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Biomedical subjects

S Rajagopalan

Publications and source records attributed to S Rajagopalan.

At least 19 recordsLinked to original sources
PubMed2006

Calcium scoring and contrast-enhanced CT angiography.

Computed tomography (CT) technology has emerged as the most promising imaging modality for the noninvasive evaluation of the coronary circulation. Of the CT-based approaches, multidetector-row computed tomography (MDCT) and to a lesser extent electron beam computed tomography offer the potential of providing not only data on the spatial extent and burden of coronary calcium content, but also angiographic data, and plaque composition characteristics with the potential for prediction of susceptibility to future cardiovascular events. A number of studies have now confirmed that CT-based assessment of the presence and amount of coronary artery calcium provides incremental prognostic information over traditional risk factors in patients with coronary artery disease and can be employed to refine risk stratification in both asymptomatic and symptomatic subjects. With the advent of several recent advances in CT imaging, it is now possible to provide high resolution (sub-millimeter, isotropic voxels) images of the coronary arteries obtained rapidly with iodinated contrast injected peripherally. MDCT is currently the preferred modality for noninvasive contrast angiography of the coronary arteries by most groups, with a new generation of 64-slice scanners promising to further improve the results of this technique. MDCT-derived angiographic information in conjunction with coronary calcium scoring and plaque characterization has the potential of replacing invasive angiography, as it potentially could provide better global assessment of risk.

Calcinosis↗
PubMed2006

Molecular determinants of vascular calcification: a bench to bedside view.

Vascular calcification (VC) is an orchestrated event, evoking the programmed process of the osteogenesis and triggered by inflammatory cytokines active at vascular level. VC is a dynamic process in which the vessel wall intima, media and also cardiac valves may be involved. Intimal calcification is an endochondral ossification process in which type II collagen is mineralized by calcium deposition. In contrast, an intra-membranous ossification process leads to medial calcification, while a dystrophic calcification process is responsible for valvular calcification. Mechanisms involved in VC may be summarized as: 1. Activation of osteogenesis in the vessel wall, 2. Loss of inhibitory factors, 3. Enhanced bone turnover, and 4. Abnormalities in mineral metabolism. The signaling axis constituted by osteoprotegerin (OPG), receptor activator nuclear factor kB (RANK) and its ligand (RANKL), along with the monocyte colony stimulating factor (M-CSF) and the transcription factor core Binding protein (Cbfa-1), play a pivotal role in the control of VC. In contrast, fetuin-A, matrix G1a protein (MGP) and osteopontin (OPN) control the inhibition of VC. In addition, abnormal mineral metabolism with enhanced phosphates availability favors calcium deposition. The inflammatory cytokines interleukin (IL-1) and tumor necrosis factor (TNF)-alpha enhance OPG and RANKL function in the vessel wall leading to VC. VC is a controlled process, depending on the balance between osteoblastic and osteoclastic influences and further modulated by the influence of risk factors like diabetes, smoking, age, hypertension and dyslipidemia. Recent advances in diagnostic tools such as with multi-detector computed tomography (MDCT) and electron beam computed tomography (EBCT), may help diagnosis and delineation of VC in the clinical setting and aid in understanding its prognostic value.

Animals↗
PubMed2001

Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults.

Vascular endothelial dysfunction (VED) is associated with obesity; however, its etiology remains controversial. By determining the predictors of fasting and postprandial endothelial function in overweight adults without other cardiovascular risk factors, we were able to investigate novel mechanisms directly linking obesity to VED. Thirty-two healthy adults (body mass index [BMI] > or =27 kg/m(2)) underwent determination of fasting low-density lipoprotein (LDL) particle size, high sensitivity C-reactive protein levels, anthropometric measurements, and endothelial function by flow-mediated dilation (FMD) of the brachial artery. Postprandial lipemia and FMD were measured 4 hours after ingestion of a high-fat meal. Blood pressures and fasting levels of lipoproteins, glucose, insulin, and fatty acids were within normal limits in all subjects. An abdominal fat pattern, as determined by an increased waist/hip ratio (WHR), was the sole significant predictor of FMD (r = -0.58, p = 0.001), despite no significant correlation between whole body obesity (BMI) and FMD. At comparable levels of BMI, obese subjects with a WHR > or =0.85 had a significantly blunted FMD compared with those with a WHR <0.85 (3.93 +/- 2.85% vs 8.34 +/- 5.47%, p = 0.016). Traditional coronary risk factors, C-reactive protein, postprandial lipemia, and LDL particle size did not predict FMD. We found no appreciable alteration in the postprandial state from fasting FMD (6.31 +/- 4.62% vs 6.25 +/- 5.47%, p = 0.95). The same results were found when women were analyzed alone. Increased abdominal adiposity determined by a simple WHR is a strong independent predictor of VED even in healthy overweight adults; this is a finding unexplained by alterations in conventional risk factors, systemic inflammation, or the atherogenic lipoprotein pattern.

Adult↗
PubMed2001

Granular drag on a discrete object: shape effects on jamming.

We study the drag force on discrete objects with circular cross section moving slowly through a spherical granular medium. Variations in the geometry of the dragged object change the drag force only by a small fraction relative to shape effects in fluid drag. The drag force depends quadratically on the object's diameter as expected. We do observe, however, a deviation above the expected linear depth dependence, and the magnitude of the deviation is apparently controlled by geometrical factors.

Journal Article↗
PubMed2001

The hunt for a cure for Parkinson's disease.

Several exciting new scientific advances have been made in the past decade toward both understanding the causes of and finding a cure for Parkinson's disease. Heartened by an acceleration in research findings in the past several years, the government has recently called for an infusion of funds from both the National Institutes of Health and private foundations into this burgeoning area of biomedical research. Most currently available conventional treatments for the disease only temporarily delay symptom presentation while doing nothing to halt disease progression. However, the rapidly accelerating pace of research in this field has left researchers hopeful that Parkinson's will be the first major age-related neurodegenerative disease for which we have a viable cure. In this article, advances in various areas of Parkinson's disease research are reviewed.

Animals↗
PubMed2001

Alpha synuclein aggregation: is it the toxic gain of function responsible for neurodegeneration in Parkinson's disease?

Protein aggregation appears to be the common denominator in a series of distinct neurodegenerative diseases yet its role in the associated neuronal pathology in these various conditions remains elusive. In Parkinson's disease, localization of alpha synuclein aggregates within intracellular Lewy body occlusions represent a major hallmark of this disorder and suggest that such aggregation may play a causative role in the resulting dopaminergic cell loss. In this Viewpoint article, recent data is reviewed related to how alpha synuclein aggregation may occur, what cellular events might be responsible, and how this may interfere with normal cellular function(s). It appears likely that while aggregation of alpha synuclein may interfere with its normal function in the cell, this is not the primary cause of the related neurodegeneration.

Animals↗
PubMed2001

Tuberculosis and aging: a global health problem.

Despite the World Health Organization's declaration that the spread of tuberculosis is a global emergency and despite the implementation of strong tuberculosis-control initiatives, this highly infectious disease continues to affect all vulnerable populations, including the elderly population (age > or =65 years). Tuberculosis in aging adults remains a clinical and epidemiological challenge. Atypical clinical manifestations of tuberculosis in older persons can result in delay in diagnosis and initiation of treatment; thus, unfortunately, higher rates of morbidity and mortality from this treatable infection can occur. Underlying illnesses, age-related diminution in immune function, the increased frequency of adverse drug reactions, and institutionalization can complicate the overall clinical approach to tuberculosis in elderly patients; maintenance of a high index of suspicion for tuberculosis in this vulnerable population is, thus, undoubtedly justifiable.

Aged↗
PubMed2001

Cutting edge: induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells.

Activated NK cells lyse tumor cells and virus-infected cells and produce IFN-gamma upon contact with sensitive target cells. The regulation of these effector responses in resting NK cells is not well understood. We now describe a receptor, KIR2DL4, that has the unique property of inducing IFN-gamma production, but not cytotoxicity, by resting NK cells in the absence of cytokines. In contrast, the NK cell-activation receptors CD16 and 2B4 induced cytotoxicity but not IFN-gamma production. The induction by KIR2DL4 of IFN-gamma production by resting NK cells was blocked by an inhibitor of the p38 mitogen-activated protein kinase signaling pathway, in contrast to the IL-2-induced IFN-gamma secretion that was sensitive to inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase pathway. These results reveal a functional dichotomy (cytokine production vs cytotoxicity) in the response of resting NK cells, as dictated by the signals of individual receptors.

Animals↗
PubMed2001

Adenovirus-mediated gene transfer of VEGF(121) improves lower-extremity endothelial function and flow reserve.

BACKGROUND: Vascular endothelial growth factor (VEGF) currently is being evaluated in clinical angiogenesis trials involving patients with peripheral arterial disease. We hypothesized that delivery of VEGF to the skeletal muscle of the lower extremity using an adenoviral vector (Ad(GV)VEGF(121.10)) would improve peripheral endothelial function. Accordingly, we investigated lower-extremity endothelial function in patients enrolled in a Phase I adenovirus-mediated gene delivery trial of VEGF(121.10). METHODS AND RESULTS: Blood flow to the index extremity was measured by thermodilution at baseline and 30 days after administration of Ad(GV)VEGF(121.10), in response to the infusion of endothelium-dependent and -independent agonists (acetylcholine and nitroglycerin, respectively) into the ipsilateral femoral artery. There was no difference in basal flow before or after treatment with Ad(GV)VEGF(121.10). In response to acetylcholine (150 microg/min and 300 microg/min), there was a 0.9-fold (0.33+/-0.03 to 0.32+/-0.03 L/min) and 1.2-fold (0.33+/-0.03 to 0.490+/-0.02 L/min) change in flow before Ad(GV)VEGF(121.10) treatment. After Ad(GV)VEGF(121.10) treatment, flow increased 2.4-fold (0.310+/-0.04 to 0.730+/-0.10 L/min) and 2.3-fold (0.31+/-0.04 to 0.7+/-0.08 L/min), respectively (P<0.05 before Ad(GV)VEGF(121.10) treatment versus after Ad(GV)VEGF(121.10) for both doses). Infusion of nitroglycerin resulted in a 1.8-fold increase in flow before Ad(GV)VEGF(121.10) (0.33+/-0.03 to 0.58+/-0.06 L/min) compared with a 2.4-fold increase (0.31+/-0.04 to 0.73+/-0.09 L/min) after Ad(GV)VEGF(121.10) (P=NS before Ad(GV)VEGF(121.10) versus after Ad(GV)VEGF(121.10)). Lower-extremity flow reserve increased in all patients in response to at least 1 dose of acetylcholine. Peak walking times increased concomitant with improvement in endothelial function. CONCLUSIONS: Adenoviral gene transfer of VEGF(121.10) appears to modulate endothelial function and lower-extremity flow reserve in patients with peripheral arterial disease.

Acetylcholine↗
PubMed2001

Analysis of chaotic motion and its shape dependence in a generalized piecewise linear map.

We analyze the chaotic motion and its shape dependence in a piecewise linear map using Fujisaka's characteristic function method. The map is a generalization of the one introduced by Artuso. Exact expressions for diffusion coefficients are obtained with previously obtained results used as special cases. A fluctuation spectrum relating to the probability density function is obtained in a parametric form. We also give limiting forms of the above quantities. The dependence of the diffusion coefficient and probability density function on the shape of the map is examined.

Journal Article↗
PubMed2001

Aldosterone antagonists in the treatment of hypertension and target organ damage.

Mineralocorticoids mediate a number of effects besides regulation of fluid and electrolyte balance. Recent evidence has revealed several nontraditional roles, sites of synthesis, and action for these steroids. Aldosterone, the principal mineralocorticoid in humans, appears to be synthesized in physiologically relevant amounts in both the heart and the vasculature, and plays an important role in vessel wall and myocardial remodeling. The genomic effects of aldosterone are mediated through activation of the classic mineralocorticoid receptor, whereas rapid nongenomic effects seem to involve a distinct receptor and result in activation of multiple downstream signaling pathways. Recently, several lines of evidence seem to suggest an important interaction between the nitric oxide and the aldosterone pathway in the adrenal gland and vasculature. The evolution of selective aldosterone receptor antagonists will help us understand the role that mineralocorticoids play in the pathogenesis of hypertension, heart failure, and atherosclerosis.

Coronary Vessels↗
PubMed2001

Antimicrobial therapy in the elderly.

This article focuses on the special characteristics of infection in the elderly and provides an update of the principles of antibiotic selection, use of specific antibiotics, and empiric use of antimicrobials in the treatment of infectious diseases in this particularly vulnerable group. Antituberculous, antifungal, and antiviral agents are mentioned briefly; detailed information regarding these classes of agents in reference to aging can be found in standard reviews of antimicrobial therapy in the elderly.

Age Factors↗