A S Lee

Singapore General Hospital, Singapore, Singapore

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Publications (8)29.27 Total impact

  • Source
    Article: Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates.
    A S Lee, A S Teo, S Y Wong
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    ABSTRACT: Novel mutations in NADH dehydrogenase (ndh) were detected in 8 of 84 (9.5%) isoniazid (INH)-resistant isolates (T110A [n = 1], R268H [n = 7]), but not in 22 INH-susceptible isolates of Mycobacterium tuberculosis. Significantly, all eight isolates with mutations at ndh did not have mutations at katG, kasA, or the promoter regions of inhA or ahpC, except for one isolate. Mutations in ndh appear to be an additional molecular mechanism for isoniazid resistance in M. tuberculosis.
    Antimicrobial Agents and Chemotherapy 08/2001; 45(7):2157-9. · 4.84 Impact Factor
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    Article: Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma.
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    ABSTRACT: Loss of heterozygosity (LOH) is frequent at the chromosomal region 11q22-q23 in several types of tumours of diverse cell origin. Previous investigations of LOH at this chromosomal region in colorectal carcinoma have been contradictory in their findings, and have only included between 1-4 loci. In order to define any regions of LOH on 11q23, we investigated 16 loci between D11S940 and D11S934 on the long arm of chromosome 11 using microsatellite analysis. Of 57 colorectal carcinomas specimens, 36 (63.2%) demonstrated LOH at one or more marker, with the highest frequencies of LOH at D11S1340 (41.0%), located between 105.13-111.97 Mb from the centromere, and D11S924 (37.1%) and D11S4107 (40.5%), both located approximately 113 Mb from the centromere. No statistically significant associations between LOH and age-of-presentation or Dukes' stage were found. LOH was observed in colorectal tumours of all Dukes' stages, including Dukes' stages A and B, suggesting that the inactivation of a tumour suppressor gene(s) on 11q23 occurs in the early stages of colorectal carcinoma. These results confirm the presence of putative tumour suppressor gene(s) at chromosome 11q23, involved in the carcinogenesis of colorectal carcinoma, and will facilitate future identification of candidate genes.
    British Journal of Cancer 10/2000; 83(6):750-5. · 5.04 Impact Factor
  • Article: Contribution of kasA analysis to detection of isoniazid-resistant Mycobacterium tuberculosis in Singapore.
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    ABSTRACT: Genotypic analysis of resistance to isoniazid (INH) in Mycobacterium tuberculosis is complex due to the various genes potentially involved. Mutations in ketoacyl acyl carrier protein synthase (encoded by kasA) were present in 16 of 160 (10%) INH-resistant isolates (R121K [n = 1], G269S [n = 3], G312S [n = 11], G387D [n = 1]). However, G312S was also present in 6 of 32 (19%) susceptible strains. kasA analysis contributed marginally to the performance of INH genotypic testing in Singapore. The significance of kasA polymorphisms in INH resistance should be carefully established.
    Antimicrobial Agents and Chemotherapy 09/1999; 43(8):2087-9. · 4.84 Impact Factor
  • Article: Rapid mycobacterial tuberculosis detection in bronchoalveolar lavage samples by polymerase chain reaction in patients with upper lobe infiltrates and bronchiectasis.
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    ABSTRACT: In areas where tuberculosis is endemic, a positive sputum acid-fast bacilli (AFB) smear is frequently regarded as almost diagnostic of pulmonary tuberculosis (PTB). The main problem arises when the AFB smear is negative. The main aim of this study was to determine the clinical utility of rapid mycobacterial tuberculosis (MTB) detection in bronchoalveolar lavage (BAL) samples by polymerase chain reaction (PCR) in 52 patients who underwent diagnostic bronchoscopy for suspected PTB. These patients had either upper lobe infiltrates (n = 31) or bronchiectasis (n = 21). Mycobacterial culture is usually used as the gold standard of diagnosis. We chose to define active PTB based on positive mycobacterial cultures and/or histological evidence of caseous necrosis and AFB, and/or when there was clinical plus radiological improvement following therapy. We compared AFB smear, respiratory mycobacterial culture, BAL PCR for MTB and clinical active PTB. Four patients who were smear and culture negative had clinical and radiological clearance following anti-tuberculous therapy showing that using mycobacterial culture as a gold standard may have its limitations. When Kappa (a chance-corrected measure of agreement) was calculated for acid-fast bacilli smear and BAL PCR against our definition of active PTB, it was 0.28 (fair agreement) and 0.73 (substantial agreement), respectively. BAL PCR gave a sensitivity, specificity, positive and negative predictive values of 66.7%, 100%, 100% and 88%, respectively, for the group with upper lobe infiltrates. We also demonstrated that BAL for PCR has a good concordance with the final diagnosis of active tuberculosis.
    Annals of the Academy of Medicine, Singapore 04/1999; 28(2):205-8. · 1.25 Impact Factor
  • Article: Lack of clinical significance for the common arginine-to-leucine substitution at codon 463 of the katG gene in isoniazid-resistant Mycobacterium tuberculosis in Singapore.
    The Journal of Infectious Diseases 11/1997; 176(4):1125-7. · 6.41 Impact Factor
  • Article: Acute viral hepatitis E: clinical and serologic studies in Singapore.
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    ABSTRACT: Seroprevalence of hepatitis E is now documented in many countries around the world, but studies of its clinical manifestations and serologic course have been confined to endemic areas. We have prospectively evaluated the occurrence, evolution, and outcome of acute hepatitis E in our patients. Fifteen patients (11 men, 4 women; median age: 41 years) were diagnosed to have acute, sporadic hepatitis E between July 1993 and January 1995; 10 of the 15 were followed up. Sera anti-hepatitis E virus (HEV) immunoglobulin (Ig)G and IgM antibodies and HEV ribonucleic acid in the blood and stool were tested at weeks 1 and 2; serial tests for hepatitis E antibodies and liver function were carried out at months 1, 3, 6, 9, 12, and 18. Coinfection with hepatitis A and superinfection on chronic hepatitis B were found in 3 and 2 patients, respectively. One patient had transient passage of virus in the stool, but none was viremic. Eighty-seven percent of patients lost their IgM antibodies within 3 months, but anti-HEV IgG, once present, persisted throughout follow-up. All patients but one had complete recovery. A higher than reported level of alanine transaminase (mean: 28.5 times normal) and the lack of viremia during acute infection in our patients may be due to increased immune-mediated viral clearance.
    Journal of Clinical Gastroenterology 07/1997; 24(4):235-8. · 3.16 Impact Factor
  • Article: Quantitation of hepatitis C viraemia by a competitive reverse transcription-polymerase chain reaction system.
    A S Lee, C J Oon, M K Chee, Y C Seo
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    ABSTRACT: Chronic hepatitis C infection is associated with the rapid development of cirrhosis and hepatocellular carcinoma. A quantitative assay to determine the level of hepatitis C (HCV) viraemia during treatment would be useful in determining the effect of antiviral agents. Such an assay has been developed with the principle of the method being the co-amplification of the viral genome isolated from the patient with an RNA competitor molecule (CM) using the competitive reverse transcription-polymerase chain reaction (RT-PCR). Known amounts of the CM compete for amplification with HCV RNA from the patient. To quantify each sample, 5 amplification reactions with titrated amounts of CM were performed. The CM can be distinguished from the normal HCV PCR product since it has been genetically altered to be a smaller molecule by the process of restriction digestion, ligation and reamplification. This quantitative method was used to monitor the viral load in 10 patients undergoing antiviral therapy with lymphoblastoid interferon. The level of HCV viraemia in these patients ranged from 10(9) to 10(12) genomes/ml serum. Declines in the level of viraemia were seen in 8 of the 10 patients after therapy. Since patients with low HCV viraemia levels are more likely to respond to interferon therapy in a sustained fashion, this method may also be employed to quantitate the level of viraemia in patients prior to interferon treatment, and may be an indicator of the dose and schedule of treatment. These results show that this quantitative method is useful in the monitoring of HCV viral load in patients.
    Annals of the Academy of Medicine, Singapore 02/1996; 25(1):98-102. · 1.25 Impact Factor
  • Article: Partial sequence analysis of the hepatitis C viral genome in Singapore patients.
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    ABSTRACT: The distribution of hepatitis C viral (HCV) genotypes in Singapore has not been previously determined. We studied the sera of 40 Singapore patients which were PCR-positive for HCV. The HCV genotypes were determined by direct sequencing of amplified sequences of the 5' non-coding region, after reverse transcription. Of the 40 samples, 35/40 (87.5%) were of HCV type 1, 2/40 (5.0%) were of type 2 and 3/40 (7.5%) were of type 3. The most common HCV genotype in this study was the type 1 genotype. Our results confirm the wide geographical distribution of HCV genotypes.
    Biochemical and Biophysical Research Communications 03/1994; 199(1):37-40. · 2.48 Impact Factor