Search PubMed⌕ Search

Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 55 records · Page 3Linked to original sources

Cell transplantation for treatment of acute myocardial infarction: unique capacity for repair by skeletal muscle satellite cells.

An adult heart injured by an ischemic episode has a limited capacity to regenerate. We administered three types of adult guinea pig cells [cardiomyocytes (CMs), cardiac fibroblasts (CFs), and skeletal myoblasts (Mbs)] to compare their suitability for repair of acute myocardial infarction. We used confocal fluorescent microscopy and a variety of specific immunomarkers and echocardiography to provide anatomic evidence for the viability of such cells and their possible functional beneficial effects. All cells were transfected with adenovirus-containing beta-galactosidase gene so that migration from the injection sites could be traced. Both freshly isolated CMs as well as CFs were found concentrated in the infarcted zone; these cells survived for at least 2 wk posttransplantation. Transplanted CMs were regularly striated and grew long projections that could form gap junctions with native CMs, which was evidenced by connexin43 labeling. In addition, CM transplantation resulted in increased angiogenesis in the infarcted areas. In contrast, transplanted CFs did not appear to make any gap junctional contacts with native CMs nor did they enhance local angiogenesis. Mbs cultured for 7 days and transfected Mbs were identified 7 days posttransplantation in the infarcted area. During that time and thereafter, Mbs proliferated and differentiated into myotubes that formed new, regularly striated myofibers that occupied most (50-70%) of the infarcted area by 2-3 wk. These newly formed myofibers maintained their Mb skeletal muscle origin as evidenced by their capacity to express myogenin and fast skeletal myosin. This skeletal phenotype appeared to downregulate with time, and Mbs partially transdifferentiated into a cardiac phenotype as indicated by labeling for cardiac-specific troponin T and cardiac myosin heavy chain. By the third week posttransplantation, new myofibers formed apparent contacts with the native CMs via putative gap junctions that expressed connexin43. Myocardial performance of animals that were successfully transplanted with Mbs was improved.

Age Factors↗

A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly.

High density lipoprotein cholesterol (HDL-C) levels are inversely associated with the incidence of coronary heart disease (CHD) in middle-aged individuals; in the elderly, the association is less clear. Genetic factors, including variations in the cholesteryl ester transfer protein (CETP) gene, play a role in determining HDL-C levels. Controversy remains about whether CETP deficiency and the resultant rise in HDL-C are antiatherogenic, or whether CETP has the opposite effect due to its role in reverse cholesterol transport. In a seven-year follow-up of 2340 men aged 71-93 in the Honolulu Heart Program, the age-adjusted CHD incidence rates were significantly lower in men with high versus low HDL-C levels. After adjustment for age, hypertension, smoking, and total cholesterol, the relative risk of CHD for those with HDL-C levels >or=60 mg/dl, compared with those with HDL-C levels <40 mg/dl, was 0.6. Men with a CETP mutation had the lowest rates of CHD, although this was not statistically significant. These data indicate that HDL-C remains an important risk factor for CHD in the elderly. Whether a CETP mutation offers additional protection against CHD warrants further investigation.

Age Factors↗

Human salivary function in relation to the prevalence of Tannerella forsythensis and other periodontal pathogens in early supragingival biofilm.

OBJECTIVE: Previously, we screened 149 subjects and established four groups high or low for salivary killing of oral bacteria, and for aggregation and live and dead adherence of oral bacteria (as a combined factor). Caries scores were significantly lower in both High Aggregation-Adherence groups. Subsequently, we found that supragingival total biofilm DNA, total streptococci and two major streptococcal rRNA variants also were significantly lower in the High Aggregation-Adherence groups. In this study, we looked at the effects of those differences in salivary function on three periodontal pathogens. DESIGN: Quantitative PCR was used to determine levels of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythensis (formerly Bacteroides forsythus) in stored DNA extracts of overnight supragingival biofilm collected from buccal upper central incisors (UC), lingual lower central incisors (LC) and buccal upper and lower first molars (BM) and lingual upper and lower first molars (LM) of subjects in the four groups. RESULTS: A. actinomycetemcomitans and P. gingivalis were almost completely absent from these samples. T. forsythensis was found in 11 of 35 persons at the buccal molar site. Only two of those subjects were in the High Aggregation-Adherence groups, and that difference was statistically significant. The mean quantity of T. forsythensis also was significantly lower in the High Aggregation-Adherence groups. CONCLUSIONS: The difference between the Low and High Aggregation-Adherence groups might reflect direct interactions of salivary proteins with T. forsythensis. Alternatively, the higher levels of total biofilm and total streptococci seen in the Low Aggregation-Adherence groups might create a favourable environment for early secondary colonization of T. forsythensis.

Aggregatibacter actinomycetemcomitans↗

Expression of cellular inhibitor of apoptosis protein-2 in human subcutaneous and omental adipose tissue.

OBJECTIVE: In the current study, we addressed the question if there is depot-specific expression of cellular inhibitor of apoptosis protein-2 (cIAP2) already in childhood and if the relative expression changes with age in parallel with increasing risk of developing visceral adiposity. SUBJECTS: Paired samples of human omental (OM) and subcutaneous (SC) adipose tissue were obtained from 23 patients (12 children and 11 adults). METHOD: mRNA level of cIAP2 was determined using reverse transcription-polymerase chain reaction (RT-PCR) and protein expression confirmed by Western blotting. Apoptosis indices were determined by terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling (TUNEL). RESULTS: cIAP2 mRNA was 1.51-fold higher in OM compared with SC adipose tissue (OM>SC in 20 of 23 subjects; P<0.001). Western blots were in agreement with mRNA expression (OM>SC in nine of 10 subjects, P<0.01). Subgroup analyses showed depot difference in both children (P<0.01) and adults (P<0.05). Contrary to the hypothesis, depot-specific difference in mRNA expression of cIAP2 was significantly higher in children compared with adults (P<0.05). We were unable to demonstrate any difference in the basal apoptosis rate between adipocytes from the two depots. There was no significant association between cIAP2 mRNA expression and BMI or sex. CONCLUSIONS: The results demonstrated for the first time that depot-specific difference in cIAP2 expression is consistent in children and adults. This suggests that the higher expression of cIAP2 in OM than in SC adipose tissue may be due to inherent properties of cells from the two depots. The more pronounced depot-specific difference in children than in adults may reflect a net gain in visceral adipose tissue during growth.

Adipocytes↗

Rate dependence of mechanically induced electrophysiological changes in right ventricle of anaesthetized lambs during pulmonary artery occlusion.

AIM: Mechanically induced early afterdepolarization (EAD) is morphologically similar but different in the mechanisms with drug-induced EAD, which lead to arrhythmia. Pacing suppresses the drug-induced EAD and arrhythmia, however the effect of pacing on mechanically induced EAD and arrhythmia is not clear. This study addressed this issue in right ventricle (RV) of anaesthetized lambs. METHODS: Six lambs were anaesthetized, and their hearts exposed. Nine monophasic action potential (MAP) electrodes were placed on RV apex, outflow and inflow regions, and recorded before, during, and after a 10 s occlusion of pulmonary artery at a number of pacing rates. RESULTS: Pacing significantly reduced the baseline MAP duration at 90% repolarization (MAPD90), decreased the reduction of MAPD at early repolarization at the peak of occlusion. Nonetheless, the percentage of reduction was not significantly different among them. Pacing was able to reduce the frequencies, size of mechanically induced EADs. MAPD90 at the peak of occlusion was all shortened during pacing rather than some lengthened at intrinsic rate. Therefore, the dispersion of MAPD90 at the peak of occlusion reduced from 86 +/- 6 ms at intrinsic rate to 42 +/- 4 ms at 120 beats min-1, 38 +/- 3 ms at 150 beats min-1 and 26 +/- 3 ms at 170 beats min-1. Ultimately, pacing reduced/suppressed mechanically induced premature ventricular beats. These alterations were inversely related to heart rates. CONCLUSION: Pacing reduces/suppresses both stretch-induced EADs and arrhythmia. These modulations are remarkably similar to those on other EADs by the pacing.

Action Potentials↗

Characteristics of patients with seasonal allergic rhinitis and concomitant asthma.

BACKGROUND: Allergic rhinitis and asthma often co-exist and appear to produce a continuum of airway disease, but whether the clinical characteristics of asthma in patients with seasonal rhinitis differ from those of persistent asthma has not been examined. OBJECTIVE: The aim of this retrospective study was to characterize the clinical features of patients with seasonal allergic rhinitis with concomitant asthma and to compare them with those in patients with persistent asthma. METHODS: The patient populations for this study were derived from nine prospective, placebo-controlled planned clinical trials of similar design. Six studies (958 patients) enrolled patients with seasonal allergic rhinitis and concomitant asthma; three (607 patients) involved patients with persistent asthma. In all studies, patients were excluded from oral corticosteroid therapy in the preceding 3 months, and from inhaled corticosteroids in the preceding month. RESULTS: Patients with seasonal rhinitis and asthma had a significantly (P<0.001) higher total asthma symptom score than those with persistent asthma. In particular, cough was three times more severe. The need for beta(2)-agonist as a rescue medication and the ratio of forced expiratory volume in 1 s/forced vital capacity (FVC) were similar in the two groups whereas forced expiratory fraction 25-75%/FVC was significantly (P<0.02) reduced in the persistent asthmatics. Asthma and nasal symptom severity scores were correlated in patients with seasonal rhinitis and asthma (P<0.0001). CONCLUSIONS: Patients with seasonal allergic rhinitis and concomitant asthma appear to differ from those with persistent asthma. A prospective study should be designed to discover whether patients with seasonal rhinitis and asthma may represent a distinct nosological entity, 'allergic airway disease'.

Adrenergic beta-Agonists↗

Haplotypic analyses of the aldosterone synthase gene CYP11B2 associated with stage-2 hypertension in northern Han Chinese.

The objective of this study was to investigate the association of polymorphisms in the aldosterone synthase gene CYP11B2 (-344T/C, Lys173/Arg, and an intronic conversion [IC]) with stage-2 hypertension in northern Han Chinese. A total of 503 hypertensives and their age-, gender-, and area-matched controls were included in this study. The female hypertensives had significantly higher frequencies of the -344T, 173Lys, and IC-conversion alleles (p = 0.002, 0.002, and 0.014, respectively). The estimated frequency of haplotype composed of the -344T, 173Lys, and IC-conversion alleles (haplotype 4) was significantly higher in the female hypertensives compared with their controls (p = 0.007). Using a multivariate score test, we found that haplotype 4 remained associated with female hypertension after the adjustment for covariates (p = 0.003), while the haplotype 3 of T-Arg-WT showed a protective effect both in the males and in the females (p = 0.03 and 0.006, respectively). The odds ratio for haplotype phase of 4-4 was 2.60 (95% CI, 1.21-5.58) and for 3-3, 0.20 (95% CI, 0.03-0.77). These results indicate that the Lys173 and the IC-conversion allele of the CYP11B2 gene confer an increased risk for stage-2 hypertension in northern Han Chinese women.

Asian People↗

Quality assessments of HMO diagnosis databases used to monitor childhood vaccine safety.

OBJECTIVE: To assess the quality of automated diagnoses extracted from medical care databases by the Vaccine Safety Datalink (VSD) study. METHODS: Two methods are used to assess quality of VSD diagnosis data. The first method compares common automated and abstracted diagnostic categories ("outcomes") in 1-2% simple random samples of study populations. The second method estimates positive predictive values of automated diagnosis codes used to identify potential cases of rare conditions (e.g., acute ataxia) for inclusion in nested case-control medical record abstraction studies. RESULTS: There was good agreement (64-68%) between automated and abstracted outcomes in the 1-2% simple random samples at 3 of the 4 VSD sites and poor agreement (44%) at 1 site. Overall at 3 sites, 56% of children with automated cerebella ataxia codes (ICD-9 = 334) and 22% with "lack of coordination" codes (ICD-9 = 781.3) met objective clinical criteria for acute ataxia. CONCLUSIONS: The misclassification error rates for automated screening outcomes substantially reduce the power of screening analyses and limit usefulness of screening analyses to moderate to strong vaccine-outcome associations. Medical record verification of outcomes is needed for definitive assessments.

Child, Preschool↗

Serum and follicular fluid leptin levels in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization cycle.

OBJECTIVE: To determine serum and follicular fluid leptin levels in patients undergoing controlled ovarian hyperstimulation (COH) for an in vitro fertilization-embryo transfer (IVF-ET) cycle and their possible correlation to COH variables. SETTING: Large university-based IVF unit. PATIENTS: 16 consecutive patients undergoing our routine IVF long gonadotrophin-releasing hormone-analog protocol. INTERVENTIONS AIND MAIN OUTCOME MEASURES: Blood was drawn three times during the COH cycle: 1) day on which adequate suppression was obtained (Day-S); 2) day of or prior to human chorionic gonadotrophin (hCG) administration (Day-hCG); and 3) day of ovum pick-up (Day-OPU). Levels of sex steroids and serum and follicular fluid leptin were compared among the three time points. Serum leptin was measured with a commercial two-site immunoradiometric assay. RESULTS: Results showed significantly higher levels of serum leptin on Day-OPU and Day-hCG than on Day-S, and significantly higher follicular than serum leptin levels on Day-OPU. Though a significant correlation was observed between serum leptin and body mass index (BMI), no correlations were found between serum or follicular fluid leptin and serum sex-steroid levels or IVF treatment variables. CONCLUSION: While serum leptin increases during COH for IVF, there is apparently no correlation of serum and follicular leptin levels with sex-steroid levels or IVF outcome.

Adult↗

Involvement of the human subthalamic nucleus in movement preparation.

BACKGROUND: Although it has long been recognized that the basal ganglia play a major role in motor control, their precise functions remain unclear. As patients with Parkinson's disease (PD) have difficulties initiating movement, the basal ganglia may be involved in movement preparation. The subthalamic nucleus (STN) is particularly suited to play a role in movement preparation because it receives direct input from the supplementary motor area through the corticosubthalamic pathway. METHODS: Taking advantage of the electrodes surgically implanted in the STN for deep brain stimulation (DBS) treatment in 13 PD patients, we recorded from the DBS electrodes and the scalp simultaneously while the patients were performing self-paced wrist extension movements. RESULTS: Scalp recordings showed a slow, negative movement-related potential (MRP) in all patients studied (onset 1,690 +/- 336 milliseconds before electromyography onset). STN recordings showed premovement MRP in 11 of 13 patients. The STN activity occurred with both ipsilateral and contralateral hand movement. The onset time for STN MRP (contralateral 2,095 +/- 1,005 milliseconds, ipsilateral 2,020 +/- 920 milliseconds) was not significantly different from that for cortical MRP. CONCLUSION: The STN or nearby structures are active before self-paced movement in humans.

Action Potentials↗

The CUSCORE test and the q-interval in cluster analyses of colon cancer and of lymphoma among asbestos workers.

Exposure to a carcinogen is likely to be reflected by temporal clustering of cancer cases among the community members. Detection of such clustering is a complicated task in general and more so in a small workplace community with low turnover rate. In this study we applied the CUSCORE test and the q-interval statistic to lymphoma and colon cancer death data among 2200 asbestos workers. The CUSCORE test was applied in order to identify clusters, and the q-interval was used to provide clues related to the cause of the cluster. We also evaluated and tested the data according to the standardized mortality ratio (SMR). Significant increases in both colon cancer and lymphoma among asbestos workers in Israel (1987-1997) were demonstrated by the CUSCORE test but not so by the SMR. The fact that an apparent clustering was observed from the pattern of the q-intervals leads to the conclusion that the detected clusters are real.

Asbestos↗

Parkin-proven disease: common founders but divergent phenotypes.

OBJECTIVE: To compare and contrast clinical and genetic findings in six probands with parkinsonism with a parkin exon 3 438- to 477-bp deletion (Ex3Delta40) to search for evidence of a common founder. METHOD: Clinical review, parkin gene sequencing, dosage studies, and high-resolution genotype/haplotype analysis were performed. RESULTS: All subjects had two or more signs consistent with a diagnosis of possible or probable PD with age at onset younger than 45 years (mean +/- SD 29.3 +/- 10.2 years, range 16 to 42 years). Affected individuals were either homozygotes, compound heterozygotes, or Ex3Delta40 carriers with one normal parkin allele. Haplotype analysis revealed both Ex3Delta40 and Ex7 924 C-->T (R275W) mutations originated from common founders, the former most probably of Irish descent. Although three cases had Ex7 924 C-->T (R275W) and Ex3Delta40 mutations, their clinical presentation and mode of inheritance were variable. CONCLUSION: Parkin mutations on common parkin haplotypes provide testable hypotheses of parkin function in genetically defined parkinsonism.

Adult↗

Pharmacological characterization of a novel antiglaucoma agent, Bimatoprost (AGN 192024).

Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.

Amides↗

Strict glycemic control in diabetic pregnancy-implications for second-trimester screening for Down syndrome.

OBJECTIVES: Studies in the early 1990s showed that the normal levels of the biochemical markers used to screen for Down syndrome in the second trimester of pregnancy differ between healthy women and women with insulin-dependent diabetes mellitus (IDDM). Thereafter, most laboratories adopted correcting factors to adjust for these differences. However, the current validity of these factors in light of the recent improvements in glycemic control in diabetic pregnancy has not been investigated. METHODS: The sample consisted of 35 pregnant women with strictly controlled IDDM and 40 healthy controls matched for age and gestational week. All women had singleton pregnancies and were followed till delivery. RESULTS: Comparison of the triple test results between the two groups after adjustment with the traditional corrective factors yielded no significant differences in serum levels of any of the markers (unconjugated estriol, human chorionic gonadotrophin, alpha-fetoprotein). CONCLUSIONS: These results suggest that the recent improvement in glycemic control of pregnant women with IDDM changes the metabolic milieu that might cause the biochemical differences with healthy pregnant patients.

Adult↗

Streptococcal diversity in oral biofilms with respect to salivary function.

OBJECTIVE: In a previous study, we screened 149 subjects and established four groups high or low for salivary killing of oral bacteria, and for aggregation and live and dead adherence of oral bacteria (as a combined factor). Caries scores were significantly lower in both High Aggregation-Adherence groups. In this study we looked at the effects of those differences in salivary function on the quantity and diversity of oral biofilm streptococci. DESIGN: Subjects from those four groups were recalled for collection of overnight oral biofilm from buccal upper central incisors, lingual lower central incisors, buccal upper and lower first molars, and lingual upper and lower first molars. At each site, groups were compared for total biofilm (by DNA concentration), total streptococci (by quantitative PCR), and streptococcal diversity (by Streptococcus-specific denaturing gradient gel electrophoresis). RESULTS: Total biofilm DNA and total streptococci were correlated. Both were highest on buccal molar surfaces and lowest on lingual lower central incisors, and both were significantly lower in the High Aggregation-Adherence groups (particularly at the buccal molar site). Fifty distinct bands were observed in denaturing gradient gels. There was great diversity within and between sites. Three major bands were present in almost every person at every site. Densities for two of those bands were significantly lower in both High Aggregation-Adherence groups. Other less-prevalent bands also showed the same pattern. CONCLUSION: These findings are consistent with our caries results in suggesting that differences in salivary function can influence the quantity and composition of streptococci in oral biofilms.

Bacterial Adhesion↗

PGE2 induction of labor for consistent decreased perception of fetal movements at term.

OBJECTIVES: To determine the effects of labor induction with vaginal prostaglandin E2 (PGE2) on mode of delivery and immediate neonatal outcome in women with consistent decreased perception of fetal movements at term. METHODS: The study group consisted of 115 women with consistent perception of decreased fetal movements admitted for induction of labor at term. Findings were compared with those of 510 women with normal spontaneous onset of labor. Women with previous cesarean section (CS) were excluded from both the study and control groups. RESULTS: The rate of CS was higher in the study group (14.8%) than in the control group (9%) (not significant). The rates of low 5-min Apgar score (<or=7) and CS performed for non-reassuring fetal heart rate were two-fold higher in the study group than in the control group (2.6% vs. 1.2%, and 6.1% vs. 3.1%, respectively, not significant in both). CONCLUSION: Induction of labor with PGE2 is successful in approximately 85% of the patients with decreased perception of fetal movements at term and apparently with no serious maternal or fetal complications. However, these pregnancies might be at higher risk of perinatal complications. We suggest that active labor induction may be currently considered as the preferred strategy in these pregnancies. Large prospective randomized studies on maternal and neonatal outcome are needed to clarify this issue.

Adult↗

Parkin mutations are rare in patients with young-onset parkinsonism in a US population.

Parkin mutations have been associated with an autosomal recessive-juvenile parkinsonism, but it is unclear how common such patients are in a US based clinic population. In this study, we screened for parkin gene mutations in a clinic-based series of 27 consecutive patients in the US with typical parkinsonism beginning before the age of 50 years. Two patients began the disease before the age of 30 years. Among the 27 patients screened, only one patient, whose disease began at the age of 24 years, was found to harbor a parkin mutation (a 40 bp deletion in exon 3). In addition, we also identified four new polymorphisms in the open reading frames of the parkin gene in this population. Our results suggest parkinsonism due to mutations in the parkin gene is extremely rare in the US population when the disease begins over the age of 30.

Adult↗