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Biomedical subjects

A Mathur

Publications and source records attributed to A Mathur.

At least 55 records · Page 3Linked to original sources

Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid.

Cytokines play an important role in the pathology associated with chronic inflammatory diseases. We measured the total amounts [picograms (pg)] and concentrations.(pg/microliter) of interleukin-1 alpha (IL-1 alpha), interleukin-8 (IL-8) and interferon-alpha (IFN-alpha) in 20 s gingival crevicular fluid (GCF) samples obtained from 2 diseased and 2 healthy sites in 20 subjects with periodontitis, and from 2 healthy sites in 20 subjects without disease. Both the mean amount and concentration of IL-1 alpha were significantly higher (p < 0.001) in diseased sites compared to healthy sites in subjects with disease. The results for IL-8 and IFN-alpha differed depending on the method of reporting. Whereas the amount of IL-8 was significantly higher (p < 0.01) in diseased sites, the mean concentration of IL-8 was lower compared to healthy sites. The mean amount of IFN-alpha was similar in health and disease; however, the concentration of IFN-alpha was significantly lower in diseased sites (p < 0.001) corresponding to the significant increase in crevicular fluid volume (p < 0.001). There were no significant differences in the amount or concentrations of the 3 cytokines between healthy sites from subjects with disease and healthy sites from healthy controls. The total amounts of both IFN-alpha and IL-8 were correlated between healthy and diseased sites in subjects. These data suggest that, while the disease status of a site is the major determinant of the levels of these cytokines locally, subjects with high levels of IL-8 and IFN-alpha in healthy sites also tend to have high levels of these cytokines in diseased sites. Finally, both the concentrations and total amounts of IL-8 and IFN-alpha were significantly correlated in diseased sites, suggesting that levels of these two cytokines rise or fall in tandem. The combination of decreased IL-8 and decreased IFN-alpha concentrations at diseased sites may reflect the reduced anti-bacterial host defense activity at that site.

Adult

Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density.

PURPOSE: To determine the relationship between capillary density, a recognized surrogate of tumor angiogenesis, and magnetic resonance (MR) imaging-derived estimates of plasma volume (PV) and microvascular permeability in two mammary carcinoma models. MATERIALS AND METHODS: Dynamic spin-echo imaging was performed by using albumin-(gadolinium-diethylenetriaminepentaacetic acid)34, a prototype blood-pool contrast medium, in 14 rats with a subcutaneously implanted slow- or fast-growing subtype of R3230 mammary carcinoma. Data were fitted to an established two-compartment kinetic model to estimate PV and permeability. RESULTS: MR imaging-derived tumor PVs and permeabilities increased exponentially with increasing capillary density. MR imaging-derived microvascular characteristics correlated strongly with histologic capillary density, with an r2 of .85. CONCLUSION: Contrast medium-enhanced MR imaging may prove useful in estimating angiogenic activity in carcinomas. MR imaging may be superior to histologic assay because it is noninvasive, can be used to "sample" the entire tumor, and reflects both anatomic and physiologic characteristics.

Albumins

Osteoporosis: association of recent fractures with quantitative US findings.

PURPOSE: To study the association of quantitative ultrasound (US) parameters and bone mineral density (BMD) in patients with and patients without recent fractures. MATERIALS AND METHODS: The authors studied 4,698 women (69 years or older) who had sustained 1,363 new fractures, including 106 hip fractures, during the 7 years prior to the study. Broadband ultrasound attenuation (BUA) and other velocity parameters were measured by means of quantitative US of the calcaneus. BMD was measured at the spine, hip, and calcaneus. RESULTS: The standardized age-adjusted odds ratio for all fractures was 1.5 (95% confidence interval [CI] = 1.4, 1.7) for BUA and up to 1.6 (95% CI = 1.5, 1.7) for BMD. For hip fractures, the odds ratio was 1.9 (95% CI = 1.5, 2.4) for BUA and up to 2.6 (95% CI = 2.0,3.4) for BMD. Sensitivity and specificity with BUA, velocity parameters, and BMD were comparable. Results of multivariate analysis showed that both BUA and BMD were independently associated with fractures and that combined measurements improved sensitivity and specificity. CONCLUSION: Quantitative US parameters are strongly associated with risk of fracture and partly independent of BMD. This simple, low-cost, portable, and radiation-free approach may complement bone densitometry in assessing risk of osteoporotic fracture.

Aged

cGMP-dependent protein kinase inhibitors block light-induced phase advances of circadian rhythms in vivo.

Synchronization of circadian rhythms is thought to be accomplished primarily through daily phase delays and advances of the endogenous circadian clock that, in mammals, is located in the hypothalamic suprachiasmatic nucleus (SCN). In the SCN, numerous second messenger pathways may participate in photic signal transduction. In these studies, the involvement of cyclic nucleotide-dependent kinases was examined in vivo using inhibitors of adenosine 3',5'-cyclic monophosphate (cAMP)- and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent kinase (PKA and PKG, respectively). In constant dark, selective and nonselective inhibitors of PKG injected near the SCN of hamsters had no effect on phase delays produced by light pulses given in the early subjective night (early in the animals' active period) but significantly attenuated phase advances induced late in the subjective night. PKA inhibition had no effect at either time point. In addition, cGMP agonists had no effect on rhythmicity in the absence of light. The results suggest that PKG activity is necessary, but not sufficient, for normal photic responsiveness and that PKA activity is not required. The phase dependence of the effect of PKG inhibition supports the notion that photic entrainment is influenced by biochemical pathways that differentially regulate sensitivity in a phase-dependent manner.

Alkaloids

Detection of local and systemic cytokines in adult periodontitis.

Periodontitis is a chronic inflammatory disease of the soft and hard supporting tissues of the teeth and is a major cause of tooth loss in adults. The local host response to periodontopathic bacteria results in the release of inflammatory mediators and cytokines. Since cytokines are indicative of effector functions, we compared the pattern of cytokine production in periodontal patients and healthy controls. Specifically, we investigated the simultaneous presence of cytokines produced by T helper (Th)1, Th 2, and inflammatory cells which could be involved in periodontitis. We also compared the expression of these cytokine mRNAs in healthy and diseased tissues. No significant differences were detected at the protein or mRNA levels of the cytokines in the systemic circulation of patients and controls. The surface markers CD16 and CD56 were expressed on significantly fewer peripheral mononuclear cells of patients when compared to controls. gamma delta + T cells were found in half of the diseased tissues, but in none of the healthy tissues of either patients or controls. Finally, significant differences were observed between healthy and inflamed gingival tissues in the cytokine mRNA profile. Expression of IL-6 and IFN-alpha mRNA was significantly higher in diseased tissues compared to healthy tissues in patients.

Adult

Quantitative CT assessment of the lumbar spine and radius in patients with osteoporosis.

OBJECTIVE: We undertook this study to quantify the relationship between bone mineral assessments of the lumbar spine using quantitative CT (QCT) and of the radius using peripheral QCT (pQCT) and to test the sensitivity of both techniques in detecting changes in bone mass that are related to age and osteoporosis. SUBJECTS AND METHODS: Forty-two healthy premenopausal, 38 healthy postmenopausal, and 97 osteoporotic postmenopausal women were examined with pQCT of the distal radius and with QCT of the lumbar spine (L1-L4). The bone mineral density (BMD), bone mineral content (BMC), and a cross-sectional area of cortical bone were assessed at the distal radius. The BMD of trabecular and total bone and the BMC of total bone were assessed at the midvertebral bodies of the lumbar spine. RESULTS: In the healthy women, correlations of radial BMD with spinal trabecular and total BMD were modest (r = .39 and r = .49, respectively) but were higher for total BMC (r = .79). All correlations in osteoporotic women (r = .19 for trabecular BMD, r = .31 for total BMD, and r = .47 for total BMC) were lower than those in healthy women. For measurement of spinal bone mass in healthy women, trabecular BMD showed a higher correlation with age (r = .81) and a larger relative annual decrease (1.2%) than did total BMD (r = .75, .78%) or total BMC (r = .54, .55%). At the radius, the highest correlations with age were found for total BMC (r = .57, .53%), cortical area (r - .52, .67%), and cortical BMC (r = .48, .78%). Age-adjusted odds ratios for prevalent vertebral fractures were highest for total (4.5) and trabecular (4.4) spinal BMD. For radial measurements, odds ratios were highest for both total BMD (2.3) and cortical area (2.3). CONCLUSION: QCT of spinal trabecular bone showed the strongest capability for assessment of age-related bone loss and for discrimination of osteoporotic vertebral fractures. In comparison, pQCT of radial trabecular bone showed the weakest capability for these applications, and pQCT of radial cortical or total bone showed intermediate capability.

Aged

HIV-2 prevalence in Uttar Pradesh.

Serum samples collected since 1989 with various patterns of reactivity for human immunodeficiency virus (HIV)-1, on the basis of screening ELISA and confirmatory Western blot (WB) test, were subjected to the detection of HIV-2 infection based on screening dot immunoassay and confirmatory WB for HIV-2. Significant prevalence of HIV-2 infection was (37.03%) among sera reactive for HIV-1 by ELISA but indeterminate by Western blot, compared with sera reactive for HIV-1 by ELISA and WB (3.29%) or negative by WB (2.63%). Out of 16 HIV-2 positive sera, 5 (31.25%) showed evidence of concomitant HIV-1 infection. This study demonstrates evidence of HIV-2 infection as early as 1989, earlier than reported so far from India.

Acquired Immunodeficiency Syndrome

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

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

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