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  1. Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia
    Tarone RE, Levine PH, Yadav M, Pandey JP
    Cancer Res, 1990 Jun 1;50(11):3186-8.
    PMID: 1692255
    The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.
    Matched MeSH terms: Disease Susceptibility/immunology; Genetic Predisposition to Disease
  2. Aberrant expression of acute-phase reactant proteins in sera and breast lesions of patients with malignant and benign breast tumors
    Doustjalali SR, Yusof R, Yip CH, Looi LM, Pillay B, Hashim OH
    Electrophoresis, 2004 Jul;25(14):2392-401.
    PMID: 15274022
    We have analyzed unfractionated sera of newly diagnosed patients (n=10) with breast carcinoma (BC), prior to treatment, and patients (n=5) with fibrocystic disease of the breast (FDB) by two-dimensional gel electrophoresis (2-DE) and silver staining. The patients' 2-DE serum protein profiles obtained were then subjected to image analysis and compared to similar data generated from sera of normal healthy female controls (n=10) of the same range of age. The relative expression of alpha1-antichymotrypsin (ACT), clusterin, and complement factor B was significantly higher in all BC patients as compared to normal controls. However, the expression of alpha1-antitrypsin (AAT) in BC patients was apparently lower than that of the controls. Similar differential expression of ACT was detected in the FDB patients. The aberrant expression of the serum acute-phase proteins of patients with BC and FDB was confirmed by competitive enzyme-linked immunosorbent assay (ELISA). Similar altered proteins expression was also observed from immunohistochemical studies of malignant (n=5) and benign (n=5) breast lesions of the respective patients performed using antisera to the aberrantly expressed proteins. However, the malignant breast lesions were instead positively stained for AAT. The differential expression of the serum proteins was apparently abrogated when a six-month follow-up study was performed on nine of the BC patients subsequent to treatment.
    Matched MeSH terms: Fibrocystic Breast Disease/metabolism*; Fibrocystic Breast Disease/pathology
  3. Management of gestational trophoblastic disease in developing countries
    Sivanesaratnam V
    Best Pract Res Clin Obstet Gynaecol, 2003 Dec;17(6):925-42.
    PMID: 14614890 DOI: 10.1016/S1521-6934(03)00097-X
    In Malaysia, the incidence of molar pregnancy and gestational trophoblastic neoplasia is 2.8 and 1.59 per 1000 deliveries, respectively; the disease is more common among the Chinese compared to the Malays and Indians. While uterine suction is the preferred method of uterine evacuation of hydatidiform mole, complete evacuation was not achieved at the first attempt in 25% of cases. Partial moles comprise 30% of all moles; these need follow up similar to that for complete moles as they are potentially malignant. In the management of invasive moles, chemotherapy should not be withheld in the presence of metastases or failure of regression of hCG. Placental site tumours are rare. Prophylactic hysterectomy and prophylactic chemotherapy are not recommended. However, in those patients with unsatisfactory hCG regression curves indicating 'at risk' in developing gestational trophoblastic neoplasia (GTN), 'selective preventive chemotherapy' appears appropriate. Chemotherapy remains the main modality of treatment for GTN. As tumour bulk and location of disease are important determinants in outcome, we categorized our patients into low, medium- and high-risk groups with survivals of 100, 98 and 61.7% respectively. Surgery and radiotherapy have a limited role.
    Matched MeSH terms: Gestational Trophoblastic Disease/surgery; Gestational Trophoblastic Disease/therapy*
  4. Newcastle disease virus Malaysian strain AF2240 induces apoptosis in MCF-7 human breast carcinoma cells at an early stage of the virus life cycle
    Ghrici M, El Zowalaty M, Omar AR, Ideris A
    Int J Mol Med, 2013 Mar;31(3):525-32.
    PMID: 23337979 DOI: 10.3892/ijmm.2013.1244
    Newcastle disease virus (NDV) AF2240 Malaysian strain is a very virulent avian virus. NDV strain AF2240 was previously demonstrated to induce apoptosis in human breast carcinoma MCF-7 cells. However, at which stage of the NDV life cycle apoptosis is induced and whether NDV replication and protein synthesis are involved in apoptosis induction have yet to be determined. In the present study, we investigated the time course of NDV strain AF2240 nucleoprotein (NP) gene expression and the early apoptotic signs in the form of activation of caspase-8 and mitochondrial transition pore opening. In addition, the induction of apoptosis by both ultraviolet-inactivated and cycloheximide-treated NDV-infected MCF-7 cells were examined. Our findings showed that NDV strain AF2240 induced apoptosis at 1 h post-infection (pi) through activation of mitochondrial transition pore opening and at 2 h through activation of caspase-8, while the NP gene was expressed at 6 h pi. The induced apoptosis was independent of both virus replication and protein synthesis. In conclusion, NDV strain AF2240 induces apoptosis at an early stage of its life cycle, possibly during virus binding or fusion with the cell membrane. The mitochondrial-related pathway may be the central activator in NDV strain AF2240-induced apoptosis.
    Matched MeSH terms: Newcastle disease virus/growth & development*; Newcastle disease virus/metabolism*
  5. Carbamoylphosphate synthetase 1 (CPS1) deficiency: clinical, biochemical, and molecular characterization in Malaysian patients
    Ali EZ, Khalid MK, Yunus ZM, Yakob Y, Chin CB, Abd Latif K, et al.
    Eur J Pediatr, 2016 Mar;175(3):339-46.
    PMID: 26440671 DOI: 10.1007/s00431-015-2644-z
    Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare autosomal recessive disorder of ureagenesis presenting as life-threatening hyperammonemia. In this study, we present the main clinical features and biochemical and molecular data of six Malaysian patients with CPS1 deficiency. All the patients have neonatal-onset symptoms, initially diagnosed as infections before hyperammonemia was recognized. They have typical biochemical findings of hyperglutaminemia, hypocitrullinemia, and low to normal urinary excretion of orotate. One neonate succumbed to the first hyperammonemic decompensation. Five neonatal survivors received long-term treatment consisting of dietary protein restriction and ammonia-scavenging drugs. They have delayed neurocognitive development of varying severity. Genetic analysis revealed eight mutations in CPS1 gene, five of which were not previously reported. Five mutations were missense changes while another three were predicted to create premature stop codons. In silico analyses showed that these new mutations affected different CPS1 enzyme domains and were predicted to interrupt interactions at enzyme active sites, disturb local enzyme conformation, and destabilize assembly of intact enzyme complex.

    CONCLUSION: All mutations are private except one mutation; p.Ile1254Phe was found in three unrelated families. Identification of a recurrent p.Ile1254Phe mutation suggests the presence of a common and unique mutation in our population. Our study also expands the mutational spectrum of the CPS1 gene.

    Matched MeSH terms: Carbamoyl-Phosphate Synthase I Deficiency Disease/diagnosis*; Carbamoyl-Phosphate Synthase I Deficiency Disease/genetics
  6. Fulltext Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
    Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, et al.
    Nat Genet, 2017 Dec;49(12):1767-1778.
    PMID: 29058716 DOI: 10.1038/ng.3785
    Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology; Genetic Predisposition to Disease/genetics*
  7. Fulltext Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets
    Umpleby AM, Shojaee-Moradie F, Fielding B, Li X, Marino A, Alsini N, et al.
    Clin Sci (Lond), 2017 Nov 01;131(21):2561-2573.
    PMID: 28923880 DOI: 10.1042/CS20171208
    Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n = 11) and low liver fat 'controls' (n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P<0.02) and low sugar (P<0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet (P<0.01), and a higher VLDL1-TAG production rate after the low sugar diet (P<0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG (P<0.02) in the controls, but in contrast, a higher production of VLDL2-TAG (P<0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.
    Matched MeSH terms: Non-alcoholic Fatty Liver Disease/blood; Non-alcoholic Fatty Liver Disease/metabolism*
  8. Comparison of posterior subthalamic area deep brain stimulation for tremor using conventional landmarks versus directly targeting the dentatorubrothalamic tract with tractography
    Low HL, Ismail MNBM, Taqvi A, Deeb J, Fuller C, Misbahuddin A
    Clin Neurol Neurosurg, 2019 Oct;185:105466.
    PMID: 31466022 DOI: 10.1016/j.clineuro.2019.105466
    OBJECTIVE: To compare posterior subthalamic area deep brain stimulation (PSA-DBS) performed in the conventional manner against diffusion tensor imaging and tractography (DTIT)-guided lead implantation into the dentatorubrothalamic tract (DRTT).

    PATIENTS AND METHODS: Double-blind, randomised study involving 34 patients with either tremor-dominant Parkinson's disease or essential tremor. Patients were randomised to Group A (DBS leads inserted using conventional landmarks) or Group B (leads guided into the DRTT using DTIT). Tremor (Fahn-Tolosa-Marin) and quality-of-life (PDQ-39) scores were evaluated 0-, 6-, 12-, 36- and 60-months after surgery.

    RESULTS: PSA-DBS resulted in marked tremor reduction in both groups. However, Group B patients had significantly better arm tremor control (especially control of intention tremor), increased mobility and activities of daily living, reduced social stigma and need for social support as well as lower stimulation amplitudes and pulse widths compared to Group A patients. The better outcomes were sustained for up to 60-months from surgery. The active contacts of Group B patients were consistently closer to the centre of the DRTT than in Group A. Speech problems were more common in Group A patients.

    CONCLUSION: DTIT-guided lead placement results in better and more stable tremor control and fewer adverse effects compared to lead placement in the conventional manner. This is because DTIT-guidance allows closer and more consistent placement of leads to the centre of the DRTT than conventional methods.

    Matched MeSH terms: Parkinson Disease/physiopathology; Parkinson Disease/therapy*
  9. Fulltext Clinical outcomes of theophylline use as add-on therapy in patients with chronic obstructive pulmonary disease: A propensity score matching analysis
    Wilairat P, Kengkla K, Thayawiwat C, Phlaisaithong P, Somboonmee S, Saokaew S
    Chron Respir Dis, 2018 12 19;16:1479973118815694.
    PMID: 30558448 DOI: 10.1177/1479973118815694
    To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (2:1 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox's proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age: 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR: 1.48, 95% CI: 1.11-1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR: 1.47, 95% CI: 1.06-2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR: 1.11, 95% CI: 0.79-1.58; p = 0.548), hospitalization for pneumonia (aHR: 1.28, 95% CI: 0.89-1.84; p = 0.185), and all-cause hospitalizations (aHR: 1.03, 95% CI: 0.80-1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/drug therapy*; Pulmonary Disease, Chronic Obstructive/physiopathology
  10. Fulltext The association between chronic airflow obstruction and poverty in 12 sites of the multinational BOLD study
    Townend J, Minelli C, Mortimer K, Obaseki DO, Al Ghobain M, Cherkaski H, et al.
    Eur Respir J, 2017 06;49(6).
    PMID: 28572124 DOI: 10.1183/13993003.01880-2016
    Poverty is strongly associated with mortality from COPD, but little is known of its relation to airflow obstruction.In a cross-sectional study of adults aged ≥40 years from 12 sites (N=9255), participating in the Burden of Obstructive Lung Disease (BOLD) study, poverty was evaluated using a wealth score (0-10) based on household assets. Obstruction, measured as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (%) after administration of 200 μg salbutamol, and prevalence of FEV1/FVC
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/diagnosis; Pulmonary Disease, Chronic Obstructive/epidemiology*
  11. Fulltext Potential of Naturally Derived Alkaloids as Multi-Targeted Therapeutic Agents for Neurodegenerative Diseases
    Kong YR, Tay KC, Su YX, Wong CK, Tan WN, Khaw KY
    Molecules, 2021 Jan 30;26(3).
    PMID: 33573300 DOI: 10.3390/molecules26030728
    Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.
    Matched MeSH terms: Alzheimer Disease/drug therapy*; Alzheimer Disease/pathology
  12. Fulltext Cost analysis of measles in refugees arriving at Los Angeles International Airport from Malaysia
    Coleman MS, Burke HM, Welstead BL, Mitchell T, Taylor EM, Shapovalov D, et al.
    Hum Vaccin Immunother, 2017 05 04;13(5):1084-1090.
    PMID: 28068211 DOI: 10.1080/21645515.2016.1271518
    Background On August 24, 2011, 31 US-bound refugees from Kuala Lumpur, Malaysia (KL) arrived in Los Angeles. One of them was diagnosed with measles post-arrival. He exposed others during a flight, and persons in the community while disembarking and seeking medical care. As a result, 9 cases of measles were identified. Methods We estimated costs of response to this outbreak and conducted a comparative cost analysis examining what might have happened had all US-bound refugees been vaccinated before leaving Malaysia. Results State-by-state costs differed and variously included vaccination, hospitalization, medical visits, and contact tracing with costs ranging from $621 to $35,115. The total of domestic and IOM Malaysia reported costs for US-bound refugees were $137,505 [range: $134,531 - $142,777 from a sensitivity analysis]. Had all US-bound refugees been vaccinated while in Malaysia, it would have cost approximately $19,646 and could have prevented 8 measles cases. Conclusion A vaccination program for US-bound refugees, supporting a complete vaccination for US-bound refugees, could improve refugees' health, reduce importations of vaccine-preventable diseases in the United States, and avert measles response activities and costs.
    Matched MeSH terms: Disease Outbreaks/economics; Disease Outbreaks/prevention & control
  13. Fulltext Deciduous DPSCs Ameliorate MPTP-Mediated Neurotoxicity, Sensorimotor Coordination and Olfactory Function in Parkinsonian Mice
    Simon C, Gan QF, Kathivaloo P, Mohamad NA, Dhamodharan J, Krishnan A, et al.
    Int J Mol Sci, 2019 Jan 29;20(3).
    PMID: 30699944 DOI: 10.3390/ijms20030568
    Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and regenerative potential. However, the effective delivery and homing of DPSCs within the lesioned brain has been one of the many obstacles faced in cell-based therapy of neurodegenerative disorders. We hypothesized that DPSCs, delivered intranasally, could circumvent these challenges. In the present study, we investigated the therapeutic efficacy of intranasally administered DPSCs in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Human deciduous DPSCs were cultured, pre-labelled with PKH 26, and intranasally delivered into PD mice following MPTP treatment. Behavioural analyses were performed to measure olfactory function and sensorimotor coordination, while tyrosine hydroxylase (TH) immunofluorescence was used to evaluate MPTP neurotoxicity in SNpc neurons. Upon intranasal delivery, degenerated TH-positive neurons were ameliorated, while deterioration in behavioural performances was significantly enhanced. Thus, the intranasal approach enriched cell delivery to the brain, optimizing its therapeutic potential through its efficacious delivery and protection against dopaminergic neuron degeneration.
    Matched MeSH terms: Parkinson Disease/metabolism; Parkinson Disease/therapy*
  14. Synthesis of some new N-(alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamides as possible therapeutic agents for Alzheimer's disease and Type-2 Diabetes
    Abbasi MA, Rehman A, Siddiqui SZ, Hadi N, Mumtaz A, Shah SAA, et al.
    Pak J Pharm Sci, 2019 Jan;32(1):61-68.
    PMID: 30772791
    In the current research work, a series of new N-(alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamides has been synthesized by reacting 1,4-benzozzdioxan-6-amine (1) with 4-chlorobenzenesulfonyl chloride (2) to yield N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamide (3) which was further reacted with different alkyl/aralkyl halides (4a-n) to afford the target compounds (5a-n). Structures of the synthesized compounds were confirmed by IR, 1H-NMR, EI-MS spectral techniques and CHN analysis data. The results of enzyme inhibition showed that the molecules, N-2-phenethyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5j) and N-(1-butyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5d), exhibited moderate inhibitory potential against acetylcholinesterase with IC50 values 26.25±0.11 μM and 58.13±0.15 μM respectively, whereas, compounds N-benzyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5i) and N-(pentane-2-yl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5f) showed moderate inhibition against α-glucosidase enzyme as evident from IC50 values 74.52±0.07 and 83.52±0.08 μM respectively, relative to standards Eserine having IC50 value of 0.04±0.0001 μM for cholinesterases and Acarbose having IC50 value 38.25±0.12 μM for α-glucosidase, respectively.
    Matched MeSH terms: Alzheimer Disease/drug therapy*; Alzheimer Disease/enzymology
  15. Fulltext Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians
    Molineros JE, Looger LL, Kim K, Okada Y, Terao C, Sun C, et al.
    PLoS Genet, 2019 04;15(4):e1008092.
    PMID: 31022184 DOI: 10.1371/journal.pgen.1008092
    Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology.
    Matched MeSH terms: Disease Susceptibility*; Genetic Predisposition to Disease
  16. Molecular investigation of Anaplasma spp. in domestic and wildlife animals in Peninsular Malaysia
    Koh FX, Panchadcharam C, Sitam FT, Tay ST
    Vet Parasitol Reg Stud Reports, 2018 08;13:141-147.
    PMID: 31014863 DOI: 10.1016/j.vprsr.2018.05.006
    Anaplasma spp. are Gram-negative obligate intracellular, tick-borne bacteria which are of medical and veterinary importance. Little information is available on Anaplasma infection affecting domestic and wildlife animals in Malaysia. This study investigated the presence of Anaplasma spp. in the blood samples of domestic and wildlife animals in Peninsular Malaysia, using polymerase chain reaction (EHR-PCR) assays targeting the 16S rRNA gene of Anaplasmataceae. High detection rates (60.7% and 59.0%, respectively) of Anaplasma DNA were noted in 224 cattle (Bos taurus) and 78 deer (77 Rusa timorensis and one Rusa unicolor) investigated in this study. Of the 60 amplified fragments obtained for sequence analysis, Anaplasma marginale was exclusively detected in cattle while Anaplasma platys/Anaplasma phagocytophilum was predominantly detected in the deer. Based on sequence analyses of the longer fragment of the 16S rRNA gene (approximately 1000 bp), the occurrence of A. marginale, Anaplasma capra and Candidatus Anaplasma camelii in cattle, Candidatus A. camelii in deer and Anaplasma bovis in a goat was identified in this study. To assess whether animals were infected with more than one species of Anaplasma, nested amplification of A. phagocytophilum, A. bovis and Ehrlichia chaffeensis DNA was performed for 33 animal samples initially screened positive for Anaplasmataceae. No amplification of E. chaffeensis DNA was obtained from animals investigated. BLAST analyses of the 16S rDNA sequences from three deer (R. timorensis), a buffalo (Bubalus bubalis) and a cow (B. taurus) reveal similarity with that of Candidatus Anaplasma boleense strain (GenBank accession no.: KX987335). Sequence analyses of the partial gene fragments of major surface protein (msp4) gene from two deer (R. timorensis) and a monitor lizard (Varanus salvator) show the detection of a strain highly similar (99%) to that of A. phagocytophilum strain ZJ-China (EU008082). The findings in this study show the occurrence of various Anaplasma species including those newly reported species in Malaysian domestic and wildlife animals. The role of these animals as reservoirs/maintenance hosts for Anaplasma infection are yet to be determined.
    Matched MeSH terms: Disease Reservoirs/microbiology; Disease Reservoirs/veterinary*
  17. Fulltext Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis
    Too CL, Murad S, Dhaliwal JS, Larsson P, Jiang X, Ding B, et al.
    Arthritis Res Ther, 2012;14(6):R250.
    PMID: 23164236 DOI: 10.1186/ar4093
    INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations.
    METHODS: A total of 320 SNPs from the 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 the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a 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 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 PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)).
    CONCLUSION: Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests additional association with a PADI2 gene. The study thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to RA development in multiple populations of Asian descent.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology; Genetic Predisposition to Disease/genetics*
  18. Fulltext Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on Nutritional and Antioxidant Status of Male Chronic Obstructive Pulmonary Disease (COPD) Patients
    Pirabbasi E, Shahar S, Manaf ZA, Rajab NF, Manap RA
    J Nutr Sci Vitaminol (Tokyo), 2016;62(1):54-61.
    PMID: 27117852 DOI: 10.3177/jnsv.62.54
    Antioxidant therapy has a potential to be introduced as therapeutic modality for chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine the effect of antioxidant supplementation [ascorbic acid and N-Acetylcysteine (NAC)] on nutritional and antioxidant status in male COPD patients. A parallel and single blind randomised controlled clinical trial (RCT) was conducted at two medical centers in Kuala Lumpur, Malaysia. Seventy-nine subjects were recruited and randomly divided into four trial arms (i.e., NAC, vitamin C, NAC+vitamin C and control groups) for six mo. The primary outcome was changes in body mass index by estimating power of 90% and significance level of p<0.05. Repeated Measure ANOVA showed that there was a significant interaction effect on BMI (p=0.046) and carbohydrate intake (p=0.030), especially in the NAC group. Plasma glutathione (GSH) increased significantly in all intervention groups, especially in vitamin C (p=0.005). A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects.
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/drug therapy*; Pulmonary Disease, Chronic Obstructive/physiopathology
  19. Fulltext Identification of Reference Genes in Chicken Intraepithelial Lymphocyte Natural Killer Cells Infected with Very-virulent Infectious Bursal Disease Virus
    Boo SY, Tan SW, Alitheen NB, Ho CL, Omar AR, Yeap SK
    Sci Rep, 2020 05 22;10(1):8561.
    PMID: 32444639 DOI: 10.1038/s41598-020-65474-3
    Due to the limitations in the range of antibodies recognising avian viruses, quantitative real-time PCR (RT-qPCR) is still the most widely used method to evaluate the expression of immunologically related genes in avian viruses. The objective of this study was to identify suitable reference genes for mRNA expression analysis in chicken intraepithelial lymphocyte natural killer (IEL-NK) cells after infection with very-virulent infectious bursal disease virus (vvIBDV). Fifteen potential reference genes were selected based on the references available. The coefficient of variation percentage (CV%) and average count of these 15 genes were determined by NanoString technology for control and infected samples. The M and V values for shortlisted reference genes (ACTB, GAPDH, HMBS, HPRT1, SDHA, TUBB1 and YWHAZ) were calculated using geNorm and NormFinder. GAPDH, YWHAZ and HMBS were the most stably expressed genes. The expression levels of three innate immune response related target genes, CASP8, IL22 and TLR3, agreed in the NanoString and RNA sequencing (RNA-Seq) results using one or two reference genes for normalisation (not HMBS). In conclusion, GAPDH and YWHAZ could be used as reference genes for the normalisation of chicken IEL-NK cell gene responses to infection with vvIBDV.
    Matched MeSH terms: Infectious bursal disease virus/genetics*; Infectious bursal disease virus/immunology
  20. Fulltext Detection and characterization of viruses causing hand, foot and mouth disease from children in Seri Kembangan, Malaysia
    Ling BP, Jalilian FA, Harmal NS, Yubbu P, Sekawi Z
    Trop Biomed, 2014 Dec;31(4):654-62.
    PMID: 25776590 MyJurnal
    Hand, foot and mouth disease (HFMD) is a common viral infection among infants and children. The major causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). Recently, coxsackievirus A6 (CVA6) infections were reported in neighboring countries. Infected infants and children may present with fever, mouth/throat ulcers, rashes and vesicles on hands and feet. Moreover, EV71 infections might cause fatal neurological complications. Since 1997, EV71 caused fatalities in Sarawak and Peninsula Malaysia. The purpose of this study was to identify and classify the viruses which detected from the patients who presenting clinical signs and symptoms of HFMD in Seri Kembangan, Malaysia. From December 2012 until July 2013, a total of 28 specimens were collected from patients with clinical case definitions of HFMD. The HFMD viruses were detected by using semi-nested reverse transcription polymerase chain reaction (snRT-PCR). The positive snRT-PCR products were sequenced and phylogenetic analyses of the viruses were performed. 12 of 28 specimens (42.9%) were positive in snRT-PCR, seven are CVA6 (58.3%), two CVA16 (16.7%) and three EV71 (25%). Based on phylogenetic analysis studies, EV71 strains were identified as sub-genotype B5; CVA16 strains classified into sub-genotype B2b and B2c; CVA6 strains closely related to strains in Taiwan and Japan. In this study, HFMD in Seri Kembangan were caused by different types of Enterovirus, which were EV71, CVA6 and CVA16.
    Matched MeSH terms: Hand, Foot and Mouth Disease/pathology; Hand, Foot and Mouth Disease/virology*
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