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Biomedical subjects

A Mathur

Publications and source records attributed to A Mathur.

At least 73 records · Page 4Linked to original sources

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

Assessment of the skeletal status by peripheral quantitative computed tomography of the forearm: short-term precision in vivo and comparison to dual X-ray absorptiometry.

In order to assess precision of peripheral quantitative computed tomography (pQCT), duplicate bone mineral density (BMD) measurements at the radius were performed in 20 healthy premenopausal, 20 healthy postmenopausal, and 20 osteoporotic postmenopausal women using a Stratec XCT-960 system. The short-term reproductibility in vivo for the total, trabecular, and cortical regions of interest (ROI) was expressed as the absolute precision error (standard deviation, SD) and as the relative precision error (SD/mean x 100, or coefficient of variation, CV, in %). Reproducibility in vivo was good in all volunteers but was influenced by the study group and the ROI. The precision error for trabecular BMD was 3 mg/cm3, or about 1.6%. This is large relative to the aging decrease of 0.22%/year, or to the difference (12 mg/cm3, or 7%) between osteoporotic women and postmenopausal controls. In order to compare pQCT to dual X-ray absorptiometry (DXA) at the forearm and at the lumbar spine (L1-L4), 40 premenopausal healthy controls, 40 postmenopausal healthy controls, and 35 postmenopausal osteoporotic women were assessed. DXA measurements performed at the ultradistal, middistal, 1/3, and total ROI of the radius showed only moderate correlations between r = 0.38--0.75, r = 0.27--0.64, and r = 0.38--0.53 for the comparison versus pQCT total BMD, versus pQCT trabecular BMD, and versus pQCT cortical BMD, respectively. Correlations of DXA at the lumbar spine and pQCT were between r = 0.18 and 0.44. DXA at radius and spine was able to discriminate between post- menopausal controls and osteoporotic women (p = 0.001--.004),but BMD measurements by pQCT did not show this ability (p = 0.15--0.52). However, two nonstandard pQCT parameters, namely the surface area of the cortical bone and the cortical BMC were factors that discriminated well between these two groups (p = 0.002, p = 0.005, respectively). These pQCT parameters also yielded the highest relative annual changes in pre- and post-menopausal control subjects. The measurement of cortical bone in the distal radius proved to be a good predictor of vertebral fracture status and was a good indicator of age-related skeletal change. Our data emphasize the importance of cortical measurements when using pQCT of the radius to assess osteoporosis.

Absorptiometry, Photon

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

Undetectable interferon-alpha serum levels in a patient with atopic dermatitis.

A 3-year-old boy [corrected] was evaluated for the possible diagnosis of hyperimmunoglobulin E syndrome (HIES). From the age of 4 months he developed significant atopy and was subsequently diagnosed with severe atopic dermatitis, asthma, and allergic rhinitis, with moderately high total serum IgE levels. Because IgE production has been shown to be regulated by cytokines produced by the CD4+ helper T lymphocyte subsets, we measured the circulating levels of cytokines representative of these cellular subsets in this patient. We therefore measured serum levels of interleukin-4 (IL-4), the Th2 subset-derived cytokine that upregulates IgE synthesis, as well as the levels of interferon-gamma and interferon-alpha (IFN-gamma/alpha), cytokines produced by the Th1 subset that inhibit IL-4-mediated IgE upregulation. We found that in this patient, IL-4 levels were normal, indicating normal Th2 activity. The levels of IFN-gamma were higher than normal, but the serum IFN-alpha levels in this patient were undetectable and were actually below the normal range. Thus, even though both IFN-gamma and IFN-alpha have been shown to be necessary for controlling IL-4 actions, the selective absence of IFN-alpha, even in the presence of normal or increased amounts of IFN-gamma, could permit IL-4 induced IgE production. Lack of IFN-alpha may explain this patient's recurrent infections, as well as IgE-induced atopic conditions. Our data in this study with the patient showing selective deficiency of IFN-alpha but not of IFN-gamma provide support for the role of IFN-alpha in the pathogenesis of atopic dermatitis. The findings in this patient clearly warrant further studies of IFN-alpha in patients with atopic disorders.

Asthma

Specific decrease of Th1-like activity in mice with plasma cell tumors.

Previously we examined the ability of the host's immune responses to regulate Ig production in an IgE-secreting murine plasma cell tumor (B53). In the present study we have examined the reverse phenomenon, in that we have investigated the effects of this and other plasma cell tumors on the immune responses of their hosts. We found that splenocytes from plasma cell tumor-bearing mice demonstrate decreased proliferation in response to polyclonal stimulation by either Con A or a combination of PMA and calcium ionophore (A23187). Fractionation of the splenocytes demonstrated that this reduction in proliferation was confined to CD4+ T cells and that the proliferation of CD8+ T cells was unaffected. In order to determine whether the down-modulatory effects of the tumor were confined to a particular CD4+ helper T cell subset, we examined the production of cytokines representing the Th1 subset (IL-2 and IFN-gamma) and the Th2 subset (IL-4 and IL-10) from stimulated splenocytes and from stimulated enriched splenic T cells. We found that both stimulated splenocytes and T cells from plasma cell tumor-bearing mice produced lower levels of the Th1 cytokines IL-2 and IFN-gamma compared with normal cultures, demonstrating that Th1-like responses are inhibited in the hosts of these tumors. However, no alterations in the production of the Th2 cytokines IL-4 and IL-10 were observed in these stimulated splenocyte or T cell cultures from the tumor-bearing mice.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Intracoronary stent placement in thrombus containing vein graft lesions.

Intracoronary stents are traditionally considered to be contraindicated in presence of thrombus. However recent advances in stent deployment technique have reduced the risk of stent thrombosis. We report the placement of a stent in a thrombus laden saphenous vein graft to the posterior descending artery. Three months later the stent site was patent with severe stenosis with thrombus in another graft which was also stented. Intracoronary stents should be considered in patients with complex lesion even in presence of intraluminal thrombus.

Angioplasty, Balloon, Coronary

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

Investigation of malaria outbreak in Rajasthan.

Jaisalmer and Barmer districts in the Thar Desert of Rajasthan experienced an unprecedented rains during 1994 leading to an outbreak of malaria. Investigations were carried out at three sites in two districts (i) Pokaran PHC and (ii) Nachana PHC in Jaisalmer district and Dhorimana in Barmer district during November 1994. Epidemiological and entomological studies in Pokaran PHC revealed presence of small foci of stable malaria. These foci were maintained by large bodies of water (ponds/lakes) drained from surrounding areas and spread over 1 to 5 sq km. Slide positivity rate (SPR), slide falciparum rate (SfR) and child spleen rate (SR) were 60.1, 56.9 and 86.9%, respectively with 3 deaths reported. Adjoining villages experienced epidemic reporting deaths fed by the reservoir from these stable foci. An. culicifacies and An. stephensi were the major malaria vectors. Nachana PHC recorded stable malaria foci of irrigation malaria due to introduction of Indira Gandhi Canal (IGC). SPR, SfR and SR recorded were 52.35, 50.58 and 80.8%, respectively. Transmission appeared to be maintained by An. stephensi, An. culicifacies and An. fluviatilis in relays. An. fluviatilis seems to have established breeding in silted grassy margins of IGC. Dhorimana PHC in border district was also found to be a stable malaria foci although with low malaria indices. However, An. culicifacies and expanded breeding potential of An. stephensi were the main factors in maintaining malaria endemicity in the region.

Animals

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