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Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 271 records · Page 15Linked to original sources
PubMed2002

Dysregulation of transforming growth factor beta signaling in scleroderma: overexpression of endoglin in cutaneous scleroderma fibroblasts.

OBJECTIVE: As an initial approach to understanding the basis of the systemic sclerosis (SSc; scleroderma) phenotype, we sought to identify genes in the transforming growth factor beta (TGF beta) signaling pathway that are up-regulated in lesional SSc fibroblasts relative to their normal counterparts. METHODS: We used gene chip, differential display, fluorescence-activated cell sorter, and overexpression analyses to assess the potential role of TGF beta signaling components in fibrosis. Fibroblasts were obtained by punch biopsy from patients with diffuse cutaneous SSc of 2-14 months' duration (mean 8 months) and from age- and sex-matched healthy control subjects. RESULTS: Unexpectedly, we found that fibroblasts from SSc patients showed elevated expression of the endothelial cell-enriched TGF beta receptor endoglin. Endoglin is a member of the nonsignaling high-affinity TGF beta receptor type III family. The expression of endoglin increased with progression of disease. Transfection of endoglin in fibroblasts suppressed the TGF beta-mediated induction of connective tissue growth factor promoter activity. CONCLUSION: SSc is characterized by overproduction of matrix; that is, genes that are targets of TGF beta signaling in normal fibroblasts. Our findings suggest that lesional SSc fibroblasts may overexpress endoglin as a negative feedback mechanism in an attempt to block further induction of profibrotic genes by TGF beta.

Antigens, CD↗
PubMed2002

Effect of water vapor treatment on apatite formation on precalcified titanium and bond strength of coatings to substrates.

In previous investigations, a simple method, precalcification, was developed for bioactivating titanium. After a titanium sample was precalcified in a boiling saturated Ca(OH)(2) solution and then immersed in a calcium phosphate supersaturated solution, an apatite coating rapidly precipitated onto its surface. In the present study, heat-treatment in water vapor was carried out prior to precalcification. Heat-treatment in water vapor stimulated the chemical reaction between titanium, calcium, and phosphate. Coating properties were improved, and the bond strength of the coating to substrate was enhanced.

Apatites↗
PubMed2002

A study on the friction of a self-correction ultrasonic stepping motor.

An experiment has been carried out to investigate the self-correction function of a self-correction ultrasonic stepping motor. When a slider (rotor) is placed on a vibrating beam (stator), it will stay at a stable equilibrium position. If the slider is slightly moved off the equilibrium position, a restoring force will urge the slider back towards its equilibrium position. The experimental result shows that the position of the maximum restoring force on the slider differs from that predicted by using the linear theory. Study found that when a quadratic form is assumed for the dynamic friction coefficient, the theoretical and experimental results are in good agreement.

Journal Article↗
PubMed2002

Effect of pertussis toxin and N-ethylmaleimide on voltage-dependent and -independent calcium current modulation in serotonergic neurons.

Introduction of GTP-gamma-S into a neuronal cell spontaneously results in G-protein activation. A possible contribution to this mechanism is that some receptors have a constitutive activity that stimulates GDP/GTP exchange resulting in increased GTPase activity of G-protein alpha subunits, leading to a facilitation of GTP-gamma-S binding. It follows that partial or complete uncoupling of receptors and G-proteins could inhibit Ca(2+) current modulation by GTP-gamma-S. This possibility was tested in acutely isolated rat dorsal raphe neurons by uncoupling the receptor and G-protein using N-ethylmaleimide and pertussis toxin. Since these compounds have been suggested to differentially block voltage-dependent inhibition, relative to voltage-independent, we investigated whether the apparent voltage-independent component of Ca(2+) channel modulation by 5-hydroxytryptamine (5-HT) shares the same mechanism as the voltage-dependent component. N-ethylmaleimide inhibited the response to 5-HT by about 50% but had no effect on the response to GTP-gamma-S. In dorsal raphe neurons 28.9% of the total response to 5-HT was voltage-independent. N-ethylmaleimide had identical effects on the voltage-dependent and -independent components as measured by tail current inhibition. The response to 5-HT was completely sensitive to pertussis toxin, and completely uncoupling the receptors and G-proteins did not affect the maximal response to GTP-gamma-S. Our results suggest that the apparent voltage-independent component of Ca(2+) channel modulation by 5-HT in dorsal raphe neurons might share the same mechanism as does the voltage-dependent component. In addition, these experiments provided evidence that partial or even complete uncoupling of receptors and G-proteins did not affect Ca(2+) current modulation by direct activators of G-proteins.

Animals↗
PubMed2002

Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: an in vivo microdialysis study.

Increased activity of the histaminergic neurons of the posterior hypothalamus has been implicated in the facilitation of behavioral wakefulness. Recent evidence of reciprocal projections between the sleep-active neurons of the preoptic/anterior hypothalamus and the histaminergic neurons of the tuberomammillary nucleus suggests that histaminergic innervation of the preoptic/anterior hypothalamic area may be of particular importance in the wakefulness-promoting properties of histamine. To test this possibility, we used microdialysis sample collection in the preoptic/anterior hypothalamic area of cats during natural sleep-wakefulness cycles, 6 h of sleep deprivation induced by gentle handling/playing, and recovery sleep. Samples were analyzed by a sensitive radioenzymatic assay. Mean basal levels of histamine in microdialysate during periods of wakefulness (1.155+/-0.225 pg/microl) did not vary during the 6 h of sleep deprivation. However, during the different sleep states, dramatic changes were observed in the extracellular histamine levels of preoptic/anterior hypothalamic area: wakefulness>non-rapid eye movement sleep>rapid eye movement sleep. Levels of histamine during rapid eye movement sleep were lowest (0.245+/-0.032 pg/microl), being significantly lower than levels during non-rapid eye movement sleep (0.395+/-0.081 pg/microl) and being only 21% of wakefulness levels. This pattern of preoptic/anterior hypothalamic area extracellular histamine levels across the sleep-wakefulness cycle closely resembles the reported single unit activity of histaminergic neurons. However, the invariance of histamine levels during sleep deprivation suggests that changes in histamine level do not relay information about sleep drive to the sleep-promoting neurons of the preoptic/anterior hypothalamic area.

Animals↗
PubMed2002

Antidepressant activity of aqueous extracts of Curcuma longa in mice.

Curcuma longa (turmeric) is a well-known indigenous herbal medicine. The aqueous extracts, when administered orally to the mice from 140 to 560 mg/kg for 14 days, were able to elicit dose-dependent relation of immobility reduction in the tail suspension test and the forced swimming test in mice. The effects of the extracts at the dose of 560 mg/kg were more potent than that of reference antidepressant fluoxetine. The extracts, at the dose of 140 mg/kg or above for 14 days, significantly inhibited the monoamine oxidize A (MAO) activity in mouse whole brain at a dose-dependent manner, however, oral administration of the extract only at a dose of 560 mg/kg produced observable MAO B inhibitory activity in animal brain. Fluoxetine showed only a tendency to inhibit MAO A and B activity in animal brain in the study. Neither the extracts of C. longa nor fluoxetine, at the doses tested, produced significant effects on locomotor activity. These results demonstrated that C. longa had specifically antidepressant effects in vivo. The activity of C. longa in antidepression may mediated in part through MAO A inhibition in mouse brain.

Administration, Oral↗
PubMed2002

Determination of stereochemistry stability coefficients of amino acid side-chains in an amphipathic alpha-helix.

We describe here a systematic study to determine the effect on secondary structure of d-amino acid substitutions in the nonpolar face of an amphipathic alpha-helical peptide. The helix-destabilizing ability of 19 d-amino acid residues in an amphipathic alpha-helical model peptide was evaluated by reversed-phase HPLC and CD spectroscopy. l-Amino acid and d-amino acid residues show a wide range of helix-destabilizing effects relative to Gly, as evidenced in melting temperatures (DeltaTm) ranging from -8.5 degrees C to 30.5 degrees C for the l-amino acids and -9.5 degrees C to 9.0 degrees C for the d-amino acids. Helix stereochemistry stability coefficients defined as the difference in Tm values for the l- and d-amino acid substitutions [(DeltaTm' = TmL and TmD)] ranging from 1 degrees C to 34.5 degrees C. HPLC retention times [DeltatR(XL-XD)] also had values ranging from -0.52 to 7.31 min at pH 7.0. The helix-destabilizing ability of a specific d-amino acid is highly dependent on its side-chain, with no clear relationship to the helical propensity of its corresponding l-enantiomers. In both CD and reversed-phase HPLC studies, d-amino acids with beta-branched side-chains destabilize alpha-helical structure to the greatest extent. A series of helix stability coefficients was subsequently determined, which should prove valuable both for protein structure-activity studies and de novo design of novel biologically active peptides.

Amino Acid Sequence↗
PubMed2002

Surveillance for work-related hearing loss in the UK: OSSA and OPRA 1997-2000.

Surveillance data on occupational audiological disorders have been collected by the Occupational Surveillance Scheme for Audiological Physicians (OSSA) since October 1997 and by the Occupational Physicians Reporting Activity (OPRA) from January 1996. During the 3 years ending in September 2000, a total of 1620 new cases were received from consultant audiological physicians; 988 new cases were estimated from reports by occupational physicians in the period from October 1997 to September 2000. The annual incidence of occupational noise-induced hearing loss (NIHL) was 1.94 and 1.23 per 100 000 workers for the OSSA and OPRA schemes, respectively. The median age at diagnosis with NIHL was 59 years in OSSA reports and 50 years in OPRA; nearly all cases were seen in men (95.6 and 92.5% male cases for OSSA and OPRA, respectively). High incidence rates based on OSSA reports were seen in foundry labourers (64.0 per 100 000 employed), coal gas and coke oven furnace workers (54.6), workers in transport and communication (43.1), metal workers (31.3), and members of the armed forces (28.3). Data from occupational physicians point to high rates in sawyers and woodworking machinists, metal furnace workers, coach and carriage builders, maintenance fitters, and engineering labourers. Among workers aged < or =45 years, those in manufacturing and the armed forces were prominent. The long latency of occupational hearing loss makes surveillance difficult, but consistent patterns in occupational risk suggest targets for preventive efforts.

Female↗
PubMed2002

Comparative analysis of allozyme, random amplified polymorphic DNA, and microsatellite polymorphism on Chinese native chickens.

Allozyme, random amplified polymorphic DNA (RAPD), and microsatellite polymorphisms were examined and compared among five native populations of Chinese chickens, two fast-growing broiler lines, and one layer line. Three assay systems resulted in a different average heterozygosity or gene diversity in each of the eight populations. The lowest average heterozygosity was obtained with allozyme analysis (0.2209), intermediate heterozygosity was obtained with RAPD (0.2632), and the highest heterozygosity was observed with microsatellite analysis (0.7591). The genetic distances among all populations measured by three methods were also different. Allozyme data showed close relationships between Chinese native chickens and the two broiler lines, but they were both remotely related to the layer line. Microsatellite polymorphism analysis was similar to the allozyme analysis but genetic distances from RAPD showed a close relationship between Chinese native chickens and broiler and layer chickens.

Albumins↗
PubMed2002

REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.

The downregulation of the Reelin gene (RELN) that occurs in schizophrenic brains, which are characterized by pyramidal neurons with shortened dendrites and by reduced expression densities of dendritic spines, may well result from hypermethylation of the RELN promoter. In the adult mammalian brain, gamma-aminoburytic acid-secreting (GABAergic) interneurons release RELN into the extracellular matrix, where it binds with high affinity to the integrin receptors present at dendritic spine postsynaptic densities and likely plays a role, elaborated in this article, in synaptic plasticity. In heterozygous reeler mice, which are haploinsufficient in RELN, inhibitors of histone deacetylase increase DNA demethylase activity and restore RELN expression. Such inhibitors could thus be of therapeutic value in mitigating vulnerability to schizophrenia among high-risk individuals.

Animals↗
PubMed2002

Orally administered RDP58 reduces the severity of dextran sodium sulphate induced colitis.

Oral administration of the novel anti-inflammatory peptide RDP58 markedly reduced the severity of dextran sulphate sodium (DSS) colitis as determined by clinical and quantitative histological criteria. The architecture of the colonic epithelium in DSS treated mice receiving RDP58 remained relatively normal compared with that of control DSS treated animals. 5-Bromo-2'-deoxyuridine (BrdU) labelling studies showed a pronounced inhibition of colonic epithelial cell proliferation during DSS treatment, which was partially reversed by RDP58 therapy. Remarkably, RDP58 almost completely prevented colonic epithelial cell death induced by DSS treatment. RDP58 therapy also inhibited the accumulation of neutrophils in the colon of DSS treated mice and effectively down regulated tumour necrosis factor (TNF) expression. Preservation of the intestinal mucosa by RDP58 may thus derive from its influence on TNF expression as well as additional anti-inflammatory properties. These findings indicate that RDP58 represents a new, orally available agent potentially useful in the treatment of inflammatory bowel disease.

Acute Disease↗
PubMed2002

Influence of family income on hospital visits for asthma among Canadian school children.

BACKGROUND: A study was undertaken to investigate the mechanisms by which socioeconomic status may influence asthma morbidity in Canada. METHODS: A total of 2968 schoolchildren aged 5-19 years with reported asthma were divided into three family income ranges. Hospital visits and risk factors for asthma, ascertained by questionnaire, were compared between the three groups. RESULTS: The mean (SE) annual period prevalence of a hospital visit was 25.0 (3.1)% among schoolchildren with household incomes of less than $20 000 Canadian compared with 16.0 (1.3)% among those with incomes of more than $60 000 (p<0.05). Students with asthma from lower income households were more likely to be younger and exposed to environmental tobacco smoke and cats, and their parents were more likely to have a lower educational attainment and be unmarried (p<0.05). Across all income groups, younger age, lower parental education, having unmarried parents, and regular exposure to environmental tobacco smoke were each associated with an increase in risk of a hospital visit (p<0.05). No increased risk was detected due to sex, having pets, and not taking dust control measures. Although not statistically significant at p<0.05, there may have been an interactive effect between income and susceptibility to environmental tobacco smoke. In the lower income group those children who were regularly exposed to second hand smoke had a 79% higher risk of a hospital visit compared with a 45% higher risk in the higher income group. In a logistic regression model the association between income and hospital visit was no longer significant after adjusting for differences in reported exposure to passive smoking. CONCLUSION: Socially disadvantaged Canadian schoolchildren have increased asthma morbidity. Exposure to cigarette smoke appears to be one important explanation for this observation.

Adolescent↗
PubMed2002

[Nphe1]nociceptin(1-13)-NH2 antagonizes nociceptin-induced hypotension, bradycardia, and hindquarters vasodilation in the anesthetized rat.

The purpose of this study was to investigate the effects of [Nphe1]nociceptin(1-13)-NH2 on nociceptin-induced decreases in mean arterial pressure (MAP), heart rate (HR), and hindquarters vascular bed resistance (HVBR) of the anesthetized rat. The results showed that i.c.v. or i.v. [Nphe1]nociceptin(1-13)-NH2 (1.5-12 nmol/kg and 5-120 nmol/kg, respectively) could antagonize the depressor effects of i.c.v. or i.v. nociceptin (3 and 30 nmol/kg, respectively) on MAP and HR. Furthermore, [Nphe1]nociceptin(1-13)-NH2 (5-120 nmol/kg) could reverse nociceptin (30 nmol/kg)-induced decrease of HVBR. However, [Nphe1]nociceptin(1-13)-NH2 had no significant effects on similar effects induced by morphine. Our results suggest that [Nphe1]nociceptin(1-13)-NH2 acts as a selective antagonist of the nociceptin receptor in the cardiovascular system of the rat.

Anesthesia↗
PubMed2002

Sex-related interactive effect of smoking and household pets on asthma incidence.

The authors examined the interactive effect of smoking and pets at home on the incidence of asthma and the difference between sexes. The longitudinal data from the first two cycles of the National Population Health Survey, conducted in Canada, were used. A total of 12,636 subjects who reported no asthma at baseline were included in the analysis. The 2-yr cumulative incidence of asthma was higher in females than in males. Female sex and household pets demonstrated a significant interaction in the development of asthma. After adjustment for age, immigration and history of allergy, the odds ratio for smoking in relation to the asthma incidence was 2.50 (95% confidence interval: 1.24-5.05) for females who had pets at home and close to unity for those who had no pets. The incidence of asthma was not associated with smoking status and household pets in males. These results indicate that smoking, having pets at home and other environmental factors can partly explain asthma morbidity among female Canadians.

Adolescent↗
PubMed2002

Postnatal hypoxemia increases angiotensin II sensitivity and up-regulates AT1a angiotensin receptors in rat carotid body chemoreceptors.

In the present study, the effects of postnatal hypoxemia on the AT1 angiotensin receptor-mediated activities in the rat carotid body were studied. Angiotensin II (Ang II) concentration-dependently increased the chemoreceptor afferent activity in the isolated carotid body. Single- or pauci-fiber recording of the sinus nerve revealed that the afferent response to Ang II was enhanced in the postnatally hypoxic carotid body. To determine whether the increased sensitivity to Ang II is mediated by changes in the functional expression of Ang II receptors in the carotid body chemoreceptors, cytosolic calcium ([Ca2+]i) was measured by spectrofluorimetry in fura-2 acetoxymethyl ester-loaded type I cells dissociated from carotid bodies. Ang II (25-100 nM) concentration-dependently increased [Ca2+]i in the type I cells. The proportion of clusters of type I cells responsive to Ang II was higher in the postnatally hypoxic group than in the normoxic control (89 vs 66%). In addition, the peak [Ca2+]i response to Ang II was enhanced 2- to 3-fold in the postnatally hypoxic group. The [Ca2+]i response to Ang II was abolished by pretreatment with losartan (1 microM), an AT1 receptor antagonist, but not by PD-123177 (1 microM), an AT(2) antagonist. Double-labeling immunohistochemistry confirmed that an enhanced immunoreactivity for AT1 receptor was co-localized to the lobules of type I cells in the hypoxic group. In addition, RT-PCR analysis of subtypes of AT1 receptors showed an up-regulation of AT1a but a down-regulation of AT1b receptors, indicating a differential regulation of the expression of AT1 receptor subtypes by postnatal hypoxia in the carotid body. These data suggest that postnatal hypoxemia is associated with an increased sensitivity of peripheral chemoreceptors in response to Ang II and an up-regulation of AT1a receptor-mediated [Ca2+]i activity of the chemoreceptors. This modulation may be important for adaptation of carotid body functions in the hypoxic ventilatory response and in electrolyte and water homeostasis during perinatal and postnatal hypoxia.

Angiotensin II↗
PubMed2002

Bone defects in latent TGF-beta binding protein (Ltbp)-3 null mice; a role for Ltbp in TGF-beta presentation.

The latent transforming growth factor (TGF)-beta binding proteins (LTBP)-1, -3 and -4 bind the latent form of the multipotent cytokine TGF-beta. To examine the function of the LTBPs, we made a null mutation of Ltbp-3 by gene targeting. The homozygous mutant animals developed cranio-facial malformations by 12 days. By three months, there was a pronounced rounding of the cranial vault, extension of the mandible beyond the maxilla, and kyphosis. The mutant animals developed osteosclerosis of the long bones and vertebrae as well as osteoarthritis between 6 and 9 months of age. These latter phenotypic changes were similar to those described for mice that have impaired TGF-beta signaling. Thus, we suggest that Ltbp-3 plays an important role in regulating TGF-beta bioavailability as the phenotype of the Ltbp-3 null mouse appears to result from decreased TGF-beta signaling. Histological examination of the skulls from null animals revealed no effects on calvarial suture closure. However, the synchondroses in the skull base were obliterated within 2 weeks of birth. This is in contrast to the wild-type synchondroses, which remain unossified throughout the life of the animal and enable growth of the skull base through endochondral ossification. Histological changes in mutant basooccipital-basosphenoid synchondrosis were observed 1.5 days after birth. Compared with wild-type or heterozygous littermates, the basooccipital-basosphenoid synchondrosis of Ltbp-3 null mice contained increased numbers of hypertrophic chondrocytes. The expression of bone sialoprotein-1 (a marker for osteoblasts) was observed in cells surrounding the synchondrosis at postnatal day 1.5 indicating ectopic ossification. The expression of Indian hedgehog (Ihh) (a marker for chondrocytes committed to hypertrophic differentiation) was found through the basooccipital-basosphenoid synchondrosis, whereas the expression of parathyroid hormone related protein (PTHrP), which inhibits chondrocyte differentiation, appeared to be diminished in Ltbp-3 null mice. This suggests that Ltbp-3 may control chondrocyte differentiation by regulating TGF-beta availability. TGF-beta may regulate PTHrP expression either downstream of Ihh or independently of Ihh signaling.

Adaptor Proteins, Signal Transducing↗