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Biomedical subjects

S F Yap

Publications and source records attributed to S F Yap.

36 records · Page 2Linked to original sources

Chronic hepatitis B infection in Malaysians.

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).

Asian People↗

Serum hepatitis B virus DNA: relationship with the e-antigen and anti-e status in chronic carriers.

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.

Carrier State↗

Hybridisation analysis for serum hepatitis B virus DNA.

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.

DNA, Viral↗

A Drosophila gene encoding a protein with similarity to diacylglycerol kinase is expressed in specific neurons.

A Drosophila gene encoding a protein with similarity to diacylglycerol kinase (DGK) was isolated by screening a genomic DNA library with a human DGK cDNA under low-stringency hybridization conditions. This putative Drosophila DGK gene (dDGK) maps to 43E on the right arm of chromosome 2. A dDGK cDNA with an open reading frame encoding a 517 amino acid protein was obtained in a screen of a 3-12-h embryonic cDNA library. In a 236-amino-acid overlap at their C-termini there is an identity of 52.5% between the dDGK protein and human DGK. The N-terminus of the Drosophila protein is not similar to human DGK, and contains clusters of polar amino acids. dDGK is transcribed in the embryonic, pupal and adult stages, with little expression during the larval stages. Transcripts of 1.7-2.2 kb, 3.5 kb, 3.7 kb and 6.6 kb are seen, although most of the smaller transcripts may be from genes with similarity to dDGK. In stage-16 and stage-17 embryos, dDGK transcripts are limited to the central nervous system and head. There is a particularly high level of expression in the cell bodies of the larval photoreceptor organ, and in the cell bodies of the ventral unpaired median neurons. The dDGK protein may be involved in regulating signal transduction in these specific neurons.

Amino Acid Sequence↗

HTLV-I antibody study in normal individuals and unselected hospital patients in Malaysia.

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.

Adult↗

A case of childhood hepatitis B virus infection related primary hepatocellular carcinoma with short malignant transformation time.

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.

Antineoplastic Combined Chemotherapy Protocols↗

Alpha-fetoprotein in hepatocellular carcinoma: a serological and histochemical study in Malaysian patients.

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.

Biomarkers, Tumor↗

Squamous cell carcinoma related antigen in uterine cervical carcinoma.

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.

Antigens, Neoplasm↗

Primary cardiac amyloidosis.

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.

Adult↗

Childhood primary hepatocellular carcinoma and hepatitis B virus infection.

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.

Carcinoma, Hepatocellular↗

Multiple myeloma in the University Hospital: a retrospective study of biodata, clinical, laboratory and radiological profiles, 1980-1987.

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.

Aged↗

Serum complement (C3 and C4) levels in the Malaysian adult population.

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.

Adolescent↗

Hepatitis B infection among Chinese STD patients in Kuala Lumpur, Malaysia.

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.

Adolescent↗