Browse publications by year: 2003

Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells

Inayat-Hussain SH, Annuar BO, Din LB, Ali AM, Ross D

Toxicol In Vitro, 2003 Aug;17(4):433-9.
PMID: 12849726

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

MeSH terms: Enzyme Activation/drug effects; Flow Cytometry; Humans; Indicators and Reagents; Membrane Potentials/drug effects; Mitochondria/physiology*; Pyrones/pharmacology*; Apoptosis/physiology*; HL-60 Cells; Caspases/metabolism*; Caspase 3; Caspase 7; Caspase 9
Camera identity from minute film-edge mark characteristics

Kuppuswamy R

Forensic Sci Int, 2003 Jul 08;134(2-3):123-5.
PMID: 12850406

A case is presented in which a camera recovered from a site of bomb blast was linked to some incriminating film negatives by the characteristic markings existing along a small portion of the edge of the film negatives.

MeSH terms: Leukocytes; Mass Media; Bombs
Mild beta-thalassemia intermedia caused by compound heterozygosity for (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia and molecular characterization of the defect in four Chinese families

Tan JAMA, Yap SF, Tan KL, Wong YC, Wee YC, Kok JL

Acta Haematol., 2003;109(4):169-75.
PMID: 12853688 DOI: 10.1159/000070965

Molecular characterization of the compound heterozygous condition - (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia - in four families showing mild beta-thalassemia intermedia was carried out using DNA amplification techniques. Using the Amplification Refractory Mutation System (ARMS) to confirm the beta-mutations and DNA amplification to detect the 100-kb Chinese-specific (G)gamma((A)gammadeltabeta)(o)-deletion, ()two families were confirmed to possess (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia with the IVSII No. 654 beta(+)-allele. In the third family, the (G)gamma((A)gammadeltabeta)(o)-deletion was confirmed in the father and the mother was a beta-thalassemia carrier with the cd 41-42 beta(o)-allele. Their affected child with (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia was found to be transfusion dependent. The same (G)gamma((A)gammadeltabeta)(o)-deletion and beta-thalassemia (cd 41-42) was also confirmed in a fourth family. In addition, the mother was also diagnosed with Hb H disease (genotype -alpha(3.7)/-(SEA)). Both the children were found to possess (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia but they were not transfusion dependent and this could be due to co-inheritance of alpha-thalassemia-2 (genotype-alpha(3.7)/alphaalpha) in the children together with their compound heterozygous condition.

MeSH terms: Adult; Alleles; Blood Protein Electrophoresis; Blood Transfusion; Child; China/ethnology; DNA/genetics; DNA Mutational Analysis; Female; Fetal Hemoglobin/analysis; Gene Amplification; Genotype; Globins/genetics*; Hemoglobin A2/analysis; Heterozygote; Humans; Malaysia; Male; Pedigree; Phenotype; Polymorphism, Restriction Fragment Length; alpha-Thalassemia/genetics*; beta-Thalassemia/genetics*; beta-Thalassemia/therapy; Sequence Deletion*
Malaysia puts biovalley under wraps

Cyranoski D

Nature, 2003 Jul 10;424(6945):118.
PMID: 12853917
MeSH terms: Academies and Institutes; Confidentiality; Malaysia; Research*; Research Support as Topic; Ecosystem*
Review of air pollution and health impacts in Malaysia

Afroz R, Hassan MN, Ibrahim NA

Environ Res, 2003 Jun;92(2):71-7.
PMID: 12854685

In the early days of abundant resources and minimal development pressures, little attention was paid to growing environmental concerns in Malaysia. The haze episodes in Southeast Asia in 1983, 1984, 1991, 1994, and 1997 imposed threats to the environmental management of Malaysia and increased awareness of the environment. As a consequence, the government established Malaysian Air Quality Guidelines, the Air Pollution Index, and the Haze Action Plan to improve air quality. Air quality monitoring is part of the initial strategy in the pollution prevention program in Malaysia. Review of air pollution in Malaysia is based on the reports of the air quality monitoring in several large cities in Malaysia, which cover air pollutants such as Carbon monoxide (CO), Sulphur Dioxide (SO2), Nitrogen Dioxide (NO2), Ozone (O3), and Suspended Particulate Matter (SPM). The results of the monitoring indicate that Suspended Particulate Matter (SPM) and Nitrogen Dioxide (NO2) are the predominant pollutants. Other pollutants such as CO, O(x), SO2, and Pb are also observed in several big cities in Malaysia. The air pollution comes mainly from land transportation, industrial emissions, and open burning sources. Among them, land transportation contributes the most to air pollution. This paper reviews the results of the ambient air quality monitoring and studies related to air pollution and health impacts.

MeSH terms: Air Pollutants/adverse effects*; Air Pollution/adverse effects*; Carbon Monoxide/adverse effects; Environmental Monitoring; Humans; Malaysia; Nitrogen Dioxide/adverse effects; Ozone/adverse effects; Respiration Disorders/etiology; Smoke/adverse effects; Sulfur Dioxide/adverse effects
The causes of haemoptysis in malaysian patients aged over 60 and the diagnostic yield of different investigations

Wong CM, Lim KH, Liam CK

Respirology, 2003 Mar;8(1):65-8.
PMID: 12856744

OBJECTIVE: In southeast Asia, pulmonary tuberculosis (TB) is the most frequently presumed diagnosis for haemoptysis. This study was designed to assess the causes of haemoptysis, the diagnostic yield of causes in different diagnostic modalities and the distribution of older patients.
METHODS: All patients presenting to the University of Malaya Medical Centre, Kuala Lumpur, Malaysia with haemoptysis were recruited prospectively and evaluated.
RESULTS: One hundred and sixty patients were evaluated for haemoptysis; 71 (44.4%) were aged 60 years or more. Significantly more patients smoked in the older age group (P = 0.002). The main causes of haemoptysis in the older patients were bronchogenic carcinoma (49.3%), pneumonia (11.3%), bronchiectasis (8.6%), cryptogenic (5.6%) and active TB (4.2%). Significantly more older patients had carcinoma (P < 0.001), while the younger patients more often had TB (P < 0.001). Chest pain was significantly more common in the older patients (P = 0.025), particularly in patients with carcinoma. Bronchoscopy alone or combined with CT of the thorax was significantly more diagnostic in the older patient (P = 0.006).
CONCLUSION: Bronchogenic carcinoma is the commonest cause of haemoptysis in patients aged 60 years and above. Presumptive anti-TB therapy should not be encouraged despite the regional high prevalence of TB.

MeSH terms: Adult; Aged; Aged, 80 and over; Carcinoma, Bronchogenic/complications; Carcinoma, Bronchogenic/diagnosis; Female; Hemoptysis/etiology*; Hemoptysis/epidemiology*; Humans; Lung Neoplasms/complications; Lung Neoplasms/diagnosis; Malaysia/epidemiology; Male; Middle Aged; Pneumonia/complications; Pneumonia/diagnosis; Probability; Prognosis; Tuberculosis, Pulmonary/complications*; Tuberculosis, Pulmonary/diagnosis; Cohort Studies; Incidence; Survival Rate; Age Distribution; Sex Distribution; Risk Assessment
Metastatic lung cancer in pregnancy

Wong CM, Lim KH, Liam CK

Respirology, 2003 Mar;8(1):107-9.
PMID: 12856752

Pregnancy complicated by lung cancer has been rarely reported. The regional incidence of this complex situation is likely to increase in the future and optimal management needs to be established to better deal with this situation. We report two patients with metastatic lung cancer complicating pregnancy to highlight the evaluation and management difficulties associated with this problem and to contribute to the limited information in the literature.

MeSH terms: Adult; Bronchoscopy; Carcinoma, Squamous Cell/pathology*; Carcinoma, Squamous Cell/secondary; Female; Gestational Age; Humans; Lung Neoplasms/diagnosis*; Malaysia; Neoplasm Metastasis; Pregnancy; Pregnancy Complications, Neoplastic/diagnosis*; Pregnancy Outcome*; Tomography, X-Ray Computed; Fatal Outcome; Risk Assessment
Method development for determination of fluroxypyr in water

Halimah M, Tan YA, Aini K, Ismail BS

J Environ Sci Health B, 2003 Jul;38(4):429-40.
PMID: 12856925

Improved methods for extraction and clean up of fluroxypyr residue in water have been established. Two methods of fluroxypyr extraction were used, namely, Direct Measurement of fluroxypyr and Concentration of fluroxypyr onto A Solid Phase Extraction (SPE) Adsorbent, followed by elution with solvent before determination of fluroxypyr. The recovery for Direct Measurement of fluroxypyr in water containing 8-100 microg L(-1), ranged from 86 to 110% with relative standard deviation of 0.7 to 2.15%. For the second method, three types of SPE were used, viz. C18, C18 end-capped and polyvinyl dibenzene (ISOLUTE ENV+). The procedure involved concentrating the analyte from fluroxypyr-spiked water at pH 3, followed by elution of the analyte with 4 mL of acentonitrile. The recovery of fluroxypyr from the spiked sample at 1 to 50 microg L(-1) after eluting through either C18 or C18 end-capped ranged from 40-64% (with relative standard deviation of 0.7 to 2.15) and 41-65% (with standard deviation of 1.52 to 11.9). The use of ISOLUTE ENV+, gave better results than the C18, C18 end-capped or the Direct Measurement Methods. The recovery and standard deviation of fluroxypyr from spiked water using ISOLUTE ENV+ ranged from 91-102% and 2.5 to 5.3, respectively.

MeSH terms: Acetates/analysis*; Acetates/isolation & purification; Adsorption; Calibration; Chromatography, High Pressure Liquid/methods*; Herbicides/analysis*; Herbicides/isolation & purification; Gas Chromatography-Mass Spectrometry/methods*; Pesticide Residues/analysis; Pesticide Residues/isolation & purification; Pyridines/analysis*; Pyridines/isolation & purification; Sensitivity and Specificity; Water/chemistry*; Water Pollutants, Chemical/analysis*; Water Pollutants, Chemical/isolation & purification
Exotic and emerging viral encephalitides

Solomon T

Curr. Opin. Neurol., 2003 Jun;16(3):411-8.
PMID: 12858080

The exotic and emerging viral encephalitides are caused by animal or human viruses and characterised by sudden unexpected outbreaks of neurological disease, usually in tropical and sub-tropical regions, but sometimes spreading to temperate areas. Although a wide range of viruses come within this label, as this review highlights, there are common research questions as to the origin and spread of the viruses, the contribution of viral and host factors to the clinical presentations and outcome, and the possibilities for treatment and vaccination.

MeSH terms: Animals; Arbovirus Infections/epidemiology; Arbovirus Infections/pathology; Asia; Encephalitis Virus, Japanese/pathogenicity; Encephalitis, Japanese/pathology; Encephalitis, Japanese/therapy; Encephalitis, Japanese/virology; Humans; Vaccines; West Nile Fever/pathology; West Nile Fever/therapy; West Nile Fever/virology; West Nile virus/pathogenicity; Interferon-alpha/therapeutic use; Paramyxovirinae/pathogenicity; Encephalitis, Viral/pathology*; Encephalitis, Viral/therapy; Encephalitis, Viral/virology*
Immunoaffinity extraction and tandem mass spectrometric analysis of human chorionic gonadotropin in doping analysis

Gam LH, Tham SY, Latiff A

J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Jul 25;792(2):187-96.
PMID: 12860026

A confirmatory and quantitative HPLC-tandem mass spectrometry (MS-MS) method for human chorionic gonadotropin hormone (hCG) at concentrations as low as 5 IU/l following immunoaffinity extraction of the glycoprotein from urine was developed. The extraction method involved retention of urinary hCG in the immunoaffinity column via specific antigen-antibody interaction. A variety of eluents were then used to quantitatively elute hCG from the immunoaffinity column. Qualitative and quantitative analysis of hCG were undertaken using MS-MS by identifying the amino acid sequence of the marker peptide betaT5 obtained from hCG by tryptic digestion and the peak areas of three product ions b(6)(+), b(9)(+) and y(11)(+), respectively.

MeSH terms: Amino Acid Sequence; Chromatography, Affinity/methods*; Chromatography, High Pressure Liquid/methods*; Chorionic Gonadotropin/urine*; Chorionic Gonadotropin/chemistry; Humans; Molecular Sequence Data; Peptide Mapping; Spectrometry, Mass, Electrospray Ionization/methods*
Lipids and coronary heart disease in Asia

Khoo KL, Tan H, Liew YM, Deslypere JP, Janus E

Atherosclerosis, 2003 Jul;169(1):1-10.
PMID: 12860245

In Western countries, it has been shown that coronary heart disease (CHD) is related to high serum total cholesterol (TC) levels. In less developed continents such as Asia and Africa, serum lipid levels are low and CHD incidence is much lower as compared with Western countries. With growing urbanization and industrialization in Asia, it has been shown that there is a concomitant rise in the level of serum TC and with it a rise in CHD. In all the Asian countries, serum TC levels are also higher in the urban compared with the rural population. Singapore, the only Asian country which is 100% urbanized since 1980, showed a rise of serum TC similar to that seen in the US and UK from the 1950s to the 1980s followed thereafter by a fall. This is reflected in the trend (rise followed by a fall) of CHD morbidity and mortality as well. In spite of a declining trend in serum TC level, CHD morbidity and mortality are still high in Singapore and comparable to the Western countries. The rest of the Asian countries show a different pattern from Singapore. In general, there is still a rising trend in serum TC level and in CHD mortality in most Asian countries. However, Japan is considered an exception in having a decreasing CHD mortality in spite of an increasing trend in serum TC. This may be attributed to a better control of other CHD risk factors such as hypertension and smoking. The rising trend in serum TC level remains a cause for concern, as this will emerge as a major problem for CHD morbidity and mortality in the future.

MeSH terms: Asia, Southeastern/epidemiology; Cholesterol/blood*; Coronary Disease/blood*; Coronary Disease/epidemiology*; Developing Countries; Far East/epidemiology; Humans; Socioeconomic Factors
Trends and ethnic differences in hospital admissions and mortality for congestive heart failure in the elderly in Singapore, 1991 to 1998

Ng TP, Niti M

Heart, 2003 Aug;89(8):865-70.
PMID: 12860859

To describe trends in hospital admissions and mortality from congestive heart failure in the elderly population aged 65 years and over in Singapore, 1991 to 1998.

MeSH terms: Aged; Aged, 80 and over; China/ethnology; Female; Heart Failure/ethnology*; Heart Failure/mortality; Hospitalization/trends*; Humans; India/ethnology; Malaysia/ethnology; Male; Singapore/epidemiology; Sex Distribution
Emotional expressiveness and the quality of life of patients with schizophrenia

Mubarak AR, Barber JG

Soc Psychiatry Psychiatr Epidemiol, 2003 Jul;38(7):380-4.
PMID: 12861444 DOI: 10.1007/s00127-003-0645-0

Background: The present research aims to study the association between emotional expressiveness of primary care-givers and quality of life of patients with schizophrenia.
Method: The data for the present study were collected from 174 purposively selected patients with schizophrenia and their primary care-givers. The Quality of Life Interview (QOLI) (Lehman 1988) was used to collect information related to the quality of life of patients. The care-givers‘ emotional expressiveness was assessed using three questions on home environment from Disability Assessment Schedule (WHO/DAS) (WHO 1988).
Results: Three components of emotional expressiveness were included in the present research, namely, emotional involvement, control and attitude of rejection. Among these three components, emotional involvement of key care-givers was found to have a significant association with quality of life of schizophrenia patients.
Conclusion: Based on this result, the present study argues that emotional involvement of key care-givers needs careful attention while planning psychosocial rehabilitation programmes aimed at enhancing the quality of life of schizophrenia patients.
Keywords: emotional expression – quality of life – schizophrenia – emotional involvement – community – Asia

MeSH terms: Adult; Cross-Sectional Studies; Female; Hospitals, General; Humans; Malaysia; Male; Middle Aged; Primary Health Care; Quality of Life*; Schizophrenic Psychology*; Caregivers/psychology*; Expressed Emotion
Nasopharyngeal carcinoma and nasal allergy: any correlation?

Prepageran N, Lingham OR, Krishnan G, Jalaludin MA, Raman R

Ear Nose Throat J, 2003 Jun;82(6):438-40.
PMID: 12861869

Although it has been observed that nasal allergy is rarely seen in patients who have nasopharyngeal carcinoma, to our knowledge, no actual study of such a lack of association has been previously reported. To fill this void, we conducted a pilot study to investigate any such inverse relationship. We conducted skin-prick allergen tests on 22 patients with newly diagnosed but not-yet-treated nasopharyngeal carcinoma. Combining these test results with findings on the history and clinical examination, we concluded that only one of the 22 cancer patients (4.5%) had allergic rhinitis. Our study also confirmed the validity of using findings on the history, clinical examination, and skin-prick testing as a reliable means of diagnosing allergic rhinitis.

MeSH terms: Adult; Aged; Female; Rhinitis, Allergic, Seasonal/complications; Rhinitis, Allergic, Seasonal/diagnosis*; Rhinitis, Allergic, Seasonal/epidemiology*; Humans; Male; Middle Aged; Nasopharyngeal Neoplasms/complications*; Pilot Projects; Rhinitis, Allergic, Perennial/complications; Rhinitis, Allergic, Perennial/diagnosis*; Rhinitis, Allergic, Perennial/epidemiology*; Skin Tests; Incidence
Treatment of phenolic wastewater using agricultural wastes as an adsorbent in a sequencing batch reactor

Lee KM, Lim PE

Water Sci Technol, 2003;47(10):41-7.
PMID: 12862215

The objective of this study is to investigate the potential of the activated rice husk to be used as an alternative adsorbent to powdered activated carbon (PAC) in the simultaneous adsorption and biodegradation processes under sequencing batch reactor (SBR) operation to treat synthetic wastewater containing phenol, p-methylphenol, p-ethylphenol and p-isopropylphenol. The rice husk (PRH) was activated by pyrolysis at 600 degrees C for 5 hours in a nitrogen atmosphere. Using the Langmuir model, the limiting adsorption capacities of PRH for the phenols were found to vary from 0.015-0.05 of those of PAC. The SBR reactors with and without adsorbent addition were operated with fill, react, settle, draw and idle periods in the ratio of 4:6:1:0.76:0.25 for a cycle time of 12 hours. For phenolic wastewater containing, 1,200 mg/L phenol, 1,200 mg/L p-methylphenol, 800 mg/L p-ethylphenol and 660 mg/L p-isopropylphenol, it was found that the biodegradation process alone was unable to produce effluent of quality which would satisfy the discharge standards of COD < or = 100 mg/L and phenol concentration < or = 1 mg/L. The addition of PAC in the ratio of PAC/phenolic compound at 0.095 g/g for phenol, 0.119 g/g for p-methylpheol, 0.179 g/g for p-ethylphenol and 0.220 g/g for p-isopropylphenol, can improve the effluent quality to satisfy the discharge standards. Equivalent treatment performance was achieved with the use of PRH at dosages of 2-3 times higher than those of PAC for all the phenolic wastewater studied. The increased adsorption capacity of PRH shown in the treatment indicates bioregeneration of the adsorbed surface during the treatment process.

MeSH terms: Adsorption; Agriculture*; Biodegradation, Environmental; Carbon; Conservation of Natural Resources; Phenols/isolation & purification*; Phenols/metabolism*; Quality Control; Oryza; Waste Disposal, Fluid/methods*; Water Purification/methods*; Plant Leaves; Bioreactors*
Biosolids accumulation and biodegradation of domestic wastewater treatment plant sludge by developed liquid state bioconversion process using a batch fermenter

Alam MZ, Fakhru'l-Razi A, Molla AH

Water Res, 2003 Sep;37(15):3569-78.
PMID: 12867323

The biosolids accumulation and biodegradation of domestic wastewater treatment plant (DWTP) sludge by filamentous fungi have been investigated in a batch fermenter. The filamentous fungi Aspergillus niger and Penicillium corylophilum isolated from wastewater and DWTP sludge was used to evaluate the treatment performance. The optimized mixed inoculum (A. niger and P. corylophilum) and developed process conditions (co-substrate and its concentration, temperature, initial pH, inoculum size, and aeration and agitation rate) were incorporated to accelerate the DWTP sludge treatment process. The results showed that microbial treatment of higher strength of DWTP sludge (4% w/w of TSS) was highly influenced by the liquid state bioconversion (LSB) process. In developed bioconversion processes, 93.8 g/kg of biosolids was enriched with fungal biomass protein of 30 g/kg. Enrichment of nutrients such as nitrogen (N), phosphorous (P), potassium (K) in biosolids was recorded in 6.2% (w/w), 3.1% (w/w) and 0.15% (w/w) from its initial values of 4.8% (w/w), 2.0% (w/w) and 0.08% (w/w) respectively after 10 days of fungal treatment. The biodegradation results revealed that 98.8% of TSS, 98.2% of TDS, 97.3% of turbidity, 80.2% of soluble protein, 98.8% of reducing sugar and 92.7% of COD in treated DWTP sludge supernatant were removed after 8 days of microbial treatment. The specific resistance to filtration (SRF) in treated sludge (1.4x10(12) m/kg) was decreased tremendously by the microbial treatment of DWTP sludge after 6 days of fermentation compared to untreated sample (85x10(12) m/kg).

MeSH terms: Aspergillus niger/enzymology*; Biodegradation, Environmental; Fermentation; Nitrogen/metabolism; Penicillium/enzymology*; Phosphorus/metabolism; Proteins/metabolism; Sewage/microbiology*; Sewage/chemistry; Waste Disposal, Fluid/methods*; Biomass; Bioreactors*
Genetic relatedness of Candida strains isolated from women with vaginal candidiasis in Malaysia

Chong PP, Lee YL, Tan BC, Ng KP

J Med Microbiol, 2003 Aug;52(Pt 8):657-66.
PMID: 12867559

The aims of this study were to compare the genetic relatedness of: (i) sequential and single isolates of Candida strains from women with recurrent vaginal candidiasis (RVC); and (ii) Candida strains from women who had only one episode of infection within a 1-year period. In total, 87 isolates from 71 patients were cultured, speciated and genotyped by random amplification of polymorphic DNA (RAPD) analysis. Patients were categorized into three groups, namely those with: (i) a history of RVC from whom two or more yeast isolates were obtained (group A); (ii) a history of RVC from whom only a single isolate was obtained (group B); and (iii) a single episode of vaginal candidiasis within a 1-year period (group C). Six yeast species were detected: Candida albicans, Candida glabrata, Candida lusitaniae, Candida famata, Candida krusei and Candida parapsilosis. Interestingly, the prevalence of non-albicans species was higher in group A patients (50 %) than in patients in groups B (36 %) or C (18.9 %). Eighty RAPD profiles were observed, with a total of 61 polymorphic PCR fragments of distinct sizes. Clustering analysis showed that, overall, the majority of patients in group A had recurrent infections caused by highly similar, but not identical, sequential strains [mean pairwise similarity coefficient (S(AB)) = 0.721 +/- 0.308]. The range of mean S(AB) values for intergroup comparisons for C. albicans isolates alone was 0.50-0.56, suggesting that there was no significant relatedness between strains from different groups. Genetic similarity of C. albicans isolates from patients in group A was lower than that of C. albicans isolates from patients in group C (mean S(AB) = 0.532 +/- 0.249 and 0.636 +/- 0.206, respectively); this difference was statistically significant (P = 0.036). These results demonstrate that the cause of recurrent infections varies among individuals and ranges between strain maintenance, strain microevolution and strain replacement; the major scenario is strain maintenance with microevolution. They also show that C. albicans strains that cause recurrent infections are less similar to each other than strains that cause one-off infections, suggesting that the former may represent more virulent subtypes.

MeSH terms: Candida/classification*; Candida/genetics*; Candida/isolation & purification; Candida/pathogenicity; Candidiasis, Vulvovaginal/microbiology*; Female; Humans; Malaysia; Phylogeny; Recurrence; Species Specificity; Genetic Variation/genetics*; Virulence; Random Amplified Polymorphic DNA Technique
Newcastle disease virus nucleocapsid protein: self-assembly and length-determination domains

Kho CL, Tan WS, Tey BT, Yusoff K

J Gen Virol, 2003 Aug;84(Pt 8):2163-2168.
PMID: 12867648 DOI: 10.1099/vir.0.19107-0

The nucleocapsid protein (NP) of Newcastle disease virus expressed in E. coli assembled as ring- and herringbone-like particles. In order to identify the contiguous NP sequence essential for assembly of these particles, 11 N- or C-terminally deleted NP mutants were constructed and their ability to self-assemble was tested. The results indicate that a large part of the NP N-terminal end, encompassing amino acids 1 to 375, is required for proper folding to form a herringbone-like structure. In contrast, the C-terminal end covering amino acids 376 to 489 was dispensable for the formation of herringbone-like particles. A region located between amino acids 375 to 439 may play a role in regulating the length of the herringbone-like particles. Mutants with amino acid deletions further from the C-terminal end (84, 98, 109 and 114 amino acids) tended to form longer particles compared to mutants with shorter deletions (25 and 49 amino acids).

MeSH terms: Animals; Binding Sites; Escherichia coli/genetics; Escherichia coli/metabolism; Newcastle Disease/virology; Newcastle disease virus/genetics; Newcastle disease virus/metabolism*; Gene Deletion; Virus Assembly*; Nucleocapsid Proteins/genetics; Nucleocapsid Proteins/metabolism*; Nucleocapsid Proteins/chemistry*
Dengue virus type 2 NS3 protease and NS2B-NS3 protease precursor induce apoptosis

Shafee N, AbuBakar S

J Gen Virol, 2003 Aug;84(Pt 8):2191-2195.
PMID: 12867651 DOI: 10.1099/vir.0.19022-0

Apoptosis was detected in Vero cell cultures expressing transfected dengue virus type 2 (DENV-2) genes. Approximately 17.5 and 51.5 % of cells expressing NS3 serine protease and NS2B-NS3(185) serine protease precursor protein [NS2B-NS3(185)(pro)] genes, respectively, were apoptotic. The percentage of apoptotic cells was significantly higher in cell cultures expressing NS2B-NS3(185)(pro). NS2B-NS3(185)(pro) was detected as NS2B-NS3(185)(pro)-EGFP fusion protein in cytoplasmic vesicular structures in the apoptotic cells. Site-directed mutagenesis which replaced His(51) with Ala within the protease catalytic triad significantly reduced the ability of the expressed NS3 and NS2B-NS3(185)(pro) to induce apoptosis. Results from the present study showed that DENV-2-encoded NS3 serine protease induces apoptosis, which is enhanced in cells expressing its precursor, NS2B-NS3(185)(pro). These findings suggest the importance of NS2B as a cofactor to NS3 protease-induced apoptosis.

MeSH terms: Amino Acid Sequence; Animals; Cercopithecus aethiops; Dengue Virus/pathogenicity*; Humans; Luminescent Proteins/genetics; Luminescent Proteins/metabolism; Molecular Sequence Data; Protein Precursors/metabolism*; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Serine Endopeptidases; Vero Cells; Apoptosis*; Viral Nonstructural Proteins/metabolism*; Viral Nonstructural Proteins/chemistry; RNA Helicases; Green Fluorescent Proteins; Mice
Ethnicity and drug therapy for hypertension

Amudha K, Wong LP, Choy AM, Lang CC

Curr Pharm Des, 2003;9(21):1691-701.
PMID: 12871202

Physiological and pharmacological responses may be influenced by ethnicity as a result of genetic factors, environmental factors and/or their interaction. This review is divided into 2 parts. Firstly, there will be overview of ethnicity as a determinant of drug metabolism and response with reference to antihypertensive agents. The concept of ethnicity has been applied extensively to the study of hypertension especially in American blacks in whom the hypertension is more common and more aggressive. Thus, the second part of this review will then focus on examining the black-white differences in physiological responses to pharmacological challenge that may provide a link between these models and known ethnic differences in drug responses. We will discuss the hypertension studies that have examined the relative effectiveness of different classes of antihypertensive agents including several recent cardiovascular outcome trials that either have a high proportion of blacks or were conducted entirely in black subjects.

MeSH terms: Antihypertensive Agents/metabolism*; Antihypertensive Agents/pharmacology; Antihypertensive Agents/therapeutic use; Clinical Trials as Topic; Humans; Hypertension/drug therapy*; Hypertension/ethnology*; Hypertension/metabolism; Polymorphism, Genetic; Treatment Outcome; African Continental Ancestry Group; European Continental Ancestry Group

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