Biomedical subjects

V Natarajan

Publications and source records attributed to V Natarajan.

At least 19 recordsLinked to original sources

PubMed2006

Compact fluorescent lamp phosphors in accidental radiation monitoring.

The application of lamp phosphors for accidental dosimetry is a new concept. Since the materials used in fluorescent lamps are good photo luminescent materials, if one can either use the inherent defects present in the phosphor or add suitable modifiers to induce thermoluminescence (TL) in these phosphors, then the device (fluorescent lamp) can be used as an accidental dosemeter. In continuation of our search for a suitable phosphor material, which can serve both as an efficient lamp phosphor and as a good radiation monitoring device, detailed examination has been carried out on cerium and terbium-doped lanthanum phosphate material. A (90)Sr beta source with 50 mCi strength (1.85 GBq) was used as the irradiation source for TL studies. The TL response as a function of dose received was examined for all phosphors used and it was observed that the intensity of the TL peak vs. dose received was a linear function in the dose range 0.1-200 Gy in each case. Incidentally LaPO(4): Ce,Tb is a component of the compact fluorescent lamp marketed recently as an energy bright light source. Besides having very good luminescence efficiency, good dosimetric properties of these phosphors render them useful for their use in accidental dosimetry also.

Beta Particles↗

PubMed2006

Diverse effects of vascular endothelial growth factor on human pulmonary endothelial barrier and migration.

Increased endothelial permeability is involved in the pathogenesis of many cardiovascular and pulmonary diseases. Vascular endothelial growth factor (VEGF) is a permeability-increasing cytokine. At the same time, VEGF is known to have a beneficial effect on endothelial cells (EC), increasing their survival. Pulmonary endothelium, particularly, may be exposed to higher VEGF concentrations, since the VEGF level is the higher in the lungs than in any other organ. The purpose of this work was to evaluate the effects of VEGF on barrier function and motility of cultured human pulmonary EC. Using transendothelial resistance measurements as an indicator of permeability, we found that 10 ng/ml VEGF significantly improved barrier properties of cultured human pulmonary artery EC (118.6+/-0.6% compared with 100% control, P<0.001). In contrast, challenge with 100 ng/ml VEGF decreased endothelial barrier (71.6+/-1.0% compared with 100% control, P<0.001) and caused disruption of adherens junctions. VEGF at both concentrations increased cellular migration; however, 10 ng/ml VEGF had a significantly stronger effect. VEGF caused a dose-dependent increase in intracellular Ca2+ concentration; however, phosphorylation of myosin light chain was detectably elevated only after treatment with 100 ng/ml. In contrast, 10 ng/ml but not 100 ng/ml VEGF caused a significant increase in intracellular cAMP (known barrier-protective stimulus) compared with nonstimulated cells (1,096+/-157 and 610+/-86 fmol/mg, respectively; P<0.024). Y576-specific phosphorylation of focal adhesion kinase was also stimulated by 10 ng/ml VEGF. Our data suggest that, depending on its concentration, VEGF may cause diverse effects on pulmonary endothelial permeability via different signaling pathways.

Adherens Junctions↗

PubMed2006

Spontaneous renal haemorrhage in the peritoneal cavity.

A 49 year old woman was admitted to hospital after a sudden onset of severe back pain. Twelve hours later, the haemoglobin had decreased to 5.9 and became unstable. She underwent emergency laparotomy that showed intraperitoneal bleeding, secondary to spontaneous kidney rupture. The patient was given a nephrectomy. Histological examination showed an angiomyolipoma as the cause of the bleeding. To the knowledge of the authors, only five previous cases of spontaneous renal bleeding into the peritoneal cavity have been reported in English literature.

Angiomyolipoma↗

PubMed2006

Significantly reduced radiation exposure to operators during kyphoplasty and vertebroplasty procedures: methods and techniques.

BACKGROUND AND PURPOSE: Vertebroplasty and kyphoplasty can be associated with significant radiation exposure to the operator. We compared the exposure levels to an operator performing vertebral fracture augmentation with vertebroplasty and kyphoplasty, to assess a cement injection and a monitoring technique designed to reduce this exposure. METHODS: A neuroradiologist performed 189 consecutive vertebral augmentation procedures in 135 patients with osteoporotic compression fractures by using a bilateral approach with biplane pulse fluoroscopy at 7.5 pulses/second. Cement delivery was performed with intermittent fluoroscopy with kyphoplasty and vertebroplasty by using syringes or continuous fluoroscopic monitoring with a cement delivery system (CDS). Data collection included time and operator exposure parameters. RESULTS: A total of 87 kyphoplasty procedures, 82 vertebroplasty procedures with a CDS (VP-CDS), and 20 vertebroplasty procedures with syringes (VP-S) were safely performed. Mean fluoroscopy time for device positioning was 4.3 minutes for each procedure type. Mean fluoroscopy time (minutes) for cement delivery was significantly different for the 3 procedure types; 2.1 for kyphoplasty, 3.7 for VP-CDS, and 1.5 for VP-S (P < .0001). Comparable mean radiation exposure rates (microsieverts/minute) were 0.8 for kyphoplasty, 1.1 for VP-CDS, and 0.3 for VP-S during device-positioning and 1.7 for kyphoplasty, 2.9 for VP-CDS, and 0.2 for VP-S during cement injection (P < .002). CONCLUSION: Use of the modified cement injection technique and intermittent fluoroscopy with kyphoplasty and vertebroplasty with syringes results in a significantly lower operator exposure rate compared with vertebroplasty with a CDS.

Adult↗

PubMed2005

Simultaneous augmentation cystoplasty is associated with earlier rather than increased artificial urinary sphincter infection.

PURPOSE: While artificial urinary sphincter infection or erosion occurs in 20% of implantations, the risk factors are poorly understood. One of the most contentious factors reported to increase prosthesis infection is simultaneous sphincter implantation and augmentation cystoplasty. In contrast to some reports, to date our results have not shown an increased infective risk with the simultaneous procedure. We reviewed the long-term infective complications of 195 sphincters to investigate for predisposing infective factors and review the role of augmentation cystoplasty. MATERIALS AND METHODS: We performed a retrospective case note review of 144 patients with a median followup of 112 months. Augmentation cystoplasty performed in 86 patients (60%) and was simultaneous in 56. All patients were reviewed within the last year or followed until death or sphincter failure. Patient, surgical and treatment factors were statistically analyzed for associations with prosthesis infection. RESULTS: A total of 108 sphincters failed from infection (25%), tissue atrophy (5%) or mechanical reasons (25%). The overall infective failure rate was similar in patients who underwent simultaneous augmentation (30%) compared with the other patients (23%), although there was a statistically significant difference within the first 3 postoperative years (log rank p = 0.009). While no other variables were significantly associated with sphincter infection, intermittent self-catheterization did not increase sphincter infection and females appeared to have more prosthesis infections. CONCLUSIONS: Our results suggest that, while simultaneous augmentation cystoplasty and artificial urinary sphincter implantation lead to an initial increase in prosthesis infection, this difference disappears after 3 years.

Adult↗

PubMed2002

Comparison of linear gradient and displacement separations in ion-exchange systems.

The linear gradient mode of chromatography is the most widely employed mode of operation in ion-exchange chromatographic separations. However, in recent years, the displacement mode has received considerable attention because of its promise of high throughput and high resolution. To enable a comparison of these two modes of chromatography, it is essential to identify the optimum operating conditions for each. We employed an iterative algorithm to carry out the necessary optimization. The Steric Mass Action model of ion-exchange chromatography is used in concert with the solid-film linear-driving force model to describe the chromatographic behavior of the solutes in these systems. The performances of displacement and gradient modes of chromatography are compared for different types of separation problems. It turns out that for "easy" separations, both the modes are equally effective. However, for challenging separations, the displacement mode is superior to the gradient mode. Our results shed significant light on the performance of gradient and displacement modes in protein ion-exchange systems.

Adsorption↗

PubMed2002

Pregnancy in patients with spina bifida and urinary diversion.

With better medical care the mortality and morbidity associated with spina bifida are improving and more such patients are reaching reproductive age. Significant problems may be encountered in the management of pregnancy in spina bifida, especially in patients with previous abdominal operations for the management of neuropathic bladder dysfunction. We report successful pregnancy outcomes in 2 such patients, both with urinary diversions, with combined obstetric and urological care. We also review the existing literature on the subject.

Adult↗

PubMed2002

Anti dermatophytic activity of Azardirachta indica (neem) by invitro study.

The leaf and seed extracts of the Plant Azardirachta indica were tested for antidermatophytic activity against dermatophytes such as Trichophyton ruberum, Trichophyton, Mentagrophytes, Trichophyton violaceum, Microsporum nanum and Epidermophyton floccosum by tube dilution technique. The minimum Inhibitory concentration (MIC) of neem seed extract was found to be lower tan that of neem leaf when tested against different species of Dermatophytes.

Antifungal Agents↗

PubMed2001

Role of Src kinase in diperoxovanadate-mediated activation of phospholipase D in endothelial cells.

We have shown earlier that oxidant-induced activation of phospholipase D (PLD) in vascular endothelial cells (ECs) is regulated by protein tyrosine kinases. To further understand the regulation of oxidant-induced PLD activation, we investigated the role of Src kinase. Treatment of bovine pulmonary artery ECs (BPAECs) with a model oxidant, diperoxovanadate (DPV), at 5 microM concentration, for 30 min, stimulated PLD activity (four- to eightfold), which was attenuated by tyrosine kinase inhibitors and by Src kinase-specific inhibitors PP-1 and PP-2, in a dose- and time-dependent fashion. Furthermore, BPAECs exposed to DPV (5 microM) for 2 min showed activation of Src kinase as observed by increased tyrosine phosphorylation and autophosphorylation in Src immunoprecipitates, which was attenuated by PP-2. Src immunoprecipitates of cell lysates from control BPAECs exhibited PLD activity in cell-free preparations, which was Arf- and Rho-sensitive and was enhanced at 2 min of DPV (5 microM) treatment. Also, Western blots of Src immunoprecipitates of control cells revealed the presence of PLD(1) and PLD(2), suggesting the association of PLD with Src kinase under basal conditions. However, exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) but not PLD(1) with Src. Western blotting of immunoprecipitates of PLD(1) and PLD(2) isoforms of control BPAECs revealed the presence of Src under basal conditions and exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) with Src in PLD(2) immunoprecipitates. Transient expression of a dominant negative mutant of Src in BPAECs attenuated DPV- but not TPA-induced PLD activation. In cell-free preparations, Src did not phosphorylate either PLD(1) or PLD(2) compared to protein kinase Calpha or p38 mitogen-activated protein kinase. These data show for the first time a direct association of Src with PLD in ECs and regulation of PLD in intact cells.

Animals↗

PubMed2001

Advances in process chromatography gradient elution using binary linear gradients.

A number of chromatography techniques utilize mobile phase gradients with changing buffer concentration to effect separation. At process scale the majority of gradients are stepwise or isocratic. There are a number of instances where process performance or economics indicate that linear gradients would deliver better theoretical performance. However, to date this process advantage has not been implemented due to concerns about the accuracy, reliability or reproducibility of equipment used to produce linear changes in gradient composition. In this manuscript, recent developments in simple feedforward control and data from the resultant process-scale performance are presented. Information is provided on the practical heuristics underlying the control strategy. The data presented in this paper illustrate how the feedforward control strategy has been implemented on a commercial system to achieve better than +/- 2% accuracy of process-scale linear gradients.

Chromatography, Liquid↗

PubMed2001

ESR dosimetry using inorganic materials: a case study of Li2CO3 and CaSO4:Dy as prospective dosimeters.

The CO2- radical ion, detected by ESR technique in bones and teeth enamel, was proved to be invaluable in high level and retrospective dosimetry. In these matrices, impurity carbonate (at phosphate sites) was the precursor to CO2-. With a view to investigate the possibility of using inorganic materials such as lithium carbonate as ESR dosimeters, studies were carried out on gamma-irradiated Li2CO3. The intensity of radiation-induced ESR signals of Li2CO3 at g = 2.0036 (CO3-) and g = 2.0006 (CO2-) was followed as a function of gamma dose in the low dose range of 1-1350 Gy. It was observed that the intensity of the ESR signal at g = 2.0036 (CO3-) was in a linear relation with the radiation dose in the dose range 10-800 Gy and the signal at g = 2.0006 (CO2-) showed linear response in the dose range 5-800 Gy. The lowest dose that could be detected in the present studies using the signal of CO2- in Li2CO3 powder samples (approximately 50 mg) is 3.2 Gy. ESR studies were also carried out on the widely used TL dosimetric material CaSO4:Dy and in pure CaSO4 after gamma irradiation. The TL materials were used in powder as well as pellet forms. The linearity of ESR response with dose for powder and pellet forms of CaSO4: Dy was also studied using the signals at g = 2.0030 (SO3-) and at g = 2.0139 (SO4-). It was observed that the range of linearity of dose response extended between 20 and 1200 Gy, for SO3- signals. The results of dosimetric study indicate that the ESR-Li2CO3 system could be used in dosimetric applications in radiotherapy. However, for the actual applications further advancement is needed to lower the detection limit. The TL phosphor, CaSO4:Dy in powder and pellet forms, could be used as ESR dosimeter in the dose range 20-600 Gy.

Alanine↗

PubMed2001

EPR studies on gamma-irradiated barley seeds: identification of trapped electrons.

Electron paramagnetic resonance (EPR) studies were conducted on barley seeds exposed to normal (H(2)O) and deuterated (D(2)O) moisture, irradiated with 750 Gy at 77 K. Reported here, for the first time, are the trapped electrons formed on gamma-irradiation of seeds at 77 K. Electrons are stabilized/solvated with an increase in the moisture content (H(2)O/D(2)O) of seeds. The recombination of the trapped electron with radical cation gave intense thermoluminescence emission at 110 K. With the increase in temperature and the destruction of singlet, unmasking of an underlying heterogeneous population of free radicals was observed. These free radicals emanate mainly from the endosperm (approximately 95% by wt of the seed), whereas irradiated embryos show a broad multiplet of comparatively low amplitude. Radiolysis of carbohydrate, proteins (approximately 95% of endosperm), and lipids could possibly be responsible for the heterogeneous population of free radicals. Peroxyl radicals were also observed on annealing.

Electron Spin Resonance Spectroscopy↗

PubMed2001

Nitric oxide attenuates H(2)O(2)-induced endothelial barrier dysfunction: mechanisms of protection.

Nitric oxide (.NO) attenuates hydrogen peroxide (H(2)O(2))-mediated injury in porcine pulmonary artery endothelial cells (PAECs) and modulates intracellular levels of cGMP and cAMP. We hypothesized that.NO attenuates H(2)O(2)-induced PAEC monolayer barrier dysfunction through cyclic nucleotide-dependent signaling mechanisms. To examine this hypothesis, cultured PAEC monolayers were treated with H(2)O(2), and barrier function was measured as transmonolayer albumin clearance. H(2)O(2) caused significant PAEC barrier dysfunction that was attenuated by intracellular as well as extracellular.NO generation.NO increased PAEC cGMP and cAMP levels, but treatment with inhibitors of soluble guanylate cyclase or protein kinase G did not abrogate.NO-mediated barrier protection. In contrast, H(2)O(2) decreased protein kinase A activity, and inhibiting protein kinase A abrogated the protective effect of.NO. H(2)O(2)-induced barrier dysfunction was not associated with decreased levels of cGMP or cAMP. 3-Isobutyl-1-methylxanthine and the cGMP analog 8-bromo-cGMP had little effect on H(2)O(2)-mediated endothelial barrier dysfunction, whereas 8-bromo-cAMP plus 3-isobutyl-1-methylxanthine was protective. These results indicate that.NO modulates vascular endothelial barrier function through cAMP-dependent signaling mechanisms.

1-Methyl-3-isobutylxanthine↗

PubMed2001

Role of p38 MAP kinase in diperoxovanadate-induced phospholipase D activation in endothelial cells.

We previously demonstrated that diperoxovanadate (DPV), a synthetic peroxovanadium compound and cell-permeable oxidant that acts as a protein tyrosine phosphatase inhibitor and insulinomimetic, increased phospholipase D (PLD) activation in endothelial cells (ECs). In this report, the regulation of DPV-induced PLD activation by mitogen-activated protein kinases (MAPKs) was investigated. DPV activated extracellular signal-regulated kinase, c-Jun NH2-terminal kinase (JNK), and p38 MAPK in a dose- and time-dependent fashion. Treatment of ECs with p38 MAPK inhibitors SB-203580 and SB-202190 or transient transfection with a p38 dominant negative mutant mitigated the PLD activation by DPV but not by phorbol ester. SB-202190 blocked DPV-mediated p38 MAPK activity as determined by activated transcription factor-2 phosphorylation. Immunoprecipitation of PLD from EC lysates with PLD1 and PLD2 antibodies revealed both PLD isoforms associated with p38 MAPK. Similarly, PLD1 and PLD2 were detected in p38 immunoprecipitates from control and DPV-challenged ECs. Binding assays demonstrated interaction of glutathione S-transferase-p38 fusion protein with PLD1 and PLD2. Both PLD1 and PLD2 were phosphorylated by p38 MAPK in vitro, and DPV increased phosphorylation of PLD1 and PLD2 in vivo. However, phosphorylation of PLD by p38 failed to affect PLD activity in vitro. These results provide evidence for p38 MAPK-mediated regulation of PLD in ECs.

Animals↗

PubMed2001

Third place--Resident Research Competition, AAO-2000. Antisense cyclin D1 inhibits growth of head and neck cancer xenografts in nude mice.

PROBLEM: Cyclin D1 is a regulatory factor essential in the progression of the cell cycle from G1 through S phase. Amplification and overexpression of cyclin D1 have been observed in many human cancers including head and neck squamous cell carcinoma (HNSCC). We have previously transfected a HNSCC control cell line (CCL23) with an antisense cyclin D1 plasmid and demonstrated inhibition of cell proliferation in vitro. In this study, we examine whether antisense cyclin D1 could inhibit tumor growth in vivo. Methods/measures: The CCL23 and its antisense cyclin D1 transfected clone (CCL23 AS) were injected into the flanks of nude mice. Tumor growth was monitored weekly. After 5 weeks, tumors were removed and studied for tumor size, cyclin D1 expression, cyclin D1-dependent kinase activity, and retinoblastoma (Rb) phosphorylation. RESULTS: Compared with the control tumors, 11 of 19 antisense tumors were smaller, 7 tumors were of equal size, and 1 tumor was larger. Immunohistochemical analysis with an anti-cyclin D1 antibody demonstrated decreased cyclin D1 expression in CCL23 AS and the smaller antisense tumors. Cyclin D1-dependent kinase activity was reduced in CCL23 AS and the smaller antisense tumors, and this was accompanied by a relative decrease in phosphorylated Rb in these samples. CONCLUSION: Antisense cyclin D1 inhibits growth of HNSCC tumors. Cyclin D1 expression, cyclin D1-dependent kinase activity, and Rb phosphorylation are decreased in these tumors. CLINICAL SIGNIFICANCE: These findings lend support for the potential use of antisense cyclin D1 as gene therapy for HNSCC.

Animals↗

PubMed2000

Human immunodeficiency virus type 1 quasi species that rebound after discontinuation of highly active antiretroviral therapy are similar to the viral quasi species present before initiation of therapy.

In an effort to identify the sources of the viruses that emerge after discontinuation of therapy, analyses of human immunodeficiency virus (HIV) quasi species were done for 3 patients with sustained levels of HIV RNA of <50 copies/mL for 1-3 years. The sequences found in the rebounding plasma virus were closely related to those of the actively replicating form of viruses present before the initiation of combination therapy. All quasi species found in the rebounding plasma virus were also present in proviral DNA, cell-associated RNA in peripheral blood mononuclear cells (PBMC), and virion RNA derived from PBMC coculture during periods when plasma HIV RNA levels were <50 copies/mL. These findings suggest that the rapid resurgence of plasma viremia observed after discontinuation of therapy and the viruses cocultured from PBMC are derived from a relatively stable pool of the replicating form of virus rather than from activation of a previously latent pool.

Adult↗

PubMed2000

Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4+ and CD8+ T cell turnover in HIV-infected patients.

To evaluate the effects of HIV infection on T cell turnover, we examined levels of DNA synthesis in lymph node and peripheral blood mononuclear cell subsets by using ex vivo labeling with BrdUrd. Compared with healthy controls (n = 67), HIV-infected patients (n = 57) had significant increases in the number and fraction of dividing CD4(+) and CD8(+) T cells. Higher percentages of dividing CD4(+) and CD8(+) T cells were noted in patients with the higher viral burdens. No direct correlation was noted between rates of T cell turnover and CD4(+) T cell counts. Marked reductions in CD4(+) and CD8(+) T cell proliferation were seen in 11/11 patients 1-12 weeks after initiation of highly active antiretroviral therapy (HAART). These reductions persisted for the length of the study (16-72 weeks). Decreases in naive T cell proliferation correlated with increases in the levels of T cell receptor rearrangement excision circles. Division of CD4(+) and CD8(+) T cells increased dramatically in association with rapid increases in HIV-1 viral loads in 9/9 patients 5 weeks after termination of HAART and declined to pre-HAART-termination levels 8 weeks after reinitiation of therapy. These data are consistent with the hypothesis that HIV-1 infection induces a viral burden-related, global activation of the immune system, leading to increases in lymphocyte proliferation.

Antiretroviral Therapy, Highly Active↗

PubMed2000

Accumulation of RXR alpha during activation of cycling human T lymphocytes: modulation of RXRE transactivation function by mitogen-activated protein kinase pathways.

We have previously reported that the activation of resting human immature peripheral blood T (PBT) lymphocytes is associated with the loss of retinoid X receptor alpha (RXRalpha) expression. In the present study, we have demonstrated that, unlike resting cells, activation of cycling human mature PBT lymphocytes, and T lymphocyte leukemia cell lines is accompanied by the accumulation of RXRalpha mRNA and protein. Interestingly, cyclosporin A further augmented RXRalpha expression, indicating the involvement of calcineurin pathways in the process. 9-cis retinoic acid inhibited the accumulation, suggesting that retinoids can regulate the synthesis of their own receptors during T cell activation. Transfection analysis in Jurkat cells, using RXRE-dependent reporter assays, showed that RXRalpha accumulated during T cell activation was transcriptionally inactive. To investigate the mechanism of such inhibition, the role of two mitogen-activated protein kinase pathways, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), in modulating RXRE-dependent transcription, was explored. The expression of constitutively active MAP/ERK kinase kinase 1 (MEKK1) inhibited RXRE-dependent transcription, whereas dominant negative MEKK1 increased the transcription, indicating the involvement of JNK signaling pathways in the process. In contrast, expression of constitutively active MEK1, which activates ERK pathway, enhanced RXRE-dependent activation. When both were activated simultaneously, JNK pathway was dominant over ERK pathway and resulted in inhibition of RXRE-mediated transcription. These data demonstrate a dual regulatory control of RXRalpha expression during the activation of resting and cycling T lymphocytes and indicate a dynamic balance between JNK and ERK pathways in modulating RXRE-mediated transactivation.

Alitretinoin↗