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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 811 records · Page 45Linked to original sources
PubMed1997

Knowledge and attitudes about depression among non-generalists and generalists.

BACKGROUND: The purpose of this study was to learn more about barriers to managing depression by comparing knowledge and attitudes about depression among physicians, internists, obstetrician-gynecologists, and a reference group of psychiatrists. Among the non-psychiatrists, we hypothesized that generalist physicians would have more favorable attitudes and greater knowledge about depression than non-generalists. METHODS: Survey questionnaires were sent to resident and faculty physicians (N = 375) of two university-affiliated medical centers. The physicians were classified as non-generalists (medicine subspecialists, transitional year interns, and obstetrician-gynecologists), generalists (general internists and family physicians), and psychiatrists. A 33-item written questionnaire assessed knowledge and three attitudinal dimensions: attitudes attributed by physicians to patients; physicians' confidence in managing depression; and physicians' psychosocial orientation. A knowledge scale and an attitudes scale were scored by adding the number of knowledge items answered correctly and the more favorable attitudinal responses. Multivariable regression was used to identify physician characteristics among non-generalists and generalists associated with higher knowledge and attitudinal scores. RESULTS: Response rate was 82%. Sixty percent of the respondents were male, 63% were resident physicians, and 14% had advanced psychosocial training. Non-generalists and generalists had similar demographic characteristics, but psychiatrists were significantly more experienced. Psychiatrists had the most favorable attitudes, followed by generalists and non-generalists. Compared with non-generalists, generalists were more confident in prescribing antidepressants (62% vs 25%), more likely to report that treating depression is rewarding (71% vs 39%), and less likely to refer to a psychiatrist (58% vs 79%). Generalist classification, increased experience, and higher levels of psychosocial training were associated with more favorable attitudes. Knowledge scores were significantly higher for psychiatrists than for non-generalists and generalists. Among non-psychiatrists, correct responses for knowledge items were: treatment efficacy (61%), treatment duration (59%), > or = 5 DSM-III-R criteria (52%), and prevalence of depression (30%). Among those with incorrect responses, both non-generalists and generalists overestimated the prevalence (52%) and underestimated the efficacy of drug therapy (30%). CONCLUSIONS: Generalists and non-generalists have similar and relatively good basic knowledge about depression. Misperceptions about treatment efficacy, and attitudinal barriers, particularly among non-generalists, may compromise the physician's ability to diagnose and manage depression.

Depression↗
PubMed1997

[Coronary artery bypass grafting in patients aged 80 years or older].

Coronary artery bypass grafting (CABG) in elderly patients was increasing in recent years. Between January 1989, and December 1996, 11 patients aged 80 years or older (mean 81) underwent CABG in our hospital. Nine patients (82%) were in New York Heart Association class III or IV. Emergency surgery was required in 4 patients (36%). Incidence of emergency surgery is higher than younger patients (p < 0.005), emergency surgery required 7.7% (46/592) in younger patients. The operative mortality was 27% for these 80 years or older. It was one in elective cases and two of four (50%) in emergency cases. One operative death in elective cases was concomitant operation with arch aneurysm. More patients of CABG operations in octogenarians required emergency surgery, and emergency surgery is high operative mortality. Thus CABG in octogenarians should be performed earlier, not be denied because of age alone.

Age Factors↗
PubMed1997

Anorexia nervosa and bulimia--a Singapore perspective.

OBJECTIVE: To study the clinical characteristics of patients with anorexia nervosa and bulimia. METHOD: Fifty patients presenting to our department from 1991-1996 were identified and studied retrospectively. RESULTS: There was an increase in presentations for anorexia and bulimia over the period studied. The majority exhibited body image disturbance, morbid fear of fatness and compulsive efforts to lose weight, not dissimilar to that described in the Western literature. Significant transcultural differences were not found. Those with significant binge eating were more likely to present at a later age, have a higher BMI, menorrhoea, associated vomiting and/or laxative use, have prominent depressive symptoms and a history of self-harm. Compared to anorexics, bulimics were more likely to have relationship stresses and a history of self-harm. CONCLUSION: The clinical characteristics of anorexics and bulimics are more striking for their similarities rather than differences to that described in the West.

Adolescent↗
PubMed1997

The study of the relationship between the activity of phospholipase A2 and acute hypoxic pulmonary arterial pressure.

The role of phospholipase A2 (PLA2) and related inflammatory mediators in the mechanism of hypoxic pulmonary arterial hypertension was studied. Thirty Sprague-Dawley rats were equally divided into three groups at random: group A was the normal control group; group B was given 10% oxygen ventilation; group C was given 10% oxygen ventilation too and, at the same time, dexamethasone was injected into the external jugular vein. The pulmonary arterial pressure (PAP) was measured by inserting a microcatheter into pulmonary artery. After 30 minutes of hypoxia, the activity of PLA2, platelet activating factor (PAF), prostaglandin E2 (PGE2) and tromboxane B2 (TXB2) were measured in blood and lung tissue. After hypoxia, the mean pulmonary arterial pressure (mPAP), the PLA2 activity, PGE2, TXB2 and PAF in blood and lung tissue of group B were significantly higher than in group A; in group C the same parameters were lower than in group B. In hypoxia, a positive correlations was found between the PLA2 activity and mPAP, PAF, PGE2, TXB2 respectively; positive correlations were also found between PAF, PGE2, TXB2 and mPAP. PLA2 induced release of inflammation mediators, plays an important role in the mechanism of the acute hypoxic pulmonary arterial hypertension.

Acute Disease↗
PubMed1997

Mpp10p, a new protein component of the U3 snoRNP required for processing of 18S rRNA precursors.

We have used the yeast, Saccharomyces cerevisiae, as a model system to identify a new protein component of the U3 small nucleolar ribonucleoprotein (snoRNP) and to study its role in pre-rRNA processing. Mpp10p, which we have cloned and characterized from humans, mice and yeast, is a 110 kDa protein in yeast. Antibodies to it immunoprecipitate the U3 snoRNA, indicating that it is a U3 snoRNP component. MPP10 is an essential gene. Depletion of Mpp10p by repression of MPP10 expressed from a conditional promoter causes slow growth. Analysis of pre-rRNA processing in the depleted cells indicates that Mpp10p is required for processing at the 3 U3 snoRNA-dependent sites in the pre-rRNA (A0, A1, A2). Truncations of terminal charged domains create Mpp10 proteins that confer slow growth at 30 degrees C and/or at 22 degrees C. Analysis of pre-rRNA processing in these mutants indicates a deficiency in processing at only two of the U3 snoRNA-dependent sites in the pre-rRNA (A1 and A2). Therefore truncated Mpp10 proteins are able to separate the function of the U3 snoRNP into a requirement for it in distinct processing events.

Animals↗
PubMed1996

Cocaethylene stimulates the secretion of ACTH and corticosterone and the transcriptional activation of hypothalamic NGFI-B.

Cocaethylene is an active cocaine metabolite formed by hepatic carboxylesterases in the presence of alcohol. The effects of cocaethylene on the hypothalamic-pituitary-adrenal (HPA) axis were investigated in vivo using adrenocorticotropic hormone (ACTH) and corticosterone secretion as indices of peripheral stimulation. To ascertain the central effects of cocaethylene on discrete neurons of the paraventricular nucleus (PVN) of the hypothalamus, a specific cRNA probe was used to follow changes in the transcriptional activation of nerve growth factor I-B (NGFI-B), a member of the family of immediate-early genes. Intravenous (i.v.) injection of cocaethylene (16 mumol/kg) to rats produced a marked but transient increase in plasma levels of ACTH and corticosterone within 10 min of drug exposure. Secretion of these hormones was accompanied by elevated levels of NGFI-B mRNA detected 30 min after i.v. or intraperitoneal (i.p., 60 mumol/kg) cocaethylene administration. The transcriptional stimulation of this immediate-early gene within parvocellular secretory neurons was relatively brief in duration, returning to basal levels by 180 min after drug exposure. As expected both routes of cocaethylene administration produced an increase in locomotor activity compared to saline-vehicle rats, with no differences between i.v. or i.p. routes with respect to duration of behavioral activation. Taken together, these findings indicate that cocaethylene has neuroendocrine properties on its own, targeting a critical region of the brain that regulates stressful events in the body. This, combined with other neurochemical properties, points to the possibility of cocaethylene augmenting the effects of a drug-dependent state.

Adrenocorticotropic Hormone↗
PubMed1996

Mixed disulfides from disulfiram inhibit the benzo[a]pyrene induced mutagenesis.

Some mixed disulfides derived from disulfiram and endogenous thiol compounds have been synthesized, biochemically characterized and their potential antigenotoxic effects have been proposed. The present study evaluated the mutagenic and antimutagenic specificities of two mixed disulfides using S. typhimurium reversion assay, namely S-(N,N-diethyldithiocarbamoyl)-N-acetylcysteine (AC-DDTC) and-L-glutathione (GS-DDTC). The two mixed disulfides were not mutagenic to Salmonella strains TA98 and TA100 in the presence or absence of S9 mixture. The increased number of revertants by benzo[a]pyrene (B(a)P) has been reduced to the control level by the preincubation with AC-DDTC or GS-DDTC. It was not due to the killing effect of B(a)P, mixed disulfides or B(a)P-disulfide mixture. The antimutagenic effect of AC-DDTC was more potent than that of GS-DDTC. These results indicate that AC-DDTC and GS-DDTC may have a role to play in reducing the risk of mutagenic effects of B(a)P.

Animals↗
PubMed1996

Central nervous system expression of HIV-1 Gp120 activates the hypothalamic-pituitary-adrenal axis: evidence for involvement of NMDA receptors and nitric oxide synthase.

The impact of HIV-1 expression in the brain on the development of AIDS is unknown. In the present study, we examined the hypothalamic-pituitary-adrenal (HPA) axis in a transgenic model in which expression of the HIV-1 envelope glycoprotein gp120 induced central nervous system (CNS) damage similar to that seen in HIV-1-infected patients. Compared with nontransgenic littermates, gp120 transgenic mice showed significant increases in plasma corticosterone and adrenocorticotrophic hormone (ACTH) levels and pituitary ACTH content. To determine whether this activation of the HPA axis could be mediated by ACTH secretagogues, the effect of recombinant gp120 on the release of these factors from hypothalamic slices was investigated in vitro. Recombinant gp120 induced release of the ACTH secretagogue arginine vasopressin from nontransgenic hypothalamic slices in a calcium-dependent fashion. This effect was inhibited by antagonists of N-methyl-D-aspartate (NMDA) receptors or of nitric oxide synthase (NOS), suggesting a role for NMDA receptor stimulation and NOS activity. Further evidence for a role of free radicals was obtained from bigenic mice coexpressing gp120 and the free radical scavenger human copper/zinc superoxide dismutase which showed normal corticosterone levels. This might relate to superoxide dismutase-mediated scavenging of superoxides generated by NOS. These findings demonstrate that CNS expression of a viral envelope protein can activate the HPA axis and thereby alter peripheral levels of immunomodulatory hormones.

Adrenocorticotropic Hormone↗
PubMed1996

Mixed Monolayer Properties of Tetradecanoic Acid with n-Perfluorocarboxylic Acids with 10, 12, 14, 16, and 18 Carbon Atoms

Surface pressure (pi) and surface potential (DeltaV)-area (A) isotherms were obtained for mixed monolayers of different perfluorocarboxylic acids (FCs) with a hydrocarbon fatty acid, tetradecanoic acid (HC14), on a substrate solution of pH 1.0 as a function of compositions in the mixture by employing the Langmuir method and the ionizing electrode method. Data for the mixed monolayers were analyzed in terms of the additivity rule. Judging from Matuo's classification of two-dimensional phase diagrams, our phase diagrams might be classified into three types. The first is a positive azeotrope type; the combinations of tetradecanoic acid (HC14) with perfluorodecanoic acid (FC10) and with perfluorododecanoic acid (FC12) seem miscible with each other. The second is a completely immiscible type; the combination of perfluorotetradecanoic acid (FC14) and tetradecanoic acid. The third might be a eutectic type, to which the combinations of HC14 with FC16 and with FC18 are assigned; they are miscible in the expanded state but immiscible in the condensed state. Furthermore, the data on the mean molecular area, the surface dipole moment, and the phase diagrams constructed enabled us to estimate the molecular orientation of the respective acids in the mixed monolayer state.

Journal Article↗
PubMed1996

Expression of glutamyl-tRNA reductase in Escherichia coli.

The biosynthesis of the hemes, chlorophylls, corrins and other tetrapyrroles begins with the synthesis of 5-aminolevulinic acid (ALA). The pathway is highly conserved except for the synthesis of ALA which is derived from glycine and succinyl CoA (C4) in most eukaryotes and from glutamate (C5) in most bacteria and in green plants. In C5, glutamyl-tRNA synthetase (GTS) converts glutamate to glutamyl-tRNA (glu-tRNA), which is reduced by glutamyl-tRNA reductase (GTR) to glutamyl-1-semialdehyde (GSA), which is converted by aminotransferase (GSA-AT) to ALA. Since GTS is also involved in protein synthesis and GSA can be converted to ALA non-enzymatically, it is highly probable that control of ALA synthesis and thus of the whole pathway resides in the GTR step. In Escherichia coli, GTR is the gene product of hemA. BL21(DE3), a protease-deficient strain which contains the T7 RNA polymerase gene in front of a lac promoter, was transformed with a pET14b-based vector, pWC01, harboring hemA in front of a T7 promoter and ORF1 which is transcribed in the opposite direction. The transformed strain, WC1201, secreted ALA and porphyrins into the medium. Induction of expression of hemA by WC1201 was optimized for concentration of inducer (IPTG, 5 mM), temperature (37 degrees C), presence of betaine and sorbitol (no change) and time of induction (2h). GTR was observable as a 46 kDa band by Brilliant blue G staining of SDS-PAGE gels. Sonicates of the induction mixture exhibited strong ALA synthesis activity which was enhanced by tRNAglu. Most of the activity was in the supernatant of the sonicate indicating that GTR is a soluble enzyme. The induced strain had more GTS activity than the uninduced strain which had more GTS activity than its parent wild-type strain. Autoradiography on native gradient PAGE showed that GTR expressed in vivo by induction of WC1201 had a molecular weight of approx. 117 kDa. Gel filtration of the induced sonicate showed a peak of enzymatic activity at about 126 kDa. When pET14b- or pUC19-based plasmids harboring hemA and ORF1, or importantly, a pUC19-based plasmid harboring only hemA and not ORF1, were expressed in an in vitro transcription-translation system, native gradient PAGE showed a product with a molecular weight of approximately 175 kDA. This expression was higher in the presence of tRNAglu. When the 117 kDa and 175 kDa proteins were excised from their native gels respectively, and run on SDS PAGE, autoradiography showed bands at 46 kDa. We conclude that GTR is present in both high molecular weight species. Since overexpression of hemA from pET14b-based plasmids is associated with increased glutamyl-tRNA synthetase activity, the 175 kDa species may represent different complexes of GTR, GTS and glutamyl-tRNA as observed in Chlamydomonas and the 117-126 kDa species may be an dimer of GTR associated with glu-tRNA or a complex of GTR, GTS and glu-tRNA. These possibilities are being investigated.

Aldehyde Oxidoreductases↗