Shahnaz Murad

National University of Malaysia, Kuala Lumpur, Kuala Lumpur, Malaysia

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Publications (26)36.09 Total impact

  • Article: Silica exposure is associated with an increased risk of developing ACPA-positive rheumatoid arthritis in an Asian population: evidence from the Malaysian MyEIRA case-control study.
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    ABSTRACT: OBJECTIVES: Silica exposure has been associated with an increased risk of developing rheumatoid arthritis (RA), especially among smokers. In this study, we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of RA in the Malaysian population. METHODS: In total, 149 cases and 213 matched controls, all men, were included between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched on sex, age and residential area. Silica exposure was defined as exposure to stone dust, rock drilling or stone crushing, and smoking status was categorized as ever/never cigarette smoking. RESULTS: An increased risk of anti-citrullinated protein antibody (ACPA)-positive RA (OR = 2.4, 95 % CI 1.0-5.6) was observed among those exposed to silica. Ever-smokers exposed to silica had a particularly high risk of developing ACPA-positive RA (OR = 7.5, 95 % CI 2.3-24.2), compared with never-smokers not exposed to silica. No association was found regarding ACPA-negative RA. CONCLUSION: Our data demonstrate that exposure to both silica and cigarette smoke comprise risks for developing RA in the Malaysian genetic context. The findings expand a link between environmental lung exposures and ACPA-positive RA to Asian populations.
    Modern Rheumatology 04/2013; · 1.58 Impact Factor
  • Article: Defining p47-phox deficient Chronic Granulomatous Disease in a Malay family.
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    ABSTRACT: The most common autosomal form of Chronic Granulomatous Disease, p47-phox deficient CGD, generally features a GT (deltaGT) deletion in the GTGT sequence at the start of exon 2 on the NCF-1 gene. This consistency is due to the coexistence of and the recombination between 2 homologous pseudogenes (psi s) and NCF-1. The GTGT: deltaGT ratio mirrors the NCF-I: NCF-1 psi ratio and is 2:4 in normal individuals. To determine the molecular basis of the Autosomal-CGD in a family with 2 children, a male and female, affected by the disease. The female patient suffered recurrent infection, retinitis pigmentosa and discoid lupus. Chemiluminescence (CL) was used to study the respiratory burst, while genetic analysis was done by RT-PCR, PCR, deltaGT and the 20bp gene scans. The CL response of the patient was profoundly low. The patient's p47-phox band was absent in the RT-PCR for NADPH-oxidase component mRNAs. The deltaGT scan showed that the patient's GTGT: deltaGT ratio was 0:6, the parents' and the younger brother's was 1:5 and the younger sister's was 2:4. Examination of other NCF-1/ NCF-1 psi s differences showed that the father had a compound deltaGT allele ie. deltaGT-20bp, inherited by the patient, and that both parents had compound GTGT alleles with a single 30bp segment in intron 1. The patient was a classic, homozygous deltaGT p47-phox deficient CGD with one allele harbouring a compound deltaGT-20bp gene. The deltaGT and 20bp gene scans offer a relatively simple and efficient means of defining a p47-phox deficient CGD patient.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 12/2012; 30(4):313-20. · 0.65 Impact Factor
  • Article: Identification of the major allergens of Charybdis feriatus (red crab) and its cross-reactivity with Portunus pelagicus (blue crab).
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    ABSTRACT: Tropomyosin and arginine kinase have been identified as the major allergens in multiple species of crab. Charybdis feriatus is an important commercial crab in this country. To characterize the major allergens of C. feriatus using a proteomics approach and subsequently to identify the allergens involved in cross-reactivity with Portunus pelagicus. Raw and boiled extracts of the crabs were prepared from crab meat. The protein profile of the extracts was determined by SDS-PAGE and two-dimensional electrophoresis (2-DE). Major allergens were identified by the immunoblotting test using sera from 50 patients with crab allergy. The major allergens were further identified by 2-DE immunoblotting. The major allergenic spots were then excised, digested by trypsin and identified by mass spectrometry analysis. The immunoblotting inhibition test was performed to study the crossreactivity between red crab and blue crab allergens using sera from 20 patients with allergy to both red and blue crabs. At least 20 protein bands between 13 to 250 kDa were detected in the SDS-PAGE gel of raw extract, while boiled extract procuced fewer protein bands. Proteins of 36 kDa and 41 kDa were recognized as the major allergens of the crab. The major allergenic spot sequences of the 36 and 41 kDa proteins were identified as crab tropomyosin and arginine kinase, respectively. All IgE-binding proteins, including both major allergens, were found to be cross-creative with P. pelagicus allergens. In addition to tropomyosin, arginine kinase was also identified as the major allergen of C. feriatus among our local crab-allergic patients. Cross-reactivity of this crab with P. pelagicus was demonstrated in this study.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 12/2012; 30(4):285-93. · 0.65 Impact Factor
  • Article: Polymorphisms in peptidylarginine deiminase (PADI) associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis.
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    ABSTRACT: INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody (ACPA) development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase Type 4 (PADI4) gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explored the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal to elucidate generalizability of association in non-Caucasian populations. METHODS: 320 SNPs from PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations. RESULTS: The overall odds ratio (ORoverall) for PADI4 (rs2240340) allelic model was 1.11 (95% CI, 1.00 to 1.23, P = 0.04) and 1.20 (95% CI, 1.01 to 1.44, P = 0.04) for genotypic model. Haplotypes analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P=0.001) and of another with protective effect (P=0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising of 5,192 RA cases and 4,317 control subjects: (ORoverall =1.23 (95% CI, 1.16 to 1.31, Pheterogeneity=0.08) and 1.31 (95% CI, 1.20 to 1.44, Pheterogeneity=0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of the PADI2 genetic variant rs1005753 with RA (ORoverall =0.87 (95% CI, 0.77 to 0.99)). CONCLUSIONS: Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests an additional association with a PADI2 gene. It thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to the RA development in multiple populations of Asian descent.
    Arthritis research & therapy 11/2012; 14(6):R250. · 4.27 Impact Factor
  • Article: Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA).
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    ABSTRACT: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent. A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated. In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA. The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.
    Arthritis research & therapy 04/2012; 14(2):R89. · 4.27 Impact Factor
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    Article: A replication study confirms the association of dendritic cell immunoreceptor (DCIR) polymorphisms with ACPA - negative RA in a large Asian cohort.
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    ABSTRACT: Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia. We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels. DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis). Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.
    PLoS ONE 01/2012; 7(7):e41228. · 4.09 Impact Factor
  • Article: Platelet-Activating Factor (PAF) Antagonistic Activity of a New Biflavonoid from Garcinia nervosa var. pubescens King.
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    ABSTRACT: The methanol extract of the leaves of Garcinia nervosa var. pubescens King, which showed strong inhibitory effects on platelet-activating factor (PAF) receptor binding, was subjected to bioassay-guided isolation to obtain a new biflavonoid, II-3,I-5, II-5,II-7,I-4',II-4'-hexahydroxy-(I-3,II-8)-flavonylflavanonol together with two known flavonoids, 6-methyl-4'-methoxyflavone and acacetin. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit PAF receptor binding to rabbit platelets using <sup>3</sup>H-PAF as a ligand. The biflavonoid and acacetin showed strong inhibition with IC<sub>50</sub> values of 28.0 and 20.4 µM, respectively. The results suggest that these compounds could be responsible for the strong PAF antagonistic activity of the plant.
    Molecules 01/2012; 17(9):10893-901. · 2.39 Impact Factor
  • Article: Identification of tropomyosin as major allergen of white squid (Loligo edulis) by two-dimensional immunoblotting and mass spectrometry.
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    ABSTRACT: IgE-mediated allergic reaction to squid is one of the most frequent molluscan shellfish allergies. Previously, we have detected a 36 kDa protein as the major allergen of Loligo edulis (white squid) by immunoblotting using sera from patients with squid allergy. The aim of this present study was to further identify this major allergen using a proteomics approach. The major allergen was identified by a combination of two-dimensional electrophoresis (2-DE), immunoblotting, mass spectrometry and bioinformatics tools. The 2-DE gel fractionated the cooked white squid proteins to more than 50 different protein spots between 10 to 38 kDa and isoelectric point (pI) from 3.0 to 10.0. A highly reactive protein spot of a molecular mass of 36 kDa and pI of 4.55 was observed in all of the patients' serum samples tested. Mass spectrometry analysis led to identification of this allergen as tropomyosin. This finding can contribute to advancement in component-based diagnosis, management of squid allergic patients, to the development of immunotherapy and to the standardization of allergenic test products as tools in molecular allergology.
    The Southeast Asian journal of tropical medicine and public health 01/2012; 43(1):185-91. · 0.60 Impact Factor
  • Article: Identification of the major allergen of Macrobrachium rosenbergii (giant freshwater prawn).
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    ABSTRACT: To characterize the major allergens of Macrobrachium rosenbergii (giant freshwater prawn). Raw and cooked extracts of the giant freshwater prawn were prepared. The IgE reactivity pattern was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting technique with the sera of 20 skin prick test (SPT) positive patients. The major allergen identified was then characterized using the proteomics approach involving a combination of two-dimensional (2-DE) electrophoresis, mass spectrometry and bioinformatics tools. SDS-PAGE of the raw extract showed 23 protein bands (15-250 kDa) but those ranging from 40 to 100 kDa were not found in the cooked extract. From immunoblotting experiments, raw and cooked extracts demonstrated 11 and 5 IgE-binding proteins, respectively, with a molecular mass ranging from 15 to 155 kDa. A heat-resistant 36 kDa protein was identified as the major allergen of both extracts. In addition, a 42 kDa heat-sensitive protein was shown to be a major allergen of the raw extract. The 2-DE gel fractionated the prawn proteins to more than 50 different protein spots. Of these, 10 spots showed specific IgE reactivity with patients' sera. Matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis led to identification of 2 important allergens, tropomyosin and arginine kinase. It can be concluded that the availability of such allergens would help in component-based diagnosis and therapy of prawn allergies.
    Asian Pacific journal of tropical biomedicine. 01/2012; 2(1):50-4.
  • Article: Platelet-activating factor (PAF) receptor binding activity of the roots of Enicosanthellum pulchrum.
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    ABSTRACT: Enicosanthellum pulchrum (King) Heusden (Annonaceae) is a coniferous tree that is confined to mountain forests. The chemical constituents of this species have been studied previously; however, its biological activity has never been investigated before and is reported here for the first time. Objective: The extracts, fractions and compounds from the roots of E. pulchrum were investigated for their inhibitory effects on platelet-activating factor (PAF) receptor binding to rabbit platelets using (3)H-PAF as a ligand. The PAF receptor binding inhibitory effect using rabbit platelets was determined in vitro by measuring the difference between total amount of bound (3)H-PAF in the presence and the absence of excess unlabelled PAF. The compounds were isolated by bioassay-guided fractionation and their structures were elucidated by spectroscopic techniques. Among the extracts tested, the ethyl acetate extract was the most active with 85.6% inhibition, while hexane and methanol extracts showed 40.2 and 42.5% inhibition, respectively. Fractionation of the ethyl acetate extract using vacuum liquid chromatography (VLC) yielded six fractions AEA(I--VI). Chromatography fraction AEA(VI) yielded a new compound, 1-(2',3',4'-trimethoxyphenyl)hexan-1-ol, while fraction AEA(III) afforded three compounds, namely liriodenine, cleistopholine and dehydroanonaine. 1-(2',3',4'-Trimethoxyphenyl)hexan-1-ol, cleistopholine and dehydroanonaine showed relatively strong inhibition with IC(50) values of 26.6, 50.2 and 45.4 µM, respectively. The results suggest that these compounds could be responsible for the PAF antagonistic activity of the ethyl acetate extract of this plant.
    Pharmaceutical Biology 11/2011; 50(3):284-90. · 0.88 Impact Factor
  • Article: Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-negative rheumatoid arthritis in Asian populations: evidence from the Malaysian MyEIRA case-control study.
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    ABSTRACT: We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.
    Modern Rheumatology 10/2011; 22(4):524-31. · 1.58 Impact Factor
  • Article: Susceptibility to aplastic anemia is associated with HLA-DRB1*1501 in an aboriginal population in Sabah, Malaysia.
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    ABSTRACT: The incidence of aplastic anemia is reported to be higher in Asia than elsewhere. We studied the frequency of human leukocyte antigen (HLA) DRB1 alleles in aplastic anemia patients from 2 genetically similar aboriginal groups, the Kadazan and the Dusun, and compared them with genetically matched community and hospital controls. HLA-DRB1*15 was significantly higher in the patients compared with controls (p = 0.005), confirming similar findings in Japanese and Caucasian studies. Further testing indicated a significantly higher frequency of HLA-DRB1*1501 in patients compared with controls (p = 0.0004) but no significant difference in the frequency of HLA-DRB1*1502. The high frequency of HLA-DRB1*15 in the Kadazan and Dusun population combined with the wide variety of environmental factors associated with aplastic anemia could be the reason for the elevated incidence of aplastic anemia in the Kadazan and Dusun in Sabah.
    Human immunology 07/2011; 72(10):889-92. · 2.55 Impact Factor
  • Article: Identification of Major and Minor Allergens of Black Tiger Prawn (Penaeus monodon) and King Prawn (Penaeus latisulcatus).
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    ABSTRACT: Prawns and shrimp are a frequent cause of seafood allergy mediated by IgE antibodies. Penaeus monodon and Penaeus latisulcatus, commonly known as black tiger prawn and king prawn, respectively, are among the most frequently consumed prawns in Malaysia. The aim of this study was to identify the IgE-binding proteins of these 2 prawn species. Raw and boiled prawn extracts were prepared and then resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). IgE-immunoblotting was then performed using sera from patients with positive skin prick tests to the raw prawn extracts. SDS-PAGE analysis of the raw extracts of both prawn species revealed 23 protein bands; the boiled extracts yielded fewer protein bands. The bands in the range of 40 to 100 kDa were sensitive to heat and therefore were not found in the boiled extracts. Immunoblot of raw extracts of black tiger prawns and king prawns yielded 14 and 11 IgE-binding proteins, respectively, with molecular weights of between 15 and 200 kDa. Proteins at 36, 42, and 49 kDa were detected as the major allergens in both species of prawns. A protein of 75 kDa was also identified as a major allergen in black tiger prawns. Other potential allergens were also observed at various molecular masses. Proteins of 36, 42, and 49 kDa were identified as the major allergens of both species of prawns. The 36 and 42 kDa proteins are hypothesised to be tropomyosin and arginine kinase, respectively. A high molecular weight protein of 75 kDa was found to be an additional major allergen in black tiger prawns.
    The Malaysian journal of medical sciences : MJMS. 07/2011; 18(3):27-32.
  • Article: Identification of major allergens of wildflower honey.
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    ABSTRACT: The aim of this study was to identify the major allergens of wildflower honey in local patients with atopic disease. SDS-PAGE revealed ten protein bands of 25 to 110 kDa, with a heavy cluster in region of 40-75 kDa. Immunoblotting demonstrated seven IgE-binding bands of 39 to 110 kDa. The 60 kDa protein had the highest frequency of IgE-binding (100%) followed by 54 kDa protein (95%), thus identified as the major allergens of wildflowerhoney. Our findings indicate that the allergen extract used for diagnosis of honey allergy contains both the 54 kDa and 60 kDa proteins.
    The Southeast Asian journal of tropical medicine and public health 03/2011; 42(2):370-5. · 0.60 Impact Factor
  • Article: Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population.
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    ABSTRACT: Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population. This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population. A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared. HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value  = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries. HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.
    International journal of dermatology 02/2011; 50(2):221-4. · 1.18 Impact Factor
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    Article: Monitoring of the h275y mutation in pandemic influenza A(H1N1) 2009 strains isolated in Malaysia.
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    ABSTRACT: Abstract. The 2009 pandemic influenza A(H1N1) infection in Malaysia was first reported in May 2009 and oseltamivir was advocated for confirmed cases in postexposure prophylaxis. However, there are cases of oseltamivir-resistance reported among H1N1-positive patients in other countries. Resistance is due to substitution of histidine by tyrosine at residue 275 (H275Y) of neuraminidase (NA). In this study, we have employed Sanger sequencing method to investigate the occurrence of mutations in NA segments of 67 pandemic 2009 A(H1N1) viral isolates from Malaysian patients that could lead to probable oseltamivir resistance. The sequencing analysis did not yield mutation at residue 275 for all 67 isolates indicating that our viral isolates belong to the wild type and do not confer resistance to oseltamivir.
    The Southeast Asian journal of tropical medicine and public health 01/2011; 42(1):100-4. · 0.60 Impact Factor
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    Article: Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA)--positive rheumatoid arthritis in three Asian ethnic groups.
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    ABSTRACT: To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia. 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping. The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups. The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.
    PLoS ONE 01/2011; 6(6):e21069. · 4.09 Impact Factor
  • Article: Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants.
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    ABSTRACT: The methanol extracts of 20 selected medicinal plants were investigated for their effects on the respiratory burst of human whole blood, isolated human polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the extracts on chemotactic migration of PMNs using the Boyden chamber technique. The extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C. xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to 0.7 μg/ml. For macrophage cells, the extracts which showed strong suppressive activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9 to 1.5 μg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.) Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic migration of cells, with IC(50) values comparable to that of ibuprofen (1.5 μg/ml). The results suggest that some of these plants were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.
    Journal of Natural Medicines 12/2010; 65(2):400-5. · 1.39 Impact Factor
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    Article: Identification of Ige-binding proteins of raw and cooked extracts of Loligo edulis (white squid).
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    ABSTRACT: Allergy to different classes of mollusks, including squid, which are members of the class Cephalopods has been reported. Tropomyosin, a major muscle protein, is the only well-recognized allergen in squid. The aim of this study was to characterize IgE-binding proteins of local Loligo edulis (white squid) consumed in Malaysia. Protein profiles and IgE-binding proteins were detected by sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE) and immunoblotting using sera from 23 patients with positive skin prick test to raw squid extract. SDS-PAGE of the raw extract exhibited 21 protein bands (10-170 kDa) but those ranging from 19 to 29 kDa and 41 to 94 kDa were not found in the cooked extract. Immunoblotting of raw extract demonstrated 16 IgE-binding bands, ranging from 13 to 170 kDa. A heat-resistant 36 kDa protein, corresponding to squid tropomyosin, was identified as the major allergen of both extracts. In addition, a 50 kDa heat-sensitive protein was shown to be a major allergen of the raw extract. Our findings indicate that the allergen extract used for diagnosis of squid allergy should contain both the 36 kDa and 50 kDa proteins.
    The Southeast Asian journal of tropical medicine and public health 05/2010; 41(3):653-9. · 0.60 Impact Factor
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    Article: Antiplatelet aggregation activity of compounds isolated from Guttiferae species in human whole blood
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    ABSTRACT: Twenty compounds isolated from Calophyllum inophyllum L., C. inophylloides King, Garcinia opaca King, G. bancana Miq., and G. parvifolia Miq. (Guttiferae) were evaluated for their ability to inhibit platelet aggregation in human whole blood induced by arachidonic acid (AA), collagen, and adenosine diphosphate (ADP). The compounds inhibited platelet aggregation in a dose-dependent manner. Among the compounds tested, 2-(3-methylbut-2-enyl)-1,3,5-trihydroxyxanthone and 2-(3-methylbut-2-enyl)-1,3,5,6- tetrahydroxyxanthone showed strong inhibitory activity on platelet aggregation induced by AA with IC50 values of 115.9 and 113.0 μM, respectively. Rubraxanthone showed inhibitory activity against aggregation caused by the three inducers, and was the most effective antiplatelet compound against collagen-induced platelet aggregation with an IC50 value of 47.0 μM. Macluraxanthone, GB-1a, pyranoamentoflavone, and a neoflavonoid showed selective inhibitory activity on platelet aggregation induced by ADP.
    10/2009; 47(11):1090-1095.