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Biomedical subjects

S L Chan

Publications and source records attributed to S L Chan.

At least 109 records · Page 6Linked to original sources
PubMed1993

Stimulation of insulin secretion by the imidazoline alpha 2-adrenoceptor antagonist efaroxan is mediated by a novel, stereoselective, binding site.

We have studied the stereospecificity of three responses mediated by the alpha 2-antagonist efaroxan in rat islets of Langerhans. alpha 2-Adrenergic inhibition of insulin secretion was relieved most effectively by the (+) enantiomer. In contrast, direct stimulation of insulin secretion and antagonism of the inhibitory effects of diazoxide were both preferentially mediated by the (-) enantiomer. Culture of islets in the presence of efaroxan resulted in loss of responsiveness to subsequent re-addition of the drug. On the basis of these results we propose the existence, in islets, of a novel 'non-adrenergic' binding site at which efaroxan acts as an agonist.

Adrenergic alpha-Antagonists↗
PubMed1993

Application of DNA fingerprinting with IS986 to sequential mycobacterial isolates obtained from pulmonary tuberculosis patients in Hong Kong before, during and after short-course chemotherapy.

A total of 266 Mycobacterium tuberculosis isolates were subjected to DNA RFLP analysis. They were obtained from monthly sputum cultures from patients treated with short-course chemotherapy and then followed up for 2 years. They originated from 42 patients who relapsed after short-course chemotherapy and from a further 42 patients who yielded a single isolated positive culture after chemotherapy. The isolates consisted of one obtained pretreatment and the last obtained during chemotherapy, together with either two isolates cultured at least 2 months apart during relapse or the single post-chemotherapy isolate. They were coded before DNA RFLP analysis and assigned to groups with identical or near identical band patterns on visual inspection. After decoding, it was evident that almost every patient was infected with a strain with a different band pattern (fingerprint). In 100 comparisons of either the pretreatment isolate against the last positive isolate obtained during chemotherapy, or of the first relapse isolate against the second relapse isolate, 15 had been recorded as different; 4 of these were retrospectively found to be due to reading error (error rate 1.5%), leaving 11 (11%) with marked differences. For 5 (12%) of the 42 patients who relapsed, the fingerprint of the relapse isolate was markedly different from that of the pretreatment isolate. In contrast, the isolated positive culture was markedly different from that initially present in 36 (90%) of 40 comparisons. The relative contributions by clinical mixed infection and laboratory cross-contamination to the remaining 10-12% discrepancy rates could not be assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗
PubMed1993

Antagonism of the stimulatory effects of efaroxan and glibenclamide in rat pancreatic islets by the imidazoline, RX801080.

1. The imidazoline alpha 2-adrenoceptor antagonist, efaroxan, stimulates insulin secretion from rat isolated islets and antagonizes the ability of diazoxide to inhibit glucose-induced insulin secretion. These effects result from closure of ATP-sensitive potassium channels although the mechanisms involved have not been elucidated. 2. In the present work, we have examined the effects of a close structural analogue of efaroxan, RX801080, in rat isolated islets of Langerhans. RX801080 was found to be ineffective as a stimulator of insulin secretion and did not prevent the inhibition of insulin secretion mediated by diazoxide. 3. RX801080 acted as an antagonist of the actions of several imidazolines (efaroxan, phentolamine and midaglizole) in rat islets. It dose-dependently inhibited the ability of efaroxan to antagonize the effects of diazoxide in islets and also completely inhibited the direct stimulation of insulin secretion mediated by efaroxan. 4. RX801080 also antagonized the effects of the non-imidazoline, ATP-sensitive potassium channel blocker, glibenclamide, in rat islets. It inhibited both the capacity of glibenclamide to stimulate insulin secretion and the ability of glibenclamide to overcome the inhibitory effects of diazoxide in rat islets. 5. Antagonism of glibenclamide responses by RX801080 was not due to inhibition of binding of the sulphonylurea to its receptor on the pancreatic beta-cell. 6. The results suggest that imidazoline compounds and sulphonylureas interact with distinct binding sites on islet cells, but that these sites can interact functionally to control islet cell ATP-sensitive potassium channel activity and insulin secretion.

Adrenergic alpha-Antagonists↗
PubMed1993

Outcome of care. Complications from radiation therapy treatment.

This study was undertaken to examine radiation treatment complications. From September 1987 through December 1989, 29,380 patients were screened at their follow-up visits for possible radiation complications. Of these patients, 1,380 were singled out for further study. These 1,380 charts were examined by a radiation oncologist and physicist to determine if there was a radiation complication, the severity of the complication, and whether a calculation or setup error could account for the complications. Of the 1,380 patients studied, 178 (3% of new patients treated each year) were determined to have radiation complications. These complications were divided into four categories of severity and entered into our computerized tumor registry as follows: complication type R1, complete recovery from symptoms, n = 59; R2, injury requiring medications to control injury, n = 104; S1, surgical intervention for one organ, n = 12; and S2, surgical intervention for two organs, n = 3. We believe that a baseline complication rate of 5% is acceptable in radiation oncology practices. However, the examination and documentation of the outcome of care in the form of radiation complications can help improve patient care and keep the radiation oncologist abreast of treatment outcome trends in the department.

Dose-Response Relationship, Radiation↗
PubMed1992

Ligand atom partial charges assignment for complementary electrostatic potentials.

The design of molecules to fit into the active site of receptors is a rapidly developing area of pharmacology and medicinal chemistry. A good ligand needs a suitable geometry and also appropriate electrostatic properties. The electrostatic properties of the ligand should complement those of the receptor. We present a method for the assignment of atom-centred point charges for a ligand, based on the electrostatic potential of the receptor. These point charges are chosen to give the best possible complementarity to the receptor electrostatic potential over the van der Waals surface of the ligand. We demonstrate that point charges can be chosen to give good electrostatic complementarity, and suggest that a molecule with similar electrostatic properties should bind well to the receptor.

Binding Sites↗
PubMed1992

Immunoprecipitation of a pertussis toxin substrate of the G(o) family from rat islets of Langerhans.

Rat islets express a pertussis toxin sensitive G-protein involved in receptor-mediated inhibition of insulin secretion. This has been assumed previously to represent "G(i)" which couples inhibitory receptors to adenylate cyclase. Incubation of islet G-proteins with 32P-NAD and pertussis toxin resulted in the labelling of a band of molecular weight 40,000. This band was very broad and did not allow resolution of individual components. Incubation of the radiolabelled proteins with an anti-G(o) antiserum resulted in specific immunoprecipitation of a 32P-labelled band. These results demonstrate that the complement of pertussis toxin sensitive G-proteins in rat islets includes G(o).

Adenylate Cyclase Toxin↗
PubMed1992

The early bactericidal activity of rifabutin measured by sputum viable counts in Hong Kong patients with pulmonary tuberculosis.

Previously untreated patients with smear-positive pulmonary tuberculosis were randomly allocated to treatment with 600, 300, 150 or 75 mg doses of rifabutin (LM427, ansamycin), 600, 300 or 150 mg of rifampicin, 300 mg isoniazid or to no drug daily for 2 days. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days, termed the early bactericidal activity (EBA), was estimated from counts of colony-forming units (cfu) on selective 7H-11 agar medium. The EBA for rifabutin ranged from -0.039 (an increase in counts) to 0.049 log10 cfu/ml/day whereas the EBA increased from 0.071 for 150 mg rifampicin to 0.293 log10 cfu/ml/day for 600 mg rifampicin and was 0.43 log10 cfu/ml/day for 300 mg isoniazid. The difference between the EBAs for rifabutin and rifampicin just attained significance (P = 0.05) suggesting that rifabutin was inactive or less active than rifampicin against the extracellular bacilli in pulmonary cavities. Peak plasma concentrations of rifabutin after the initial doses were found to be proportional to dose size and were approximately 7 times lower than those after the same dose size of rifampicin. The lower EBA of rifabutin as compared to rifampicin is probably due to the low plasma concentrations which are not fully compensated for by slightly greater antituberculosis activity of rifabutin in vitro.

Adolescent↗
PubMed1992

Predictors of mortality in silicosis.

The mortality of a cohort of 1487 male patients with silicosis in a population-based register followed up from 1980 to 1986 was evaluated with reference to the mortality rates of the general male population. A striking excess of deaths from all causes (observed 368, standardized mortality ratio, SMR 3.00) was noted. Seventy-four percent of the deaths were due to respiratory conditions and complications directly or indirectly related to silicosis. The risk of death was especially higher than expected in younger patients under 45 years of age. Patients with simple silicosis of profusion category 1 did not appear to be at any increased risk of death relative to the general population, but increasing excesses of death were associated with greater extent of simple and conglomerate disease. These increased mortality risks were observed in tuberculosis-free patients as well as in those who never smoked. For the same extent of silicotic disease, the risk of death was higher if tuberculosis occurred. There was no evidence, however, that patients who smoked were more likely to suffer a worse mortality outcome than those who did not. Age at diagnosis, extent of silicotic disease and the occurrence of tuberculosis were therefore strong predictors of mortality in patients with silicosis.

Adult↗
PubMed1992

Lung function in relation to silicosis and silica exposure in granite workers.

Lung function tests (forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC %) were related to silica exposure and the extent of radiological opacities in a study of 206 active and 132 previously employed granite workers from two quarries. The investigations included detailed personal interviews, spirometric testing and radiographic examination of the chest. The chest X-ray films were read randomly and independently by three readers, using International Labour Office (ILO) standard films. Cumulative exposure to respirable silica (mg.m-3-yr) and total granite dust (million particles per cubic foot (mppcf-yr)) were estimated for each subject based on his years of employment at various jobs and historical and current measurements of quarry-, period- and job-specific exposures. The results suggest that chronic simple silicosis, especially for profusion category 2 and 3, was associated with significant lung function loss. As expected, mixed dust fibrosis was associated with little or no functional disturbance. Massive fibrosis was associated with significant obstructive and restrictive impairment. No additional effect of exposure to respirable silica on lung function loss was found after allowing for the presence of "silicosis". However, exposure to total dust (mppcf-yr) appeared to be associated with some lung function loss independent of silicosis. Our results indicate that chronic simple silicosis is not a benign disease; silica exposure is the primary cause, but the lung function loss in silicotics is directly attributable to the fibrotic lung disease. However, exposure to total granite dust beyond the respirable size range may separately produce additional lung function loss.

Adult↗
PubMed1991

The alpha 2-adrenoceptor antagonist efaroxan modulates K+ATP channels in insulin-secreting cells.

The actions of efaroxan, a highly selective and potent alpha 2-adrenoceptor antagonist, on insulin secretion, cAMP levels, 86Rb+ efflux and ATP-regulated potassium (K+ATP) channels have been studied using isolated pancreatic islets of Langerhans and RINm5F cells. In the absence of an adrenoceptor agonist, efaroxan (1-100 microM) potentiated glucose-induced secretion over the range 4-10 mM glucose, but was without effect upon the maximal rate of secretion induced by 20 mM glucose. Efaroxan did not affect cAMP levels. Suppression of insulin release by the potassium channel opener diazoxide, was partially alleviated by efaroxan and was associated with an inhibition of the diazoxide-induced increase in the rate of 86Rb+ efflux. Using isolated patches of membrane we found efaroxan to be an effective blocker of K+ATP channels, with a KI value of 12 microM and a Hill coefficient of approximately 1. These data indicate that efaroxan promotes insulin secretion, in the absence of exogenous agonists, by a mechanism that involves inhibition of ATP-regulated K+ channels.

Adenosine Triphosphate↗
PubMed1991

Mechanisms involved in stimulation of insulin secretion by the hypoglycaemic alpha-adrenergic antagonist, DG-5128.

The selective alpha 2-antagonist DG-5128 provoked a dose-dependent stimulation of insulin release from isolated rat islets. DG-5128 was only weakly effective as an antagonist of noradrenaline-induced inhibition of insulin secretion but, surprisingly, was able to reverse the suppression of secretion and increase in 86Rb efflux from preloaded islets, mediated by diazoxide. These effects were not reproduced with more effective alpha-antagonists, suggesting that stimulation of insulin secretion by DG-5128 is independent of alpha-receptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1991

Factors associated with massive fibrosis in silicosis.

Data on 1432 patients with silicosis on a register in Hong Kong were analysed to examine the association of massive fibrosis with possible predisposing factors. Detailed occupational and clinical histories, clinical records, radiographic readings according to the International Standard Classification of Radiographs of Pneumoconioses, and environmental dust measurements from hygiene surveys were used to obtain information for several variables--namely, age at first exposure, relative dust exposure level, duration of exposure, smoking, previous recorded history of tuberculosis, and background profusion of small opacities. The most significant risk factors associated with massive fibrosis were high relative dust exposure level, a history of tuberculosis, and increased background profusion of small opacities.

Adult↗
PubMed1991

Purification of transferrins and lactoferrin using DEAE affi-gel blue.

1. A simple method for purifying transferrins and lactoferrin is described. 2. The method consists of a preliminary step of dye-ligand chromatography using DEAE Affi-Gel Blue as the gel matrix at pH 7.5. In this chromatographic step, the transferrins and lactoferrin were readily separated from the bulk of the other proteins by start buffer elution. 3. Differences in the chromatographic behaviour of the various serum transferrins (monkey, human, rabbit, pig, chicken and duck) and ovotransferrin upon DEAE Affi-Gel Blue chromatography can be attributed to differences in the anionic charge of the transferrins in 0.02 M potassium phosphate buffer, pH 7.5, thus resulting in the differential retardation of these protein molecules by the gel matrix. 4. The result of DEAE Affi-Gel Blue chromatography of human lactoferrin is different from that for the transferrins. This may possibly reflect the differences in the strength of interaction between lactoferrin and transferrin with this gel matrix.

Amino Acid Sequence↗
PubMed1990

Stimulation of insulin secretion by efaroxan may involve interaction with potassium channels.

The imidazoline alpha 2-antagonist efaroxan was found to stimulate insulin secretion from isolated rat pancreatic islets incubated in glucose concentrations between 4 and 12 mM. This response could not be attributed to interaction of efaroxan with either classical alpha 2-receptors or with a B-cell 'imidazoline receptor', since the effect was not reproduced by the structural analogue idazoxan. Stimulation of insulin secretion by efaroxan correlated with the ability of the drug to reverse the inhibition of secretion mediated by the potassium channel agonist diazoxide. The data suggest that the capacity of efaroxan to stimulate insulin secretion may be related to an interaction with potassium channels in the pancreatic B-cell.

Animals↗
PubMed1990

Mortality of a cohort of men in a silicosis register: further evidence of an association with lung cancer.

Lung cancer mortality from 1980 to 1986 was studied in a cohort of 1,419 men in a silicosis register who had no previous exposure to asbestos and polyaromatic hydrocarbons. The 28 deaths from lung cancer were statistically in excess of expected (SMR 2.03; 95% CI 1.35-2.93). Excess risks of lung cancer were found in both underground workers (SMR 3.41; 95% CI 1.10-7.97; based on 5 deaths) and surface workers (SMR 1.87, 95% CI 1.18-2.81; based on 23 deaths). All lung cancer deaths were smokers. There was an increase in SMRs with longer latency periods and years of exposure, with the greatest risk found in those who had worked for 30 or more years after more than 30 years since first exposed (SMR 3.07, based on 16 deaths). The risk for lung cancer was higher in those with tuberculosis (SMR 2.52; 95% CI 1.52-3.94) and showed an increasing trend with severity of silicosis, from category 1 to 3 and from category A to C, with highest risk in those with tuberculosis and category 3 (SMR 4.44 based on 3 deaths) or tuberculosis and category C (SMR 7.63 based on 7 deaths). Most of the excess lung cancer risk in silicotics is due to smoking, but a synergistic effect between smoking and silica/silicosis on the risk of lung cancer is also likely. In particular, a possible role of silicosis and tuberculosis as the fibrotic seedbed for malignant growth in the lung is strongly supported.

Adult↗
PubMed1990

Serodiagnosis of tuberculosis using an ELISA with antigen 5 and a hemagglutination assay with glycolipid antigens. Results in patients with newly diagnosed pulmonary tuberculosis ranging in extent of disease from minimal to extensive.

Hemagglutination tests with three glycolipid antigens, A1, B1, and C, and ELISA with antigen 5 were done on serum from Chinese patients with pulmonary tuberculosis and from normal subjects in Hong Kong. Tests with all four antigens were of similar efficiency, giving positive results in 30 to 52% of 88 smear-positive patients, in 16 to 22% of 37 smear-negative, culture-positive patients, in 5 to 13% of 76 culture-negative patients with radiologically active disease, in 5 to 11% of 217 culture-negative patients with inactive disease, and in 1 to 4% of 140 normal subjects. If tests were combined so that an overall positive was scored when all tests were positive, there was worse discrimination between patients and normal subjects; however, as suggested by the poor correlation between the results with pairs of the tests, better discrimination was obtained if an overall positive was scored when any of the tests was positive. A positive result in any of the four tests was found in 22% of all cases, including 58% of smear-positive patients, 32% of smear-negative, culture-positive patients, and 0.7% of normal subjects.

Antigens, Bacterial↗
PubMed1990

Nosocomial tuberculosis in hospital staff. The size of the problem in a Hong Kong chest hospital.

In the past three decades, among 831 staff (over 6,862 staff-years) under regular chest radiographic survey in the Grantham Hospital, Hong Kong, the cumulative incidence of active pulmonary tuberculosis requiring treatment was 27 (belonging to 23 staff). Number of cases detected per year ranged from 0 to 3. The mean duration from the beginning of employment to the first evidence of disease was 6.43 years. Although this incidence is low, yet the hospital caters for quite a large number of patients with bacteriologically confirmed tuberculosis, we feel that the active screening program for hospital staff should be maintained, and that review of the situation is also recommended.

Adolescent↗