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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 847 records · Page 47Linked to original sources
PubMed1996

Natural-product inhibitors of human DNA ligase I.

Enzymatic activity mediated by recombinant human DNA ligase I (hLI), in conjunction with tannin removal procedures, has been applied to a natural-product screen involving approximately 1000 plant extracts and various pure compounds. The primary hLI activity assay involved the measurement of the amount of radiolabelled phosphate in a synthetic nucleic acid hybrid that becomes resistant to alkaline phosphatase as a result of ligation. A bioactivity-guided fractionation scheme resulted in the isolation of ursolic [IC50=100 micrograms/ml (216 microM)] and oleanolic [IC50=100 micrograms/ml (216 microM)] acids from Tricalysia niamniamensis Hiern (Rubiaceae), which demonstrated similar DNA ligase inhibition profiles to other triterpenes such as aleuritolic acid. Protolichesterinic acid [IC50=6 micrograms/ml (20 microM)], swertifrancheside [IC50 = 8 micrograms/ml(11)microM)] and fulvoplumierin [IC50=87 micrograms/ml (357 microM)] represent three additional natural-product structural classes that inhibit hLI. Fagaronine chloride [IC50=10 micrograms/ml (27 micronM] and certain flavonoids are also among the pure natural products that were found to disrupt the activity of the enzyme, consistent with their nucleic acid intercalative properties. Further analyses revealed that some of the hLI-inhibitory compounds interfered with the initial adenylation step of the ligation reaction, indicating a direct interaction with the enzyme protein. However, in all cases, this enzyme-inhibitor interaction did not disrupt the DNA relaxation activity mediated by hLI. These results indicate that, although the same enzyme active site may be involved in both enzyme adenylation and DNA relaxation, inhibitors may exert allosteric effects by inducing conformational changes that disrupt only one of these activities. Studies with inhibitors are important for the assignment of specific cellular functions to these enzymes, as well as for their development into clinically useful antitumour agents.

Adenosine Triphosphate↗
PubMed1996

Nuclear/cytoplasmic localization of the von Hippel-Lindau tumor suppressor gene product is determined by cell density.

The product of the von Hippel-Lindau (VHL) tumor suppressor gene, the gene inactivated in VHL disease and in sporadic clear-cell renal carcinomas, has recently been shown to have as a functional target the transcription elongation complex, elongin (also called SIII). Here it is shown that there is a tightly regulated, cell-density-dependent transport of VHL into and/or out of the nucleus. In densely grown cells, the VHL protein is predominantly in the cytoplasm, whereas in sparse cultures, most of the protein can be detected in the nucleus. We have identified a putative nuclear localization signal in the first 60 and first 28 amino acids of the human and rat VHL protein, respectively. Sequences in the C-terminal region of the VHL protein may also be required for localization to the cytosol. These findings provide the initial indication of a novel cell density-dependent pathway that is responsible for the regulation of VHL cellular localization.

3T3 Cells↗
PubMed1996

Glycinergic inhibition in the turtle spinal cord regulates the intensity and pattern of fictive flexion reflex motor output.

Application of strychnine sulfate (10-50 mu M) to the anterior hindlimb enlargement of the turtle spinal cord increased the amplitude of the ipsilateral fictive flexion reflex and revealed a contralateral (crossed) fictive flexion reflex response to cutaneous stimulation of the foot. Strychnine abolished the crossed inhibition of fictive flexion reflex that was normally evoked by contralateral foot stimulation, unmasking the crossed excitation. Our observations are consistent with the hypothesis that intraspinal inhibition mediated by strychnine-sensitive glycine receptors regulates the amplitude of fictive flexion reflex motor output and confines the response to the appropriate neural pathways.

Animals↗
PubMed1996

Pancreatic islet expression of the homeobox factor STF-1 relies on an E-box motif that binds USF.

The commitment of cells to specific lineages during development is determined in large part by the relative expression of various homeodomain (HOX) selector proteins, which mediate the activation of distinct genetic programs. But the mechanisms by which individual HOX genes are themselves targeted for expression in different cell types remain largely uncharacterized. Here, we demonstrate that STF-1, a homeodomain protein that functions in pancreatic morphogenesis and in glucose homeostasis is encoded by an "orphan" homeobox gene on mouse chromosome 5. When fused to a beta-galactosidase reporter gene, a 6.5-kilobase genomic fragment of 5'-flanking sequence from the STF-1 gene shows pancreatic islet specific activity in transgenic mice. Two distinct elements within the STF-1 promoter are required for islet-restricted expression: a distal enhancer sequence located between -3 and -6.5 kilobases and a proximal E-box sequence located at -104, which is recognized primarily by the helix loop helix/leucine zipper nuclear factor USF. As point mutation within the -104 E-box that disrupt USF binding correspondingly impair STF-1 promoter activity, our results demonstrate that USF is an important component of the regulatory apparatus which directs STF-1 expression to pancreatic islet cells.

Animals↗
PubMed1996

Synthesis of [6"-3H]-, (6"-2H)- and (2-2H)-maltotriose.

To prepare labeled precursors for biosynthetic studies, methods for the specific introduction of tritium and deuterium into the reducing and the terminal glucose unit of maltotriose were developed. Thus [6"-3H]- and (6"-2H)-maltotriose (17) and (18) were prepared via selective methoxytritylation, deprotection and subsequent modified Pfitzner-Moffatt oxidation, followed by reduction with sodium borotritiide or sodium borodeuteride, respectively. A simple two step procedure utilizing the Lobry de Bruyn/van Ekenstein transformation gave (2-2H)maltotriose (20).

Carbohydrate Sequence↗
PubMed1996

Stress-wave-induced injury to retinal pigment epithelium cells in vitro.

BACKGROUND AND OBJECTIVE: To determine the survival of in vitro retinal pigment epithelium (RPE) cells subjected to laser-generated stress transients (shock waves) and compare it to that of other cell lines. STUDY DESIGN/MATERIALS AND METHODS: Normal and transformed human retinal pigment epithelium cell lines were used. The cells were imbedded in a gel to prevent motion and cavitation and located in a thin layer at the bottom of a pipette tube closed at one end by a polyimide film. Stress transients were generated by pulsed excimer laser (193 nm and 248 nm wavelength) ablation of the polyimide film. Cell survival, compared to that of unirradiated cells, was assessed by counting surviving cells. The stress was varied from 300 to 740 bars and the number of shock wave pulses applied varied from 5 to 150. RESULTS: Cell survival decreased sharply at the higher stresses but some cells always survived. The lowest survival rate was 50%. Increasing the number of shock wave pulses did not increase cell killing after 20 pulses, demonstrating a saturation effect. In contrast to the transformed cell line, normal cells could not be killed at the highest stress available to us. CONCLUSION: The susceptibility of RPE cells to damage by stress waves varies with cell line. Transformed retinal pigment epithelium cells are more susceptible than normal ones. Saturation of the damage versus number of pulses is observed and a threshold-like behavior for cell killing versus stress is found. Because at least 50% of the cells survived, normal cell growth can serve to replenish damaged cells.

Cell Death↗
PubMed1996

Body dissatisfaction among Chinese undergraduates and its implications for eating disorders in Hong Kong.

OBJECTIVES: To study the body dissatisfaction of Chinese undergraduates and its implications for eating disorders in Hong Kong. METHOD: A large sample of 1,581 subjects completed a "Body Dissatisfaction Questionnaire" (BDQ) which included 25 items about various body parts and questions on body indices, body shape dissatisfaction, and dieting. RESULTS: Whereas male subjects wanted to be taller and stronger in their upper body, the majority of female subjects felt fat in their lower body and were cognitively inclined to weigh less even though they were not obese. They desired a slimming of the stomach, thighs, waist and hip, but not the breasts. Body dissatisfaction was substantially intensified in females who reported a history of dieting in the previous year. Factor analysis of the BDQ affirmed the gender specificity and multidimensionality of body dissatisfaction. DISCUSSION: The typically "Western" pattern of body dissatisfaction has overshadowed the traditional Chinese notions of female beauty based on the face and other nontruncal features. In the context of a rapidly urbanizing Chinese society, this will predispose more females to weight control behavior and eating disorders.

Adolescent↗
PubMed1996

Disordered eating and its psychosocial correlates among Chinese adolescent females in Hong Kong.

OBJECTIVES: To study the prevalence of disordered eating and its relationship with body dissatisfaction, family dysfunction, and depression among Chinese adolescent females in Hong Kong. METHOD: Two hundred ninety-four schoolgirls completed a demographic and weight history sheet, Eating Attitudes Test-26, Body Dissatisfaction Scale, cohesion and conflict subscales of the Family Environment Scale, and the Beck Depression Inventory. RESULTS: 6.5% of subjects were EAT-26 high scores. Disordered eating was positively predicted by body dissatisfaction and, to a lesser extent, family cohesion and conflict. Body dissatisfaction was in turn positively predicted by depression, which was negatively predicted by family cohesion. DISCUSSION: Western patterns of body dissatisfaction and disordered eating attitudes are common among Chinese adolescent females. In the presence of psychosocial vulnerability factors, more weight control behavior and eating disorders may be expected to arise in Hong Kong.

Adolescent↗
PubMed1996

Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10:interferon-gamma-secreting cells in the peripheral blood.

OBJECTIVE: To compare the phenotype and frequency of cells that actively secrete type 1 and type 2 cytokines in systemic lupus erythematosus (SLE) patients (n = 46), versus normal controls (n = 60). METHODS: ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC). RESULTS: T cells were the major source of interleukin-2 (IL-2), IL-4, and interferon gamma (IFN gamma), whereas monocytes were the primary source of IL-6 and IL-10 in the PB of lupus patients. Significantly fewer PBMC spontaneously secreted IFN gamma and IL-2 (P > or = 0.03), while significantly more PBMC produced IL-6 and IL-10 (P < 0.001), in lupus patients versus controls. Disease severity in lupus patients correlated with an elevated ratio of IL-1O:IFN gamma-secreting cells (P < 0.001). CONCLUSION: SLE is characterized by an imbalance in the ratio of type 1:type 2 cytokine-secreting PBMC.

Adult↗
PubMed1996

Cultures in psychiatric nosology: the CCMD-2-R and international classification of mental disorders.

This essay reviews the Chinese Classification of Mental Disorders, Second Edition, Revised (CCMD-2-R, 1995), by assuming the theoretical stance that symptom recognition, disease construction, and taxonomic strategy in psychiatry reflect, and are constrained by, the cultural norms and values as well as the political and economic organizations of the society in which they are embedded. The CCMD-2-R is an ethnomedical classification grounded in both symptomatology and etiology, in which Chinese psychiatrists seek to conform with international classifications on the one hand, and to sustain a nosology with Chinese cultural characteristics on the other. Although broad similarities between the ICD-10 and CCMD-2-R are evident, their blending is legitimately incomplete. Thus, the particular additions (e.g., travelling psychosis, qigong induced mental disorders), deletions (e.g., somatoform disorders, pathological gambling, a number of personality and sexual disorders), retentions (e.g., unipolar mania, neurosis, hysteria, homosexuality), and variations (e.g., depressive neurosis, neurasthenia) reveal not only the changing notions of illness but also the shifting social realities in contemporary China. The CCMD-2-R will be widely used by Chinese psychiatrists and should standardize diagnostic practice and facilitate research, but its impact on everyday clinical work and psychiatric training remains to be evaluated. For Western researchers, it is one avenue for achieving an understanding of the Chinese social world, and should usefully be contrasted with the ICD-10 and DSM-IV as the move towards an international nosology continues.

China↗
PubMed1996

Effect of recombinant human interleukin 2 on neutrophil adherence to endothelial cells in vitro.

Human neutrophils were demonstrated to possess interleukin-2 receptor (IL-2R) beta and gamma chains, not alpha chain and the binding of IL-2 to the IL-2R beta chain on neutrophils plays an important regulatory role in neutrophil functions. We have investigated in this study the hypothesis that recombinant human IL-2 (rhIL-2) can directly activate human neutrophils and increase their adherence to human umbilical vein endothelial cells (HUVEC). In an in vitro microtiter adherence assay, rhIL-2 significantly stimulated neutrophil adherence to HUVEC in a dose- and time-dependent manner, rhILI-2 concentration at 2000 u/ml and 2 hour incubation gave the best neutrophil stimulation. Treatment of neutrophils with rhIL-2 increased the expression of adhesion molecule CD18. Pretreatment of the stimulated neutrophils with a blocking monoclonal antibody to CD18 decreased but not completely blocked the adherence of neutrophils to HUVEC. These data suggest than rhIL-2 can directly stimulate and increase neutrophil adherence to HUVEC by enhancing the expression of CD18 and possibly other adhesion molecules on neutrophil surface. This may be a critical step in the early stage of the vascular leak syndrome (VLS) associated with high dose IL-2 therapy.

Adult↗