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N Patel

Publications and source records attributed to N Patel.

At least 109 records · Page 6Linked to original sources
PubMed2001

Insulin-induced cortical actin remodeling promotes GLUT4 insertion at muscle cell membrane ruffles.

Insulin stimulates glucose uptake by recruiting glucose transporter 4 (GLUT4) from an intracellular compartment to the cell surface; this phenomenon is defective in type 2 diabetes. Here we examine the involvement of actin filaments in GLUT4 translocation and their possible defects in insulin resistance, using L6 myotubes expressing myc-tagged GLUT4. Insulin caused membrane ruffling, a dynamic distortion of the myotube dorsal surface. Fluorescence microscopy and immunogold staining of surface GLUT4myc coupled to backscatter electron microscopy revealed a high density of this protein in membrane ruffles. The t-SNAREs syntaxin4 and SNAP-23 were also abundant in these regions. Below the membrane, GLUT4 and the vesicular protein VAMP2, but not VAMP3, colocalized with the actin structures supporting the membrane ruffles. GLUT4myc externalization and membrane ruffles were reduced by jasplakinolide and by swinholide-A, drugs that affect actin filament stability and prevent actin branching, respectively. Insulin resistance generated by prolonged (24 hours) exposure of myotubes to high glucose and insulin diminished the acute insulin-dependent remodeling of cortical actin and GLUT4myc translocation, reminiscent of the effect of swinholide-A. We propose that GLUT4 vesicle incorporation into the plasma membrane involves insulin-dependent cortical actin remodeling and that defective actin remodeling contributes to insulin resistance.

Actins↗
PubMed2001

Spray-dried insulin particles retain biological activity in rapid in-vitro assay.

The purpose of this study was to rapidly determine, without the use of extensive animal studies, whether biological activity is retained after spray drying insulin with two excipients, lactose and xanthan gum. This was achieved by the detection of protein kinase B (PKB), which is activated by phosphorylation in response to insulin binding to cellular receptors. A myeloid cell line was cultured and stimulated with the reconstituted insulin powders. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was then utilised to allow in-vitro detection of phosphorylated PKB using an anti-phospho-PKB antibody. A single band specific to phosphorylated PKB was found on the Western blots, indicating that the active conformation of insulin was retained when spray dried in combination with lactose and with xanthan gum over the spray-drying inlet temperature range of 110-170 degrees C. Evidence of inactivation/denaturation was observed when insulin was spray dried at an inlet temperature of 200 degrees C. The assay may be of use as a more rapid and economic means to screen insulin formulations for inhalation and other purposes as opposed to conventional monitoring of blood glucose levels in animals.

Desiccation↗
PubMed2001

Patterns of fluid accumulation on screening ultrasonography for blunt abdominal trauma: comparison with site of injury.

The objectives of this study were to define where fluid accumulation is shown on screening ultrasonography after blunt abdominal trauma and to determine how fluid accumulation patterns are associated with the site of injury. From 1994 to 1998, 2,693 screening examinations for blunt abdominal trauma were performed, in which 7 regions were examined for fluid. On the basis of a preliminary analysis of patients with solitary injuries, all 194 patients with sonographically detected fluid were grouped by fluid accumulation pattern. Fluid patterns were compared with sites of injury. The patterns differed between hepatic and splenic injuries. Fluid in the left upper quadrant, in both upper quadrants, or diffusely distributed suggested splenic injury, whereas fluid in the right upper quadrant or the right upper quadrant and lower recesses suggested hepatic injury (P < .0001). Fluid accumulation was random after enteric injury. Patients with extraperitoneal injury had no fluid or had fluid focally at the injury site. The ability to predict the injury site on the basis of fluid patterns should expedite treatment of hemodynamically unstable patients with blunt abdominal trauma.

Abdominal Injuries↗
PubMed2001

Quantification of fluid on screening ultrasonography for blunt abdominal trauma: a simple scoring system to predict severity of injury.

A simple ultrasonographic method of fluid quantification, which counted the number of fluid recesses, was developed to predict the severity of injury after blunt abdominal trauma. From 1994 to 1998, 2,693 screening ultrasonographic examinations were performed for blunt abdominal trauma. Of this group, 2,499 patients had a fluid score of 0 (no fluid), and 1.4% had injuries (0.4% requiring surgery); 110 had a score of 1 (fluid in a single examined region), and 59% had injuries (13% requiring surgery); 33 had a score of 2, and 85% had injuries (36% requiring surgery); 30 had a score of 3, and 83% had injuries (63% requiring surgery); and 21 had a score of 4, and 95% had injuries (81 % requiring surgery). Patients with scores of 3 or greater had significantly higher rates of injury (P < .002) and injury requiring surgery (P < .0001) than patients with lower scores. The ability to predict injury severity on the basis of a simple ultrasonographic scoring system should expedite treatment of patients with severe trauma.

Abdominal Injuries↗
PubMed2001

Betamethasone alteration of the one-hour glucose challenge test in pregnancy.

OBJECTIVE: To determine if betamethasone administration alters the one-hour (50-g) glucose challenge test (GCT) and, if so, to determine the duration of this effect. STUDY DESIGN: Pregnant women with singleton gestations eligible to receive antenatal betamethasone (24-34 weeks) with no evidence of infection, diabetes mellitus, hepatic or pancreatic disease, betamimetic therapy or prolonged steroid use were invited to participate. Betamethasone (12 mg) was administered intramuscularly upon admission and repeated in 24 hours. After an 8-hour fast, a 50-g GCT was administered 24 hours (day 1) and 72 hours (day 3) after the second betamethasone injection. Plasma glucose samples were drawn one hour after the glucose challenge. Statistical analysis utilized the McNemar exact test. RESULTS: Seven patients, all with normal GCTs 7-10 days outside the study period, were enrolled. Six had abnormal GCT results on day 1 (P = .03). Three had abnormal results on day 3. CONCLUSION: Betamethasone administration results in abnormal one-hour GCTs in pregnant women.

Adult↗
PubMed2001

Quality of life after great auricular nerve sacrifice during parotidectomy.

OBJECTIVE: To determine the impact of great auricular nerve (GAN) sacrifice during parotidectomy on patients' quality of life. DESIGN: Historical cohort survey of patients who had undergone GAN sacrifice during parotidectomy. SETTING: Tertiary academic otolaryngologic practice. PATIENTS AND METHODS: Fifty-three patients who had undergone GAN sacrifice during parotidectomy completed an 8-item quality-of-life survey with a 7-point response scale designed to measure outcome after GAN sacrifice during parotidectomy. RESULTS: Thirty patients (57%) reported experiencing at least 1 abnormal symptom, but the mean number of symptoms decreased significantly with time, from a mean of 2.3 during the first year to 0.2 after 5 years (P<.001). Even among patients experiencing symptoms, 23 (77%) reported only a little or no bother caused by the symptoms, and 27 (90%) reported no interference or almost none with their daily activities. The degree of bother or interference reported had a moderate positive correlation with the number of abnormal sensations reported. CONCLUSIONS: The results suggest that, while many patients experienced sensory deficits, the overall quality of life was not significantly affected after GAN sacrifice during parotidectomy. Patients who report multiple abnormal sensations, however, would benefit from additional counseling and from reassurance that the number of sensations will diminish with time. Further study evaluating the effect of preservation of the posterior branch of the GAN during parotidectomy on patients' quality of life is needed.

Adult↗
PubMed2001

Endoscopic radial artery harvest: a new approach.

BACKGROUND: Although early attempts to use the radial artery (RA) as a conduit for cardiac revascularization met with disappointing results, recent data have shown the RA to achieve very good short-term patency as well as promising mid-term patency results. The recent increase in the frequency of coronary reoperations, with their limited options for vascular conduits, has also stimulated an interest in the RA graft. The success of minimally invasive vein harvesting techniques encouraged us to develop a minimally invasive technique for harvesting the RA from the forearm, which is reviewed in this article. METHODS: The endoscopic harvest technique was employed on more than 120 nonselected patients at our facility over a 12-month period. The procedure involved exposure of the RA under direct visualization and without direct manipulation, using an endoscopic dissector and harmonic shears. Side branches of the RA were isolated and divided, and the vessel was removed and side branch occlusion verified. The harvested RA was then prepared for the revascularization surgery. RESULTS: The patients who underwent the procedure showed no evidence of graft spasm or occlusion in the immediate postoperative period. Patients also preferred the small endoscopic incision to the full forearm incision of the "open" technique. CONCLUSIONS: Our experience indicates that endoscopic radial artery harvesting is a safe technique that achieves good short-term patency results and improved patient satisfaction. Evaluation of long-term vessel integrity is needed, and a comparison of the minimally invasive and the open technique has been initiated.

Angioscopy↗
PubMed2000

TOF-SIMS characterization and imaging of controlled-release drug delivery systems.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for the analysis of multilayer drug beads that serve as controlled-release drug delivery systems. TOF-SIMS analysis of a cross section of each bead system allowed molecular chemical information to be gained from all of the layers simultaneously, in situ. The integrity of each of the layers was evaluated through imaging of specific ion species for the drug, excipient, and coating materials. The three beads in this study each showed a unique distribution of ingredients. Images of the parent molecular ion for each drug (theophylline, paracetamol, prednisolone) showed their distribution ranged from micrometer-sized particles in one bead cross section to almost homogeneous in another bead cross section. The chemical composition of each of the layers in the beads was evaluated through mass spectrometry; the ingredients did not always match the manufacturer's specification. In addition, many common drug bead ingredients were analyzed as pure substances, providing TOF-SIMS reference spectra of these materials for the first time.

Drug Delivery Systems↗
PubMed2000

Low dose fractionated radiation enhances the radiosensitization effect of paclitaxel in colorectal tumor cells with mutant p53.

BACKGROUND: The current study was undertaken to investigate the influence of wild-type or mutant p53 status on the radiosensitizing effect of paclitaxel in colorectal tumor cell lines. METHODS: HCT-116 (contains wild-type p53) and HT-29 (contains mutant p53) established from moderately differentiated colorectal carcinomas were used in this study. Colony-forming assay was performed after exposure to either different radiation doses (0.5-6 gray [Gy]) or paclitaxel (1-10 nM) or in combination. Induction of p53 and p21(waf1/cip1) by these treatments were determined by immunocytochemistry and Western blot analysis. RESULTS: Radiation caused an increase in nuclear p53 and p21(waf1/cip1) proteins in HCT-116 cells, indicating that p53 functionally induced p21(waf1/cip1). However, induction of nuclear p53 and p21(waf1/cip1) protein was not evident in HT-29 cells, suggesting that p53 was not functional in these cells. Survival data showed that the HCT-116 cells (survival fraction of exponentially growing cells that were irradiated at the clinically relevant dose of 2 Gy [SF(2)] = 0.383; dose required to reduce the fraction of cells to 37% [D(0)] = 223 centigray [cGy]) were significantly sensitive to ionizing radiation (P < 0.008) when compared with the HT-29 cells (SF(2) = 0.614; D(0) = 351 cGy). Paclitaxel caused a higher degree of clonogenic inhibition in HCT-116 (D(0) = 0.7 nM) than HT-29 (D(0) = 1.11 nM) cells (P < 0.06). When paclitaxel and radiation were combined, an enhanced radiosensitizing effect (P < 0.05) was observed in HCT-116 cells (SF(2) = 0.138; D(0) = 103 cGy), whereas in HT-29 cells no significant radiosensitization of paclitaxel was observed (SF(2) = 0.608; D(0) = 306 cGy). However, pretreatment with paclitaxel followed by multifractionated low dose radiation (0.5- or 1-Gy fractions for a total dose of 2 Gy) significantly enhanced the radiosensitizing effect in both HCT-116 and HT-29 cells. CONCLUSIONS: The results of the current study suggested that multifractionated radiation given at very low doses after exposure of cells to paclitaxel conferred a potent radiation sensitizing effect irrespective of p53 status.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury.

Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.

Adrenalectomy↗
PubMed2000

The influence of viewing conditions on radiological diagnosis of periapical inflammation.

OBJECTIVES: To determine the effect of viewing conditions upon diagnosis of early periapical inflammatory pathosis on intra-oral radiographs, and to examine the effect of observer experience upon diagnostic performance in this task. METHODS: 50 observers examined 18 periapical radiographs using three different viewing conditions (room lighting; viewing box; viewing box with x2 magnification and masking). Their diagnoses were compared with an 'expert' diagnosis provided by repeated viewings of the films by two dental radiologists. Sensitivities and specificities were determined. RESULTS: When 'ideal' viewing conditions were used, optimal sensitivity (78%) and specificity (78%) were obtained. Use of a viewing box was associated with significantly higher specificity than the use of room lighting (P = 0.0016). Use of masking and x2 magnification was associated with significantly higher sensitivity than a viewing box alone (P = 0.004). There were few significant differences in diagnostic performance between observers, but qualified dental staff had significantly higher specificities than 4th year (P = 0.01) and 5th year (P = 0.01) students when a viewing box was used alone. CONCLUSIONS: This study on early periapical inflammatory pathosis gives support to guidelines which recommend the use of a viewing box, x2 magnification and masking for interpreting intra-oral radiographs. It also suggests that observer experience may influence interpretation of early periapical pathosis.

Clinical Competence↗
PubMed2000

Adult bone marrow stromal cells differentiate into neural cells in vitro.

Bone marrow stromal cells (BMSC) normally give rise to bone, cartilage, and mesenchymal cells. Recently, bone marrow cells have been shown to have the capacity to differentiate into myocytes, hepatocytes, and glial cells. We now demonstrate that human and mouse BMSC can be induced to differentiate into neural cells under experimental cell culture conditions. BMSC cultured in the presence of EGF or BDNF expressed the protein and mRNA for nestin, a marker of neural precursors. These cultures also expressed glial fibrillary acidic protein (GFAP) and neuron-specific nuclear protein (NeuN). When labeled human or mouse BMSC were cultured with rat fetal mesencephalic or striatal cells, a small proportion of BMSC-derived cells differentiated into neuron-like cells expressing NeuN and glial cells expressing GFAP.

Animals↗
PubMed2000

Vascularized bone marrow transplantation: A new surgical approach using isolated femoral bone/bone marrow.

BACKGROUND: Orthotopic composite tissue (limb) transplantation in rats is a unique model for vascularized bone marrow transplantation because bone marrow cells and bone marrow stroma are transplanted by microsurgical means, thus creating immediate bone marrow space and engraftment. However, it contains a skin component and other musculoskeletal tissues that complicate issues related to tolerance induction. MATERIALS AND METHODS: To study only aspects of vascularized bone marrow transplantation, we created a new isolated vascularized bone marrow transplant model in rats. The common iliac (or femoral) artery and vein were microsurgically anastomosed to the recipient abdominal aorta and inferior vena cava in an end-to-side fashion, respectively. Syngeneic male Lewis (RT1(1), n = 20) and allogeneic male BN (RT1(n), n = 10) donors were transplanted to female Lewis recipients. To establish rejection criteria, we examined histopathology and used the polymerase chain reaction (PCR) to assess microchimerism of donor male bone marrow cells in the peripheral blood of female recipients using rat Y chromosome (sex-determining region Y)-specific primers. RESULTS: All recipients were healthy and remained stable without major complications for up to 300 days posttransplant. Morphologically, syngeneic male Lewis bone marrow showed a near-normal appearance. Allogeneic male BN bone marrow was clearly rejected. Male bone marrow cells were detected by PCR in the peripheral blood of all syngeneic recipients, but not in allogeneic blood specimens. CONCLUSIONS: A new surgical approach to bone marrow transplantation was established. This consisted of the vascularized femoral bone/bone marrow transplant. Further analyses regarding the ability of vascularized femoral bone marrow transplants to induce systemic transplantation tolerance in adult rats will provide insights into not only various issues of immunology but also the potential clinical application of vascularized bone marrow transplantation.

Animals↗
PubMed2000

Intracellular pH measurements of the whole head and the basal ganglia in chronic liver disease: a phosphorus-31 MR spectroscopy study.

The purpose of this study was to determine the intracellular pH of the whole head and in voxels localized to the basal ganglia in patients with chronic liver disease using phosphorus-31 magnetic resonance spectroscopy (31P MRS). The study group compromised 82 patients with biopsy-proven cirrhosis (43 Child's grade A, 25 Child's grade B and 14 Child's grade C). Eleven subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, 37 showed evidence of minimal hepatic encephalopathy and 34 had overt hepatic encephalopathy. Unlocalized 31P MRS of the whole head was performed in 48 patients and 10 healthy volunteers. Localized 31P MRS of the basal ganglia was performed in the 34 patients and in 20 healthy volunteers. The intracellular pH values were calculated from the chemical shift difference between the inorganic phosphate (P) and phosphocreatine (PCr) resonances. The percentage inorganic phosphate (%Pi), phosphocreatine (%PCr) and betaNTP signals, relative to the total 31P signal, and peak area ratios of inorganic phosphate and phosphocreatine, relative to betaNTP were also measured. There were no differences between patients and volunteers in intracellular pH in 31P MR spectra measured from the whole head or the basal ganglia. There was no correlation between the severity of encephalopathy (West Haven criteria) or liver dysfunction (Child score) and intracellular pH values. There was also no significant change in the inorganic phosphate, phosphocreatine or betaNTP resonances in spectra acquired from the whole head. However, in spectra localized to the basal ganglia, there was a significant increase in mean P/NTP (p=0.02) and PCr/NTP (p=0.009). The mean %Pi and mean %PCr were also increased (p=0.06; p=0.05, respectively), but there was no significant change in mean %betaNTP. When the patient population was classified according to the severity of encephalopathy, those with overt disease had a higher mean P/NTP and %Pi (p=0.03; p=0.01), compared to the reference population. Our results suggest that there are detectable bioenergetic abnormalities in patients with minimal hepatic encephalopathy or stable, overt chronic hepatic encephalopathy, but any associated intracellular pH change is probably a secondary, rather than a primary phenomenon.

Adult↗
PubMed2000

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution.

Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages.

Animals↗
PubMed2000

Effect of genetic cross on the detection of quantitative trait loci and a novel approach to mapping QTLs.

A genome-wide scan was conducted in two F(2) intercrosses, C57BL/6J (B6)xDBA/2J (D2) and BALB/cJ (C)xLP/J (LP), for three different phenotypes: basal locomotor activity, ethanol-induced locomotor activity, and haloperidol-induced catalepsy. For basal activity, significant quantitative trait loci (QTLs, LOD> or =4.3) were detected on chromosomes 9 and 19 for the CxLP intercross and chromosome 1 for the B6xD2 intercross. Significant QTLs for ethanol-induced activation were detected on chromosome 6 for the CxLP intercross, and on chromosomes 1 and 2 for the B6xD2 intercross. For haloperidol-induced catalepsy, significant QTLs were detected on chromosome 14 (two different QTLs) in the CxLP intercross, and chromosomes 1 and 9 in the B6xD2 intercross. These data illustrate the importance of the genetic cross for QTL detection. Finally, the data reported here, and elsewhere, are also used to demonstrate a novel approach to QTL detection and localization.

Animals↗
PubMed2000

Accuracy of CO2 angiography in vessel diameter assessment: a comparative study of CO2 versus iodinated contrast material in an aortoiliac flow model.

PURPOSE: Precise vessel sizing prior to endovascular intervention is critical to achievement of technical success. Diameter measurements obtained with CO2 and iodinated contrast material in an aortoiliac flow model were compared. MATERIALS AND METHODS: Aortoiliac flow was simulated in a compliant, silicone elastomer phantom of the aortoiliac system using an autoperfusion pump (flow volume, approximately 1100 mL/min; mean arterial pressure, 70-80 mm Hg at 80-90 cycles/minute) and a glycerol solution (40% by weight; viscosity 3.7 centipoise at 20 degrees C). Digital subtraction angiography was performed with the phantom in the anteroposterior (AP) plane and in three oblique planes with both CO2 and iodinated contrast material. Five sets of images for both CO2 and iodinated contrast material were obtained for each projection. Two readers independently performed vessel diameter measurements at seven sites (distal abdominal aorta, bilateral proximal and distal common iliac, and mid-external iliac arteries). The model was then evaluated with intravascular ultrasound (IVUS) using a 20-MHz imaging catheter. Actual diameter measurements were taken from the inner wall to inner wall in orthogonal planes at the same locations within the model, as described previously. Analysis was performed to determine local difference in measurements (t tests), difference when compared to the standard AP projection with iodinated contrast material (Dunnett's test) and inter-reader variability (Pitman's test). RESULTS: The contralateral iliac vessel segment did not opacify when imaging with CO2 in the 45 degrees obliquities; thus, 22 of 28 sites were available for comparison. At 18 of 22 (81.8%) sites, there was significant difference in vessel measurements (P < .01), with CO2 yielding a significantly larger diameter at 17 of 22 (77.3%) of the sites. The difference in mean diameter ranged from -1.28 to 4.47 mm. With use of the AP iodinated contrast material run as the standard, there were significant differences (P < .05) in vessel diameter at 17 of 22 (77.3%) and four of 21 (19%) sites for CO2 and iodinated contrast material respectively, with CO2 tending toward greater diameter measurements. Significant differences (P < .05) in variance between the two readers were present but occurred primarily with CO2 in the AP projection and iodinated contrast material in the 45 degrees left obliquity. With use of IVUS as the standard, there were significant differences (P < .05) in the measured vessel diameters with CO2 at nine of 22 (40.9%) of the sites and with iodinated contrast material at 17 of 28 (60.7%) of the sites. Of the measurements made with CO2, seven of nine (77.8%) of the measurements were of larger diameter than those obtained with IVUS. By contrast, of the measurements made with iodinated contrast material angiography, IVUS measured larger diameters in 16 of 17 (94.1%). CONCLUSION: CO2 angiography consistently yielded significantly larger vessel measurements when compared to both iodinated contrast angiography and WVUS. These results have important implications in regards to planning intervention based solely on CO2 angiography. Further evaluation is needed before recommending CO2 for vessel sizing in clinical practice.

Angiography, Digital Subtraction↗