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Biomedical subjects

A Chopra

Publications and source records attributed to A Chopra.

At least 19 recordsLinked to original sources

Cloning of the guinea pig 5-lipoxygenase gene and nucleotide sequence of its promoter.

The guinea pig 5-lipoxygenase (5-LO) gene and its promoter were cloned from a guinea pig genomic DNA library. Sequencing analysis of the guinea pig promoter revealed that expression of the 5-LO gene in this rodent is probably governed by cis acting nucleotide sequences quite similar to the human gene. Nucleotide sequences that bind factors like Sp-1, AP-2, NF-kB and c-Ha-ras were identified in the guinea pig 5-LO promoter region.

Amino Acid Sequence

A rapid survey on substance abuse disorders in the urban slums of New Delhi.

The results are presented of a rapid survey screening method of general population for identifying dependent and non dependent drug abusers, especially in vulnerable groups such as slum dwellers. The results showed that with the help of instrument with modified DSM III and interviewing only the heads of the households it was possible to get reliable estimates of dependence disorder in the community. This method can be of assistance to health planners for a quick assessment of the magnitude of the problem leading to better allocation of funds and developing services for the affected population. The method is an improvement on key informant technique and a full fledged survey.

Adolescent

When outside the norm is normal: interpreting lab data in the aged.

Laboratory tests that are frequently ordered in a primary care practice include complete blood count, arterial blood gases, erythrocyte sedimentation rate, creatinine clearance, and glucose tolerance. Yet, the impact of age-associated physiologic changes on interpretation of laboratory data has only recently been elucidated. With advancing age, many laboratory parameters increase or decrease, some remain unchanged, and the effect of age on still others remains unclear. Interpreting lab data in the elderly is further confounded by the multiple disease states, polypharmacy, and atypical disease presentations commonly found in this population. Additional clinical research is needed to better establish reference laboratory values in elderly patients.

Aged

Genetic characterization of adenovirus transformed cell revertants resistant to methylglyoxal bis(guanylhydrazone): evidence for the involvement of three genetic loci.

Five new independent rat somatic cell mutants resistant to the antileukemic drug methylglyoxal bis(guanylhydrazone) (MGBG) were isolated after mutagen treatment. The mutants were 7- to 10-fold more resistant to MGBG than were the parental wild-type cells. When the MGBG-resistant (MGR) mutants were exposed to the drug in the presence of Tween-80, a nonionic detergent, they became as sensitive (MGS) to MGBG as the wild-type cells, indicating that they were probably permeability mutants. Genetic analysis of hybrids between MGR mutants and wild-type cells showed that MGR and the nontransformed alleles to be recessive to the MGS (wild-type) and transformed phenotype, respectively. Complementation analysis of the seven mutants revealed three functional genetic units or loci responsible not only for the MGR phenotype but also for tumorigenicity as determined in nude mice. Only the MGS hybrids produced tumors in the nude mice, whereas the MGR hybrids and mutants did not. Our results suggest the existence of cellular membrane components that are responsible both for cellular tumorigenicity and resistance to MGBG.

Adenoviridae

New mouse somatic cell mutants resistant to cadmium affected in the expression of their metallothionein genes.

Fluctuation tests à la Luria and Delbruck were performed with mouse LMTK cells, and the results indicate that the appearance of variants resistant to cadmium is due to random spontaneous mutations and not to epigenetic events. The rate of spontaneous mutations leading to cadmium resistance was calculated to be 0.92 x 10(-6) per cell per generation. This rate increased 14-fold on treatment with ethyl methane sulfonate. Several stable mutant cell lines resistant to cadmium were selected and characterized with respect to metallothionein (MT) induction. Based on the copy number of mt+ genes and the levels of MT proteins and mRNA, the mutants could be divided into two classes, A and B. Although group A mutants have the same number of mt1+ and mt2+ genes as wild-type cells, upon induction with cadmium, the amount of MT proteins and mRNA in the mutants are greatly increased over wild-type levels. This observation strongly suggests a mutation that regulates MT gene transcription in these cells. In group B mutants, the mt+ genes are amplified about three- to fourfold, and their MT protein and mRNA basal levels are, as expected, much higher than in the wild-type cells, under uninduced and induced conditions.

Animals

Cross-resistance and biochemical characteristics of second-step mutants of HeLa cells resistant to cardiac glycosides.

From ouabain-resistant (OuaR) mutants of HeLa cells which do not show any cross resistance to the digoxin analog SC4453, stable second-step mutants resistant to either SC4453 or those exhibiting increased resistance to digoxin have been isolated. The mutants obtained exhibited highly specific cross resistance towards different cardiac glycosides (CGs) and, based on their cross-resistance patterns, contained more than one type of genetic lesion. Biochemical studies with these mutants showed that cellular uptake of 86Rb was inhibited by specific CGs to which they showed increased resistance. The mutants showed reduced binding of [3H]ouabain and [3H]digoxin in comparison with the parental OuaR cells and about 50-60% of the Na+, K(+)-ATPase activity in the mutant cell extract was highly resistant to inhibition by ouabain and digoxin. In contrast to the above changes, these mutants showed no evidence of amplification, enhanced transcription, or gross alterations in the genes for the alpha or beta subunits of Na+, K(+)-ATPase. These observations indicated that these mutants involved a second-specific alteration in Na+, K(+)-ATPase. In contrast to these mutants, Chinese hamster ovary cells, which naturally exhibit comparable levels of resistance to CGs, showed no significant binding of either [3H]ouabain or [3H]digoxin and all of their Na+, K(+)-ATPase activity was resistant to inhibition by CGs.

Animals

Systemic manifestations of systemic lupus erythematosus.

Twenty five cases with systemic lupus erythematosus admitted to a referral service hospital over a period of 6 years have been studied to analyse the pattern of multisystem involvement. Febrile polyarthritis, renal involvement and skin changes dominated the clinical picture. Important serological abnormalities included the presence of antinuclear antibody and anti ds DNA. Renal biopsy carried out in all cases helped to reveal lupus nephritis in subclinical cases. The pattern of renal involvement varied, with diffuse proliferative glomerulonephritis being the commonest. Oral steroids was given to all cases and cyclophosphamide was given to severe and resistant cases. The severity of system involvement, especially renal, influenced the response to treatment. Changes in presentation between Indian and Western patients are highlighted.

Adult

Spectrum of seronegative spondarthritides (SSA) with special reference to HLA profiles.

The present study describes the profile of seronegative spondarthritides (SSA) in young servicemen. SSA was diagnosed in 63 patients from a prospective study on spondyloarthropathy. The SSA group consisted of ankylosing spondylitis (AS, 40 patients), Reiter's syndrome (RS, 6) and SSA undifferentiated (SSA-U, 17). The chief clinical and radiological features of the group were due to sacro-iliitis/spondylitis, peripheral arthritis and enthesopathy. Except for RS, extra-articular features were sparse. Mucosal lesions were not evident. Radiologically, sacro-iliitis varied from 24% in SSA-U to 100% in AS, and was disproportionately less when compared to its clinical extent. Dominant lower limb arthritis (poly and oligo) was seen in AS (40%), SSA-U (88.2%) and RS (100%). HLA A and B were typed in patients and controls. HLA AI had a significant negative association (p less than 0.05) with AS and the SSA group, and its relative risk (R) was consistently low (0.2-0.3). HLA B27 was present in 65.7%, 73%, 67%, 41% and 9% of the SSA group, AS, RS, SSA-U and controls respectively (p less than 0.05). Significant R values of A and B loci antigens in disease groups are presented. When compared with available Indian literature, this study highlights the variability and overlap in the disease. Disease markers currently available have limitations in defining the various subsets of SSA.

Adult

Myocardial fibrosis in the elderly.

The increasing interest in geriatric medicine demands an understanding of aging in human tissues. The changes in the human heart are an important aspect of this understanding because cardiovascular diseases are a leading medical problem in the elderly. The published data about age-related changes in the human myocardium remain incomplete and occasionally are controversial. An ongoing study of the hearts of people aged 80 years and older is being conducted at our institution. Various aspects of morphologic changes in these hearts were studied. In this report, we discuss the presence and extent of myocardial fibrosis, namely, the interstitial type. Two types of fibrosis are recognized: (1) scarring, the fibrotic replacement of lost myocardium, usually of vascular origin; and (2) interstitial, in which a delicate fibrotic net encircles single myocardial fibers. The morphologic findings were correlated with the following clinical findings: hypertension, congestive heart failure, emphysema, cor pulmonale, and coronary artery disease. The results support the hypothesis that interstitial fibrosis develops independently of the above-mentioned clinical conditions and may be considered as a true aging process.

Aged

Development of a specific assay for cardiac glycoside-like compounds based on cross-resistance of human cell mutants.

The cross-resistance patterns of single- and two-step mutants of HeLa cells resistant to SC4453 (a digoxin analog) and digoxin, which involve specific alteration in Na+, K+-ATPase towards numerous other compounds, have been examined. The mutants exhibited increased resistance to all of the steroidal compounds known to elicit a digitalis-like positive inotropic response (viz. various cardiac glycosides and their genins, erythrophleum alkaloid cassaine), but they showed no cross-resistance to any of a large number of other compounds which do not show cardiac glycoside (CG)-like biological activity. Based on the above characteristics of the mutants, a new cross-resistance assay for identifying compounds that show CG-like activity has been developed. In this assay, a sample is considered to possess CG-like activity if, in comparison to the parental HeLa cells, the CGR mutants exhibit increased resistance to it. From the known D10 value (drug concentration which reduces cloning efficiency of cells to 10%) of the drug for HeLa cells and the sample dilution necessary to produce equivalent cytotoxicity, the concentration of CGs in a given sample can be estimated. In blind studies the assay correctly identified all of the samples containing CGs; none of the other samples which lacked such activity tested positive. In the blind studies the assay also provided a good estimate of the concentration of CGs (+/- 50% of the actual concentration) that was not affected by the presence of either serum components or a 20-fold excess of various steroidal compounds known to interfere in other assays. In view of the high specificity of the present assay for CG-like compounds, it should prove very useful in establishing/characterizing the presence of such activity in various biological (namely endogenous digitalis-like substances) and other samples.

Cardiac Glycosides

Chronic inflammatory polyarthritides in a select population of young men. A prospective study.

Twenty young servicemen suffering from chronic inflammatory polyarthritides (CIP) were studied. While rheumatoid arthritis (RA) was the final diagnosis in 15 patients, the arthritis remained 'unclassifiable' in the rest. An acute onset of asymmetric deforming arthritis, dominant in the lower limbs, was the usual pattern. Sacroiliitis and enthesopathy were uncommon. Extra-articular features were sparse and sub-cutaneous nodules absent. Rheumatoid factor was present in 86.7% of RA patients. Radiologic erosions were evident in 73.3% RA patients. Arthritis robustus variant of RA was diagnosed in 4 patients. HLA B27 was present in 45.5% of RA patients in this atypical setting. An overlap of RA and seronegative spondarthritides was considered probable in 3 patients.

Adolescent

Cloning, nucleotide sequence and molecular evolution of a rabbit processed metallothionein MT-2 pseudogene.

A rabbit metallothionein-2 pseudogene (MT-2 psi) has been isolated from a partial rabbit genomic library. Its unusual sequence shows evidence of complex rearrangements involving recombination and deletion events. There are no intervening sequences, 3' poly A tract or 5' regulatory DNA sequences. The pseudogene is flanked by two sets of direct repeats (CT)3 GT(CT)4 and CTGG(G)CTC. They are most probably the sites of insertion of MT-2 psi in the rabbit genome. In addition, a number of repetitive DNA sequences are observed flanking the MT-2 psi gene. These are features of a processed retrogene.

Amino Acids

Cloning, nucleotide sequence and characterization of a New Zealand rabbit metallothionein-I gene.

We have isolated a rabbit metallothionein-I gene from a lambda gt10 library. The coding sequence of this gene is interrupted by two introns occurring at amino acid positions 9 1/3 and 30 1/3. Comparison of the promoter sequence of this gene with the promoters of other metallothionein genes identified a number of oligonucleotide sequences which are recognized by trans-acting proteins involved in the regulation of these genes by heavy metals, glucocorticoids and alpha interferon.

Amino Acid Sequence