Biomedical subjects

Sanjeev Kumar

Publications and source records attributed to Sanjeev Kumar.

At least 19 recordsLinked to original sources

PubMed2025

Multiscale dispersion entropy of resting-state EEG in older adults with Alzheimer's disease, mild cognitive impairment, and remitted major depressive disorder.

BackgroundMultiscale dispersion entropy (MDEnt) is a nonlinear EEG measure that quantifies brain complexity across time scales, reflecting both local and global brain dynamics. Previous research indicates lower complexity at short time scales in Alzheimer's disease (AD) compared to mild cognitive impairment (MCI) and healthy controls (HCs), with MCI also showing lower values than HCs. Major depressive disorder (MDD) has also been preliminarily linked to reduced complexity during acute episodes.ObjectiveTo assess whether MDEnt at short time scales can distinguish AD from MCI and HCs, and to examine complexity differences across additional groups, remitted MDD (rMDD) and rMDD + MCI, while exploring associations with cognitive performance.MethodsThe study included 316 older adults: 44 HCs, 46 with rMDD, 114 with MCI, 71 with rMDD + MCI, and 41 with AD. Resting-state, eyes-closed EEGs were analyzed using MDEnt at 24 ms (short) and 60 ms (long) time scales. Cognitive function was measured with the Montreal Cognitive Assessment and a composite cognitive score.ResultsShort time scale complexity was lowest in AD, followed by MCI, and highest in HCs; rMDD presence had no impact. Only AD showed reduced complexity at long time scales. Complexity at both time scales was significantly correlated with cognitive performance.ConclusionsThis study highlights the value of MDEnt to assess complexity at short time scale and differentiate individuals with AD, MCI, or HCs. Reduced complexity in these individuals may underlie their cognitive impairment. In contrast, our study suggests that any MDD impact on complexity is likely related to active depressive symptoms.

Humans↗

PubMed2006

Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity.

The discovery of novel acyclic amide cannabinoid-1 receptor inverse agonists is described. They are potent, selective, orally bioavailable, and active in rodent models of food intake and body weight reduction. A major focus of the optimization process was to increase in vivo efficacy and to reduce the potential for formation of reactive metabolites. These efforts led to the identification of compound 48 for development as a clinical candidate for the treatment of obesity.

Animals↗

PubMed2006

Infectivity rate and transmission potential of Hyalomma anatolicum anatolicum ticks for Babesia equi infection.

The infectivity rate of Babesia equi in the salivary glands of Hyalomma anatolicum anatolicum was assessed. The hungry nymphs were fed on a donkey experimentally infected with B. equi. The engorged dropped-off nymphs were collected at different levels of parasitaemia and kept in BOD incubator. After ecdysis, the hungry adults were prefed on rabbits for different time intervals, thereafter the salivary glands were dissected out and acini were examined after methyl green pyronin (MGP) staining. A total of 134 male and 139 female ticks were dissected out. Average infected acini per tick were found to be significantly higher (p<0.05) in male as compared to the female ticks. Further, maximum infected acini in both male and female ticks were found at 24h of prefeeding on rabbits and overall infected acini per tick increased with rise in parasitaemia. The release of infected ticks on susceptible donkeys resulted in development of clinical babesiosis.

Animals↗

PubMed2006

Domain formation and orbital ordering transition in a doped Jahn-Teller insulator.

The ground state of a double-exchange model for orbitally degenerate e(g) electrons with Jahn-Teller lattice coupling and weak disorder is found to be spatially inhomogeneous near half filling. Using a real-space Monte Carlo method we show that doping the half-filled orbitally ordered insulator leads to the appearance of hole-rich disordered regions in an orbitally ordered environment. The doping driven orbital order to disorder transition is accompanied by the emergence of metallic behavior. We present results on transport and optical properties along with spatial patterns for lattice distortions and charge densities, providing a basis for an overall understanding of the low-doping phase diagram of La1 - xCaxMnO3.

Journal Article↗

PubMed2006

Ischemic acidosis causes apoptosis in coronary endothelial cells through activation of caspase-12.

OBJECTIVE: Myocardial ischemia has been shown to induce apoptosis of endothelial cells (EC). However, the mechanism of this endothelial injury is still poorly understood. To analyse the signaling pathway of ischemia-induced EC apoptosis was the aim of the present study. METHODS: The primary culture of rat coronary EC was exposed to simulated ischemia (glucose-free anoxia at pH(o) 6.4). Apoptosis was defined by staining of nuclei with Hoechst-33342 and TUNEL. Cytosolic Ca2+ and pH were measured with Fura-2 and BCECF, respectively. RESULTS: Apoptosis (29.2+/-1.7% of cells) induced by exposure to simulated ischemia for 2 h was accompanied by cytosolic Ca2+ overload (1090+/-52 nmol/l) and acidosis (pHi = 6.52+/-0.13). Simulated ischemia had no significant effect on caspase-8 cleavage, but induced cleavage of caspase-3 and caspase-12 and led to a slight release of cytochrome C. Prevention of cytosolic acidosis (anoxia at pH(o) 7.4) had no effect on cytochrome C release, but significantly reduced apoptosis, attenuated cytosolic Ca2+ overload, and prevented cleavage of caspase-12. A similar effect was achieved by inhibition of Ca2+ release channels in the endoplasmic reticulum with ryanodine and xestospongin C. Knock-down of caspase-12 with small interfering RNA suppressed caspase-3 activation and reduced apoptotic cell number by about 70%. CONCLUSION: Acidosis, rather than anoxia, is an important trigger of apoptosis in EC under simulated ischemia. The main pathway of the simulated ischemia-induced apoptosis consists of the Ca2+ leak from the ER followed by activation of caspase-12 and caspase-3.

Acidosis↗

PubMed2006

A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell mucosal response characterized by high levels of alpha4beta7 integrin and an effector memory phenotype.

In this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime-oral Listeria boost amplifies the SIV-Gag-specific CD8 mucosal response. SIV-specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test vaccine groups, but not the control group. SIV-Gag-specific CD8 T cells in the PB expressed alpha4beta7 integrin, the gut-homing receptor; a minor subset co-express alphaEbeta7 integrin. SIV-Gag-specific CD8 T cells were also detected in the gut tissue, intraepithelial (IEL) and lamina propria lymphocytes (LPL) of the duodenum and ileum. These cells were characterized by high levels of beta7 integrin expression and a predominance of the effector memory phenotype. Neither Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut. Thus, the DNA prime-oral Listeria boost strategy induced a mucosal SIV-Gag-specific CD8 T cell response characterized by expression of the alpha4beta7 integrin gut-homing receptor.

AIDS Vaccines↗

PubMed2006

Effect of electrolytes on the cloud point of chlorpromazine hydrochloride solutions.

Cloud point (CP) phenomenon occurring in amphiphilic drug chlorpromazine hydrochloride (CPZ) solutions with and without salts is reported herein. The CP of a 50mM CPZ solution (prepared in 10mM sodium phosphate, SP, buffer) was found to decrease with increasing pH, both in the absence as well as presence (50mM) of added salts (NaCl, NaBr, LiBr, KBr, tetra-n-butylammonium bromide). Whereas, at a fixed concentration of NaCl, the CP increased with increasing CPZ concentration, addition of increasing amounts of salts (NaF, NaCl, NaBr, LiCl, KCl) to 50 mM CPZ solution (at pH 6.7) caused continuous increase in CP. On the basis of these studies the binding-effect orders of counterions and co-ions have been deduced, respectively, as: Br(-) > Cl(-) > F(-) and Li+ >Na+ >K+. The similar trend of increasing CP with addition of increasing amounts of quaternary bromides (tetramethylammonium bromide, TMeAB; tetraethylammonium bromide, TEtAB; tetra-n-propylammonium bromide, TPrAB; tetra-n-butylammonium bromide, TBuAB; tetra-n-pentylammonium bromide, TPeAB) to 50 mM CPZ solutions (at pH 6.7) was found to be dependent upon the alkyl chain length of the particular salt. The overall behaviour has been discussed in terms of electrostatic interactions, micellar growth, and mixed micelle formation.

Chlorpromazine↗

PubMed2006

Clouding phenomenon and SANS studies on tetra-n-butylammonium dodecylsulfate micellar solutions in the absence and presence of salts.

Clouding phenomenon in aqueous micellar solutions of an anionic surfactant tetra-n-butylammonium dodecylsulfate (TBADS) has been observed as a function of surfactant concentration. Small-angle neutron scattering (SANS) experiments in these systems show clustering of micelles as the temperature approaches the cloud point (CP). The individual micelles and the clusters of micelles coexist at CP. The clustering of micelles depends on the surfactant concentration and temperature. It is proposed that clustering is due to depletion of H-bonded water present around the butyl chains at the micellar surface. This is associated with entropy gain which is considered to be the major thermodynamic factor related to micellar aggregation. The structures (clusters) that emerge depend on the relative lengths of the alkyl chains of the counterion and can be tuned by the temperature.

Micelles↗

PubMed2006

Influence of urea additives on micellar morphology/protein conformation.

The present study highlights the fact that the effect of additives (urea, monomethylurea, thiourea) on the supramolecular assemblies and proteins is strikingly similar. To investigate the effect, a viscometeric study on sphere-to-rod transition (s-->r) was undertaken in a system (3.5% tetradecyltrimethylammonium bromide+0.05 M NaBr + 1-pentanol [P.M. Lindemuth, G.L. Bertand, J. Phys. Chem. 97 (1993) 7769]) in the presence and absence of the said additives. [1-pentanol] needed for s-->r (i.e. [1-pentanol]s-->r) was determined from the relative viscosity versus [1-pentanol] profiles. It was observed that the additives preponed as well as postponed s-->r depending upon their nature and concentrations. These effects are explained in terms of increased polarity of the medium and the adsorption ability of urea/monomethylurea on the charged surfactant monomers of the micelle. In case of thiourea, postponement of s-->r was observed throughout which is attributed to its structure. To derive an analogy between micelles and proteins the additive-induced conformational changes of the protein, bovine serum albumin (BSA) was taken to monitor secondary structural changes and tryptophanyl fluorescence. A marked increase in secondary structure (far-UVCD) and increased tryptophanyl fluorescence with a marked blue shift in lambdamax was observed in presence of low concentrations of urea or alkylurea. This indicates that a more compact environment is created in presence of these additives, if added judiciously. Addition of thiourea to BSA caused a marked quenching without any significant change in lambdamax. The large decrease in tryptophanyl emission in presence of low thiourea concentrations seems to be specific and related to thiourea structure as no corresponding changes were observed in urea/alkylurea. All these effects pertaining to protein behavior fall in line with that of morphological observations on the present as well as surfactant systems studied earlier [S. Kumar, N. Parveen, Kabir-ud-Din, J. Phys. Chem. B 108 (2004) 9588].

Animals↗

PubMed2006

The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1.

The Vpr protein of HIV-1 functions as a vital accessory gene by regulating various cellular functions, including cell differentiation, apoptosis, nuclear factor of kappaB (NF-kappaB) suppression and cell-cycle arrest of the host cell. Several reports have indicated that Vpr complexes with the glucocorticoid receptor (GR), but it remains unclear whether the GR pathway is required for Vpr to function. Here, we report that Vpr uses the GR pathway as a recruitment vehicle for the NF-kappaB co-activating protein, poly(ADP-ribose) polymerase-1 (PARP-1). The GR interaction with Vpr is both necessary and sufficient to facilitate this interaction by potentiating the formation of a Vpr-GR-PARP-1 complex. The recruitment of PARP-1 by the Vpr-GR complex prevents its nuclear localization, which is necessary for Vpr to suppress NF-kappaB. The association of GR with PARP-1 is not observed with steroid (glucocorticoid) treatment, indicating that the GR association with PARP-1 is a gain of function that is solely attributed to HIV-1 Vpr. These data provide important insights into Vpr biology and its role in HIV pathogenesis.

Active Transport, Cell Nucleus↗

PubMed2006

Insulator-metal phase diagram of the optimally doped manganites from the disordered Holstein-double exchange model.

We study the Holstein-double exchange model in three dimensions in the presence of substitutional disorder. Using a new Monte Carlo technique we establish the phase diagram of the clean model and then focus on the effect of varying electron-phonon coupling and disorder at fixed electron density. We demonstrate how extrinsic disorder controls the interplay of lattice polaron effects and spin fluctuations and leads to widely varying regimes in transport. Our results on the disorder dependence of the ferromagnetic T(C) and metal-insulator transitions bear direct comparison to data on the "optimally doped," x = 0.3-0.4, manganites. We highlight disorder induced polaron formation as a key effect in these materials, organize a wide variety of data into a simple "global phase diagram," and make several experimental predictions.

Journal Article↗

PubMed2006

Comparison of the relation between renal impairment, angiographic coronary artery disease, and long-term mortality in women versus men.

Mild to moderate renal impairment has recently been associated with increased cardiovascular mortality. However, gender differences in the association of mild to moderate renal impairment with the presence of angiographic coronary artery disease and long-term mortality remain unknown. We examined a prospective cohort of consecutive patients who underwent coronary angiography from the ACRE study in the Royal Hospitals Trust (London, United Kingdom) with referral from 5 contiguous health authorities. Among 1,609 patients (465 women) who had angiographic and serum creatinine measurements at baseline, renal impairment at modification of diet in renal disease glomerular filtration rates of 45 to 59, 30 to 44, and <30 ml/min/1.73 m(2) was more common in women than in men and was significantly associated with the presence of angiographic coronary artery disease in women but not in men. At each level of glomerular filtration rate, multivariate adjusted hazard ratios of 7-year all-cause mortality for women compared with men were higher: 2.64 (95% confidence intervals [CI] 1.21 to 5.73) versus 1.34 (95% CI 0.995 to 1.79); 2.62 (95% CI 1.12 to 16.12) versus 2.35 (95% CI 1.60 to 3.43); and 10.42 (95% CI 3.97 to 27.39) versus 4.77 (95% CI 2.95 to 7.70), respectively. Similar patterns were observed in cardiovascular and coronary deaths. In conclusion, mild to moderate renal impairment may be a marker for unmeasured proatherogenic factors for women only, and women may bear a greater mortality burden that is attributable to renal impairment compared with men. Gender may influence the prognostic effect of renal impairment in coronary disease.

Aged↗

PubMed2006

Development of a candidate DNA/MVA HIV-1 subtype C vaccine for India.

Development of a vaccine against human immunodeficiency virus type-1 (HIV-1) is the mainstay for controlling the AIDS pandemic. An ideal HIV vaccine should induce neutralizing antibodies, CD4+ helper T cells, and CD8+ cytotoxic T cells. While the induction of broadly neutralizing antibodies remains a highly challenging goal, there are a number of technologies capable of inducing potent cell-mediated responses in animal models, which are now starting to be tested in humans. Naked DNA immunization is one of them. The present study focuses on the stimulation cell-mediated and humoral immune responses by recombinant DNA-MVA vaccines, the areas where this technology might assist either alone or as a part of more complex vaccine formulations in the HIV vaccine development. Candidate recombinant DNA-MVA vaccine formulations expressing the human immunodeficiency virus-1 env and gagprotease genes from HIV-1 Indian subtype C were constructed and characterized. A high level of expression of the respective recombinant MVA (rMVA) constructs was demonstrated in BHK-21 cells followed by the robust humoral as well as cell mediated immune (CMI) responses in terms of magnitude and breadth. The response to a single inoculation of the rDNA vaccine was boosted efficiently by rMVA in BALB/c mice. This is the first reported candidate HIV-1 DNA/MVA vaccine employing the Indian subtype C sequences and constitutes a part of a vaccine scheduled to enter a preclinical non-human primate evaluation in India.

AIDS Vaccines↗

PubMed2006

Importance of endothelial nitric oxide synthase for the hypothermic protection of lungs against ischemia-reperfusion injury.

OBJECTIVES: The hypothesis that the protective effects of mild hypothermia against the pulmonary ischemia-reperfusion injury are mediated by endothelial nitric oxide synthase was tested. METHODS: Endothelial nitric oxide synthase knock-out and wild-type mice were sham operated or underwent a 1-hour occlusion of the left pulmonary hilum, followed by 5 hours of reperfusion. Temperature in the left pleural cavity during ischemia was maintained at either 36 degrees C (normothermia) or 32 degrees C (hypothermia). Inflammatory response (myeloperoxidase activity), endothelial barrier function (extravasation of Evans blue-labeled albumin), and endothelial nitric oxide synthase expression and phosphorylation were determined at the end of reperfusion. RESULTS: After normothermic ischemia both strains had a similar mortality (wild-type, 22.9%; knock-out, 15.4%), which was completely abolished by hypothermia. Endothelial barrier function was disturbed after normothermic ischemia in both wild-type and knock-out mice. Mild hypothermia significantly reduced pulmonary Evans blue extravasation in wild-type mice, but not in knock-out mice. Myeloperoxidase activity increased after normothermic ischemia to the same degree in both strains. This response was significantly attenuated by hypothermia in wild-type mice, but not in knock-out mice. In wild-type mice, endothelial nitric oxide synthase expression and phosphorylation were higher after hypothermic ischemia than after normothermic ischemia. No effect of ischemia on expression of inducible nitric oxide synthase was found in wild-type or knock-out mice. CONCLUSION: Hypothermic protection against pulmonary ischemia-reperfusion injury is dependent on endothelial nitric oxide synthase and is associated with increased expression and phosphorylation of endothelial nitric oxide synthase.

Animals↗

PubMed2006

Complication avoidance: thoracolumbar and lumbar burst fractures.

Most thoracolumbar and lumbar burst fractures can be treated conservatively. Unstable fractures or fractures resulting in neurologic deficits usually require surgical treatment. Choosing an appropriate surgical approach requires a thorough understanding of the various techniques for decompression, fusion, and stabilization. Surgical options include an anterior approach, a posterior approach, or a combined anteroposterior approach. Each surgical option has unique advantages and disadvantages. Generally, the anterior approaches are best used at the thoracolumbar junction, posterior approaches are ideal for low lumbar injuries and lumbar injuries that result in complete spinal cord injuries,and anteroposterior surgeries typically are reserved for highly unstable fracture subluxations. Case illustrations show the various treatment options.

Decompression, Surgical↗

PubMed2006

Immunogenicity testing of a novel engineered HIV-1 envelope gp140 DNA vaccine construct.

DNA vaccines expressing the envelope (env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating strong immune responses. In this study, we described the development of a recombinant plasmid DNA (pEK2P-B) expressing an engineered codon-optimized envelope gp140 gene of primary (nonrecombinant) HIV-1 subtype B isolate 6101. Codon usage and RNA optimization of HIV-1 structural genes has been shown to increase protein expression in vitro as well as in the context of DNA vaccines in vivo. To further increase the expression, a synthetic IgE leader with kozak sequences were fused into the env gene. The cytoplasmic tail of the gene was also truncated to prevent recycling. The expression of env by the recombinant pEK2P-B was evaluated using T7 coupled transcription/translation. The construct demonstrated high expression of the HIV-1 env gene in eukaryotic cells as demonstrated in transfected 293-T and RD cells. Immunogenicity of pEK2P-B was evaluated in mice using IFN-gamma ELISpot assay, and the construct was found to be highly immunogenic and crossreactive with HIV-1 clade C env peptides. Three immunodominant peptides were also mapped out. Furthermore, by performing a CFSE flow cytometry-based proliferation assay, 2.4 and 1.5% proliferation was observed in CD4+, CD8+, and CCR+ memory T cells, respectively. Therefore, this engineered synthetic optimized env DNA vaccine may be useful in DNA vaccine and other studies of HIV-1 immunogenicity.

AIDS Vaccines↗

PubMed2006

Performance analysis of motion-compensated de-interlacing systems.

A lot of research has been conducted on motion-compensated (MC) de-interlacing, but there are very few publications that discuss the performances of de-interlacing quantatively. The various methods are compared through their performance on known video sequences. Linear system analysis of interlaced video and de-interlacer are proposed in. It is well established that the performance of the MC methods outperform the fixed or motion-adaptive methods when the motion vectors used are reliable and true to the scene content. Being an open-loop process the performance of the MC de-interlacers degrade drastically when there are motion vector errors. In this paper, a linear system analysis of MC video upconversion systems is presented and the effects of motion vector accuracy on system performance are analyzed. We investigate the various factors that contribute to the motion vector inaccuracy, such as incorrect motion modelling, acceleration between the frames, and insufficient interpolation kernel.

Algorithms↗

PubMed2006

Initiation of antiretroviral therapy during chronic SIV infection leads to rapid reduction in viral loads and the level of T-cell immune response.

In the present era of increasing resistance of human immunodeficiency virus (HIV) to antiviral drugs, exploration of adjunct therapies directed at immune responses in combination with antiretroviral drugs may be of value for the treatment of acquired immunodeficiency syndrome. In this study, we designed a model for immune therapy using SIVmac251 infection in rhesus macaques. We explored the outcomes of primary infection on viral loads and the resulting T-cell immune responses in primates. The SIV-infected rhesus macaque model exhibited features similar to those observed in HIV-1 infection of humans. Major histocompatibility complex (MHC) segregation with viral loads were found to associate with viral containment and hence the duration of the disease-free latency period. Thus a better understanding of the relative roles of MHC class I allele in control of viral replication may provide important information for prophylactic or therapeutic vaccine designs. Mamu-A01 is significantly associated with higher immune response and control of viral replication. This allele is frequent in rhesus macaques of Indian origin (22%). Interestingly, Mamu-B01 (26% animals) was associated with lower immune responses and higher viral loads. Another allele, A08 was also predominantly present in 37% of the animals in this study. We observed higher viral replication in individual SIV-infected rhesus monkeys that did not demonstrate strong cellular immune responses. The results are important for understanding SIV disease progression in different MHC Mamu alleles and also for improving the interpretation and quality of pre-clinical studies in rhesus monkeys.

Alleles↗