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Biomedical subjects

J W Mak

Publications and source records attributed to J W Mak.

At least 19 recordsLinked to original sources
PubMed2004

Research on cancer diagnosis in Malaysia: current status.

Cancer is a major morbidity and mortality concern in Malaysia. Based on National Cancer Registry data, the Malaysian population is estimated to bear a cancer burden of about 40,000 new cases per year, and a cumulative lifetime risk of about 1:4. Cancer research in Malaysia has to consider needs relevant to our population, and resources constraints. Hence, funding bodies prioritise cancers of high prevalence, unique to our community and posing specific clinical problems. Cancer diagnosis is crucial to cancer management. While cancer diagnosis research largely aims at improvements in diagnostic information towards more appropriate therapy, it also impacts upon policy development and other areas of cancer management. The scope of cancer diagnosis upon which this paper is based, and their possible impact on other R&D areas, has been broadly categorized into: (1) identification of aetiological agents and their linkages to the development of precancer and cancer (impact on policy development, cancer prevention and treatment), (2) cancer biology and pathogenesis (impact on cancer prevention, treatment strategies and product development), (3) improvements in accuracy, sensitivity and specificity in cancer detection, monitoring and classification (impact on technology development) and (4) prognostic and predictive parameters (impact on treatment strategies). This paper is based on data collected by the Working Group on Cancer Diagnosis Research for the First National Conference on Cancer Research Coordination in April 2004. Data was collated from the databases of Institutions/Universities where the authors are employed, the Ministry of Science, Technology and Innovation (MOSTI) and targeted survey feedback from key cancer researchers. Under the 7th Malaysia Plan, 76 cancer projects were funded through the Intensified Research in Priority Areas (IRPA) scheme of MOSTI, amounting to almost RM15 million of grant money. 47(61.8%) of these projects were substantially in cancer diagnosis, accounting for 65.6% (RM 9.7 million) of cancer project funds. The 8th Malaysia Plan saw a change in research strategy. The IRPA agency fielded several top-down projects which encouraged a multicentre and multidisciplinary approach. This resulted in larger funding per project i.e. RM32 million for 49 projects. There was also a surge of interest in drug development and natural products. Because of this shift in direction, cancer diagnosis projects constituted only 51% of IRPA-funded cancer projects. Nonetheless funding for cancer diagnosis research has exceeded that of the 7th Malaysia Plan, being RM12.5 million by March 2004. The majority of such research is carried out at the Universities, engaging a large number of young scientists and postgraduate students (51 MSc and 21 PhD). A lot of research findings presented at scientific meetings have not yet been published and there is a glaring shortage of patents and commercialization of research findings (such as creation of test kits). Because diagnosis is very much a part of clinical practice, many researchers felt satisfied and confident that their work will be translated into practice and will significantly improve diagnostic services in Malaysia. National guidelines and consensus development on at least three malignancies i.e. breast cancer, oral cancer and lymphoma, have substantial basis in local R&D work. Problems encountered in research included (1) insufficient funding to realize research objectives, (2) lack of local expertise (most research assistants are inexperienced BSc graduates with no or minimal research experience), (3) inadequate technical support from vendors during equipment failure, (4) inexperienced Institutional development units to assist in product development, (5) lack of venture capital for commercialization of findings, and (6) inadequate incentives to undertake research. Researchers pointed out that plans to promote research should include the establishment of (1) regional and national cancer tissue banks, (2) a National Cancer Research Institute, (3) a dedicated cancer research fund, (4) a registry of cancer researchers, (5) national research coordinators, (6) improved coverage by the National Cancer Registry, (7) more international collaboration, (8) a better career structure for researchers, (9) improved Institutional support for product realization, and (10) better recognition for cancer researchers.

Humans↗
PubMed2004

Antifilarial compounds in the treatment and control of lymphatic filariasis.

Diethylcarbamazine citrate (DEC) has been used for treatment and control of lymphatic filariasis since the 1950s. Although this remarkable drug is still useful and modified strategies in its usage have been developed, a number of newer antifilarial compounds are now available. Numerous field trials evaluating their efficacy in the control of lymphatic filariasis have been conducted. In particular, ivermectin (IVM), albendazole (ALB), and DEC have been tested singly and in combinations and the results of such field studies should be evaluated. While most of the studies were based on efficacy in the clearance of microfilaraemia, a few clinical trials evaluated the adulticidal activity of these compounds. Some antibiotics are effective in killing Wolbachia bacteria symbionts of filarial worms, but their role in the chemotherapy of lymphatic filariasis is still undefined. This review of randomised controlled field studies and randomised controlled clinical trials with these compounds will summarise the findings and give recommendations on their appropriate use for the control and treatment of lymphatic filariasis.

Journal Article↗
PubMed2004

Important zoonotic intestinal protozoan parasites in Asia.

Intestinal protozoa are increasingly being studied because of their association with acute and chronic diarrhoea in immunocompromised as well as immunocompetent patients. Various community outbreaks due to contamination of water or food with these protozoa have further highlighted their importance in public health. Among these important pathogens are Giardia duodenalis, Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanensis, Isospora belli, and microsporidia. Except for the cyst-forming G. duodenalis and E. histolytica, the others are intracellular and form spores which are passed out with the faeces. These organisms are also found in various animals and birds and zoonotic transmission is thought to occur. These infections are distributed worldwide, with a higher prevalence in developing compared to developed countries. However, the relative importance of zoonotic infections especially in developing countries has not been studied in detail. The prevalence rates are generally higher in immunodeficient compared to immunocompetent patients. Higher prevalence rates are also seen in rural compared to urban communities. Most studies on prevalence have been carried out in developed countries where the laboratory and other health infrastructure are more accessible than those in developing countries. This relative inadequacy of laboratory diagnosis can affect accurate estimates of the prevalence of these infections in developing countries. However, reports of these infections in travellers and workers returning from developing countries can provide some indication of the extent of these problems. Most studies on prevalence of amoebiasis in developing countries were based on morphological identification of the parasite in faecal smears. As the pathogenic E. histolytica is morphologically indistinguishable from that of non-pathogenic E. dispar, estimates of amoebiasis may not be accurate. The epidemiology of human microsporidia infections is not completely understood. Two species, Enterocytozoon bieneusi and Encephalitozoon intestinalis, are associated with gastrointestinal disease in humans and it is believed that human to human as well as animal to human infections occur. However, the importance of zoonotic infections has not been fully characterised. G. duodenalis cysts, microsporidia and Cryptosporidium oocysts have been detected in various ground water resources, but their role in community outbreaks and maintenance of the infection has not been fully characterised. The taxonomic classification and pathogenic potential of B. hominis are still controversial. While considered by many as yeast, fungi or protozoon, recent sequence analysis of the complete SSUrRNA gene has placed it within an informal group, the stramenopiles. This review covers recent published data on these zoonotic infections and examines their public health importance in Asian countries.

Journal Article↗
PubMed2003

An outbreak of acute haemorrhagic conjunctivitis in Melaka, Malaysia.

This paper reports a second outbreak of acute haemorrhagic conjunctivitis due to coxsackievirus A24 in peninsular Malaysia. Between June 2002 and early October 2003, 10,327 patients, comprising 3,261 children and 7,066 adults, were treated for acute conjunctivitis in 11 government health clinics in the Melaka Tengah district of the state of Melaka. The figure grossly underestimates the size of the outbreak; as no patients treated in private clinics in the same district were included. Institution and household surveillance showed that the commonest presenting clinical feature of the illness was eye-discharge (91.2%), followed by foreign body sensation (81.8%), pain (78.3%) and subconjunctival haemorrhage (74.4%). The mean duration of illness was 6.5 and five days for patients with and without subconjunctival haemorrhage respectively.

Adolescent↗
PubMed2003

Polypeptides associated with in vitro cyst formation of Blastocystis hominis.

The objective of this study was to characterize the polypeptides associated with cysts of Blastocystis hominis. This form is believed to be infective and plays a role in parasite resistance to anti-B. hominis drugs currently used for treatment of Blastocystis associated diarrhea. Cysts were induced through in vitro culture of the parasite in complete medium supplemented with bacterial extract with trypticase, metronidazole or doxycycline. SDS-PAGE analysis showed almost similar polypeptide patterns of parasite extracts obtained from in vitro cultured parasites before and after exposure with the three supplements. Polypeptide bands at 76, 58.5, 48, 45, 40, 38, 32, 25 and 22 kDa were constantly seen in all antigenic preparations and no specific cyst-associated polypeptide was present. However, on immunoblot analysis, 3 out of 16 blastocystosis human sera identified a cyst-associated polypeptide at 60 kDa in all parasite extracts prepared from cultures with the three supplements. In addition, there were associated morphological changes detected in these parasites stained with acridine orange and observed under fluorescence microscopy. Metronidazole induced cyst forms (reddish cells) as early as 12 hours post-exposure; more cyst production (with stronger immunoblot bands) occurred after 24 hours exposure. However, cysts rupture with release and destruction of B. hominis daughters cells occurred after 48 hours exposure. Doxycycline induced less cyst-like forms at 24 hours (weaker 60 kDa band) and less destruction of the cysts (60 kDa band still present at 72 hours post exposure). Bacterial extract and trypticase also induced cysts at 12 hours with increasing numbers up to 72 hours exposure (corresponding increase in intensity of 60 kDa band from samples harvested at 12 to 72 hours post exposure) without any sign of deleterious effect on the parasite.

Animals↗
PubMed2000

Development of a highly specific recombinant Toxocara canis second-stage larva excretory-secretory antigen for immunodiagnosis of human toxocariasis.

The specificity of the recombinant Toxocara canis antigen developed for the immunodiagnosis of human toxocariasis was compared with that of the excretory-secretory antigen from T. canis second-stage larvae (TES) by enzyme-linked immunosorbent assay. A total of 153 human serum samples from patients infected with 20 different helminths, including 11 cases of toxocariasis, were examined. No false-negative reactions were observed for the toxocariasis cases. When the TES was used at concentrations of 0.5 and 0.125 microg/ml, cross-reactions were observed in 79 (55.6%) and 61 (43.0%) of 142 cases, respectively. In contrast, when the recombinant antigen was tested at a concentration of 0.5 microg/ml, cross-reactions were observed in 19 (13.4%) of 142 cases. At a concentration of 0.125 microg/ml, however, the cross-reaction rate decreased sharply to only 2.1%, corresponding to 3 of 142 cases. The cross-reactions occurred with one case each of gnathostomiasis, paragonimiasis with Paragonimus miyazakii, and spirometriasis, in which high antibody titers were detected. In addition, the recombinant antigen showed negative reactions with serum samples from patients infected with Ascaris and hookworms, which are the most common parasites in the world. These findings are also supported by experiments with animals infected with Ascaris and hookworm. From these results, the recombinant antigen is highly specific for toxocariasis and may provide more reliable diagnostic results than other methods.

Animals↗
PubMed1999

Seroprevalence of antibodies to hepatitis E virus in the normal blood donor population and two aboriginal communities in Malaysia.

The prevalence of antibodies to hepatitis E virus (HEV) has been examined in many countries, but such studies have generally been limited to majority populations such as those represented in healthy blood donors or cross sections of urban populations. Due to its major route of enteric transmission, large differences in HEV prevalence might be expected between populations in the same country but with different living conditions. Using an ELISA based on GST-ORF2.1 antigen, the prevalence of IgG-class antibodies to HEV was examined in three distinct populations in Malaysia: the normal (urban) blood donor population and two aboriginal communities located at Betau, Pahang and Parit Tanjung, Perak. IgG anti-HEV was detected in 45 (44%) of 102 samples from Betau and 15 (50%) of 30 samples from Parit Tanjung, compared to only 2 (2%) of 100 normal blood donors. The distribution of sample ELISA reactivities was also consistent with ongoing sporadic infection in the aboriginal communities, while there was no significant relationship between HEV exposure and age, sex, or malaria infection. The high prevalence of antibodies to HEV in the two aboriginal communities indicates that this group of people are at high risk of exposure to HEV compared to the general blood donors, and the results suggest that studies of HEV seroprevalence within countries must take into account the possibility of widely varying infection rates between populations with marked differences in living conditions.

Adolescent↗
PubMed1999

Strain differences in Blastocystis isolates as detected by a single set of polymerase chain reaction primers.

A total of 20 isolates of Blastocystis were characterized using a single set of polymerase chain reaction (PCR) primers. The amplification product revealed five types of pattern. All four isolates from Singapore yielded PCR products quite different from those of the local isolates. However, most of the local isolates showed a major product at either 280 or 500 bp, or both. We also suspected that the amplification product detected at 280 bp might be an indicator of the pathogenicity of this parasite. One isolate (M12) obtained from a monkey showed patterns similar to those of human isolates (10203 and KP1) and probably belongs to the same strain. The results indicate that the intraspecific or interstrain variations in these 20 Blastocystis isolates belong to 5 different patterns. The differences among isolates of the same strain revealed by the presence or absence of certain amplification products showed further intrastrain variations in this parasite.

Animals↗
PubMed1999

Blastocystis in animal handlers.

The present study investigated whether people working closely with animals were at higher risk of getting infected with Blastocystis hominis. The prevalence of the parasite was determined in two population groups, i.e., animal handlers and normal healthy individuals who did not work with animals. In all, 105 stool samples were collected from animal handlers from 2 local research institutions, a local zoo, and a local abattoir and 163 stool samples were collected from normal healthy individuals residing in high-rise flats in the city. The in vitro culture method used in the study detected that 41% of 105 animal handlers and 17% of 163 flat-dwellers in the city were positive for Blastocystis. This statistically significant finding (P = 0.0000313) shows that people who work closely with animals do stand at risk of acquiring Blastocystis infection.

Animal Technicians↗
PubMed1998

In vitro susceptibility studies of Malaysian Plasmodium falciparum isolates and clones against schizontocidal drugs.

Five Malaysian isolates of the protozoan Plasmodium falciparum Welch were cultured in vitro following the method of Trager and Jensen (1976, 1977) and subsequently cloned using the limiting dilution method of Rosario (1981). Thirty clones were obtained and were later characterized against schizontocidal drugs, chloroquine, mefloquine and quinine, using the modified in vitro microtechnique. Results showed that these local isolates were heterogeneous and most of the clones exhibited similar pattern of susceptibility as their parent isolate except for ST 168 clone and two ST 195 clones that were sensitive but two ST 165 clones, two ST 168 clones and five ST 195 clones were resistant against quinine, respectively. Results also indicated that they were pure clones compared to their parent isolate because their drug susceptibility studies were significantly different (p < 0.05).

Animals↗
PubMed1997

Plasma lipids and apolipoproteins in a population of Orang Asli ('aborigines') from West Malaysia.

Plasma total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDLC) and apolipoproteins Al (apo Al) and B (apo B) were measured in a sample of subjects from the Semai tribe of Orang Asli in peninsular Malaysia. They appeared to exhibit the lowest TC ever recorded (1.6 for males and 1.9 mmol/l for females) and relatively high TG (1.4 mmol/l for males and 1.5 mmol/l for females)(means for the whole sample). There was little apparent aging gradient in any of the plasma analytes. but the group of men aged 21-40 had lower HDLC than the corresponding female group. Both low density lipoprotein cholesterol (LDLC) (calculated) and HDLC as well as their corresponding apolipoproteins were correspondingly very low. There was a significant correlation between apo AI and HDLC in both sexes.

Adult↗
PubMed1997

Electrophoretic variations of peptidase E (PEPE) in characterizing clones and isolates of Plasmodium falciparum from different geographical areas.

Six clones were obtained from each Plasmodium falciparum (Welch, 1897) isolate from different geographical areas, Gombak A (Malaysian), Gombak C (Malaysian), ST 9 (Malaysian, ST 12 (Malaysian), ST 85 (Malaysian, ST 148 (Malaysian), Gambian (African) and TGR (Thailand) isolates using the limiting dilution method (Rosario 1981). Forty-eight clones were obtained and were characterized by an electrophoresis isoenzyme analysis of PEPE (Peptidase E) (EC. 3.4.11 or 13). Results showed that they were pure clones as they were monovariant with regards to this enzyme unlike their parent isolates which were divariant.

Aminopeptidases↗
PubMed1997

Genotype associations among seven apolipoprotein B polymorphisms in a population of Orang Asli of western Malaysia.

Associations among seven apolipoprotein B (APOB) gene polymorphisms [C-T promoter site; Leu-Ala-Leu signal peptide (SP) insertion/deletion; AG C,G site at codon 71; AG A1,D site at codon 591; XbaI site at codon 2488; AG H,I site at codon 3611; and AG T,Z site at codon 4154] were investigated in 195 members of an Orang Asli (aborigine) population from western Malaysia. Frequencies of the rare alleles for all these polymorphisms turned out to be low when compared with European but not Asian populations. The AG H,I site was not polymorphic. The highly polymorphic sites are in linkage disequilibrium among themselves, as shown by their delta values: SP 24,27 and AG C,G, 0.68; SP 24,27 and AG A1,D, 0.71; XbaI and AG C,G, 0.64; XbaI and AG A1,D, 0.57; SP 24,27 and XbaI, 0.48; and AG C,G and AG A1,D, 0.68. Ten unequivocal haplotypes on the basis of six sites (excluding the promoter polymorphism) were observed, and they represent 80% of the sample. The frequency of haplotype SP27,G,A1,X-,I,T, defined by the common homozygotes at all the sites for the APOB gene was 0.7, compared with 0.22 in Europeans. The ancestral haplotype SP27,G,D,X-,I,T was present at low frequency (0.01) in both the Orang Asli and Europeans. A cladogram constructed on the basis of haplotypes in the Orang Asli shows two different lines of evolution and that other haplotypes evolved by subsequent mutations on the ancestral haplotype.

Apolipoproteins B↗
PubMed1997

Detection of circulating antigens of Parastrongylus cantonensis in human sera by dot-blot ELISA and sandwich ELISA using monoclonal antibody.

A dot-blot ELISA was compared with a previously performed sandwich ELISA for the detection of Parastrongylus cantonensis antigens in sera from patients. Using the same monoclonal antibody and the same sera, 6 of 10 sera (60%) from parastronglyiasis patients were positive in dot-blot ELISA, whereas with sandwich ELISA, 5 of the same patient sera (50%) were positive. The specificity in both assays was 100% using 50 sera from patients with other parasitic diseases; of these, 10 each were from patients with cysticercosis, filariasis, gnathostomiasis, malaria and toxocariasis. The control group consisted of 53 sera from normal health Thais and Malaysians. The sensitivity of the assays was, however, slightly better with dot-blot ELISA and because it is simple, quick and cost-effective, it may be a test of choice for specific diagnosis of human parastrongyliasis.

Angiostrongylus cantonensis↗
PubMed1997

Detection of circulating antigens of Parastrongylus cantonensis in human sera by sandwich ELISA with specific monoclonal antibody.

A specific monoclonal antibody (AW-3C2) as revealed by ELISA was produced against the adult worm antigens of Parastrongylus cantonensis and used in a sandwich ELISA for the detection of circulating antigens in the sera of parastrongyliasis patients and those with other parasitic diseases. A total of 60 sera was used in this study. Of these, 10 each were from patients with parastrongyliasis filariasis, gnathostomiasis, malaria and toxocariasis. The control group consisted of 53 serum samples from normal healthy Thais and Malaysians. The mean +/- optical density (OD) values for the normal Thai and Malaysian groups were 0.126 +/- 0.028 and 0.124 +/- 0.029, respectively. Mean OD values of parastrongyliasis patient group differed significantly from that of the normal groups as well as those of other parasitic infections. Using a cut-off point of mean OD +/- 3SD of the normal control groups as indicating a positive reading, the specificity of the assay with this monoclonal antibody was 100% while the sensitivity was 50%.

Angiostrongylus cantonensis↗