Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 505 records · Page 28Linked to original sources

PubMed2001

Abrogation of estrogen-mediated cellular and biochemical effects by indole-3-carbinol.

The use of naturally occurring phytoantiestrogens for prevention and therapy of breast cancer is an alternative to synthetic antiestrogens. We have been examining the mechanism of action of the antiestrogen indole-3-carbinol (I3C), a constituent of compounds present in cruciferous vegetables. I3C abrogates the cell-proliferative effect of 17 beta-estradiol (E2), as observed in several different estradiol-responsive breast cancer cell lines and isolated cell clones. Modulation of E2 activity by I3C, in part, was by the induction of the 2-hydroxylation pathway, one of the two competing hydroxylation pathways of estrone conversion that resulted in the formation of metabolites with antiestrogenic properties. I3C-mediated induction of the 2-hydroxylation pathway correlated with a selective induction of cytochrome P-450 1A1 by I3C in E2-responsive human breast cancer cells. Induction of neither the 2-hydroxylation pathway nor cytochrome P-450 1A1 was observed in estrogen-nonresponsive human breast cancer cells. This selective effect warranted a further search for biochemical targets of I3C related to E2 function. To this end, we observed that E2-mediated phosphorylation of the estrogen receptor is inhibited by I3C. Our results are consistent with the hypothesis that I3C exerts its antiestrogenic effect by intervention in the E2-estrogen receptor signal transduction pathways and by alterations in E2 metabolism that resulted in the formation of metabolites with antiestrogenic activity.

Brassicaceae↗

PubMed2001

Bacteremia after spinal cord injury in initial versus subsequent hospitalizations.

BACKGROUND: Individuals with spinal cord injury (SCI) have a high lifelong risk for systemic infection. For optimal therapy, it is important to characterize the organisms involved in bacteremic episodes and the sites of primary infection. The increase in drug-resistant bacteria in recent years underscores the importance of gathering accurate microbiological information. METHODS: We performed a retrospective study of hospitalized people with SCI using a computerized Microbiology Laboratory Database. We compared the microbiology of bacteremic episodes during initial versus unplanned subsequent hospitalizations. Data were collected on 55 bacteremic episodes in 30 people during initial hospitalization for SCI and 50 episodes in 29 people who were rehospitalized. RESULTS: Among cases in which a site of origin could be identified, the respiratory tract was the origin of the majority of bacteremias during initial hospitalizations, and the urinary tract was the primary origin during rehospitalizations. Polymicrobial bacteremia occurred in 14 of 55 (25%) initial versus 14 of 50 (28%) subsequent hospitalization episodes. The most common pathogens were coagulase-negative staphylococci, followed by Staphylococcus aureus and Enterobacteriaceae. Bacteremia was more common in people with tetraplegia and complete neurologic lesions than in those with paraplegia and incomplete lesions. One person in the rehospitalization group died from complications of bacteremia. All others were successfully treated. CONCLUSIONS: This study describes the frequency and characteristics of bacteremia during initial and subsequent hospitalizations following SCI and examines differences in original sites of infection. This information should be considered when planning infection control measures and empiric antibiotic regimens for patients with SCI.

Adolescent↗

PubMed2001

Prediction of drug content and hardness of intact tablets using artificial neural network and near-infrared spectroscopy.

The purpose of this study was to predict drug content and hardness of intact tablets using artificial neural networks (ANN) and near-infrared spectroscopy (NIRS). Tablets for the drug content study were compressed from mixtures of Avicel PH-101, 0.5% magnesium stearate, and varying concentrations (0%, 1%, 2%, 5%, 10%, 20%, and 40% w/w) of theophylline. Tablets for the hardness study were compressed from mixtures of Avicel PH-101 and 0.5% magnesium stearate at varying compression forces ranging from 0.4 to 1 ton. An Intact Analyzer was used to obtain near infrared spectra from the tablets with varying drug contents, whereas a Rapid Content Analyzer (RCA) was used to obtain spectral data from the tablets with varying hardness. Two sets of tablets from each batch (i.e., tablets with varying drug content and hardness) were randomly selected. One set of tablets was used to generate appropriate calibration models, while the other set was used as the unknown (test) set. A total of 10 ANN calibration models (5 each with 10 and 160 inputs at appropriate wavelengths) and five separate 4-factor partial least squares (PLS) calibration models were generated to predict drug contents of the test tablets from the spectral data. For the prediction of tablet hardness, two ANN calibration models (one each with 10 and 160 inputs) and two 4-factor PLS calibration models were generated and used to predict the hardness of test tablets. The PLS calibration models were generated using Vision software. Prediction of drug contents of test tablets using the ANN calibration models generated with 10 inputs was significantly better than the prediction obtained with the ANN calibration models with 160 inputs. For tablets with low drug concentrations (less than or equal to 2% w/w) prediction of drug content was better with either of the two ANN calibration models than with the PLS calibration models. However, prediction of drug contents of tablets with greater than or equal to 5% w/w drug was better with the PLS calibration models than with the ANN calibration models. Prediction of tablet hardness was better with the ANN calibration models generated with either 10 or 160 inputs than with the PLS calibration models. This work demonstrated that a well-trained ANN model is a powerful alternative technique for analysis of NIRS data. Moreover, the technique could be used in instances when the conventional modeling of data does not work adequately.

Calibration↗

PubMed2001

A sensitive in situ ELISA for quantitative measurements of cytokines and antibodies secreted by culture lymphocytes.

Cytokines are usually measured using ELISA and ELISPOT. We have developed an in situ ELISA by combining the advantages of the highly sensitive ELISPOT and the quantitative conventional ELISA techniques to measure cytokines and antibodies secreted by culture lymphocytes. In this assay, lymphocytes were cultured on ELISA plates pre-coated with either a special antigen or mAbs against IL-4, IFN-gamma. The caprtured lymphokines or immunoglobulins were subsequently measured by conventional ELISA procedures. As a comparison, a conventional ELISA was carried out in parallel. The in situ ELISA measured a 5-fold increase in antigen-stimulated IL-4 and IFN-gamma, compared to the conventional ELISA. It also rquired 10,000 times fewer lymphocytes to produce a detectable level of antigen-specific antibodies than the conventional ELISA. We conclude that the in situ ELISA is much more sensitive than a conventional ELISA and less costly and easier to perform than ELISPOT, providing a useful tool to quantitatively measure cell-secreted molecules.

Animals↗

PubMed2001

A comparison of reflectance and transmittance near-infrared spectroscopic techniques in determining drug content in intact tablets.

Drug contents of intact tablets were determined using non-destructive near infrared (NIR) reflectance and transmittance spectroscopic techniques. Tablets were compressed from blends of Avicel PH-101 and 0.5% w/w magnesium stearate with varying concentrations of anhydrous theophylline (0, 1, 2, 5, 10, 20 and 40% w/w). Ten tablets from each drug content batch were randomly selected for spectral analysis. Both reflectance and transmittance NIR spectra were obtained from these intact tablets. Actual drug contents of the tablets were then ascertained using a UV-spectrophotometer at 268 nm. Multiple linear regression (MLR) models at 1116 nm and partial least squares (PLS) calibration models were generated from the second derivative spectral data of the tablets in order to predict drug contents of intact tablets. Both the reflectance and the transmittance techniques were able to predict the drug contents in intact tablets over a wide range. However, a comparison of the results of the study indicated that the lowest percent errors of prediction were provided by the PLS calibration models generated from spectral data obtained using the transmittance technique.

Bronchodilator Agents↗

PubMed2001

The MLC tongue-and-groove effect on IMRT dose distributions.

We have investigated the tongue-and-groove effect on the IMRT dose distributions for a Varian MLC. We have compared the dose distributions calculated using the intensity maps with and without the tongue-and-groove effect. Our results showed that, for one intensity-modulated treatment field, the maximum tongue-and-groove effect could be up to 10% of the maximum dose in the dose distributions. For an IMRT treatment with multiple gantry angles (> or = 5), the difference between the dose distributions with and without the tongue-and-groove effect was hardly visible, less than 1.6% for the two typical clinical cases studied. After considering the patient setup errors, the dose distributions were smoothed with reduced and insignificant differences between plans with and without the tongue-and-groove effect. Therefore, for a multiple-field IMRT plan (> or = 5), the tongue-and-groove effect on the IMRT dose distributions will be generally clinically insignificant due to the smearing effect of individual fields. The tongue-and-groove effect on an IMRT plan with small number of fields (< 5) will vary depending on the number of fields in a plan (coplanar or non-coplanar), the MLC leaf sequences and the patient setup uncertainty, and may be significant (> 5% of maximum dose) in some cases, especially when the patient setup uncertainty is small (< or = 2 mm).

Bone Neoplasms↗

PubMed2001

Production of cloned goats from enucleated oocytes injected with cumulus cell nuclei or fused with cumulus cells.

This study was designed to produce cloned goats from cumulus cells. Cloning donor nuclei were from cumulus cells either freshly isolated or cultured in vitro. Enucleated oocytes were either injected with cumulus cell nuclei without piezo-driven manipulator (injection method) or fused with cumulus cells (fusion method). The survival rate of cloned embryos, obtained by injection, was higher than that derived from fusion (62.7 and 45.9%, respectively). Two cloned goats were derived by fusion with in vitro cultured cumulus cells without starvation, but died shortly after natural birth, from respiratory difficulties. Their birth weights (2.23 kg and 2.03 kg) were within the normal range (2.0-2.7 kg) and postmortem analysis revealed no morphological abnormalities. The third cloned goat, derived by injection of nuclei from freshly isolated cumulus cells, weighed 3.3 kg at birth, and was 37% overweight compared with the average weight of the same species. This goat is healthy and well as this paper is being prepared. Nested PCR-RFLP analysis confirmed that all the cloned goats were derived from the donor cells.

Animals↗

PubMed2001

Catalytic oxidation of zinc/sulfur coordination sites in proteins by selenium compounds.

Zinc/thiolate (cysteine) coordination occurs in a very large number of proteins. These coordination sites are thermodynamically quite stable. Yet the redox chemistry of thiolate ligands confers extraordinary reactivities on these sites. The significance of such ligand-centered reactions is that they affect the binding and release of zinc, thus helping to distribute zinc, and perhaps controlling zinc-dependent cellular events. One new aspect focuses on the thiolate ligands of zinc as targets for the redox action of selenium compounds. A distinctive feature of this chemistry is the capacity of selenols to catalyze the oxidation of zinc/thiolate sites. We here use a chromophoric compound, 2-nitrophenylselenocyanate, to investigate its reaction mechanism with the zinc/thiolate clusters of metallothionein, a protein that is a cellular reservoir for zinc and together with its apoprotein, thionein, is involved in zinc distribution as a zinc donor/acceptor pair. The reaction is particularly revealing as it occurs in two steps. A selenenylsulfide intermediate is formed in the fast oxidative step, followed by the generation of 2-nitrophenylselenol that initiates the second, catalytic step. The findings demonstrate the high reactivity of selenium compounds with zinc/thiolate coordination sites and the potent catalytic roles that selenoproteins and selenium redox drugs may have in affecting gene expression via modulation of the zinc content of zinc finger proteins.

Anticarcinogenic Agents↗

PubMed2001

Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells.

The androgen receptor (AR) is involved in the development and progression of prostate cancer. In order to find new compounds that may present novel mechanisms to attenuate the function of AR, we investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific, androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase (ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level. Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level. Our result suggests that quercetin can attenuate the function of AR by repressing its expression and has the potential to become a chemopreventive and/or chemotherapeutic agent for prostate cancer.

Androgens↗

PubMed2001

Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells.

It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

Base Sequence↗

PubMed2001

The relationship between third-codon position nucleotide content, codon bias, mRNA secondary structure and gene expression in the drosophilid alcohol dehydrogenase genes Adh and Adhr.

To gain insights into the relationship between codon bias, mRNA secondary structure, third-codon position nucleotide distribution, and gene expression, we predicted secondary structures in two related drosophilid genes, Adh and Adhr, which differ in degree of codon bias and level of gene expression. Individual structural elements (helices) were inferred using the comparative method. For each gene, four types of randomization simulations were performed to maintain/remove codon bias and/or to maintain or alter third-codon position nucleotide composition (N3). In the weakly expressed, weakly biased gene Adhr, the potential for secondary structure formation was found to be much stronger than in the highly expressed, highly biased gene Adh. This is consistent with the observation of approximately equal G and C percentages in Adhr ( approximately 31% across species), whereas in Adh the N3 distribution is shifted toward C (42% across species). Perturbing the N3 distribution to approximately equal amounts of A, G, C, and T increases the potential for secondary structure formation in Adh, but decreases it in Adhr. On the other hand, simulations that reduce codon bias without changing N3 content indicate that codon bias per se has only a weak effect on the formation of secondary structures. These results suggest that, for these two drosophilid genes, secondary structure is a relatively independent, negative regulator of gene expression. Whereas the degree of codon bias is positively correlated with level of gene expression, strong individual secondary structural elements may be selected for to retard mRNA translation and to decrease gene expression.

Alcohol Dehydrogenase↗

PubMed2001

Is equity being sacrificed? Willingness and ability to pay for schistosomiasis control in China.

Decentralization of the health care system in China has led to an increasing need for income generation at all operational levels, both for curative services and for public health programmes. In general, people have accepted the costs of curative services, although the impact of charges on health-seeking behaviour has yet to be assessed. Public health programmes present particular problems in terms of revenue generation, however, because of the less direct impact of these activities on individual health and well-being. In this paper, we report the results of a cross-sectional study of willingness and ability to pay for schistosomiasis control. Questionnaires were administered to household heads of six representative villages in the Dongting Lake Region of Hunan Province, China. A total of 628 valid questionnaires were analyzed. The yearly mean household expenditure on schistosomiasis diagnosis and treatment was RMB 59.50 +/- 146.04 Yuan (US$1 = 8 RMB Yuan), accounting for 0.94% of the total yearly household income. Most household heads (514, 82%) thought schistosomiasis was the greatest health threat in their communities, but only 30.9% of them were willing to pay for screening, diagnosis and treatment of the infection. On the other hand, 72.3% of the respondents were willing to undertake volunteer work for control.

Adult↗

PubMed2001

A de novo complex chromosomal rearrangement with a translocation 7;9 and 8q insertion in a male carrier with no infertility.

A de novo complex chromosomal rearrangement (CCR) involving chromosomes 7, 8 and 9 in a male carrier was ascertained through his healthy wife's recurrent spontaneous abortions. Six pregnancies over eight years resulted in four spontaneous abortions and two livebirths who died perinatally due to abnormal vital signs. Cytogenetic analyses utilizing high resolution chromosome banding technique showed a deletion of band in a der(7) chromosome and an extra band inserting at 8q21.2. Another extra band was also observed at the band 9p24, but it could not be karyotypically determined. Fluorescent in-situ hybridization using chromosome 7 and 8 specific microdissected library as probes confirmed the insertion of a segment from the translocated chromosome 7 into a chromosome 8, and additionally revealed a translocation between chromosomes 7 and 9. The karyotype of the CCR carrier was determined as 46,XY,t(7;9)(q22;p24),ins(8;7)(q21.2;q22q32).ish der(9)(wcp7+);ins(8;7)(wcp8+,wcp7+). Comparing with previously reported male CCR carriers with our case, we conclude that male CCR carriers may not always present with infertility or subfertility phenotypes. This may suggest that rare transmission of male carriers could result from abnormal chromosomal rearrangements during meiosis and gametogenesis in addition to frequent infertility.

Abortion, Habitual↗

PubMed2001

CpG DNA induces cyclooxygenase-2 expression and prostaglandin production.

Unmethylated CpG motifs found in bacterial DNA are potent activators of the innate and acquired immune systems, and rapidly induce the production of proinflammatory cytokines. We hypothesized that CpG DNA may also elicit the production of prostaglandins (PG), which are central lipid mediators of the immune and inflammatory response. To test our hypothesis, we stimulated murine spleen cells and RAW 264.7 murine macrophage cells with CpG DNA and assessed the effects on the PG synthesis pathway. Compared to control, DNA-containing CpG motifs induced >5-fold increase in PGE (2) production and rapidly up-regulated cyclooxygenase-2 (COX-2) at both the mRNA and protein level. CpG DNA was an extremely strong inducer of COX-2 as concentrations as low as 3 ng/ml induced COX-2 protein expression. The CpG DNA-induced PGE (2) down-regulated the immune response elicited by CpG. Blockade of PGE (2) production with selective COX-2 inhibitors or neutralizing anti-PGE (2) antibody markedly enhanced IFN-gamma secretion in vitro from CpG DNA-stimulated spleen cells. Moreover, selective COX-2 inhibition increased CpG DNA-induced IFN-gamma secretion in vivo. Inhibition of COX-2 also increased CpG DNA-induced lytic activity of NK cells. Taken together, these data indicate that DNA containing CpG motifs is a potent inducer of COX-2 and PGE (2) production. CpG-induced PG may subsequently down-regulate the immune and inflammatory responses elicited by the CpG DNA.

Adjuvants, Immunologic↗

PubMed2001

SWORD '99: surveillance of work-related and occupational respiratory disease in the UK.

Systematic reports from chest and occupational physicians under the SWORD and OPRA (Occupational Physicians Reporting Activity) surveillance schemes continue to provide a picture of the incidence of occupational respiratory disease in the UK. An estimated total of 4393 incident cases (comprising 4530 diagnoses) were reported during the 1999 calendar year, an increase of 1427 cases over the previous year. Benign pleural disease was the single most frequently reported condition (28% of all diagnoses reported). Occupational asthma cases (1168; 26%) remained high, as did mesothelioma (1032; 23%). Analysis of trends over the past 8 years shows an increase in mesothelioma cases, but little change in asthma. The annual incidence per 100,000 employed people, 1996-1999, for mesothelioma, lung cancer and pneumoconiosis was high amongst construction workers (28.7), miners and quarrymen (26.5), woodworkers (18.9) and gas, coal and chemical workers (15.2). Trends in mesothelioma incidence by birth cohort continue to show an increase in construction workers and a continuing decline in shipyard and insulation workers. The relative proportion of pneumoconiosis cases attributed to coal mining has fallen steadily in workers born since approximately 1920 and most cases are now in men who have been employed in quarrying and rock drilling.

Adult↗

PubMed2001

The reported incidence of work-related musculoskeletal disease in the UK: MOSS 1997-2000.

Consultant rheumatologists participate in surveillance of work-related musculoskeletal conditions under the Musculoskeletal Occupational Surveillance Scheme (MOSS), which has been in operation since 1997. During the first 3 years of the scheme, an estimated total of 8070 cases and 8442 diagnoses were obtained, an average of slightly less than 2700 estimated cases each year. Disorders of the upper limb accounted for approximately 66% (5502) of the total, with hand/wrist/arm conditions (3693 cases) comprising the majority of these. Conditions of the lumbar spine and trunk (13% of cases), the cervical spine (12%) and the shoulder (12%) were also frequently reported. Pain with ill-defined pathology was reported in 35% of cases with hand and forearm disorders. Overall, 82% of cases were related to repetitive rather than single injury. The largest numbers of cases were seen in workers in craft occupations (1659) and in clerical and secretarial workers (1524). High rates of musculoskeletal conditions, particularly of upper limb disorders, are notable in mining. In most occupations, and overall, women were at greater risk than men.

Female↗

PubMed2001

Effect of genetic selection for group productivity and longevity on immunological and hematological parameters of chickens.

A line of White Leghorn chickens was selected for high group productivity and longevity resulting in improved survival and feather score as well as reduced cannibalism and flightiness. Improvements in survival might have also been due to improved immunity. The present study was designed to test the hypothesis that selection for high (HGPS) and low (LGPS) group productivity and survivability also altered immune and hematological parameters. The LGPS line was an intense reverse selected line of the HGPS line at the eighth generation of development. Hens were randomly assigned to individual cages at 17 wk of age. Blood samples were collected from the hens at 21 wk of age. Subsets of T lymphocytes (CD4+, CD8+, and gammadelta cells) were measured using flow cytometry. Concentrations of plasma IgG were quantified with western blot analysis and immunoprecipitation assay. Hematological parameters were collected from blood smears. The HGPS hens had significantly higher percentages of blood lymphocytes and CD4+:CD8+ ratios of circulating T cells (P < 0.01) and tended to have more, but not significantly, gammadelta T cells (P = 0.07) than the LGPS hens. In contrast, the LGPS hens exhibited eosinophilia and heterophilia and greater heterophil:lymphocyte ratios (P < 0.01). The concentrations of plasma IgG were also significantly higher in the LGPS hens (P < 0.01). These results suggest that genetic selection for group productivity and longevity also alters the immunological and hematological systems of hens. The line difference in regulation of T cells, leukocytes, and production of IgG may suggest that different genes or modes of gene action are involved.

Animals↗

PubMed2001

Effects of group selection for productivity and longevity on blood concentrations of serotonin, catecholamines, and corticosterone of laying hens.

Selection of a line of White Leghorn chickens for high group productivity and longevity resulted in reducing cannibalism and flightiness in multiple-hen cages. Improvements in survival might have been due to changes of physiological homeostasis. The objective of the present study was to test the hypothesis that genetic selection for high (HGPS) and low (LGPS) group productivity and survivability also altered regulation of neuroendocrine homeostasis. Hens were randomly assigned to individual cages at 17 wk of age. At 21 wk of age, blood concentrations of dopamine, epinephrine, norepinephrine, and serotonin were measured using HPLC assay. Blood concentrations of corticosterone were measured using radioimmunoassay. The LGPS hens had greater blood concentrations of dopamine and epinephrine than the HGPS hens (P < 0.01). The blood concentration of norepinephrine was not significantly different between the lines, but the ratio of epinephrine to norepinephrine was greater in the LGPS hens (P < 0.01). The blood concentrations of serotonin were also higher in the LGPS hens compared to those in the HGPS hens (P < 0.01). Although the HGPS hens tended to have a higher level of blood corticosterone, the difference was not significant (1.87 +/- 0.19 vs. 1.49 +/- 0.21 ng/mL; P = 0.08). The results suggest that selection for group productivity and survivability alters the chickens' neuroendocrine homeostasis, and these changes may correlate with its line-unique coping ability to domestic environments and survivability.

Animals↗