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Y Chen

Publications and source records attributed to Y Chen.

At least 559 records · Page 31Linked to original sources
PubMed2001

Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia.

Chronic renal failure (CRF) is associated with resistance to the growth-promoting and anabolic actions of growth hormone (GH). In rats with CRF induced by partial renal ablation, 7 days of GH treatment had a diminished effect on weight gain and hepatic IGF-1 and IGFBP-1 mRNA levels, compared with sham-operated pair-fed controls. To assess whether GH resistance might be due to altered signal transduction, activation of the JAK-STAT pathway was studied 10 or 15 minutes after intravenous injection of 5 mg/kg GH or vehicle. Hepatic GH receptor (GHR) mRNA levels were significantly decreased in CRF, but GHR protein abundance and GH binding to microsomal and plasma membranes was unaltered. JAK2, STAT1, STAT3, and STAT5 protein abundance was also unchanged. However, GH-induced tyrosine phosphorylation of JAK2, STAT5, and STAT3 was 75% lower in the CRF animals. Phosphorylated STAT5 and STAT3 were also diminished in nuclear extracts. The expression of the suppressor of cytokine signaling-2 (SOCS-2) was increased twofold in GH-treated CRF animals, and SOCS-3 mRNA levels were elevated by 60% in CRF, independent of GH treatment. In conclusion, CRF causes a postreceptor defect in GH signal transduction characterized by impaired phosphorylation and nuclear translocation of GH-activated STAT proteins, which is possibly mediated, at least in part, by overexpression of SOCS proteins.

Animals↗
PubMed2001

Role of AMP-activated protein kinase in mechanism of metformin action.

Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.

AMP-Activated Protein Kinases↗
PubMed2001

Regulation and actions of Smad7 in the modulation of activin, inhibin, and transforming growth factor-beta signaling in anterior pituitary cells.

Activins and transforming growth factor-beta (TGF beta) are crucial autocrine, paracrine, and endocrine modulators of anterior pituitary function. Activins regulate most pituitary cells and lactotropes are targets of TGF beta. Smad2 and Smad3 are two cellular mediators of activin/TGF beta signaling, whereas Smad7 is as an inducible, negative modulator of the pathway. This study was undertaken to evaluate Smad7 regulation in the pituitary. Activin A rapidly and transiently increased Smad7 messenger RNA (mRNA) levels of rat anterior pituitary (RAP), clonal gonadotrope (alpha T 3-1 and L beta T2), and corticotrope (AtT20) cells with an EC(50) of 0.1-0.2 nM. In RAP cells, activin A or TGF beta 1 had equivalent effects that were additive. Follistatin, known to bind and inactivate activins, prevented Smad7 induction by activin. Inhibin A partially antagonized activin A, perhaps reflecting gonadotrope-selective actions. This antagonism was also evident with alpha T 3-1 and L beta T2 gonadotropes. Forskolin had no measurable effect in RAP cells, but increased Smad7 mRNA levels in alpha T3-1 cells and decreased them in L beta T2 cells. Transient transfection of Smad7 along with 3TPLux, an activin/TGF beta-responsive reporter, blocked activin-mediated promoter activation in alpha T3-1 and AtT20 cells. In alpha T3-1 cells, which express endogenous follistatin mRNA, a follistatin-luciferase reporter, rFS(rin3)-Luc, was transcriptionally activated by activin A, or when cotransfected with a constitutively active ActRIB [Alk4(T>D)], Smad2, or Smad3. Smad7 blocked rFS(rin3)-Luc activation by activin A or Alk4(T>D). Together, these results point to a role of Smad7 in modulating activin/TGF beta signaling in the pituitary.

Activins↗
PubMed2001

A-6G variant of the angiotensinogen gene and essential hypertension in Han, Tibetan, and Yi populations.

To investigate the relationship between the A-6G variant in the promoter of the angiotensinogen gene and essential hypertension in Han, Tibetan, and Yi populations. All patients with essential hypertension were selected by WHO criteria. And the polymorphism of the A-6G variant was determined by PCR/RFLP. The data were analyzed by t test and chi2 test. There was no significant difference in the genotype or allele frequencies between normotensives and hypertensives in the Han, Tibetan, and Yi populations, respectively. However, when the subjects were divided into male and female subgroups, the genotype distributions among hypertensives and normotensives of the Tibetan female group were as follows: AA, 37% vs. 48%; AG, 52% vs. 48%; GG, 11% vs. 4%, respectively and the frequency of the G allele was significantly higher in hypertensives than in normotensives in the Tibetan female group (0.37 vs. 0.28, chi2=4.25, p<0.05). In addition, we observed that there was a significant difference between the Han and Tibetan normotensive groups in the distributions of the allele and genotype frequencies of the A-6G variant. The frequency of the G allele was 0.29 and 0.17 in the Tibetan normotensive and Han groups, respectively (p<0.001). The G allele of the A-6G variant was associated with hypertension in the Tibetan females, but not in the Yi or Han females. And we confirmed that there was a significant difference in the prevalence of the allele frequencies of the A-6G variant between the Han and Tibetan normotensive groups.

Adult↗
PubMed2001

Ramosetron for the management of chemotherapy-induced gastrointestinal events in patients with hematological malignancies.

The objective of this study was to evaluate the efficacy and safety of ramosetron hydrochloride for the management of nausea and vomiting induced by chemotherapy in patients with hematological malignancies. A total of 30 patients with hematological malignancies were included in the ramosetron group. Ramosetron (0.3 mg i.v.) was administered 0.5 h before chemotherapy. The impact of ramosetron on anorexia, nausea and vomiting as well as other adverse effects were assessed. Meanwhile, another 39 patients received tropisetron (o.d. for 3 days). As compared to the tropisetron group, the response rate of the ramosetron group in controlling anorexia within 18-24 h after chemotherapy was higher (p < 0.05); within 18-24 h after chemotherapy, the complete response rate and effective rate in controlling nausea was higher (p < 0.05); within 12-18 h and 18-24 h after chemotherapy, the complete response rate and effective rate in controlling vomiting was higher (p < 0.05). The incidence of adverse effects was similar in both groups. We conclude that ramosetron belongs to a new generation of 5-HT3 receptor antagonists and that it is a safe, economic and effective antiemetic drug.

Adolescent↗
PubMed2001

Theoretical, experimental, and computational aspects of optical property determination of turbid media by using frequency-domain laser infrared photothermal radiometry.

In this work, the optical and thermal properties of tissuelike materials are measured by using frequency-domain infrared photothermal radiometry. This technique is better suited for quantitative multiparameter optical measurements than the widely used pulsed-laser photothermal radiometry (PPTR) because of the availability of two independent signal channels, amplitude and phase, and the superior signal-to-noise ratio provided by synchronous lock-in detection. A rigorous three-dimensional (3-D) thermal-wave formulation with a 3-D diffuse and coherent photon-density-wave source is applied to data from model phantoms. The combined theoretical, experimental, and computational methodology shows good promise with regard to its analytical ability to measure optical properties of turbid media uniquely, as compared with PPTR, which exhibits uniqueness problems. From data sets obtained by using calibrated test phantoms, the reduced optical scattering and absorption coefficients were found to be within 20% and 10%, respectively, of the values independently derived by using Mie theory and spectrophotometric measurements.

Journal Article↗
PubMed2001

Asthma and the risk of hospitalization in Canada : the role of socioeconomic and demographic factors.

OBJECTIVE: Asthma is an important determinant of hospitalization. The study aims to examine the modifying effects of demographic and socioeconomic factors on the relationship between asthma and the overall number of hospitalizations. METHODS: We examined the data on 17,601 Canadians who were > or = 12 years of age to explore the combined effects of asthma and other factors on hospitalization within the context of a publicly funded health-care system. Asthma was determined by an affirmative response to the question: "Do you have asthma diagnosed by a health professional?" The subjects also were asked whether they had been an overnight patient in a hospital during the past 12 months. RESULTS: Asthma as a risk factor explained 3.7% of all hospitalizations of men and 2.4% of all hospitalizations of women. Overall, hospitalization was positively associated with female gender, old age, and low household income. The odds ratio for asthma as a risk factor for overall hospitalization (ie, hospitalization for any reason and all causes, not only for asthma) was greater for younger men than for older men, for less-educated women than for well-educated women, and for men with middle or high incomes than for men with low incomes. CONCLUSIONS: These results suggest that demographic and socioeconomic factors play a role in the relationship between asthma and the overall number of hospitalizations, with certain population subgroups being at greater risk of hospitalization in relation to asthma.

Adolescent↗
PubMed2001

A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies and interacts with neurofibromatosis type 2 gene product schwannomin.

We report the identification of a full-length novel beta-spectrin II gene (betaSpIIsigma2) in human brain. The betaSpIIsigma2 gene has 32 exons encoding an actin-binding domain, followed by 17-spectrin repeats, and a short COOH-terminal regulatory region that lacks the Pleckstrin homology (PH) domain. Pair-wise sequence analysis showed an additional 36 and 28 amino acids located at the NH2 and COOH-terminal regions of betaSpIIsigma2, respectively. Northern-blot analysis showed an abundant expression of betaSpIIsigma2 transcripts in brain, lung, and kidney. Western-blot analysis confirmed the predicted approximately 225 kD molecular size of betaSpIIsigma2 protein in these same tissues. In brain, immunofluorescent staining revealed that betaSpIIsigma2 was enriched in cerebellar neurons, with specific enrichment in Purkinje cell bodies, but not in dendrites. Of considerable interest, neurofibromatosis type 2 (NF2) gene product schwannomin was found to co-immunoprecipitate with betaSpIIsigma2 in cultured Purkinje cells. These results suggest that betaSpIIsigma2 may play an important role in the assembly of the specialized plasma membrane domain of Purkinje neurons and that schwannomin may be involved in actin-cytoskeleton organization by interacting with betaSpIIsigma2.

Amino Acid Sequence↗
PubMed2001

Fluorescence fluctuation analysis for the study of interactions between oligonucleotides and polycationic polymers.

The interactions between a cationic polymer, poly(2-dimethylamino)ethyl methacrylate (pDMAEMA), and negatively charged rhodamine-labeled 25-mer phosphodiester oligonucleotides (Rh-ONs) were studied by fluorescence fluctuation spectroscopy and other techniques. The composition of the pDMAEMA/Rh-ON complexes was investigated as a function of the charge ratio (+/-) by increasing the pDMAEMA concentration and keeping the Rh-ON concentration constant. We applied two different methods for analyzing the fluorescence fluctuation profiles of the pDMAEMA/Rh-ON complexes, which depended on their composition. First, we analyzed the data with the photon counting histogram (PCH) technique, which determines the molecular brightness and the concentration of fluorophores (Chen et al, 1999). A particular challenge for the data analysis is the occurrence of sudden fluorescence bursts in the fluorescence fluctuation profiles, which are linked to the appearance of multimolecular complexes (i. e. when several Rh-ONs were present in one complex). A quantitative interpretation of the analysis for the complexes remains challenging and is connected to the rarity of the fluorescent bursts, which do not provide sufficient data statistics. To specifically address the problem of the fluorescent bursts we employed a method described by Van Craenenbroeck et al. (1999). This method, applicable only when data were integrated over much longer time bins, allowed us to estimate the number of fluorescence bursts which could be considered as a relative measure of the amount of multimolecular complexes present. When monomolecular complexes were formed, i. e. at high values of the charge ratio, highly intense fluorescence peaks were not present and the interpretation of the PCH analysis was more straightforward. The molecular brightness of the species (epsilon), as revealed from PCH analysis, was greater than epsilon for the free Rh-ONs, indicating that the Rh-ONs were attached to pDMAEMA chains.

Cations↗
PubMed2001

Percutaneous transsplenic embolization of esophageal and gastrio-fundal varices in 18 patients.

AIM: Clinical application and potential complication of percutaneous transsplenic varices embolization (PTSVE) of esophageal or gastrio-fundal varices in patients with hepatocellular carcinoma (HCC) complicated with portal vein cancerous thrombosis (PVCT). METHODS: 18 patients with HCC complicated with PVCT and esophageal or gastrio-fundal varices who underwent PTSVE were collected. The rate of success, complication, mortality of the procedure and postoperative complication were recorded and analyzed. RESULTS: PTSVE were successfully performed in 16 of 18 cases, and the rate of success was 89%. After therapy erythrocyte counts decreased in all of the natunts. 5 of patients needed blood transfusion, 2 patients required surgical intervention because of and 11 patients with ascites were alleviated by diuresis. Among these 18 patients, the procedure-related mortality was 11% (2/18), one died of acute hepatic failure on the forth day after procedure, another died of acute renal failure on the fifth day. The patients were follow up for 1-12 mon exceptone. 13 of them died of their tumors but none of them experienced variceal bleeding. CONCLUSION: PTSVE is a relatively safe and effective method to treat esophageal or gastrio-fundal varices in HCC patients with PVCT when percutaneous transhepatic varices embolization (PTHVE) of varices is impossible.

Adult↗
PubMed2001

Enhanced TRAIL sensitivity by p53 overexpression in human cancer but not normal cell lines.

The cytotoxic ligand TRAIL is a promising anti-cancer agent that is entering into clinical trials. We previously identified a major subgroup of TRAIL resistant cancer cell lines with absent, or reduced DR4 expression containing a K441R polymorphism or harboring elevated levels of the caspase activation inhibitor FLIP. In the present study, we explored the use of a gene therapeutic approach utilizing p53, delivered by an adenovirus-p53 (Ad-p53) vector, which directly controls expression of the TRAIL receptor KILLER/DR5 in a panel of 8 cell lines including normal and TRAIL sensitive or resistant cancers. The functional status of the delivered p53 was monitored by detection of induced p21WAF1 expression by immunocytochemistry. In normal cells, which are TRAIL resistant, TRAIL did not reduce cell viability over and above the effect of Ad-p53 alone. All cancer cell lines were sensitive to Ad-p53 and up-regulated expression of the TRAIL receptor KILLER/DR5. TRAIL-resistant cancer cells became more sensitive to TRAIL at low Ad-p53 multiplicities of infection but TRAIL resistance was not completely overcome in one TRAIL-resistant cell line probably because of a high level of expression of FLIP. The results reveal that Ad-p53 induces the TRAIL receptor KILLER/DR5 and, like radiation or chemotherapy may effectively reverse TRAIL resistance.

Adenoviridae↗
PubMed2001

Down-regulation of the desmosomal cadherin desmocollin 3 in human breast cancer.

In previous studies using cDNA microarray analysis, we have identified an expressed sequence tag which is consistently down-regulated in six human breast tumor cell lines. In the current study, we have determined this tag to be part of the mRNA sequence of human desmocollin 3, a member of the cadherin superfamily of proteins and an integral component of desmosomes. Desmosomes are sites of adhesion between adjacent cells in layers of epithelia, as well as in some non-epithelial tissues, and play an important role in the maintenance of tissue structure. Northern analysis, quantitative real-time polymerase chain reaction assay and Western blot analysis showed that desmocollin 3 is present in normal and immortalized human mammary epithelial cells, but consistently exhibits a significant, and often complete, down-regulation in breast cancer cell lines and primary breast tumors, both at the mRNA and protein levels.

Blotting, Northern↗
PubMed2001

Quantification and variability analysis of bacterial cross-contamination rates in common food service tasks.

This study investigated bacterial transfer rates between hands and other common surfaces involved in food preparation in the kitchen. Nalidixic acid-resistant Enterobacter aerogenes B199A was used as a surrogate microorganism to follow the cross-contamination events. Samples from at least 30 different participants were collected to determine the statistical distribution of each cross-contamination rate and to quantify the natural variability associated with that rate. The transfer rates among hands, foods, and kitchen surfaces were highly variable, being as low as 0.0005% and as high as 100%. A normal distribution was used to describe the variability in the logarithm of the transfer rates. The mean +/- SD of the normal distributions were, in log percent transfer rate, chicken to hand (0.94 +/- 0.68), cutting board to lettuce (0.90 +/- 0.59), spigot to hand (0.36 +/- 0.90), hand to lettuce (-0.12 +/- 1.07), prewashed hand to postwashed hand (i.e., hand washing efficiency) (-0.20 +/- 1.42), and hand to spigot (-0.80 +/- 1.09). Quantifying the cross-contamination risk associated with various steps in the food preparation process can provide a scientific basis for risk management efforts in both home and food service kitchens.

Animals↗
PubMed2001

Glove barriers to bacterial cross-contamination between hands to food.

Human hands are an important source of microbial contamination of foods. However, published data on the effectiveness of handwashing and glove use in a foodservice setting are limited. Bacterial transfer through foodservice quality gloves was quantified using nalidixic acid-resistant Enterobacter aerogenes (a nonpathogenic surrogate with attachment characteristics similar to Salmonella). Five transfer rates were determined: chicken to bare hand, chicken to hand through gloves, bare hand to lettuce, hand to lettuce through gloves (with low inoculum on hands), and hand to lettuce through gloves (with high inoculum on hands). At least 30 observations were made for each percent transfer rate using 30 individual volunteers. The logarithm of percent transfer data were then fit to distributions: chicken to bare hand, normal (0.71, 0.42); chicken to hand through gloves, gamma (5.91, 0.40, -5.00); bare hand to lettuce, logistic (1.16, 0.30); hand to lettuce through gloves (low inoculum), normal (0.35, 0.88); hand to lettuce through gloves (high inoculum), normal (-2.52, 0.61). A 0.01% transfer was observed from food to hands and from hands to food when subjects wore gloves and a 10% transfer was observed without a glove barrier. These results indicate that gloves are permeable to bacteria although transfer from hands to food through a glove barrier was less than without a glove barrier. Our results indicate that gloves may reduce both bacterial transfer from food to the hands of foodservice workers and in subsequent transfer from hands back to food.

Colony Count, Microbial↗
PubMed2001

Iron signalling regulated directly and through oxygen: implications for sepsis and the acute respiratory distress syndrome.

Reactive oxygen species produced at toxic levels are damaging species. When produced at sub-toxic levels, however, they are involved as second messengers in numerous signal transduction pathways. In addition to these findings, we can add the concept that iron (often viewed as the "villain" in free radical biology) can also be considered as a signalling species. Iron is intimately involved in the regulation of its own storage, compartmentalization and turnover. During adult respiratory distress syndrome (ARDS) and sepsis, such regulation may be aberrant or altered in some predisposed way. Such changes may have profound implications for tissue damage, and for the modulation of the inflammatory response in these patients. The search for a genetic predisposition in patients that leads to the development of ARDS associated with abnormalities in iron turnover and signalling would seem to be an important and logical progression for studies into the disease. These may lead eventually to the design of effective treatment regimens that involve the control of iron.

Adult↗
PubMed2001

[Study on the mode of inheritance for familial polycystic ovary syndrome].

OBJECTIVE: To investigate the mode of inheritance of polycystic ovary syndrome(PCOS). METHODS: The first female relatives with irregular cycle and the first male relatives with premature balding in each nuclear family were designated the affected. Their prevalence rates in families were respectively calculated. Analyses of segregation ratio were carried out among 139 nuclear families with PCOS by the methods of simple segregation and complex segregation of genetic epidemiology, respectively. RESULTS: The prevalence rates of irregular cycle among mothers and sisters with PCOS were 37.4% and 33.1% respectively, and the prevalence rates of premature balding among fathers and brothers of patients were 19.4% and 6.5%, respectively. The simple segregation analysis indicated that the segregation ratio of PCOS trait in siblings was 0.3023, the complex segregation analysis indicated that it fitted in with the inheritance model of co-dominant disorder with full penetrance and sporadic cases. The frequency of homozygote of disease gene in population was 0.046. CONCLUSION: PCOS presents the mode of co-dominant inheritance with complete penetrance.

Female↗
PubMed2001

[Effect on manganese exposure on blood prolactin and plasma renin activity].

In order to study the adverse effects of manganese on neuro-endocrine and cardiovascular system, radioimmunoassay (RIA) was used to test the blood prolactin concentration and plasma renin activity among manganese-exposed workers. The result showed that the blood prolactin concentration and Plasma renin activity in manganese exposed workers were significantly higher than those of control group. It suggested that manganese exposure might affect the function at tubero-infundibular area and renin-angiotensin aldosterone system.

Adult↗