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Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 379 records · Page 21Linked to original sources

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.

Animals↗

Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects.

STUDY OBJECTIVE: To evaluate the effect of steady-state bupropion SR sustained-release (BUP) on the pharmacokinetics of a single 100-mg dose of lamotrigine (LTG). DESIGN: Randomized, open-label, two-way crossover study SETTING: Clinical Studies Ltd., Fort Lauderdale, Florida. PATIENTS: Twelve healthy subjects. INTERVENTION: Treatment A: LTG 100 mg with steady-state BUP 150 mg twice/day; treatment B: LTG 100 mg. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of LTG were determined by noncompartmental methods using plasma and urine concentrations. Geometric least squares mean ratios and 90% confidence intervals were calculated for treatment comparison. Safety assessments included clinical laboratory tests, vital signs, and adverse events monitoring. Pharmacokinetic parameters of LTG were not significantly different between treatments. Five subjects experienced seven mild, potentially drug-related adverse events (insomnia [2]; nausea, headache, facial pain, fatigue, and depression [1 each]) that resolved spontaneously. CONCLUSION: Steady-state BUP caused no clinically relevant changes in the pharmacokinetics of a single dose of LTG.

Adult↗

A novel immunoadsorbent for rheumatoid arthritis therapy--preparation and efficacy evaluation.

AIM: To develop a novel immunoadsorbent for rheumatoid arthritis (RA) therapy. METHODS: A RA immunoadsorbent was developed by binding heat-aggregated human IgG(HAHIgG) to porous agar gel beads. Its adsorption capacity for rheumatoid factors (RFs), storage stability and blood compatibility were evaluated. RESULTS: The coupling yield of HAHIgG on the carrier was 6.0 mg/g wet gel. Saturation adsorption capacity of the adsorbent for IgMRF, IgGRF and IgARF were 3400, 2240 and 2400 IU/g, respectively. The adsorbent can be stored at 4 degrees C for three months without significant variance in its activity. Its fine permeability and hemocompatibility were demonstrated by extracorporeal hemoperfusion on rabbits. CONCLUSION: HAHIgG/agar gel is a safe and effective immunoadsorbent for RA therapy, its potential clinical use is promising in the future.

Agar↗

Efficacy of community-based second trimester genetic ultrasonography in detecting the chromosomally abnormal fetus.

We sought to assess prospectively the efficacy of community-based genetic ultrasonography in detecting chromosomally abnormal fetuses in a high-risk population and determine independent markers of aneuploidy. Patients 18 years old and older who were between 14 and 24 weeks' gestation were included if referred for maternal age greater than 35 years, increased risk of Down syndrome or trisomy 18 by second trimester serum screen, or prior affected offspring. All women had a targeted ultrasonographic examination between April 1997 and June 1999 and were offered fetal chromosomal analysis. Markers of aneuploidy and pregnancy outcomes were recorded prospectively. The primary outcome was prenatally or postnatally detected chromosomal abnormalities. Of the 1030 fetuses seen during the study, 789 had outcome data available and constituted the study group. In this group, 694 (87.9%) ultrasonograms were normal, 73 (9.2%) had one marker present, 17 (2.2%) had two markers present, and 5 (0.6%) had three or more markers present. Fourteen of 17 (82.3%) aneuploid fetuses had an abnormal ultrasonogram (one or more markers present), including 5 of 7 (71.4%) with Down syndrome. Logistic regression showed abnormal four-chamber view, structural anomaly, and intracardiac echogenic focus to be significant aneuploidy markers. The amniocentesis rate was 334 of 1030 (32.4%), and it increased with the number of sonographic markers noted (0 = 29.9%, 1 = 60.2%, 2 = 70.6%, 3 or more = 80%). Genetic ultrasonography is highly effective in identifying chromosomally abnormal fetuses in a community-based practice.

Adolescent↗

Resin activation capture technology: libraries from stabilized acyl-pyridinium on solid support.

REsin Activation/Capture APproach or REACAP Technology, a novel approach to the synthesis of compound libraries, capitalizes on the formation and retention of a resin-bound reactive intermediate, which can be subsequently transformed into a stable, covalently attached molecule. Any unreacted "reactive intermediate" is quenched and removed from the resin upon work-up, leaving only the desired product on the solid support. In contrast to more traditional solid-supported chemistry that must address issues such as resin-loading, capping of unreactive functionalized moieties, and reaction yields, REACAP offers an attractive alternative with the focus more on the purity of the released products and less on yield. In an endeavor to generate truly non-peptide leads, we describe herein the synthesis of N-acyl-2-substituted-dihydro-4-pyridones, dihydro-4-pyridones, 4-ketopiperidines, tetrahydropyridines, and 2-acyl-3,7,8-substituted-5-oxo-2-azabicyclo[2.2.2]octane and triaza analogs using REACAP Technology.

Databases as Topic↗

Identification and chromosomal location of a new tandemly repeated DNA in maize.

Two clones of a new family of tandemly repeated DNA sequences have been isolated from a maize random genomic DNA library. MR68 is 410 bp, representing a monomeric unit and MR77 is 1222 bp, containing three units. The copy number was estimated to be about 3000 per 1C maize genome. Its methylation pattern was also determined. Fluorescent in situ hybridization (FISH) indicates that the sequence is located on the subtelomeric region of the long arm of chromosomes 3 and 6, as well as on the satellite of chromosome 6.

Base Sequence↗

Lack of association between the C677T MTHFR polymorphism and colorectal hyperplastic polyps.

Colorectal hyperplastic polyps are benign lesions that share many risk factors with colorectal adenomas and cancers. Low folate intakes are associated with an increased risk of colon cancer. The enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) may be linked to DNA methylation and nucleotide synthesis and thus play a role in the etiology of colorectal neoplasia. We investigated an association between the common MTHFR polymorphism (C677T) and colorectal hyperplastic polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases (n = 200) were diagnosed with colonoscopically confirmed hyperplastic polyps; controls (n = 645) were derived from the same gastroenterology practice and were polyp-free at colonoscopy. Dietary intakes were estimated from a self-administered food-frequency questionnaire prior to colonoscopy. Multivariate adjusted odds ratios (ORs) and 95% confidence intervals for MTHFR status were 0.8 (0.6-1.2; CT versus CC wild-type) and 0.9 (0.5-1.6; TT versus CC). In subgroup analyses stratified on dietary intakes of folate, vitamin B12, vitamin B6, or methionine, those with the TT genotype and either low intakes of folate or vitamin B6 were at increased risk relative to those with normal or high vitamin intake. However, most 95% confidence intervals included 1.0, and no consistent trends were observed. In contrast to our findings on colorectal adenomas, increasing alcohol consumption was associated with an elevated risk of colorectal hyperplastic polyps, regardless of genotype. The MTHFR (C677T) variant genotype does not appear to be related to risk of colorectal hyperplastic polyps, and there is no convincing evidence that MTHFR shows a different relation to risk, dependent on dietary intakes of nutrients related to its pathway.

Adenoma↗

Glutathione S-transferase theta 1 gene deletion and risk of acute myeloid leukemia.

Individuals with a homozygous deletion of the glutathione S-transferase theta 1 (GSTT1) gene lack GSTT1 enzymatic detoxification of environmental carcinogens by conjugation with glutathione. The GSTT1 gene deletion has been associated with carcinogen-induced chromosomal changes in lymphocytes, and some but not all epidemiological evidence has suggested that the GSTT1 gene deletion may increase susceptibility to myelodysplasia. We conducted a case-control study to test whether individuals with an inherited homozygous deletion of the GSTT1 gene are at increased risk of acute myeloid leukemia (AML). The GSTT1 and GST mu 1 (GSTM1) genotypes were determined by PCR using lymphocyte or bone marrow DNA from 297 AML patients and 152 controls. AML patients were selected from Southwest Oncology Group clinical studies, and controls were identified by random digit dialing in Washington state. No association was observed between the GSTT1 gene deletion and AML [race-adjusted odds ratio (OR), 0.94; 95% confidence interval (CI), 0.55-1.60] or between the GSTM1 gene deletion and AML (race-adjusted OR, 1.26; 95% CI, 0.85-1.88). Patients with secondary AML had a slightly higher prevalence of the GSTT1 and GSTM1 gene deletions compared with de novo AML patients or controls, but this was consistent with chance. Exploratory analyses of AML cytogenetics suggested a few associations, i.e., between the GSTT1 gene deletion and trisomy 8, and between the GSTM1 gene deletion and non-8 trisomies or inv(16). These results do not support the hypothesis that the GSTT1 gene deletion is related to the incidence of AML.

Acute Disease↗

Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets.

Induction or inhibition of biotransformation enzymes, enzymes that activate or detoxify numerous xenobiotics, is one mechanism by which vegetables may alter cancer risk. Using a randomized crossover design, we examined the effect of various vegetable diets on cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT2) and xanthine oxidase activity in humans. Men and women, non-smokers, on no medication and 20-40 years of age ate four 6-day controlled diets: basal (vegetable-free) and basal with three botanically defined vegetable groups. Enzyme activities were determined by measuring urinary caffeine metabolite ratios after a 200 mg caffeine dose on the last day of each feeding period. Mean CYP1A2 activity for 19 men and 17 women (least squares means adjusted for sex, GSTM1 genotype, urine volume and feeding period) with basal, brassica, allium and apiaceous vegetable diets differed significantly (P </=ISOdia</= 0. 0005) by diet, irrespective of the caffeine metabolite molar ratio used to describe CYP1A2 activity; brassica vegetables increased (P <0.04) and apiaceous vegetables decreased (P </=ISOdia</= 0.02) activity compared with the basal and allium diets. There was no effect of diet on NAT2 and xanthine oxidase activities and none of the subjects differed by GSTM1 genotype. These results demonstrate that while one vegetable subgroup induces human CYP1A2 activity, another subgroup inhibits it. This points to a complex association between consumption of a typical diet of various vegetables and biotransformation enzyme activities in humans, an association that may be difficult to interpret in observational studies.

Adult↗

A model and its implications for denitrification in soil environment.

We analyzed the mechanisms of a soil nitrogen (N) sub-model, which is a subroutine of the Crop-Environment Resources Synthesis (CERES)-maize; a model which was originally designed to simulate crop yield and has been calibrated and validated in Taiwan. Some experiments designed specifically for testing the N sub-model proved the capability of the model in reflecting field observations. With the mechanisms, we could write computer programs for calculating the relative sensitivities of major parameters in the model, and for simulating different treatments of organic matter. The purposes were to find how they affected N transformations, especially the processes of denitrification, which are considered to be responsible for N losses in upland soils and are an important environmental issue related to human disturbance of the N cycle. The results implied that soil water content and temperature were, respectively, the first and second dominant factors. They were much more sensitive than any other parameters, such as the decomposition rate coefficients, soil pH and bulk density. Decomposition of organic matter could slow down if organic matter with different carbon/nitrogen (C/N) ratios were treated in fractions. This treatment could also decrease the process of denitrification unless the organic matter was extremely large in quantity and has a high C/N ratio.

Calibration↗

Modulation of human glutathione S-transferases by botanically defined vegetable diets.

Glutathione S-transferases (GSTs) conjugate activated xenobiotics with glutathione; thus, GST induction may improve detoxification and excretion of potentially harmful compounds. Using a randomized cross-over design, we tested the hypothesis that, in humans, serum GST-alpha concentration (GST-alpha) and GST activity increase with vegetable consumption and that this effect is GSTM1 genotype dependent. Twenty-one men (10 GSTM1-null and 11 GSTM1+) and 22 women (15 GSTM1-null and 7 GSTM1+), nonsmokers, 20-40 years of age and not on medications, ate four 6-day controlled diets: basal (vegetable-free), and basal supplemented with three botanically defined groups of vegetables (i.e., brassica, allium, and apiaceous). Fasting blood samples, collected on the last 2 days of each feeding period, were analyzed for GST-alpha, serum GST activity [against 1-chloro-2,4-dinitrobenzene (CDNB) and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)] and peripheral-lymphocyte GST-mu activity (against trans-stilbene oxide). The brassica, but not allium or apiaceous, vegetable diets (relative to the basal diet) increased GST-alpha by 26% (P = 0.005) and GST (NBD-Cl) activity by 7% (P = 0.02) in the GSTM1-null individuals, particularly the women. Apiaceous vegetable supplementation decreased GST-alpha in the GSTM1+ men (P = 0.03). Among the GSTM1+ women, both brassica and the allium diets increased GST-mu activity by 18% (P = 0.02) and 26% (P = 0.001), respectively. The vegetable diets had no effect on GST (CDNB) activity, irrespective of GSTM1 genotype or sex. These results demonstrate that GSTM1 genotype has a significant effect on GST responses to diet and that brassica vegetables are most effective at inducing GST-alpha, whereas both brassica and allium vegetables induce GST-mu. GST responses were more pronounced in women than men, but it is not clear from this study whether this is a dose-per-body-weight or a sex-specific effect.

Adult↗

Prolonged neuromuscular block with mivacurium in a patient with cholinesterase deficiency.

Mivacurium is a short-acting, nondepolarizing neuromuscular blocking agent hydrolyzed by plasma cholinesterase. Because it allows fast recovery, it is a commonly used muscle relaxant for patients undergoing short surgical procedures. We report the case of a 5-year-old boy who underwent outpatient inguinal herniorraphy and developed unexpected prolonged neuromuscular block after the use of mivacurium. He required mechanical ventilation support in the intensive care unit because he could not attain adequate muscle power 1 hour after termination of anesthesia; the muscular paralysis persisted for 5 hours after the bolus dose of 0.3 mg/kg mivacurium. Subsequent investigation revealed an extremely low plasma cholinesterase concentration (115 U/L), and this was later determined to be a congenital condition. This is the first reported case of cholinesterase deficiency diagnosed as a result of general anesthesia in Taiwan.

Child, Preschool↗

Measurement of mRNAs for TGFss and extracellular matrix proteins in corneas of rats after PRK.

PURPOSE: To assess the role of the transforming growth factor (TGF)ss system in formation of corneal haze after excimer laser photorefractive keratectomy (PRK), levels of mRNAs for three TGFss isoforms (TGFss1, TGFss2, and TGFss3), the TGFss type II receptor (TssRII), and extracellular matrix (ECM) genes including fibronectin (FN), collagen I, collagen III, and collagen IV were measured in rat corneas. METHODS: Corneas were graded for corneal haze at 0, 1.5, 7, 21, 42, and 91 days after PRK. Total RNA was isolated from pooled corneas, and the levels of mRNAs were measured using competition-based quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Severe corneal haze developed by day 42 and persisted to day 91. Levels of TGFss1 mRNA were high in rat corneas before PRK and remained relatively constant. In contrast, levels of TGFss2 and TGFss3 mRNAs were very low in normal corneas, increased 300-fold and 25-fold, respectively, on day 21, and remained elevated on day 91. Levels of mRNA for TssRII increased, with a peak elevation of 50-fold on day 42 after PRK. Levels of mRNAs for ECM proteins also increased. Fibronectin mRNA was nondetectable in normal corneas but rapidly increased to 675 copies/cell on day 7 and remained elevated to day 91. Collagen III mRNA levels peaked on day 21 with a 700-fold increase compared with a very low level of expression in normal cornea, and then decreased on day 91. Expression of collagen I mRNA lagged expression of collagen III mRNA and peaked at day 42 after PRK with a 1200-fold increase over normal cornea. In contrast, mRNA for collagen alpha(1)IV, a major component in basement membranes, remained relatively stable through day 21 and then increased slightly on days 42 and 91. CONCLUSIONS: The synchronized increase in mRNA synthesis for both the TGFss system and key ECM genes supports the hypothesis that TGFss is a key growth factor promoting stromal haze formation in corneas after PRK and suggests that limiting TGFss system may reduce corneal scarring after excimer laser ablation.

Animals↗

[A preliminary study on the activation of superoxide dismutase by Tiopronin in patients with chronic hepatitis B].

OBJECTIVE: To observe the clearance effect of Tiopronin on oxygen free radicals in chronic hepatitis B patients. METHODS: The ranthine oxidase assay was used to detect superoxide dismutase (SOD) in 80 chronic hepatitis B patients, the ALT, TBil, TP and AIG ratio of the patients were also tested. The 80 chronic hepatitis B patients were divided into two groups, the control group was treated with routine liver protective and jaundice regressing drugs while the treated group was additionally administered with Tiopromin besides the routine treatment. RESULTS: In two groups of patients with similar ages and sexes, there showed no differences in levels of SOD, ALT, TBil, TP and ALB before treatment, as the SOD in treated group and control group were 106.57 (40.68 NU/ml and 105.18(44.59 NU/ml respectively, while the normal value for SOD in 16 normal persons was 165.9(23.36 NU/ml. After treatment, there were significant differences (P< 0.01) in SOD, ALT, TBil and ALB levels which showed SOD 187.93(35.24 NU/ml, ALT 38.41(22.22 U/L, TBil 23.15(12.46 micromol/L, ALB 43.28 (4.21 g/L in the treated group and SOD 157.96(47.29 NU/ml, ALT 68.52(34.19 U/L, TBil 30.38(21.80 micromol/L and ALB 40.36(5.19 g/L in the control group. CONCLUSIONS: There showed a good therapeutic effect of Tiopronin on the clearance of oxygen free radicals in chronic hepatitis B patients and also it can improve the liver function.

Adult↗

[Mechanism of Se-Indocalamus tessdatus polycassine(S-ITPS) against human immunodeficiency virus type 1 (HIV-1)].

OBJECTIVE: To study the mechanism of Se- Indochalamus tessdatus polycassine (S-ITPS) against HIV-1 and to provide a theoretical support for developing the anti-HIV drugs. METHODS: S-ITPS was added to MT4 cells before viral inoculation, at the same time of viral inoculation, then the cells were cultured with or without S-ITPS for 1-4 weeks, finally, cytopathic effect (CPE), MTT staining method for viable cells(MTT assay),p24 antigen titer (ELISA), or infectivity (TCID50 assay) of the cultural supernatants were used as markers to monitor the virus growth. RESULTS: S-ITPS can inhibit HIV-induced CPE (1C50 = l0microg/ml)and viral replication (1C50 = 156 microg/ml)in dose dependent manner. The virus infectivity in the presence of S-ITPS was greatly decreased than that of the control. The virus inhibition was enhanced under the presence of noncytotoxic drug concentration of <1250 microg/ml in cell culture, inhibition of viral replication by S-ITPS was 73.7%, 63.5%, 87.7% and 95.4% at week 1, week 2, week 3 and week 4 of cultured cells respectively. It can also inhibit absorption of HIV-1 to MT-4 cells, but no inhibition of HIV-1 was seen when MT-4 cells were pretreated with S-ITPS. Virus can be inactivated by the agent also. CONCLUSIONS: S-ITPS is a potent anti-HIV- 1 agent in MT-4 /HIV- 1 cultural system, at least two mechanisms were included inhibition both of HIV-1 absorption to MT-4 cells and viral replication in HIV-infected cells. S-ITPS inhibition of CPE is stronger than that of p24 antigen production.

Anti-HIV Agents↗

Asymmetry of brain functional activation: fMRI study under language and music stimulation.

OBJECTIVE: To determine the asymmetry of the human brain functional activation. METHODS: With the help of GE Signa Horizon MRI system, 14 cases of right-handed volunteers were examined and the blood oxygenation level dependent method was used. The T1-weighted images were obtained with spin echo pulse sequence and the functional imaging (T2*-weighted) was performed using a single shot echo planar imaging pulse sequence. Data analysis was done with Sun Sparc Workstation and by the method of student t test or correlation analysis. RESULTS: Most of activation areas were in the left hemisphere under language stimulation, while they were in the right side under music stimulation. Besides, a few brain areas in the contralateral cerebral cortex were also activated under both stimulations. CONCLUSION: The present study supported the hypothesis of the asymmetry of brain functional activation and many brain areas of the cerebral cortex as well as both hemispheres worked in coordination. In addition, it also proved that fMRI is a feasible method in the study of human brain in vivo.

Acoustic Stimulation↗

Reactive oxygen species contribute to the induction of superoxide dismutase during heat shock in cultured rat neonatal cardiomyocytes.

OBJECTIVE: To explore the influence of reactive oxygen species (ROS) during heat shock on the activity of superoxide dismutase (SOD) and the endurance of cardiomyocytes against hypoxia-reoxygenation damage. METHODS: Cultured rat neonatal cardiomyocytes were divided into 5 groups (n = 6/group): normal control, anoxic control, heat shock, heat shock + SOD (150 U/ml) and exogenous ROS pretreated. Myocytes were first incubated in a CO2 incubator (37 degrees C) with Hank's solution for 30 min, followed by specific pretreatment. Heat shock was performed by incubating the cells in a 43 degrees C incubator for 30 min; exogenous ROS were generated by the reaction of xanthine oxidase with xanthine. After the dishes were returned to normal incubation conditions for 24 h, myocytes underwent hypoxia (3 h) and reoxygenation (1 h). RESULTS: Compared with control groups, ROS production increased after the cells experienced heat shock (1.28 +/- 0.34 nmol/mg.1 protein vs 0.80 +/- 0.23 nmol/mg.protein and 0.74 +/- 0.20 nmol/mg.protein, P < 0.05) or ROS pretreatment (3.30 +/- 0.58 nmol/mg.protein, P < 0.05). 24 hours later, accompanied by attenuated cellular injury, significantly increased SOD activity was found in heat shock (2.55 +/- 0.43 U/mg.protein vs 0.77 +/- 0.12 U/mg.protein and 0.63 +/- 0.09 U/mg.protein, P < 0.05) and exogenous ROS pretreated (2.34 +/- 0.31 U/mg.protein, P < 0.05) groups following reoxygenation. Moreover, opposite results were found when myocytes were treated with SOD during heat shock. CONCLUSIONS: The release of ROS during heat shock triggers delayed myocardial protection by altering the activity of SOD. ROS may play an important pathophysiological role in heat shock induced myocardial protection.

Animals↗