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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 775 records · Page 43Linked to original sources
PubMed1997

Neuroanatomical substrates of late-life minor depression. A quantitative magnetic resonance imaging study.

OBJECTIVE: To examine the neuroanatomical correlates of late-life minor depression using magnetic resonance imaging. DESIGN: Cross-sectional quantitative magnetic resonance imaging study of elderly patients with minor depression and age-matched controls. SETTING: Patients and controls were recruited from the community through advertisements to the Section of Geriatric Psychiatry, University of Pennsylvania, Philadelphia. PARTICIPANTS: Our sample included 18 subjects diagnosed as having minor depression using the modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, research criteria and 31 controls without depression. Patients were free of other central nervous system disease and both groups had comparable degrees of medical comorbidity. MAIN OUTCOME MEASURES: All images were acquired on a 1.5-T scanner and absolute and normalized quantitative measures of global and focal brain and cerebrospinal fluid volumes were compared between groups. RESULTS: Prefrontal lobe volume was significantly smaller in the group with minor depression (P = .002) compared with controls after controlling for age, sex, and age by sex interactions. More global measures of brain and cerebrospinal fluid volumes were comparable in both groups. CONCLUSIONS: These data suggest that focal prefrontal atrophy may provide an important neuroanatomical substrate in late-life minor depression.

Aged↗
PubMed1997

Argyrophilic nucleolar organizer regions: their value and correlation with clinical prognostic factors in breast carcinoma.

BACKGROUND AND OBJECTIVES: Argyrophilic nucleolar organizer regions (AgNORs) have been recently identified as a marker of proliferative index in various tumors. These were evaluated in 46 patients with primary breast carcinoma and were correlated with clinical prognostic parameters of breast cancer. Ten patients with benign breast tumors served as controls in the study. METHODS: AgNORs were stained in paraffin sections of the tissues using Ploton's silver technique. For each specimen, the number of AgNORs, within the nuclei of 100 tumor cells were calculated. The average number of AgNORs per nucleus was calculated and the results expressed as mean +/- S.D. RESULTS: AgNOR count was significantly higher in breast carcinoma (6.61 +/- 1.75) than in benign breast tumors (1.88 +/- 0.19). Further, the AgNOR count in breast carcinoma showed a statistically significant increase in correlation with the increase in the size of the tumor, stage of the cancer, number of metastatic lymph nodes, and tumor recurrence at various sites. However, the differences in AgNOR count at different lymph node levels and histologic grading were not statistically significant. CONCLUSIONS: These results indicate that breast tumors with a higher AgNOR count, even at the initial stage, have a poor prognosis and require aggressive treatment for better control of the disease. Further, it is suggested that the patients with a benign tumor and more than three AgNORs per nucleus need careful surveillance.

Adult↗
PubMed1997

Epinephrine attenuates down-regulation of monocyte tumor necrosis factor receptors during human endotoxemia.

Epinephrine inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production by increasing intracellular cAMP concentrations. Because agents that increase cAMP levels can enhance TNF receptor expression in vitro, granulocyte and monocyte TNF receptors were determined by FACS-analysis in 7 normal humans who were receiving a constant 24-h infusion of epinephrine (30 ng/kg/min), and in 15 normal subjects after intravenous injection of LPS (2 ng/kg), while they were receiving a continuous infusion of epinephrine started either 3 h (EPI-3) or 24 h (EPI-24) before LPS injection or an infusion of normal saline (LPS; n = 5 per group). Infusion of epinephrine per se did not influence TNF receptor expression. LPS induced a transient decrease in monocyte TNF receptors and a more sustained decrease in granulocyte TNF receptors (both P < 0.05). EPI-3 partly prevented LPS-induced down-modulation of monocyte TNF receptors (P < 0.05 vs. LPS only), but did not affect LPS-induced down-modulation of granulocyte TNF receptors. EPI-24 had no effect on TNF receptor expression. These data suggest that epinephrine not only influences the bioavailability of TNF by an effect on the production of this proinflammatory cytokine, but also by modulating the expression of its receptors.

Adult↗
PubMed1997

Analysis of spin diffusion and cross correlation on the net nuclear Overhauser effect in NMR.

The effect of dipole-dipole cross correlations on the net nuclear Overhauser effect (NOE) has been analyzed here for realistic systems by extending the three-spin calculations to four and five spins in order to account for additional cross correlations and spin diffusion. These have been compared with the addition of leakage terms to the three-spin system. The additional spins enhance cross-correlation effects on one hand but on the other act as supplementary relaxation pathways for the magnetization to diffuse. This analysis shows that for a linear array of spins in the long-correlation limit, dipole-dipole cross correlations increase net NOE, while spin diffusion decreases it, and that the cumulative effect is a reduced effect of cross correlations. In other geometries and correlation limits, the effect of cross correlations on net NOE is generally small.

Magnetic Resonance Spectroscopy↗
PubMed1997

Outcome of polyarteritis nodosa in northern India.

Over the last 10 years, 17 patients (13 males and 4 females) diagnosed as having classical polyarteritis nodosa (PAN) were treated and followed up in the rheumatology clinic of our institute. The median age and duration of symptoms at presentation were 29 years (range 13-59) and 9.5 months, respectively. Patients presented with the typical clinical picture of classical PAN. The diagnosis was established with the help of an aortogram (7/10), sural nerve biopsy (7/8), muscle biopsy (5/7) and renal biopsy (3/4). For reasons not known, none of the 17 patients was HBsAg positive. Patients were treated with a combination of oral prednisolone (1 mg/kg per day) for 6 weeks, which was slowly tapered off over 6 months, and monthly intravenous cyclophosphamide pulses (15 mg/kg) for the first 6 months, followed by 3-monthly pulses for a total of 2 years. Remission was achieved in 14 patients after a median of 5 months of treatment. Remission was stable for a median of 5 years of follow-up. Three patients did not respond well and died within 6 months of diagnosis. The causes of death in these were intracerebral haemorrhage in one patient and gastrointestinal bleeding in two patients. This experience is in accord with the reported literature that classical PAN is mostly a monophasic disease with either an excellent response to the appropriate immunosuppressive therapy and a long remission or a downhill course culminating in death. A chronic course is rare.

Administration, Oral↗
PubMed1997

Simultaneous bilateral thalamic hemorrhages following the administration of intravenous tissue plasminogen activator.

A patient suffered the onset of simultaneous bilateral thalamic hemorrhage several hours after the administration of intravenous tissue plasminogen activator. The patient exhibited features of the paramedian diencephalic syndrome, including executive dysfunction, anterograde amnesia, inattention, and disturbances of visual perception. During rehabilitation, she made significant gains in overlearned activities of daily living tasks, but her inability to retain new information left her severely disabled. The use of intravenous thrombolytic therapy is believed to account for this patient's unusual stroke syndrome. With recent evidence supporting the efficacy of intravenous thrombolysis in acute stroke, patients with multiple hemorrhagic strokes as a result of thrombolysis may become more common on rehabilitation services.

Aged↗
PubMed1997

A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum.

OBJECTIVES: Prostate-specific antigen (PSA) is a widely used serum marker for human prostate cancer (PCa). The majority of PSA in serum is present as a complex with alpha-1-antichymotrypsin (ACT). In recent years, the ratio of free (uncomplexed) to total PSA has shown improved discrimination of PCa from benign prostatic hyperplasia. This study examines the nature of the free PSA from detected in PCa serum and shows that some of the uncomplexed PSA is an inactive precursor of PSA (pPSA). METHODS: Western blot analysis was used to detect clipped, fragment forms of PSA in sera and seminal fluid. Hydrophobic interaction chromatography-high performance liquid chromatography (HIC-HPLC) was used to identify forms of PSA present in the free PSA population. Pooled sera was passed over a PSA immunoaffinity column, and the eluted PSA components were further resolved by HIC-HPLC. RESULTS: Western blot analysis of whole sera showed complexed PSA and the intact, approximately 34 kilodalton free PSA. Only negligible levels of clipped or degraded forms of PSA, as found in seminal fluid, were detected. Column fractions measured for uncomplexed PSA using the Tandem-MP free PSA assay showed that about 25% of the free PSA eluted as pPSA beginning at the [-4]amino acid. Studies with purified recombinant [-4]pPSA showed that this proenzyme form is inactive and does not complex with ACT. CONCLUSIONS: These results suggest that the uncomplexed PSA in PCa serum is primarily unclipped PSA that contains a significant fraction of pPSA.

Humans↗
PubMed1997

Effect of centrally administered endothelin agonists on systemic and regional blood circulation in the rat: role of sympathetic nervous system.

The aims of the present study were to determine (1) the hypotensive and regional circulatory effects of centrally administered endothelin (ET) ETA and ETB agonists, and (2) the role of the sympathetic nervous system in the mediation of hypotensive effects due to centrally administered ET-1. The systemic haemodynamics and regional blood circulation in urethane anaesthetized rats following intracerebroventricular (i.c.v.) administration of ET-1, ET-2, SRT6b, ET-3 and SRT6c (10, 30 and 90 ng) were determined by a radioactive microsphere technique. The effect of centrally administered ET-1 on sympathetic nerve activity was also analysed. Systemic haemodynamics and regional blood circulation were determined before (baseline) and 30 min after administration of ET agonists. Cumulative administration of three doses of saline (5 microliters, i.c.v. at 30 min intervals) did not produce any significant cardiovascular effects. ET-1, ET-2 and SRT6b produced a decrease in blood pressure (51%, 47% and 41%, respectively) along with a decrease in cardiac output (58%, 60% and 45%, respectively) and stroke volume. Heart rate and total peripheral resistance were not affected. ET-1, ET-2 and SRT6b also produced a significant reduction in blood flow to the brain, kidneys, heart, portal, mesentery and pancreas, gastrointestinal tract (GIT) and musculoskeletal system. The effect of ET-2 on the cardiovascular system was less intense in comparison with ET-1 and SRT6b. Centrally administered specific ETB receptor agonists ET-3 and SRT6c did not produce any change in systemic haemodynamics and regional blood flow. Centrally administered ET-1 (90 ng) produced a significant decrease (61%) in sympathetic nerve activity 30 min after drug administration, along with a fall in blood pressure. It is concluded that centrally administered ETA agonists produce significant cardiovascular effects mediating through the sympathetic nervous system.

Animals↗
PubMed1997

Autologous lymphoblastoid cell lines stably transfected with Plasmodium falciparum circumsporozoite protein as targets in cytotoxic T-lymphocyte assays.

To produce cell lines that can be used as a continuous source of antigen presenting cells for stimulating T-cell lines and clones and as targets in cytotoxic T-lymphocyte (CTL) assays, we used a retroviral vector with a simian virus (SV40) early promotor to transfer a Plasmodium falciparum circumporozoite (PfCSP) gene into human EBV transformed B-lymphoblastoid cell lines (B-LCL). We herein report successful, stable transfection and cell surface expression of this gene, as confirmed by PCR, Western blot analysis and immunoelectron microscopy. One of three successfully transfected autologous cell lines expressed PfCSP on the cell surface and was lysed by CD8+ T-cell dependent CTL from a donor volunteer who had been immunized with irradiated P. falciparum sporozoites. Such cell lines should provide excellent tools for characterizing human CD8+ T-cell responses against Plasmodium sp. proteins.

Animals↗
PubMed1997

Effect of prolactin on nitric oxide and interleukin-1 production of murine peritoneal macrophages: role of Ca2+ and protein kinase C.

In vitro treatment of macrophages with prolactin (PRL) was found to increase the production of nitric oxide (NO) and interleukin-1 (IL-1). Production of NO and IL-1 by macrophages got additively enhanced on simultaneous treatment with LPS and PRL. The production of NO was, however, decreased when the macrophages were treated with a combination of PRL and nifedipine, a Ca2+ blocker indicating a role of Ca2+ in the activation of macrophages with PRL. PRL-treated macrophages showed an enhanced translocation of protein kinase C (PKC) from cytosol to the membrane, indicating that PRL activates macrophages via the activation of PKC.

Animals↗
PubMed1997

Effect of ETA receptor antagonists on cardiovascular responses induced by centrally administered sarafotoxin 6b: role of sympathetic nervous system.

The present study was carried out to investigate the cardiovascular effects of centrally administered SRT6b in saline, BQ123 and BMS182874 pretreated male Sprague-Dawley rats, using a radioactive microsphere technique. SRT6b (100 ng, ICV) produced a transient increase (40%) in blood pressure at 5 min followed by a sustained decrease (-42%) at 30 and 60 min in control rats. Total peripheral resistance and heart rate were not significantly altered. Cardiac output increased (16%) at 5 min and decreased 30 and 60 min following SRT6b administration. Central venous pressure was not affected by SRT6b. Regional blood flow and vascular resistance did not change at 5 min following administration of SRT6b. However, a significant decrease in blood flow to the brain, heart, kidneys, liver, spleen, gastrointestinal tract and mesentery and pancreas was observed 30 and 60 min following administration of SRT6b in control (saline treated) rats. Pretreatment with ETA selective receptor antagonists, BQ123 (10 micrograms, ICV) or BMS182874 (50 micrograms, ICV) significantly attenuated the pressor and depressor effects of centrally administered SRT6b. SRT6b induced decrease in blood flow was completely blocked by pretreatment with BQ123 or BMS182874. ET-1 (100 ng, ICV) produced an increase followed by a decrease similar to SRT6b. Reserpine (5 mg/kg, IP) pretreatment attenuated the cardiovascular effects of ET-1. Role of sympathetic nervous system was determined by measuring splanchnic nerve activity. SRT6b when administered in the lateral cerebral ventricle did not produce any significant effect at 5 min, however, a significant decrease in sympathetic nerve activity was observed 30 min after its administration. It is concluded that centrally administered SRT6b produces significant changes in systematic and regional blood circulation which can be completely blocked by ETA receptor antagonist. The cardiovascular effects of centrally administered SRT6b appear to be mediated through the sympathetic nervous system.

Animals↗
PubMed1997

Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain.

Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei including medial septum and the vertical limb of the diagonal band. Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A. These changes were accompanied by enhanced M1-muscarinic cholinergic receptor binding in lateral and medial septum as well as in frontal cortices, whereas the M2-muscarinic receptor binding sites were increased in a number of cortical regions including cingulate, frontal, piriform, parietal and retrosplenial cortex. Treatment with Shilajit or the defined extract from Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The data suggest that Shilajit and the defined extract from Withania somnifera affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from Withania somnifera observed in animals and humans.

Acetylcholinesterase↗
PubMed1997

Immune complex glomerulonephritis in patients coinfected with human immunodeficiency virus and hepatitis C virus.

Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, "collapsing" glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and "collapsing" glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group.

AIDS-Associated Nephropathy↗