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Biomedical subjects

R Misra

Publications and source records attributed to R Misra.

At least 37 records · Page 2Linked to original sources

Autoantibodies against cytoskeletal proteins in rheumatoid arthritis.

We determined the prevalence and antigenic specificity of autoantibodies against cytoskeletal proteins in patients affected with various autoimmune diseases. Sera collected from patients with rheumatoid arthritis, systemic lupus erythematosus or progressive systemic sclerosis, and normal volunteers, were examined for the presence of autoantibodies against cytoskeletal proteins by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Patients with rheumatoid arthritis had the highest reactivity to cytoskeletal antigens on immunofluorescence assays using isolated muscle myofibrils (41/50) and L929 cells (37/50). Antigen-specific ELISA revealed significant immunoreactivity against actin (11/50) and myosin (15/50). In nine patients, immunoreactivity was seen against multiple cytoskeletal antigens. We concluded that the prevalence of IgG autoantibodies against cytoskeletal antigens, especially myofibrillar components actin and myosin, is elevated in patients with rheumatoid arthritis.

Animals↗

The F158V polymorphism in FcgammaRIIIA shows disparate associations with rheumatoid arthritis in two genetically distinct populations.

OBJECTIVES: To investigate the association of the FcgammaRIIIA gene with rheumatoid arthritis (RA) in two genetically distinct groups: a white group from the United Kingdom and a northern Indian group. METHODS: The distributions of the two alleles of the FcgammaRIIIA F158V polymorphism were determined in 398 white patients from the United Kingdom and 63 Indian patients with RA and compared with those from 289 United Kingdom and 93 Indian healthy controls, respectively. RESULTS: Among the Indian patients, the frequency of the rare 158V allele and the proportion of 158VV homozygotes were reduced (relative risk (RR)=0.3, 95% confidence interval (95% CI) 0.1 to 1.1, p<0.06), reaching statistical significance for carrying the 158VV phenotype relative to 158FV or FF (RR=0.2, 95% CI 0.05-0.9, p<0.02). Conversely, no significant deviation in allelic frequencies was noted between the patients and controls from the United Kingdom. CONCLUSIONS: The 158VV phenotype showed a weak protective effect against developing RA in the Indian group. However, this sample was small (resulting in a low power for statistical analysis) and no independent confirmation was found in the larger white United Kingdom group. Thus the FcgammaRIIIA locus is unlikely to be of major importance in causing RA.

Alleles↗

Does cyclophosphamide benefit relapsing thrombotic thrombocytopenic purpura?

Thrombotic thrombocytopenic purpura (TTP) is a rare disease. A high index of suspicion is required for early diagnosis and treatment. It can present in acute as well as chronic forms. Cyclophosphamide has been reported to be beneficial in relapsing TTP. Herein a case of acute TTP evolving into relapsing phase of the disease is presented. Cyclophosphamide in our case achieved partial remission without the need for plasma exchange therapy. The rationale of cyclophosphamide in management of relapsing TTP is discussed.

Adult↗

The TolC protein of Escherichia coli serves as a cell-surface receptor for the newly characterized TLS bacteriophage.

The TolC protein of Escherichia coli is implicated in a variety of diverse cellular functions, including antibiotic efflux and alpha-hemolysin secretion. An incidental role of TolC is to facilitate the entry of the bacteriophage TLS and colicin E1 into the bacterial cell. Despite the resolution of TolC's atomic structure, the roles of specific residues in its diverse functions are unknown. Here, we describe a genetic strategy for isolating missense tolC mutations that abolish the bacteriophage receptor activity of the TolC protein without influencing its role in antibiotic efflux. These spontaneous mutations affected two regions of the TolC protein and included base-pair substitutions, insertions, and deletions. Comparison of the TolC sequence with those of its homologues revealed two hypervariable stretches that were predicted to represent loops. Interestingly, all but one of the TolC alterations preventing phage binding were located in these two hypervariable regions, which are likely to be exposed on the cell surface. This was substantiated by the recently solved three-dimensional structure of TolC. Curiously, all the phage-resistant TolC mutants showed varying degrees of resistance to colicin E1, suggesting the involvement of overlapping regions of TolC in colicin E1 import and phage binding. The phage used in this study, TLS, was earlier reported as a strain of U3. However, we show here that, unlike the previously reported lipopolysaccharide-specific U3 phage, this phage displays a distinctly different host range and discrete morphological features and, in addition to utilizing TolC as receptor, it requires the inner core of a lipopolysaccharide.

Adsorption↗

Epidemiology of undernutrition.

OBJECTIVE: The present study was undertaken to find out the magnitude of the problem of under nutrition among the children under 5 years of age and also to identify the important factors influencing the nutritional status of the children. METHODS: 30 cluster sampling technique had been applied in the study. A total of 600 children below five years of age were covered. Twenty under five children from each cluster were chosen for the study which was carried out during January to February '97. As per IAP criteria a total of 60.29% children were undernourished and 3.92% were severely undernourished. According to NCHS standard 46.57% & 6.86% children had weight below-2SD and -3SD respectively. RESULTS: A statistically significant relationship was found between the different age groups and nutritional status of under 5 children. Severe degree of malnutrition had highest prevalence under two years of age. The influence of variables like age, sex, religion, literacy status of parents and morbidity of the children were significantly associated with malnutrition. CONCLUSION: Practice of exclusive breast feeding, introduction of timely complementary feeding, education for maintaining personal hygiene, proper implementation of UIP immunization, periodic deworming, standard case management of diarrhoea and ARI as well as continuation of feeding during illness may reduce malnutrition of under-five children.

Age Distribution↗

Intragenic suppressors of an OmpF assembly mutant and assessment of the roles of various OmpF residues in assembly through informational suppressors.

We employed two separate genetic approaches to examine the roles of various OmpF residues in assembly. In one approach, intragenic suppressors of a temperature-sensitive OmpF assembly mutant carrying a W214E substitution were sought at 42 degrees C, or at 37 degrees C in a genetic background lacking the periplasmic folding factor SurA. In the majority of cases (58 out of 61 revertants), the suppressors mapped either at the original site (position 214) or two residues downstream from it. In the remaining three revertants that were obtained in a surA background, an alteration of N230Y was located 16 residues away from the original site. The N230Y suppressor also corrected OmpF315 assembly at 42 degrees C in a surA(+) background, indicating that the two different physiological environments imposed similar assembly constraints. The specificity of N230Y was tested against five different residues at position 214 of mature OmpF. Clear specificity was displayed, with maximum suppression observed for the original substitution at position 214 (E214) against which the N230Y suppressor was isolated, and no negative effect on OmpF assembly was noted when the wild-type W214 residue was present. The mechanism of suppression may involve compensation for a specific conformational defect. The second approach involved the application of informational suppressors (Su-tRNA) in combination with ompF amber mutations to generate variant OmpF proteins. In this approach we targeted the Y40, Q66, W214, and Y231 residues of mature OmpF and replaced them with S, Q, L, and Y through the action of Su-tRNAs. Thus, a total of 16 variant OmpF proteins were generated, of which three were identical to the parental protein, and two variants carrying W214Q and Y231Q substitutions were similar to assembly-defective proteins isolated previously (R. Misra, J. Bacteriol. 175:5049-5056, 1993). The results obtained from these analyses provided useful information regarding the compatibility of various alterations in OmpF assembly.

Amino Acid Sequence↗

Isolation and characterization of Escherichia coli tolC mutants defective in secreting enzymatically active alpha-hemolysin.

This study describes the isolation and characterization of a unique class of TolC mutants that, under steady-state growth conditions, secreted normal levels of largely inactive alpha-hemolysin. Unlike the reduced activity in the culture supernatants, the cell-associated hemolytic activity in these mutants was identical to that in the parental strain, thus reflecting a normal intracellular toxin activation event. Treatment of the secreted toxin with guanidine hydrochloride significantly restored cytolytic activity, suggesting that the diminished activity may have been due to the aggregation or misfolding of the toxin molecules. Consistent with this notion, sedimentation and filtration analyses showed that alpha-hemolysin secreted from the mutant strain has a mass greater than that secreted from the parental strain. Experiments designed to monitor the time course of alpha-hemolysin release showed delayed appearance of toxin in the culture supernatant of the mutant strain, thus indicating a possible defect in alpha-hemolysin translocation or release. Eight different TolC substitutions displaying this toxin secretion defect were scattered throughout the protein, of which six localized in the periplasmically exposed alpha-helical domain, while the remaining two mapped within the outer membrane-embedded beta-barrel domain of TolC. A plausible model for the secretion of inactive alpha-hemolysin in these TolC mutants is discussed in the context of the recently determined three-dimensional structure of TolC.

Bacterial Outer Membrane Proteins↗

Anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizures.

The aim of this study was to examine whether the clinical features of antiphospholipid antibody syndrome are associated with anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with SLE. Seventy-six patients (71 females), who fulfilled 1982 ACR criteria for SLE, were prospectively studied for the clinical features of antiphospholipid antibody syndrome (APS), and their sera were analysed for the presence of IgG/IgM/IgA anti-cardiolipin antibodies (aCL) by an in-house ELISA and, in 65 of them, for the presence of IgG anti-beta2 glycoprotein I antibodies (anti-beta2 GPI) by a commercial kit. Thirty-nine (51%) patients were positive for aCL, all of which were positive for IgG aCL, either alone (79.6%) or along with IgM and/or IgA. Twenty-seven (69.3%) out of 39 aCL-positive and seven (26.9%) out of 26 aCL-negative sera were positive for IgG antibodies to beta2 GPI. There was a significant correlation (r = 0.66, P < 0.05) between the levels of aCL and anti-beta2 GPI antibodies. Forty-one patients had features of definite or suggestive APS. Thrombocytopenia, recurrent pregnancy loss and CNS manifestations (seizures eight, infarct one) were seen in 20, 13 and nine patients, respectively. Thrombosis of the peripheral vessels was seen in only one patient. Only the presence of seizures was significantly associated with the presence of aCL and anti-beta2 GPI antibodies (P < 0.05). The characteristic association of definite APS (recurrent pregnancy loss and arterial/venous thrombosis) was lacking.

Adolescent↗

Reproductive health needs and care seeking behaviour of pavement dwellers of Calcutta.

An unabated growth of street dwellers in the city of Calcutta is reported to be due to twin reasons like, migration of rural poor people as well as uncontrolled fertility among these poor settlers of the city. A community-based study on reproductive health, fertility and related care seeking behaviour was studied among a sample of women of child bearing age living on streets of Calcutta. Besides, the quite common conditions like leucorrhoea (28.5%), menstrual irregularities (12.3%), infertility (2.5%) and STDs (1.3%) were also reported. But most of these illnesses (three-fourth) were uncared for, and the remaining one-fourth sought treatment from govemment institutions, private agencies or even from untrained practitioners (quacks). The reproductive behaviour of street dwelling women was characterised by early marriage, teenage pregnancies, and scarce use of contraceptives (32%) as well as frequent abortions (2.8%). Very few pregnant women received adequate antenatal care (3.8%). Coverage of tetanus toxoid immunisation (68.5%) and proper iron and folic acid supplementation (16.7%) were also poor. Whereas, antenatal care was received mostly from government health institutions (71%), home delivery (ie, on street) was a common practice and conducted mostly by untrained birth attendants (51.8%).

Adolescent↗

Arthritis in sarcoidosis.

AIMS AND METHODS: Sarcoidosis is systemic granulomatous disorder. Articular manifestations have received little attention in the literature. Case records of patients with sarcoidosis, presenting with articular symptoms between 1990-1999, were retrospectively analysed. RESULTS: Twenty nine patients, 15 males and 14 females, median age 44 years (range 15-67 years) and median duration of articular symptoms of eight months diagnosed clinically (n=9) and on biopsy (n=20) were studied. Twenty five patients had arthritis as the presenting manifestation. Fifteen patients had chronic arthritis (> six months). Lofgren's syndrome was seen in 7% of the patients. Acute arthritis was episodic (n=4), more common in males (M:F = 9:5), predominantly affected lower limb joints and mimicked reactive arthritis. Chronic arthritis was more frequently observed in females (M:F = 1:2) and presented with involvement of bilateral symmetric hand joints, mimicking rheumatoid arthritis. Extra-articular manifestations like neuropathy and constitutional symptoms were observed in acute arthritis. Skin plaque, splenomegaly and interstitial lung disease were seen with chronic arthritis. At a median follow up of 12 months, 10/14 and 5/15 achieved complete remission whereas 2/14 and 9/15 achieved partial remission of the articular symptoms in the acute and chronic groups, respectively. CONCLUSION: Arthritis in sarcoidosis is an early manifestation of disease and may mimic reactive or rheumatoid arthritis. Unsatisfactory response in chronic arthritis highlights the need for immunosuppressive drugs in addition to steroids.

Adolescent↗

Plasmid mediated antibiotic resistance in Klebsiella pneumoniae.

Klebsiella pneumoniae species (108) isolated from tertiary care hospitalized patients were investigated for antibiotic resistance patter. 74% isolates were from urine, 13.5% from pus, 4.5% from blood and 8% from sputum. The resistance pattern of the organisms to various antibiotics were as follows: ampicillin 93.3%, cefotaxime 70%, ceftazidime 81%, gentamicin 68.5%, amikacin 63.75%, netilmicin 74%, norfloxacin 55%, ofloxacin 53%, chloramphenicol 82%, tetracycline 85%, sulphamethoxazole 96%, trimethoprim 94%. 2-4 drug resistance was found in 34.5%, 5-8 drug resistance was in 25.1% and 9-12 drug resistance was found in 40.4% of strains. Out of 65 strains, 25 strains could be successfully conjugated. Common drugs which were transferred to transconjugants were sulphamethoxazole, trimethoprim, gentamicin, netilmicin, amikacin, chloramphenicol, tetracycline, ampicillin, cefotaxime and ceftazidime. A large plasmid of 98.7% kb could be demonstrated in these strains by alkali denaturation method and agarose gel electrophoresis.

Anti-Bacterial Agents↗

Modeling the X-Ray Timing Properties of Cygnus X-1 Caused by Waves Propagating in a Transition Disk.

We show that waves propagating in a transition disk can explain the short-term temporal behavior of Cygnus X-1. In the transition-disk model, the spectrum is produced by saturated Comptonization within the inner region of the accretion disk where the temperature varies rapidly with radius. Recently, the spectrum from such a disk has been shown to fit the average broadband spectrum of this source better than that predicted by the soft-photon Comptonization model. Here we consider a simple model in which waves are propagating cylindrically symmetrically in the transition disk with a uniform propagation speed (cp). We show that this model can qualitatively explain (1) the variation of the power spectral density with energy, (2) the hard lags as a function of frequency, and (3) the hard lags as a function of energy for various frequencies. Thus, the transition-disk model can explain the average spectrum and the short-term temporal behavior of Cyg X-1.

Journal Article↗