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Biomedical subjects

Y L Chen

Publications and source records attributed to Y L Chen.

At least 109 records · Page 6Linked to original sources
PubMed1998

alpha-Methylene-gamma-butyrolactones: synthesis and vasorelaxing activity assay of coumarin, naphthalene, and quinoline derivatives.

Certain alpha-methylene-gamma-butyrolactone derivatives of coumarin, naphthalene, and quinoline were synthesized and evaluated for vasorelaxing effects on isolated rat thoracic aorta. The 7-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2-furanyl)methoxy]-2H- 1- benzopyran-2-ones, which have an aliphatic methyl substituent at the lactone C2, were more active than their C2-phenyl counterparts against high-K+ (80 mM) medium, Ca2+ (1.9 mM)-induced vasoconstriction and the norepinephrine (NE, 3 microM)-induced phasic and tonic constrictions (2a vs. 2b; 2c vs. 2d; 2e vs. 2f; 2g vs. 2h). Although 3-chloro-7-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2- furanyl)methoxy]-4-methyl-2H-1-benzopyran-2-one (2g) demonstrated the most potent inhibitory activities on the NE-induced phasic and tonic constrictions at concentrations of as low as 10 micrograms/ml, it possesses both affinity for NE-receptor and intrinsic activity to trigger the vasoconstriction. However, 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2- furanyl)methoxy]quinoline (10a) and other quinoline derivatives (11a, 12a) are pure irreversible non-competitive blockers of NE-receptor with no intrinsic activity. The aromatic ring played an important role in the vasorelaxing effects of alpha-methylene-gamma-butyrolactones; naphthalene was inactive, quinolines exhibited only affinity to the alpha-receptor, and coumarins possessed both affinity and intrinsic activity.

4-Butyrolactone↗
PubMed1998

Genetic analysis of N-acetyltransferase polymorphism in a Chinese population.

AIM: To study the genetic basis of N-acetylatransferase polymorphism in Chinese. METHODS: Genotypes in 120 healthy Han volunteers from 19 provinces of China were assayed. The 3 common mutant alleles (M1, M2, M3) and one normal wild-type (WT) allele of the N-acetyltransferase (NAT2) gene were detected by allele-specific polymerase chain reaction technique. RESULTS: The NAT2 allele frequencies in 120 Chinese (WT = 0.625, M1 = 0.0458, M2 = 0.188, M3 = 0.142) were different (P < 0.01). The NAT2 genotype distribution for all detected combinations of NAT2 alleles in 120 Chinese subjects was consisitent with Hardy-Weinberg equilibrium (chi 2 = 7.27, nu = 8, 0.7 > P > 0.5). Fifty subjects (41.7%) were homozygous wildtypes, 50 subjects (41.7%) were heterozygous mutants, and 20 subjects (16.7%) were homozygous mutants. CONCLUSION: The lower frequency of mutant M1 allele compared with that of Caucasians explains the low frequency of slow acylators in Chinese.

Acetyltransferases↗
PubMed1998

Chinese midlife women's perceptions and attitudes about menopause.

OBJECTIVE: The purpose of this research was to discover and describe the meaning of and attitudes toward menopause in midlife Chinese women in Taiwan. How these women learned about menopause was also explored. DESIGN: Questionnaires were distributed to a convenience sample of 208 Chinese women aged 35 to 55 living in Taiwan; 168 responded. Qualitative data were analyzed using content analysis. Percentage and chi-square were used to examine the quantitative data. RESULTS: The findings revealed that 154 (91.7%) women perceived menopause as a natural phenomenon. No statistically significant differences in attitude toward menopause were found between women grouped by different menopausal levels, by use or not use of hormones, or by religious preference. Some women described menopause as, "no longer young, getting old." Others described menopause as, "wisdom and maturation," "a symbol of achievement," and "a time to start enjoying life." Sixty-eight (40.5%) of the sample indicated they obtained menopausal information from friends and printed materials such as books, newspapers, and magazines. CONCLUSIONS: Study findings indicate that Chinese women in Taiwan perceive menopause in a positive and holistic way. Culturally sensitized Western practitioners can utilize this study's findings to more appropriately individualize care for Chinese midlife women.

Adult↗
PubMed1997

Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: a centrally active corticotropin-releasing factor1 receptor antagonist.

The syntheses of a centrally active nonpeptide CRF1 receptor antagonist 2, butylethyl[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo [2,3-d]pyrimidin-4-yl]amine (CP-154,526), and its analogs 11-14 and [3H]-2 are reported. The in vitro CRF1 receptor binding affinity in the series 2, the pharmacokinetic properties of 2 in rats, and the anxiolytic-like effects of orally administered 2 are presented.

Animals↗
PubMed1997

Antidepressant-like effects of CP-154,526, a selective CRF1 receptor antagonist.

The effects of CP-154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6 -trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine), a selective corticotropin releasing factor (CRF1) receptor antagonist, were examined in the learned helplessness procedure, a putative model of depression with documented sensitivity to diverse classes of antidepressant drugs. Rats were exposed to a series of inescapable foot shocks on three consecutive days and tested in a shock-escape procedure on the fourth day. Animals exposed to 'helplessness' training performed poorly in the shock-escape test compared with control animals not receiving inescapable shocks. CP-154,526 (10-32 mg/kg, intraperitoneally) dose-dependently reversed the escape deficit when administered 60 min prior to the test session, but had no effect on the performance of control rats not receiving prior exposure to inescapable stress. In comparison, the tricyclic antidepressant imipramine (17.8 mg/kg) reversed the escape deficit after repeated, but not acute, administration. These data support evidence implicating stress systems in the pathophysiology of depression, and suggest potential efficacy of small-molecule CRF receptor antagonists in the treatment of affective disorders.

Analysis of Variance↗
PubMed1997

Electron microscopic studies of phenotypic modulation of smooth muscle cells in coronary arteries of patients with unstable angina pectoris and postangioplasty restenosis.

BACKGROUND: Proliferation and matrix protein secretion of coronary smooth muscle cells (SMCs) have been suggested as one of the mechanisms responsible for the development of postangioplasty restenosis and an alternative cause of unstable angina. Phenotypic modulation of SMCs may produce a pool of cells potentially responsive to growth stimulation that can synthesize abundant extracellular matrix. This study tested the hypothesis that phenotypic modulation of SMCs occurred during the evolution of postangioplasty restenosis and unstable angina. METHODS AND RESULTS: The SMCs of coronary atherectomy specimens from 24 patients were identified under electron microscope. Volume fractions of synthetic organelles (VFSOs) and other features related to phenotypic modulation of SMCs were measured. The results showed that the VFSO in SMCs from 5 patients with unstable angina (group 2) resembled those from 9 patients with postangioplasty restenosis (group 3; 0.42 +/- 0.13 versus 0.36 +/- 0.10; P = NS), and both were significantly higher than those from 6 patients with stable angina (group 1; 0.21 +/- 0.11). Four patients with restenosis lesions who underwent angioplasty > 6 months ago (group 4) also had a low VFSO in SMCs (0.19 +/- 0.05). This value was significantly less than those in groups 2 and 3 (P < .05) but similar to that in group 1. CONCLUSIONS: The coronary lesions from patients with unstable angina resembled those from patients with postangioplasty restenosis in terms of the phenotypic modulation and VFSO in SMCs. Our findings therefore suggest that after phenotypic modulation, the SMCs may become responsive to growth stimulation, with an ability to massively proliferate and synthesize abundant extracellular matrix. These processes may lead to plaque expansion and eventually to the development of unstable angina and restenosis.

Aged↗
PubMed1997

Relationship between endothelial cell turnover and permeability to horseradish peroxidase.

The quantitative relations between cell turnover (cell mitosis and death) and macromolecular leakage were studied at the level of individual endothelial cells (ECs) in the thoracic aortae of 32 adult male Sprague-Dawley rats. The experiments were performed on en face preparations of aortic specimens obtained 1, 3, 5 or 10 min after the intravenous administration of horseradish peroxidase (HRP). Mitotic ECs were identified by hematoxylin nuclear staining; dying or dead ECs containing cytoplasmic immunoglobulin G were detected by indirect immunocytochemistry and endothelial leakages to HRP were visualized by light microscopy. The number and size of HRP spots increased with time and the spots fused to form large brown areas in 10 min. Quantitative data on the contributions of EC mitosis and EC death to the transendothelial leakages of HRP were obtained in the same animals. Although mitotic ECs (0.01%) and dying ECs (0.1%) were infrequent in occurrence, the great majority (over 90%) of these ECs were associated with focal HRP uptake. These mitotic and dying ECs, however, accounted for only 17% of the total leakage sites indicating that significant leakage of the 4-5 nm HRP also occurs in normal ECs not morphologically identified as being in mitosis or death. The percentages of leaky spots attributable to mitosis or cell death were greater for the 6 nm albumin and the 22 nm low density lipoprotein (LDL) which probably cannot traverse the normal junctions and use the leaky junctions during cell turnover as the major pathway.

Animals↗
PubMed1997

Generation of infectious virus particles by transient co-expression of human immunodeficiency virus type 1 gag mutants.

We have demonstrated that COS7 cells transiently co-expressing myristylation-defective (Myr-) and protease-defective (PR-) human immunodeficiency virus (HIV) mutants can release infectious virions when co-transfected with an amphotropic murine leukaemia virus envelope protein expression plasmid (SV-A-MLV-env). In contrast, no infectious virions were detected when a PR-, noninfectious HIV gag mutant was co-expressed with the Myr- mutant, although the Myr- mutant could still process the immature core particles in trans. This result indicates that generation of functionally normal Gag proteins is required for virus infectivity in our complementation system. A mutant with a 56-amino-acid deletion in the N-terminal region of the capsid (CA) domain could still complement the PR- mutant to generate infectious virions, suggesting that the deletion mutant could provide a functional protease for processing in the PR- mutant. This result is consistent with the concept that mutations within the N-terminal region of the CA domain have no major effects on Gag-Pol incorporation into particles.

Animals↗
PubMed1997

Evaluation of the antioxidant and hepatoprotective activity of Terminalia catappa.

The free radical scavenging and antihepatotoxic activity from Terminalia catappa was studied. Treatment with T. catappa water extracts showed antihepatotoxic activity against CCl4-induced toxicity in the rat liver that was tested. The crude drug also exhibited anti-oxidant effects in FeCl2-Ascorbic acid induced lipid peroxidation in the rat liver homogenate. Moreover, the superoxide radical scavenger effect of T. catappa was demonstrated using electron spin resonance (ESR) and spintrapping technique. The results indicate that T. catappa possesses good antihepatotoxic activity and superoxide radical scavenger activity.

Animals↗
PubMed1996

Local alcohol delivery may reduce phenotype conversion of smooth muscle cells and neointimal formation in rabbit iliac arteries after balloon injury.

Local delivery of pharmacological agents into the vessel wall has been extensively studied to prevent restenosis after coronary angioplasty. Alcohol solution was found to affect cellular responses to growth stimulation. This study was carried out to examine the effect of local delivery of alcohol solution on intimal proliferation following balloon injury. New Zealand white rabbits of 2-3 kg underwent balloon denudation of bilateral iliac arteries. Following denudation, 2 ml 10% or 15% alcohol solution was infused into one iliac arterial wall using a Wolinsky porous balloon catheter. The other iliac artery of the same animal received local delivery of normal saline and was used as the control. The animals were killed at 2 weeks. The neointimal areas of alcohol treated vascular segments were significantly less than those of control segments in both 10% (n = 10) and 15% (n = 11) groups (65 +/- 16 versus 113 +/- 20 x 10(3) microns2 in 10% group, P < 0.0001; 48 +/- 15 versus 107 +/- 10 x 10(3) microns2 in 15% group, P = 0.002). In order to determine the effect of alcohol solution on smooth muscle cell proliferation, a method of quantifying phenotypic conversion of smooth muscle cells was chosen. This consists of a measurement of volume fraction of the synthetic organelles (VFSO) of vascular smooth muscle cell profiles (SMC) using transmission electron micrographs taken in the animals killed at day 8. The VFSO of SMC of the control sites were significantly greater than those of paired 10% alcohol treated arteries in both intima (0.39 +/- 0.02 versus 0.21 +/- 0.01, P < 0.0001) and media (0.33 +/- 0.03 versus 0.19 +/- 0.02, P < 0.0001). Similar findings were noted in the 15% alcohol treated group. It is concluded that intramural alcohol delivery using porous balloon catheter is effective in reducing neointimal proliferation in rabbit iliac arteries after balloon injury. The mechanisms of action may involve direct inhibition of cellular responses to growth stimulation.

Angioplasty, Balloon↗
PubMed1996

CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors.

Here we describe the properties of CP-154,526, a potent and selective nonpeptide antagonist of corticotropin (ACTH) releasing factor (CRF) receptors. CP-154,526 binds with high affinity to CRF receptors (Ki < 10 nM) and blocks CRF-stimulated adenylate cyclase activity in membranes prepared from rat cortex and pituitary. Systemically administered CP-154,526 antagonizes the stimulatory effects of exogenous CRF on plasma ACTH, locus coeruleus neuronal firing and startle response amplitude. Potential anxiolytic activity of CP-154,526 was revealed in a fearpotentiated startle paradigm. These data are presented in the context of clinical findings, which suggest that CRF is hypersecreted in certain pathological states. We propose that a CRF antagonist such as CP-154,526 could affirm the role of CRF in certain psychiatric diseases and may be of significant value in the treatment of these disorders.

Acoustic Stimulation↗
PubMed1996

Probing the domain structure of abrin-a by tryptic digestion.

Abrin-a is a potent plant toxin that consists of A and B chains linked by a disulfide bond. The abrin-a A chain (AaTA) has N-glycosidase activity while the abrin-a B chain (AaTB) has galactose-binding activity. By partial tryptic digestion, the domain structure of abrin-a was investigated. Seven tryptic fragments with molecular masses greater than 3500 Da were isolated and characterized. One fragment, designated T-21 and consisting of 153 amino acid residues, contained the major part of the second domain of AaTB and, after cross-linking of T-21 with glutaraldehyde, the reaction product had the same level of hemagglutinating activity as native abrin. When the T-21 fragment was conjugated with AaTA, the conjugate inhibited protein biosynthesis in HeLa cells. This suggests that the T-21 fragment is able to bind specifically to cells; its conjugate facilitates membrane translocation of AaTA into cells and consequently inhibits protein biosynthesis. T-21, with a molecular mass less than AaTB, is therefore a potentially useful substance for the preparation of immunotoxins.

Abrin↗
PubMed1996

Increased ferritin gene expression in atherosclerotic lesions.

To identify genes potentially implicated in atherogenesis, a cDNA library was constructed from human atherosclerotic aorta and differentially screened with 32P-labeled-cDNAs prepared from human normal and atherosclerotic aortas. Two cDNA clones exhibiting higher hybridization to the 32P-labeled cDNAs from atherosclerotic vessels were isolated and identified to be genes encoding L-ferritin and H-ferritin, respectively. Northern blot analysis confirmed that the expression of both ferritin genes was notably higher in human and rabbit atherosclerotic aortas than in their normal counterparts. A time-course study illustrated that both L- and H-ferritin mRNAs were markedly increased in aortas of rabbits after feeding with a high cholesterol diet for 6 wk, which was also the time period after which the formation of lesions became evident. In situ hybridization revealed that both L- and H-ferritin mRNAs were induced in endothelial cells and macrophages of human early lesions. The signals were also detected in the smooth muscle cells of advanced lesions. Immunostaining further identified the presence of ferritin protein in atherosclerotic lesions. On the other hand, Prussian blue stain revealed the presence of iron deposits in advanced lesions but not in early human or rabbit lesions. Further experiments with cultured human monocytic THP-1 cells and aortic smooth muscle cells demonstrated that ferritin mRNAs were subjected to up-regulation by treatment with IL-1 or TNF, while TGF, PDGF, and oxidized LDL did not affect the expression of either ferritin gene in both cell lines. Collectively, these results clearly demonstrate that ferritin genes are susceptible to induction in the course of plaque formation.

Animals↗
PubMed1996

Functional and sequence characterization of coagulation factor IX/factor X-binding protein from the venom of Echis carinatus leucogaster.

A new coagulation factor IX/factor X-binding protein (IX/X-bp) from Echis carinatus leucogaster venom has been purified and designated ECLV IX/X-bp. ECLV IX/X-bp binds factor IX and X in a Ca(2+)-dependent manner and is devoid of thrombin-inhibitory and platelet-aggregating activities. The apparent dissociation constants (Kd) for binding of ECLV IX/X-bp to factor IX and factor X are 6.6 and 125 nM, respectively. Upon the addition of Mg2+, the required Ca2+ concentration for optimal binding of ECLV IX/X-bp to factor IX and factor X was prominently reduced. Mg2+ also increases the affinity of factor X for the venom protein. Direct binding of IX/X-bp to factor IX and X could also be detected by far-Western blotting, and results of the experiment ruled out the lectin-like mechanism of ECLV IX/X-bp. The complete amino acid sequence and the disulfide pattern of ECLV IX/X-bp was deduced by enzymatic hydrolysis and automated sequencing of the S-pyridylethylated protein. The venom protein is a heterodimer with one subunit of 131 amino acid residues and another of 125 residues. Both subunits are homologous to each other and to other snake venom proteins of the C-type lectin superfamily.

Amino Acid Sequence↗
PubMed1996

Mutational analysis of HIV-1 Nef: identification of two mutants that are temperature-sensitive for CD4 downregulation.

The Nef protein of HIV-1 is capable of performing at least two functions: reduction of cell-surface expression of CD4, the viral receptor, and enhancement of HIV-1 infectivity. Here we report the results of assays of CD4 downregulation by nef point mutants. Areas of high charge density and highly conserved sequence motifs were targeted. In general, mutations in the carboxyl-terminal half of the protein had more deleterious effects than did those in the amino-terminal half. A single mutant nef allele was identified which encoded a stable protein but was completely inactive. Two mutant Nef proteins exhibited temperature-sensitive phenotypes in assays of CD4 downregulation.

Amino Acid Sequence↗