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Human T- and B-lymphocyte populations in blood: local population studies

Pang T, Parasakthi N, Yap SF

Med J Malaysia, 1979 Mar;33(3):243-6.
PMID: 316496
Serum complement (C3 and C4) levels in the Malaysian adult population

Yap SF, Pang T

Asian J Infect Dis, 1979 Jun;3(2):85-7.
PMID: 120736

Serum C3 and C4 values were determined in 236 normal adults of three racial groups, using the single radial immunodiffusion techniques. The C3 levels varied from 47 to 119 mg/dl and C4 levels from 16 to 66 ml/dl (mean +/- 2SD). The values were found to be comparable to the normals reported in some Western series. No significant differences in the levels related to sex and race were found.
The immunology laboratory services in Malaysia

Yap SF

Malays J Pathol, 1982 Aug;5:11-3.
PMID: 7187453
Childhood primary hepatocellular carcinoma and hepatitis B virus infection

Cheah PL, Looi LM, Lin HP, Yap SF

Cancer, 1990 Jan 1;65(1):174-6.
PMID: 2152851

In the 7-year period between 1980 and 1987, six cases of childhood primary hepatocellular carcinoma (PHC) were confirmed histologically in our institution. Hepatitis B surface antigen (HBsAg) seropositivity was confirmed in five of the cases, and tissue HBsAg was shown in four of these using the Shikata's orcein stain. An associated maternal HBsAg seropositivity was shown in two of the seropositive children. The youngest seropositive patient who developed PHC was 7 years old. The mother of this patient was also seropositive. These observations support a causal relation between childhood Hepatitis B virus infection and PHC. The importance of vertical or perinatal transmission of HBV in the causation of childhood PHC and the prophylactic role of childhood vaccination is emphasized. Attention is also drawn to the relative short malignant transformation time seen in some of these patients.
Fulltext Multiple myeloma in the University Hospital: a retrospective study of biodata, clinical, laboratory and radiological profiles, 1980-1987

Wong KT, Ng SC, Kuperan P, Yap SF, Menaka N, Bosco J

Med J Malaysia, 1990 Jun;45(2):136-43.
PMID: 2152018

A retrospective study of 37 cases of multiple myeloma admitted from 1980 to 1987 to the University Hospital Kuala Lumpur, Malaysia, was carried out to analyse the biodata, clinical presentation, laboratory and radiological profiles. The cases were selected after they had satisfied preset diagnostic criteria. The mean age was 60 years. There was no sex or ethnic preponderance. The most common symptom was bone pain. Pallor was detected in 73% of the patients. Haemoglobin was less than 120 g/L in 95%, and ESR was greater than 100 mm/hr in 70% of cases. Bone marrow and trephine biopsies were diagnostically important. Hypercalcaemia occurred in seven cases out of which three were IgA myelomas. Either serum creatinine or blood urea was raised in nearly 50% of cases. The most common heavy chain paraprotein was IgG while Kappa light chain was the commoner light chain type. 86% of cases had osteolytic lesions. These findings are, in general, similar to those of larger studies on multiple myeloma.

Study site: University Malaya Medical Centre (UMMC)
A case of childhood hepatitis B virus infection related primary hepatocellular carcinoma with short malignant transformation time

Cheah PL, Looi LM, Lin HP, Yap SF

Pathology, 1991 Jan;23(1):66-8.
PMID: 1648195

A case of primary hepatocellular carcinoma (PHC) developing in a 10 year old boy who contracted Hepatitis B virus (HBV) infection in the course of maintenance phase chemotherapy for acute lymphoblastic leukemia was seen at University Hospital, Kuala Lumpur. This case is of interest in that it (1) supports an etiological relationship between HBV infection and PHC, (2) manifested a distinctly short malignant transformation time, and (3) draws attention to the possible contributory role of chemotherapy in increasing the risk of developing PHC.
Hepatitis B infection among Chinese STD patients in Kuala Lumpur, Malaysia

Gan CY, Yap SF, Ngeow YF, Wong HC

Sex Transm Dis, 1991 4 1;18(2):84-8.
PMID: 1862464 DOI: 10.1097/00007435-199118020-00006

This study documents the prevalence of Hepatitis B serological markers among STD patients who have had multiple sexual partners in Kuala Lumpur, Malaysia, and compares the rates with those of a sample of the population with single or no sexual partners. A total of 336 Chinese STD patients (multiple partners group) and 234 Chinese control subjects (non-multiple partner group) were screened. Those with a history of blood transfusion or parenteral drug abuse had been excluded from the study, and all study subjects were heterosexuals. The overall carrier rate was 9.2% for the multiple partner group (MP group) and 6.8% for the non-multiple partner group (NMP group). Infection rates were 64.3% for the MP-group and 38.9% for the NMP group. After adjustments for age and sex, there was no significant difference in carrier rates between the two groups, but infection rates were significantly different with the MP group, being 3.2 times more likely to acquire infection than the NMP group. The study concludes that in heterosexuals, those with multiple sexual partners have increased chances of acquiring HBV infection.
Squamous cell carcinoma related antigen in uterine cervical carcinoma

Cheah PL, Yap SF, Looi LM, Sivanesaratnam V

Malays J Pathol, 1991 Jun;13(1):37-41.
PMID: 1795560

Squamous cell carcinoma-related antigen (SCC-Ag), first described by Kato and Torigoe in 1977, has been cited by various workers as a serological marker for some epithelial neoplasms. The most well-studied is its association with carcinoma of the uterine cervix. In January 1989, we embarked on a prospective, multivariate study at the University Hospital, Kuala Lumpur to assess the usefulness of serologically assaying SCC-Ag (using the Abbott RIA diagnostic kit) in our patients with carcinoma of the uterine cervix. We were also interested to ascertain whether SCC-Ag is a 'general' marker for all histological types of cervical carcinoma or specific for squamous carcinoma. From the time of commencement to June 1990, 35 newly-diagnosed and histologically-proven cases were entered into the study. Of these, 4 were keratinising squamous carcinoma, 18 large cell non-keratinising carcinoma, 3 adenosquamous carcinoma, 7 adenocarcinoma and 3 carcinoma-in-situ. Our preliminary results show that all keratinising squamous carcinoma and 1/3 each of large cell non-keratinising carcinoma, adenosquamous carcinoma and carcinoma-in-situ had positive pre-therapy serum SCC-Ag levels (i.e greater than 2 ng/ml, 2 ng/ml being an arbitrarily selected 'cut-off' value). In contrast, no adenocarcinoma was serologically positive. In addition, keratinising squamous carcinoma had the highest mean pre-therapy serum SCC-Ag level. The results imply that serum SCC-Ag is related to the (1) presence of squamous and not glandular differentiation and (2) degree of squamous differentiation.
Primary cardiac amyloidosis

Jeyamalar R, Pathmanathan R, Yap SF, Kannan P

Ann Acad Med Singap, 1991 Nov;20(6):795-7.
PMID: 1803972

Cardiac amyloidosis is an uncommon and often unrecognised cause of cardiac failure. It is an infiltrative disease that may mimic either a restrictive or hypertrophic cardiomyopathy, constrictive pericarditis, coronary artery disease or valvular heart disease. The diagnosis should be suspected in a patient with cardiac failure who has low voltage complexes on the electrocardiogram, in association with increased myocardial mass and echogenicity on the echocardiogram. The definitive diagnosis, however, can only be made by endomyocardial biopsy or biopsy of any involved organ in systemic amyloidosis. Prognosis is poor and treatment ineffective.
Alpha-fetoprotein in hepatocellular carcinoma: a serological and histochemical study in Malaysian patients

Yap SF, Peh SC

Malays J Pathol, 1991 Dec;13(2):115-8.
PMID: 1726642

Serum alpha-fetoprotein (AFP) levels and its expression in liver tissue was studied in 50 cases of histologically confirmed hepatocellular carcinoma (HCC). Serum AFP levels were elevated (greater than 20iu/ml) in 35/50 (70%) of the cases, 28 of whom had levels greater than 500 iu/ml, which is highly suggestive of HCC. These results indicate that serum AFP, by itself, is a relatively insensitive diagnostic test for HCC. Although elevated levels in high risk patients provide a specific clue, a negative result does not exclude the diagnosis of HCC. Expression of AFP by tumour cells paralleled that of serum in the majority of cases. However, tissue AFP was negative in 7 patients who had markedly elevated serum AFP. This observation may be a reflection of preferential excretion of the tumour antigen or differential expression of the antigen by the tumour cells. None of the patients with normal serum AFP demonstrated a reaction for tissue AFP. There was no correlation between AFP production and tumour differentiation.
HTLV-I antibody study in normal individuals and unselected hospital patients in Malaysia

Yap SF, Peh SC, Chan L, Wong HC, How VJ, Looi LM

Southeast Asian J. Trop. Med. Public Health, 1992 Mar;23(1):26-9.
PMID: 1355930

A serological investigation for human T cell leukemia virus I (HTLV-I) infection was carried out at the University Hospital, Kuala Lumpur. A total of 626 sera from a non-patient population and 1,038 sera from unselected in-patients were screened for HTLV-I antibodies using an enzyme-linked immunosorbent assay (ELISA). 27/1664 (1.6%) were found to be reactive. However, on Western blotting, only 2 sera were confirmed positive, both showing reactions for the major core (p19 and p24) and the envelope (gp46) proteins. Both of the serum samples were from unselected hospital patients. Most of the remaining sera which were reactive on screening showed indeterminate results on Western blotting. These were further tested by radioimmunoprecipitation assay (RIPA) and none of these sera gave a positive reaction. Therefore, only 2/1038 (0.19%) unselected patients could be confirmed to have antibodies to HTLV-I. None of the normal individuals screened showed a positive Western blot result. Our data indicate that HTLV-I infection is present in our population, but at a low prevalence rate.
Serum hepatitis B virus DNA: relationship with the e-antigen and anti-e status in chronic carriers

Yap SF, Wong NW, Goh KL

Malays J Pathol, 1994 Jun;16(1):57-62.
PMID: 16329577

The relationship between serum Hepatitis B virus DNA (HBV-DNA) and the Hepatitis B e-antigen/ anti-Hepatitis Be (HBeAg/anti-HBe) serological status in Malaysians was studied. 212 cases of asymptomatic HBV carriers were recruited for this study. 92 cases were positive for the HBeAg at the point of recruitment. 85 (92.4%) of these patients tested positive for HBV-DNA, of whom 55 (64.7%) had levels over 100pg/ml of serum. Three of the remaining 7 HBeAg positive cases who were negative for HBV-DNA subsequently seroconverted. The other 4 cases remained negative for HBV-DNA for periods of 6-12 months. Out of 113 cases who were anti-HBe positive, 12 (10.6%) gave a positive HBV-DNA result. 2 of these 12 patients were recent seroconverters; the remaining cases had transiently increased viral replicative activity which later subsided. 7 out of the 212 carriers were in the e-window period; all 7 tested negative for HBV-DNA. Our data confirm a high frequency of HBV-DNA in HBeAg positive carriers and a negative correlation between HBV-DNA and anti-HBe. An atypical profile of anti-HBe associated with HBV-DNA was observed in 10.6% of the carriers. An inverse relationship between serum HBV-DNA levels and age was also observed.
Chronic hepatitis B infection in Malaysians

Yap SF

Malays J Pathol, 1994 Jun;16(1):3-6.
PMID: 16329567

Chronic hepatitis B virus (HBV) infection constitutes a major public health problem particularly in developing countries in East Asia, South-East Asia, the Pacific Basin and Africa. In Malaysia, a developing nation in the South East Asian region, the chronic HBV carrier rate varies between < 1% to about 10% depending on the ethnic group studied. The highest frequency is seen among the Chinese, followed by the Malays and lastly the Indians, with a male preponderance of between 2 : 1 and 3 : 1. Exposure to the virus among the adult population is estimated to be about 15%, 26% and 36% among the Indians, Malays and Chinese respectively. Serological study of adult chronic HBV carriers showed a frequency of HBe antigenemia of about 35%, with a significant decreasing trend with age. HBV DNA status generally correlated with the HBe status. An atypical profile of anti-HBe associated with serum HBV DNA is found in some carriers; in most instances, this is related to seroconversion from HBe antigenemia to anti-HBe. Chronic complications of HBV infection include the development of hepatocellular carcinoma (HCC), the occurrence of which closely parallel that of HBsAg carrier rate. In Malaysia, HCC is the third most common malignant neoplasm and among the 10 leading causes of death. About 80% of our HCC cases are HBV associated. All 3 ethnic groups are afflicted, the highest frequency being among the Chinese. Males show a disproportionate risk with an odds ratio of 3.93 (p < 0.0001).
Squamous cell carcinoma antigen as an adjunct tumour marker in primary carcinoma of the lung

Cheah PL, Liam CK, Yap SF, Looi LM

J Clin Pathol, 1994 Jun;47(6):535-7.
PMID: 8063936

AIMS: To determine (1) the detection rate of primary carcinoma of the lung by serological assay of CEA (carcinoembryonic antigen); and (2) whether addition of seroassay of squamous cell carcinoma related antigen before treatment improves detection sensitivity.
METHODS: A prospective study spanning 27 months was conducted at the University Hospital, Kuala Lumpur. Serum CEA (Abbott IMx) and serum squamous cell carcinoma antigen (Abbott IMx) from patients clinically suspected of having primary carcinoma of the lung, were assayed using the microparticle enzyme immunoassay method.
RESULTS: Thirty seven cases of histologically confirmed primary lung carcinoma were studied. Of these, 17 were squamous cell carcinomas, 10 adenocarcinomas, nine small cell carcinomas, and one large cell carcinoma. The patients' ages ranged from 34-82 years. The male:female ratio was 3.6:1. Squamous cell carcinoma antigen was raised above the cutoff value of 1.5 ng/ml in 94.1% of squamous cell carcinomas, 20.0% of adenocarcinomas, and 11.1% of small cell carcinomas. By comparison, CEA was raised above the cutoff value of 3.0 ng/ml in 70.6% of squamous cell carcinomas, 77.8% of small cell carcinomas, and 100% of adenocarcinomas. CEA and squamous cell carcinoma antigen were not raised in the patient with large cell carcinoma and in 14 healthy volunteers. None of 15 patients with a variety of benign lung diseases showed a rise of CEA, while two patients--a 25 year old Indian woman with pneumonia and a 64 year old Malay man with bronchial asthma--had raised squamous cell carcinoma antigen values above the cutoff. Serum CEA and squamous cell carcinoma antigen values did not seem to correlate with stage or degree of differentiation of the tumours.
CONCLUSIONS: The findings suggest that CEA is a good general marker for carcinoma, particularly adenocarcinoma. In contrast, squamous cell carcinoma antigen is more specific for squamous carcinoma.
Hybridisation analysis for serum hepatitis B virus DNA

Yap SF, Wong PW, Kenneth-Raj

Br J Biomed Sci, 1994 Dec;51(4):336-40.
PMID: 7756940

A study was carried out to determine optimal assay conditions for an in-house hybridisation assay for detection of hepatitis B virus (HBV) genome in serum samples. Pre-treatment of samples, blot treatment and hybridisation conditions were found to affect assay performance. The indirect serum blot procedure was more robust and reliable than direct serum blotting. In the former, viral particles were isolated from the sample, lysed and then extracted. In comparison, no approaches to the direct serum spot method performed adequately. Sensitivity studies showed that labelling of the nucleic acid probe with dCTP was more efficient than with dATP. Using probes labelled to a specific activity of > 1 x 10(8) and an autoradiography period of about 48 h we could achieve a detection limit of < 1 pg. Specificity was achieved by use of a highly purified probe and moderately stringent hybridisation and wash conditions. Background binding was minimal and there was no non-specific binding of probe to negative control samples. Factors affecting speed of the assay were studied to identify steps that could be modified to shorten assay time without sacrificing performance. A shorter centrifugation step and the use of a high specific-activity probe permitted completion of an assay within four days.
Oxidative susceptibility of low density lipoprotein from rabbits fed atherogenic diets containing coconut, palm, or soybean oils

Yap SC, Choo YM, Hew NF, Yap SF, Khor HT, Ong AS, et al.

Lipids, 1995 Dec;30(12):1145-50.
PMID: 8614305

The oxidative susceptibilities of low density lipoproteins (LDL) isolated from rabbits fed high-fat atherogenic diets containing coconut, palm, or soybean oil were investigated. New Zealand white rabbits were fed atherogenic semisynthetic diets containing 0.5% cholesterol and either (i) 13% coconut oil and 2% corn oil (CNO), (ii) 15% refined, bleached, and deodorized palm olein (RBDPO), (iii) 15% crude palm olein (CPO), (iv) 15% soybean oil (SO), or (v) 15% refined, bleached, and deodorized palm olein without cholesterol supplementation [RBDPO(wc)], for a period of twelve weeks. Total fatty acid compositions of the plasma and LDL were found to be modulated (but not too drastically) by the nature of the dietary fats. Cholesterol supplementation significantly increased the plasma level of vitamin E and effectively altered the plasma composition of long-chain fatty acids in favor of increasing oleic acid. Oxidative susceptibilities of LDL samples were determined by Cu2(+)-catalyzed oxidation which provide the lag times and lag-phase slopes. The plasma LDL from all palm oil diets [RBDPO, CPO, and RBDPO(wc)] were shown to be equally resistant to the oxidation, and the LDL from SO-fed rabbits were most susceptible, followed by the LDL from the CNO-fed rabbits. These results reflect a relationship between the oxidative susceptibility of LDL due to a combination of the levels of polyunsaturated fatty acids and vitamin E.
Correlation between histological grade and c-erbB2 oncoprotein overexpression in infiltrating ductal carcinoma of breast

Looi LM, Cheah PL, Yap SF

Malays J Pathol, 1997 Jun;19(1):35-9.
PMID: 10879240

One hundred and twelve infiltrating ductal carcinoma of breast were studied by the standard avidinbiotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2 oncoprotein. The same tumours were assessed and scored according to the Bloom and Richardson criteria into three histological grades. The distribution of tumours according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade I tumours. This study shows a good correlation between c-erbB-2 expression and histological grade, a known prognostic indicator of invasive breast carcinoma. Because the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor gene, its overexpression can be expected to result in more aggressive tumour behaviour. While it may be regarded as another indicator of poor prognosis breast cancers, its value in the selection of carcinomas less responsive to hormonal therapy and those more suitable for immunotherapy than chemotherapy has been mooted but remains to be clarified.
Correlation between oestrogen receptor protein expression in infiltrating ductal carcinoma of the breast by immunohistochemistry and cytosol measurements

Looi LM, Yap SF, Cheah PL

Ann Acad Med Singap, 1997 Nov;26(6):750-3.
PMID: 9522973

Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas were analysed for cytosolic oestrogen receptor (ER) protein content using a solid phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER-EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same carcinomas were examined for nuclear immunoreactivity against a monoclonal antibody for ER protein (Dako) using the standard avidin-biotin complex immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER positivity by IP was also scored according to a visual estimation of the percentage of cells expressing immunopositivity and the intensity of staining. Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER-negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3 (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may be variously due to inadequate antigen retrieval, faulty technique and the possibility that the two methods do not measure identical ER proteins. IP appears to have an advantage over EIA in that it has a higher pick-up rate, does not require fresh tissue and can be applied to archival material. However, to reduce false negative estimations, it may be necessary to run IP staining using more than one ER antibody. Standardisation of the IP method for ER is desirable before this method is to be widely adopted in Malaysian laboratories. Quantitation of ER positivity by IP scoring correlated poorly with actual cytosolic levels. Caution should be exercised in attaching patient management value to visual IP scoring.
Fulltext Enhanced major histocompatibility complex (MHC) class II antigen expression in lupus nephritis

Cheah PL, Looi LM, Chua CT, Yap SF, Fleming S

Malays J Pathol, 1997 Dec;19(2):115-20.
PMID: 10879251

Thirty-eight cases of lupus nephritis, all satisfying the American Rheumatism Association criteria for diagnosis of systemic lupus erythematosus (SLE), with renal involvement and biopsy were immunohistochemically studied for the expression of HLA-DR (DAKO: HLA-DR/alpha, TAL.1B5), one of the three known families belonging to the class II major histocompatibility complex (MHC), using a standard streptavidin-biotin-peroxidase method. 20 nephrectomies performed for renal trauma and tumours constituted the normal controls. Of the lupus nephritis cases, 34 were females and 4 males. Ethnically, 20 were Chinese, 13 Malay, 4 Indian and 1 of indigenous origin. Their ages ranged from 16 to 59 years (mean of 31 years). Histologically, 23 expressed World Health Organisation (WHO) class IV (diffuse proliferative), 10 WHO class V (diffuse membranous), 4 WHO class II (pure mesangiopathy) and 1 WHO class III (segmental and focal proliferative) nephritis. Activity scores ranged between 5 to 19 (mean = 8.6) and chronicity scored between 2 to 7 (mean = 3.2) on a standard scoring system. Similar to other studies, HLA-DR was expressed in the glomerular capillaries and peritubular capillaries of all and mesangium, tubules (proximal, distal and collecting), veins and arterioles of some normal controls. Interestingly, HLA-DR expression was noted in the arteries of 25% of the normal controls, a finding hitherto not reported. The frequency of lupus nephritis cases expressing HLA-DR in the various anatomical components did not differ significantly from the normal controls except that HLA-DR expression in arteries and arterioles was seen at a significantly increased frequency (p < 0.01) in lupus nephritis. This increased expression did not correlate with the WHO class, activity or chronicity scores. It therefore appears that MHC class II shows increased expression in the arterial system of lupus nephritis kidneys. The significance of this is unclear but could be related to heightened (gamma-interferon activation which may be a de novo phenomenon or result of T cell proliferation and activation in SLE.
Detection of Mycobacterium tuberculosis in bronchoalveolar lavage from patients with sputum smear-negative pulmonary tuberculosis using a polymerase chain reaction assay

Liam CK, Chen YC, Yap SF, Srinivas P, Poi PJ

Respirology, 1998 Jun;3(2):125-9.
PMID: 9692522

The objective of this study was to evaluate the utility of a polymerase chain reaction (PCR) assay in detecting Mycobacterium tuberculosis in bronchoalveolar lavage (BAL) specimens of patients suspected of having active pulmonary tuberculosis (TB) but who were sputum smear-negative. Patients undergoing investigation for suspected pulmonary TB at the University Hospital, Kuala Lumpur, and who were sputum smear-negative underwent fibreoptic bronchoscopy and BAL. One portion of each lavage specimen was submitted for smear examination for acid-fast bacilli and mycobacterial culture and the other portion assayed by PCR for the presence of a 562-base pair DNA segment belonging to the insertion sequence IS986, unique to the M. tuberculosis complex. As controls, lavage specimens from patients with other lung lesions were also similarly tested. The PCR assay gave a positivity rate of 80.9% (55 of 68) compared with 8.8% of smear examination and 7.4% of culture for detecting M. tuberculosis in BAL specimens. The assay was positive in two of 45 BAL specimens from 35 control subjects. The PCR assay was more sensitive than smear and culture in detecting M. tuberculosis in BAL specimens of patients with sputum smear-negative pulmonary TB.

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