Displaying publications 1 - 20 of 27 in total

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  1. Colorectal carcinoma in Malaysians: DNA mismatch repair pattern in a multiethnic population
    Cheah PL, Looi LM, Teoh KH, Rahman NA, Wong LX, Tan SY
    Asian Pac J Cancer Prev, 2014;15(7):3287-91.
    PMID: 24815484
    BACKGROUND: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between 1st January 2005 and 31st December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ≥50-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.
    Matched MeSH terms: Nuclear Proteins/genetics
  2. Contribution of the MLH1 -93G>a promoter polymorphism in modulating susceptibility risk in Malaysian colorectal cancer patients
    Nizam ZM, Abdul Aziz AA, Kaur G, Abu Hassan MR, Mohd Sidek AS, Yeh LY, et al.
    Asian Pac J Cancer Prev, 2013;14(2):619-24.
    PMID: 23621208
    BACKGROUND: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable.

    AIM: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk.

    METHODS: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs).

    RESULTS: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253).

    CONCLUSION: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

    Matched MeSH terms: Nuclear Proteins/genetics*
  3. Fulltext Identification of Potential Genes for Benign Prostatic Hyperplasia and Prostate Cancer Susceptibility in Four X-chromosome Regions with High Frequency of Microvariant Alleles
    Albujja MH, Messaudi SA, Vasudevan R, Al Ghamdi S, Chong PP, Ghani KA, et al.
    Asian Pac J Cancer Prev, 2020 08 01;21(8):2271-2280.
    PMID: 32856855 DOI: 10.31557/APJCP.2020.21.8.2271
    BACKGROUND: The X-chromosome has been suggested to play a role in prostate cancer (PrCa) since epidemiological studies have provided evidence for an X-linked mode of inheritance for PrCa based on the higher relative risk among men who report an affected brother(s) as compared to those reporting an affected father. The aim of this study was to examine the potential association between the forensic STR markers located at four regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28 and the risk of BPH and PrCa to confirm the impact of ChrX in the PrCa incidence. This may be helpful in the incorporation of STRs genetic variation in the early detection of men population at risk of developing PrCa.

    METHODS: DNA samples from 92 patients and 156 healthy controls collected from two medical centers in Riyadh, Saudi Arabia were analyzed for four regions located at X-chromosome using the Investigator® Argus X-12 QS Kit.

    RESULTS: The results demonstrated that microvariant alleles of (DXS7132, DXS10146, HPRTB, DXS10134, and DXS10135) are overrepresented in the BPH group (p < 0.00001). Allele 28 of DXS10135 and allele 15 of DXS7423 could have a protective effect, OR 0.229 (95%CI, 0.066-0.79); and OR 0.439 (95%CI, 0.208-0.925). On the other hand, patients carrying allele 23 of DXS10079 and allele 26 of DXS10148 presented an increased risk to PrCa OR 4.714 (95%CI, 3.604-6.166).

    CONCLUSION: The results are in concordance with the involvement of the X chromosome in PrCa and BPH development. STR allele studies may add further information from the definition of a genetic profile of PrCa resistance or susceptibility. As TBL1, AR, LDOC1, and RPL10 genes are located at regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28, respectively, these genes could play an essential role in PrCa or BPH.

    Matched MeSH terms: Nuclear Proteins/genetics*
  4. Fulltext Identification of FLT3 and NPM1 Mutations in Patients with Acute Myeloid Leukaemia
    Mat Yusoff Y, Abu Seman Z, Othman N, Kamaluddin NR, Esa E, Zulkiply NA, et al.
    Asian Pac J Cancer Prev, 2019 06 01;20(6):1749-1755.
    PMID: 31244296 DOI: 10.31557/APJCP.2019.20.6.1749
    Objective: The most frequent acquired molecular abnormalities and important prognostic indicators in patients
    with Acute Myeloid Leukaemia (AML) are fms-like tyrosine kinase-3 gene (FLT3) and nucleophosmin-1 (NPM1)
    mutations. Our study aims to develop a cost effective and comprehensive in-house conventional PCR method for
    detection of FLT3-ITD, FLT3-D835 and NPM1 mutations and to evaluate the frequency of these mutations in patients
    with cytogenetically normal (CN) AML in our population. Methods: A total of 199 samples from AML patients (95
    women, 104 men) were included in the study. Mutation analyses were performed using polymerase chain reaction
    (PCR) and gene sequencing. Result: Sixty-eight patients were positive for the mutations. FLT3-ITD mutations were
    detected in 32 patients (16.1%), followed by FLT3-D835 in 5 (2.5%) and NPM1 in 54 (27.1%). Double mutations of
    NPM1 and FLT3-ITD were detected in 23 cases (11.6%). Assays validation were performed using Sanger sequencing
    and showed 100% concordance with in house method. Conclusion: The optimized in-house PCR assays for the
    detection of FLT3-ITD, FLT3-D835 and NPM1 mutations in AML patients were robust, less labour intensive and cost
    effective. These assays can be used as diagnostic tools for mutation detection in AML patients since identification of
    these mutations are important for prognostication and optimization of patient care.
    Matched MeSH terms: Nuclear Proteins/genetics*
  5. Fulltext Allele-specific polymerase chain reaction for the detection of Alzheimer's disease-related single nucleotide polymorphisms
    Darawi MN, Ai-Vyrn C, Ramasamy K, Hua PP, Pin TM, Kamaruzzaman SB, et al.
    BMC Med Genet, 2013;14:27.
    PMID: 23419238 DOI: 10.1186/1471-2350-14-27
    The incidence of Alzheimer's disease, particularly in developing countries, is expected to increase exponentially as the population ages. Continuing research in this area is essential in order to better understand this disease and develop strategies for treatment and prevention. Genome-wide association studies have identified several loci as genetic risk factors of AD aside from apolipoprotein E such as bridging integrator (BIN1), clusterin (CLU), ATP-binding cassette sub-family A member 7 (ABCA7), complement receptor 1 (CR1) and phosphatidylinositol binding clathrin assembly protein (PICALM). However genetic research in developing countries is often limited by lack of funding and expertise. This study therefore developed and validated a simple, cost effective polymerase chain reaction based technique to determine these single nucleotide polymorphisms.
    Matched MeSH terms: Nuclear Proteins/genetics
  6. Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells through up-regulation of p73
    Wong SW, Tiong KH, Kong WY, Yue YC, Chua CH, Lim JY, et al.
    Breast Cancer Res Treat, 2011 Jul;128(2):301-13.
    PMID: 20686837 DOI: 10.1007/s10549-010-1055-0
    Recent gene expression profiling studies have identified five breast cancer subtypes, of which the basal-like subtype is the most aggressive. Basal-like breast cancer poses serious clinical challenges as there are currently no targeted therapies available to treat it. Although there is increasing evidence that these tumors possess specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and the development of drug resistance. To overcome this limitation, our goal was to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a validated kinase inhibitor library, we showed that inhibition of the mTOR, TGFβRI, NFκB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468 cells to cisplatin treatment. Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect of rapamycin plus cisplatin on basal-like breast cancer cells was mediated through the induction of p73. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects. In conclusion, combination therapy with mTOR inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of basal-like breast cancers.
    Matched MeSH terms: Nuclear Proteins/genetics
  7. Tocotrienol-treated MCF-7 human breast cancer cells show down-regulation of API5 and up-regulation of MIG6 genes
    Ramdas P, Rajihuzzaman M, Veerasenan SD, Selvaduray KR, Nesaretnam K, Radhakrishnan AK
    Cancer Genomics Proteomics, 2011 Jan-Feb;8(1):19-31.
    PMID: 21289334
    Tocotrienols belong to the vitamin E family and have multiple anticancer effects, such as antiproliferative, antioxidant, pro-apoptosis and antimetastatic. This study aimed to identify the genes that are regulated in human breast cancer cells following exposure to various isomers of vitamin E as these may be potential targets for the treatment of breast cancer.
    Matched MeSH terms: Nuclear Proteins/genetics*
  8. Fulltext WDR5, ASH2L, and RBBP5 control the efficiency of FOS transcript processing
    Teoh PL, Sharrocks AD
    Cell Mol Biol Lett, 2014 Jun;19(2):215-32.
    PMID: 24715476 DOI: 10.2478/s11658-014-0190-8
    H3K4 trimethylation is strongly associated with active transcription. The deposition of this mark is catalyzed by SET-domain methyltransferases, which consist of a subcomplex containing WDR5, ASH2L, and RBBP5 (the WAR subcomplex); a catalytic SET-domain protein; and additional complexspecific subunits. The ERK MAPK pathway also plays an important role in gene regulation via phosphorylation of transcription factors, co-regulators, or histone modifier complexes. However, the potential interactions between these two pathways remain largely unexplored. We investigated their potential interplay in terms of the regulation of the immediate early gene (IEG) regulatory network. We found that depletion of components of the WAR subcomplex led to increased levels of unspliced transcripts of IEGs that did not necessarily reflect changes in their mature transcripts. This occurs in a manner independent from changes in the H3K4me3 levels at the promoter region. We focused on FOS and found that the depletion of WAR subcomplex components affected the efficiency of FOS transcript processing. Our findings show a new aspect of WAR subcomplex function in coordinating active transcription with efficient pre-mRNA processing.
    Matched MeSH terms: Nuclear Proteins/genetics
  9. Role of Epithelial-to-Mesenchymal Transition Markers in Different Stages of Endometriosis: Expression of the Snail, Slug, ZEB1, and Twist Genes
    Kazmi I, Alharbi KS, Al-Abbasi FA, Almalki WH, G SK, Yasmeen A, et al.
    Crit Rev Eukaryot Gene Expr, 2021;31(2):89-95.
    PMID: 34347983 DOI: 10.1615/CritRevEukaryotGeneExpr.2021037996
    Among various epithelial-to-mesenchymal transition (EMT)-related transcription factors (TFs), altered expression levels of Snail-1, Snail-2/Slug, Twist, and ZEB1 have shown a significant association in different cancers having a higher risk of metastasis. However, their role in the circulation of endometriosis patients is not well understood. Hence, the present study was designed to evaluate the crucial role of these TFs in defining the molecular pathogenesis for endometriosis progression and differentiation from control subjects. The qualitative and quantitative expression analysis of Snail-1, Snail-2/Slug, Twist, and ZEB1 were analyzed in peripheral blood samples of 75 different stages of endometriosis patients and compared with 50 control subjects. Total RNA was extracted and converted into complementary DNA (cDNA) for relative quantification of each gene transcript using SYBRGreen-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The Livak method of relative quantification was used for calculating the fold change in each TF compared with endogenous control. All four selected TFs showed significantly upregulated expression levels in endometriosis patients compared with control subjects. A three-fold increase was observed for Snail-1 (p = 0.0001), and a two-fold increase was observed for Snail-2 (p = 0.01), Twist (p = 0.0002), and ZEB1 (p = 0.001) in stage III and IV compared with stage I and II of endometriosis patients. The present study revealed that EMT-related TFs play a crucial role in the pathogenesis and differentiating different stages of endometriosis patients through expression analysis of specific molecular cascades using non-invasive tools.
    Matched MeSH terms: Nuclear Proteins/genetics*
  10. Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in Malaysia
    Abdul Murad NA, Othman Z, Khalid M, Abdul Razak Z, Hussain R, Nadesan S, et al.
    Dig Dis Sci, 2012 Nov;57(11):2863-72.
    PMID: 22669205 DOI: 10.1007/s10620-012-2240-2
    BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown.

    AIMS: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes.

    METHODS: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations.

    RESULTS: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC).

    CONCLUSIONS: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.

    Matched MeSH terms: Nuclear Proteins/genetics*
  11. Fulltext Evolutionary and functional analysis of RBMY1 gene copy number variation on the human Y chromosome
    Shi W, Louzada S, Grigorova M, Massaia A, Arciero E, Kibena L, et al.
    Hum Mol Genet, 2019 Aug 15;28(16):2785-2798.
    PMID: 31108506 DOI: 10.1093/hmg/ddz101
    Human RBMY1 genes are located in four variable-sized clusters on the Y chromosome, expressed in male germ cells and possibly associated with sperm motility. We have re-investigated the mutational background and evolutionary history of the RBMY1 copy number distribution in worldwide samples and its relevance to sperm parameters in an Estonian cohort of idiopathic male factor infertility subjects. We estimated approximate RBMY1 copy numbers in 1218 1000 Genomes Project phase 3 males from sequencing read-depth, then chose 14 for valid ation by multicolour fibre-FISH. These fibre-FISH samples provided accurate calibration standards for the entire panel and led to detailed insights into population variation and mutational mechanisms. RBMY1 copy number worldwide ranged from 3 to 13 with a mode of 8. The two larger proximal clusters were the most variable, and additional duplications, deletions and inversions were detected. Placing the copy number estimates onto the published Y-SNP-based phylogeny of the same samples suggested a minimum of 562 mutational changes, translating to a mutation rate of 2.20 × 10-3 (95% CI 1.94 × 10-3 to 2.48 × 10-3) per father-to-son Y-transmission, higher than many short tandem repeat (Y-STRs), and showed no evidence for selection for increased or decreased copy number, but possible copy number stabilizing selection. An analysis of RBMY1 copy numbers among 376 infertility subjects failed to replicate a previously reported association with sperm motility and showed no significant effect on sperm count and concentration, serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels or testicular and semen volume. These results provide the first in-depth insights into the structural rearrangements underlying RBMY1 copy number variation across diverse human lineages.
    Matched MeSH terms: Nuclear Proteins/genetics*
  12. Fulltext Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation
    Campa D, Pastore M, Capurso G, Hackert T, Di Leo M, Izbicki JR, et al.
    Int J Cancer, 2018 01 15;142(2):290-296.
    PMID: 28913878 DOI: 10.1002/ijc.31047
    Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous  = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous  = 2.07 (1.55-2.77, ptrend  = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.
    Matched MeSH terms: Nuclear Proteins/genetics
  13. Prevalence of mupirocin resistance in methicillin-resistant Staphylococcus aureus strains isolated from a Malaysian hospital
    Lim KT, Hanifah YA, Mohd Yusof MY, Thong KL
    Jpn J Infect Dis, 2010 Jul;63(4):286-9.
    PMID: 20657072
    Mupirocin is used topically to treat skin infection caused by methicillin-resistant Staphylococcus aureus (MRSA). One hundred eighty-eight strains (isolated in 2003, 2004, 2007, and 2008) were tested for mupirocin susceptibility using disk diffusion method and minimum inhibitory concentration (MIC). Mupirocin resistance was detected in 10 (5%) strains with 2 of them showing MIC of 256 mg/l. PCR detection using gene-specific primers showed that all 10 mupirocin-resistant strains harbored ileS2 gene whereas mupA gene was detected in 2 mupirocin-resistant strains with MIC of 256 mg/l. Amplification of agr grouping and SCCmec typing showed that all 10 strains were agr group I and SCCmec type III. Sequence analysis of region X of the spa gene yielded 4 distinct spa types (t037, t363, t421, and t6405) which were clonally related. In conclusion, the rate of mupirocin resistance in Malaysia is still low but is much higher than previous reports in Malaysia.
    Matched MeSH terms: Nuclear Proteins/genetics
  14. Fulltext Reduced cardiomyocyte Na+ current in the age-dependent murine Pgc-1β-/- model of ventricular arrhythmia
    Ahmad S, Valli H, Smyth R, Jiang AY, Jeevaratnam K, Matthews HR, et al.
    J Cell Physiol, 2019 Apr;234(4):3921-3932.
    PMID: 30146680 DOI: 10.1002/jcp.27183
    Peroxisome proliferator-activated receptor-γ coactivator-1 deficient (Pgc-1β-/- ) murine hearts model the increased, age-dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na+ current in these electrophysiological phenotypes by applying loose patch-clamp techniques in intact young and aged, wild-type (WT) and Pgc-1β-/- , ventricular cardiomyocyte preparations for the first time. This allowed conservation of their in vivo extracellular and intracellular conditions. Depolarising steps elicited typical voltage-dependent activating and inactivating inward Na+ currents with peak amplitudes increasing or decreasing with their respective activating or preceding inactivating voltage steps. Two-way analysis of variance associated Pgc-1β-/- genotype with independent reductions in maximum peak ventricular Na+ currents from -36.63 ± 2.14 (n = 20) and -35.43 ± 1.96 (n = 18; young and aged WT, respectively), to -29.06 ± 1.65 (n = 23) and -27.93 ± 1.63 (n = 20; young and aged Pgc-1β-/- , respectively) pA/μm2 (p 
    Matched MeSH terms: Nuclear Proteins/genetics
  15. Fulltext Age-dependent atrial arrhythmic phenotype secondary to mitochondrial dysfunction in Pgc-1β deficient murine hearts
    Valli H, Ahmad S, Chadda KR, Al-Hadithi ABAK, Grace AA, Jeevaratnam K, et al.
    Mech Ageing Dev, 2017 Oct;167:30-45.
    PMID: 28919427 DOI: 10.1016/j.mad.2017.09.002
    INTRODUCTION: Ageing and several age-related chronic conditions including obesity, insulin resistance and hypertension are associated with mitochondrial dysfunction and represent independent risk factors for atrial fibrillation (AF).

    MATERIALS AND METHODS: Atrial arrhythmogenesis was investigated in Langendorff-perfused young (3-4 month) and aged (>12 month), wild type (WT) and peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts modeling age-dependent chronic mitochondrial dysfunction during regular pacing and programmed electrical stimulation (PES).

    RESULTS AND DISCUSSION: The Pgc-1β-/- genotype was associated with a pro-arrhythmic phenotype progressing with age. Young and aged Pgc-1β-/- hearts showed compromised maximum action potential (AP) depolarization rates, (dV/dt)max, prolonged AP latencies reflecting slowed action potential (AP) conduction, similar effective refractory periods and baseline action potential durations (APD90) but shortened APD90 in APs in response to extrasystolic stimuli at short stimulation intervals. Electrical properties of APs triggering arrhythmia were similar in WT and Pgc-1β-/- hearts. Pgc-1β-/- hearts showed accelerated age-dependent fibrotic change relative to WT, with young Pgc-1β-/- hearts displaying similar fibrotic change as aged WT, and aged Pgc-1β-/- hearts the greatest fibrotic change. Mitochondrial deficits thus result in an arrhythmic substrate, through slowed AP conduction and altered repolarisation characteristics, arising from alterations in electrophysiological properties and accelerated structural change.

    Matched MeSH terms: Nuclear Proteins/genetics*
  16. Methicillin-susceptible and -resistant Staphylococcus aureus with high-level antiseptic and low-level mupirocin resistance in Malaysia
    Ghasemzadeh-Moghaddam H, van Belkum A, Hamat RA, van Wamel W, Neela V
    Microb Drug Resist, 2014 Oct;20(5):472-7.
    PMID: 24841796 DOI: 10.1089/mdr.2013.0222
    The prevalence and spread of mupirocin and antiseptic resistance among colonizing and infectious Staphylococcus aureus were determined. S. aureus isolated from anterior nares and infection sites of patients hospitalized in the largest tertiary care referral hospital in Malaysia was investigated for mupirocin and antiseptic susceptibility testing, and for PCR detection of mupA, qacA/B, and smr genes. Twelve isolates showed resistance to mupirocin by disk diffusion, of which 10 (3.8%) harbored the mupA gene. Minimum inhibitory concentrations (MICs) ranged from 64 to 768 μg/ml for mupA positive and below 46 μg/ml for negative isolates. The mupA was more common among ST239 isolates (70%). The qacA/B was carried in 67 out of 95 methicillin-resistant Staphylococcus aureus (MRSA) (70.5%) and 3 out of 164 methicillin-susceptible Staphylococcus aureus (MSSA) (1.8%), while smr was carried in 6 out of 95 MRSA (6.3%) strains. MICs ranged from 3.9 to 15.6 μg/ml for benzethonium chloride (BTC) and benzalkonium chloride (BKC), and from 10.3 to 20.7 μg/ml for chlorhexidine digluconate (CHG). Isolates with qacA/B and smr or qacA/B alone showed higher MIC (20.7 μg/ml for CHG and 15.6 μg/ml for BTC and BKC) than the isolates that lacked antiseptic resistance genes (10.3 μg/ml for CHG and 3.9 μg/ml for BTC and BKC). In 16 cases, ST239 was isolated from the infection site and the nares simultaneously, and shared identical resistance patterns (qacAB or qacAB+smr), suggesting possible endogenous infection. Spread of low-level mupirocin resistance expressing ST239 MRSA and high-level resistance expressing emerging ST1, co-existing with antiseptic-resistant genes showing elevated MICs, should be monitored for effective infection control.
    Matched MeSH terms: Nuclear Proteins/genetics
  17. Fulltext Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4
    Psychiatric GWAS Consortium Bipolar Disorder Working Group
    Nat Genet, 2011 Sep 18;43(10):977-83.
    PMID: 21926972 DOI: 10.1038/ng.943
    We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
    Matched MeSH terms: Nuclear Proteins/genetics*
  18. A rare case of metastatic lung carcinoma with t(15;19)(q13;p13.1) and trisomy 12
    Tay Za K, Bee PC, Shanmugam H
    Pathology, 2020 Feb;52(2):273-276.
    PMID: 31883672 DOI: 10.1016/j.pathol.2019.10.013
    Matched MeSH terms: Nuclear Proteins/genetics*
  19. X-linked dyskeratosis congenita in Malaysia
    Hamidah A, Rashid RA, Jamal R, Zhao M, Kanegane H
    Pediatr Blood Cancer, 2008 Feb;50(2):432.
    PMID: 17417794
    Matched MeSH terms: Nuclear Proteins/genetics*
  20. Fulltext Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore
    Phuah SY, Lee SY, Kang P, Kang IN, Yoon SY, Thong MK, et al.
    PLoS One, 2013;8(8):e73638.
    PMID: 23977390 DOI: 10.1371/journal.pone.0073638
    The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.
    Matched MeSH terms: Nuclear Proteins/genetics*
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