Browsing by Author "James, J"

Now showing 1 - 5 of 5
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    Diffusion Tensor Imaging and Tractography of the Human Language Pathways: Moving Into the Clinical Realm
    (JOURNAL OF MAGNETIC RESONANCE IMAGING, 2014) Muthusami, P; James, J; Thomas, B; Kapilamoorthy, TR; Kesavadas, C
    The functional correlates of anatomical derangements are of interest to the neurological clinician. Diffusion tensor tractography (DTT) is a relatively new tool in the arsenal of functional neuroimaging, by which to assess white matter tracts in the brain. While much import has been given to tracking corticospinal tracts in neurological disease, studying language pathway interconnections using DTT has largely remained in the research realm. Hardware and software advances have allowed this tool to ease into clinical practice, with several radiologists, neurologists, and neurosurgeons now familiar with its applications. DTT images, although visually appealing, are founded in mathematical equations and assumptions, and require a more than basic understanding of principles and limitations before they can be integrated into routine clinical practice. Cognitive pathways like that of language, that are normally hard to assess and especially more so when pathologically affected, have been at the receiving end of several opposing and often controversial hypotheses, and the past decade has seen the clarification, validation or rejection of several of these by the in vivo charting of functional connectivity using DTT. The focus of this review is to illustrate DTT of the language pathways with emphasis on practical considerations, clinical applications, and limitations.
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    Molecular basis and functional significance of Angiotensin II-induced increase in Discoidin Domain Receptor 2 gene expression in cardiac fibroblasts
    (JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2016) George, M; Vijayakumar, A; Dhanesh, SB; James, J; Shivakumar, K
    Delineation of mechanisms underlying the regulation of fibrosis-related genes in the heart is an important clinical goal as cardiac fibrosis is a major cause of myocardial dysfunction. This study probed the regulation of Discoidin Domain Receptor 2 (DDR2) gene expression and the regulatory links between Angiotensin II, DDR2 and collagen in Angiotensin II-stimulated cardiac fibroblasts. Real-time PCR and western blot analyses showed that Angiotensin II enhances DDR2 mRNA and protein expression in rat cardiac fibroblasts via NADPH oxidase-dependent reactive oxygen species induction. NF-kappa B activation, demonstrated by gel shift assay, abolition of DDR2 expression upon NF-kappa B inhibition, and luciferase and chromatin immunoprecipitation assays confirmed transcriptional control of DDR2 by NF-kappa B in Angiotensin II-treated cells. Inhibitors of Phospholipase C and Protein kinase C prevented Angiotensin II-dependent p38 MAPK phosphorylation that in turn blocked NF-kappa B activation. Angiotensin II also enhanced collagen gene expression. Importantly, the stimulatory effects of Angiotensin II on DDR2 and collagen were inter-dependent as siRNA-mediated silencing of one abolished the other. Angiotensin II promoted ERK1/2 phosphorylation whose inhibition attenuated Angiotensin II-stimulation of collagen but not DDR2. Furthermore, DDR2 knockdown prevented Angiotensin II-induced ERK1/2 phosphorylation, indicating that DDR2-dependent ERK1/2 activation enhances collagen expression in cells exposed to Angiotensin II. DDR2 knockdown was also associated with compromised wound healing response to Angiotensin II. To conclude, Angiotensin II promotes NF-kappa B activation that up-regulates DDR2 transcription. A reciprocal regulatory relationship between DDR2 and collagen, involving cross-talk between the GPCR and RTK pathways, is central to Angiotensin II-induced increase in collagen expression in cardiac fibroblasts. (C) 2015 Elsevier Ltd. All rights reserved.
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    Molecular mechanisms in H2O2-induced increase in AT1 receptor gene expression in cardiac fibroblasts: A role for endogenously generated Angiotensin II
    (JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2016) Anupama, V; George, M; Dhanesh, SB; Chandran, A; James, J; Shivakumar, K
    The AT1 receptor (AT1R) mediates the manifold actions of angiotensin II in the cardiovascular system. This study probed the molecular mechanisms that link altered redox status to AT1R expression in cardiac fibroblasts. Real-time PCR and western blot analysis showed that H2O2 enhances AT1R mRNA and protein expression via NADPH oxidase-dependent reactive oxygen species induction. Activation of NF-kappa B and AP-1, demonstrated by electrophoretic mobility shift assay, abolition of AT1R expression by their inhibitors, Bay-11-7085 and SR11302, respectively, and luciferase and chromatin immunoprecipitation assays confirmed transcriptional control of AT1R by NF-kappa B and AP-1 in H2O2-treated cells. Further, inhibition of ERK1/2, p38 MAPK and c-Jun N-terminal kinase (JNK) using chemical inhibitors or by RNA interference attenuated AT1R expression. Inhibition of the MAPKs showed that while ERK1/2 and p38 MAPK suffice for NF-kappa B activation, all three kinases are required for AP-1 activation. H2O2 also increased collagen type I mRNA and protein expression. Interestingly, the AT1R antagonist, candesartan, attenuated H2O2-stimulated AT1R and collagen mRNA and protein expression, suggesting that H2O2 up-regulates AT1R and collagen expression via local Angiotensin II generation, which was confirmed by real-time PCR and ELISA. To conclude, oxidative stress enhances AT1R gene expression in cardiac fibroblasts by a complex mechanism involving the redox-sensitive transcription factors NF-kappa B and AP-1 that are activated by the co-ordinated action of ERK1/2, p38 MAPK and JNK. Importantly, by causally linking oxidative stress to Angiotensin II and AT1R up-regulation in cardiac fibroblasts, this study offers a novel perspective on the pathogenesis of cardiovascular diseases associated with oxidative stress. (C) 2016 Elsevier Ltd. All rights reserved.
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    Seizure induces activation of multiple subtypes of neural progenitors and growth factors in hippocampus with neuronal maturation confined to dentate gyrus
    (BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010) Indulekha, CL; Sanalkumar, R; Thekkuveettil, A; James, J
    Adult hippocampal neurogenesis is altered in response to different physiological and pathological stimuli. GFAP(+ve)/nestin(+ve) radial glial like Type-1 progenitors are considered to be the resident stem cell population in adult hippocampus. During neurogenesis these Type-1 progenitors matures to GFAP(-ve)/nestin(+ve) Type-2 progenitors and then to Type-3 neuroblasts and finally differentiates into granule cell neurons. In our study, using pilocarpine-induced seizure model, we showed that seizure initiated activation of multiple progenitors in the entire hippocampal area such as DG, CA1 and CA3. Seizure induction resulted in activation of two subtypes of Type-1 progenitors, Type-1a (GFAP(+ve)/nestin(+ve)/BrdU(-ve)) and Type-1b (GFAP(+ve)/nestin(+ve)/BrdU(-ve)). We showed that majority of Type-1b progenitors were undergoing only a transition from a state of dormancy to activated form immediately after seizures rather than proliferating, whereas Type-la showed maximum proliferation by 3 days post-seizure induction. Type-2 (GFAP(-ve)/nestin(+ve)/BrdU(+ve)) progenitors were few compared to Type-1. Type-3 (DCX(+ve)) progenitors showed increased expression of immature neurons only in DG region by 3 days after seizure induction indicating maturation of progenitors happens only in microenvironment of DG even though progenitors are activated in CA1 and CA3 regions of hippocampus. Also parallel increase in growth factors expression after seizure induction suggests that microenvironmental niche has a profound effect on stimulation of adult neural progenitors. (C) 2010 Elsevier Inc. All rights reserved.