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Biomedical subjects

P Chan

Publications and source records attributed to P Chan.

At least 91 records · Page 5Linked to original sources

Indoor air quality and the law in Singapore.

With the greater use of air-conditioned offices in Singapore, achieving good indoor air quality has become an important issue. The laws that impose duties upon designers and contractors with respect to the design and construction of air-conditioning and mechanical ventilation (ACMV) systems are set out in the Building Control Regulations and the Singapore Standard Code of Practice for Mechanical Ventilation and Air-conditioning in Buildings (hereinafter "SS CP 13:1980"). ACMV maintenance is governed by the Environmental Public Health Act, the Building and Common Property (Maintenance and Management) Act, and the Land Titles (Strata) Act, as well as by lease or tenancy agreements. Designers, contractors, developers, building owners and management corporations may also be liable to the workers, occupants and other premises users for indoor air quality (IAQ)-related injuries under the general principles of contract and tort. Recently, the Guidelines for Good Indoor Air Quality in Office Premises was issued by the Ministry of Environment to complement SS CP 13:1980 toward improving the indoor air quality of air-conditioned office premises. Although the Guidelines have no statutory effect, they may be adopted as contractual requirements in construction, lease and maintenance contracts. They may also be used to determine the relevant standard of duty of care required to discharge tortious liability. This paper looks at the existing laws and rules affecting the design, construction and maintenance of air-conditioned offices in light of Part III of the Ministry's Guidelines.

Air Conditioning↗

Epstein-Barr virus infection of human astrocyte cell lines.

Epstein-Barr virus (EBV) is implicated in different central nervous system syndromes. The major cellular receptor for EBV, complement receptor type 2 (CR2) (CD21), is expressed by different astrocyte cell lines and human fetal astrocytes, suggesting their susceptibility to EBV infection. We demonstrated the infection of two astrocyte cell lines, T98 and CB193, at low levels. As infection was mediated by CR2, we used two stable CR2 transfectant astrocyte cell lines (T98CR2 and CB193CR2) to achieve a more efficient infection. We have monitored EBV gene expression for 2 months and observed the transient infection of T98 and T98CR2 cells and persistent infection of CB193 and CB193CR2 cells. The detection of BZLF1, BALF2, and BcLF1 mRNA expression suggests that the lytic cycle is initiated at early time points postinfection. At later time points the pattern of mRNA expressed (EBER1, EBNA1, EBNA2, and LMP1) differs from latency type III in the absence of LMP2A transcription and in the expression of BALF2 and BcLF1 but not BZLF1. A reactivation of the lytic cycle was achieved in CB193CR2 cells by the addition of phorbol esters. These studies identify astrocyte cell lines as targets for EBV infection and suggest that this infection might play a role in the pathology of EBV in the brain.

Astrocytes↗

An additional dimension to health inequalities: disease severity and socioeconomic position.

OBJECTIVE: To investigate the association between the severity of hip pain and disability, and a number of measures of socioeconomic position, using a range of individual and ecological socioeconomic indicators. DESIGN: Interviewer administered and self completed questionnaires on symptoms of pain and disability, general health and socioeconomic indicators, completed by people reporting hip pain in a cross sectional, postal, screening questionnaire. SETTING: 40 general practices from inner city, suburban and rural areas of south west England. PARTICIPANTS: 954 study participants who had reported hip pain in a postal questionnaire survey of 26,046 people aged 35 and over, selected using an age/sex stratified random probability sample. DATA: Individual indicators of socioeconomic position: social class based on occupation, maximum educational attainment, car ownership, gross household income, manual or non-manual occupation and living alone. Area level measures of socioeconomic position: Townsend scores for material deprivation at enumeration district level; urban or rural location based on the postcode of residence. Severity of hip disease, measured by the pain, disability and independence components of the New Zealand score for major joint replacement. Self reported comorbidity validated using general practice case notes and summary measures of general health. MAIN RESULTS: Increasing disease severity was strongly associated with increasing age and a variety of measures of general health, including comorbidity. The data provide considerable evidence for the systematic association of increased severity of hip disease with decreasing socioeconomic position. Measures of socioeconomic position that were systematically associated with increasing disease severity, standardised for age and sex, included educational attainment (relative index of inequality 1.95 (95% confidence intervals 1.29 to 2.62) and income (relative index of inequality 4.03 (95% confidence intervals 3.43 to 4.64). Those with access to a car (mean disease severity 15.5) had statistically significant lower severity of hip disease than those without (mean 17.5, p < 0.01). Similar results were found for access to higher or further education and living with others. For a given level of income, people with greater comorbidity had more severe hip pain and disability. The gradient in disease severity between rich and poor was steepest among those with the most comorbidity. CONCLUSIONS: People with lower socioeconomic position experience a greater severity of hip disease. The poorest sector of the population seem to be in double jeopardy: they not only experience a greater burden of chronic morbidity but also a greater severity of hip disease. This study has implications for health care provision, if the National Health Service is to live up to its principle of equal treatment for equal medical need.

Adult↗

Effects of losartan on the sexual behavior of male rats.

Many commonly used antihypertensive drugs such as diuretics and beta-blockers can interfere with sexual function in both sexes, causing loss of libido, impairment of erectile function and ejaculation in men, and delay or prevent orgasm in women. Newly developed antihypertensive drugs should ideally not interfere with the patients' quality of life including sexual function. This study examined the effects of losartan, a nonpeptide, specific antagonist for type I angiotensin II receptors, on the male sexual behavior of rats. Spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were treated with losartan 30 mg/ kg/day or saline control for 7, 30 and 90 days. Dark-cycle video recording was used to analyze the male sexual activities of the rats. No significant alteration in male sexual performance was observed after 7 and 30 days of treatment with losartan. In contrast, SHRs treated with propranolol 5 mg/kg/day showed increases in intromission latency, ejaculation latency and postejaculatory period indicating decreased libido and erectile and ejaculatory function. Upon completion of 90 days of losartan administration, the mount latency of the SHR was significantly increased, suggesting a decrease in libido although other parameters were unchanged and there was no effect in WKY rats. It is therefore concluded that losartan may have an advantage in preservation of sexual function when used clinically for the treatment of hypertensive disorders.

Animals↗

Changes of superoxide dismutase in cultured rat aortic smooth muscle cells (A7r5) by an incubation of vitamin E.

Supplementation of antioxidants such as vitamin E and vitamin C as health promotion food is popular recently. Epidemiological studies supported the beneficial effect of these antioxidants because oxygen free radicals have been linked to the process of diseases and aging. The present study evaluated the effect of alpha-tocopherol (vitamin E) on the changes of superoxide dismutase (SOD) in cultured rat aortic smooth muscle cells (A7r5) after a short-term (2 days) or long-term (7 days) incubation. Incubation of A7r5 cells with vitamin E at a concentration of 50 micromol/l for 2 days caused an increase of both the activity and mRNA level of SOD. At higher concentrations, such as 100 or 200 micromol/l, vitamin E failed to enhance SOD more effectively. However, after incubation for 7 days, vitamin E caused a decrease in both the activity and mRNA level of SOD in a concentration-dependent manner. Otherwise, the protein amount of SOD remained the same in these samples regardless of the concentration of vitamin E or the duration of incubation. The obtained results suggest that vitamin E can increase the effect of SOD to result in the beneficial influence of this antioxidant only at low concentration under a short-term supplementation because a down-regulation of SOD was observed in cells receiving a long-term incubation.

Animals↗

The antihypertensive effect of the berberine derivative 6-protoberberine in spontaneously hypertensive rats.

Berberine is a natural isoquinoline alkaloid found in plants of the Ranunculaceae and Berberidaceae families. Extracts from berberine-containing plants have been used as traditional Chinese folk remedies for centuries. The antihypertensive effects of the berberine derivative 6-protoberberine (PTB-6) were studied in spontaneously hypertensive rats (SHRs). In conscious SHRs, PTB-6 lowered the systolic blood pressure in a dose-dependent manner (6-PTB: 5 mg/kg, -31.1 +/- 1.6 mm Hg; 10 mg/kg, -42.4 +/- 3.1 mm Hg). Cardiac output using the thermodilution method was reduced in PTB-6-treated anesthetized SHRs with a tendency to decrease in heart rate. Injection of PTB-6 into the intracerebral ventricles of SHRs lowered the systolic arterial blood pressure and heart rate. The berberine derivative PTB-6 is an effective antihypertensive agent. The mechanism of the antihypertensive effect of PTB-6 is probably through a central sympatholytic effect.

Animals↗

Current popularity of pneumatic retinopexy.

PURPOSE: To compare the popularity of pneumatic retinopexy (PR) in 1997 with its popularity in 1990 among retinal specialists. METHODS: In 1997, a survey was mailed to the 1994-1995 members of the Retina or Vitreous Societies who lived in the United States or Canada, asking how they would manage a hypothetical retinal detachment. The choices were limited to PR, segmental scleral buckling, scleral bucking with encircling, primary vitrectomy, and Lincoff balloon. The results of the survey were compared with those previously reported by a similar survey in 1990. RESULTS: The majority (55%) of respondents selected PR, which is a twofold increase over those who preferred it in 1990 (odds ratio 2.08; 95% confidence interval 1.53, 2.85). The popularity of PR was inversely proportional to the length of time the respondents had been in practice. If the eye with the hypothetical detachment had pseudophakia, only 30% of respondents selected PR. If the eye had additional tears, vitreous hemorrhage, or lattice degeneration, only about one-sixth preferred PR. CONCLUSION: Pneumatic retinopexy was much more popular in 1997 than it was in 1990. Its popularity continues to be influenced by the age of the surgeon and by the complexity of the detachment.

Data Collection↗

Respiratory syncytial virus infection in young Malaysian children.

UNLABELLED: Respiratory syncytial virus (RSV) is the most important agent causing respiratory illness in the young paediatric age group. OBJECTIVE: To determine the clinical profile and risk factors for respiratory distress in young Malaysian children with RSV infection. METHOD: The study was a retrospective review of 185 children below the age of 24 months hospitalised with RSV infection. Respiratory distress at admission was categorised into mild, moderate and severe using a modified respiratory distress assessment instrument (RDAI) score. RESULTS: RSV infection occurred most frequently in the 3-6 months age group with a male predominance. A small number of patients had extrapulmonary symptoms of diarrhoea (8%) and seizures (7%). Forty-seven patients (25%) had an underlying illness. The majority of patients (63%) had mild respiratory distress. All patients (8%) with severe respiratory distress required intensive care and 80% of them required assisted ventilation. The overall mean duration of hospital stay was 7.0 +/- 5.0 days. There was only one death. Risk factors associated with respiratory distress included age less than 3 months, a family history of bronchial asthma and presence of an underlying disease. CONCLUSION: The majority of Malaysian children with RSV infection had a mild illness but a small number of them who developed severe illness had a higher incidence of respiratory failure requiring assisted ventilation.

Female↗

Relationship between hemostatic factors and known cardiovascular disease correlates in two suburban populations in Taiwan.

The Cardiovascular Disease (CVD) Risk Factor Two-Township Study is a longitudinal cardiovascular epidemiologic study of two suburban towns in Taiwan. Analyzing baseline data from 1,080 men and 1,510 women aged 18 and above, this paper focuses on the relationship of several hemostatic factors to CVD correlates: blood lipids, apolipoproteins, glucose, and uric acid, and blood pressure. Information on these relationships can shed light on whether hemostatic factors contribute to the pathogenesis of CVD independently or through known mechanisms. Pearson correlation and multiple regression analysis were used to analyze the data. In the population studied, cholesterol, and apolipoprotein B had the strongest correlations with all hemostatic factors tested. Triglyceride was also strongly associated with factor VIIc. Factor VIIIc, factor VIIc, and fibrinogen, ordered by the strength of the correlation, were positively and significantly correlated with glucose, uric acid, and blood pressure levels. The associations of apolipoprotein B and cholesterol with fibrinogen (p = 0.14-0.20) were not as strong as those with factors VIIc (p = 0.28-0.37) and VIIIc (p = 0.15-0.30). Factors VIIc and VIIIc were independently associated with most clinical variables studied, including the levels of cholesterol components, triglyceride, glucose, uric acid, and diastolic blood pressure. These finding indicate that states of coagulating factors correlated, to varied degrees, with levels of blood lipid parameters, uric acid, and blood pressure in the population studied.

Apolipoproteins↗

Superoxide dismutase gene expression and activity in the brain of spontaneously hypertensive rats and normotensive rats.

OBJECTIVE: To determine if changes in superoxide dismutase (SOD) in the brain occur in the hypertensive state. METHODS: We compared the levels of the two main subtypes of this enzyme in spontaneously hypertensive rats (SHR) with age-matched normotensive Wistar Kyoto (WKY) rats using enzyme activity estimation, Western blotting for enzyme contents, and Northern blotting of mRNA level. Five discrete brain regions, cerebrocortex, hypothalamus, hippocampus, the remaining non-cortex cerebrum (NCC area), and cerebellum, were employed for comparison in 30-31 weeks old rats. RESULTS: A lower level of both Mn-SOD activity and Mn-SOD mRNA expression was found in all areas of the brain of SHR as compared with WKY rats. Also, the mRNA levels of Cu, Zn-SOD in the brain of SHR differed from WKY rats in parallel to the enzyme activities. The activity and mRNA expression of Cu, Zn-SOD were lower in the hypothalamus and cerebellum of SHR but the mRNA level and the activity in hippocampus were significantly higher in the SHR compared to WKY rats. No differences for Cu, Zn-SOD were observed in cerebrocortex or NCC area in the two species. However, the amount of SOD enzyme subtypes, determined by Western blotting analysis, was not different between SHR and WKY rats. CONCLUSIONS: The results indicate a lower gene expression and less activity of Mn-SOD in SHR brain. This alternation of SOD may be one of the important factors for the vulnerability of the brain from oxygen free radicals or may be related to the pathogenesis of hypertension in this species.

Animals↗

[Genetic polymorphism and susceptibility to occupational chronic manganism: a case-control study].

OBJECTIVE: In a case-control study, the possible genetic factors relevance to occupational chronic manganism were investigated. METHODS: Forty-nine manganisms who were welders and ferromanganese smelters occupationally exposed to manganese dust and fume from three metallurgical industries, and fifty unrelated healthy control subjects who were working same workshops were recruited. The subjects were matched for sex, age, cigarette and alcohol intake. The manganese exposure duration was also matched in this case-control study. Genetic polymorphism of cytochrome P450 2D6L (CYP2D6L) gene and NAD(P)H: quinone oxidreductase (NQO1) genes from all subjects were investigated. The mutations of CYP2D6L gene located exon 6 were analyzed by a polymerase chain reaction (PCR)-based DNA amplification combined with Hha I restriction fragment length polymorphism (RFLP). The substitution of 609(C-T) at exon 6 of DT-diaphroase gene was analyzed by PCR combined Hinf I RFLP. RESULTS: The frequency of polymorphic allels, a mutation of CYP2D6, was significantly lower in patients with manganism (16.3%) than that of the controls (29.0%). A significant association was also found between the homozygote variant of CYP2D6L gene and occupational manganism. These results suggest that the CYP2D6 gene might be one of the susceptibility genes for Mn-induced neurotoxicity. The allele and genotype frequencies of NQO1 gene were similar in the manganism cases and control subjects. CONCLUSION: It is possible that CYP2D6 gene may be a valuable susceptibility biomarker responded to Mn-induced central nervous system disorders in workers exposed to manganese.

Adult↗

Characterization of a regulatory region in the N-terminus of rabbit kv1.3.

The N-terminus of rabbit Kv1.3 contains a signal sequence which regulates expression of Kv1.3 proteins in the plasma membrane. Removal of an N-terminal region (aa3-39) produced an increase in expressed K+ current. Progressive deletion at the N-terminus demonstrated that the shortest deletion required for the elevation of K current is D6-34. Since the functional signal sequence must include both ends of the peptide segment aa6-34 where charged residues are densely distributed, it is conceivable that this N-terminal signal sequence is related to charge or its associated hydrophilicity. Removal of two charged residues (31R, 33E) through amino acid substitution which converts deletion construct D3-27 to D3-27* effectively raises the amplitude of expressed current, further indicating the importance of charged residues. With the use of a mutated dynamin and a soluble N-terminal peptide, we also revealed that the N-terminal signal sequence may not act through the endocytotic pathway.

Amino Acid Sequence↗

Vein graft stenosis and the heparin responsiveness of human vascular smooth muscle cells.

BACKGROUND: Vascular smooth muscle cell (VMSC) proliferation is an essential component of myointimal hyperplasia, which is implicated in the failure of 30% to 50% of vascular interventions, such as coronary angioplasty and peripheral vein grafting. We have shown that cells derived from stenotic lesions in infrainguinal vein grafts were significantly more resistant than controls to growth inhibition by heparin. METHODS AND RESULTS: In a prospective study, we correlated antiproliferative responses to heparin in vitro with graft patency after 1 year. Sixty-two patients with infrainguinal vein grafts were entered into a graft surveillance program for > or = 1 year. At operation, saphenous vein segments were explanted for VSMC culture. Cell proliferation in response to fetal calf serum was later determined in the presence and absence of heparin. In 35 cell cultures, including 13 from the above-mentioned patients, [3H]heparin binding was also estimated. VSMCs from patients with patent grafts were significantly more sensitive to growth inhibition by heparin than cells from patients with stenoses (median, 54% versus 20.9%, P<0.001), and [3H]heparin binding was strongly correlated with inhibition of proliferation (r=0.81). CONCLUSIONS: Responsiveness to heparin in cultured VSMCs is a strong predictor of outcome for infrainguinal vein grafts, and reduced sensitivity to heparin is correlated with decreased heparin binding. Relative resistance to the antiproliferative action of heparin may be a marker for aberrant regulation of VSMC growth.

Adult↗

Hepatic and extra-hepatic transcription of inter-alpha-inhibitor family genes under normal or acute inflammatory conditions in rat.

The expression and level of the mRNAs for the five genes that code for a set of plasma proteins collectively referred to as the inter-alpha-inhibitor family have been studied in rat under a normal condition or in the course of a turpentine-induced, systemic inflammation. In healthy rats, all five mRNAs [H1, H2, H3, H4, and alpha1-microglobulin/bikunin precursor (AMBP)] are expressed primarily in liver and two of them (H2 and H3) are found to a lower extent in brain. By in situ hybridization onto sections of a normal brain, the H3 mRNA has been precisely localized to the hypothalamus, amygdala, pontine area, optic tectum, and cerebellum. By reverse transcriptase-polymerase chain reaction of total RNAs obtained from a panel of organs, low amounts of one or more mRNA(s) could be detected in other locations (e.g., intestine and stomach). Furthermore, the extrahepatic expressions of several of these genes are up- or downregulated at 20 h after the start of a turpentine-induced inflammation. In liver, the contents of H3 and H4 mRNA are upregulated, whereas those of AMBP and H2 are downregulated during the acute phase. This is accounted for by changes in gene transcription, the kinetics of which is gene-specific. This behavior of H1, H2, H3, H4, and AMBP mRNAs in rat liver is in keeping with more limited analyses made at mRNA and/or protein levels in other species (human, pig) suffering from an acute inflammation. Therefore, the inflammation-associated regulation of these five genes that is conserved between species indicates that the inter-alpha-inhibitor family members are likely to be important partners of the acute phase response.

Alpha-Globulins↗

Novel alpha-synuclein-immunoreactive proteins in brain samples from the Contursi kindred, Parkinson's, and Alzheimer's disease.

A specific mutation (A53T) in the encoding region for alpha-synuclein has been identified in a large multigenerational family with an autosomal dominant parkinsonism known as the Contursi kindred. In this study, we used a monoclonal antibody directed against alpha-synuclein in order to identify novel proteins in the brain of an affected member of this kindred who had come to autopsy. Homogenates from the frontal cortex and caudate nucleus were examined using Western blot techniques and compared to matched autopsy specimens from control subjects and patients with various forms of parkinsonism. Western blots, using a 15-min exposure time, revealed the expected 19-kDa band representing alpha-synuclein in all brain samples examined. However, a novel band in the 36-kDa range was also present in the Contursi brain which was not seen in cortex or caudate from control brains or in frontal cortex from 14 cases of typical Parkinson's disease. With a 24-h exposure time, this band was faintly seen in the caudate nucleus of three of the Parkinson's disease cases. Surprisingly, the 36-kDa band (as well as other high-molecular-weight bands) was also present in frontal cortex and caudate nucleus in 3 additional cases that met diagnostic criteria for both Parkinson's disease and Alzheimer's disease. A preliminary analysis of samples from the frontal cortex of 10 Alzheimer's disease cases revealed a 36-kDa band in only one instance. The identification of novel alpha-synuclein-immunoreactive bands in these various forms of parkinsonism may open new research avenues for exploring the relationship between abnormal protein deposition in the brain and one or more neurodegenerative disorders, including the Contursi form of familial parkinsonism.

Adult↗

Clinical risk associated with contrast angiography in metformin treated patients: a clinical review.

Recently, concern has been expressed about the hazards of lactic acidosis following the use of intravascular iodinated contrast agents in patients taking metformin. In response the Royal College of Radiologists have issued guidelines for the management of these patients. We have reviewed the reported cases of lactic acidosis and identified that in all cases underlying renal impairment existed. To examine this further we reviewed the notes of 33 in-patients receiving metformin who underwent contrast angiography in our hospital. Twenty-nine patients had a normal serum creatinine prior to the procedure and none had a rise following angiography. Four patients had an abnormal serum creatinine prior to angiography, all four patients showed significant deterioration and all four patients died, two from unrelated causes and two from acute renal failure and acidosis. These data strongly highlight the hazards of intravascular contrast radiology in diabetic patients with pre-existing renal impairment. We have failed to find evidence in support of the Royal College of Radiologists recommendation; instead we recommend that in those patients taking metformin with evidence of renal impairment metformin should be stopped and diabetic control obtained using alternative therapy before proceeding with angiography. Patients with normal renal function taking metformin are not at risk of lactic acidosis following the use of iodinated contrast agents for angiography.

Acidosis, Lactic↗

The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats.

Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used as a substitute for non-alcoholic sweetener. It has previously been shown to reduce blood pressure in studies in animals and human. The effect of intravenous stevioside on the blood pressure was studied in spontaneously hypertensive rats (SHR). The hypotensive effect on both systolic and diastolic blood pressure was dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious SHR. The maximum reductions in systolic and diastolic blood pressure were 31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg. Serum dopamine, norepinephrine and epinephrine levels were not changed significantly 60 min after intravenous injection of stevioside 100 mg/kg in anesthetized SHR. The present data show that stevioside given intravenously to conscious SHR was effective in blood pressure reduction and there was no change in serum catecholamines in anaesthetized animals with this natural compound.

Animals↗