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Biomedical subjects

R Misra

Publications and source records attributed to R Misra.

At least 73 records · Page 4Linked to original sources

Raised IgM antibodies to parvovirus B19 in juvenile rheumatoid arthritis.

To delineate the role of human parvovirus B19 in the etiopathogenesis of juvenile rheumatoid arthritis (JRA), IgM and IgG antibodies specific for parvovirus B19 surface protein antigen(s) were estimated in the sera using commercial ELISA kits. Sera of 69 JRA patients (median age 16 yr, male : female ratio 1.1:1) satisfying the criteria of American Rheumatism Association along with 26 sera of rheumatoid arthritis (RA) and 12 sera of healthy children as disease and normal controls respectively were screened. Of the 69 patients with JRA, 19 (27.5%), 35 (50.7%) and 9 (13%) were positive for IgM, IgG and both IgG and IgM antibodies respectively. Of the 26 disease control sera, 11 (42.3%) were positive for IgG antibodies while none had elevated IgM antibodies. Among 12 healthy controls, 7 (58.3%) were positive for IgG and 1 was positive for both IgG and IgM antibodies. Thus, a statistically significant proportion of children with JRA had evidence of parvovirus B19 infection.

Adolescent↗

In vitro effect of gold sodium thiomalate and methotrexate on tumor necrosis factor production in normal healthy individuals and patients with rheumatoid arthritis.

We studied the in vitro action of gold sodium thiomalate (GSTM) and Methotrexate (MTX) on spontaneous and lipopolysaccharide (LPS) stimulated TNF alpha production by peripheral blood mononuclear cells (PBMC) of patients with rheumatoid arthritis (RA) and normal healthy individuals. GSTM and MTX (10 microg) each were added to the cultures of PBMC either in medium alone (spontaneous) or in the presence of 10 microg of LPS. GSTM and MTX augmented spontaneous TNF alpha production in normal individuals and patients with RA but did not influence LPS stimulated TNF alpha production. However, TNF alpha production by the PBMC of normal individuals was inhibited if the PBMC were stimulated with LPS, for 6 or 12 h, washed to remove LPS and subsequently incubated with GSTM. These data indicate that GSTM can inhibit TNF alpha production when the PBMC are preactivated by LPS.

Animals↗

Plant immunomodulators for termination of unwanted pregnancy and for contraception and reproductive health.

Neem (Azadirachta indica) seed and leaf extracts have spermicidal, anti-microbial, anti-fungal and anti-viral properties. They are also immunomodulators that induce primarily a TH1 type response. These properties are being exploited to develop two different useful methods of fertility control. Neem extracts given orally at early post-implantation stage terminate pregnancy in rodents and primates. Treatment has no residual permanent effect and fertility is regained in subsequent cycles. The mechanism by which the action occurs is not fully clear. A transient increase in CD4 and more significantly in CD8 cells is noticed in mesenteric lymph nodes and spleen. A rise in immunoreactive and bioactive TNF-alpha and IFN-gamma in draining lymph nodes, serum and foetal-placental tissue is observed. A polyherbal cream and pessary have been developed containing three active ingredients of plant origin. These have synergistic spermicidal properties on human sperm as determined by the Sander Cramer test. Their use before mating has high contraceptive efficacy in rabbits and baboons. Another interesting property is their inhibitory action on a wide spectrum of micro-organisms, including Candida albicans, C. tropicalis, Neisseria gonorrhoeae, the multidrug-resistant Staphylococcus aureus and urinary tract Escherichia coli, Herpes simplex-2 and HIV-1. Phase I clinical trials have been completed in India, Egypt and the Dominican Republic, and indicate the safety of the formulation, its acceptability and beneficial action invaginosis due to infections.

Abortion, Induced↗

Is undifferentiated seronegative spondyloarthropathy a forme fruste of reactive arthritis?

Undifferentiated spondyloarthropathy (USpa) may either represent a forme fruste of other spondyloarthropathies like reactive arthritis or be a different disease entity. To study the link between USpa and reactive arthritis, we studied the presence of IgA antibodies to Yersinia enterocolitica, Salmonella typhimurium, Shigella flexneri, Campylobacter jejuni and Chlamydia trachomatis in sera from 14 patients with USpa (European Spondyloarthropathy Study Group criteria) using ELISA. Escherichia coli was used as a control antigen. An OD value of more than the mean +/- 2 S.D. of 51 blood donors was considered positive. Five patients had elevated IgA antibodies to S. flexneri, while two patients each had elevated antibody levels to S. typhimurium and Chlamydia. No patient had elevated antibodies to Y. enterocolitica, C. jejuni and E. coli. Among 51 normals, 1, 4, 3, 2 and 3 had elevated antibodies to S. flexneri, S. typhimurium, Y. enterocolitica, C. jejuni and E. coli, respectively. Nine of 14 patients with USpa had antibodies to one of the bacteria implicated in reactive arthritis: of these, antibodies to Shigella were the most frequent. Thus, a proportion of patients with USpa may in fact have reactive arthritis.

Adolescent↗

Superintendents' perceptions of schoolsite health promotion in Missouri.

This study assessed school district superintendents' perceptions of schoolsite health promotion in Missouri using a telephone survey method. Superintendents of 150 school districts were surveyed using The Worksite Health Promotion for Faculty and Staff section of the Eight-Component Assessment. Staff identification of blood pressure, healthful cafeteria menus, and smoke-free school policies were perceived as the most frequently offered health-promoting activities. Quality of programs as perceived by district superintendents ranged from "average" to "exemplary." For school districts not offering programs, healthful cafeteria menus, staff identification of blood pressure, and stress management were perceived by superintendents as highly necessary. The number of programs offered in each area differed significantly by demographic characteristics: accreditation classification, assessed valuation, size, and residence. Supportive attitudes by superintendents are critical to attain schoolsite health promotion programs for faculty and staff as part of a comprehensive school health program in Missouri.

Administrative Personnel↗

IgM rheumatoid factor estimation by ELISA in seronegative rheumatoid arthritis before and after IgM fractionation: does seronegative RA exist?

We looked for the presence of IgM rheumatoid factor (RF) using an enzyme-linked immunosorbent assay (ELISA) in 25 patients with active seronegative rheumatoid arthritis. In unfractionated sera, 12 patients (48%) were positive for IgM RF (classical), but after IgM fractionation of 23 samples (2 samples were not available) using high performance liquid chromatography for fractionating IgM, 12 patients were positive for RF by ELISA indicating the presence of hidden RF. Finally, three patients were labelled as truly seronegative for IgM RF. Classical IgM RF as detected by ELISA correlated significantly with erosive disease. Hidden RF did not correlate with disease activity or severity in this cross-sectional study, and though its presence was associated with shorter disease duration this did not reach statistical significance.

Adolescent↗

Cellular immune responses of patients with juvenile chronic arthritis to retinal antigens and their synthetic peptides.

The objective of this study was to determine the proliferative responses of peripheral blood lymphocytes of ocular antigens like retinal S-antigen, peptides M and G of S-antigen, yeast histone H3 peptide 106-121 homologous to peptide M and peptide R16 of interphotoreceptor retinoid binding protein (IRBP) in children with juvenile chronic arthritis (JCA). We have studied the in vitro proliferative response of peripheral blood lymphocytes from 41 patients with JCA (10 with and 31 without uveitis) and 23 healthy controls against the above antigens. The responders were retested after 1 or 6 months. Fifty (5/10) and 9.7% (3/31) of JCA patients with and without uveitis, respectively, responded (stimulation index > 3) to S-antigen or one of its peptide listed above or yeast histone H3 peptide or R16 of IRBP. None of the healthy controls responded to any of these antigens. The difference in the frequency of responders (SI > 3) between JCA associated with uveitis and healthy controls was statistically significant (p = 0.001). Similarly, the difference between JCA with and without uveitis was also significant (p = 0.013). Our findings suggest that these antigens may have a role in the pathogenesis of uveitis in a subset of patients with JCA.

Amino Acid Sequence↗

A genetic approach for analysing surface-exposed regions of the OmpC protein of Escherichia coli K-12.

Phage attachment sites on bacterial cell surfaces are provided by the exposed regions of outer membrane proteins and lipopolysaccharide (LPS). We have identified surface exposed residues of OmpC that are important for phage binding. This was accomplished by employing a genetic scheme in which two simultaneous selections enriched for ompC mutants defective in phage attachment, but retained functional channels. Mutational alterations were clustered in three regions of the OmpC protein. These regions also showed the greatest divergence from the analogous regions of the highly related OmpF and PhoE proteins. The majority of alterations (8 out of 11) occurred in a region of OmpC that is predicted to form a large exterior loop (loop 4). Interestingly, while the removal of this loop prevented phage binding, the deletion conferred enhanced channel activities. Another type of phage-resistant mutants synthesized defective LPS molecules. Biochemical analysis of mutant LPS revealed it to be of the Re-type LPS, lacking the heptose moieties from the LPS inner core. As a result of this LPS defect, many outer membrane proteins were present in somewhat reduced levels. The phage resistance seen in these mutants could be a result of both the presence of defective LPS and reduced OmpC levels.

Amino Acid Sequence↗

Cancer detection: how effective is public education?

The American Cancer Society has been educating the public about cancer detection methods since 1922. Originally, only two warning signs were published; however, for more than 40 years, there have been seven cancer warning signs. In an attempt to evaluate the public knowledge of cancer detection and prevention, this pilot study examined the attitudes, knowledge and behaviors of 172 laypersons. The instrument used consisted of four sections and was designed by the investigator and the graduate nursing research class. The first section contained 30 questions about the individual, health practices, and risk status in a forced-choice format. Ability to identify the seven cancer warning signals was the second section. Attitudes toward Cancer Detection methods were evaluated in a semantic differential format as the third section. The list section contained 24 Likert-formatted statements of beliefs about the importance of cancer detection. Before data analysis, a Cronbach's alpha was obtained on each scale and ranged from 0.8031 to 0.8897. Eighty nine (52%) of the respondents were women and 83 (48%) were men. The sample was 85% white, 11% African-American, and 4% other ethnic groups. Ninety-four percent of the population had some form of health insurance. Gender was not significantly related to scores on the Attitudes toward Cancer Detection or the Beliefs about Cancer Scale. Race was significantly related to scores on the Attitudes toward Cancer Detection Scale. Nineteen percent of the sample could not identify any of the cancer warning signs. The median number of warning signs correctly identified as warning signals was three. Thirty-two items were incorrectly listed as warning signs. Survival of cancer is linked with early detection. The inability to influence changes in knowledge and practices over the past 50 years is examined. Implications for nurses and teaching related to cancer warning signs are explored.

Adult↗

Examination of AsmA and its effect on the assembly of Escherichia coli outer membrane proteins.

asmA mutations were isolated as extragenic suppressors of an OmpF assembly mutant, OmpF315. This suppressor locus produced a protein that was present in extremely low levels and could only be visualized by Western blotting in cells where AsmA expression was induced from a plasmid. Detailed fractionation analyses showed that AsmA localized with the inner membrane. Curiously, however, the mutant OmpF assembly step influenced by AsmA occurred in the outer membrane, perhaps indicating an indirect involvement of AsmA in the assembly of outer membrane proteins. Biochemical examination of the outer membrane showed that asmA null mutations reduce lipopolysaccharide (LPS) levels, thereby lowering the ratios of glycerolphospholipids to LPS and envelope proteins to LPS in the outer membrane. Despite these quantitative alterations, no apparent structural changes in LPS or major phospholipids were noted. Reduced LPS levels in asmA mutants indicate a possible role of AsmA in LPS biogenesis. Data presented in this study suggest that asmA-mediated OmpF assembly suppression may have been achieved by altering the outer membrane fluidity, thus making it more amenable for the assembly of mutant proteins.

Bacterial Outer Membrane Proteins↗

asmB, a suppressor locus for assembly-defective OmpF mutants of Escherichia coli, is allelic to envA (lpxC).

A novel genetic scheme allowed us to isolate extragenic suppressor mutations that restored mutant OmpF assembly. One group of these mutations, termed asmB for assembly suppressor mutation B, permitted mutant OmpF assembly in a non-allele-specific manner. Genetic mapping analyses placed the asmB mutations at the 2-min region of the Escherichia coli K-12 chromosome. Further analyses revealed that the asmB mutations map within the envA (lpxC) gene, which encodes an enzyme needed for the synthesis of the lipid A moiety of lipopolysaccharide (LPS). Nucleotide sequence analysis showed that the asmB mutations caused a change from F-50 to S (F50S substitution) (asmB2 and asmB3) or a G210S substitution (asmB1) in EnvA. Cells bearing the asmB alleles displayed increased sensitivity to various hydrophobic compounds and detergents, suggesting an alteration within the outer membrane. Direct examination (of the LPS showed that its amounts were reduced by the asmB mutations, with asmB1 exerting a greater effect than asmB2 or asmB3. Thus, it appears that the asmB mutations achieve mutant OmpF assembly suppression by reducing LPS levels, which in turn may alter membrane fluidity.

Alleles↗

Assembly-defective OmpC mutants of Escherichia coli K-12.

Novel ompC(Dex) alleles were utilized to isolate mutants defective in OmpC biogenesis. These ompC(Dex) alleles also conferred sensitivity to sodium dodecyl sulfate (SDS), which permitted the isolation of SDS-resistant and OmpC-specific phage-resistant mutants that remained Dex+. Many mutants acquired resistance against these lethal agents by lowering the OmpC level present in the outer membrane. In the majority of these mutants, a defect in the assembly (metastable to stable trimer formation) was responsible for lowering OmpC levels. The assembly defects in various mutant OmpC proteins were caused by single-amino-acid substitutions involving the G-39, G-42, G-223, G-224, Q-240, G-251, and G-282 residues of the mature protein. This assembly defect was correctable by an assembly suppressor allele, asmA3. In addition, we investigated one novel OmpC mutant in which an assembly defect was caused by a disulfide bond formation between two nonnative cysteine residues. The assembly defect was fully corrected in a genetic background in which the cell's ability to form disulfide bonds was compromised. The assembly defect of the two-cysteine OmpC protein was also mended by asmA3, whose suppressive effect was not achieved by preventing disulfide bond formation in the mutant OmpC protein.

Alleles↗

Pregnancy outcome in systemic sclerosis.

The outcome of pregnancy in systemic scleroderma (SSc) has been a subject of much interest. In a retrospective analysis of 59 pregnancies of 17 mothers with SSc, the effect of disease on pregnancy outcome was variable. There was no adverse effect on fertility. While there was an apparent decrease in fertility in the limited cutaneous disease, this was not seen in the diffuse variety. There was an decreased incidence of live birth after the onset of disease as compared prior to the onset of disease. The foetal wastage after the onset of disease was contributed equally by spontaneous abortions as well as induced terminations of pregnancies. The presence of anticardiolipin antibodies was not related with adverse outcome. The effect of pregnancy on disease was variable with the disease being stable in five patients, regressing in five and progressing in three. The increased terminations of pregnancy reflects the uncertainities of positive outcome both by parent and attending physicians.

Adolescent↗

Cervical spine involvement in rheumatoid arthritis: prevalence and relationship with overall disease severity.

Rheumatoid arthritis (RA) affects the cervical spine in 20-90% of patients in Western countries. We report the prevalence of cervical spine involvement in RA and its relationship with duration of disease, seropositivity, hand joint erosions and symptoms and signs suggestive of cervical spine involvement. 100 patients with RA criteria were included. Apart from clinical history and examination, study included X-rays of the cervical spine in AP, open mouth and lateral views and posteroanterior view of hands and rheumatoid factor estimation. All X-rays were read by a radiologist who was unaware of the clinical details. Cervical spine involvement was seen in 65% of patients. The commonest abnormality was erosions of the odontoid process (47%), followed by atlanto-axial dislocation and apophyseal joint involvement (24%). Only 5% of patients had abnormalities of spinous processes or vertebral bodies. Patients with abnormal cervical spine radiographs had higher prevalence of rheumatoid factor and erosions on hand radiographs. Severity of cervical spine changes was related to duration of disease (> 5 years). No correlation was seen between symptoms and radiological abnormalities except when neurological deficit was present. Patients with seropositivity, erosive disease and disease duration greater than five years should be screened for cervical spine disease.

Adolescent↗

Oocyte activation and passage through the metaphase/anaphase transition of the meiotic cell cycle is blocked in clams by inhibitors of HMG-CoA reductase activity.

Cell cycle progression for postembryonic cells requires the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), the enzyme which catalyzes the production of the isoprenoid precursor, mevalonate. In this study, we examine the requirements of HMG-R activity for cell cycle progression during the meiotic and early mitotic divisions using oocytes and dividing embryos from the surf clam, Spisula solidissima. Using two different inhibitors of HMG-R, we find that the activity of this enzyme appears to be required at three distinct points of the cell cycle during meiosis. Depending on the stage at which these inhibitors are added to synchronous clam cultures, a reversible cell cycle block is triggered at the time of activation or at metaphase of either meiosis I or II, whereas there is not block to the mitotic cell cycle. Inhibition of HMG-R activity in activated oocytes does not affect the transient activation of p42MAPK but results in a block at metaphase of meiosis I that is accompanied by the stabilization of cyclins A and B and p34cdc2 kinase activity. Our results suggest that metabolites from the mevalonate biosynthetic pathway can act to influence the process of activation, as well as the events later in the cell cycle that lead to cyclin proteolysis and the exit from M phase during clam meiosis.

Animals↗

Compound heterozygosity of HLA-DR4 and DR1 antigens in Asian Indians increases the risk of extra-articular features in rheumatoid arthritis.

The relationship of HLA-DR antigens in rheumatoid arthritis (RA) patients with the presence of rheumatoid factor (RF), extra-articular features, joint erosions, functional status and response to disease modifying anti-rheumatic drugs (DMARDs) was studied. Seventy-four patients with RA were serologically typed for class II antigens. Clinical features were recorded before starting DMARDs and during follow-up to assess response and side-effects. HLA-DR1 and DR4 antigens were present more frequently in patients with RA than in the general population. The presence of DR4 correlated with RF seropositivity (P < 0.001) while DR1 was associated with seronegativity (P < 0.02). Ten of the 11 patients with extra-articular features had DR1 and/or DR4. Patients with both DR4 and DR1 had a significantly higher frequency of extra-articular features compared with those with only one of these (P < 0.01). HLA-DR4 and DR1 had no relation with the presence of subcutaneous nodules, erosive changes, deformities, response to drugs and side-effects of DMARDs.

Adult↗

Arthritis in scleroderma.

Thirty-four patients (24 females and 10 males) selected from 300 consecutive patients with established systemic sclerosis (SSc), with a current or past history of articular symptoms, were clinically documented and further studied using thermography and bone scan to define the pattern of arthritis. Clinical evidence of synovitis was observed in 30 (88%) and joint inflammation was detected in 31 (91%) by the above-mentioned imaging techniques. A distinctive subset of 10 patients with deforming arthritis was characterized in which seven (70%) patients fulfilled criteria for both rheumatoid arthritis and SSC; three of these satisfied the criteria for diagnosis of CREST, but none met the criteria of mixed connective tissue disease. These patients, as a group, when compared with the rest showed limited skin involvement (skin score of 19 +/- 11 vs 33 +/- 14; P < 0.05) and were positive for rheumatoid factor (80 vs 13%; P < 0.05) and anticentromere antibodies (37 vs 4%; P < 0.05).

Adult↗