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W Chiou

Publications and source records attributed to W Chiou.

7 recordsLinked to original sources
PubMed2002

Change in demographic picture and increase of drug resistance in pulmonarytuberculosis in a 10-year interval in Taiwan.

BACKGROUND: This study was designed to compare the change in demographics, medical characteristics and drug resistance of patients with active pulmonary tuberculosis (TB) between two time periods within a 10-year interval. PATIENTS AND METHODS: We retrospectively reviewed the clinical records and chest radiographs of 1,826 patients with active pulmonary TB for two time periods from 1992-1996 (n = 884) and 1982-1986 (n = 942). RESULTS: The mean age was significantly higher and there were significantly more female patients in the 1992-1996 period than in the 1982-1986 period. In the 1992-1996 period, there were significantly fewer patients with the main complaints of cough, fever and body weight loss at the time of diagnosis but significantly more patients who had diabetes mellitus, obstructive airway disease, cancer other than lung cancer or who were on corticosteroid therapy. During the 1992-1996 period, single drug resistance against isoniazid (INH), rifampin (RIF) and streptomycin increased by 0.5%, 3% and 0.7%, respectively. Multiple drug resistance against both INH and RIF increased by 2% in the 1992-1996 period. A history of pulmonary TB and extensive pulmonary involvement were two significant factors for drug resistance against INH, RIF or ethambutol (EMB). CONCLUSION: In the 1992-1996 period, the mean age of patients and number of female patients significantly increased. There were more patients with diabetes mellitus, obstructive airway diseases, cancer other than lung cancer and prior steroid therapy but fewer patients presenting with classic clinical symptoms of TB. In consideration of the high prevalence and increasing rate of single and multiple drug resistance, we recommend an initial four-drug regimen (INH, RIF, EMB, pyrazinamide) for the treatment of pulmonary TB in Taiwan.

Adolescent↗
PubMed1996

Human astrocytoma U138MG cells express predominantly type-A endothelin receptor.

Endothelin-1 (ET-1) binding to human astrocytoma U138MG cells was time-dependent, and bound [125I]ET-1 was difficult to dissociate. The B(max) and Kd values of [125I]ET-1 binding were 70 fmol/mg and 0.07 nM, respectively. Interestingly, different from other astrocytoma cells and astrocytes, the U138MG cells expressed predominantly ETA receptor as shown by RT-PCR results and binding studies. ET-1, FR139317, BQ123, PD142893 and Ro46-2005 inhibited specific [125I]ET-1 binding with Ki values of 0.10, 0.53, 4.3, 22, and 320 nM, respectively. ETB selective ligands ET-3 and IRL1620 were much less potent. The inhibitory effects of antagonists BQ123 and PD142893 on [125I]ET-1 binding diminished following the incubation time. ET-1 binding caused a modest stimulation in phosphatidylinositol hydrolysis with an EC50 value of 24 nM. In comparison to the human U373MG cells, ET-1-induced receptor internalization in U138MG cells was less efficient with 42% of bound ET-1 internalized after 30 min of incubation. These results imply that human astrocytoma cells/astrocytes are able to express either ETA or ETB receptor under different pathophysiological conditions.

Astrocytoma↗
PubMed1996

Azole endothelin antagonists. 1. A receptor model explains an unusual structure-activity profile.

The pseudotetrapeptide FR-139317 is a potent and highly selective antagonist of the endothelin-A (ET(A)) receptor; however, its peptidic nature leads to poor oral absorption characteristics which make it an unlikely drug candidate. In an attempt to improve these properties, we have replaced a portion of the amide bond framework of FR-139317 with a heterocyclic surrogate. The resultant analogs are also ET(A)-selective antagonists, but show a structure-activity profile substantially different from that of the peptidic series, particularly with regard to the requirements for the side chain group that has been incorporated into the heterocycle. The nature of the heterocycle itself also has profound effects on the activity of the compounds. Both of these surprising results can be rationalized through examination of a 3D model of ET ligand--receptor binding that has previously been developed in our laboratories.

Animals↗
PubMed1996

Azole endothelin antagonists. 2. Structure-activity studies.

Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or arylureas led to substantial improvements in activity. Conformational restriction of these groups provides an additional benefit. N-Methylation of the indole moiety which is part of the heterocyclic dipeptide surrogate also improves potency. The effects of these two modifications appear to be synergistic, with the best of the resultant doubly modified analogs (e.g. 14q, 15y, and 15ff) exhibiting an 80-200-fold improvement over the original leads.

Animals↗
PubMed1996

Azole endothelin antagonists. 3. Using delta log P as a tool to improve absorption.

The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter delta log P. Comparison of urea 2 with a series of well-absorbed compounds using delta log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between delta log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NH groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.

Administration, Oral↗
PubMed1993

Identification and characterization of type A endothelin receptors in MMQ cells.

Recently the identification of endothelin (ET) receptors and ET in the pituitary gland has induced much interest in studying the potential role of ET in neuroendocrine regulation. MMQ, isolated from rat pituitary, is a prolactin-secreting cell line. Similar to primary pituitary cells, the secretory response in MMQ cells is regulated by calcium and cAMP. In this report, by combining radioligand binding, cross-linking, and reverse transcription-polymerase chain reaction (RT-PCR) techniques, we characterized the properties of ET receptors in MMQ cells. 125I-ET-1 bound to membranes prepared from MMQ cells in a time-dependent manner, reaching a plateau at 150 min at 25 degrees. 125I-ET-1 binding was inhibited by ET-1 with an IC50 value of 0.17 nM but was only partially (approximately 60%) inhibited by 1 microM ET-3. BQ123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]) and FR139317 (cC6N-L-Leu-D-Trp-Me-D-2Pya-OH), two antagonists that are selective for the ETA receptor, inhibited 125I-ET-1 binding with IC50 values of 5 nM and 0.9 nM, respectively. RT-PCR detected mRNA for the ETA receptor but not the ETB receptor. RT-PCR detected mRNA for both ETA and ETB receptors in control experiments using rat kidney RNA. 125I-ET-1 binding was saturable, reaching a plateau at 0.1 nM. Scatchard analysis of the data from saturation studies yielded a straight line, with Bmax and Kd values of 0.11 pmol/mg and 0.038 nM, respectively. The number of receptors was 6.6 x 10(10) sites/mg of protein or 13,200 sites/cell. Cross-linking studies using bis(sulfosuccinimidyl)suberate revealed an apparent molecular mass of 65 kDa for the ET receptor. Labeling of the 65-kDa protein was abolished by ET-1, BQ123, or FR139317 at 0.1 microM. ET-1 stimulated the formation of total inositol phosphates in a dose-dependent manner, with an EC50 of 0.1 nM. The phosphatidylinositol hydrolysis response was also inhibited by BQ123 and FR139317. We conclude that MMQ cells express the ETA receptor, which is coupled to phosphatidylinositol hydrolysis. MMQ cells may be useful for elucidating the mechanisms through which ET exerts its regulatory effects on pituitary cells.

Animals↗