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Biomedical subjects

Y S Wang

Publications and source records attributed to Y S Wang.

At least 19 recordsLinked to original sources
PubMed1998

Interaction of a novel GDP exchange inhibitor with the Ras protein.

Mutated, tumorigenic Ras is present in a variety of human tumors. Compounds that inhibit tumorigenic Ras function may be useful in the treatment of Ras-related tumors. The interaction of a novel GDP exchange inhibitor (SCH-54292) with the Ras-GDP protein was studied by NMR spectroscopy. The binding of the inhibitor to the Ras protein was enhanced at low Mg2+ concentrations, which enabled the preparation of a stable complex for NMR study. To understand the enhanced inhibitor binding and the increased GDP dissociation rates of the Ras protein, the conformational changes of the Ras protein at low Mg2+ concentrations was investigated using two-dimensional 1H-15N HSQC experiments. The Ras protein existed in two conformations in slow exchange on the NMR time scale under such conditions. The conformational changes mainly occurred in the GDP binding pocket, in the switch I and the switch II regions, and were reversible. The Ras protein resumed its regular conformation after an excess amount of Mg2+ was added. A model of the inhibitor in complex with the Ras-GDP protein was derived from intra- and intermolecular NOE distance constraints, and revealed that the inhibitor bound to the critical switch II region of the Ras protein.

Amino Acid Sequence↗
PubMed1997

Assessment of the insecticide carbofuran's potential to contaminate groundwater through soils in the subtropics.

The possible contamination of groundwater by the insecticide carbofuran was assessed with the behavior assessment model (BAM) and groundwater pollution-potential model (GWP). Dissipation coefficients of this insecticide in two subtropical soils at different moisture contents and soil temperatures were studied by determining the degradation and adsorption of the herbicide in soils. Movement of carbofuran was studied by leaching the insecticide in a soil column in the laboratory. Under 40% field capacity and at 25 degrees C, more than 80% of carbofuran residue was found in both Luchu clay and Yuanlin silty clay loam after incubation for 63 days. The results indicate that the higher the moisture content in the soil, the less the carbofuran residue under the soil moisture below the field capacity. Carbofuran tends to dissipate more easily in Yuanlin soil than in Luchu soil. The distribution coefficient (Kd) with r2 of 0.69 and 0.92 for Luchu and Yuanlin soils, respectively, was found using the first-order kinetics law. In leaching experiment, carbofuran exhibited easier movement in Luchu than in Yuanlin soil.

Carbofuran↗
PubMed1997

Ras oncoprotein inhibitors: the discovery of potent, ras nucleotide exchange inhibitors and the structural determination of a drug-protein complex.

The nucleotide exchange process is one of the key activation steps regulating the ras protein. This report describes the development of potent, non-nucleotide, small organic inhibitors of the ras nucleotide exchange process. These inhibitors bind to the ras protein in a previously unidentified binding pocket, without displacing bound nucleotide. This report also describes the development and use of mass spectrometry, NMR spectroscopy and molecular modeling techniques to elucidate the structure of a drug-protein complex, and aid in designing new ras inhibitor targets.

Crystallography, X-Ray↗
PubMed1997

Detection and structural characterization of ras oncoprotein-inhibitors complexes by electrospray mass spectrometry.

MS based methodology employing electrospray ionization (ESI) is described for the detection of ternary complexes in which SCH 54292 or SCH 54341 and GDP are noncovalently bound to oncogenic ras protein. The observed molecular weights of 19,816 and 19,570 Da confirmed the presence of noncovalent complexes of ras-GDP-SCH 54292 and ras-GDP-SCH 54341, respectively. We have also performed selective chemical modification of lysine residues of the ras protein complex followed by enzymatic digestion and on-line LC-ESI MS peptide mapping to determine protein-drug binding topography. There was a good correlation between nucleotide exchange inhibition as determined by the enzyme assay and evidence of complex formation as determined by MS.

Amino Acid Sequence↗
PubMed1997

Induction of apoptosis and cytokine gene expression in T-cell lines by sera of patients with systemic lupus erythematosus.

Accelerated apoptosis and improper expression of cytokine genes have been considered as important defects of lymphocytes for the development of systemic lupus erythematosus (SLE). This study was undertaken to test the possible contribution of serum factors obtained from SLE patients to these abnormalities. Molt-4 and Jurkat cells constantly exhibited a slower growth rate as well as more dead cells in culture with SLE sera tested than controls, although the cell cycle progression was apparently unaffected. Increased apoptosis was demonstrable among SLE sera-cultured cells by ELISA for apoptosis-specific DNA fragments and terminal deoxynucleotidyl transferase (TdT) in situ death analysis. Different levels of Fas, Fas-L, and Bcl-2 gene products were not detected between SLE sera-treated cells and the controls. The transcripts of interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) genes of these two T cell lines were evidently increased in the presence of SLE sera, while IL-2 and IL-4 were unaffected. Elevated expression of IL-5 was also found in Molt-4 cells. By contrast, SLE sera reduced the transcripts of IL-6 gene in Jurkat cells. The effects of SLE sera were independent of corticosteroid medication. These results suggest that serum abnormalities may also play a role in T cell dysfunction.

Apoptosis↗
PubMed1996

Transient induction of apoptosis in serum-starved glioma cells by insulin and IGF-1.

Insulin has a wide variety of biological effects. One of them is a mitogen-like activity whereby cell proliferation is stimulated. In this study we found a heretofore unreported insulin-elicited transient apoptosis of glioma cells. When serum-starved glioma cells were fed with a fresh regular medium, in the 6- to 12-h post-starvation period, the growth rate as determined by cell number was significantly suppressed by insulin, although cell cycle progression and DNA synthesis were actually accelerated. Increase in apoptosis in those growth-retarded cultures was demonstrable by Hoechst staining, detection of histone-associated DNA fragment, and in situ cell death detection. Apoptosis occurred among cells in all stages of cell cycle. After 24 h post-starvation, insulin increased the total cell number like a typical growth-promoting mitogen. In this regard, IGF-1, but not EGF nor TGF-beta 1, behaved like insulin.

Apoptosis↗
PubMed1996

Chemical shift assignments and secondary structure of the Grb2 SH2 domain by heteronuclear NMR spectroscopy.

The growth factor receptor-bound protein-2 (Grb-2) is an adaptor protein that mediates signal transduction pathways. Chemical shift assignments were obtained for the SH2 domain of Grb2 by heteronuclear NMR spectroscopy, employing the uniformly 13C-/15N-enriched protein as well as the protein containing selectively 15N-enriched amino acids. Using the Chemical Shift Index (CSI) method, the chemical shift indices of four nuclei, 1H alpha, 13C alpha, 13C beta and 13CO, were used to derive the secondary structure of the protein. Nuclear Overhauser enhancements (NOEs) were then employed to confirm the secondary structure. The CSI results were compared to the secondary structural elements predicted for the Grb2 SH2 domain from a sequence alignment [Lee et al. (1994) Structure, 2, 423-438]. The core structure of the SH2 domain contains an antiparallel beta-sheet and two alpha-helices. In general, the secondary structural elements determined from the CSI method agree well with those predicted from the sequence alignment.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Discrepant pattern of solid and liquid gastric emptying in Chinese patients with type II diabetes mellitus.

While abnormal gastric emptying has been widely reported in patients with diabetes, its clinical relevance is still uncertain. We conducted scintigraphic gastric emptying studies in patients with Type II diabetes mellitus who had symptoms suggestive of delayed gastric emptying in an attempt to evaluate the incidence of abnormal gastric emptying and to assess the clinical parameters of the different patterns of gastric emptying. Seventy male diabetic patients were included in the study. The patients were divided into four groups according to the results of liquid and solid gastric emptying: group 1, normal liquid and solid emptying (n = 22); group 2, normal liquid but delayed solid emptying (n = 30); group 3, delayed liquid but normal solid emptying (n = 7); group 4, delayed liquid and solid gastric emptying (n = 11). To assess clinical significance, we compared duration of disease, status of blood sugar control, presence or absence of vascular complications and of peripheral neuropathy among the four groups. Of the 70 patients, 18 (25.7%) showed delayed liquid gastric emptying and 41 (58.6%) delayed solid gastric emptying. There were no significant differences in the clinical parameters of the four groups, except that patients with good sugar control were likely to have normal liquid gastric emptying. Based on the results of this study, delayed solid gastric emptying is more common than liquid gastric emptying in symptomatic Type II diabetes mellitus patients. Of the different patterns of gastric emptying, delayed liquid gastric emptying with normal solid gastric emptying is the most unusual. For Type II diabetic patients with symptoms suggestive of delayed gastric emptying, both liquid and solid gastric emptying studies should be performed.

Aged↗
PubMed1996

The effect of exclusive breastfeeding on development and incidence of infection in infants.

Of 145 normal fullterm infants studied during the first year after birth, those exclusively breastfed for the first four months differed significantly from those not exclusively breastfed in physical and behavioral development, and resistance to infection. At four months of age, the mean weight of the exclusively breastfed group was higher (p < 0.05). At one year, the exclusively breastfed group showed more advanced. Personal-Social (p = 0.05) and gross Motor development (p < 0.05) on the Denver Developmental Screening TEst, and lesser cumulative incidence of infectious diseases (p < 0.05). This study demonstrated the beneficial effects of breastfeeding on development and resistance to infection in infants.

Bottle Feeding↗
PubMed1996

[Experimental study on effects of mailuotong granule on anti-thromboangiitis obliterans].

Using experimental model of thromboangitis obliterans (TAO) in rats induced by injection of lauric acid into the femoral artery, the anti-thromboangitis obliterans effects of Mailuotong (MLT) Granule were observed. The results showed that MLT not only decreased significantly the lesion severity and extent of affected limb, plasma viscosity and level of fibrinogen, but also suppressed the arterial thrombosis, endotheliocytosis and inflammatory cell infiltration in vascular wall. MLT also reduced the organization of thrombus and facilitated thrombolysis. It showed that the therapeutic effect of MLT on TAO might be achieved by improving blood rheology, antithrombosis, thrombolysis, inhibiting endotheliocytosis and inflammatory reaction in vascular wall.

Animals↗
PubMed1995

Synthesis, antitumor activity, and chemical properties of silaplatin and related platinum (II) and platinum (IV) complexes derived from beta-silyl amines.

Platinum (II) and platinum (IV) coordination complexes derived from beta-silyl-substituted amines were prepared. The solubility of selected complexes in water and physiological saline was measured, and the effect of the beta-silicon on the reactivity of the complex in aqueous solution was determined by HPLC. The stabilities of selected silyl complexes were compared to the carbon analogues. The cyclic complexes 2a ("silaplatin") and its Pt(IV) analogue, 2b, were very active against L1210 leukemia in vivo. Both the platinum (II) complex 2a and the platinum (IV) complex 2b produced a significant number of cures over the dose range 10-40 mg/kg. The platinum (II) complex 2a, silaplatin, was very active in vivo against an L1210 leukemia subline that was resistant to cisplatin; 2a was also active, when given ip, against ic implanted L1210. The cyclobutanedicarboxylic acid complex 3c was synthesized; this complex was active against both cisplatin sensitive and resistant L1210 leukemia but was less potent than the analogous dichloro compound 2a. The acyclic platinum (II) and platinum (IV) complexes 1a,b were synthesized and unexpectedly found to be inactive in vivo against L1210 leukemia. More lipophilic silaplatin analogues were prepared--Pt(II) complex 2c and Pt(IV) complex 2d have one additional methylene carbon compared to 2a,b, whereas Pt(II) complex 2e and Pt(IV) complex 2f have two additional methylene carbons. Cyclization of the alkyl groups attached to the silicon gave the spiro bicyclic Pt(II) complexes 10a and 11a and the Pt(IV) complexes 10b and 11b.

Animals↗
PubMed1995

A proposal for a theory and detection method of cavitation potential of mitral bileaflet heart valve.

We believe that cavitation damage to mitral bileaflet heart valve (MBHV) is caused by microcracks of hydrophobic pyrolite carbon. Our proposal is to detect cavitation potential of MBHV with an acoustic technique under various conditions of transvalvular pressures, ventricular dp/dt, leakage flow, and gas concentration in fluid, This modality, different from recent research in theory and technique, will lead to a standardized noninvasive and sufficiently sensitive technique for the detection of MBHV, to reject those valves believed to cause cavitation damage, and to develop cavitation-resistant MBHV.

Biomechanical Phenomena↗
PubMed1995

Impact of alcohol consumption and cigarette smoking on stroke among the elderly in Taiwan.

BACKGROUND AND PURPOSE: We investigated the influence of alcohol consumption and cigarette smoking on all types of stroke and cerebral infarction, in particular among a representative sample of elderly residents in Taiwan. METHODS: This study was a component of a nationwide survey of health and living status of residents aged 65 years or older in Taiwan in which subjects received detailed physical, neurological, and laboratory examinations. Inquiries were made about medical history, and information on the amount and duration of drinking and smoking was obtained. Diagnoses of stroke were made according to the results of brain computed tomography at the onset of disease or were based on criteria established by the World Health Organization. RESULTS: Of the 2600 subjects, there were 155 elderly persons with stroke (prevalence, 6%). Excessive drinking of more than 367.6 g/wk of alcohol was associated with a high prevalence of cerebral infarction. Consumption of < or = 367.5 g/wk of alcohol did not have an influence on stroke prevalence. The relationship between duration of alcohol drinking and stroke was equivocal. More than 30 pack-years of cigarette smoking was a significant risk factor for all types of stroke and cerebral infarction in particular. Using multiple logistic regression to control for possible confounders, it was found that smoking was an independent risk factors for all stroke and was of borderline significance for cerebral infarction. Although excessive drinking was a significant risk factor for cerebral infarction in univariate analysis, this effect was lost after adjustment for other confounders. CONCLUSIONS: Cigarette smoking was a more important risk factor for stroke and cerebral infarction than excessive drinking of alcohol.

Aged↗
PubMed1994

Dissipation and movement of acaricide chlorobenzilate in the environment.

The dissipation of acaricide chlorobenzilate in selected soil and river water samples was studied. Under incubation conditions at 25 degrees C and 90% field capacity of moisture for 21 days, the residues of chlorobenzilate were 14 and 55% in Lukang silty clay loam and Pincheng clay, respectively. More than 80% of chlorobenzilate remained in the natural water (pH 7.2 and 7.3, respectively) and in the water adjusted to pH 5.0 when water samples collected from Green Lake and Wai-Shuang River near Taipei were treated with chlorobenzilate and then incubated for 34 days. But when the pH was adjusted to 9.0, only 60% was found in Green Lake water and 29% in Wai-Shuang River water. The dissipation of chlorobenzilate in the soil was fitted to first-order kinetics with half-lives of 5 to 36 days under various conditions in the laboratory experiments. No chlorobenzilate was detected in the leachate by a leaching experiment on the soil column for 18 days; most chlorobenzilate remained in the upper 3 cm of the column. According to assessment by the groundwater pollution-potential model (GWP), chlorobenzilate seemed to be safe in regard to groundwater contamination.

Benzilates↗
PubMed1994

Anaerobic biodegradability of cellulose and hemicellulose in excavated refuse samples using a biochemical methane potential assay.

Improved techniques are needed to predict potential methane generation from refuse buried in landfills. The Biochemical Methane Potential (BMP) test was used to measure the methane potential of ten refuse samples excavated from a Berkeley, CA, landfill. The test was conducted in 125-ml serum bottles containing phosphate-buffered medium and inoculated with anaerobically digested sewage sludge. Comparison of the measured BMP to the theoretical BMP calculated from measured cellulose and hemicellulose concentrations indicated that cellulose plus hemicellulose is not well correlated with the measured BMP. The average of the measured to theoretical BMP was 19.1% (range 0-53%, s.d. = 16.9%). Measured sulfate concentrations showed that sulfate was an insignificant electron sink in the samples tested. Once methane production from the refuse was complete, 0.072 g of Whatman no. 1 filter paper was added to two of the four serum bottles incubated for each sample. An average of 84.9% (s.d. = 2.5%) of the added filter paper was recovered as methane, suggesting that some cellulose and hemicellulose present in refuse is recalcitrant or otherwise not bioavailable.

Anaerobiosis↗