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Biomedical subjects

N Desai

Publications and source records attributed to N Desai.

At least 19 recordsLinked to original sources
PubMed2006

Altruistic living donors: evaluation for nondirected kidney or liver donation.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral. During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attention-seeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible large-scale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.

Adult↗
PubMed2005

High LET-induced H2AX phosphorylation around the Bragg curve.

We investigated the spatial distribution of the induction of the phosphorylated form of the histone protein H2AX (gamma-H2AX), known to be activated by DSBs. Following irradiation of human fibroblast cells with 600 MeV/nucleon silicon and 600 MeV/nucleon iron ions we observed the formation of gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in an x/y plane. Polyethylene shielding was used to achieve a Bragg curve distribution with beam geometry parallel to the monolayer of cells. We present data that highlights the formation of immunofluorescent gamma-H2AX tracks showing the ion trajectories across the Bragg peak of irradiated human fibroblast cells. Qualitative analyses of these distributions indicated potentially increased clustering of DNA damage before the Bragg peak, enhanced gamma-H2AX distribution at the peak, and provided visual evidence of high-linear energy transfer particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. Spatial assessment of gamma-H2AX fluorescence may provide direct insights into DNA damage across the Bragg curve for high charge and energy ions including the biological consequences of shielding and possible contributors to bystander effects.

Bystander Effect↗
PubMed2005

HIV-1 seronegativity in a child with proved perinatal HIV infection on HAART.

OBJECTIVES: To report the unexpected absence of HIV-1 antibodies and provirus in the peripheral blood of a 4 year old with previously diagnosed perinatal HIV infection. METHODS: Case study including review of clinic and laboratory records and confirmation of results of HIV-1 enzyme linked immunosorbent assay (ELISA), western blot, and HIV-1 DNA PCR from reference laboratory. RESULTS: This child had high plasma viral load at the initiation of highly active antiretroviral therapy (HAART) at 10 months of age. Following undetectable HIV viraemia continuously for a 3 year period, he had normal CD4 and immunoglobulin levels. When retested at the request of the parent, HIV-1 ELISA, western blot, and HIV DNA PCR were all negative, raising the question of misdiagnosis and the parental misperception of a "cure." A rebound increase in viral load on cessation of therapy led to these diagnostic tests becoming positive again, with better parental acceptance of the diagnosis and treatment plan. CONCLUSIONS: Patients and providers should exercise caution in interpreting negative serological tests in children on HAART.

Antibodies, Viral↗
PubMed2005

Immunofluorescence detection of clustered gamma-H2AX foci induced by HZE-particle radiation.

We studied the spatial and temporal distributions of foci of the phosphorylated form of the histone protein H2AX (gamma-H2AX), which is known to be activated by double-strand breaks after irradiation of human fibroblast cells with high-energy silicon (54 keV/microm) and iron (176 keV/microm) ions. Here we present data obtained with the ion path parallel to a monolayer of human fibroblast cells that leads to gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in an x/y plane, thus enabling the analysis of the fluorescence distributions along the ion trajectories. Qualitative analyses of these distributions provide insights into DNA damage processing kinetics for high charge and energy (HZE) ions, including evidence of increased clustering of DNA damage and slower processing with increasing LET.

Cells, Cultured↗
PubMed2004

Simultaneous measurement of multiple radiation-induced protein expression profiles using the Luminex(TM) system.

Space flight results in the exposure of astronauts to a mixed field of radiation composed of energetic particles of varying energies, and biological indicators of space radiation exposure provides a better understanding of the associated long-term health risks. Current methods of biodosimetry have employed the use of cytogenetic analysis for biodosimetry, and more recently the advent of technological progression has led to advanced research in the use of genomic and proteomic expression profiling to simultaneously assess biomarkers of radiation exposure. We describe here the technical advantages of the Luminex(TM) 100 system relative to traditional methods and its potential as a tool to simultaneously profile multiple proteins induced by ionizing radiation. The development of such a bioassay would provide more relevant post-translational dynamics of stress response and will impart important implications in the advancement of space and other radiation contact monitoring.

Antibodies↗
PubMed2004

Elasticity and adhesion force mapping reveals real-time clustering of growth factor receptors and associated changes in local cellular rheological properties.

Cell surface macromolecules such as receptors and ion channels serve as the interface link between the cytoplasm and the extracellular region. Their density, distribution, and clustering are key spatial features influencing effective and proper physical and biochemical cellular responses to many regulatory signals. In this study, the effect of plasma-membrane receptor clustering on local cell mechanics was obtained from maps of interaction forces between antibody-conjugated atomic force microscope tips and a specific receptor, a vascular endothelial growth factor (VEGF) receptor. The technique allows simultaneous measurement of the real-time motion of specific macromolecules and their effect on local rheological properties like elasticity. The clustering was stimulated by online additions of VEGF, or antibody against VEGF receptors. VEGF receptors are found to concentrate toward the cell boundaries and cluster rapidly after the online additions commence. Elasticity of regions under the clusters is found to change remarkably, with order-of-magnitude stiffness reductions and fluidity increases. The local stiffness reductions are nearly proportional to receptor density and, being concentrated near the cell edges, provide a mechanism for cell growth and angiogenesis.

Animals↗
PubMed2004

Multidrug resistant proteins: P-glycoprotein and lung resistance protein expression in retinoblastoma.

BACKGROUND/AIM: Retinoblastoma is the commonest primary intraocular tumour in children. Chemotherapy now plays a big part in the treatment of these tumours. There is not much information about the role of the multidrug resistance proteins (MDR)-P-glycoprotein (P-gp) and vault protein lung resistance protein (LRP)-in retinoblastoma. The authors investigated the expression of P-gp and LRP in retinoblastoma and correlated them clinicopathologically. METHODS: Among 60 retinoblastomas, 40 tumours were not subjected to preoperative or postoperative chemotherapy and 20 tumours were subjected to postoperative chemotherapy. In this cohort 27 tumours had no invasion and 33 tumours had invasion of choroid, optic nerve, and orbit. P-gp and LRP expression were studied by immunohistochemistry. Immunoanalysis was done semiquantitatively. RESULTS: Among the 60 tumours P-gp was expressed in 23 (38%) tumours and LRP was expressed in 35 (58%). P-gp was expressed in 11/27 (40%) tumours with no invasion and in 12/33 (36%) tumours with invasion. LRP was expressed in 15/27 (55%) tumours with no invasion and in 20/33 (60%) tumours with invasion. Both P-gp and LRP were negative in three tumours with invasion, which had later developed bone marrow metastasis. There was no correlation between P-gp and LRP expression with invasion, differentiation and laterality of the tumours and response to treatment. CONCLUSION: Retinoblastoma expresses P-gp and LRP intrinsically before chemotherapy and none of these proteins predicted the response to chemotherapy. Thus, further studies are needed to understand the significance of the expression of the P-gp and LRP proteins in retinoblastoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Selective transmission of multidrug resistant HIV to a newborn related to poor maternal adherence.

OBJECTIVES: To report perinatal transmission of multidrug resistant (MDR) HIV related to variable maternal adherence antenatally. METHODS: Case study including review of clinic records, adherence information, laboratory data, and HIV genotyping results in mother and infant. RESULTS: Poor maternal adherence to clinic visits and antiretroviral therapy contributed to detectable viraemia antenatally. When tested for the first time at age 6 months, the infant was found to have virus with resistance to multiple drugs. In this case, prophylaxis with zidovudine (AZT) failed to prevent the transmission of the MDR strain. CONCLUSIONS: Perinatal transmission of MDR HIV can occur despite standard peripartum prophylaxis with AZT. Perinatal prophylaxis should be tailored to the mother's treatment history and resistance profile. Paediatric HIV specialists should be prepared to deal with a small, but slowly increasing number of babies with a "nightmare" multidrug resistant virus with limited treatment options.

Adult↗
PubMed2003

In vitro study on sustained release capsule formulation of acetazolamide.

In the present study formulation of sustained release capsule of acetazolamide 250 mg was tried using nonpareil seeds. Nonpareil seeds were coated with drug, polyvinylpyrrolidone, glyceryl monostearate, microcrystalline wax, and glyceryl distearate either individually or in combination to achieve sustained release capsule 250 mg. In successful formulation 20% drug coated pellets and 80% wax coated pellets were taken. Wax coated pellets for successful formulation contained coating of microcrystalline wax and glyceryl distearate on drug coated pellets of the same concentration of 1.6% w/w. Successful formulated sustained release capsule 250 mg of acetazolamide was compared in in vitro study with theoretical sustained release formulation suggested by wagner and one marketed sustained release capsule 250 mg. Formulated capsule showed result superior to or on par with marketed capsule. For successful formulation pellets were filled in '1' size hard gelatin capsule and stability study was carried out in hot air over at room temperature and 45 degrees C for 5 weeks. The formulation was found stable in respect of drug content and release rate.

Acetazolamide↗
PubMed2002

Plasma vascular endothelial growth factor level is a predictor of the severity of postoperative capillary leak syndrome in neonates undergoing cardiopulmonary bypass.

Capillary leak syndrome (CLS), characterized by extravascular fluid accumulation and significant organ dysfunction, is a serious complication in children undergoing cardiopulmonary bypass (CPB). We examined the relationship between plasma vascular endothelial growth factor (VEGF) levels and severity of CLS. The kinetics of VEGF in the plasma of 11 neonates and 7 older children undergoing CPB were investigated, correlating plasma VEGF levels and CLS clinical presentation. The degree of postoperative CLS was quantified by measuring parameters of extracellular volume and end-organ dysfunction. A chest-wall soft-tissue-width index (CSTWI) was designed in order to standardize the extracellular fluid accumulation. Most CLS parameters were significantly more prominent in the neonatal patients. Low plasma VEFG levels (>35 pg/ml) were found in 3 neonatal control patients and all but, sample from the older group patient. The neonates had significantly higher preoperative VEGF plasma levels (684.4 +/- 559.1 pg/ml, P = 0.02), which decreased during the operation to levels below 35 pg/ml and increased again 24 h postoperatively to levels significantly higher than in the older patients (484 +/- 270.3 pg/ml, P = 0.001). Multilinear regression analysis found preoperative VEGF levels to independently correlate with CLS as represented by CSTWI (P < 0.01, r = 0.726). Both the occurrence of post-CPB CLS and plasma VEGF levels pre- and postoperatively were thus higher in neonates than in children. Plasma VEGF level is a predictor of the severity of postoperative CLS.

Capillary Leak Syndrome↗
PubMed2001

Chiral separations of transition metal complexes using capillary zone electrophoresis.

Several buffer additives that may facilitate chiral separation for optically active transition metal (TM) systems are investigated using capillary zone electrophoresis. The TM complexes evaluated exhibit considerable heterogeneity with respect to total complex charge (0 to 4+), ligand type, and identity of the central metal including Ru2+, Ni2+, Cr3+, and Co3+, threo-D[+]-Isocitrate, potassium antimonyl-d-tartrate and dibenzoyl-L-tartrate are identified as the most efficient chiral selectors. Interestingly, TM complexes exhibiting a (3+) total complex charge exhibit a reversal of enantiomer elution order versus all other complexes when separated using the tartrate additives. Operating parameters including pH, temperature, and capillary length are discussed, and chiral separations of complex mixtures are demonstrated.

Electrophoresis, Capillary↗
PubMed2001

Intra- and inter-generic plasmid-mediated spread of cephalosporin and aminoglycoside resistance amongst Klebsiella aerogenes K41 and other enterobacteria.

Klebsiella aerogenes K41, resistant to third generation cephalosporins and aminoglycosides, was isolated from clinical samples of 153 in-patients. Blood cultures accounted for 24 (15.7%) of isolates. The MIC(90) of ceftazidime for the isolates of 84 patients was >512 mg/l and was reduced to 2.0 by 4 mg/l of clavulanic acid, but only to 64 by 4 mg/l of sulbactam. Isolates of K. aerogenes K41 produced extended-spectrum beta-lactamase (ESBL) SHV-5 and TEM-1, identified by isoelectric focusing. Plasmid profiles showed that co-dissemination of cephalosporin and aminoglycoside resistance, plus ESBL production, coincided with the acquisition of a 116-kb plasmid. This plasmid was transferable in vitro from K. aerogenes K41 to other serotypes and genera of the Enterobacteriaceae.

Aminoglycosides↗
PubMed2001

Modifying the temporal profile of the high-potency sweetener neotame.

It is possible, using hydrophobic organic acids (such as cinnamate) or hydroxyamino acids (such as serine and tyrosine), to modify the temporal profile of the high-potency sweetener neotame. On the basis of Monte Carlo simulations, it was concluded that it is unlikely that this effect is due to direct interaction between the neotame molecule and the taste modifier. It is shown, using conformational analysis and molecular modeling, that the taste modifiers can adopt low-energy conformers which mimic the proposed active conformation of neotame, which suggests that the modifiers may compete for binding at the receptor site.

Cinnamates↗
PubMed2001

Duodenal leiomyoma--a rare cause of haematemesis.

Leiomyoma of the duodenum is a rare tumour. Small intestinal tumours contributing to upper gastrointestinal bleed is still rare. They usually present with malena and anaemia, rarely hematemesis. We report a case of leiomyoma of duodenum diagnosed on endoscopic ultrasound that presented with massive haematemesis.

Adult↗
PubMed2000

Active conformations of neotame and other high-potency sweeteners.

We carried out extensive conformational analysis of three high-potency sweeteners: neotame, superaspartame, and SC-45647. We then identified six possible pharmacophore features (carboxylate, two hydrophobic groups, and three NH groups) and wrote a computer program to exhaustively compare intramolecular distances among all possible sets of five-point pharmacophores (carboxylate + two hydrophobic groups + two NH groups) for the three compounds. The best pharmacophore model superimposes low-energy conformers of the three compounds in such a way that the five pharmacophore points match well both sterically and with respect to orientation of hydrogen bond donors and acceptors.

Dipeptides↗
PubMed2000

Retinoic acid suppresses interleukin-6 production in human endometrial cells.

OBJECTIVE: To determine whether retinoic acid (RA) can regulate the expression of interleukin (IL)-6 in human endometrial cells in a manner that might be beneficial to women with endometriosis. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Patients with endometriosis and controls. INTERVENTION(S): Endometrial cell cultures were treated with RA. MAIN OUTCOME MEASURE(S): Interleukin-6 protein secretion, messenger RNA expression, and IL-6-promoter activity. RESULT(S): Using a human endometrial cell line (EM42), as well as primary stromal and epithelial endometrial cells, we demonstrated that RA suppresses IL-6 protein and messenger RNA expression in a time- and dose-dependent fashion, showing maximal effects at pharmacologically achievable blood serum concentrations (micromoles per liter). Retinoic acid specifically inhibited the activity of IL-6-promoter reporter constructs that were transiently transfected into EM42 cells. Mutational analysis of reporter constructs indicated that RA suppression of IL-6 expression was mediated, at least in part, through the nuclear factor IL-6 binding site located in the IL-6 promoter. CONCLUSION: Retinoids may play a fundamental role in altering the pathophysiology of endometriosis related to aberrant production of IL-6.

Cells, Cultured↗
PubMed2000

Effect of temperature, pH, and ions on sweet taste.

The purpose of this experiment was to determine the effects of temperature (50 degrees C and 6 degrees C), pH (pH 3.0, 4.0, 5.0, 6. 0, and 7.0) and the addition of monovalent and divalent cations (5 mM Na(+), 5 mM K(+), and 5 mM Ca(2)+ ) on the sweetness intensity ratings of sweeteners ranging widely in chemical structure. A trained panel provided intensity evaluations for prototypical tastes (sweet, bitter, sour, and salty) as well as aromatic and mouth-feel attributes. The following sweeteners were included in this experiment: three sugars (fructose, glucose, sucrose), three terpenoid glycosides (monoammonium glycyrrhizinate, rebaudioside-A, stevioside), two polyhydric alcohols (mannitol, sorbitol), two dipeptide derivatives (alitame, aspartame), two N-sulfonylamides (acesulfame-K, sodium saccharin), one sulfamate (sodium cyclamate), one protein (thaumatin), one dihydrochalcone (neohesperidin dihydrochalcone), and one chlorodeoxysugar (sucralose). Two to five levels of each sweetener reflecting a range of sweetness intensities were tested, using formulae developed by DuBois et al. The main finding from this three-part study was that temperature, pH, and ions had little effect on perceived sweetness intensity. Even when significant differences were found in the temperature study, the effects were very small.

Calcium↗