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Biomedical subjects

Yue Chen

Publications and source records attributed to Yue Chen.

At least 109 records · Page 6Linked to original sources
PubMed2004

[Hfgl2/fibroleukin expression in liver and peripheral blood mononuclear cells (PBMC) and its correlation with disease severity].

OBJECTIVE: Viral hepatitis remains a major public health problem and the most common type of liver disease worldwide. There are an increasing number of patients with chronic hepatitis B who develop acute hepatitis on chronic condition (AOC) and die of acute hepatic failure both as a result of lack of understanding of the pathogenesis of the disease and lack of effective treatment. The hallmark of AOC is the extreme rapidity of the necromicroinflammatory process resulting in widespread or total hepatocellular necrosis in weeks or even days. Our previous studies have shown in an experimental animal model of fulminant viral hepatitis caused by murine hepatitis virus strain 3, the importance of macrophage activation, and expression of a unique gene mfgl 2 which encodes a serine protease capable of directly cleaving prothrombin to thrombin, resulting in widespread fibrin deposition within the liver and hepatocyte necrosis. The undergoing study in this report is designed to identify the role of hfgl 2 (human fibrinogen like protein 2) /fibroleukin in patients with viral hepatitis. METHODS: Liver tissues were obtained from 23 patients with AOC hepatitis B, and from 13 patients with inactive chronic hepatitis B (CHB) and 14 patients with chronic hepatitis B with cirrhosis during the year of 1995 to the end of 2001. Liver biopsies were performed within 30 min after the patients were diagnosed with death as a result of acute hepatic failure. Liver samples were also obtained from 4 liver donors as normal controls. In addition, peripheral blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with AOC hepatitis B and 10 patients with CHB during the May of 2001 to March of 2002 and 10 healthy volunteer as negative control. PBMCs were freshly isolated and smeared on slides and kept at -80 degree C for further use. Histological sections were stained with hemotoxylin and eosin. A 169 bp of hfgl 2 cDNA probe and a polyclonal or monoclonal antibody against hfgl 2 were used to detect the expression of hfgl 2 mRNA and protein in liver samples as well as PBMC by immune histochemistry separately. RESULTS: Liver tissues from the patients with acute on chronic hepatitis had classical pathological features of acute necroinflammation. Hfgl 2 was detected by immune histochemistry in 21 of 23 patients (91.3%) in liver sections from patients with acute on CHB, while only 1 of 13 patients (7.7%) with CHB and cirrhosis and no evidence of active disease had hfgl 2 mRNA or protein expression. 28 of 30 patients (93.3%) with acute on CHB and 1 of 10 with CHB were detected with hfgl 2 expression in PBMC. There was no hfgl 2 expression in either the liver tissue or the PBMC from the normal donors. There was positive correlation of hfgl 2 expression and the severity of the disease displayed by the value of bilirubin and PT. CONCLUSION: The molecular and cellular results reported here in patients with acute on chronic hepatitis and who died of acute hepatic failure correlates with previous report in 8 patients with fulminant hepatic failure (FHF) and mimic closely the changes observed in the murine model of fulminant viral hepatitis in which the pathogenesis of the disease has been studied in a stepwise fashion. This study further suggests that virus induced hfgl 2 prothrombinase/fibroleukin expression and the potent function of the protein it encodes plays a pivotal role in initiating acute severe hepatitis on the baseline of chronic hepatitis. The measurement of hfgl 2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of disease in patients with the AOC hepatitis B and a target for therapeutic intervention.

Adolescent↗
PubMed2004

[Purification and separation of mannan-binding lectin (MBL) and MBL-associated serine proteases complex from human plasma].

OBJECTIVE: To separate mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) from human plasma. METHODS: A two-step affinity chromatography on underivatized sepharose 4B was employed for purification of MBL-MASP complex, followed by gel filtration on a Sephacryl S-300 column for separation of MBL and MASPs from the complex. The purification procedures were performed at 4 degrees Celsius with the addition of two proteolytic inhibitors, phenyl methylsulfonyl fluoride and 1,10-phenanthroline during affinity chromatography but not in the gel filtration buffer. RESULTS: Preparations of highly purified MBL and proenzyme MASPs were obtained. The purified MBL was shown by SDS-PAGE and Western blotting to be a functional multimer composed of 28,000 and 32,000 peptide chains, with high bioactivity as demonstrated by ligand-binding assay and yeast agglutination experiment. CONCLUSION: A simple and convenient procedure is established successfully for the purification of MBL and the proenzyme MASPs.

Chromatography, Affinity↗
PubMed2003

Conformation-activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone.

The conformation-activity relationships for the biologically active polyketide, epothilone, have been determined. Computer-based molecular modeling and high field NMR techniques have provided the solution preferences for epothilones and. For the C1-C8 polypropionate region, two conformational families, conformers 1 and 2, have been identified as having significant populations in polar and non-polar solvents. In the C11-C15 region, additional flexibility was observed and two local conformations have been identified as important, conformers 3 and 4. Epothilone analogues with altered conformational profiles have been designed and synthesized. Conformational analysis and the results of biological assays have been correlated to provide increased understanding of the biologically active conformation for the epothilone class of natural product. Conformation-activity relationships have been shown to be an important complement to structure-activity data.

Drug Design↗
PubMed2003

Cardioprotective effects of ingliforib, a novel glycogen phosphorylase inhibitor.

Interventions such as glycogen depletion, which limit myocardial anaerobic glycolysis and the associated proton production, can reduce myocardial ischemic injury; thus it follows that inhibition of glycogenolysis should also be cardioprotective. Therefore, we examined whether the novel glycogen phosphorylase inhibitor 5-Chloro-N-[(1S,2R)-3-[(3R,4S)-3,4-dihydroxy-1-pyrrolidinyl)]-2-hydroxy-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide (ingliforib; CP-368,296) could reduce infarct size in both in vitro and in vivo rabbit models of ischemia-reperfusion injury (30 min of regional ischemia, followed by 120 min of reperfusion). In Langendorff-perfused hearts, constant perfusion of ingliforib started 30 min before regional ischemia and elicited a concentration-dependent reduction in infarct size; infarct size was reduced by 69% with 10 microM ingliforib. No significant drug-induced changes were observed in either cardiac function (heart rate, left ventricular developed pressure) or coronary flow. In open-chest anesthetized rabbits, a dose of ingliforib (15 mg/kg loading dose; 23 mg.kg(-1).h(-1) infusion) selected to achieve a free plasma concentration equivalent to an estimated EC(50) in the isolated hearts (1.2 microM, 0.55 microg/ml) significantly reduced infarct size by 52%, and reduced plasma glucose and lactate concentrations. Furthermore, myocardial glycogen phosphorylase a and total glycogen phosphorylase activity were reduced by 65% and 40%, respectively, and glycogen stores were preserved in ingliforib-treated hearts. No significant change was observed in mean arterial pressure or rate-pressure product in the ingliforib group, although heart rate was modestly decreased postischemia. In conclusion, glycogen phosphorylase inhibition with ingliforib markedly reduces myocardial ischemic injury in vitro and in vivo; this may represent a viable approach for both achieving clinical cardioprotection and treating diabetic patients at increased risk of cardiovascular disease.

Animals↗
PubMed2003

[Expression of human fibroleukin gene acute on chronic hepatitis B and its clinical significance].

OBJECTIVE: To investigate the mRNA and protein expressions of human fibroleukin gene (hfg12) in acute on chronic (AOC) hepatitis B and its clinical significance. METHODS: Liver tissues were obtained from 23 patients with AOC hepatitis B, 13 patients with chronic hepatitis, and 14 patients with cirrhosis to be examined histologically. Immunohistochemistry and in situ hybridization were used to detect the mRNA and protein expressions of hfg12 in the liver tissues. Double staining was used to the hfg12 positive samples to examine both the hfg12 and fibrin. Four specimens of liver tissue from normal donors were used as controls. RESULTS: Immunohistochemistry showed that hfg12 was expressed in the liver tissues of 21 out of the 23 patients with AOC hepatitis B (91.30%) and only one out of the 13 patients with chronic hepatitis (7.69%). In situ hybridization showed that hfg12 was expressed in the liver tissues of 13 out of he 23 patients with AOC hepatitis B and in none of the 27 patients with chronic hepatitis or cirrhosis. In patients with AOC hepatitis Kupffer's cell, CD68 positive, was numerous and big, mainly distributed in the necrosis areas. It was identified as the same of hfg12-expressing cells. CONCLUSION: High expression of hfg12 is one of the molecular mechanisms of necrosis of liver cells in AOC hepatitis.

Adolescent↗
PubMed2003

Conformation-activity relationships in polyketide natural products: a new perspective on the rational design of epothilone analogues.

The syntheses of C14-methyl analogues of epothilone B and D are described. Conformational analysis using computational methods, X-ray crystallography, and NMR studies showed that the stereochemistry at C14 has a pronounced effect on the conformation of the epoxide region. Biological assays indicated significant differences in their biological activity. Substitution which stabilized conformer I retained significant biological activity. In contrast, substitution which stabilized conformer II provided analogues with no measurable cytotoxicity. The conformation-activity relationships strongly support the importance of conformer I as the bioactive conformation of the epoxide region of epothilone. The approach presented here offers a new perspective on rational design of modified biologically active polyketides.

Antineoplastic Agents↗
PubMed2003

Hospital readmissions for asthma in children and young adults in Canada.

To examine the incidence rate of hospital readmission for asthma in relation to sex and age among Canadian children and young adults, we used data from 86,863 subjects under age 20 years when they had a first admission for asthma as 1 of first 5 diagnoses in Canada between April 1, 1994 and March 31, 1997. We calculated age- and sex-specific incidence rates, and used the Cox proportional hazards model for multivariate analysis. Of these subjects, 20,277 (23.3%) were readmitted to hospital for asthma during the study period. After adjusting for length of stay for first admission and province, the rate ratio for females vs. males was 0.86 for those under age 1 year, and close to unity for the 1-4-year and 5-9-year age groups, whereas it was 1.47 and 1.35 for the 10-14-year and 15-19-year age groups, respectively. The data showed similar trends for rehospitalization asthma as a primary diagnosis. The incidence rate of rehospitalization showed little sex difference between ages 1-9 years, but was markedly higher in females than in males 10-19 years of age. Airway size, female hormonal changes, increased use of cosmetic products, and cigarette smoking among adolescent girls may contribute to the age- and sex-differences in adolescence.

Adolescent↗
PubMed2003

Sex difference in hospitalization due to asthma in relation to age.

To describe the sex and age differences in asthma hospitalization among the Canadian population, we conducted an analysis based on a total of 9,486,173 hospital records in Canada for a 3-year period (1994/1995, 1995/1996, and 1996/1997), including 204,304 asthma patients and 288,977 asthma-related records. Asthma as one of the first five diagnoses, accounted for 3.0% of total hospitalizations, which was almost constant across the 3-year study period. The 3-year cumulative incidence of asthma hospitalization was substantially higher for young boys than girls, and it was reversed for adults. The incidence ratio for females vs. males for asthma hospitalization reached 2.8 for individuals 25 to 34 years of age, decreased gradually with increasing age, and then approached unity for those aged 80 years or more. The data suggest that sex is an important determinant for asthma, and the sex effect varies considerably over a life span.

Adolescent↗
PubMed2003

A time-series study of air pollution, socioeconomic status, and mortality in Vancouver, Canada.

We evaluated the relationship between daily levels of particulate and gaseous phase pollutants and mortality within a dynamic cohort of approximately 550,000 individuals whose vital status was ascertained between 1986 and 1999. Time-series methods were applied to evaluate whether there were differential pollutant effects on daily aggregated numbers of deaths in the cohort that was stratified into quintiles of income as defined by the 1991 and 1996 Canadian censuses. The percent change in all-cause, cardiovascular, respiratory, and cancer daily mortality was calculated in relation to short-term changes in levels of a number of particulate (PM(2.5), PM(10-2.5), total suspended particle co-efficient of haze PM(10), SO(4)) and gaseous (O(3), CO, SO(2), NO(2)) pollutants. The estimated effects of air pollution on mortality were adjusted for day of week effects, and several meteorologic variables including temperature, change in barometric pressure, and relative humidity. Several gaseous pollutants were associated with an increased risk of mortality. Specifically for an increase equivalent to the difference between the 90th and 10th percentiles, the estimated percent change in daily mortality based on the 3-day average of NO(2), and SO(2) was 4.0% and 1.3%, respectively. The corresponding changes in mortality associated with SO(2) were much higher when analyses were restricted to death from respiratory disease. Specifically, a difference between the 90th and 10th percentiles was associated with a 5.6% (95% CI= -0.7% to 12.3%). The daily mean coarse fraction (PM(10-2.5)) was associated with increased cardiovascular mortality (estimated change=5.9%, 95% CI=1.1-10.8%). PM(2.5) was not found to be an important predictor of mortality. For NO(2), CO, and SO(2), there was some suggestion of increased risk of all-cause and cardiovascular mortality at lower levels of socioeconomic status. However, these results should be interpreted cautiously due to the small number of deaths observed within each stratum of socioeconomic status.

Aged↗
PubMed2003

Association between ozone and respiratory admissions among children and the elderly in Vancouver, Canada.

In this study, we examine the impact of ozone on daily respiratory admissions in both young children and the elderly in greater Vancouver, British Columbia. Study subjects included children less than 3 yr of age and adults 65 yr of age or over living in greater Vancouver who had acute hospital admissions for any respiratory diseases (ICD-9 codes 460-519) during the 13-yr period 1986-1998. Bidirectional case-crossover analysis was used to investigate associations between ambient ozone and respiratory hospitalizations after adjustment for other pollutants, including carbon monoxide, nitrogen dioxide, sulfur dioxide, and coefficient of haze. Potential effect modification by socioeconomic status as measured by household income was also examined. Respiratory admissions were associated with ozone levels 2, 3, 4, and 5 days prior to admission in both children and the elderly, with the strongest association observed at a lag of 4 days. Odds ratios for hospital admission of 1.22 (95% CI: 1.15-1.30) for children and 1.13 (1.09-1.18) for the elderly, respectively, were found, based on an increment in exposure corresponding to the interquartile range for ozone. Adjusting for other pollutants did not attenuate the ozone effect on respiratory admissions. Nor did socioeconomic status appear to modify the association between ozone and respiratory admissions in either children or the elderly. We concluded that ambient ozone is positively associated with respiratory hospital admission among young children and the elderly in Vancouver, British Columbia. These associations persisted after adjustment for both copollutant exposures and socioeconomic status.

Age Factors↗
PubMed2003

Gender-related differences in the association between socioeconomic status and self-reported diabetes.

BACKGROUND: The prevalence of diabetes has been steadily increasing in Western countries. We investigated the impact of socioeconomic status (SES) on the prevalence of self-reported diabetes, and its differences between genders. METHODS: Data for this investigation were derived from the second cycle of the National Population Health Survey conducted in 1996-1997. A total of 39 021 subjects (17 730 males and 21 291 females) >/=40 years of age who answered the question about diabetes were included in the present analysis. Educational attainment and income adequacy were used as indicators of SES. Multiple logistic regression models were constructed for men and women separately to assess the effects of SES on the prevalence of diabetes after adjustment for age, area of residence, body mass index, and physical activity. RESULTS: and The prevalence of diabetes was 6.6% among men and 5.5% among women. The CONCLUSIONS: prevalence increased with decreasing income category and educational attainment in both genders. The odds ratios for income and education in relation to diabetes after adjustment remained significant in women, but attained unity in men. Canadian women >/=40 years of age of low SES have a relatively high prevalence of diabetes, independent of age, area of residence, obesity, and physical inactivity.

Adult↗
PubMed2003

Comparison of time series and case-crossover analyses of air pollution and hospital admission data.

BACKGROUND: Time series analysis is the most commonly used technique for assessing the association between counts of health events over time and exposure to ambient air pollution. Recently, case-crossover analysis has been proposed as an alternative analytical approach. While each technique has its own advantages and disadvantages, there remains considerable uncertainty as to which statistical methodology is preferable for evaluating data of this type. METHODS: The objective of this paper is to evaluate the performance of different variations of these two procedures using computer simulation. Hospital admission data were generated under realistic models with known parameters permitting estimates based on time series and case-crossover analyses to be compared with these known values. RESULTS: While accurate estimates can be achieved with both methods, both methods require some decisions to be made by the researcher during the course of the analysis. With time series analysis, it is necessary to choose the time span in the LOESS smoothing process, or degrees of freedom when using natural cubic splines. For case-crossover studies using either uni- or bi-directional control selection strategies, the choice of time intervals needs to be made. CONCLUSIONS: We prefer the times series approach because the best estimates of risk that can be obtained with time series analysis are more precise than the best estimates based on case-crossover analysis.

Air Pollutants↗
PubMed2003

The epidemiology of chronic rhinosinusitis in Canadians.

OBJECTIVE: To study the prevalence of chronic rhinosinusitis and its risk factors among Canadians. STUDY DESIGN: Complex survey design incorporating stratification, multiple stages of selection, and unequal probabilities of selection of respondents. METHODS: We used the cross-sectional data from 73,364 subjects (34,241 male and 39,123 female subjects) 12 years of age or older who participated in the second cycle of the National Population Health Survey, which was conducted from 1996 to 1997. All these individuals were asked whether they had certain chronic health conditions that had lasted or were expected to last 6 months or longer, including rhinosinusitis. RESULTS: The prevalence of rhinosinusitis was higher in female (5.7%) than in male (3.4%) subjects. The sex difference was consistent across age groups. The prevalence increased with age and leveled off after the age of 60 years. In female but not in male subjects, the prevalence was slightly higher among those living the eastern region or among native Canadians as compared with those living in the central or western regions or immigrants. Cigarette smoking and low income were associated with a higher prevalence of rhinosinusitis in both sexes. The smoking effect was modified by allergy history in male subjects. Rhinosinusitis was more common among subjects with allergy history, asthma, or chronic obstructive pulmonary disease. The prevalence of rhinosinusitis was similar in subjects with or without reporting regular alcohol drinking and exercise. CONCLUSION: Previous data indicating an increased susceptibility of women to asthma and chronic obstructive pulmonary disease, together with the similar finding for rhinosinusitis, suggest that women have a general increase in susceptibility to respiratory tract disease.

Adolescent↗
PubMed2003

The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis.

Fibrin deposition and thrombosis within the microvasculature is now appreciated to play a pivotal role in the hepatocellular injury observed in experimental and human viral hepatitis. Importantly, the pathways by which fibrin generation is elicited in viral hepatitis may be mechanistically distinct from the classical pathways of coagulation induced by mechanical trauma or bacterial lipopolysaccharide (LPS). In the setting of murine hepatitis virus strain-3 (MHV-3) infection, a member of the Coronaviridae, activated endothelial cells and macrophages express distinct cell-surface procoagulants, including a novel prothrombinase, Fgl2/fibroleukin, which are important for both the initiation and localization of fibrin deposition. To assess the role of Fgl2/fibroleukin in murine viral hepatitis we generated a Fgl2/fibroleukin-deficient mouse. Peritoneal macrophages isolated from Fgl2/fibroleukin-/- mice did not generate a procoagulant response when infected with MHV-3. Fibrin deposition and liver necrosis were markedly reduced, and survival was increased in mice infected with MHV-3. To address the relevance of Fgl2/fibroleukin in human chronic viral hepatitis we studied patients with minimal and marked chronic hepatitis B. We detected robust expression of Fgl2/fibroleukin mRNA transcripts and protein in liver tissue isolated from patients with marked chronic hepatitis B. Fibrin deposition was strongly associated with Fgl2/fibroleukin expression. Collectively, these data indicate a critical role for Fgl2/fibroleukin in the pathophysiology of experimental and human viral hepatitis.

Adult↗
PubMed2003

Effects of typical, atypical, and no antipsychotic drugs on visual contrast detection in schizophrenia.

OBJECTIVE: Visual contrast detection has been reported in some studies to be normal in schizophrenia patients, but in other studies impairments have been reported. Because contrast detection in the visual processing system is mediated by dopamine, and because the pharmacotherapy of schizophrenia involves blocking dopamine postsynaptic receptor sites, the authors investigated the effects of dopamine-blocking antipsychotic drugs on visual contrast detection in schizophrenia. METHOD: Visual contrast detection thresholds were measured in healthy subjects and schizophrenia patients receiving typical and atypical antipsychotic drugs; a two-alternative, forced-choice psychophysical method was used. Also included were six patients receiving no antipsychotic treatment as well as clinically unaffected first-degree relatives of the schizophrenia patients. RESULTS: Patients receiving atypical antipsychotic drugs showed unimpaired visual contrast detection, those given typical antipsychotic drugs exhibited higher visual contrast detection thresholds, and the unmedicated schizophrenic patients showed visual contrast detection thresholds significantly below those of healthy subjects. CONCLUSIONS: Dopamine modulation via D(2) receptor blockade affects sensory processes in schizophrenia, shifting visual contrast detection from hypersensitivity in the unmedicated state to normal and even to hyposensitive levels. Thus, antipsychotic drug treatment may account for the inconsistent reports concerning visual contrast detection in schizophrenia.

Adult↗
PubMed2003

Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver, Canada.

The association between ambient air pollution and adverse health effects, such as emergency room visits, hospitalizations, and mortality from respiratory and cardiovascular diseases, has been studied extensively in many countries, including Canada. Recently, studies conducted in China, the Czech Republic, and the United States have related ambient air pollution to adverse pregnancy outcomes. In this study, we examined association between preterm birth, low birth weight, and intrauterine growth retardation (IUGR) among singleton live births and ambient concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone in Vancouver, Canada, for 1985-1998. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for such effects. Low birth weight was associated with exposure to SO2 during the first month of pregnancy (OR = 1.11, 95% CI, 1.01-1.22, for a 5.0 ppb increase). Preterm birth was associated with exposure to SO2 (OR = 1.09, 95% CI, 1.01-1.19, for a 5.0 ppb increase) and to CO (OR = 1.08, 95% CI, 1.01-1.15, for a 1.0 ppm increase) during the last month of pregnancy. IUGR was associated with exposure to SO2 (OR = 1.07, 95% CI, 1.01-1.13, for a 5.0 ppb increase), to NO2 (OR = 1.05, 95% CI, 1.01-1.10, for a 10.0 ppb increase), and to CO (OR = 1.06, 95% CI, 1.01-1.10, for a 1.0 ppm increase) during the first month of pregnancy. In conclusion, relatively low concentrations of gaseous air pollutants are associated with adverse effects on birth outcomes in populations experiencing diverse air pollution profiles.

Adult↗
PubMed2003

[Application of image analysis system to the study of biomedicine].

Image analysis plays an important role in morphological study of tissues and cells and their quantitative analysis. It also contributes to clinical pathological diagnosis. With the rapid development of computer technology great progress has been made in the image analysis system, its measurement, rapidity, accuracy and the extent of automation have been greatly enhanced. In the meantime advances in medicine give impetus to its improvement. In this paper, the process of development, the basic structure and mechanism of image analysis system are discussed and the application of image analysis system to the study of biomedicinal is presented.

Image Processing, Computer-Assisted↗