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Displaying publications 81 - 87 of 87 in total

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Absence of beta-amyloid deposition in the central nervous system of a transgenic mouse model of distal myopathy with rimmed vacuoles

Anada RP, Wong KT, Malicdan MC, Goh KJ, Hayashi Y, Nishino I, et al.

Amyloid, 2014 Jun;21(2):138-9.
PMID: 24601867 DOI: 10.3109/13506129.2014.889675
Fulltext Analysis of CTG repeat length variation in the DMPK gene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia

Ambrose KK, Ishak T, Lian LH, Goh KJ, Wong KT, Ahmad-Annuar A, et al.

BMJ Open, 2017 03 31;7(3):e010711.
PMID: 28363916 DOI: 10.1136/bmjopen-2015-010711

OBJECTIVE: The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia.
DESIGN, SETTING AND PARTICIPANTS: We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion.
OUTCOME MEASURES: The number of individuals not known to be affected by DM with (CTG)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation.
RESULTS: Of the 754 chromosomes studied, (CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation.
CONCLUSIONS: The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries.
Fulltext Deregulation of microRNAs in blood and skeletal muscles of myotonic dystrophy type 1 patients

Ambrose KK, Ishak T, Lian LH, Goh KJ, Wong KT, Ahmad-Annuar A, et al.

Neurol India, 2017 5 11;65(3):512-517.
PMID: 28488611 DOI: 10.4103/neuroindia.NI_237_16

INTRODUCTION: MicroRNAs (miRNAs) are short RNA molecules of approximately 22 nucleotides that function as post-transcriptional regulators of gene expression. They are expressed in a tissue-specific manner and show different expression patterns in development and disease; hence, they can potentially act as disease-specific biomarkers. Several miRNAs have been shown to be deregulated in plasma and skeletal muscles of myotonic dystrophy type 1 (DM1) patients.
METHODS: We evaluated the expression patterns of 11 candidate miRNAs using quantitative real-time PCR in whole blood (n = 10) and muscle biopsy samples (n = 9) of DM1 patients, and compared them to those of normal control samples (whole blood, n = 10; muscle, n = 9).
RESULTS: In DM1 whole blood, miRNA-133a, -29b, and -33a were significantly upregulated, whereas miRNA-1, -133a, and -29c were significantly downregulated in the skeletal muscles compared to controls.
CONCLUSIONS: Our findings align to those reported in other studies and point towards pathways that potentially contribute toward pathogenesis in DM1. However, the currently available data is not sufficient for these miRNAs to be made DM1-specific biomarkers because they seem to be common to many muscle pathologies. Hence, they lack specificity, but reinforce the need for further exploration of DM1 biomarkers.
Fulltext Clinicopathological Features of Telbivudine-Associated Myopathy

Ambang T, Tan JS, Ong S, Wong KT, Goh KJ

PLoS One, 2016;11(9):e0162760.
PMID: 27611456 DOI: 10.1371/journal.pone.0162760

Telbivudine, a thymidine nucleoside analog, is a common therapeutic option for chronic hepatitis B infection. While raised serum creatine kinase is common, myopathy associated with telbivudine is rare. Reports on its myopathological features are few and immunohistochemical analyses of inflammatory cell infiltrates have not been previously described. We describe the clinical, myopathological and immunohistochemical features of four patients who developed myopathy after telbivudine therapy for chronic hepatitis B infection. All four patients presented with progressive proximal muscle weakness, elevation of serum creatine kinase and myopathic changes on electromyography. Muscle biopsies showed myofiber degeneration/necrosis, regeneration, and fibers with cytoplasmic bodies and cytochrome c oxidase deficiency. There was minimal inflammation associated with strong sarcolemmal overexpression of class I major histocompatibility complex (MHC class I). Upon withdrawal of telbivudine, muscle weakness improved in all patients and eventually completely resolved in three. In our series, telbivudine-associated myopathy is characterized by necrotizing myopathy which improved on drug withdrawal. Although the occasional loss of cytochrome c oxidase is consistent with mitochondrial toxicity, the overexpression of MHC class I in all patients could suggest an underlying immune-mediated mechanism which may warrant further investigation.
Fulltext Metabolic Profile of Scytalidium parasiticum-Ganoderma boninense Co-Cultures Revealed the Alkaloids, Flavonoids and Fatty Acids that Contribute to Anti-Ganoderma Activity

Ahmad R, Lim CK, Marzuki NF, Goh YK, Azizan KA, Goh YK, et al.

Molecules, 2020 Dec 16;25(24).
PMID: 33339375 DOI: 10.3390/molecules25245965

In solving the issue of basal stem rot diseases caused by Ganoderma, an investigation of Scytalidium parasiticum as a biological control agent that suppresses Ganoderma infection has gained our interest, as it is more environmentally friendly. Recently, the fungal co-cultivation has emerged as a promising method to discover novel antimicrobial metabolites. In this study, an established technique of co-culturing Scytalidium parasiticum and Ganoderma boninense was applied to produce and induce metabolites that have antifungal activity against G. boninense. The crude extract from the co-culture media was applied to a High Performance Liquid Chromatography (HPLC) preparative column to isolate the bioactive compounds, which were tested against G. boninense. The fractions that showed inhibition against G. boninense were sent for a Liquid Chromatography-Time of Flight-Mass Spectrometry (LC-TOF-MS) analysis to further identify the compounds that were responsible for the microbicidal activity. Interestingly, we found that eudistomin I, naringenin 7-O-beta-D-glucoside and penipanoid A, which were present in different abundances in all the active fractions, except in the control, could be the antimicrobial metabolites. In addition, the abundance of fatty acids, such as oleic acid and stearamide in the active fraction, also enhanced the antimicrobial activity. This comprehensive metabolomics study could be used as the basis for isolating biocontrol compounds to be applied in oil palm fields to combat a Ganoderma infection.
The utility of ALS staging systems in a multi-ethnic patient cohort

Abdul Aziz NA, Toh TH, Loh EC, Capelle DP, Goh KJ, Abdul Latif L, et al.

Amyotroph Lateral Scler Frontotemporal Degener, 2021 08;22(5-6):341-349.
PMID: 33726578 DOI: 10.1080/21678421.2021.1893336

Objective: To compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using prospective data from a multi-ethnic cohort of ALS patients. Methods: The stages of disease were determined prospectively based on existing definitions. The two systems were compared for timing of stages using box plots, correspondence using chi-square tests and association using Spearman's rank correlation. Results: The distribution of stages differed between the two systems. The proportions of disease stages of the King's staging system were more evenly distributed whereas in MiToS, there was greater weight seen at the later stages of disease. At the early stages, patients moved consecutively in the MiToS staging system but not in the King's staging system where patients tended to skip stages to reach later stages. Both systems had good correlation (Spearman's rho = 0.869) and the King's stage 4 most frequently corresponded to MiToS stage 2. Conclusion: We found the King's staging was helpful in determining the stages of disease burden, whereas both were helpful in determining the time to functional dependence with MiToS further refining the levels of dependence.
Natural history and clinical features of ALS in Malaysia

Abdul Aziz NA, Toh TH, Goh KJ, Loh EC, Capelle DP, Abdul Latif L, et al.

Amyotroph Lateral Scler Frontotemporal Degener, 2021 02;22(1-2):108-116.
PMID: 33084408 DOI: 10.1080/21678421.2020.1832121

OBJECTIVE: Studies from multiethnic populations are rarely reported but do indicate differences in phenotypic presentation and survival in amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the natural history of a cohort of ALS patients from a multiethnic population. Methods: Data from ALS patients presenting to our multidisciplinary ALS clinic were prospectively collected from January 2015 to June 2020 as part of an ongoing hospital-based patient registry. Kaplan-Meier and Cox regression model were performed to identify potential prognostic factors. Results: A total of 144 ALS patients were recruited. We estimated the crude ALS incidence as 0.53 per 100,000 for 2019 but rises to 2 per 100,000 in patients aged 60-74 years. The majority of patients were of Chinese ethnicity (59.7%), followed by Malay (24.3%), Indian (11.1%), and others (4.9%). Malaysian Indians had a significantly steeper ALSFRS-R slope at diagnosis (p = 0.040). We found a worse prognosis in patients with bulbar-onset (HR = 1.915, p = 0.019), older age (HR = 1.052, p = 0.000), and who were fast-progressors (HR = 1.274, p = 0.000). In contrast, a higher body mass index (HR = 0.921, p = 0.007) and a longer time to diagnosis (HR = 0.967, p = 0.006), noninvasive ventilation (HR = 0.820, p = 0.000) and percutaneous endoscopic gastrostomy insertion (HR = 0.823, p = 0.000) were associated with better survival. On multivariate analysis, diagnostic delay and slow disease progression were associated with better survival. Conclusions: In our cohort, diagnostic delay and a slow disease progression were significantly associated with better survival in ALS. We also found ethnic variation with Chinese preponderance and more rapid disease progression in patients of Indian descent.