Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 1,045 records · Page 58Linked to original sources

PubMed1999

Increased effects of smoking and obesity on asthma among female Canadians: the National Population Health Survey, 1994-1995.

To assess smoking, obesity, and other risk factors for asthma, the authors examined 17,605 subjects aged 12 years or more who participated in the National Population Health Survey in 1994-1995. Asthma was considered present if an affirmative response was given to the question, "Do you have asthma diagnosed by a health professional?" The authors used analytic weights incorporating a design effect to take the complex survey design into account. The prevalence of asthma was 10.4% for males and 11.2% for females aged 12-24 years. Among the subjects aged 25 years or more, the prevalence varied from 4.1% to 5.8% for men and from 4.9% to 6.4% for women. Female smokers demonstrated a 1.7-fold increase in the prevalence of asthma compared with female nonsmokers, with the smoking effect more pronounced among female children and young adults. In contrast, there was no significant relation between smoking and asthma in males. The prevalence of asthma increased with increasing body mass index in females, but not in males. Immigrant status, history of allergy, and household income were significant predictors for both genders. Low household income was associated with a higher prevalence of asthma in men and women.

Adolescent↗

PubMed1999

G(i) protein-mediated functional compartmentalization of cardiac beta(2)-adrenergic signaling.

In contrast to beta(1)-adrenoreceptor (beta(1)-AR) signaling, beta(2)-AR stimulation in cardiomyocytes augments L-type Ca(2+) current in a cAMP-dependent protein kinase (PKA)-dependent manner but fails to phosphorylate phospholamban, indicating that the beta(2)-AR-induced cAMP/PKA signaling is highly localized. Here we show that inhibition of G(i) proteins with pertussis toxin (PTX) permits a full phospholamban phosphorylation and a de novo relaxant effect following beta(2)-AR stimulation, converting the localized beta(2)-AR signaling to a global signaling mode similar to that of beta(1)-AR. Thus, beta(2)-AR-mediated G(i) activation constricts the cAMP signaling to the sarcolemma. PTX treatment did not significantly affect the beta(2)-AR-stimulated PKA activation. Similar to G(i) inhibition, a protein phosphatase inhibitor, calyculin A (3 x 10(-8) M), selectively enhanced the beta(2)-AR but not beta(1)-AR-mediated contractile response. Furthermore, PTX and calyculin A treatment had a non-additive potentiating effect on the beta(2)-AR-mediated positive inotropic response. These results suggest that the interaction of the beta(2)-AR-coupled G(i) and G(s) signaling affects the local balance of protein kinase and phosphatase activities. Thus, the additional coupling of beta(2)-AR to G(i) proteins is a key factor causing the compartmentalization of beta(2)-AR-induced cAMP signaling.

Adrenergic beta-2 Receptor Agonists↗

PubMed1999

Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response.

BRCA1 encodes a tumor suppressor that is mutated in familial breast and ovarian cancers. Here, it is shown that BRCA1 interacts in vitro and in vivo with hRad50, which forms a complex with hMre11 and p95/nibrin. Upon irradiation, BRCA1 was detected in discrete foci in the nucleus, which colocalize with hRad50. Formation of irradiation-induced foci positive for BRCA1, hRad50, hMre11, or p95 was dramatically reduced in HCC/1937 breast cancer cells carrying a homozygous mutation in BRCA1 but was restored by transfection of wild-type BRCA1. Ectopic expression of wild-type, but not mutated, BRCA1 in these cells rendered them less sensitive to the DNA damage agent, methyl methanesulfonate. These data suggest that BRCA1 is important for the cellular responses to DNA damage that are mediated by the hRad50-hMre11-p95 complex.

Acid Anhydride Hydrolases↗

PubMed1999

APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome.

BACKGROUND: Alzheimer disease (AD) neuropathology is present in Down syndrome (DS) after age 35, but dementia onset varies from ages 40 to 70 years. Because of small sample sizes and nonuniform determination of dementia, previous studies produced differing results on the influence of APOE subtypes on AD in DS. OBJECTIVE: To determine the influence of the APOE genotype and gender on development of AD in adults with DS to ascertain similarities with AD in the general population. METHODS: A total of 100 adults with DS (ages 35 to 79 years), almost all of whom were longitudinally assessed by neurologists, underwent APOE genotyping. Dementia onset was determined using criteria applied from the Tenth International Classification of Mental and Behavioral Disorders. This cohort contains the largest number of DS subjects with dementia (n = 57) in a single study, thus increasing reliability of the results. RESULTS: The epsilon2 allele frequency was 4% in those with dementia versus 13% in those without dementia (p = 0.03); epsilon4 allele frequency was 18% in those with dementia versus 13% in those without dementia (p = 0.45). Using APOE-epsilon3/3 as the reference group, the risk ratio for the development of AD at any given time was 0.34 for the APOE-epsilon2/3 group (p = 0.04) and 1.44 for the APOE-epsilon(3/4,4/4) group (p = 0.25). Women were 1.77 times as likely to dement as men at any given point in time (p = 0.04). CONCLUSIONS: The epsilon2 allele confers a protective effect, and women with DS have an increased risk for AD, as in the general population. In this sample, epsilon4 does not confer a significantly increased risk for AD in DS.

Adult↗

PubMed1999

Electrostatic repulsion of positively charged vesicles and negatively charged objects

A positively charged, mixed bilayer vesicle in the presence of negatively charged surfaces (for example, colloidal particles) can spontaneously partition into an adhesion zone of definite area and another zone that repels additional negative objects. Although the membrane itself has nonnegative charge in the repulsive zone, negative counterions on the interior of the vesicle spontaneously aggregate there and present a net negative charge to the exterior. Beyond the fundamental result that oppositely charged objects can repel, this mechanism helps to explain recent experiments on surfactant vesicles.

Journal Article↗

PubMed1999

Genomic structure, chromosomal location, and mutation analysis of the human CDC14A gene.

Human CDC14A is a dual-specificity phosphatase that shares sequence similarity with the recently identified tumor suppressor, MMAC1/PTEN/TEP1. By radiation hybrid mapping, we localized CDC14A to chromosome band 1p21, a region that has been shown to exhibit loss of heterozygosity in highly differentiated breast carcinoma and malignant mesothelioma. We have mapped the exon-intron structure of CDC14A gene and found an in-frame ATG at 14 codons upstream of the previously reported start site (GenBank Accession No. AF000367). In screening a panel of 136 cDNAs from tumor cell lines for coding mutations, we have identified a 48-bp in-frame deletion in the cDNA of the breast carcinoma cell line, MDA-MB-436. This deletion is the result of an acceptor splice site mutation (AG to AT) in intron 12 that causes the skipping of exon 13 in the gene. Loss of expression of the wildtype allele in the same breast cell line supports the possibility that CDC14A may be a tumor suppressor gene that is targeted for inactivation during tumorigenesis.

Alternative Splicing↗

PubMed1999

Preparation, Characterization, and Catalytic Properties of Ultrafine Mixed Fe-Mo Oxide Particles.

Ultrafine mixed Fe-Mo oxide particles are prepared by the sol-gel technique using citric acid as a complex agent. The formation process of the ultrafine oxides is studied by using XRD, DTA-TG, FT-IR, TEM, and BET surface area measurement. It is found that the morphology and structure of the oxide particles are significantly dependent on the process parameters such as thermal treatment temperature (T), pH of the starting solution, and the molar ratio of citric acid to metallic ions (L/M). The formation temperature of crystalline Fe(2)(MoO(4))(3) by the sol-gel process is much lower than that by the coprecipitation method. The catalytic properties of ultrafine Fe-Mo oxide particles are tested and compared with those of large oxide particles having the same composition. It is shown that for selective oxidation of toluene to benzaldehyde the ultrafine Fe-Mo oxide particles exhibit higher benzaldehyde selectivity and toluene conversion than the large oxide particles. The unique catalytic properties of ultrafine Fe-Mo oxide particles may be correlated to the higher mobility of lattice oxygen species in the ultrafine oxide particles and their higher BET surface area. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Cellular proteinases trigger the infectivity of the influenza A and Sendai viruses.

It has been proposed that the pathogenicity of the influenza and Sendai virus is primarily determined by host cellular proteases that activate viral infectivity. We isolated trypsin-type serine proteases from rat lungs, candidates for the processing proteases of viral envelope glycoproteins, such as tryptase Clara localized in the Clara cells of the bronchial epithelium and mini-plasmin. These enzymes specifically cleave the precursor of fusion glycoprotein HA of influenza virus at Arg325, and the F0 of Sendai virus at Arg116 in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in the induction of infectivity of these viruses. Proteolytic activation of viruses by these enzymes occurs extracellularly, probably on the surface and/or in the lumen of the respiratory tract. On the other hand, we isolated two compounds from human bronchial lavage, which inhibit the activity of tryptase Clara. One was a mucus protease inhibitor and the other was a pulmonary surfactant. These compounds inhibited multiple cycles of virus replication in vitro and in vivo, but did not themselves affect the hemagglutination and the infectivity of the virus. Administration of these compounds in the airway may be useful for preventing and treating infection with influenza virus and Sendai virus.

Animals↗

PubMed1999

[Comparison of three methods in detection of rotavirus infection in neonates].

OBJECTIVE: To compare, three methods in detection of rotavirus infection in neonates. METHODS: 252 fecal samples from neonates with acute gastroenteritis, healthy neonates and under 4-month-old babies with diarrhoea were detected with ELISA, PAGE and EM. RESULTS: Using ELISA and PAGE to check 5 fecal samples from neonates with diarrhoea, the positive number of ELISA was 4 and the PAGE was all negative. One fecal sample from neonate of one month old with diarrhoea detected with ELISA was strong positive and result with EM was negative. By checking 119 fecal samples from normal neonates of less than ten days old, the positive rate of ELISA was 54.6% and results of PAGE were all RNA negative. 128 fecal samples from less than 4-month-old babies with diarrhoea showed coincident detection rate of ELISA and PAGE (81.2%), but which was going up with increasing of their ages. We also checked 55 fecal samples from less than 4-month-old babies with diarrhoea by ELISA, PAGE, EM and the positive rates were 27.3%, 38.2% and 20% respectively, the coincident rate of the three was 63.6% and the differentiation rate 36.4%. CONCLUSION: The differentiation rate between ELISA and PAGE was obvious, as in the elisa there showed a sirong positive and in PAGE the weak. The diffesence went down with increasing of the ages of the babies with diarrhoea. This indicated that the false positive rate of ELISA existed. PAGE is more reliable and objective and is the better method to check neonate diarrhoea.

Electrophoresis, Polyacrylamide Gel↗

PubMed1999

A mechanism for tamoxifen-mediated inhibition of acidification.

Tamoxifen has been reported to inhibit acidification of cytoplasmic organelles in mammalian cells. Here, the mechanism of this inhibition is investigated using in vitro assays on isolated organelles and liposomes. Tamoxifen inhibited ATP-dependent acidification in organelles from a variety of sources, including isolated microsomes from mammalian cells, vacuoles from Saccharomyces cerevisiae, and inverted membrane vesicles from Escherichia coli. Tamoxifen increased the ATPase activity of the vacuolar proton ATPase but decreased the membrane potential (Vm) generated by this proton pump, suggesting that tamoxifen may act by increasing proton permeability. In liposomes, tamoxifen increased the rate of pH dissipation. Studies comparing the effect of tamoxifen on pH gradients using different salt conditions and with other known ionophores suggest that tamoxifen affects transmembrane pH through two independent mechanisms. First, as a lipophilic weak base, it partitions into acidic vesicles, resulting in rapid neutralization. Second, it mediates coupled, electroneutral transport of proton or hydroxide with chloride. An understanding of the biochemical mechanism(s) for the effects of tamoxifen that are independent of the estrogen receptor could contribute to predicting side effects of tamoxifen and in designing screens to select for estrogen-receptor antagonists without these side effects.

Acids↗

PubMed1999

Sigma receptor photolabeling and sigma receptor-mediated modulation of potassium channels in tumor cells.

Recent work has indicated that sigma receptor ligands can modulate potassium channels. However, the only sigma receptor characterized at the molecular level has a novel structure unlike any other receptor known to modulate ion channels. This 26-kDa protein has a hydropathy profile suggestive of a single membrane-spanning domain, with no apparent regions capable of G-protein activation or protein phosphorylation. In the present study patch clamp techniques and photoaffinity labeling were used in DMS-114 cells (a tumor cell line known to express sigma receptors) to investigate the role of the 26-kDa protein in ion channel modulation and probe the mechanism of signal transduction. The sigma receptor ligands N-allylnormetazocine (SKF10047), ditolylguanidine, and (+/-)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin all inhibited voltage-activated potassium current (IK). Iodoazidococaine (IAC), a high affinity sigma receptor photoprobe, produced a similar inhibition in IK, and when cell homogenates were illuminated in the presence of IAC, a protein with a molecular mass of 26 kDa was covalently labeled. Photolabeling of this protein by IAC was inhibited by SKF10047 with half-maximal effect at 7 microM. SKF10047 also inhibited IK with a similar EC50 (14 microM). Thus, physiological responses to sigma receptor ligands are mediated by a protein with the same molecular weight as the cloned sigma receptor. This indicates that ion channel modulation is indeed mediated by this novel protein. Physiological responses were the same when cells were perfused internally with either guanosine 5'-O-(2-thiodiphosphate) or GTP, indicating that signal transduction is independent of G-proteins. These results demonstrate that ion channels can be modulated by a receptor that does not have seven membrane-spanning domains and does not employ G-proteins. Sigma receptors thus modulate ion channels by a novel transduction mechanism.

Antipsychotic Agents↗

PubMed1999

Novel bioartificial liver support system: preclinical evaluation.

Preclinical safety and efficacy evaluation of a novel bioartificial liver support system (BLSS) was conducted using a D-galactosamine canine liver failure model. The BLSS houses a suspension of porcine hepatocytes in a hollow fiber cartridge with the hepatocytes on one side of the membrane and whole blood flowing on the other. Porcine hepatocytes harvested by a collagenase digestion technique were infused into the hollow fiber cartridge and incubated for 16 to 24 hours prior to use. Fifteen purpose-bred male hounds, 1-3 years old, 25-30 kg, were administered a lethal dose, 1.5 g/kg, of D-galactosamine. The animals were divided into three treatment groups: (1b) no BLSS treatment (n = 6); (2b) BLSS treatment starting at 24-26 h post D-galactosamine (n = 5); and (2c) BLSS treatment starting at 16-18 h post D-galactosamine (n = 4). While maintained under isoflurane anesthesia, canine supportive care was guided by electrolyte and invasive physiologic monitoring consisting of arterial pressure, central venous pressure, extradural intracranial pressure (ICP), pulmonary artery pressure, urinary catheter, and end-tidal CO2. All animals were treated until death or death-equivalent (inability to sustain systolic blood pressure > 80 mmHg for 20 minutes despite massive fluid resuscitation and/or dopamine administration), or euthanized at 60 hours. All animals developed evidence of liver failure at 12-24 hours as evidenced by blood pressure lability, elevated ICP, marked hepatocellular enzyme elevation with microscopic massive hepatocyte necrosis and cerebral edema, elevated prothrombin time, and metabolic acidosis. Groups 2b and 2c marginally prolong survival compared with Group 1b (pairwise log rank censored survival time analysis, p = 0.096 and p = 0.064, respectively). Since survival times for Groups 2b and 2c are not significantly different (p = 0.694), the groups were combined for further statistical analysis. Survival times for the combined active treatment Groups 2b and 2c are significantly prolonged versus Group 1b (p = 0.047). These results suggest the novel BLSS reported here can have a significant impact on the course of liver failure in the D-galactosamine canine liver failure model. The BLSS is ready for Phase I safety evaluation in a clinical setting.

Animals↗

PubMed1999

Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses.

The fate of cells exposed to ionizing radiation (IR) may depend greatly on changes in gene expression, so that an improved view of gene induction profiles is important for understanding mechanisms of checkpoint control, repair and cell death following such exposures. We have used a quantitative fluorescent cDNA microarray hybridization approach to identify genes regulated in response to 7-irradiation in the p53 wild-type ML-1 human myeloid cell line. Hybridization of the array to fluorescently-labeled RNA from treated and untreated cells was followed by computer analysis to derive relative changes in expression levels of the genes present in the array, which agreed well with actual quantitative changes in expression. Forty-eight sequences, 30 not previously identified as IR-responsive, were significantly regulated by IR. Induction by IR and other stresses of a subset of these genes, including the previously characterized CIP1/ WAF1, MDM2 and BAX genes, as well as nine genes not previously reported to be IR-responsive, was examined in a panel of 12 human cell lines. Responses varied widely in cell lines with different tissues of origin and different genetic backgrounds, highlighting the importance of cellular context to genotoxic stress responses. Two of the newly identified IR-responsive genes, FRA-1 and ATF3, showed a p53-associated component to their IR-induction, and this was confirmed both in isogenic human cell lines and in mouse thymus. The majority of the IR-responsive genes, however, showed no indication of p53-dependent regulation, representing a potentially important class of stress-responsive genes in leukemic cells.

Animals↗

PubMed1999

An Approach of a Nonlinear Dynamic Model for Micellar Effects on Bimolecular Reactions.

The effects of micellar solutions on bimolecular reactions were studied in detail using a newly established nonlinear dynamic model with a far-from-equilibrium reaction scheme, by which the incorporation of organic substrates with the micellar phase was imitated. Through the linear stability analysis of the steady state solutions given by the rate equation of the change of substrate concentration within a micellar phase with time, it leads to some explicit relationships between the incorporated substrate concentration and the relevant parameters. Based on this model the micellar effects on the kinetics of the alkaline hydrolysis of esters have been interpreted. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

The binding interface between an E2 (UBC9) and a ubiquitin homologue (UBL1).

Human UBC9 is a member of the E2 (ubiquitin conjugation enzyme) family of proteins. Instead of conjugating to ubiquitin, it conjugates with a ubiquitin homologue UBL1 (also known as SUMO-1, GMP1, SMTP3, PIC1, and sentrin). UBC9 has been shown to be involved in cell cycle regulation, DNA repair, and p53-dependent processes. The binding interfaces of the UBC9 and UBL1 complex have been determined by chemical shift perturbation using nuclear magnetic resonance spectroscopy. The binding site of UBL1 resides on the ubiquitin domain, and the binding site of UBC9 is located on a structurally conserved region of E2. Because the UBC9-UBL1 system shares many similarities with the ubiquitin system in structures and in conjugation with each other and with target proteins, the observed binding interfaces may be conserved in E2-ubiquitin interactions in general.

Humans↗

PubMed1999

Optical properties of an ionic-type phononic crystal

An ionic-type phononic crystal composed of two ferroelectric media with opposite spontaneous polarization aligned periodically in a superlattice structure was studied theoretically and experimentally. The coupling between vibrations of the superlattice and the electromagnetic waves results in various long-wavelength optical properties, such as microwave absorption, dielectric abnormality, and polariton excitation, that exist originally in ionic crystals. The results show that this artificial crystal structure can be used to simulate the microscopic physical processes in real crystals.

Journal Article↗

PubMed1999

Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production.

Thalidomide, (1), is a known inhibitor of TNF-alpha release in LPS stimulated human PBMC. Herein we describe the TNF-alpha inhibitory activity of amino substituted analogs of thalidomide (1) and its isoindolin-1-one analog, EM-12 (2). The 4-amino substituted analogs were found to be potent inhibitors of TNF-alpha release in LPS stimulated human PBMC.

Blood↗

PubMed1999

[Study on the existence, distribution and bioaccumulation of chlorophenols in crucian carps].

Four representative chlorophenols (CPs) and their conjugates in fish tissues were determined by gas chromatography with electron capture detector(GC-ECD). Crucian carps were exposed to water contaminated with CPs or not contaminated water separately at room temperature(22 +/- 5 C) for 96 h. If the contaminated water samples are continuously replaced at 24 h interval, the concentration of CPs can be maintained constant throughout the experiment. The presence of fish will not have influence on the concentration of CPs. The experiment results showed that both free and conjugated CPs existed in fish tissues. The total amount of these chlorophenols in fish tissues is bile > liver and kidney > muscle. The proportion of conjugated CPs increases with the number of chlorine atoms in each compound, nevertheless, the proportion of conjugated CPs in PCP is less than that of TCP. Conjugated CPs in bile are composed of glucuronide and sulfate ester conjugates, and glucuronide conjugate is over 93%. The bio-accumulation of CPs in fish tissues is expressed by bio-concentration factors (BCF). The BCF abstained from free CPs and their sulfate ester conjugate in bile has no correlation with the partition coefficient of 1-octanol/water system(Kow). On the other hand, a good correlation is observed between BCF and Kow abstained from glucuronide conjugate and total amount of CPs(r > 0.96). The bioconcentration factors(BCF) of CPs in bile are 2.0 x 10(3)-6.3 x 10(3).

Animals↗