-hexosaminidase, catalase and acyl coenzyme A oxidase, showed neither an influence of cholestyramine feeding nor a time of sacrifice dependent variation.

Animals↗
PubMed1986

Stimulation of the LDL receptor activity in the human hepatoma cell line Hep G2 by high-density serum fractions.

The regulation of the LDL receptor activity in the human hepatoma cell line Hep G2 was studied. In Hep G2 cells, in contrast with fibroblasts, the LDL receptor activity was increased 2.5-fold upon increasing the concentration of normal whole serum in the culture medium from 20 to 100% by volume. Incubation of the Hep G2 cells with physiological concentrations of LDL (up to 700 micrograms/ml) instead of incubation under serum-free conditions resulted in a maximum 2-fold decrease in LDL receptor activity (10-fold decrease in fibroblasts). Incubation with physiological concentrations of HDL with a density of between 1.16 and 1.20 g/ml (heavy HDL) resulted in an approximately 7-fold increase in LDL receptor activity (1.5-fold increase in fibroblasts). This increased LDL receptor activity is due to an increase in the number of LDL receptors. Furthermore, simultaneous incubation of Hep G2 cells with LDL and heavy HDL (both 200 micrograms/ml) resulted in a 3-fold stimulation of the LDL receptor activity as compared with incubation in serum-free medium. 3-Hydroxy-3-methylglutaryl-CoA reductase activity was also stimulated after incubation of Hep G2 with heavy HDL (up to 3-fold). The increased LDL receptor activity in Hep G2 cells after incubation with heavy HDL was independent of the action of lecithin:cholesterol acyltransferase during that incubation. However, previous modification of heavy HDL by lecithin:cholesterol acyltransferase resulted in an enhanced ability of heavy HDL to stimulate the LDL receptor activity. Our results indicate that in Hep G2 cells the heavy HDL-mediated stimulation of the LDL receptor activity overrules the LDL-mediated down-regulation and raises the suggestion that in man the presence of heavy HDL and the action of lecithin:cholesterol acyltransferase in plasma may be of importance in receptor-mediated catabolism of LDL by the liver.

Blood↗
PubMed1986

Intraoperative streptokinase. An adjunct to mechanical thrombectomy in the management of acute ischemia.

Streptokinase was injected directly into the arterial tree following balloon-catheter embolectomy on 13 occasions to remove residual thrombus that could not be mechanically retrieved in 12 patients with imminent limb (ten patients) or kidney (two patients) necrosis. Effective lysis, confirmed by arteriography, pulse return, and increased ankle pressures, was achieved in 11 trials (85%). Bleeding complications, minor in three patients and severe in two patients, were ascribed to systemic lysis although other factors were contributory. One of five deaths was related to therapy. Six limbs were salvaged. The average total dose of streptokinase used, 110,000 units, was given in intermittent boluses of 25,000 to 50,000 units injected below a clamp placed to temporarily occlude distal circulation. Safe application of this technique requires intraoperative monitoring of coagulation parameters, aggressive replacement therapy, and prudent patient selection. This preliminary experience suggests that intraoperative lytic therapy (1) is an effective method for clearing thrombus not amenable to mechanical extraction and (2) may improve patency and tissue salvage.

Acute Disease↗
PubMed1986

The fate of the small micromeres in sea urchin development.

We show that in sea urchin embryos, the daughter cells of the small micromeres become part of the coelomic sacs, in contrast to the long-held view that these sacs are purely of macromere origin. In addition, after prolonged mitotic quiescence, and following their incorporation into the coelomic sacs, these cells resume dividing, contrary to the previous view that they do not divide. Since coelomic sac cells give rise to much of the adult urchin, our results indicate that the small micromeres are founders of cell lineages involved in the formation of adult tissues. The setting aside of these cells in a nondividing state may be analogous to a phenomenon in Drosophila development, in which primordial imaginal and germ cells divide approximately once after the blastoderm stage and do not resume dividing until the larval stage.

Animals↗