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Kuala Selangor, Malaysia

Chow Z.,Monash University | Banerjee A.,Institute of Medical Research | Hickey M.J.,Monash University
Immunology and Cell Biology

Regulatory T cells have essential roles in regulating immune responses and limiting inappropriate inflammation. Evidence now indicates that to achieve this function, regulatory T cells must be able to migrate to the most appropriate locations within both lymphoid and non-lymphoid organs. This function is achieved via the spatiotemporally controlled expression of adhesion molecules and chemokine receptors, varying according to the developmental stage of the regulatory T cell and the location and environment where they undergo activation. In this Review, we summarise information on the roles of adhesion molecules and chemokine receptors in mediating regulatory T-cell migration and function throughout the body under homeostatic and inflammatory conditions. In addition, we review recent studies that have used in vivo imaging to examine the actions of regulatory T cells in vivo, in lymph nodes, in the microvasculature and in the interstitium of peripheral organs. These studies reveal that the capacity of regulatory T cells to undergo selective migration serves a critical role in their ability to suppress immune responses. As such, the cellular and molecular requirements of regulatory T-cell migration need to be completely understood to enable the most effective use of these cells in clinical settings. © 2015 Australasian Society for Immunology Inc. All rights reserved. Source

Gompel A.,University of Paris Descartes | Burger H.,Institute of Medical Research

The incidence of ovarian cancer is tenfold lower than that of breast cancer. The goal of the recently published meta-analysis by Beral and colleagues, using 'individual participant datasets from 52 epidemiological studies', was to provide an updated assessment of the effect of menopausal hormone therapy (MHT) on ovarian cancer risk. The relative risk generated from the cited prospective studies was significantly increased but the relative risk from the retrospective studies was not. This is quite unusual since retrospective studies usually display higher levels of relative risk. No further increase was observed with increasing duration. Moreover, a number of the studies could not be adjusted for important ovarian cancer risk factors. From the metaanalysis, it can be calculated that the absolute excess risk of 5 years of MHT for a 50-year-old UK woman is 1 in 10 000 per year, indicating a very low risk. We conclude that this meta-analysis mostly reflects the previously published data from the Million Women Study, from which the majority of this new publication is derived. © 2015 International Menopause Society. Source

Weinger J.G.,Yeshiva University | Davies P.,Yeshiva University | Davies P.,Institute of Medical Research | Acker C.M.,Yeshiva University | And 5 more authors.
Journal of Neuropathology and Experimental Neurology

The abundant axonal microtubule-associated protein tau regulates microtubule and actin dynamics, thereby contributing to normal neuronal function. We examined whether mice deficient in tau (Tau -/-) or with high levels of human tau differ from wild-type (WT) mice in their susceptibility to neuroaxonal injury in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. After sensitization with MOG 35-55, there was no difference in clinical disease course between human tau and WT mice, but Tau -/- mice had more severe clinical disease and significantly more axonal damage in spinal cord white matter than those in WT mice. Axonal damage in gray matter correlated with clinical severity in individual mice. By immunoblot analysis, the early microtubule-associated protein-1b was increased 2-fold in the spinal cords of Tau -/- mice with chronic experimental autoimmune encephalomyelitis versus naive Tau -/- mice. This difference was not detected in comparable WT animals, which suggests that there was compensation for the loss of tau in the deficient mice. In addition, levels of the growth arrest-specific protein 7b, a tau-binding protein that is stabilized when bound to tau, were higher in WT than those in Tau -/-spinal cord samples. These data indicate that loss of tau exacerbates experimental autoimmune encephalomyelitis and suggest that maintaining tau integrity might reduce the axonal damage that occurs in inflammatory neurodegenerative diseases such as multiple sclerosis. © 2012 by the American Association of Neuropathologists, Inc. Source

Mohamed Saini S.,University of Kuala Lumpur | Nik Jaafar N.R.,University of Kuala Lumpur | Sidi H.,University of Kuala Lumpur | Midin M.,University of Kuala Lumpur | And 2 more authors.
Comprehensive Psychiatry

Objectives The risk variants have been shown to vary substantially across populations and a genetic study in a heterogeneous population might shed a new light in the disease mechanism. This preliminary study aims to determine the frequency of the serotonin transporter gene polymorphism (5-HTTLPR) in the three main ethnic groups in Malaysia and its association with bipolar disorder. Methods This is a candidate gene association study of randomly selected forty five unrelated bipolar disorder probands and sixty six controls. Diagnosis was evaluated using the Mini International Neuropsychiatric Interview (M.I.N.I). The control group consisted of healthy volunteers without personal psychiatric history and family history of mood disorder. Patients' whole blood was collected for genotyping. Results This study revealed that the frequency of the short variant of 5-HTTLPR in healthy control group was highest in Indians (42.9%) followed by Malays (23.5%) and was absent in Chinese. The association between the homozygous ss genotype of the 5-HTTLPR polymorphism with bipolar disorder was not found in the pooled subjects (χ2 = 1.52, d.f. = 1, p = 0.218, OR = 4.67, 95% C.I. = 0.69-7.58) and after stratification into Malays (p = 0.315, OR = 2.03, 95% CI = 0.50-8.17), Indians (p = 0.310; OR = 0.44, 95% CI = 0.21-0.92) and Chinese. Conclusion The differences in the frequency of the short allele of 5-HTTLPR across the three main ethnic groups in Malaysia were noteworthy. The present study showed no significant association between the homozygous short variant of the 5-HTTLPR and bipolar disorder in the pooled subject and after stratification into the three main ethnic groups in Malaysia. © 2014 Elsevier Inc. All rights reserved. Source

Goh P.,Hospital Selayang | Omar M.A.,Institute of Health Management | Yusoff A.F.,Institute of Medical Research
Singapore Medical Journal

Introduction: Diabetic retinopathy (DR) is the commonest complication of diabetes mellitus (DM), and is the leading cause of blindness among working adults. Modification of the associated risk factors as well as early detection and treatment of sight-threatening DR can prevent blindness. Clinical practice guidelines recommend annual eye screening for patients with DM. The proportion of patients in Malaysia who adhere to this recommendation was initially unknown. Methods: The Malaysian National Health and Morbidity Survey is a population-based survey conducted once every decade on the various aspects of health, behaviour and diseases. The DM questionnaire on eye screening was administered as face-to-face interviews with 2,373 patients with known DM who were aged 18 years and older. Results: In all, 55 percent of patients with known DM had never undergone an eye examination. Among patients who had undergone eye examinations, 32.8 percent had the last examination within the last one year, 49.8 percent within the last one to two years, and 17.4 percent more than two years ago. A signifcantly lower proportion of younger patients and patients who received treatment for DM from non-government facilities had previously undergone eye examinations. Conclusion: The prevalence of DM observed among Malaysians aged 30 and above is 14.9 percent; thus, there is a signifcant number of people with potential blinding DR. Adherence to eye screening guidelines and the prompt referral of sight-threatening DR are essential in order to reduce the incidence of blindness among patients with DM. Source

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