Search PubMed⌕ Search

Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 253 records · Page 14Linked to original sources
PubMed1999

Effect of carcinogen dose fractionation, diet and source of F344 rat on the induction of colonic aberrant crypts by 2-amino-3-methylimidazo[4,5-f]quinoline.

Carcinogen dose fractionation, diet and source of laboratory animal were examined as variables in the induction of colonic aberrant crypt foci (ACF) by the heterocyclic amine 2-amino-3-methylimidazo [4, 5-f]quinoline (IQ). In the first experiment, male F344 rats from the National Cancer Institute (NCI rats) were fed AIN-93G diet and, starting in the third week, IQ was given by gavage on alternating days, the total carcinogen dose of 105 mg being fractionated proportionally over 2, 4, 8 or 14 weeks. Only the high dose (2 week) treatment with IQ was effective for the induction of ACF at 16 weeks, producing on average 3.8 ACF/colon versus 0.5 ACF/colon in all other groups (P < 0.05). The 2 week IQ dosing protocol was used in a second experiment in which male F344 rats from Simonsen Laboratories (SN) or NCI were fed AIN-93G, AIN-76A or chow diet. On average, SN rats on chow diet had twice the number of aberrant crypts compared with NCI rats given the same diet and three to four times as many aberrant crypts as NCI rats fed AIN diets. Hepatic cytochrome P4501A1 (CYP1A1) levels were essentially unaffected by diet, but methoxyresorufin O-demethylase activities and CYP1A2 protein levels were increased 2- to 3-fold in animals fed chow versus AIN diets. During the 2 week period of carcinogen administration, IQ markedly induced CYP1A proteins and negated the differences among groups related to diet. No consistent diet-related changes were detected in the activities of aryl sulfotransferase or N-acetyltransferase, but UDP-glucuronosyltransferase activities were elevated 2- to 3-fold in rats given chow versus AIN diets. In summary, high dose treatment with IQ was required for the induction of ACF, rats on the chow diet had more aberrant crypts than those given AIN diets and male F344 rats purchased from different vendors and fed chow diet differed with respect to their sensitivity to induction of ACF.

Animals↗
PubMed1999

A transfected cell model for the renal toxin transporter, rOCT2.

A cDNA for the organic cation transporter (rOCT2) of the rat kidney was inserted into the retroviral plasmid pLXSN. This plasmid was used to stably transfect NIH3T3 cells. The transfected cell line exhibited an enhanced rate of tetraethylammonium (TEA) uptake and efflux compared to wild-type NIH3T3 cells. Uptake of TEA by the transfected cells was markedly reduced upon incubation at 4 degrees C. When the extracellular pH was lowered from 8.1 to 5.9, uptake was also reduced, suggesting inhibition of rOCT2 by extracellular protons. The apparent K(m) for TEA in the transfected cells was 141 microM. The classical organic cation transport inhibitors, cyanine 863 and cimetidine, produced noncompetitive inhibition with apparent Ki values of 0.81 and 198 microM, respectively. Daunomycin, vinblastine, and the deoxyadenosine analogs, 2'-deoxytubercidin and 2-chlorodeoxyadenosine, did not appear to be substrates for rOCT2. However, the anticancer drug, cisplatin, competitively inhibited TEA uptake by rOCT2 with an apparent Ki value of 925 microM, suggesting that rOCT2 may play a role in its renal secretion. In summary, transfected NIH3T3 cells provide a facile system by which this and other organic ion transporters can be studied.

3T3 Cells↗
PubMed1999

Comparison of PET [15O]water studies with 6-minute and 10-minute interscan intervals: single-subject and group analyses.

The authors recently showed that [15O]water PET data obtained with a short interscan interval (6 minutes) produced similar results whether or not the residual background from the previous scan is subtracted. The purpose of the present study was to compare scans obtained during motor activation using a short (6-minute) interscan interval protocol with those obtained with a standard (10-minute) protocol in the same scanning session. Single-subject and group analyses were performed using Worsley's method, which uses a pooled variance estimate and statistical parametric mapping with a local variance estimate. High consistency in both the activation maps, i.e., the number of activated motor brain structures and the Talairach coordinates of peak intensities of the activated regions, was obtained in the 6- and 10-minute studies in both single-subject and group analyses. However, in comparison to the 6-minute studies, a larger cluster size of activated brain regions and an approximately 20% higher peak activation in these regions were observed in the 10-minute studies with the same number of replicates. Analysis of these results suggests that using a 6-minute interval with an increased number of replications, i.e., without changing the subject's total study duration, should produce comparable statistical power to that of the 10-minute interval for group analysis and increased statistical power for single-subject analyses that use a local variance estimate because of increased degrees of freedom. Alternatively, with a small increase in the number of scans and the use of a 6-minute interscan interval, a comparable level of statistical significance may be achieved for single-subject experiments that use a local variance estimate, with an overall shortening of the study duration.

Adult↗
PubMed1999

Crystallization and preliminary X-ray diffraction studies of monomeric isocitrate dehydrogenase from Corynebacterium glutamicum.

A monomeric isocitrate dehydrogenase has been crystallized for the first time. This enzyme catalyzes the conversion of isocitrate to oxalosuccinate and subsequently to alpha-ketoglutarate and CO(2); the coenzyme NADP(+) is reduced to NADPH during the reaction. Polyethylene glycol 2000 monomethyl ether was used to crystallize the enzyme in space group C2 with unit-cell parameters a = 137.1, b = 54.6, c = 126.4 A, beta = 108.2 degrees. The very small crystal (0. 05 x 0.20 x 0.05 mm) diffracted to 3.5 A d spacing using synchrotron radiation.

Bacterial Proteins↗
PubMed1999

Health effects of solvent exposure among dockyard painters: mortality and neuropsychological symptoms.

OBJECTIVES: To study mortality and prevalence of neuropsychological symptoms among a cohort of painters known to have been heavily exposed to organic solvents. METHODS: A mortality study of 1292 male painters who had worked in a dockyard in Scotland for > or = 1 year between 1950 and 1992 comprised a nested cross sectional study of 953 surviving painters from the cohort and 953 male non-painters randomly selected from the local population and a case-control study of those with high symptom scores. Mortality, symptoms, and risks associated with painting, adjusting for age, education, smoking, alcohol, and personality were measured. RESULTS: The proportional mortality ratio for all cancers was not increased significantly (110 (95% confidence interval (95% CI) 84 to 143), except for a possible excess of deaths from ischaemic heart disease (132, 105 to 164). Standardised mortality ratios were not significantly increased. Among the 260 surviving painters and 539 community controls who responded to the questionnaire there was a significant excess of symptoms among painters; adjusted relative risk (RR) increased significantly with increasing symptom score. These RRs suggested an exposure-response relation; for a high score (12-22) for all symptoms RR was 2.27 (1.20 to 4.30) for 1-4 years of exposure, 2.42 (1.18 to 4.95) for 5-9 years, 2.89 (1.42 to 5.88) for 10-14 years, and 3.41 (1.82 to 6.36) for 15-41 years, compared with controls. In multivariate analyses, painting exposure, and aging were associated with high symptom scores and there was again an increased risk relative to time worked as a painter. CONCLUSION: This study supports the hypothesis that heavy and prolonged exposure to paint solvents leads to neuropsychological ill health.

Adult↗
PubMed1999

Neuropsychological symptoms in Chinese male and female painters: an epidemiological study in dockyard workers.

OBJECTIVES: To study the prevalences of neuropsychological symptoms in male and female dockyard painters in China and to compare them with those in British dockyard painters. METHODS: All 116 painters were identified, active and retired, who had been employed in two Chinese dockyards for at least 1 year together with a matched random sample of 263 dockyard non-painters. Neuropsychological and personality questionnaires that we had used previously in a study of United Kingdom dockyard painters were used, translated into Chinese. Neuropsychological symptoms in painters and controls were compared, adjusting for age, educational level, smoking, alcohol intake, and personality. RESULTS: The response rate was 94% for painters and 97% for controls. Highly significant excesses of symptoms were found in painters, suggestive of neuropsychological dysfunction. Both male and female painters showed higher relative risks than were found in similar tradespeople in the United Kingdom. The relative risk increased with increasing score of both neurological and psychological symptoms. Relative risk of having a high symptom score, compared with controls and adjusted for confounders, was 6.61 (95% confidence interval (95% CI) 2.36 to 18.50) for 2-15 years exposure, 14.88 (5.74 to 38.56) for 16-22 years and 9.42 (3.97 to 22.36) for > or = 22 years. CONCLUSION: These results indicate that neuropsychological symptoms are associated with heavy exposure to painting work in China, and that the phenomenon is likely to be found worldwide wherever there is such exposure to solvent based paints. The high response rate in this study answers a possible criticism of the earlier United Kingdom study.

Adolescent↗
PubMed1999

Intravenous pyruvate prolongs survival during hemorrhagic shock in swine.

Pyruvate improves cellular and organ function during hypoxia and ischemia and stabilizes the NADH redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on cardiovascular and neocortical function, indexes of the cytosolic redox state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during controlled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Na+ pyruvate was infused 1 h before (1 g. kg(-1). h(-1)) and 2 h during (0.5 g. kg(-1). h(-1)) hemorrhage to attain arterial pyruvate levels of 6 mM. Volume (0.9% NaCl) and osmotic (10% NaCl) effects were matched in controls. Time to peak hemorrhage (57 min) and peak hemorrhage volume (43 ml/kg) were similar in all groups. The volume and osmotic groups experienced spontaneous cardiovascular decompensation between 60 and 90 min, with an average time until death of 82.7 +/- 5.5 and 74.8 +/- 8.2 min. In contrast, survival in the pyruvate group was 151.2 +/- 10.0 min (P < 0.001). During hemorrhage, the pyruvate group had better cardiovascular and cerebrovascular function with significantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyruvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevented the net efflux of ADO + HX + Ino into the sagittal sinus. The findings reveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.

Animals↗
PubMed1999

A nucleoside-sensitive organic cation transporter in opossum kidney cells.

Renal secretion of organic cations and anions are pleiotropic, active processes in mammals. Some nucleosides such as deoxyadenosine (dAdo), 2-chlorodeoxyadenosine, and azidothymidine are secreted by human and rodent kidneys. Previous work (J. A. Nelson, J. F. Kuttesch, Jr., and B. H. Herbert. Biochemical Pharmacology 32: 2323-2327, 1983) indicated a role for the classic organic cation transporter (OCT) in the secretion of the dAdo analog, 2'-deoxytubercidin, by mouse kidney. Using [14C]tetraethylammonium bromide ([14C]TEA) as a substrate, we tested several renal cell lines for a nucleoside-sensitive OCT. American opossum kidney proximal tubule cells (OK) express a cimetidine-sensitive and metabolic-dependent ability to efflux TEA. Other classic OCT inhibitors and several nucleosides also inhibit TEA efflux by these cells in a manner reflecting structural specificity for the carrier. Inhibition of OCT by nucleosides is not a universal feature of OCTs, since TEA transport mediated by cloned rat kidney OCT2 in the Xenopus laevis oocyte system was not inhibited by the same nucleosides. In conclusion, OK cells appear to possess an OCT that may also transport some nucleosides by a novel carrier.

Animals↗
PubMed1999

Enrichment of transiently transfected mesangial cells by cell sorting after cotransfection with GFP.

Early passage mesangial cells, like many other nonimmortalized cultured cells, can be difficult to transfect. We devised a simple method to improve the efficiency of transient protein expression under the transcriptional control of promoters in conventional plasmid vectors in rat mesangial cells. We used a vector encoding modified green fluorescent protein (GFP) and sterile fluorescence-activated cell sorting (FACS) to select a population consisting of >90% GFP-expressing cells from passaged nonimmortalized cultures transfected at much lower efficiency. Only 10% transfection efficiency was noted with a beta-galactosidase expression vector alone, but cotransfection with GFP followed by FACS and replating of GFP+ cells yielded greater than fivefold enrichment of cells with detectable beta-galactosidase activity. To demonstrate the expression of a properly oriented and processed membrane protein, we cotransfected GFP with a natriuretic peptide clearance receptor (NPR-C) expression vector. Plasmid-dependent cell surface NPR-C density was enhanced by 89% after FACS, though expression remained lower in selected mesangial cells than in the CHO cell line transfected with the same vector. We conclude that cotransfection of rat mesangial cells with GFP, followed by FACS, results in improvement in transient transfection efficiencies to levels that should suffice for many applications.

Adenoviridae↗
PubMed1999

Appropriate regulation of renin and blood pressure in 45-kb human renin/human angiotensinogen transgenic mice.

The renin-angiotensin system is normally subject to servo control mechanisms that suppress plasma renin levels in response to increased blood pressure and increase plasma renin levels when blood pressure falls. In most species, renin is rate limiting, and angiotensinogen circulates at a concentration close to the Km, so varying the concentration of either can affect the rate of angiotensin formation. However, only the plasma renin level responds to changes in blood pressure and sodium balance to maintain blood pressure homeostasis. Therefore, the high plasma human renin levels and the hypertension of mice and rats containing both human renin and angiotensinogen transgenes indicate inappropriate regulation of renin and blood pressure. These anomalies led us to develop new lines of transgenic mice with a longer human renin gene fragment (45 kb) than earlier lines (13 to 15 kb). Unlike their predecessors, the 45-kb hREN mice secrete human renin only from the kidneys, and both the human and mouse renins respond appropriately to physiological stimuli. To determine whether blood pressure is also regulated appropriately, we crossed these new 45-kb hREN mice with mice containing the human angiotensinogen gene. All doubly transgenic mice were normotensive like their singly transgenic and nontransgenic littermates. Moreover, among doubly transgenic mice, both human and mouse plasma renin concentrations were suppressed relative to the singly transgenic 45-kb hREN mice. These findings demonstrate the importance of appropriate cell and tissue specificity of gene expression in constructing transgenic models and affirm the pivotal role played by renal renin secretion in blood pressure control.

Aging↗
PubMed1999

Assessment of abdominal muscle contractility, strength, and fatigue.

We evaluated abdominal muscle contractility and fatigue by measuring twitch gastric pressure (Pgat) after percutaneous supramaximal electrical stimulation of the abdominal wall before and after sit-ups to task failure. Mouth pressures during maximal voluntary expulsive maneuvers (PEmax) at TLC and FRC with superimposed twitches, and maximum voluntary ventilation (MVV) were also assessed. Mean fresh Pgat was 36.1 +/- 3.0 cm H2O with a coefficient of variation that ranged between 3.0 to 4.8%. Pgat decreased by 25% (p < 0.001) and 37% (p < 0.001) at 1 and 30 min after sit-ups. During maximal voluntary contraction twitch occlusion never occurred. PEmax at TLC and FRC decreased by 15% (p < 0.001) and 11% (p < 0.017) at 1 min, and 8% (p < 0.036) and 9% (p < 0.030) at 30 min after sit-ups, respectively. Despite the abdominal muscle fatigue, MVV values at 1 and 30 min after sit-ups were not significantly different from the value obtained before the sit-ups. We conclude that (1) Pgat is a useful objective indicator of abdominal muscle contractility and fatigue; (2) during maximal voluntary expulsive maneuvers the abdominal muscles are never fully activated; (3) sit-ups lead to substantial low-frequency fatigue but little high-frequency fatigue of the abdominal muscles, which has little effect on maximal breathing capacity.

Abdominal Muscles↗
PubMed1999

Community-based case-control study of depression in older people. Cases and sub-cases from the MRC-ALPHA Study.

BACKGROUND: Risk factors of depression in later life, particularly for sub-cases and for psychotic and neurotic types of depression, are unclear. AIMS: To identify such risk factors. METHOD: Over 5200 older people (> or = 65 years), randomly selected from Liverpool, were interviewed using the Geriatric Mental State (GMS) and the Minimum Data Set (MDS). The computer-assisted diagnosis AGECAT identified 483 cases and 575 sub-cases of depression and 2451 with no mental problems. Logistic regression was employed to examine factors relevant to caseness. RESULTS: In multiple logistical regression, odds ratios (ORs) were significantly high for being female (2.04, 95% CI 1.56-2.69), widowed (2.00, 1.18-3.39), having alcohol problems (4.37, 1.40-2.94), physical disablement (2.03, 1.40-2.94), physical illness (1.98, 1.25-3.15), taking medications to calm down (10.04, 6.41-15.71), and dissatisfaction with life (moderate 4.54, 3.50-5.90; more severe 29.00, 16.00-52.59). Good social networks reduced the ORs. If sub-cases were included as controls, the statistical significance was reduced. CONCLUSIONS: Age was not associated with depression in later life whereas gender, physical disablement and dissatisfaction with life were. The sub-cases shared many risk factors with cases, suggesting that prevention may need to be attempted at an early stage.

Age Factors↗
PubMed1999

Socio-economic deprivation and the prevalence and prediction of depression in older community residents. The MRC-ALPHA Study.

BACKGROUND: The Townsend index is a measure of social deprivation. It can be applied to postal districts and has been employed in studies examining the ecological associations of mental illness. AIMS: We examine the utility of the Townsend index in identifying older populations with a high prevalence and risk of developing depression. METHOD: The study was carried out in the context of a cohort study of an age- and gender-stratified sample of 5222 community residents aged 65 years and over. Subjects were interviewed at intervals of two years. The relationships between Townsend score and psychiatric diagnoses (in particular, depression) were examined. RESULTS: High Townsend scores were associated with increased prevalence and incidence of depression and prevalence of organic psychiatric illness. CONCLUSIONS: The Townsend index can be used to prioritize psychiatric and primary care resources so as to cater for older populations likely to suffer from depression and organic psychiatric conditions.

Aged↗
PubMed1999

Signaling by the TGF-beta homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila.

Retinal cell fate determination in Drosophila is controlled by an interactive network of genes, including eyeless, eyes absent, sine oculis and dachshund. We have investigated the role of the TGF-beta homolog decapentaplegic in this pathway. We demonstrate that, during eye development, while eyeless transcription does not depend on decapentaplegic activity, the expression of eyes absent, sine oculis and dachshund are greatly reduced in a decapentaplegic mutant background. We also show that decapentaplegic signaling acts synergistically with and at multiple levels of the retinal determination network to induce eyes absent, sine oculis and dachshund expression and ectopic eye formation. These results suggest a mechanism by which a general patterning signal such as Decapentaplegic cooperates reiteratively with tissue-specific factors to determine distinct cell fates during development.

Animals↗
PubMed1999

Gene transfer into the CNS using recombinant adeno-associated virus: analysis of vector DNA forms resulting in sustained expression.

Recombinant adeno-associated virus (rAAV) vectors have shown significant promise as vehicles for in vivo gene transfer, particularly for transduction of organs composed primarily of non-dividing cells (i.e., muscle, CNS, and liver). However, the mechanistic basis for this desirable property remains unclear. To investigate the fate of rAAV genomes in mouse brain, we stereotactically injected an rAAV vector carrying the E. coli lacZ gene into the caudate of BALB/c mice and demonstrate efficient transduction of mouse brain cells that possess cellular morphology consistent with post-mitotic neurons. We observed a significant increase in beta-galactosidase expression from 5 to 56 days after injection that paralleled the disappearance of single-stranded DNA input genomes. Analysis of in vivo viral DNA forms over time out to 5 months after inoculation revealed that rAAV genomes associated with high molecular weight mouse chromosomal DNA by 14 days after injection and persisted for the length of this study. The pattern of Southern hybridization was consistent with random viral integration in predominantly head-to-tail concatameric arrays. Importantly, we also documented an additional DNA species that appears to be a monomeric episomal circular form based on nuclease sensitivity assays. These data are the first to document the existence of multiple vector DNA forms present within the adult murine brain following direct rAAV inoculation and therefore, provide insight into the molecular events that ultimately result in long-term rAAV mediated transgene expression.

Animals↗
PubMed1999

[A gene analysis of familial lipoprotein lipase deficiency in China].

OBJECTIVE: To investigate the gene mutation of lipoprotein lipase(LPL) of familial LPL deficiency in China. METHODS: The DNA sequencing of LPL gene of the patients was performed with the dideoxy method based on the polymerase chain reaction amplification using the genomic DNA as a template. RESULTS: It was identified that a missense mutation in exon 6 of LPL gene (6G(979)-->A) resulted in the substitution of Glu(242) by Lys in a heterozygous state. CONCLUSION: The missense mutation of LPL may play a key role in the decrease of LPL activity. This is the first report about the gene mutation of LPL at this site in familial LPL deficiency. Moreover, it contributes to the elucidation of the pathophysiological mechanisms of atherosclerosis and some metabolic diseases.

Adult↗