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Biomedical subjects

S L Chan

Publications and source records attributed to S L Chan.

At least 73 records · Page 4Linked to original sources
PubMed1998

Clonidine-displacing substance and its putative role in control of insulin secretion: a minireview.

1. Imidazoline-binding sites, or I-sites, are a class of recently defined nonadrenoceptor recognition sites whose most potent ligands are imidazolines and related compounds. 2. The pancreatic islet beta-cell I-site, which mediates imidazoline-induced stimulation of insulin release, appears to be the first site to be pharmacologically defined with selective agonists and antagonists. 3. The natural ligand for imidazoline recognition sites is still unknown. The strongest candidate is clonidine-displacing substance (CDS), originally identified in extracts of rat and bovine brain. However, the bioactive molecule has not been identified definitively. Agmatine, a decarboxylated derivative of arginine, also binds to both I-sites and alpha2-adrenoceptors (Li et al., 1994), and is, by definition, a CDS molecule. 4. In the endocrine pancreas, agmatine is a weak insulin secretagogue, which induces a slowly developing secretory response. However, this profile does not correlate with interaction at the islet I-site, and thus agmatine is unlikely to be an endogenous secretagogue acting functionally at the islet I-site. 5. Crude preparations of CDS from rat brain can potentiate glucose-induced insulin release and reverse the effects of diazoxide in rat and human islets of Langerhans. These two effects are also subject to blockade by the imidazoline antagonists RX801080 and KU14R. Furthermore, islets that were desensitized to the effects of the imidazoline secretagogue efaroxan (after 18-hr culture with imidazoline) were refractory to the actions of CDS. 6. Overall, CDS displays many characteristics expected of an endogenous regulator of insulin secretion acting through the islet beta-cell imidazoline site. This evidence strengthens the hypothesis that the islet beta-cell imidazoline site mediating control of insulin release in the endocrine pancreas is a biologically relevant receptor. Furthermore, a physiological role of CDS in the endocrine pancreas cannot be excluded.

Agmatine↗
PubMed1998

Evidence-based care of Chinese men having transurethral resection of the prostate (TURP).

AIM OF STUDY: To measure the effect of specific preoperative information on postoperative anxiety, satisfaction with information, and demand for analgesia, of Chinese males having transurethral resection of the prostate (TURP). DESIGN: A controlled experimental design. The researchers allocated all patients (n = 30) undergoing TURP in a general hospital in Hong Kong, during a 3-month period, to one of two groups. The experimental group (n = 15) received a specific information pamphlet and a general preoperative counselling video. The control group (n = 15) received a video alone. PROCEDURE AND MEASURES: Following ethical approval, a researcher took baseline measures of state and trait anxiety using the Chinese State-Trait Anxiety Inventory (C -STAI). Five days after surgery the researcher administered the C-STAI (A-State), a patients' satisfaction questionnaire, and, recorded requests for analgesia during the first 5 postoperative days. RESULTS: Experimental subjects reported significantly lower anxiety levels post-operatively and a significantly higher level of satisfaction with the preoperative information, than controls. Postoperative demand for analgesia did not significantly differ between groups. CONCLUSIONS: The findings support the importance of providing patients with specific, written preoperative information about their surgery and its effects to minimize their postoperative anxiety levels, and improve their satisfaction with the care provided.

Anxiety↗
PubMed1998

Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Initial report.

A randomized comparison has been made of three times weekly rifampin plus isoniazid (HR3) with rifapentine plus isoniazid given once weekly (HRp1) or on 2 of 3 wk (HRp1.2/3) in the continuation phase of 6-mo regimens (each starting with an initial 2 mo of 4-drug therapy) for the treatment of pulmonary tuberculosis in 672 Chinese patients in Hong Kong. Because of poor bioavailability of the rifapentine used (produced in China), its dose size was increased from 600 mg initially to about 750 mg in the last third of patients to obtain serum concentrations similar to those with rifapentine of Western origin; all doses were given after a meal promoting absorption. After initial exclusions, an intent to treat analysis, done on the remaining 592 patients, showed 45 adverse treatment events in 7 of 190 HR3 patients, in 17 of 199 HRp1 patients, and in 21 of 203 HRp1.2/3 patients; of these, 42 were bacteriological or radiographic relapses after the end of treatment (HR3 versus HRp1, p = 0.04; HR3 versus HRp1.2/3, p = 0.01). Patients with organisms initially sensitive or resistant to isoniazid or streptomycin had similar relapse rates. The high relapse rate in the HRp1 regimen suggests that the rifapentine dose should be increased. Similarity of relapse rates, 8.9% and 10.4%, after the HRp1 and HRp1.2/3 regimens, respectively, indicates that irregularity in taking rifapentine/isoniazid could be tolerated. The few adverse side effects in the continuation phase in the rifapentine regimens were less frequent than in the HR3 regimen.

Adolescent↗
PubMed1998

Long-term trends in tuberculosis. Comparison of age-cohort data between Hong Kong and England and Wales.

The caseload of tuberculosis in developing countries is increasingly associated with the elderly. This is possibly due to increased longevity today and a change in the lifetime risk of tuberculosis within birth cohorts. Published data for tuberculosis notifications for Hong Kong and England and Wales have been used to calculate age-specific rates of disease by different age groups for different birth cohorts. In Hong Kong, each birth cohort showed a similar pattern of disease by age, with rates peaking in the 25 to 39-yr age groups and gradually declining thereafter. After 1978, regardless of age at that time, all age cohorts showed an increase in tuberculosis rates with increasing age. This trend was more marked in males than females. A similar pattern was seen for birth cohorts in England and Wales except that the peak occurred earlier in life (before 25 yr of age) and the decline with age ceased in 1984. Thereafter, rates increased in males born before 1930 but showed only a leveling off in females. If these data represent a true increase in tuberculosis rates, rather than resulting from a change in reporting accuracy and completeness, the burden of tuberculosis in the elderly is likely to continue to increase substantially.

Adolescent↗
PubMed1998

Intermittent intussusception caused by colonic lipoma.

Colonic lipomas are rare, usually small, and occur most often in the right colon, particularly in the cecum. They are most common in elderly women. Intermittent episodes of intussusception are not uncommon in patients with colonic lipoma, but they are usually caused by larger pedunculated lipomas. We report a 43-year-old woman with a large colonic submucosal lipoma that induced intermittent colocolic intussusception. The patient presented with symptoms of peptic ulcer, including intractable upper abdominal pain, which did not resolve with treatment. Abdominal sonography showed typical findings of intussusception caused by a lipoma, but the manifestations on barium enema and computed tomography mimicked a malignant colonic tumor. The patient's abdominal pain disappeared after right hemicolectomy and the tumor was demonstrated to be a lipoma. The postoperative course was uneventful; there was no evidence of recurrence at follow-up 6 months later. Physicians should be aware that surrounding organs should also be evaluated in cases of chronic peptic ulcer with intractable upper abdominal pain.

Adult↗
PubMed1998

Identification of nuclear proteins interacting with the liver-specific enhancer B element of the antifreeze protein gene in winter flounder.

The intron of the winter flounder antifreeze protein (AFP) gene contains a liver-specific enhancer element B as demonstrated by transient expression in mammalian cells. Element B interacts with rat C/EBPalpha and a novel protein, tentatively designated as the antifreeze enhancer-binding protein (AEP). Present studies revealed that nuclear proteins from the winter flounder liver interact similarly and specifically to element B as shown by footprinting analysis and gel retardation assays. The presence of C/EBP in the flounder liver was confirmed by Western blot analysis. In vitro transcription assays in its homologous system further demonstrated the transactivation activity of the AFP gene intron. The present findings suggest that the mechanisms for regulating liver-specific transcription are evolutionarily conserved.

Animals↗
PubMed1997

Ubiquitin (Ub) interacts non-covalently with Alzheimer amyloid precursor protein (betaPP): isolation of Ub-betaPP conjugates from brain extracts.

Ubiquitin (Ub)-immunocytochemistry on Alzheimer's disease (AD) brain sections shows diverse Ub-associated deposits in the neuropil and senile plaques, elevated levels of Ub reactivity in hippocampal neurons and glia, and co-localization of Ub and beta-amyloid precursor protein (betaPP) epitope reactivity in dystrophic axons. These observations may suggest a role for Ub and stress-related mechanisms in AD pathogenesis. Here we show for the first time that Ub interacts avidly but non-covalently with betaPP and such complexes, apparently formed in vivo, can be isolated from AD brain extracts by Ub-gel matrix affinity chromatography. Polyclonal antibodies specific to Ub and to different regions of betaPP were employed to characterize these proteins. The implication of Ub-betaPP complex formation is discussed in the context of betaPP processing.

Aged↗
PubMed1997

The role of CCAAT/enhancer-binding protein alpha and a protein that binds to the activator-protein-1 site in the regulation of liver-specific expression of the winter flounder antifreeze protein gene.

Winter flounder, Pleuronectes americanus, produces antifreeze proteins (AFPs) to avoid freezing during winter. The AFP in the blood is synthesized by the liver and its annual level is regulated by environmental factors and somatotropin. The only intron (+106 to +602) of the AFP gene contains putative binding sites for liver-enriched transcription activators. Due to the lack of an appropriate fish liver cell line, a mammalian model system was used to demonstrate the liver-specific enhancer activity of the intron. Deletion analysis of the intron indicated nucleotide sequences between +192 bp and +334 bp were important for the enhancer activity. Further refinement showed that the element B (+303 to +322 bp) resided in this region interacted with proteins from rat nuclear extracts by DNase I footprinting and mobility shift analysis. Gel retardation with competition and supershift experiments defined element B to include binding sites for CCAAT/enhancer binding protein a (C/EBP alpha), a liver-enriched transcription factor, and a novel activator protein-1 (AP-1) site binding protein, designated as antifreeze enhancer binding protein (AEP). Residues important to DNA-protein interaction in element B were mapped by methylation interference. Mutations in element B by site-directed mutagenesis destroyed the enhancer activity of the intron. Ultraviolet crosslinking experiments using element B revealed the specific binding of two proteins of approximately 43 and 80 kDa. The present findings provide a mechanism(s) by which the tissue specificity of AFP gene expression can be achieved. Integration of the present information with the somatotropin-mediated signal transduction pathways has generated a working model for the hormonal regulation and seasonal expression of the AFP gene.

Animals↗
PubMed1997

Evidence that the ability of imidazoline compounds to stimulate insulin secretion is not due to interaction with sigma receptors.

Recent studies have suggested that a variety of ion channels possess a binding site for ligands such as phencyclidine (PCP), dizocilpine and certain sigma ligands and that some imidazoline compounds can also bind to this site. We have investigated whether interaction with this binding site could account for the ability of imidazolines to stimulate insulin secretion from rat islets. Neither PCP nor dizocilpine shared the insulin secretory activity of the imidazoline efaroxan in rat islets suggesting that they do not have similar actions in the pancreatic B-cell. Further, we were able to define a new antagonist, KU14R (2(2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole), which selectively blocks the insulin secretory response to imidazolines. The results suggest that imidazolines do not stimulate insulin secretion by causing physical blockade of the K(+)-ATP channel in pancreatic B-cells and show that their effects are not reproduced by PCP or sigma receptor ligands.

Adenosine Triphosphate↗
PubMed1997

1-(5-Isoquinolinesulfonyl)-2-methylpiperazine induces apoptosis in human neuroblastoma cells, SH-SY5Y, through a p53-dependent pathway.

We have studied the effect of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a protein kinase inhibitor, on the regulation of apoptosis in the human neuroblastoma cell line, SH-SY5Y. H-7 (20-100 microM) induced apoptosis in these cells characterized by DNA fragmentation and chromatin condensation. Immunoblot analyses were performed with specific antibody against BCL-2, BCL-XS/L, BAX, JUNB, c-JUN, ICH-1L, c-FOS, RB, CDK-2, and p53. H-7 treatment did not significantly alter the level of these proteins with the exception of p53. H-7, but not staurosporine, caused a dramatic nuclear accumulation of p53. The kinetics of nuclear accumulation of p53 correlates well with the kinetics of induction of apoptosis. The effect of H-7 was further assessed in a group of human cell lines. Only cell lines harboring the wild-type p53 gene were responsive to the stimulatory effect of H-7 on nuclear accumulation of p53. Furthermore, cell lines carrying a mutated p53 gene were resistant to the cytotoxic effect of H-7. The ability of H-7 in mediating apoptosis in the SH-SY5Y line expressing a dominant negative mutant of p53 was significantly diminished. Taken together, these data strongly suggest that a p53-dependent mechanism contributes to the cytotoxicity of H-7 in human neuroblastoma cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Clotrimazole and efaroxan stimulate insulin secretion by different mechanisms in rat pancreatic islets.

It is now well established that the imidazoline insulin secretagogue efaroxan mediates its effects by inducing closure of ATP-sensitive potassium channels in the pancreatic beta-cell, leading to membrane depolarisation, Ca2+ influx and increased insulin secretion. However, a recent study has shown that efaroxan may also act as a blocker of a second class of potassium channel (the Kmaxi channel) in red blood cells, raising the possibility that its effects in islets could be mediated by interactions with both types of channel. Since the antimycotic imidazole compound clotrimazole is a highly potent blocker of Kmaxi channels, we have studied the effects of this drug on insulin secretion. Clotrimazole stimulated insulin secretion from rat islets of Langerhans incubated in the presence of 6 mM glucose, in a dose-dependent manner. Experiments performed at different glucose concentrations showed that the actions of clotrimazole were most prominent at low glucose concentrations whereas it did not enhance secretion beyond the rate induced by 20 mM glucose. The insulinotropic action of clotrimazole was temperature dependent but was independent of extracellular calcium. Clotrimazole appeared to block ATP-sensitive potassium channels in islets since, like efaroxan and glibencamide, it was able to prevent the inhibitory effects of diazoxide on glucose-induced insulin secretion. However, neither the direct stimulatory effect of clotrimazole on insulin release nor the abilty of clotrimazole to reverse the inhibitory actions of diazoxide was sensitive to blockade by the imidazoline secretagogue antagonist KU14R. Overall, the results suggest that clotrimazole exerts an insulinotropic effect in pancreatic beta-cells that is distinct from the actions of imidazoline secretagogues such as efaroxan. Clotrimazole can increase insulin secretion at sub-maximal glucose concentrations by an action which appears to be independent of membrane ion channel events.

Animals↗
PubMed1997

Chemical contaminants in harbor porpoise (Phocoena phocoena) from the north Atlantic coast: tissue concentrations and intra- and inter-organ distribution.

Concentrations of chlorinated hydrocarbons (CHs), such as polychlorinated biphenyls (PCBs), were measured in subsamples taken from different anatomical locations of blubber and liver of three apparently healthy harbor porpoises (Phocoena phocoena) incidentally caught in a gill-net fishery along the northwest Atlantic coast; selected elements (e.g., mercury) were measured in subsamples of liver. The vertical distribution (skin to muscle) of contaminants within blubber was also determined. Additionally, the concentrations of CHs and elements were determined in individual samples of brain, lung, kidney, and testis to assess how the disposition of toxic chemicals may be dependent on the physiological characteristics of a specific organ. Statistical analyses of the results showed that the anatomical location of the blubber or liver sample had no significant effect on concentrations of either CHs in blubber and liver, or of selected elements in liver. However, there were statistical differences between strata of blubber (skin to muscle) for the concentrations of CHs. As expected, the results showed that the CH concentrations, based on wet weight, were considerably higher in the blubber than in the other tissues; however, the concentrations of CHs in the different tissues were more comparable when values were based on total lipid weight with the exception of the brain where lipid normalized concentrations were lower than in all other tissues: This low relative accumulation of lipophilic contaminants in the brain tissue may be due to the presence of the blood-brain barrier, or due to a lower proportion of neutral lipids, such as triglycerides, as analysis for percent lipid and for the proportion of specific lipid classes showed.

Adipose Tissue↗
PubMed1997

Prospective randomized study of thrice weekly six-month and nine-month chemotherapy for cervical tuberculous lymphadenopathy.

The aim of this study is to compare the efficacy of a thrice weekly 6-month regimen, 4S3H3R3Z3/2H3R3 (which consists of an initial 4 months of streptomycin (S), isoniazid (H), rifampicin (R), and pyrazinamide (Z) followed by 2 months of isoniazid and rifampicin), with a thrice weekly 9-month regimen, 4S3H3R3Z3/5H3R3 (which consists of an initial 4 months of streptomycin, isoniazid, rifampicin, and pyrazinamide followed by 5 months of isoniazid and rifampicin), in the treatment of cervical tuberculous lymphadenopathy. A total of 113 patients were recruited between August 1987 and December 1993. Twenty-two patients were excluded from the analysis because of defaulting treatment or modification of regimen. Ninety-one patients were included in the analysis. Forty-three patients were given the 6-month regimen, and 48 patients were given the 9-month regimen. Two (5%) patients of the 6-month regimen and one (2%) patient of the 9-month regimen had primary failure after completion of treatment (relative risk, 2.23; 95% confidence interval, 0.21 to 23.76). Of the 88 patients who had initial clinical remission after completion of treatment, the 5-year actuarial remission rates were 89% for the 6-month regimen and 90% for the 9-month regimen (Wilcoxon, p = 0.44). There were no significant differences of both primary failure rate and 5-year actuarial remission rate of the two regimens. The 6-month regimen is recommended as the initial treatment of tuberculous lymphadenopathy.

Administration, Oral↗
PubMed1997

Differential expression of alpha 2-adrenoceptor subtypes in purified rat pancreatic islet A- and B-cells.

In the endocrine pancreas, alpha 2-adrenoceptor stimulation reduces glucose-induced insulin secretion from islet B-cells. There is, however, controversy with regard to the effects of alpha 2-agonists on islet A-cell function. In this paper, we have used RNA samples prepared from whole rat islets and from FACS-purified rat A- and B-cells to study alpha 2-adrenoceptor subtype expression. RNase protection assays detected transcripts encoding alpha 2a and alpha 2b subtypes in the RNA pool of rat islets. Reverse transcription-PCR revealed that transcripts for all three alpha 2-adrenoceptor subtypes are present in rat islet cells in purified A-cell RNA. In contrast, RT-PCR of islet B-cell RNA yielded products corresponding to alpha 2a and alpha 2c, with no evidence for the presence of alpha 2b. Thus, the results reveal that both islet cell types express more than one receptor subtype and suggest that the distribution of the subtypes may differ between rat islet A- and B-cells.

Animals↗
PubMed1997

The effect of the putative endogenous imidazoline receptor ligand, clonidine-displacing substance, on insulin secretion from rat and human islets of Langerhans.

1. The effects of a rat brain extract containing clonidine-displacing substance (CDS), a putative endogenous imidazoline receptor ligand, on insulin release from rat and human isolated islets of Langerhans were investigated. 2. CDS was able to potentiate the insulin secretory response of rat islets incubated at 6 mM glucose, in a dose-dependent manner. The magnitude of this effect was similar to that in response to the well-characterized imidazoline secretagogue, efaroxan. 3. CDS, like other imidazoline secretagogues, was also able to reverse the inhibitory action of diazoxide on glucose-induced insulin release, in both rat and human islets. 4. These effects of CDS on secretion were reversed by the imidazoline secretagogue antagonists, RX801080 and the newly defined KU14R, providing the first evidence that imidazoline-mediated actions of CDS can be blocked by specific imidazoline antagonists. 5. The effects of CDS on insulin secretion were unaffected when the method of preparation involved centri-filtration through a 3,000 Da cut-off membrane or when the extract was treated with protease. These results confirm that the active principle is of low molecular weight and is not a peptide. 6. Overall, the data suggest that CDS behaves as a potent endogenous insulin secretagogue acting at the islet imidazoline receptor.

Adrenergic alpha-Antagonists↗
PubMed1997

Interactions between imidazoline compounds and sulphonylureas in the regulation of insulin secretion.

1. Imidazoline alpha 2-antagonist drugs such as efaroxan have been shown to increase the insulin secretory response to sulphonylureas from rat pancreatic B-cells. We have investigated whether this reflects binding to an islet imidazoline receptor or whether alpha 2-adrenoceptor antagonism is involved. 2. Administration of (+/-)-efaroxan or glibenclamide to Wistar rats was associated with a transient increase in plasma insulin. When both drugs were administered together, the resultant increase in insulin levels was much greater than that obtained with either drug alone. 3. Use of the resolved enantiomers of efaroxan revealed that the ability of the compound to enhance the insulin secretory response to glibenclamide resided only in the alpha 2-selective-(+)-enantiomer; the imidazoline receptor-selective-(-)-enantiomer was ineffective. 4. In vitro, (+)-efaroxan increased the insulin secretory response to glibenclamide in rat freshly isolated and cultured islets of Langerhans, whereas (-)-efaroxan was inactive. By contrast, (+)-efaroxan did not potentiate glucose-induced insulin secretion but (-)-efaroxan induced a marked increase in insulin secretion from islets incubated in the presence of 6 mM glucose. 5. Incubation of rat islets under conditions designed to minimize the extent of alpha 2-adrenoceptor signalling (by receptor blockade with phenoxybenzamine; receptor down-regulation or treatment with pertussis toxin) abolished the capacity of (+)- and (+/-)-efaroxan to enhance the insulin secretory response to glibenclamide. However, these manoeuvres did not alter the ability of (+/-)-efaroxan to potentiate glucose-induced insulin secretion. 6. The results indicate that the enantiomers of efaroxan exert differential effects on insulin secretion which may result from binding to effector sites having opposite stereoselectivity. Binding of (-)-efaroxan (presumably to imidazoline receptors) results in potentiation of glucose-induced insulin secretion, whereas interaction of (+)-efaroxan with a second site leads to selective enhancement of sulphonylurea-induced insulin release.

Adrenergic alpha-Antagonists↗