To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre.
The search for the dengue virus receptor has generated many candidates often identified only by molecular mass. The wide host range of the viruses in vitro combined with multiple approaches to identifying the receptor(s) has led to the notion that many receptors or attachment proteins may be involved and that the different dengue virus serotypes may utilize different receptors on the same cells as well as on different cell types.
MeSH terms: Animals; Cell Line; Dengue Virus/metabolism*; Gene Expression Regulation; Protein Binding; Radioligand Assay; Swine; Viral Proteins; Receptors, Laminin/genetics; Receptors, Laminin/metabolism*; Lamin Type B
Hepatitis B virus (HBV) has been classified into eight genotypes, designated A-H. These genotypes are known to have distinct geographic distributions. The clinical importance of genotype-related differences in the pathogenicity of HBV has been revealed recently. In Malaysia, the current distribution of HBV remains unclear. The aim of this study was to determine the genotypes and subtypes of HBV by using PCR, followed by DNA sequencing, as well as to analyse the mutations in the immunodominant region of preS and S proteins. The S gene sequence was determined from HBV DNA of four apparently healthy blood donors' sera and three sera from asymptomatic chronic hepatitis B carriers. Of this batch of sera, the preS gene sequence was obtained from HBV DNA from three out of the four blood donors and two out of the three chronic carriers. Due to insufficient sera, we had to resort to using sera from another blood donor to make up for the sixth DNA sequence of the preS gene. Based on the comparative analysis of the preS sequences with the reported sequences in the GenBank database, HBV DNA from two normal carriers was classified as genotype C. Genotype B was assigned to HBV from one blood donor and two hepatitis B chronic carriers, whereas HBV of one chronic carrier was of genotype D. Based on the S gene sequences, HBV from three blood donors was of genotype C, that of one blood donor and one chronic carrier was of genotype B, and the remaining, of genotype D. In the five cases where both preS and S gene sequences were determined, the genotypes assigned based on either the preS or S gene sequences were in concordance. The nature of the deduced amino acid (aa) sequences at positions 125, 127, 134, 143, 159, 161 and 168 of the S gene enabled the classification of these sequences into subtypes, namely, adrq+, adw2 and ayw2. The clustering of our DNA sequences into genotype groups corresponded to their respective subtype, that is, adw2 in genotype B, adrq in genotype C and ayw in genotype D. Analysis of the point mutations revealed that five of the sequences contained aa substitutions at immunodominant epitopes involved in B or/and T cell recognition. In conclusion, despite the low numbers of samples studied, due to budget constraints, these data are still worthwhile reporting, as it is important for the control of HBV infections. In addition, the genotype and mutational data obtained in this study may be useful for designing new treatment regimes for HBV patients.
MeSH terms: Amino Acid Sequence; Carrier State; DNA, Viral; Genotype; Hepatitis B Surface Antigens/genetics*; Hepatitis B Surface Antigens/chemistry; Hepatitis B virus/classification; Hepatitis B virus/genetics*; Humans; Malaysia/epidemiology; Molecular Sequence Data; Protein Precursors/genetics; Hepatitis B, Chronic/virology*
A non-redundant database of 4536 structural domains, comprising more than 790,000 residues, has been used for the calculation of their solvent accessibility in the native protein environment and then in the isolated domain environment. Nearly 140,000 (18%) residues showed a change in accessible surface area in the above two conditions. General features of this change under these two circumstances have been pointed out. Propensities of these interfacing amino acid residues have been calculated and their variation for different secondary structure types has been analyzed. Actual amount of surface area lost by different secondary structures is higher in the case of helix and strands compared to coil and other conformations. Overall change in surface area in hydrophobic and uncharged residues is higher than that in charged residues. An attempt has been made to know the predictability of interface residues from sequence environments. This analysis and prediction results have significant implications towards determining interacting residues in proteins and for the prediction of protein-protein, protein-ligand, protein-DNA and similar interactions.
MeSH terms: Amino Acids/chemistry*; DNA/chemistry*; Ligands; Models, Molecular; Predictive Value of Tests; Protein Conformation; Proteins/chemistry*; Solvents/chemistry*; Surface Properties; Databases, Protein; Hydrophobic and Hydrophilic Interactions
A hybrid neural network comprising Fuzzy ARTMAP and Fuzzy C-Means Clustering is proposed for pattern classification with incomplete training and test data. Two benchmark problems and a real medical pattern classification task are employed to evaluate the effectiveness of the hybrid network. The results are analyzed and compared with those from other methods.
We have developed a novel single cell real-time quantitative PCR technique, which incorporates harvesting marker-identified single cells using laser-capture. Here, for the first time in a vertebrate species, using this innovative single cell gene profiling technique, we report the presence of G-protein coupled receptors in individual gonadotropin-releasing hormone (GnRH) neurons and endocrine cells of the pituitary of the tilapia Oreochromis niloticus. The differential expression of multiple combinations of three GnRH receptor types (R1, R2 and R3) in individual gonadotropic and nongonadotropic cells demonstrates cellular and functional heterogeneity. The differential use of GnRH receptors in corticotropes, melanotropes and thyrotropes during gonadal maturation and reproductive behaviors suggests new roles for these hormones. Further, we provide evidence of the structure of a novel nonmammalian G-protein coupled receptor (GPR54) for kisspeptins, encoded by Kiss-1 gene, which is highly conserved during evolution and expressed in GnRH1, GnRH2 and GnRH3 neurons. We hypothesize GPR54 stimulates GnRH secretion and is crucial for pubertal maturation. We speculate, the use of this method will allow the identification and quantification of known and unknown genes in single cells, which would greatly facilitate our understanding of the complex interactions that govern the physiology of individual cells in vertebrates species.
Presented here is a case of a pharyngocutaneous fistula which was closed primarily using a sternomastoid muscle flap, without skin coverage, thus obviating the need for a three-layered closure. Providing an intermediate cover was sufficient for the closure because the mucosal lining on the inside and the cutaneous covering on the outside grew using the muscle for support.
This study tested the hypotheses that ambulatory heart rate and blood pressure would be higher for individuals high but not low in hostility when they experienced negative affect or social stress and that this interaction would be stronger for Indians compared with other Singapore ethnic groups. Ambulatory blood pressure monitoring was done on 108 male Singapore patrol officers as they went about their daily duties. After each BP measurement participants completed a computerized questionnaire including items on emotional experience. Individuals high in hostility showed higher systolic blood pressure when reporting negative affect whereas this was not true for those low in hostility. Ethnic differences were obtained such that Indians showed an increase in mean arterial pressure when angered whereas MAP was negatively related to anger for Malays and unrelated for Chinese. Also a three-way interaction between ethnicity, hostility, and social stress indicated that hostility and social stress interacted in their effects on DBP for Indian participants but not for Chinese or Malays. Finally, a three-way interaction was obtained between ethnicity, hostility and negative affect for heart rate in which heart rate increased with increasing levels of negative affect for Chinese high in hostility and Malays low in hostility but decreased with increasing negative affect for all other participants. These data are consistent with higher CHD rates among individuals high in hostility and also provide additional evidence on ethnic differences in cardiovascular reactivity in Singapore.
Four tropical PSP toxins-producing dinoflagellates, Alexandrium minutum, Alexandrium tamiyavanichii, Alexandrium tamarense and Alexandrium peruvianum from Malaysian waters were studied to investigate the influences of salinity on growth and toxin production. Experiments were conducted on constant temperature 25 degrees C, 140 microE mol m(-2) s(-1) and under 14:10 light:dark photo-cycle with salinity ranged from 2 to 30 psu. The PSP-toxin congeners, GTX 1-6, STX, dcSTX, NEO and C1-C2 were analysed by high performance liquid chromatography. Salinity tolerance of the four species in decreasing order is A. minutum>A. peruvianum>A. tamarense>A. tamiyavanichii. Specific growth rates and maximum densities varied among these species with A. minutum recorded as the highest, 0.5 day(-1) and 6 x 10(4) cells L(-1). Toxin content decreased with elevated salinities in A. minutum, the highest toxin content was about 12 fmole cell(-1) at 5 psu. In A. tamiyavanichii, toxin content peaked at optimal growth salinity (20 and 25 psu). Toxin content of A. tamarense, somehow peaked at sub-optimal growth salinity (15 and 30 psu). Results of this study implied that salinity fluctuation not only influenced the growth physiology but also toxin production of these species.
MeSH terms: Animals; Chromatography, High Pressure Liquid; Dinoflagellida/growth & development*; Dinoflagellida/metabolism*; Malaysia; Marine Toxins/biosynthesis*; Sodium Chloride/analysis*; Species Specificity; Water/chemistry*; Photoperiod
Disjunctive distributions across paleotropical regions in the Indian Ocean Basin (IOB) often invoke dispersal/vicariance debates. Exacum (Gentianaceae, tribe Exaceae) species are spread around the IOB, in Africa, Madagascar, Socotra, the Arabian peninsula, Sri Lanka, India, the Himalayas, mainland Southeast Asia including southern China and Malaysia, and northern Australia. The distribution of this genus was suggested to be a typical example of vicariance resulting from the breakup of the Gondwanan supercontinent. The molecular phylogeny of Exacum is in principle congruent with morphological conclusions and shows a pattern that resembles a vicariance scenario with rapid divergence among lineages, but our molecular dating analysis demonstrates that the radiation is too recent to be associated with the Gondwanan continental breakup. We used our dating analysis to test the results of DIVA and found that the program predicted impossible vicariance events. Ancestral area reconstruction suggests that Exacum originated in Madagascar, and divergence dating suggests its origin was not before the Eocene. The Madagascan progenitor, the most recent common ancestor of Exacum, colonized Sri Lanka and southern India via long-distance dispersals. This colonizer underwent an extensive range expansion and spread to Socotra-Arabia, northern India, and mainland Southeast Asia in the northern IOB when it was warm and humid in these regions. This widespread common ancestor retreated subsequently from most parts of these regions and survived in isolation in Socotra-Arabia, southern India-Sri Lanka, and perhaps mainland Southeast Asia, possibly as a consequence of drastic climatic changes, particularly the spreading drought during the Neogene. Secondary diversification from these surviving centers and Madagascar resulted in the extant main lineages of the genus. The vicariance-like pattern shown by the phylogeny appears to have resulted from long-distance dispersals followed by extensive range expansion and subsequent fragmentation. The extant African species E. oldenlandioides is confirmed to be recently dispersed from Madagascar.
A 16-year-old boy was referred with features of Parkes Weber syndrome (PWS) involving the right lower limb. He had presented at birth with cutaneous vascular malformations (VM) in the right thigh and at the age of 7 years developed congestive cardiac failure, which was controlled with drugs. He received alpha interferon and steroids during this period without any benefit. He defaulted follow-up and at 12 years of age presented with further enlargement of the VM in the right thigh and leg with skin and soft tissue thickening. At this stage, embolization and subsequent excision of the VM were tried, but the surgery was abandoned because of massive hemorrhage. Over the next 4 years, the boy became totally bedridden because of massive increase in the size of the limb, repeated hemorrhages, and secondary infection of the VM. Right hip disarticulation was considered the best option to improve his quality of life. To prevent uncontrollable hemorrhage during surgery, the disarticulation was done under cardiopulmonary bypass with low circulatory flow. Postoperatively, the patient required intensive care nursing for a week. He is presently ambulatory with crutches. Cardiopulmonary bypass with low flow has been used for treating posttraumatic arteriovenous malformations. However, its use in surgery for PWS has not been reported earlier.
The population genetic structure of Plasmodium falciparum differs between endemic regions, but the characteristics of a population recently fragmented by effective malaria control have been unknown.
Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia.
This study was undertaken to evaluate physician counselling practices and resuscitation decisions for extremely preterm infants in countries of the Pacific Rim. We sought to determine the degree to which physician beliefs, parents' opinion and medical resources influence decision-making for infants at the margin of viability.
A 5-year-old Chinese girl with 1-year history of progressive jaundice, steatorrhoea and pruritus was referred. Physical examination showed failure to thrive, marked jaundice, finger clubbing and hepatomegaly. There was laboratory evidence of cholestatic jaundice and autoimmunity, with marked elevation of alkaline phosphatase (ALP) and gamma-glutamyl transferase (gammaGT). Histology of percutaneous liver biopsy revealed hepatitis around the portal triad, as well as features of liver cirrhosis. Primary sclerosing cholangitis (PSC) overlapping with autoimmune hepatitis (AIH) was suspected. Endoscopic retrograde cholangiopancreatography (ERCP) was not feasible as there was no weight-appropriate ERCP scope available. Magnetic resonance cholangiopancreatography (MRCP) was performed and revealed areas of irregularity and slight attenuation of the right and left hepatic ducts, representing stricturing, in keeping with PSC. PSC/AIH overlap syndrome was diagnosed in this child in which MRCP has contributed to its diagnosis.
In 1997, a Motorcycle Safety Programme (MSP) was introduced to address the motorcycle-related accident problem. The MSP was specifically targeted at motorcyclists. In addition to the MSP, the recent economic recession has significantly contributed to a reduction of traffic-related incidents. This paper examines the effects of the recent economic crisis and the MSP on motorcycle-related accidents, casualties and fatalities in Malaysia. The autocorrelation integrated moving average model with transfer function was used to evaluate the overall effects of the interventions. The variables used in developing the model were gross domestic product and MSPs. The analysis found a 25% reduction in the number of motorcycle-related accidents, a 27% reduction in motorcycle casualties and a 38% reduction in motorcycle fatalities after the implementation of MSP. Findings indicate that the MSP has been one of the effective measures in reducing motorcycle safety problems in Malaysia. Apart from that, the performance of the country's economy was also found to be significant in explaining the number of motorcycle-related accidents, casualties and fatalities in Malaysia.
MeSH terms: Accidents, Traffic/mortality*; Accidents, Traffic/prevention & control; Economics*; Government Programs; Humans; Malaysia/epidemiology; Motorcycles*; Safety*; Wounds and Injuries/etiology*; Wounds and Injuries/mortality*; Wounds and Injuries/prevention & control; Models, Statistical
The National Breastfeeding Survey 2001 was the first comprehensive study on breastfeeding conducted on a national level in Singapore. It aimed to establish the prevalence of breastfeeding among Chinese, Malay and Indian mothers and to identify factors influencing breastfeeding. A total of 2098 mothers were interviewed in this two-phase study, with the first interview conducted 2 months after delivery and the second interview 6 months after birth among mothers who were still breastfeeding at 2 months. Frequency distributions of breastfeeding prevalence and types of breastfeeding practices at different time intervals (from birth to 6 months) were produced. Multivariate logistic regression was carried out to construct a model with predictive information on factors which influence continued breastfeeding till 2 months and 6 months after delivery respectively. The study found that about 94.5% of the mothers attempted breastfeeding. At 1 month, 71.6% were still breastfeeding, 49.6% continued to do so at 2 months, and 29.8% persisted till 4 months. By 6 months, the breastfeeding prevalence rate fell to 21.1%. The results of this study show higher breastfeeding prevalence rates compared to past studies in Singapore. Despite this, exclusive breastfeeding is still not a common practice. Various factors were found to be significant in influencing mothers' decision to breastfeed. Factors such as ethnicity, age, educational attainment, religion and baby's sex are non-modifiable in the short term or at an individual level. However, factors such as awareness of breastfeeding benefits, advice from health professionals and previous breastfeeding experience are potentially modifiable. Efforts aimed at promoting breastfeeding in Singapore need to take these modifiable factors into consideration so as to better tailor health promotion efforts on breastfeeding to women.
MeSH terms: Adult; Data Collection; Female; Humans; India/epidemiology; Interviews as Topic; Malaysia/epidemiology; Middle Aged; Singapore/epidemiology