Search PubMedSearch

Biomedical subjects

A Mathur

Publications and source records attributed to A Mathur.

At least 19 recordsLinked to original sources

Psychologic stress in the workplace and spontaneous abortion.

The relation of work-related psychologic stress to spontaneous abortion was examined in a prospective study of 3,953 pregnant, employed members of a prepaid health plan in California, recruited between 1990 and 1991. Information on occupation, psychologic stress-related factors at work, social support at work, physical exertion at work, life events, pregnancy worries, and potential confounders was obtained by a telephone interview. Psychologic job stress and social support at work were assessed using an abbreviated version of the instrument developed by Karasek and colleagues (Los Angeles: University of Southern California, 1986). Results from the multivariate model indicated that, overall, stressful work was not associated with an increased risk of spontaneous abortion. However, interactions were observed between stressful work and maternal age over 32 years (p = 0.04), cigarette smoking (p = 0.02), and primigravidity (p = 0.06). Relative to the odds ratio for stressful work in young, nonsmoking, multigravid women without a history of two or more spontaneous abortions, the odds ratios for spontaneous abortion given stressful work were higher by 2.45 (95% confidence interval (CI) 1.03-5.81) for older women, 2.96 (95% CI 1.16-7.52) for smokers, and 2.27 (95% CI 0.97-5.27) for primigravid women.

Abortion, Spontaneous

Plasma cells tumors decrease CD23 mRNA expression in vivo in murine splenic B cells.

CD23, the low-affinity Fc receptor for IgE, is constitutively expressed on mature, naive B cells, but is lost following B cell activation. We and others have shown that CD23 expression on B cells decreases in mice bearing plasma cell tumors. In contrast to these findings, we find that IgE-secreting tumors do not cause a loss of CD23 expression on host splenic B cells. Decreased expression of CD23 on B cells induced by plasma cell tumors requires direct contact between tumor cells and B cells; and other host cells are not involved. The loss of surface CD23 expression is associated with a decrease in steady-state CD23 mRNA levels in B cells from plasma cell tumor-bearing mice. Interestingly, loss of CD23 mRNA is observed even in B cells from mice with IgE-secreting tumors, where we find surface CD23 protein expression to be similar to that of normal mice. The maintenance of surface CD23 expression on B cells in mice with IgE-secreting tumors is dependent solely on the presence of IgE, and is not a tumor-specific effect. Therefore, we conclude that in vivo, IgE secreted by plasma cell tumors can result in the maintenance of normal levels of surface CD23 expression by a post-transcriptional mechanism, even when the tumor induces a down-regulation of CD23 mRNA levels.

Animals

Functional evaluation of peripheral-nerve repair and the effect of hyperbaric oxygen.

The effect of hyperbaric oxygen (HBO) on peripheral-nerve recovery following devascularization and repair was studied, using the rat sciatic-nerve model. The right sciatic nerve was mobilized, stripped of the extrinsic blood supply, transected, and repaired in an epineurial fashion, using microsurgical technique. Following repair, animals were randomized into one of two groups: 1) control--no HBO (n = 20); 2) HBO treatment--twice daily for one week (1.75 hr dives, 100 percent O2, 2.5 ATA) (n = 16). Nerve recovery was assessed weekly (total of 10 weeks) by walking-track analysis, from which the sciatic function index (SFI) was calculated for each animal. Mean SFI scores were improved in the HBO-treatment group over controls, becoming statistically significant at weeks 7 through 10. These results suggest that functional recovery in transected, devascularized, peripheral nerves may be improved by 1 week of HBO treatment following microsurgical repair.

Animals

Influence of periodontal bacteria and disease status on V beta expression in T cells.

Some bacterial antigens such as S. aureus enterotoxins can selectively stimulate T cells that express specific V beta genes of the T cell antigen receptor (TCR). The purpose of this study was to investigate whether or not periodontal bacteria could similarly alter the expression of V beta families within the TCR complex. Peripheral blood mononuclear cells (PBMNCs) were isolated from 12 patients with early onset periodontitis and 11 periodontally-healthy controls. PBMNCs were incubated in media alone, or co-cultured for 48 h with heat-inactivated A. actinomycetemcomitans, P. gingivalis and P. intermedia. Expression of five V beta families (V alpha beta 2, V beta 5, V beta 6, V beta 8, and V beta 12) was determined by use of monoclonal antibodies. Mean unstimulated expression of V alpha beta 2 and V beta 8 was significantly higher (p < 0.05) in patients than healthy controls. Co-culture with the three bacteria resulted in significant changes (increases or decreases) in V beta expression in 27% of the trials. There were no significant differences in the number or direction of changes in samples from patients and controls. When compared to unstimulated controls, 18 significant increases but no decreases in the percentage of cell expressing V alpha beta 2, V beta 5 or V beta 6 were noted following co-culture with P. intermedia. Overall, co-culture with P. intermedia significantly (p < 0.05) up-regulated expression of the five V beta families studied. These data suggest that periodontal bacteria may alter V beta expression within the T cell receptor complex.

Adult

Musculoskeletal neoplasm: perineoplastic edema versus tumor on dynamic postcontrast MR images with spatial mapping of instantaneous enhancement rates.

PURPOSE: To evaluate the utility of fast, contrast-enhanced, sequential magnetic resonance (MR) imaging in differentiating between extraosseous tumor and perineoplastic edema. MATERIALS AND METHODS: Fourteen patients underwent sequential MR imaging (3.5 seconds per image) after bolus administration of gadopentetate dimeglumine. Initial rates of enhancement (initial slope) were calculated on a pixel-by-pixel basis and displayed as a "slope image"' in which pixel intensity reflected the slope value. Close correlation with wedge biopsy specimens was performed. RESULTS: Mean initial slope values were viable extraosseous tumor, 9.33 (standard deviation, 2.23); infiltrated muscle, 9.07 (2.31); edematous muscle without tumor infiltration, 5.48 (1.27); normal muscle, 1.11 (0.65). Differences in initial slope between all neoplastic and nonneoplastic tissues were statistically significant. Within individual patients, initial slope of edematous muscle was always 20% or more lower than that of neoplastic tissue. Slope images highlighted areas of viable extraosseous tumor and infiltrated muscle against edematous and normal tissues. CONCLUSION: Computer-generated slope images derived from sequential postcontrast MR images allow differentiation between tumor and nonneoplastic edema and may thereby guide the surgeon in planning limb-sparing procedures.

Adolescent

Effect of IL-7 or IL-4 on reconstitution of donor lymphoid cells in congenic murine bone marrow transplantation.

IL-7 and IL-4 are known to influence the growth of cells of the lymphoid lineage. In this study, we investigated the effects of in vivo administration of IL-7 or IL-4 in mice subjected to congenic BM transplant. C57BL/6 Ly5.1+ mice were subjected to TBI, followed by transfer of B and T cell-depleted BM from C57BL/6 Ly5.2+ donor mice. Recipient mice were implanted with 14-day miniosmotic pumps that delivered IL-7, IL-4 or PBS and were examined for reconstitution of lymphoid cells using flow cytometry on different days. We observed no significant difference in the number of splenocytes, thymocytes and PBLs between recipient mice administered with cytokines or normal control mice. However, we observed that IL-4 infusion resulted in appearance of increased numbers of donor CD23+B220+ cells and also donor cells expressing Fc receptors for IgM (Fc micro R) and B220. Since CD23 is present only on mature B cells, our data demonstrate that following BMT, IL-4 treatment results in the development of more mature B cells compared to control mice. Additionally, we observed that IL-7 infusion resulted in significantly decreased expression of donor sIgM+B220+ cells. However, the effects of IL-7 or IL-4 were observed when the cytokines were actively administered and rapidly abated upon cessation of cytokine therapy.

Animals

Viruria during acute Japanese encephalitis virus infection.

In this study, viruria following Japanese encephalitis virus (JEV) infection in mice has been shown to appear earlier in pregnant than in normal mice with proteinuria and haematuria. This was related to the production of splenic macrophage derived neutrophil chemotactic factor (MDF) following JEV infection. Intravenous inoculation of MDF in mice resulted in leakage of cells, proteins and erythrocytes in the urine as a result of altered capillary permeability. The isolation of virus from kidney did not correlate with the shedding of virus in the urine. The histological examination of sections of kidneys showed no morphological damage; however, ultrastructural degenerative changes in the mesangial cells were observed following JEV infection. These data suggest that JEV-induced macrophage derived factor regulates the leakage of proteins, erythrocytes and cells into the urine.

Acute Disease

Immunoregulatory abnormalities in patients with Epstein-Barr virus-associated B cell lymphoproliferative disorders.

EBVirus-associated B cell lymphoproliferative disorder (BLPD) is a recognized complication of primary immunodeficiency and organ as well as bone marrow transplantation. Although the nature of the immune defects that predispose to the development of BLPD are unknown, it is postulated that aberrant T cell responses are involved. It is our hypothesis that unbalanced lymphokine production is a major contributory factor to abnormal B cell growth in response to EBV, resulting in BLPD. Since IFN-alpha and IL-4 are important regulators of B cell proliferation and also regulate the synthesis of IgE, we determined serum levels of IFN-alpha, IL-4, and IgE in 8 patients with newly diagnosed BLPD. Comparison was made to healthy recipients of organ transplants on immunosuppressive therapy without BLPD, and normal EBV seropositive controls. Levels of serum IL-4 were significantly elevated in both patients with BLPD as well as in healthy immunosuppressed organ transplant recipients as compared with normal healthy individuals. Patients with BLPD exhibited a combination of significantly lower levels of serum IFN-alpha, and significantly higher levels of serum IgE than either healthy EBV seropositive individuals or healthy recipients of organ transplants on immunosuppressive therapy. These results suggest that imbalance in the proportions of circulating cytokines favoring B cell proliferation may be contributing to the development of EBV-associated BLPD. The potential significance of the finding of low IFN-alpha in patients who develop BLPD is exemplified by our recent success in the treatment of BLPD with IFN-alpha and intravenous IgG.

Adolescent

12-Deoxyphorbol-13-O-phenylacetate 20 acetate [an agonist of protein kinase C beta 1 (PKC beta 1)] induces DNA synthesis, interleukin-2 (IL-2) production, IL-2 receptor alpha-chain (CD25) and beta-chain (CD122) expression, and translocation of PKC beta isozyme in human peripheral blood lymphocytes: evidence for a role of PKC beta 1 in human T cell activation.

To determine a role of protein kinase C (PKC) isozymes in lymphocyte activation, human peripheral blood mononuclear cells were activated with 12-deoxyphorbol-13-O-phenylacetate (dPP; an agonist of both calcium-dependent and calcium-independent PKC isozymes), thymeleatoxin (TX; an activator of calcium-dependent PKC alpha, beta, and gamma), and 12-deoxyphorbol-13-O-phenylacetate 20 acetate (dPPA; an activator of PKC beta 1 isozyme) and examined for DNA synthesis, lymphocyte proliferation, interleukin-2 (IL-2) production, expression of IL-2 receptor alpha and beta chains on CD3+, CD4+, and CD8+ T lymphocytes and CD20+ B lymphocytes, and translocation of PKC beta isozyme from cytosol to membrane fraction. The results show that dPPA activates lymphocytes by inducing the above changes in a manner analogous to that of dPP, TX, and phorbol myristate acetate. These data suggest that PKC beta 1 is involved in the activation of human peripheral blood T and B lymphocytes.

DNA

Regulation of vascular permeability by macrophage-derived chemotactic factor produced in Japanese encephalitis.

The vascular effects of Japanese encephalitis virus (JEV)-stimulated splenic macrophage-derived neutrophil chemotactic factor (MDF) were evaluated in mice. Intraperitoneal injection of MDF in mice resulted in a rapid increase in capillary permeability in a dose-dependent manner as assessed by leakage of intravenously injected radiolabelled albumin ([125I]-albumin) or Evans blue dye. Intradermal inoculation of MDF in rabbits caused [51Cr]-labelled neutrophil emigration and accumulation into injected sites. Peak plasma leakage and neutrophil infiltration were observed at 1 h following MDF inoculation, and plasma leakage was restored by 2.5 h. The increase in capillary permeability was sensitive to pretreatment of mice with avil and ranitidine (H1 and H2 histamine receptor blockers, respectively), resulting in abrogation of the response; indomethacin, a prostaglandin synthetase inhibitor, did not have any effect.

Animals

Radiological and neurophysiological changes in Japanese encephalitis.

Six patients with Japanese encephalitis, four males and two females whose age ranged between 2 and 47 years, were subjected to neurophysiological and radiological studies. An EEG in five of the patients showed diffuse delta wave activity and one had an alpha coma. Delta activity seems to be due to thalamic involvement, which was seen on CT of two and MRI of all the patients. The thalamic lesions were characteristically bilateral and were haemorragic in five. Changes on MRI included abnormalities of the brainstem in three and the basal ganglia and spinal cord in one patient each. Lower motor neuron signs were present in three patients but abnormal MRI signals in the spinal cord were present in only one out of three patients in whom spinal MRI was carried out. Central motor conduction time in the upper limb was prolonged in three patients (five sides) and in the lower limbs in one (both sides), which was consistent with involvement of the cerebral cortex, thalamus, brainstem, and spinal cord. Changes in MRI and EEG in the acute stage may provide early diagnostic clues in patients with Japanese encephalitis.

Acute Disease

Clinical predictors of Japanese encephalitis.

Over a 5-year period, virological investigations for Japanese encephalitis (JE) were conducted in children presenting with acute encephalopathic illness. Clinical features of JE-positive patients (n = 116) were compared with patients in whom the diagnosis could be excluded (n = 57). Multivariate analysis by logistic regression revealed that two clinical signs--central hyperpneic breathing pattern and extrapyramidal signs--were significant predictors of the diagnosis. Application of the model yielded a sensitivity of 41.3% and a specificity of 80.7% with positive and negative predictive values of 81.3 and 40.3%, respectively. This indicates that the model may be helpful in making the diagnosis but not in excluding it. The model should be further validated in different areas where the disease is prevalent.

Child

Role of calcium in neutrophil activation by Japanese encephalitis virus-induced macrophage derived factor.

The role of cytosolic Ca2+ concentration in neutrophils stimulated with macrophage derived neutrophil chemotactic factor (MDF) produced following Japanese encephalitis virus (JEV) infection in mice was correlated with cell functions. MDF-induced Ca2+ influx from extracellular milieu and release from intracellular store resulted in rise of cytosolic Ca2+ in a dose-dependent manner and was independent of protein kinase C. Macrophages and B cells did not show cytosolic Ca2+ changes while T lymphocytes showed slight rise when stimulated with MDF. Neutrophil chemotaxis in the absence of Ca2+ was slightly different from that in presence of Ca2+. Pretreatment of neutrophils with 3,4,5-trimethoxy-benzoic acid-8-(diethylamine)-octylester (TMB-8) inhibited the chemotaxis. It was observed that superoxide production and degranulation by neutrophils after stimulation with MDF was not dependent on the presence of extracellular calcium, but stripping of intracellular calcium resulted in abrogation of neutrophil activation. Thus, mobilization of intracellular calcium seems to be necessary for neutrophil activation by MDF.

Alkaloids

Lymphoproliferative disorders and other tumors complicating immunodeficiencies.

Lymphoproliferative disorders and selected carcinomas which occur as complications of primary or secondary immunodeficiencies are frequently fatal. The incidence rates of these cancers vary from 1% to as high as 25% among specific groups of persons with primary (genetically-determined) immunodeficiencies as well as acquired immunodeficiencies, including immunosuppressed organ transplant recipients and individuals infected with HIV. Lymphoproliferative disorders including Epstein Barr virus (EBV) associated B cell lymphoproliferative disease (BLPD) and Hodgkin's disease represent the predominant category of tumors in both primary and acquired immunodeficiencies. EBV is an important cofactor common to many, but not all, B cell "lymphomas." Immunodeficient individuals who are at risk for developing EBV BLPD may demonstrate both inadequate immune responses to the virus as well as generalized immunoregulatory dysfunction reflected as imbalances in cytokine production favoring the proliferation of transformed B lymphocytes. Historically, the success of treatment of lymphoproliferative disorders in immunodeficiencies with conventional multi agent chemotherapies and/or radiation has been limited by unfavorable tumor response rates and high morbidity and mortality related to intercurrent opportunistic infections. With improvements in supportive care and the use of recombinant biologic response modifiers such as alpha interferon and/or other immunotherapies to treat EBV BLPD, survival of immunodeficient hosts following tumor diagnosis may improve. In addition to lymphoproliferative disorders, patients with congenital immunodeficiencies associated with IgA deficiency (including ataxia telangiectasia and Common Variable Immunodeficiency) are at increased risk for gastrointestinal carcinomas. Early detection and surgical excision of such tumors can result in prolonged survival in such patients.

Humans

Thrombin-fibrinogen interaction: pH dependence and effects of the slow-->fast transition.

A recently developed strategy capable of measuring the equilibrium dissociation constant for thrombin-fibrinogen interaction has been used to explore the pH dependence of the interaction and the effects of thrombin conformational transitions. The dependence of fibrinogen binding to thrombin in the pH range 6-10 is bell-shaped and remarkably similar to that obtained in the case of the small synthetic amide substrate tosyl-Gly-Pro-Arg-p-nitroanilide-AcOH. Since the synthetic substrate contains no groups that can ionize in the pH range 6-10, the bell-shaped curve must reflect ionization reactions of two groups of the enzyme with pK1 = 7.53 +/- 0.09 and pK2 = 8.80 +/- 0.09. These groups can be identified as the catalytic histidine, His57, and the amino terminus of the B chain, Ile16, respectively. Deprotonation of His57 in the acidic region is important for optimal binding, while protonation of Ile16 in the alkaline region is critical for the formation of a salt bridge with Asp194, which guarantees the conformational stability of the enzyme. The loss of binding free energy at low (< 7.0) and high (> 9.0) pH values is linked to protonation of His57 and deprotonation of Ile16, respectively. The first 51 residues of the A alpha chain of fibrinogen are known to be necessary and sufficient for optimal recognition by thrombin, but none of them contributes to the pH dependence of fibrinogen binding in the pH range examined. Hence, the two possible ionizable groups of the A alpha chain, i.e., the amino terminus Alal and His24, make no contacts with the thrombin surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation

Rewarding brain stimulation: role of tegmental cholinergic neurons that activate dopamine neurons.

Cholinergic neurons of the pedunculopontine nucleus (Ch5) are believed to monosynaptically excite ventral tegmental dopamine neurons. Muscarinic blockers injected near dopamine cells block the rewarding effect of hypothalamic or dorsal tegmental rewarding brain stimulation (RBS) in rats. Because Ch5 cells are inhibited by muscarinic agonists, we injected muscarinic drugs unilaterally near Ch5 neurons to inhibit or disinhibit them. Carbachol raised thresholds for hypothalamic self-stimulation bilaterally by over 400%, whereas scopolamine reduced thresholds by 20%-80%. Pretreatment with either carbachol or scopolamine blocked the effect of the other drug, which suggests that both acted through the same receptors near Ch5 cells. Therefore, activation of Ch5 neurons is critical for hypothalamic RBS. A mechanism for the involvement of Ch5 neurons in drug rewards and antimuscarinic psychosis is also proposed.

Animals

Marital adjustment and subjective well-being in Indian-educated housewives and working women.

We compared marital adjustment and subjective well-being in Indian-educated housewives (N = 200) and working women (N = 200) who were administered a Marital Adjustment Questionnaire (Kumar & Rastogi, 1976) and 10 measures of subjective well-being (Warr, 1984). Results indicated significantly better marital adjustment and subjective well-being for the working women than for the housewives. Specifically, working women reported higher scores on general health, life satisfaction, and self-esteem measures and lower scores on hopelessness, insecurity, and anxiety, compared with the housewives, although the housewives had lower scores on negative affect than the working women. Findings were insignificant on positive affect and depression.

Adaptation, Psychological