Search PubMed⌕ Search

Biomedical subjects

A Chopra

Publications and source records attributed to A Chopra.

At least 55 records · Page 3Linked to original sources
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

Human cell mutants affected in the interaction of the 12 beta-OH group of cardiac glycosides with the digitalis receptor.

The cross-resistance patterns of two different types of mutants of HeLa cells selected for resistance to the digoxin analog SC4453 (SCR mutants) in which the Na+/K+-ATPase is affected [A. Chopra and R. S. Gupta, J. biol. Chem. 261, 2034 (1986)], and towards numerous cardiac glycosides (CGs) and genins, were examined. One type of SCR mutant (designated as group C) was highly resistant to all CGs and genins investigated. In contrast, the other type of SCR mutant (group D) showed a high degree of cross-resistance towards selected CG derivatives (viz. digoxin, SC4453, digoxigenin, lanatoside C, alpha- and beta-methyldigoxin, dihydrodigoxin, alpha- and beta-acetyldigoxin, alpha,beta-diacetyldigoxin), all of which contained a free 12 beta-OH group in the steroid structure. Slight cross-resistance of the group D mutants was also observed for other compounds (viz. ouabain, ouabagenin, dihydroouabain) that contain a free 11 alpha-OH group in the molecule. However, these mutants exhibited no cross-resistance to other CG derivatives, which either lacked the above groups (viz. digitoxin, digitoxigenin, dihydrodigitoxin, digitoxigenin mono- and bisdigitoside, nerifolin, gitoxigenin, gitoxin, 16-acetylgitoxin, lanatosides A and B, cymarin, convallatoxin, oleandrin, strophanthidin, actodigin and bufalin) or in which the 12 beta-OH group was acetylated (viz. as in the case of 12-acetyldigoxin). Since the 12 beta-OH group is not required for CG-like activity, to account for these observations it is suggested that the genetic lesion in the group D mutant leads to the creation of a new binding site in the digitalis receptor, which specifically interacts with the 12 beta-OH group (the site presumably also interacts weakly with the 11 alpha-OH group) and either prevents or distorts the binding of the compounds to the drug binding site on the receptor. Further investigations with the different classes of CG-resistant mutants at the molecular level should prove very useful in identifying the drug receptor site and in understanding how these drugs interact with it.

Cardiac Glycosides↗
PubMed1987

Plasma levels of beta-endorphin in young and aged human males during the morning hours.

Age-related alterations in plasma levels of beta-endorphin (BE) were investigated in young and aged human males. This was accomplished by obtaining repeated measurements of BE levels in the plasma of young and aged human male subjects during the morning hours, when a diurnal elevation of BE in the plasma is reported to occur. BE was extracted from the plasma and measured by radioimmunoassay. No differences were found in plasma levels of BE between young and elderly males at any time during the time period studied. In addition, the mean level of BE in the plasma during the entire sampling period did not differ between the two age groups. These data suggest that in human males, the levels of BE in the plasma during the morning hours are not modified by aging.

Adolescent↗
PubMed1986

Biochemical and cross-resistance studies with HeLa cell mutants resistant to cardiac glycoside SC4453. Regulation of the resistant form of Na+/K+-ATPase in the mutant cells.

In HeLa cells, stable mutants which are between 25-to about 200-fold resistant to the cardiac glycoside derivative SC4453 (a digoxin analog which contains a pyridazine ring in place of a lactone ring in the C-17 position) have been isolated after a single step selection in the presence of the drug. Based on their cross-resistance pattern towards various cardiac glycosides, the mutants resistant to SC4453 (SCR mutants) appear to be of two different kinds and they differ from the two classes of ouabain-resistant mutants described previously (Gupta, R. S., and Chopra, A. (1985) J. Biol. Chem. 260, 6843-6850). One type of SCR mutants (designated as group C) exhibit a high degree of cross-resistance to all cardiac glycosides and their genins (viz. ouabain, digitoxin, digoxin, digoxigenin, convallatoxin, gitoxin, strophanthidin, and bufalin). In contrast, the second type of SCR mutant (group D) exhibit considerable resistance to only SC4453, digoxin, and digoxigenin, but showed very little or no cross-resistance to the other cardiac glycosides examined. The cross-resistance of the mutants towards cardiac glycosides was highly specific as they exhibited no cross-resistance towards a large number of other structurally and functionally related compounds (viz. ethacrynic acid, sanguinarine nitrate, penicillic acid, methyl quinolizinum bromide, 5,5'-diphenylhydantoin, deoxycorticosterone, vanadium pentoxide, and adriamycin). The cellular uptake of 86Rb in the mutant cells was found to be resistant to specific cardiac glycosides. Studies on the sensitivity of plasma membrane Na+/K+-ATPase to cardiac glycosides show that about 10-15% of the enzymic activity in the mutant cells was highly resistant to inhibition by the specific drugs to which the mutants exhibit increased resistance. Very interestingly, when the mutant cells are grown in cardiac glycoside-containing medium, the resistant form of the enzyme accounts for about 50-60% of the total enzyme. These results show that both classes of SCR mutants are affected in Na+/K+-ATPase and that the amount of the resistant enzyme in the mutant cells is regulated in response to cardiac glycosides.

Cardiac Glycosides↗
PubMed1986

Cellular basis for the species differences in sensitivity to cardiac glycosides (digitalis).

The relative toxicity of numerous cardiotonic steroids (viz. ouabain, digitoxin, digoxin, convallatoxin, SC4453, bufalin, gitaloxin, digoxigenin, actodigin, oleandrin, digitoxigenin, gitoxin, strophanthidin, gitoxigenin, lanatosides A, B and C, alpha- and beta-acetyl digoxin, alpha- and beta-methyl digoxin) and related compounds towards a number of independent cell lines established from human, monkey, mouse, Syrian hamster, and Chinese hamster have been determined. All cardiac glycosides and their genins, as well as the cardiotonic alkaloid cassaine, exhibited greater than 100-fold higher toxicity towards cultured human and monkey cells in comparison to the cell lines of mouse, Syrian hamster, and Chinese hamster origins. These differences are species-related as all cell lines (both normal as well as transformed) from any one species, as well as cells from the closely related species (e.g., man and monkey or mouse, Chinese hamster, and Syrian hamster), showed similar sensitivity towards these drugs. The failure to see any significant differences in cellular toxicity for a larger number of other compounds which either bear limited structural resemblance to cardiac glycosides (viz. estradiol 17-beta-acetate, testosterone propionate, 21-acetoxy pregnenolone, beta-estradiol, digitonin, tigogenin, and tomatine) or interact with the Na+/K+ ATPase in a different manner (viz. veratridine, sanguinarine nitrate, penicillic acid, vanadium pentoxide, harmaline-HCI,5,5'-diphenyl hydantoin, quindonium bromide, and methyl quinolizinum bromide) provides strong evidence that the observed species-related differences are highly specific for cardiotonic steroids. Studies on the binding of [3H]ouabain show that, in comparison to human and monkey cell lines, no significant binding of the drug is observed in cells derived from the resistant species (i.e., mouse and Chinese hamster). The Na+/K+ ATPase from cells of the resistant species is inhibited at much higher concentrations of ouabain and digitoxin in comparison to the enzyme from human cells, and a good correlation is observed between these concentrations and those reported for inhibition of the enzyme from isolated heart muscles of the same species. These results provide strong evidence that the species-related differences in sensitivity to digitalis have a cellular basis and that the cultured cells from various mammalian species provide a useful model system for investigating the mechanism of action of cardiac glycosides.

Animals↗
PubMed1986

Ouabain-resistant mutants of Chinese hamster ovary cells are not directly affected in Na+, K+-ATPase.

The nature of biochemical lesions in a number of independent single-step ouabain-resistant (OuaR) mutants of Chinese hamster ovary cells has been examined. The cellular uptake of 86Rb in the mutant cells was found to be resistant to inhibition by ouabain and correlated with the degree of resistance of the mutants to the drug. However, the plasma membrane Na+, K+-ATPase from all five of the OuaR mutants examined showed similar sensitivity to inhibition by ouabain as seen for the enzyme from the parental sensitive cells. These results provide evidence that, contrary to the general assumption, OuaR mutants of Chinese hamster ovary cells, which are widely used for genetic and quantitative mutagenesis studies, are not directly affected in the Na+, K+-ATPase.

Animals↗