Biomedical subjects
Publications and source records attributed to S L Huang.
A novel double-clad Cr4+:YAG crystal fiber is demonstrated by use of a codrawing laser-heated pedestal growth method. Up to 10 dB of gross gain at a wavelength of 1.52 microm is achieved at a pump power of 0.83 W, which, to our knowledge, is the first Cr4+-doped fiber amplifier in the optical fiber communication band.
The biotransformation of octylphenol polyethoxylate surfactant (Triton X-100) and bacterial communities in soil microcosms was investigated. The soil microcosms were designed to simulate real sites of bioremediation. The soil used in this study was contaminated with pesticides and alkylphenol polyethoxylate surfactants over a long period of time. The nitrogen source, (NH4)2SO4 and the mineral salt basal solution were added to the microcosm and the water content was adjusted to 50% with distilled water. The microcosms were aerated using an aeration system with an air flow rate of 0.3 l min(-1). The exogenous bacterial strain Pseudomonas sp. SH4 was added to the microcosms to increase the rate of biotransformation of the Triton X-100. The number of microorganisms and the theoretical extent of formation of carbon dioxide were estimated to evaluate the biotransformation of Triton X-100 in the microcosms. The analytical results revealed that the exogenous bacteria could increase the rate of transformation of Triton X-100 by approximately 50%. Aeration of the microcosm increased the biotransformation of Triton X-100 by 45%. Bacterial count of 6.8x10(10) MPN g(-1) of soil was achieved in the M5 microcosm. Analysis of the bacterial community by 16S rDNA sequences revealed that Pseudomonas sp. SH4 could dominate all the microcosms to which it was added as an exogenous bacteria. The quantity of the indigenous bacterial strains Stenotrophomonas maltophilia, Stenotrophomonas sp. and clone 4-70 were also enhanced in the microcosms by the aeration, and the addition of carbon and nitrogen source.
Cervical cancer is common among women all over the world. Although infection with high-risk types of human papillomavirus (HPV) has been identified as the primary cause of cervical cancer, only some of those infected go on to develop cervical cancer. Obviously, the progression from HPV infection to cancer involves other environmental and host factors. Recent population-based twin and family studies have demonstrated the importance of the hereditary component of cervical cancer, associated with genetic susceptibility. Consequently, single-nucleotide polymorphism (SNP) markers and microsatellites should be considered genetic factors for determining what combinations of genetic factors are involved in precancerous changes to cervical cancer. This study employs a Bayesian network and four different decision tree algorithms, and compares the performance of these learning algorithms. The results of this study raise the possibility of investigations that could identify combinations of genetic factors, such as SNPs and microsatellites, that influence the risk associated with common complex multifactorial diseases, such as cervical cancer.
Recurrent endometrial cancer with both local and distant metastasis is very difficult to treat. A 55-year-old endometrial adenocarcinoma patient with bulky central recurrences and pelvic and inguinal lymph node metastases underwent laparotomy and paraaortic, pelvic and inguinal lymphadenectomy followed by concurrent chemoradiation (with cisplatin) to the paraaortic and inguinal lymph nodes as well as the whole pelvis. Neck and mediastinal lymph node metastasis emerged during treatment. Neck-node radiation and epirubicin was added followed by paclitaxel and carboplatin. Complete remission was achieved. Ten months later, isolated central re-recurrence happened and total pelvic exenteration was performed. The patient has survived without further recurrence for more than five years after the exenteration. Therefore, a multimodality approach with a combination of radical resection (even pelvic exenteration), radiotherapy and chemotherapy could be offered to well-selected patients with recurrent endometrial cancer despite out-of-field progression during therapy and in-field local failure to initial salvage treatment.
The prevalence of allergic rhinitis, a common respiratory disorder, may be rapidly increasing. Epidemiological studies, however, indicate little about its association with climatic factors and air pollution. The relationship between traffic-related air pollutants and allergic rhinitis in middle-school students was therefore investigated. In a nationwide survey of middle-school students in Taiwan conducted in 1995/1996, the lifetime prevalence of physician-diagnosed allergic rhinitis and typical symptoms of allergic rhinitis were compared with air-monitoring station data on temperature, relative humidity, sulphur dioxide (SO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO) and particulate matter with a 50% cut-off aerodynamic diameter of 10 microm (PM10). A total of 331,686 nonsmoking children attended schools located within 2 km of 55 stations. Mean (range) annual exposures were: CO 853 (381-1,610) parts per billion (ppb), NOx 35.1 (10.2-72.4) ppb, SO2 7.57 (0.88-21.2) ppb, PM10 69.2 (40.1-116.2) microg x m(-3), O3 21.3 (12.4-34.1) ppb, temperature 22.9 (19.6-25.1) degrees C, and relative humidity 76.2 (64.8-86.2)%. The prevalence of physician-diagnosed allergic rhinitis was 28.6 and 19.5% in males and females, respectively, with prevalence of questionnaire-determined allergic rhinitis 42.4 and 34.0%. After adjustment for age, parental education and history of atopic eczema, physician-diagnosed allergic rhinitis was found to be associated with higher nonsummer (September-May) warmth and traffic-related air pollutants, including CO, NOx and O3. Questionnaire-determined allergic rhinitis correlated only with traffic-related air pollutants. Nonsummer warmth and traffic-related air pollution, probably mediated through exposure to common allergens such as dust mites, are possible risk factors for allergic rhinitis in middle-school-aged children.
Rhodostomin (Rho) is a snake venom protein isolated from Calloselasma rhodostoma. Rho is a disintegrin that inhibits platelet aggregation by blocking the binding of fibrinogen to the integrin alpha(IIb)beta3 of platelets. Rho produced in Escherichia coli inhibited platelet aggregation with a K(I) value of 263 nM. Although functional, Rho produced in E. coli is misfolded based on our 2D and 3D NMR studies. In order to correct the folding problem, Rho was expressed in Pichia pastoris. The recombinant Rho expressed in P. pastoris inhibited platelet aggregation with a resulting K(I) value of 70 nM. This is the same potency as that of native Rho. CD analysis showed that the secondary structures of Rho are pH-independent and contain 3.5-7.9% alpha-helix, 48.2-50.5% beta-structures, and 42.3-47% coil. The sequential assignment and structure analysis of Rho were obtained using 2D and 3D 15N-edited NMR spectra. These results provide the first direct evidence that highly disulfide-bonded disintegrin can be expressed in P. pastoris with the correct fold. This evidence may serve as the basis for exploring the structure and function relationships as well as the dynamics of disintegrin and its variants.
Targeted echogenic liposome dispersions for ultrasonic enhancement of vasoactive and pathological components of endothelium and atherosclerosis have recently been developed. The component lipids required for acoustic and targeting properties include phosphatidylcholine, phosphatidylethanolamine phosphatidylglycerol (PG), and cholesterol (CH), initially in a 60:8:2:30 mol % ratio. Component lipids, lyophilization, sugars, and freezing conditions were varied to optimize acoustic ultrasound reflectivity and acoustic stability. Echogenic liposome dispersions were made by using the dehydration-rehydration process. The lipid concentrations were varied (CH in the range 1 to 40 mol % and PG from 1 to 16 mol %). Variations in type and concentration of sugars were examined. The effect of freezing conditions and re-lyophilization was examined. Ultrasound reflectivity was assessed by using a 20-MHz intravascular ultrasound catheter and computer-assisted videodensitometry. Ultrasound reflectivity was optimized at a CH concentration of 10 mol %; PG concentration variation had essentially no effect on initial values of echogenicity. Optimal acoustic stability was observed with concentrations of 10-15 mol % CH and with a PG concentration greater than 4 mol %. Preparations made with 0.2 M mannitol were more ultrasound reflective than those made with lactose, trehalose, and sucrose. Re-lyophilization and freezing temperatures below -20 degrees C increased ultrasound reflectivity. We optimized the ultrasound properties of echogenic liposomal dispersions, the conditions of which provide some insight into the underlying lipid structures responsible. The preparations developed are now more stable and acoustically reflective than our previous preparations. This advances the development of echogenic lipid dispersions as targeted ultrasound contrast agents for use in general ultrasound as well as cardiovascular imaging.
The mechanism sediment motion that affects cadmium (Cd) adsorption on sediment particles was studied in a turbulence tank in the presence (and absence) of bed mud. The experimental results were verified by a mathematical model for heavy metal transport-transformation developed for the turbulence tank. The mathematical model includes the equations of water flow, sediment motion, heavy metal transport-transformation, heavy-metal reaction kinematics and equations for prescribing the initial conditions and boundary conditions for the experiment. The model conforms the transport-transformation of heavy-metal pollutants in surface waters to following the law of convective-diffusive of common tracers and the characteristics of fate and transport of sediment motion. Variations of dissolved Cd concentrations and suspended particulate Cd concentrations with time and in the water column were measured and computed. The experimental measurements correspond with the computed results. Both the experimental measurements and computed results show that it takes about 6 h to reach equilibrium condition for cadmium adsorption by sediment particles. This is different from the result obtained from experiments conducted in continuously stirred tank reactors (or batch reactors) in which adsorption equilibrium can be achieved in about 20 min. Determination of the model parameters for sediment adsorption-desorption of metals in the tank is discussed. The experimental and computed results obtained in this study are useful to solve practical engineering problems in surface waters.
AIMS: The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects. METHODS: A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5-7 half-lives and fluoxetine, and norfluoxetine were determined by reversed-phase high performance liquid chromatography. RESULTS: Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128% increase in area under the concentration vs time curve (AUC(0, infinity), P < 0.001), 113% increase in terminal elimination half-life (t(1/2)) (P < 0.001), and 55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean +/- (s.d) norfluoxetine AUC(0, 192 h) was significantly lower in PMs than that in EMs (1343 +/- 277 vs 2935 +/- 311, P < 0.001). Mean fluoxetine Cmax and AUC(0, infinity) in wild-type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower than that in PMs (22.4 +/- 3.9 vs 36.7 +/- 8.9, P < 0.001; 732 +/- 42 vs 2152 +/- 492, P < 0.001, respectively). Mean oral clearance in individuals with the wild type homozygous genotype was significantly higher than that in heterozygotes and that in PMs (54.7 +/- 3.4 vs 36.0 +/- 8.7, P < 0.01; 54.7 +/- 3.4 vs 20.6 +/- 6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0, 192 h) in PMs was significantly lower than that in wild type homozygotes (1343 +/- 277 vs 3163 +/- 121, P < 0.05) and that in heterozygotes (1343 +/- 277 vs 2706 +/- 273, P < 0.001), respectively. CONCLUSIONS: The results indicated that CYP2C19 appears to play a major role in the metabolism of fluoxetine, and in particular its N-demethylation among Chinese healthy subjects.
The occurrence of asthma and allergy are related to lifestyle factors, and dietary pattern may be one of the contributing factors. To examine the possible association between dietary intake and the prevalence of asthma and allergic rhinitis in teenagers. In a population-based cross-sectional survey, the relationship was sought between food frequency and physician-diagnosed asthma and allergic rhinitis in 1166 adolescents aged 13-17. The prevalence was 4.0% for asthma and 12.4% for rhinitis. Living in an urbanized area was a significant predictor of asthma and rhinitis. In univariate analysis, higher frequencies of oily fish, butcher's meat, liver and deep-fried foods were associated with asthma. Relevant food frequency variables were dichotomized at the 75th percentile for multivariate logistic regression analysis, which included adjustment for two levels of urbanization. Asthma was associated with intakes of liver (OR = 2.32, 95%CI 1.11-4.80), deep-fried foods (OR = 2.13, 95%CI 1.06-4.30) and butcher's meat (OR 1.84, 95%CI 0.89-3.80). In a similar analysis, allergic rhinitis was associated with liver (OR = 1.67, 95%CI 1.06-2.63). No protective effect was demonstrated for any of the food items examined. Protein-rich and fat-rich foods of animal origin were associated with a higher prevalence of asthma in teenagers.
BACKGROUND: The occurrence of asthma may be associated with dietary factors. OBJECTIVE: To examine the association between nutrient intake and physician-diagnosed asthma and allergic rhinitis. METHODS: A stratified, multiple-staged sampling design was used to select study areas, in which household interviews were carried out to gather information on health status and 24-h food recall. Data from 1166 adolescents, 13-17 years of age, were analysed. RESULTS: In univariate analysis, total calorie and energy-adjusted fat intake were associated with the prevalence of asthma, whereas vitamin A and vitamin C intake showed negative association with asthma. Multivariate logistic regression was used to adjust for sex and levels of urbanization; intake of saturated fats was associated with increased risk (OR = 2.02 for an increase of one SD, 95%CI 1.40-2.90), while monounsaturated fats were inversely related to asthma (OR = 0.65 for an increase of one SD, 95%CI 0.43-0.99). Vitamin C intake in the lowest quartile was associated with elevated risk for asthma with marginal significance (OR = 1.81, 95%CI 0.88-3.71, P = 0.10). None of the nutritional factors was associated with allergic rhinitis. CONCLUSION: Results from this cross-sectional survey suggest that saturated and monounsaturated fats may have different effects on airway inflammation.
OBJECTIVES: Our goal was to establish and validate a modified cocktail approach including probe drugs caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam for simultaneous phenotyping of CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A. METHODS: The study was conducted in 14 healthy, nonsmoking male volunteers with a cocktail of 5 drugs consisting of 100 mg caffeine, 200 mg chlorzoxazone, 100 mg mephenytoin, 100 mg metoprolol, and 7.5 mg midazolam in a randomized manner with a 7 x 7 Latin square design. Plasma was obtained at 1, 4, and 6 hours, and urine was collected from 0 to 8 hours after oral drug administration. RESULTS: The phenotypic indexes determined for caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam were not significantly different when the drugs were given in different combinations. There were no metabolic interactions or analytic interference of these probe drugs. CONCLUSIONS: This cocktail approach can simultaneously provide independent in vivo phenotypic measures for the cytochrome P450 (CYP) enzymes CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A.
A novel fibrous-bed trickling filter was developed to remove toluene present in contaminated air. Pure culture of Pseudomonas putida F1 was attached on fibrous-bed and utilized toluene as the carbon source. Experimental results indicated the removal efficiency decreased with the increase of inlet concentration. In general, the removal efficiency of toluene was greater than 90% when the inlet loading capacity was below 70 g m-3h-3. The elimination capacity increased with increasing inlet loading capacity, but the increased rate decreased gradually. When the inlet loading capacity increased to 300 g m-3h-1, the elimination capacity could approach to 130 g m-3h-1. The first order kinetics model was useful to describe the removal of toluene in this filter and an excellent linear relationship was found between the apparent first order parameter and inlet concentration (ranging from 1.2 g m-3 to 3.5 g m-3). Also, the performance of fibrous-bed trickling filter was relatively stable during the four-month period of continuous operation. Slight clogging phenomena of filters were observed only under high loading capacity.
BACKGROUND: Epidemiological studies have suggested that the dietary pattern may be associated with the prevalence of asthma. We previously reported that an increased intake of foods of animal origin was associated with the occurrence of allergic rhinitis and asthma in adolescents. Here we examined the effect of dietary cholesterol in a murine model of allergic pulmonary inflammation. METHODS: Weanling C57BL/6 mice were fed a control diet containing 0.02% cholesterol or a diet supplemented with 1% or 2% cholesterol. Four weeks later the mice were sensitized with intraperitoneal ovalbumin (OVA) followed by OVA or saline inhalation 2 weeks later. OVA aerosol-induced inflammation was significantly enhanced by dietary supplementation of 1% or 2% cholesterol. RESULTS: Among OVA-challenged mice, leukocyte numbers, particularly those of eosinophils, in the bronchoalveolar space increased by 3- to 5-fold with the cholesterol supplement. Among OVA aerosol-challenged mice, the levels of interleukin-5 and cysteinyl leukotrienes in the bronchoalveolar lavage fluid were significantly higher in those fed the 2% cholesterol diet compared with mice on the control diet. CONCLUSIONS: Dietary cholesterol may enhance pulmonary allergic inflammation.
Growth of three strains of Staphylococcus aureus and two strains of Escherichia coli on nutrient agar (NA) supplemented with ethanol and NaCl was investigated. S. aureus did not grow on NA containing > or =10% ethanol (wt/wt) combined with > or =0% NaCl (wt/wt), or 7.5% ethanol combined with 7.5% NaCl. Neither E. coli nor E. coli O157:H7 grew on NA containing > or =7.5% ethanol combined with > or =0% NaCl, 5% ethanol combined with > or =2.5% NaCl, or > or =5% NaCl combined with > or =0% ethanol. It is apparent that NaCl enhanced the inhibitory effect of ethanol on growth of S. aureus and E. coli When cells were suspended in nutrient broth containing 12.5, 20, or 40% ethanol combined with NaCl, viable cells decreased with an increase of ethanol concentration. Ethanol sensitivity among strains and between genera varied in a limited range. When the cells were exposed to 20% ethanol in combination with 5% NaCl, S. aureus and E. coli lost viability after 30 and 10 min, respectively. When treated with 40% ethanol combined with > or =0% NaCl, all test strains lost viability within 5 min.
AIM: The present study was designed to define the kinetic behavior of fluoxetine N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P-450 (CYP) involved in this metabolic pathway. METHODS: The kinetics of Ne formation of norfluoxetine was determined in human liver microsomes from six genotyped CYP2C19 extensive metabolizers (EM). The correlation studies between the fluoxetine N-demethylase activity and various CYP enzyme activities were performed. Selective inhibitors or chemical probes of various cytochrome P-450 isoforms were also employed. RESULTS: The kinetics of norfluoxetine formation in all liver microsomes were fitted by a single-enzyme Michaelis-Menten equation (mean Km=32 micromol/L+/-7 micromol/L). Significant correlations were found between N-demethylation of fluoxetine at both 25 micromol/L and 100 micromol/L and 3-hydroxylation of tolbutamide at 250 micromol/L (r1=0.821, P1=0.001; r2=0.668, P2=0.013), respectively, and S-mephenytoin 4'-hydroxylase activity (r=0.717, P=0.006) at high substrate concentration of 100 micromol/L. S-mephenytoin (SMP) (a CYP2C19 substrate) at high concentration and sulfaphenazole (SUL) (a selective inhibitor of CYP2C9) substantially inhibited norfluoxetine formation. The reaction was minimally inhibited by coincubation with chemical probe, inhibitor of CYP3A4 (triacetyloleandomycin, TAO). The inhibition of fluoxetine N-demethylation at high substrate concentration (100 micromol/L) was greater in PM livers than in EM livers (73 % vs 45 %, P < 0.01) when the microsomes were precoincubated with SUL plus TAO. CONCLUSION: Cytochrome P-450 CYP2C9 is likely to be a major CYP isoform catalyzing fluoxetine N-demethylation in human liver microsomes at a substrate concentration close to the therapeutic level, while polymorphic CYP2C19 may play a more important role in this metabolic pathway at high substrate concentration.
AIM: To compare the level and/or activity of several important cytochrome P-450 (CYP) enzymes in liver microsomes prepared from different Chinese subjects. METHODS: Individual CYP contents, including CYP1A2, CYP2C9, and CYP3A4, in liver microsomes of 17 Han, 17 Zhuang, and 8 Miao subjects were determined by using Western blot analysis and densitometric scanning. The substrates for measuring the activity of individual CYP in vitro included phenacetin, tolbutamide, debrisoquine, and omeprazole. RESULTS: There was a large interindividual variability in the content and activity of CYP1A2, 2C9 and 3A4. And the activity of CYP2D6 also varied greatly between individual samples. CYP3A4 (32 %) is the most abundant CYP in Chinese liver microsomes, and the levels of CYP2C9 (19 %) and CYP1A2 (16 %) were also considerable. No clear ethnic, sex- and age-related differences in individual CYP content and catalytic activity were detected in 42 Chinese liver samples, except that there were somewhat ethnic and sex-related differences in the content and activity of CYP1A2. Good correlation between enzyme protein content and activity was found for CYP1A2, 2C9 and 3A4. CONCLUSION: Our results may provide useful information for the study of drug metabolism by liver microsomes in Chinese.
AIM: To constitute a method to determine the estradiol metabolites in human liver microsome in low concentration of estradiol. METHODS: Use high performance liquid chromatography after solvent extraction, evaporation, and reconstitution to separate the metabolites and use a electrochemistry detector to detect the metabolites. RESULTS: With a mobile phase of acetic acid buffer-acetonitrile (50:50, v/v, pH 4.5) at flow rate of 1.0 mL/min and a potential of +0.7 V vs Ag/AgCl, all six composition were well separated and satisfactorily detected. There are E3, 16alpha-OHE1, 2-OHE2, E1, and two unidentified composition. The minimum detectable amount is about 100 p g on column. This method is sensitive enough to detect E1 in a substrate concentration of 1 micromol/L. CONCLUSION: The method can be used to study the metabolism mechanism of estradiol in liver microsome.