Rajesh Kumar

Bio: Rajesh Kumar is an academic researcher from Himachal Pradesh University. The author has contributed to research in topics: Medicine & Materials science. The author has an hindex of 149, co-authored 4439 publications receiving 140830 citations. Previous affiliations of Rajesh Kumar include Guru Nanak Dev University & Intuitive Surgical.

High Diversity of Group A Streptococcal emm Types in an Indian Community: The Need to Tailor Multivalent Vaccines

Abstract: Background. Concern about the emergence of antibiotic-resistant strains and about morbidity and/ormortality related to rheumatic fever and rheumatic heart disease has been a continuous impetus for the development of a safe, effective vaccine against group A Streptococcus (GAS). To date, 1120 GAS M types are known, as identified by serological typing. In general, serum immunoglobulin G directed to the hypervariable NH2 terminal portion of M protein leads to complement fixation and opsonophagocytosis of the homologous streptococcal serotype by polymorphonuclear leukocytes, and the protection is type specific. The sequence variation at the N terminus ultimately affects the binding of opsonic antibodies. Because of hypervariability in these opsonic sequences from different M types, it was relevant to use epitopes derived from these multiple sequences in a "multivalent vaccine" design for evaluation of protection against these M types of GAS. Thus, any attempts to design vaccines for a given community will require information on N terminal-sequence typing and variation. Methods. In the present study, we performed molecular characterization of isolates recovered from patients in northern India-to our knowledge, for the first time-in an attempt to study the circulating M types and their N terminal sequence variability. Results. We report tremendous diversity in GAS strains recovered from symptomatic patients, with implications on the design of appropriate vaccines. Fifty-nine isolates represented 33 different sequence types. Very few novel types and no predominant clones were found. Conclusions. The high diversity of emm types encountered in a single year suggests that any M protein-based multivalent vaccine would have to be specifically tailored for this region.

Design, Development and Optimization of Nimesulide-Loaded Liposomal Systems for Topical Application

Abstract: Nimesulide, a non-steroidal anti-inflammatory drug, was incorporated into multilamellar liposomes to improve its performance on topical administration. The drug was loaded onto liposomes employing thin film hydration technique. Various process and formulation variables were investigated to obtain the liposomal products of desired quality. Liposomes were monitored for percent drug entrapment, after separating the unentrapped drug by mini column centrifugation, for vesicular properties (such as size distribution profile, morphological attributes and agglomeration tendency), drug diffused through synthetic semipermeable membrane, and drug leakage. Systematic optimization studies were carried out using 32 factorial design to select the optimized liposomal composition with reference to percent drug entrapment, drug diffusion and leakage. The optimized batch of liposomes was subjected to drug permeation and drug retention studies employing rat skin and human cadaver skin. In comparison to methanolic solution of pure nimesulide, liposomal formulations were found to retain higher amounts of nimesulide in the skin. Anti-inflammatory studies, using carragenan-induced rat paw edema model, indicated significantly better performance of liposomally entrapped nimesulide in comparison to the marketed gel formulation and the Carbopol gel containing nimesulide.

Selective deletion of exon 1 beta of the p19ARF gene in metastatic melanoma cell lines.

Abstract: The INK4A locus on 9p21 is deleted or rearranged in a large number of human cancers. The locus encodes two unrelated and independently acting negative cell-cycle regulators, p16 and p19ARF, arising in alternate reading frames from a partly shared sequence. We analyzed five human melanoma cell lines for deletions at the INK4 loci and flanking microsatellite markers on 9p21. All the cell lines displayed deletions of varying sizes. The metastatic cell line IGR-1 showed a large deletion between the markers D9S736 and D9S171. In the cell lines WM-115 and WM-266–4, the deletion included exon 1α of p16, exon 1β of p19ARF, and exon 2 of the INK4B (p15) gene. Two cell lines, SK-MEL-5 and A2058, had deletions confined to exon 1β and the microsatellite marker D9S942. RT-PCR experiments showed the presence of the p16 and p15 transcripts and absence of p19ARF expression in both SK-MEL-5 and A2058 cell lines. The selective loss of the exon 1β of p19ARF and retention of the p16 and p15 genes and their expressions in these two cell lines support the putative tumor suppressor role for the alternate reading frame p19ARF gene. Genes Chromosomes Cancer 23:273–277, 1998. © 1998 Wiley-Liss, Inc.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Fast parallel algorithms for short-range molecular dynamics

Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

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