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W M Chan

Publications and source records attributed to W M Chan.

50 records · Page 3Linked to original sources
PubMed1998

Glycolytic pathway intermediates activate cardiac ryanodine receptors.

During myocardial ischaemia and reperfusion, enhancement of glycolytic activity occurs and this may lead to fluctuating levels of glycolytic intermediates. We demonstrate that sugar phosphate intermediates of glycolysis, particularly fructose-1,6-diphosphate (FDP; 100 microM-10 mM), can activate sheep cardiac ryanodine receptor (RyR) channels incorporated into bilayers (open probability (Po) increases up to approximately 0.6) and stimulate [3H]ryanodine binding (> 200%) to isolated cardiac sarcoplasmic reticulum (SR) membrane vesicles. The relative effectiveness of the sugar phosphates in stimulating [3H]ryanodine binding and increasing the Po of the channels was FDP > glucose-1-phosphate (G-1-P) > fructose-6-phosphate (F-6-P) > glucose-6-phosphate (G-6-P). These novel properties of the sugar phosphate compounds indicate that changes in glycolytic flux may influence the release of SR Ca2+ by modulating RyR channel gating.

Animals↗
PubMed1998

Beta blockers in heart failure: a comparison of a vasodilating beta blocker with metoprolol.

OBJECTIVE: To determine whether a third generation vasodilating beta blocker (celiprolol) has long term clinical advantages over metoprolol in patients with chronic heart failure. DESIGN: A double blind placebo controlled randomised trial. SETTING: University teaching Hospital. PATIENTS: 50 patients with stable chronic heart failure (NYHA class II-IV) due to idiopathic dilated, ischaemic, or hypertensive cardiomyopathy, with left ventricular ejection fraction < 0.45. INTERVENTIONS: Celiprolol 200 mg daily (n = 21), metoprolol 50 mg twice daily (n = 19), or placebo (n = 10) for three months with a four week dose titration period. After the double blind period, patients entered an open label study (with placebo group receiving beta blockers) and were assessed after one year. MAIN OUTCOME MEASURES: Clinical response, efficacy, and tolerance were assessed by the Minnesota heart failure symptom questionnaire six minute walk test, Doppler echocardiography (systolic and diastolic function), radionuclide ventriculography, and atrial and brain natriuretic peptides measured at baseline and after three months. RESULTS: In the metoprolol group at 12 weeks v baseline there was a 47% reduction in symptom score (p < 0.001), improvement of NYHA class (mean (SEM), 2.6 (0.12) to 1.9 (0.13), p = 0.001), exercise distance (1246 (54) to 1402 (52) feet, p < 0.001), and left ventricular ejection fraction (26.9(3.1)% to 31(3.0)%, p = 0.016), and a fall in heart rate (resting, 79 (3) to 62 (3) beats/min, p < 0.001). In the celiprolol group there was a 38% reduction in symptom score (p = 0.02), less improvement in exercise distance (1191 (55) to 1256 (61) feet, p = 0.05), and no significant changes in NYHA class, left ventricular ejection fraction, or heart rate. Mortality at one year was 11% in metoprolol and 19% in the celiprolol group, and symptomatic improvement was maintained in the survivors. CONCLUSIONS: Both drugs were well tolerated but the vasodilator properties of celiprolol do not seem to provide any obvious additional benefit in the long term treatment of heart failure.

Adrenergic beta-Antagonists↗
PubMed1992

Modulation of cell cycle kinetics in human cancer with total parenteral nutrition.

Prior DNA flow cytometric data from the laboratory of the Division of Surgical Oncology, Massey Cancer Center, demonstrated an increase in the hyperdiploid compartment of tumor cells taken from patients with squamous cell carcinoma of the head and neck after a course of total parenteral nutrition (TPN). To assess a putative increase in the percentage of tumor cells actively synthesizing DNA in this system, the authors administered bromodeoxyuridine (BrdU) intravenously to ten patients before and after the administration of TPN. Cell suspensions prepared from biopsy specimens of normal oral mucosa and tumor tissue were analyzed with flow cytometric study. Before TPN administration, the mean percentage of tumor cells incorporating BrdU was 2.47 +/- 1.11%. After TPN administration, the percentage of S-phase cells increased significantly (P less than 0.05) to a mean of 4.52 +/- 2.67%. Before TPN was given, normal mucosa demonstrated a mean of 7.97 +/- 2.69% of cells incorporating BrdU. After TPN was given, a mean of 8.47 +/- 2.51% was seen (not significant [NS]). A potential strategy for the use of TPN to enhance tumor cell susceptibility to S-phase-specific chemotherapy is strongly suggested by these data.

Adult↗
PubMed1986

Effects of parenteral nutrition on cell cycle kinetics of head and neck cancer.

We attempted to determine whether nutritional supplementation with total parenteral nutrition (TPN) of malnourished patients with untreated squamous cell carcinoma of the head and neck alters tumor growth. Fourteen patients underwent biopsies of normal and malignant tissues and were then placed in either a control or adjuvant TPN group. Nutritional parameters and biopsies were repeated over the ensuing three to 17 days. Biopsy specimens were analyzed by flow cytometry for changes in the percentage of hyperdiploid cells (PHC) and aneuploidy. The PHC of tumor biopsy specimens in patients given TPN increased significantly from 15.1 +/- 2.0 to 27.3 +/- 3.3, while no such change occurred in normal mucosa. The PHC after TPN was significantly greater in the patients with cancer than that observed in the controls. These data demonstrate that TPN may have a stimulatory effect on tumor cell cycle kinetics in humans.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Endothelium-dependent dilation of the coronary arteries in syndrome X: effects of the cold pressor test.

The coronary flow reserve is abnormal in syndrome X, but the response to the cold pressor test, which in normals produces flow-mediated endothelium-dependent epicardial coronary dilation, has not been studied. In this study, in 12 patients with typical syndrome X and angiographically normal coronary arteries, the response to the cold pressor test was abnormal with a mean fall in diameter (10 +/- 8%) in 6 patients, no change in 1, and a minimal increase (4 +/- 2%) in 5 patients (normal increase 12 +/- 1%). The coronary blood flow fell slightly during the cold pressor test, and the coronary vascular resistance increased significantly (from 2.4 +/- 1.1 to 3.2 +/- 1.7 mm Hg/cm.s-1.mm2; p = 0.05), both abnormal responses. This study confirms that in syndrome X patients there is coronary endothelial dysfunction which is apparent in response to physiological stimuli induced by the cold pressor test.

Adult↗