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Biomedical subjects

Sanjay Kumar

Publications and source records attributed to Sanjay Kumar.

At least 73 records · Page 4Linked to original sources
PubMed2005

Is routine use of stentless aortic prostheses justified in an elderly (aged > or =75 years) population?

BACKGROUND AND AIM OF THE STUDY: Stentless prostheses in the aortic position produce a superior hemodynamic profile in comparison to that with stented valves. To determine whether routine use of stentless valves in an elderly population is justified, a 10-year retrospective review was performed of a consecutive series of patients aged > or =75 years undergoing stentless aortic valve replacement (AVR). METHODS: Demographic, operative and mortality data were obtained retrospectively. Survivors were interviewed by telephone according to a defined protocol. Univariate and multivariate analysis was used to identify independent predictors of 30-day and overall medium-term mortality. Definitions and analyses were in accordance with joint STS/AATS guidelines. RESULTS: A total of 103 patients (57 males, 46 females; mean age 79.8 years; range: 75-91 years) underwent AVR with a either a Toronto stentless porcine valve (size range: 21-29 mm; n = 74) or an aortic homograft (n = 29). Twenty-eight patients (27%) had either urgent/emergency surgery, 12 (11%) underwent redo surgery, and in 54 cases (52%), the preoperative left ventricular function was significantly impaired (ejection fraction <50%). Forty patients (39%) also underwent concomitant coronary artery bypass grafting. The mean cross-clamp and cardiopulmonary bypass times were 105+/-22 min and 144+/-47 min, respectively. The overall 30-day mortality was 11.6% (n = 12). The 30-day mortality for all elective cases was 5.3%, but for isolated elective AVR was only 2.5%. Using a multivariate model, the only independent predictor of 30-day mortality and medium-term overall mortality was increasing age. The mean follow up period was 3.6 years (range: 0.1-9.3 years), and the Kaplan-Meier actuarial five-year survival was 52%. At follow up, 92% of patients were in NYHA functional classes I and II. CONCLUSION: Stentless AVR in elderly patients is associated with excellent functional and survival outcome in the medium term. Furthermore, in elective cases, age alone should not be a deterrent to the routine use of stentless aortic valves.

Age Factors↗
PubMed2004

Structural basis for peptidoglycan binding by peptidoglycan recognition proteins.

Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition receptors of the innate immune system that bind and, in some cases, hydrolyze bacterial PGNs. We determined the crystal structure, at 2.30-A resolution, of the C-terminal PGN-binding domain of human PGRP-Ialpha in complex with a muramyl tripeptide representing the core of lysine-type PGNs from Gram-positive bacteria. The peptide stem of the ligand is buried at the deep end of a long binding groove, with N-acetylmuramic acid situated in the middle of the groove, whose shallow end can accommodate a linked N-acetylglucosamine. Although most interactions are with the peptide, the glycan moiety also seems to be essential for specific recognition by PGRPs. Conservation of key PGN-contacting residues shows that all PGRPs employ this basic PGN-binding mode. The structure pinpoints variable residues that likely mediate discrimination between lysine- and diaminopimelic acid-type PGNs. We also propose a mechanism for PGN hydrolysis by Zn(2+)-containing PGRPs.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2004

Modulation of repulsive forces between neurofilaments by sidearm phosphorylation.

Recent studies have advanced the notion that the axonal organization of neurofilaments (NFs) is based on mutual steric repulsion between the unstructured "sidearm" domains of adjacent NFs. Here, we present experimental evidence that these repulsive forces are modulated by the degree of sidearm phosphorylation. When NFs are sedimented into a gelatinous pellet, pellet volume falls with increasing ionic strength and enzymatic dephosphorylation; sedimentation of phosphorylated NFs in the presence of divalent cations also dramatically reduces pellet volume. Further, atomic force microscopy imaging of isolated mammalian NFs reveals robust exclusion of colloidal particles from the NF backbone that is reduced at high ionic strength and attenuated when the filaments are enzymatically dephosphorylated. Phosphate-phosphate repulsion on the NF sidearm appears to modulate NF excluded volume in a graded fashion, thereby controlling axonal NF organization through interfilament forces.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Effect of confinement on coil-globule transition.

The equilibrium thermodynamic properties of a linear polymer chain confined to a space between two impenetrable walls (lines) at a distance D under various solvent conditions have been studied using series analysis and exact enumeration technique. We have calculated the end-to-end distance of polymer chain, which shows a nonmonotonic behavior with inter wall separation D. The density distribution profile shows a maxima at a particular value of (D=)D*. Around this D*, our results show that the collapse transition occurs at higher temperature as compared to its bulk value of 2d and 3d. The variation of theta-temperature with D shows a re-entrance behavior. We also calculate the force of compression exerted by the walls (lines) on the polymer.

Journal Article↗
PubMed2004

On the slowing of S phase in response to DNA damage in fission yeast.

Eukaryotic cells slow their progression through S phase upon DNA damage. The mechanism that leads to this slowing is called the intra-S-phase checkpoint. Previous studies demonstrated that in the fission yeast Schizosaccharomyces pombe this checkpoint is mediated by a pathway that includes Rad3 (similar to human ATR and ATM) and Cds1 (similar to human Chk1 and Chk2). Here we present evidence that a major downstream target of this pathway is the cyclin-dependent kinase, Cdc2. We also present evidence suggesting that the intra-S-phase checkpoint makes a relatively minor contribution to the survival of cells with damaged DNA.

CDC2 Protein Kinase↗
PubMed2004

Cofactor-independent phosphoglycerate mutase has an essential role in Caenorhabditis elegans and is conserved in parasitic nematodes.

Phosphoglycerate mutases catalyze the interconversion of 2- and 3-phosphoglycerate in the glycolytic and gluconeogenic pathways. They exist in two unrelated forms that are either cofactor (2,3-diphosphoglycerate)-dependent or cofactor-independent. The two enzymes have no similarity in amino acid sequence, tertiary structure, or catalytic mechanism. Certain organisms including vertebrates have only the cofactor-dependent form, whereas other organisms can possess the independent form or both. Caenorhabditis elegans has been predicted to have only independent phosphoglycerate mutase. In this study, we have cloned and produced recombinant, independent phosphoglycerate mutases from C. elegans and the human-parasitic nematode Brugia malayi. They are 70% identical to each other and related to known bacterial, fungal, and protozoan enzymes. The nematode enzymes possess the catalytic serine, and other key amino acids proposed for catalysis and recombinant enzymes showed typical phosphoglycerate mutase activities in both the glycolytic and gluconeogenic directions. The gene is essential in C. elegans, because the reduction of its activity by RNA interference led to embryonic lethality, larval lethality, and abnormal body morphology. Promoter reporter analysis indicated widespread expression in larval and adult C. elegans with the highest levels apparent in the nerve ring, intestine, and body wall muscles. The enzyme was found in a diverse group of nematodes representing the major clades, indicating that it is conserved throughout this phylum. Our results demonstrate that nematodes, unlike vertebrates, utilize independent phosphoglycerate mutase in glycolytic and gluconeogenic pathways and that the enzyme is probably essential for all nematodes.

Amino Acid Sequence↗
PubMed2004

Vibrationally inelastic collisions in H+ +CO system: comparing quantum calculations with experiments.

State-resolved cross beam experiments [H. Udseth et al., J. Chem. Phys. 60, 3051 (1974); J. Krutein and F. Linder, J. Chem. Phys. 71, 599 (1979); G. Niedner-Schatteburg and J. P. Toennies, Adv. Chem. Phys. LXXXII, 553 (1992)], coupled with proton energy loss spectroscopy for the inelastic scattering of H(+) from CO in the collision range of 10-30 eV show very low vibrational excitation of the target molecule. Stimulated by the experimentally observed low vibrational inelasticity in the system the ground and the first two low-lying excited electronic potential-energy surfaces have been computed using the ab initio multireference configuration interaction method. Quantum dynamics has been performed on the ground potential energy surface in the framework of vibrational close-coupling rotational infinite-order sudden approximation. The various computed dynamical attributes such as differential and integral cross sections, and average vibrational energy transfer are analyzed in detail, and compared successfully with the available experimental results.

Journal Article↗
PubMed2004

Shuttling components of nuclear import machinery involved in nuclear translocation of steroid receptors exit nucleus via exportin-1/CRM-1* independent pathway.

The nucleocytoplasmic transport processes are mediated by soluble transport factors constantly navigating between nuclear and cytoplasmic compartments. Our understanding about nuclear export of general 'nuclear import factors' that deliver the cargo to the nucleus is still fragmentary. Utilizing green fluorescent protein tagged glucocorticoid receptor (GR) and relA as our working model and with judicious use of LMB, we show in living cells that all the soluble components of the nuclear import machinery exit nucleus via exportin1/CRM1 independent pathway(s).

Active Transport, Cell Nucleus↗
PubMed2004

Changing the enzymatic activity of T7 endonuclease by mutations at the beta-bridge site: alteration of substrate specificity profile and metal ion requirements by mutation distant from the catalytic domain.

Phage-encoded resolvase T7 endonuclease I is a structure-specific endonuclease. The enzyme acts on a broad spectrum of substrates with a variety of DNA structures. The enzyme is a dimer with two separated catalytic domains connected by an elongated beta-sheet bridge. The activities of enzymes with mutations in the beta-bridge segment were studied. Mutations that did not affect catalytic domain folding and function but did alter the relative positions of these domains retained catalytic activity but with altered specificity and metal ion dependence. Our results suggest that the enzyme recognizes its substrates by DNA conformation exclusion and offer a simple explanation for the broad substrate specificity of phage resolvase.

Bacteriophage T7↗