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Biomedical subjects

P K Lim

Publications and source records attributed to P K Lim.

At least 19 recordsLinked to original sources

Fourier transform ultraviolet-visible spectrometer based on a beam-folding technique.

A beam-folding technique in optical interferometry, where the number of beam folds used can be very large, is reported. This technique can be used as a low-cost position-tracking method in a Fourier transform spectrometer (FTS) to cover the broad spectral range from UV to IR. The main advantage gained is the simple position-tracking algorithm used in sampling the interferogram. We have developed a UV-visible FTS, whose wavelength coverage is limited only by the optical elements (350 nm(-1) microm with off-the-shelf components). Preliminary results show that it can achieve a resolution of approximately 4 cm(-1) even with a ball-bearing translation stage.

Algorithms↗

Flavonoids from Blumea balsamifera.

3,4',5-Trihydroxy-3',7-dimethoxyflavanone was isolated from the ligroin extract of the leaves of Blumea balsamifera, while the acetone extract yielded 3',4',5-trihydroxy-7-methoxyflavanone and a new biflavonoid identifed as 3-O-7''-biluteolin (1). The isolation of 1 is significant since a biflavonoid with a C-O-C linkage of the type [I-3-O-II-7] has not been previously reported from a plant.

Asteraceae↗

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↗

Effects of insulin-like growth factors I and II on oestrone sulphatase activity in human breast cancer cell lines.

Oestrogens play an important role in the development of breast cancer. A very important source of active oestrogens in the breast is oestrone sulphate which is converted to oestrone by oestrone sulphatase. The aim of this study was to assess the effects of IGF-I and IGF-II on oestrone sulphatase activity in, as well as cell growth of, MCF-7 and MDA-MB-231 human breast cancer cell lines. Cells were grown in supplemented DMEM and treated with varying concentrations of IGFs. At the end of the treatment period, intact cell monolayers were washed and assayed for oestrone sulphatase activity and the number of cell nuclei determined on a Coulter Counter. Oestrone sulphatase activity was significantly stimulated by IGF-I and II at concentrations of 100 ng/ml and 200 ng/ml in MCF-7 cells. IGF-I had no effect on oestrone sulphatase activity in MDA-MB-231 cells over the range of concentrations tested. Significant inhibition of oestrone sulphatase was observed in MDA-MB-231 cells at higher concentrations of IGF-II (50 ng/ml, 100 ng/ml and 200 ng/ml). Both IGF-I and IGF-II at higher concentrations (100 ng/ml and 200 ng/ml) significantly inhibited MCF-7 and stimulated MDA-MB-231 cell growth. Since IGF-I and II have effects on cell growth and oestrone sulphatase activity in breast cancer cell lines they may play a role in the development and progression of human breast cancer.

Breast Neoplasms↗

Recent advances in diagnostic techniques in filariasis.

Accurate diagnosis of human filarial infections still remains a problem for clinicians and co-ordinators of filariasis control programs. Diagnosis of filariasis is based on parasitological, histopathological, clinical and immunological approaches. No significant advances have been made for the first three approaches although some refinements in their use and interpretation of results have occurred. For the immunological approach, intradermal tests and antibody detection assays using crude parasite extracts generally lack specificity and/or sensitivity to discriminate between past and present filarial infections in humans. Antigen detection assays would therefore provide a more accurate indication of active filarial infections. Several monoclonal antibodies to various stages of lymphatic filarial parasites have been developed and appear potentially useful for filarial antigen detection.

Animals↗

Epidemiology and control of malaria in Malaysia.

In spite of more than 30 years of control activities, malaria continues to be the most important parasitic infection in Malaysia, accounting for 39,189 confirmed cases in 1991, giving an annual parasite incidence rate of 2.2 per 1,000 population. Some factors contributing to the continued transmission of malaria are the development of drug resistant Plasmodium falciparum, changes in vector behavior, and ecological changes due to socio-economic reasons. Malaria parasite rates are higher among the Aborigines, land scheme settlers and those in intimate contact with the jungle, like loggers. There has been no substantial change in the proportion of the three common malaria species responsible for infections, P. falciparum, P. vivax, P. malariae and mixed infections accounting for about 70%, 28%, 1% and 1%, respectively of all infections. Drug resistant P. falciparum is unevenly distributed in Malaysia, but based on clinical experience and in vitro drug sensitivity studies, chloroquine resistance is frequently encountered. There has been clinical and laboratory evidence of resistance to sulfadoxine/pyrimethamine combination as well as quinine, but all these have so far been successfully treated with a combination of quinine and tetracycline. The eradication of the disease is impossible in the near future but there is confidence that with better surveillance techniques and the use of alternative control measures like permethrin impregnated bed-nets to complement existing ones, the target of bringing down the annual parasite incidence to 2 per 1,000 population during the Sixth Malaysian Plan period (1991-1995) can be achieved.

Animals↗

Detection of circulating plasmodial antigens in human sera by sandwich ELISA with monoclonal antibodies.

Two monoclonal antibodies (MAbs), one produced against Plasmodium falciparum (PF-IG8) and the other against P. cynomolgi (PC-IE12) schizont antigens were used in a sandwich ELISA for the detection of circulating plasmodial antigens in sera of patients infected with either P. falciparum, P. vivax or P. malariae. The mean +/- SD optical density (OD) values for the normal control group using PF-108 and PC-1E12 were 0.351 +/- 0.036 and 0.205 +/- 0.044, respectively. Mean OD values for the three infected groups were found to be significantly higher than those of the normal control group for both MAbs. However, ELISA values for individual serum specimens did not correlate with the level of parasitemia in the infected blood. Using a cut-off point of mean OD +/- 3 SD of the normal control group as indicating a positive reading, the specificity of this assay with both MAbs was 100%. The sensitivity of the assay using PF-1G8 was 95% while that obtained with PC-1E12 was 98%.

Animals↗

The effect of diethylcarbamazine citrate on incidence and recovery rates of Brugia malayi microfilaremia in Sabah, Malaysia.

Mass drug administration via 3 modes of delivery reduced the incidence and prevalence rates and intensity of Brugia malayi infection in 3 rural villages in the Bengkoka Peninsula, Sabah, in 1982-1983. A dosage of 6 mg diethylcarbamazine citrate (DEC-C)/kg body weight was administered either daily or weekly (total of 6 doses, 36 mg/kg body weight), and impact on B. malayi cases were comparable in the 3 villages. A total of 384 people participated in the DEC-C regimens, and all pregnant women and children under 2 years were excluded from the study. Bekessy's method of estimation of incidence and recovery rates was applied to data on B. malayi microfilaremia before drug administration. Treatment with DEC-C by any of the 3 modes of delivery drastically reduced the number of episodes of patent microfilaremia, incidence and prevalence, and median microfilarial density. Reduction was sustained for at least 18 to 24 months after treatment.

Adolescent↗

Applications of biotechnology in parasitic diseases in Malaysia.

Biotechnological tools are being used in malaria, filariasis and dengue research. The main emphasis has been on the production of reagents for immunodiagnosis and research. In this respect monoclonal antibodies (McAbs) against various species and stages of the above pathogens have been produced. It is hoped that these McAbs will be useful not only in immunodiagnosis but also for seroepidemiological applications. A DNA probe against Brugia malayi has been tested in Malaysia and was found to be sensitive and specific.

Animals↗

Parasitological and serological surveys for malaria among the inhabitants of an aborigine village and an adjacent Malay village.

Malaria surveys in an Orang Asli (aborigine) and an adjacent Malay village showed significantly higher parasite rates in the age-group 0-9 years in the former. Parasite rates declined progressively from a maximum at 0-4 years in the Orang Asli to zero at 30-39 years while in the Malays it rose progressively with age. Indirect fluorescent antibody test (IFAT) titres against schizont antigens of Plasmodium falciparum and P. cynomolgi were higher in the Orang Asli in all age-groups with a statistically significant inverse relationship between IFAT titres and parasite rates. IFAT titres in the Malay population also increased with age but were very much lower. Antibody levels detected by the enzyme-linked immunosorbent assay (ELISA) using soluble schizont antigens were also much higher in the Orang Asli and values with P. cynomolgi were higher than those with P. falciparum antigens. These differences are attributed to the higher malaria transmission in the younger age-groups of the Orang Asli and presumably greater immunological experience to a wider diversity of antigens than the Malays, thus explaining the presence of "protective" antibodies in the former but not the latter group.

Age Factors↗

Diffusion-in-gel enzyme-linked immunosorbent assay, ELISA and IFA test in the detection of malarial antibodies.

Malarial antibodies in 80 patients were measured using the diffusion-in-gel enzyme linked immunosorbent assay (DIG-ELISA), enzyme-linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) test. Good correlations were obtained between all three tests in terms of sensitivity and reliability. DIG-ELISA has the advantage of being a rapid diagnostic tool for the detection of malarial antibodies.

Animals↗

Neuropathy and fatal hepatitis in a patient receiving amiodarone.

Muscle weakness, neuropathy, and transient rises in hepatic enzyme activity have been reported with the use of the antiarrhythmic agent amiodarone. A 68 year old teetotaller with normal liver function was given amiodarone for resistant supraventricular arrhythmias. He presented 19 months later with vomiting, muscle weakness and wasting, sensory neuropathy, and hepatomegaly. Liver biopsy showed fibrosis and the presence of hyaline. The amiodarone was withdrawn. Three months later he developed ascites. Oesophageal varices were found and he later died. The liver showed micronodular cirrhosis. The large volume of distribution and long half life of amiodarone may explain the persistence of toxicity, which may have been aggravated by simultaneously administered doxepin in this case. Amiodarone should be withdrawn if abnormal liver function or neuropathy develops.

Aged↗

Studies on the chemoprophylaxis of subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos) with diethylcarbamazine citrate.

The chemoprophylactic use of diethylcarbamazine citrate at total oral doses of 15--180 mg/kg body weight was tested against subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos). A total dose of 45 mg/kg body weight given over 9 days killed all developing infective larvae. Similarly, a total dose of 35 mg/kg body weight given over 7 days killed all fourth stage larvae. The minimum effective dose that prevents infection would be 5 mg/kg body weight daily for 7 days every month.

Administration, Oral↗

Brugia malayi and B. pahangi: cultivation in vitro of infective larvae to the fourth and fifth stages.

Cultivation of fourth stage Brugia pahangi and B. malayi larvae from infective larvae (stage 3) were obtained in culture medium RPMI 1640 supplemented with 10% human AB serum and an LCC-MK2 rhesus monkey kidney continuous cell line feeder layer. This culture system kept larvae alive in excess of 7 weeks, and served as a source for collection of the worms' secretory, excretory, and moulting antigens.

Animals↗

Studies on the epidemiology of subperiodic Brugia malayi in Malaysia: problems in its control.

The dynamics of the transmission of subperiodic Brugia malayi in a typical endemic area in Malaysia was studied over a period of 4 years. Mass chemotherapeutic control with diethylcarbamazine citrate was found to be inefficient, new cases being detected even after the fifth treatment cycle of 6 mg/kg X 6 days per cycle. This is in marked contrast to the situation in periodic b. malayi areas where mass treatment efficiently controlled the infection. The disparity in results in these two areas is attributed to zoonotic transmission of subperiodic B. malayi from non-human primates where a mean infection rate of 76.3% was found.

Animals↗