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Biomedical subjects

S L Wang

Publications and source records attributed to S L Wang.

At least 55 records · Page 3Linked to original sources
PubMed2000

Novel gallium phosphate framework encapsulating trinuclear Mn3(H2O)6O8 cluster: hydrothermal synthesis and characterization of Mn3(H2O)6Ga4(PO4)6.

A new manganese gallium phosphate, Mn3(H2O)6Ga4(PO4)6, has been synthesized under hydrothermal conditions at 150 degrees C and characterized by single-crystal X-ray diffraction, thermogravimetric analysis, magnetic susceptibility, and electron paramagnetic resonance (EPR) spectroscopy. It crystallized in the monoclinic space group, P2(1)/n, with a = 8.9468(4) A, b = 10.148(5) A, c = 13.5540(7) A, beta = 108.249(1) degrees, and Z = 2. The compound is unusual in that it is not only the first nonoranically templated MnGaPO phase but also the first instance where edge-shared trinuclear manganese-oxygen clusters are encapsulated in a metal phosphate lattice. The trimer involves a central Mn(H2O)4O2 octahedron, which links to two Mn (H2O)2O4 octahedra at trans edges. The Mn3(H2O)6O8 clusters reside in tunnels built from GaO5 trigonal bipyramids and PO4 tetrahedra. Our magnetic study revealed that superexchange interactions occurred between the neighboring MnII centers. A good fit of the magnetic susceptibility data for the isolated trimers was obtained by using a derived expression based on Van Vleck's equation. Unlike all existing linear trinuclear MnII complexes, the chi MT product in the range 8-4 K remains at a constant value corresponding to one spin S = 5/2 per three MnII centers. The Curie behavior at such low temperatures has been confirmed by EPR data. According to the thermogravimetric analysis/differential thermal analysis (TGA/DTA) results, the title compound is thermally stable up to ca. 200 degrees C.

Journal Article↗
PubMed2000

Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes.

Double-stranded RNA interference (RNAi) is an effective method for disrupting expression of specific genes in Caenorhabditis elegans and other organisms. Applications of this reverse-genetics tool, however, are somewhat restricted in nematodes because introduced dsRNA is not stably inherited. Another difficulty is that RNAi disruption of late-acting genes has been generally less consistent than that of embryonically expressed genes, perhaps because the concentration of dsRNA becomes lower as cellular division proceeds or as developmental time advances. In particular, some neuronally expressed genes appear refractory to dsRNA-mediated interference. We sought to extend the applicability of RNAi by in vivo expression of heritable inverted-repeat (IR) genes. We assayed the efficacy of in vivo-driven RNAi in three situations for which heritable, inducible RNAi would be advantageous: (i) production of large numbers of animals deficient for gene activities required for viability or reproduction; (ii) generation of large populations of phenocopy mutants for biochemical analysis; and (iii) effective gene inactivation in the nervous system. We report that heritable IR genes confer potent and specific gene inactivation for each of these applications. We suggest that a similar strategy might be used to test for dsRNA interference effects in higher organisms in which it is feasible to construct transgenic animals, but impossible to directly or transiently introduce high concentrations of dsRNA.

Animals↗
PubMed2000

Association of CYP1A1 and microsomal epoxide hydrolase polymorphisms with lung squamous cell carcinoma.

Lung cancer is the leading cause of death among cancers in Taiwan. Although the etiology of lung cancer has yet to be defined, genetic variability in activities of metabolic enzymes has been correlated with lung cancer. In the present study, the possibility of association of CYP1A1 and microsomal epoxide hydrolase (HYL1) genetic polymorphisms with lung cancer was examined among 132 lung cancer patients and 259 controls in Taiwan. No significant association was observed for either CYP1A1 or HYL1 polymorphism alone and the overall incidence of lung cancer after adjusting for age, gender and smoking status. When cases were stratified according to histological type, there was significant association between CYP1A1*2A homozygote and squamous cell carcinoma (SCC) (odds ratio (OR) 2.86; 95% confidence interval (CI) 1.33-6.12). Similarly, the proportion of HYL1 genotypes corresponding to high or normal enzyme activities was higher in SCC than in controls (OR 1.96; 95% CI 1.04-3.70). A combination of susceptible CYP1A1 and HYL1 genotypes was found to be highly associated with lung cancer, especially with SCC (OR 6.76; 95% CI 2.29-19.10). Our results suggest that the combination of CYP1A1 and HYL1 polymorphisms is an important risk factor for lung SCC.

Base Sequence↗
PubMed2000

Proline inhibits aggregation during protein refolding.

The in vitro refolding of hen egg-white lysozyme is studied in the presence of various osmolytes. Proline is found to prevent aggregation during protein refolding. However, other osmolytes used in this study fail to exhibit a similar property. Experimental evidence suggests that proline inhibits protein aggregation by binding to folding intermediate(s) and trapping the folding intermediate(s) into enzymatically inactive, "aggregation-insensitive" state(s). However, elimination of proline from the refolded protein mixture results in significant recovery of the bacteriolytic activity. At higher concentrations (>1.5 M), proline is shown to form loose, higher-order molecular aggregate(s). The supramolecular assembly of proline is found to possess an amphipathic character. Formation of higher-order aggregates is believed to be crucial for proline to function as a protein folding aid. In addition to its role in osmoregulation under water stress conditions, the results of this study hint at the possibility of proline behaving as a protein folding chaperone.

Animals↗
PubMed2000

Predictors of survival among elders suffering strokes in Taiwan: observation from a nationally representative sample.

BACKGROUND AND PURPOSE: Cerebrovascular disease was the leading cause of death in Taiwan from 1963 to 1982. Deaths due to stroke now rank second only to cancer, with more deaths resulting from strokes than from any other single pathology. It is important to understand stroke prognosis among elderly stroke survivors, with respect to survival and attendant predictive factors, because aged population in Taiwan is growing rapidly. The aim of the present study was to discern factors affecting survival in stroke patients from a nationally representative elderly sample. METHODS: A total of 99 stroke survivors, from a representative national sample of elders aged >/=65 years on December 31, 1988, whose strokes occurred in the period 1989-1993, were followed for mortality until July 1, 1995. Personal data were gathered through home interviews conducted by well-trained community nurses, and mortality data were obtained from the national census office by using identification card numbers. Cox proportional hazards regression analysis and the stepwise technique were used to search for important prognostic factors of survival. RESULTS: Women experienced a higher mortality rate (139.8 per 1000 person-years) than men (126.4 per 1000 person-years), as age-adjusted for World Health Organization world-population figures. Stroke patients who received continuous treatment for diabetes experienced mortality risks similar to those of patients without diabetes and much lower risks than those with discontinuous diabetes treatment. Cognitive impairment was also an independent predictor of survival (relative risk 2.69, P<0.05). In addition, patients with both cognitive and mobility impairments had a 2- to 3-fold greater risk of mortality than those with only a single abnormality. CONCLUSIONS: This first report on the various prognostic factors related to survival of elderly stroke patients in Taiwan's Chinese population emphasized the benefit of continuous diabetes treatment in improving survival chances. These stroke patients should also be monitored for cognitive and mobility impairments and undergo rehabilitation.

Aged↗
PubMed2000

Thermal-Dependent dehydration process and intramolecular cyclization of lisinopril dihydrate in the solid state.

The pathway of dehydration and intramolecular cyclization of lisinopril dihydrate in the solid state was investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and a combination of thermal analyzer with Fourier transform infrared microspectroscopy (thermal FT-IR microscopic system). The results indicate that the dehydration from the solid-state lisinopril dihydrate had a two-step process from dihydrate to monohydrate at 76 degrees C and then from monohydrate to anhydrate at 99-101 approximately C, which could be clearly observed from the above three methods. Only the thermal FT-IR microscopic system could give vital information on diketopiperazine (DKP) formation via intramolecular cyclization in anhydrous lisinopril. A new peak at 1670 cm(-1) assigned to the carbonyl band of DKP formation was clearly evidenced. The water of reaction byproduct was liberated at a temperature >157 degrees C and appeared on the IR spectra near 3200-3400 cm(-1). Moreover, the peak at 1574 cm(-1) assigned to carboxylate shifted to 1552 cm(-1) due to the DKP formation. The peak at 1670 cm(-1) related to the DKP formation changed slightly in intensity from 147 degrees C and significantly near 157 degrees C. DSC and TGA methods were poor for use in supplying information on DKP formation in lisinopril. The thermal FT-IR microscopic system is useful from the view point that it can quickly and directly show the solid-state stability of drug.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

[The study of mechanism by which mild hypothermia reduced delayed neuronal death after cerebral ischemia in gerbils].

AIM: To study the effect of mild hypothermia on delayed neuronal death as well as the relationship between hydroxyl radicals generation in hippocampus and the change of dopamine and ATP content in striatum following ischemia/reperfusion in gerbils. METHODS: The ischemia was induced by occlusion the both carotid common arteries for 10 minutes in gerbils. Animals were divided into four groups: sham-operated group, ischemic group, ischemia/reperfusion group and mild hypothermic ischemia/reperfusin group. The numbers of delayed neuronal death were assessed by histological examination. OH. outputs in hippocampus and dopamine content in striatum were specifically identified and quantitated by high performance liquid chromatography (HPLC) coupled with electrochemical detection (ECD). ATP content in striatum was also determined by HPLC. RESULTS: Mild hypothermia significantly reduced the numbers of damaged neurons in hippocampus CA1 subfield after ischemia in gerbils. In MH group, 2,3-DHBA outputs were much less than that in IR group (P < 0.01). Dopamine and ATP content in striatum were higher than those in IR group (P < 0.01). CONCLUSION: Mild hypothermia could decrease the delayed neuronal death in gerbils by reducing hydroxyl radicals production in hippocampus and inhibiting dopamine release as well as prompting the recovery of ATP content in striatum following ischemia/reperfusion in gerbils.

Animals↗
PubMed2000

[Expression of CD44s and CD44v6 in laryngeal squamous cell carcinoma and their significance].

OBJECTIVE: To study the correlation between the expression of CD44s, CD44v6 and the clinicopathological characters of laryngeal squamous cell carcinoma (LSCC) so as to analyze the role of them in occurrence and progression of LSCC. METHOD: Expression of CD44 and CD44v6 in 46 cases of LSCC and 20 cases of adjacent normal tissues was inspected with immunohistochemical SP method. RESULT: The expression of CD44s increased significantly in lymphnode metastasis group (94.4%) and stage III-IV group (96.2%), but decreased in non-lymphnode metastasis group (67.9%) and stage I-II group (55.0%). The expression of CD44v6 was lower (21.7%), which wasn't associated with any clinicopathological characters. CONCLUSION: The role of CD44 and CD44v6 in carcinoma maybe dependent on the species, type of carcinoma, and the expression of CD44s may be a biologic marker to evaluate metastasis of LSCC.

Aged↗
PubMed1999

NAD(P)H: quinone oxidoreductase polymorphism and lung cancer in Taiwan.

Lung cancer is one of the leading causes of death in Taiwan since 1996. Genetic variation in metabolic activation or detoxification enzymes has been associated with the occurrence of lung cancer. NAD(P)H:quinone oxidoreductase (NQO1) enzyme is a cytosolic two-electron reductase thought to be involved in bioactivation and detoxification of environmental carcinogens. The possible association between NQO1 genetic polymorphism and lung cancer risk was examined among 95 male smokers without cancer and 100 male smokers with lung cancer in Taiwan. There was no significant difference in the proportion of wild-type NQO1 among all cancer cases and controls. When cases were stratified according to histological subtypes, the wild-type NQO1 was more common in adenocarcinoma than in controls. The odds ratio was 2.93 (95% confidence interval, 1.23-7.02; p = .02). This is the first observation for the positive association of this locus with lung cancer in an Asian population. These results suggest that NQO1 polymorphism is an important genetic risk factor for lung adenocarcinoma among smokers in Taiwan.

Adenocarcinoma↗
PubMed1999

The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID.

Drosophila Reaper (RPR), Head Involution Defective (HID), and GRIM induce caspase-dependent cell death and physically interact with the cell death inhibitor DIAP1. Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly. Based on these results, we propose that RPR, HID, and GRIM promote apoptosis by disrupting productive IAP-caspase interactions and that DIAP1 is required to block apoptosis-inducing caspase activity. Supporting this hypothesis, we show that elimination of DIAP1 function results in global early embryonic cell death and a large increase in DIAP1-inhibitable caspase activity and that DIAP1 is still required for cell survival when expression of rpr, hid, and grim is eliminated.

Acridine Orange↗
PubMed1999

Retinoid and androgen regulation of cell growth, epidermal growth factor and retinoic acid receptors in normal and carcinoma rat prostate cells.

Recent in vivo and in vitro studies suggest that retinoic acid receptor (RAR)-mediated processes may be involved in androgen regulation of prostate cells in a manner that may be altered during prostatic carcinogenesis. We tested this hypothesis in the newly established carcinoma and non-carcinoma rat prostate epithelial cell lines, NRP-154 and NRP-152, respectively. In DMEM/F-12 medium supplemented with 10% charcoal stripped fetal calf serum (cFCS), the number of both NRP-152 and NRP-154 cells were stimulated by testosterone (T), with a 4-fold greater effect in NRP-152 than in NRP-154 cells. Retinoic acid (RA) alone also stimulated the growth of NRP-152 cells, but failed to induce cell growth of NRP-154 cells. Importantly, the level of RAR alpha mRNA was elevated whereas the levels of RAR gamma and androgen receptor (AR) mRNA were lower in NRP-154 cells compared to those in NRP-152 cells. Treatment of NRP-152 cells with increasing doses of T resulted in a dose-dependent decrease and rebound of the level of RAR alpha and gamma mRNA in NRP-152 cells; these effects were not apparent, if not reversed, in NRP-154 cells. Both ligand binding and Western blot analyses revealed that epidermal growth factor receptor (EGF-R) was stimulated by 20 nM T but was suppressed by 0.1 microM RA, which also attenuated the stimulating effects of T on EGF-R in NRP-152 and to a lesser extent in NRP-154 cells. The differences in the level and androgen regulation of RAR mRNAs and reciprocal regulation of EGF-R expression by T and RA between NRP-154 and NRP-152 cells suggest that variations in the EGF-R and RAR signal events may contribute to differences in growth rate between these two cell lines.

Animals↗
PubMed1999

A cloning method to identify caspases and their regulators in yeast: identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1.

Site-specific proteases play critical roles in regulating many cellular processes. To identify novel site-specific proteases, their regulators, and substrates, we have designed a general reporter system in Saccharomyces cerevisiae in which a transcription factor is linked to the intracellular domain of a transmembrane protein by protease cleavage sites. Here, we explore the efficacy of this approach by using caspases, a family of aspartate-specific cysteine proteases, as a model. Introduction of an active caspase into cells that express a caspase-cleavable reporter results in the release of the transcription factor from the membrane and subsequent activation of a nuclear reporter. We show that known caspases activate the reporter, that an activator of caspase activity stimulates reporter activation in the presence of an otherwise inactive caspase, and that caspase inhibitors suppress caspase-dependent reporter activity. We also find that, although low or moderate levels of active caspase expression do not compromise yeast cell growth, higher level expression leads to lethality. We have exploited this observation to isolate clones from a Drosophila embryo cDNA library that block DCP-1 caspase-dependent yeast cell death. Among these clones, we identified the known cell death inhibitor DIAP1. We showed, by using bacterially synthesized proteins, that glutathione S-transferase-DIAP1 directly inhibits DCP-1 caspase activity but that it had minimal effect on the activity of a predomainless version of a second Drosophila caspase, drICE.

Animals↗
PubMed1999

Translocation-arrested apolipoprotein B evades proteasome degradation via a sterol-sensitive block in ubiquitin conjugation.

In this study, we explored how sterol metabolism altered by the expression of cholesterol-7alpha-hydroxylase NADPH:oxygen oxidoreductase (7alpha-hydroxylase) affects the ubiquitin-dependent proteasome degradation of translocation-arrested apoB53 in Chinese hamster ovary cells. Stable expression of two different plasmids that encode either rat or human 7alpha-hydroxylase inhibited the ubiquitin conjugation of apoB and its subsequent degradation by the proteasome. Oxysterols (25-hydroxycholesterol and 7-ketocholesterol) reversed the inhibition of apoB degradation caused by 7alpha-hydroxylase. The combined results suggest that the normally rapid proteasome degradation of translocation-arrested apoB can be regulated by a sterol-sensitive polyubiquitin conjugation step in the endoplasmic reticulum. Blocked ubiquitin-dependent proteasome degradation caused translocation-arrested apoB to become sequestered in segregated membrane domains. Our results described for the first time a novel mechanism through which the "quality control" proteasome endoplasmic reticulum degradative pathway of translocation-arrested apoB is linked to sterol metabolism. Sterol-sensitive blocked ubiquitin conjugation appears to selectively inhibit the proteasome degradation of apoB, but not 7alpha-hydroxylase protein, with no impairment of cell vitality or function. Our findings may help to explain why the hepatic production of lipoproteins is increased when familial hypertriglyceridemic patients are treated with drugs that activate 7alpha-hydroxylase (e.g. bile acid-binding resins).

Animals↗
PubMed1999

Cytochrome P4502E1 genetic polymorphisms and lung cancer in a Taiwanese population.

Cytochrome P4502E1 (CYP2E1) is involved in metabolic activation of carcinogenic nitrosamines, benzene and low molecular weight halogenated hydrocarbons. In this study, we assessed the association between CYP2E1 RsaI and DraI genetic polymorphisms and lung cancer in a Taiwanese population. The RsaI genotype distribution was significantly different between 119 lung cancer patients and 231 non-cancer controls. The homozygote variants of RsaI genotypes were more common in controls (6.9%) than in lung cancer patients (0.8%). The estimated odds ratio (OR) was 0.11 (95% confidence interval (CI), 0.01-0.87). After adjusting for age, sex, and smoking status, the OR was 0.12 (95%, CI, 0.02-0.95). This is the first observation of a positive association between this locus and lung cancer in an Asian population. No significant differences in CYP2E1 DraI genotype distributions were found between cases and controls. The results of this study indicate that CYP2E1 RsaI polymorphism, but not DraI polymorphism, may contribute to the development of lung cancer in Taiwan.

Cytochrome P-450 CYP2E1↗
PubMed1999

G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese.

The molecular basis of the reduced ability of a Chinese to metabolize debrisoquine was explored by sequencing all of the nine exons of the CYP2D6 gene. The subject has T188, A1846, T2938, and C4268 (CYP2D6*14) instead of C188, G1846, C2938, and G4268 as in wild-type subjects. XbaI restriction fragment length polymorphism indicated that the subject has a 29-kb allele and a gene deletion (11.5 kb) in another allele (CYP2D6*5). A CYP2D6*14 allele together with a CYP2D6*5 allele may cause the poor metabolism of the subject. T188, T2938, and C4268 are common haplotypes in Chinese-extensive metabolizers. The effect of G1846 to A mutation in CYP2D6 metabolism has not been reported. A polymerase chain reaction-based endonuclease digestion test was designed for the G/N1846 polymorphism and 124 Chinese subjects were screened. With DNA sequencing, two other subjects showed the heterozygous G/A1846 and have a relatively high metabolic ratio of debrisoquine hydroxylation. The site-directed mutagenesis was used to create recombinant CYP2D6 cDNA with T188, A1846, or C4268. The cDNA was then transfected into Rat-1 cells. The transfection was confirmed by Southern, Northern, and Western blots. Based on the same microsomal protein level, the bufuralol 1'-hydroxylation activity of CYP2D6(T188) or CYP2D6(A1846) was significantly lower than that of the wild-type CYP2D6. P34S mutation (C188 to T) significantly decreased CYP2D6 activity. G169R mutation (G1846 to A) also decreased CYP2D6 activity and may further reduce the metabolic activity of CYP2D6 protein with P34S, R296C, and S486T mutations.

Alleles↗
PubMed1998

Physical training modifies the age-related decrease of GAP-43 and synaptophysin in the hippocampal formation in C57BL/6J mouse.

We investigated the effect of a moderate amount of prolonged physical training initiated at 3 months of age on the expression of GAP-43 and synaptophysin in the hippocampal formation. C57BL/6J mice were divided into three groups which were trained (24 months old), sedentary (24 months old) and young (3 months old). From 3 months of age on, mice of trained group were treated with voluntary running wheel for 1 h each day (5 days per week) until 24 months of age (21 months running), whereas mice of sedentary group were put in immobilized wheels for the same time. Using immunohistochemistry and image analysis system, GAP-43 and synaptophysin were analysed quantitatively in the CA1, CA3 areas and the dentate gyrus of the hippocampal formation. As compared with young mice, the densities of GAP-43 and synaptophysin immunostaining showed a significant decrease in the hippocampal formation in sedentary group (P<0.01). After 21 months of running, the densities of GAP-43 and synaptophysin immunostaining significantly increased in the examined areas of the hippocampal formation in trained mice compared to their age-matched sedentary controls (P<0.05, 0.01). These results indicate that a moderate amount of prolonged physical training could modify the age-related decrease of the expression of GAP-43 and synaptophysin in the hippocampal formation, and that the increased expression of GAP-43 and synaptophysin might be associated with the anatomical sprouting and synaptogenesis.

Aging↗
PubMed1998

Effect of physical training on the age-related changes of acetylcholinesterase-positive fibers in the hippocampal formation and parietal cortex in the C57BL/6J mouse.

We investigated the effect of a moderate amount of prolonged physical training initiated at 3 months of age on the age-related changes of the hippocampal and cortical cholinergic fibers. A total of 80 male C57BL/6J mice were divided into five groups which were trained (including adult and old trained, AT and OT), sedentary (adult and old sedentary, AS and OS) and young (Y). From 3 months old, the mice of the trained groups were treated with a voluntary running wheel for 1 h each day, 5 days per week. AT had been trained up to 13-month-old whereas OT up to 24 months old. At the same time, the mice of the sedentary groups were put in immobilized wheels. We set the criterion for effective training in the trained mice such that the heart-to-body weight ratio should be at least 2 S.D. above the mean in the age-matched groups. Using AChE histochemistry and stereology, the AChE-positive fibers were analyzed quantitatively in the molecular layers in CA1, CA3 and the dentate gyrus of the hippocampal formation, and in III, V layers in the motor and somatosensory cortex. Comparison of Y, AS and OS (3, 13 and 24 months of age) showed minimum AChE-positive fiber density in the hippocampal formation and the cortex in OS (P < 0.01). After 10 and 21 months of running, the AChE-positive fibers in all regions examined in the trained groups were significantly increased compared to their age-matched controls (P < 0.05 or 0.01). In the hippocampal formation, the increase was about 17% in AT and 23% in OT, whereas, in the cortex, it was 13% in AT and 22% in OT. These results indicated that a moderate amount of prolonged physical training could modify the age-related loss of cholinergic fibers in the hippocampal formation and cortex, furthermore the modified loss of cholinergic fibers might be associated with the regeneration of hippocampal and cortical cholinergic fibers stimulated by chronic running.

Acetylcholinesterase↗