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K Patel

Publications and source records attributed to K Patel.

At least 37 records · Page 2Linked to original sources
PubMed2001

Molecular and cellular analysis of embryonic avian tongue development.

Signalling cascades first described in Drosophila have been found to regulate patterning and outgrowth in a number of structures in higher vertebrates. We sought to determine whether the evolutionarily conserved genes were important during the development of the tongue. In situ hybridisation was used to determine the temporo-spatial expression of a panel of conserved genes. Histological examination and incorporation of BrdU were used to determine the mechanism by which the tongue develops. We show that evolutionarily conserved genes were expressed in distinct dynamic patterns during tongue development. Sonic Hedgehog (Shh) and Patched (Ptc) were found only in the dorsal tongue epithelium. Shh expression was only observed in the suprabasal layers, whereas Ptc was observed in both basal and suprabasal layers. Cell division in the epithelium was concentrated in regions devoid of Shh. Expression of bone morphogenetic protein-7 (BMP) was identical to that of Shh. Shh and Ptc expression were never detected in the mesenchyme. Ectopic expression of Noggin (a potent antagonist of the BMPs) caused severe abnormalities in tongue morphology, including swelling of the mesenchymal component and a thickening of the epithelial layer. Data from this study suggests that the epithelium and mesenchyme express quite different genes during development. However BMP activity acts to inhibit growth in both tissues.

Activins↗
PubMed2001

Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine.

Development of noninvasive methods for the diagnosis of transitional cell carcinoma (TCC) of the bladder remains a challenge. A ProteinChip technology (surface enhanced laser desorption/ionization time of flight mass spectrometry) has recently been developed to facilitate protein profiling of biological mixtures. This report describes an exploratory study of this technology as a TCC diagnostic tool. Ninety-four urine samples from patients with TCC, patients with other urogenital diseases, and healthy donors were analyzed. Multiple protein changes were reproducibly detected in the TCC group, including five potential novel TCC biomarkers and seven protein clusters (mass range, 3.3 to 133 kd). One of the TCC biomarkers (3.4 kd) was also detected in bladder cancer cells procured from bladder barbotage and was identified as defensin. The TCC detection rates provided by the individual markers ranged from 43 to 70% and specificities from 70 to 86%. Combination of the protein biomarkers and clusters, increased significantly the sensitivity for detecting TCC to 87% with a specificity of 66%. Interestingly, this combinatorial approach provided sensitivity of 78% for detecting low-grade TCC compared to only 33% of voided urine or bladder-washing cytology. Collectively these results support the potential of this proteomic approach for the development of a highly sensitive urinary TCC diagnostic test.

Adult↗
PubMed2001

FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent.

Here we report the use of fluorescence recovery after photobleaching (FRAP) to examine the intranuclear dynamics of fluorescent oestrogen receptor-alpha (ER). After bleaching, unliganded ER exhibits high mobility (recovery t1/2 < 1 s). Agonist (oestradiol; E2) or partial antagonist (4-hydroxytamoxifen) slows ER recovery (t1/2 approximately 5-6 s), whereas the pure antagonist (ICI 182,780) and, surprisingly, proteasome inhibitors each immobilize ER to the nuclear matrix. Dual FRAP experiments show that fluorescent ER and SRC-1 exhibit similar dynamics only in the presence of E2. In contrast to reports that several nuclear proteins show uniform dynamics, ER exhibits differential mobility depending upon several factors that are linked to its transcription function.

Bacterial Proteins↗
PubMed2001

USMLE-style exam.

Explore the source record for details and available documents.

Education, Medical, Undergraduate↗
PubMed2001

Induction and excretion of ultraviolet-induced 8-oxo-2'-deoxyguanosine and thymine dimers in vivo: implications for PUVA.

Molecular epidemiology has linked ultraviolet-induced DNA damage with mutagenesis and skin carcinogenesis. Ultraviolet radiation may damage DNA in one of two ways: either directly, leading to lesions such as cyclobutane thymine dimers (T<>T), or indirectly, via photosensitizers that generate free radical species that may ultimately produce such oxidative lesions as 8-oxo-2'-deoxyguanosine. We report the results of a pilot, case control study in which seven, healthy, human volunteers (skin type II; aged 23-56 y; three male, four female) received a suberythemal dose of whole body irradiation from ultraviolet-A-emitting fluorescent tubes used in psoralen plus ultraviolet A therapy. First void, mid-stream urine samples were collected pre-exposure and daily postexposure, for up to 13 d. Analysis of urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers was by competitive enzyme-linked immunosorbent assay (interassay coefficient of variation < or = 10%) and compared with a matched, control group of unirradiated individuals. A maximal increase in levels of urinary 8-oxo-2'-deoxyguanosine was seen 4 d post-ultraviolet exposure. A subsequent reduction was noted, before finally returning to baseline. Similarly, cyclobutane thymine dimer levels peaked 3 d postexposure, before returning to baseline. In contrast to the 8-oxo-2'-deoxyguanosine analysis, however, a second peak was noted at days 9-11, before again returning to baseline. This is the first report examining urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers following ultraviolet exposure of healthy human subjects. This work illustrates the induction and time course for excretion of ultraviolet-induced lesions, perhaps alluding to repair and ultimately offering the potential to define psoralen plus ultraviolet A dosage regimes in terms of minimizing DNA damage and hence cancer risk.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Spinal ultrasound in cloacal exstrophy.

AIM: To assess the diagnostic value of spinal ultrasound in cloacal exstrophy, a caudal malformation which is associated with spinal dysraphism, and to assess the prevalence of spinal dysraphism in cloacal exstrophy. MATERIALS AND METHODS: Ten infants under 1 year old with cloacal exstrophy underwent spinal ultrasound at presentation. Three patients also had a magnetic resonance imaging (MRI) examination. Ultrasound and MRI images were reviewed and correlated. RESULTS: Nine of 10 patients had no external signs of spinal dysraphism. One patient had a clinically apparent myelomeningocele. Five of 10 patients (50%) had spinal dysraphism on ultrasound: there were two patients with a low cord, two with tethered cords and a lipoma, and one patient with tethering and a myelomeningocele. Thus, in four of these five patients spinal dysraphism was occult. In a small number of patients (n = 3) MRI was also performed-in these cases the MRI and ultrasound appearances correlated, however MRI was not performed in those patients in whom spinal ultrasound was normal. CONCLUSION: In three cases where spinal ultrasound detected occult dysraphism and MRI was performed, spinal ultrasound and MRI correlated. Advantages of spinal ultrasound include ease of examination, production of high quality multi-planar images and the facility for portable imaging at the bedside. Spinal ultrasound should be the first investigation in all babies with cloacal exstrophy to diagnose occult and non-occult spinal dysraphism.

Cloaca↗
PubMed2001

Reference values of amniotic fluid neuron-specific enolase.

OBJECTIVE: Enolase is a dimeric cytoplasmic enzyme whose double gamma isoenzyme, neuron-specific enolase, is predominantly found in neuronal and neuroendocrine tissues. Cell injury causes its release into the blood and cerebrospinal fluid (CSF). Neuron-specific enolase has been measured in the serum and CSF of adults and full-term asphyxiated neonates as a marker of neurological injury. We recently observed an elevation of neuron-specific enolase in the amniotic fluid of women whose neonates subsequently developed intraventricular hemorrhage or periventricular leukomalacia. The purpose of our study was to establish reference values of neuron-specific enolase in the amniotic fluid as a function of gestational age. METHODS: A total of 110 amniotic fluid samples, obtained primarily for genetic studies (16-20 weeks, n = 22), for evaluation of preterm labor (21-35 weeks, n = 66) and for fetal lung maturity studies (36-40 weeks, n = 22), were analyzed for neuron-specific enolase. Samples were from women who subsequently delivered term neonates with normal neurological examinations or who delivered preterm neonates with normal neurosonograms up to the 7th day of life. Descriptive statistics and non-parametric correlations were used for analysis. RESULTS: There was no correlation between gestational age and concentration of neuron-specific enolase (Spearman's r = 0.059, p = 0.63). The overall mean neuron-specific enolase value was 2.5 +/- 1.39 microg/l. The highest value obtained was 6 microgl. Of the 110 women, 105 (95.5%) had neuron-specific enolase values of less than 5 microg/l, while five (4.5%) had values ranging from 5 to 6 microg/l. CONCLUSIONS: The amniotic fluid level of neuron-specific enolase does not change as a function of gestational age. These stable levels may have utility in the evaluation of cases with fetal neurological injury.

Adult↗
PubMed2001

The anatomical distribution of colorectal polyps at colonoscopy.

BACKGROUND: Colorectal carcinoma is one of the most common causes of cancer-related deaths in Australia. The distribution of polyps in the colon may effect the efficacy of a screening modality. The aim of this study was to determine the age-matched anatomic location and histologic type of colorectal polyps observed at colonoscopy over a 10-year period at our endoscopy unit. STUDY: Endoscopy reports on 2,578 patients were reviewed; polyp/lesion histology and location (left, right, or both) were determined in 2,553. RESULTS: Of all polyps observed, 1,310 (51%) cases were left-sided, 510 (20%) were right-sided, and 733 (29%) were synchronous. Adenomas were present in 1,659 cases (65%); of these, 734 (44%) were left-sided only and 405 (24.5%) were right-sided only. Carcinoma was observed in 189 (7%) cases, of which 71 (37.5%) were left-sided only. There was an increased right-sided prevalence of adenoma or carcinoma with age (p = 0.0029). CONCLUSION: This was not a screening study, but it has shown that a significant number of adenomas and carcinomas lie proximal to the splenic flexure. Thus, in the absence of left-sided lesions, it is expected that examination of the colon limited to the splenic flexure would miss 23% of such lesions. The increasing right-sided prevalence of these lesions with age suggests that evaluation of the proximal bowel is particularly important in older people.

Adenomatous Polyps↗
PubMed2001

Ethanol-induced reduction in myocardial oxygen consumption can be attenuated by inhibiting guanylyl cyclase.

We tested the hypothesis that low-dose ethanol-induced reductions in myocardial metabolism were related to increased cyclic guanosine monophosphate (GMP). Anesthetized open chest rabbits were divided into four groups: control (Ringers lactate and vehicle), ETOH (250 mg/kg i.v. ethanol and vehicle), ODQ (Ringers lactate and 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ 10(-4) M ), and ETOH-ODQ (ethanol and ODQ). ODQ, a soluble guanylyl cyclase inhibitor, or vehicle was applied topically to the epicardium for 15 min, while either Ringers lactate or ethanol was administered intravenously. Oxygen consumption (VO2 ) in both the subepicardium (EPI) and subendocardium (ENDO) was determined from coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry). Cyclic GMP was determined by radioimmunoassay. ETOH significantly decreased VO2 in the subepicardium (9.2 +/- 1.0-5.6 +/- 0.7 ml O2 /min/100 g) and subendocardium (9.7 +/- 0.8-7.1 +/- 0.8) and increased cyclic GMP in the subepicardium (10.2 +/- 1.7-13.8 +/- 0.8 pmol/g) and subendocardium (11.0 +/- 0.5-13.7 +/- 0.9). With ODQ, there was no significant change in the subepicardial (9.5 +/- 1.3) or subendocardial (9.0 +/- 0.9) VO2. However, ODQ caused a significant increase in both wall thickening (12.9 +/- 0.9-17.2 +/- 1.2%) and maximal rate of change in wall thickness (10.8 +/- 0.9-16.3 +/- 1.9 mm/s) and decreased subepicardium (8.3 +/- 1.3) and subendocardium (7.8 +/- 1.2) cyclic GMP. The ETOH-ODQ group had cyclic GMP (subepicardium 9.0 +/- 1.8, subendocardium 8.6 +/- 2.4) and VO2 (subepicardium 7.9 +/- 0.5, subendocardium 8.4 +/- 0.4) values similar to control. Thus, the ethanol-induced rise in cyclic GMP was associated with a decrease in myocardial O2 consumption. When this rise was blocked with a soluble guanylyl cyclase inhibitor, the reduction in metabolic demand was also eliminated. This demonstrated that the alcohol-induced reduction in myocardial metabolism was related to increased cyclic GMP and suggests a novel mechanism for the effect of ethanol.

Administration, Topical↗
PubMed2001

Rapid oscillometric blood pressure measurement compared to conventional oscillometric measurement.

BACKGROUND: There have been few reports studying the necessary interval between blood pressure measurements, after the initial rest period. METHODS: Blood pressure was measured in 50 patients using the conventional oscillometric technique (COT) and the rapid oscillometric technique (ROT). RESULTS: The difference between COT and ROT was -1.1 / -0.1 mmHg, which was not significantly different (p = 0.8 / 1.0) and the pulse difference was -0.8 beats per minute (p = 0.8). CONCLUSIONS: It is concluded that a 15-second interval between blood pressure readings is as accurate as a one-minute interval providing that these measurements are started after a 5-minute rest period.

Adult↗
PubMed2001

CD40 and CD86 upregulation with divergent CMRF44 expression on blood dendritic cells in inflammatory bowel diseases.

OBJECTIVE: Dendritic cells (DC) are the only antigen-presenting cells that can activate naïve T lymphocytes and initiate a primary immune response. They are also thought to have a role in immune tolerance. DC traffic from the blood to peripheral tissue where they become activated. They then present antigen and the costimulating signals necessary to initiate an immune response. In this study, we investigated the number, subsets, and activation pattern of circulating and intestinal DC from patients with clinically mild ulcerative colitis (UC) or Crohn's disease. METHODS: Patients were recruited, if they were not taking immunosuppressive therapy, and were assessed for clinical severity of their disease using for UC, the Clinical Activity Index, and for Crohn's disease, the Crohn's Disease Activity Index. Blood CD11c+ and CD11c- DC subsets, expression of costimulatory antigens, CD86 and CD40, and the early differentiation/activation antigen, CMRF44, were enumerated by multicolor flow cytometry of lineage negative (lin- = CD3-, CD19-, CD14-, CD16-) HLA-DR+ DC. These data were compared with age-matched healthy and the disease control groups of chronic noninflammatory GI diseases (cGI), acute noninflammatory GI diseases (aGI), and chronic non-GI inflammation (non-GI). In addition, cryostat sections of colonoscopic biopsies from healthy control patients and inflamed versus noninflamed gut mucosa of inflammatory bowel disease (IBD) patients were examined for CD86+ and CD40+ lin- cells. RESULTS: Twenty-one Crohn's disease and 25 UC patients, with mean Crohn's Disease Activity Index of 98 and Clinical Activity Index of 3.1, and 56 healthy controls, five cGI, five aGI, and six non-GI were studied. CD11c+ and CD11c- DC subsets did not differ significantly between Crohn's, UC, and healthy control groups. Expression of CD86 and CD40 on freshly isolated blood DC from Crohn's patients appeared higher (16.6%, 31%) and was significantly higher in UC (26.6%, 46.3%) versus healthy controls (5.5%, 25%) (p = 0.004, p = 0.012) and non-GI controls (10.2%, 22.8%) (p = 0.012, p = 0.008), but not versus cGI or aGI controls. CD86+ and CD40+ DC were also present in inflamed colonic and ileal mucosa from UC and Crohn's patients but not in noninflamed IBD mucosa or normal mucosa. Expression of the CMRF44 antigen was low on freshly isolated DC, but it was upregulated after 24-h culture on DC from all groups, although significantly less so on DC from UC versus Crohn's or healthy controls (p = 0.024). The CMRF44+ antigen was mainly associated with CD11c+ DC, and in UC was inversely related to the Clinical Activity Index (r = -0.69, p = 0.0002). CONCLUSIONS: There is upregulation of costimulatory molecules on blood DC even in very mild IBD but surprisingly, there is divergent expression of the differentiation/activation CMRF44 antigen. Upregulation of costimulatory molecules and divergent expression of CMRF44 in blood DC was also apparent in cGI and aGI but not in non-GI or healthy controls, whereas intestinal CD86+ and CD40+ DC were found only in inflamed mucosa from IBD patients. Persistent or distorted activation of blood DC or divergent regulation of costimulatory and activation antigens may have important implications for gut mucosal immunity and inflammation.

Adolescent↗
PubMed2001

Escherichia coli CdtB mediates cytolethal distending toxin cell cycle arrest.

We previously reported that the CdtB polypeptide of Escherichia coli cytolethal distending toxin (CDT) shares significant pattern-specific homology with mammalian type I DNases. In addition, the DNase-related residues of CdtB are required for cellular toxicity. Here we demonstrate that purified CdtB converts supercoiled plasmid DNA to relaxed and linear forms and promotes cell cycle arrest when combined with an E. coli extract containing CdtA and CdtC. CdtB alone had no effect on HeLa cells, however; introduction of the polypeptide into HeLa cells by electroporation resulted in cellular distension, chromatin fragmentation, and cell cycle arrest, all of which are consequences of CDT action. In contrast to these findings, purified CdtB(H154A) lacked both DNA-nicking and cell cycle arrest activities. These results suggest a functional relationship between DNase-related residues in CdtB and CDT biological activity.

Bacterial Toxins↗
PubMed2001

Ligand-mediated assembly and real-time cellular dynamics of estrogen receptor alpha-coactivator complexes in living cells.

Studies with live cells demonstrate that agonist and antagonist rapidly (within minutes) modulate the subnuclear dynamics of estrogen receptor alpha (ER) and steroid receptor coactivator 1 (SRC-1). A functional cyan fluorescent protein (CFP)-tagged lac repressor-ER chimera (CFP-LacER) was used in live cells to discretely immobilize ER on stably integrated lac operator arrays to study recruitment of yellow fluorescent protein (YFP)-steroid receptor coactivators (YFP-SRC-1 and YFP-CREB binding protein [CBP]). In the absence of ligand, YFP-SRC-1 is found dispersed throughout the nucleoplasm, with a surprisingly high accumulation on the CFP-LacER arrays. Agonist addition results in the rapid (within minutes) recruitment of nucleoplasmic YFP-SRC-1, while antagonist additions diminish YFP-SRC-1-CFP-LacER associations. Less ligand-independent colocalization is observed with CFP-LacER and YFP-CBP, but agonist-induced recruitment occurs within minutes. The agonist-induced recruitment of coactivators requires helix 12 and critical residues in the ER-SRC-1 interaction surface, but not the F, AF-1, or DNA binding domains. Fluorescence recovery after photobleaching indicates that YFP-SRC-1, YFP-CBP, and CFP-LacER complexes undergo rapid (within seconds) molecular exchange even in the presence of an agonist. Taken together, these data suggest a dynamic view of receptor-coregulator interactions that is now amenable to real-time study in living cells.

Amino Acid Motifs↗
PubMed2001

Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.

Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).

Administration, Oral↗
PubMed2001

Slit proteins are not dominant chemorepellents for olfactory tract and spinal motor axons.

Members of the Slit family are large extracellular glycoproteins that may function as chemorepellents in axon guidance and neuronal cell migration. Their actions are mediated through members of the Robo family that act as their receptors. In vertebrates, Slit causes chemorepulsion of embryonic olfactory tract, spinal motor, hippocampal and retinal ganglion cell axons. Since Slits are expressed in the septum and floor plate during the period when these tissues cause chemorepulsion of olfactory tract and spinal motor axons respectively, it has been proposed that Slits function as guidance cues. We have tested this hypothesis in collagen gel co-cultures using soluble Robo/Fc chimeras, as competitive inhibitors, to disrupt Slit interactions. We find that the addition of soluble Robo/Fc has no effect on chemorepulsion of olfactory tract and spinal motor axons when co-cultured with septum or floor plate respectively. Thus, we conclude that although Slits are expressed in the septum and floor plate, their proteins do not contribute to the major chemorepulsive activities emanating from these tissues which cause repulsion of olfactory tract and spinal motor axons.

Animals↗
PubMed2001

Down and out in America: children and health care.

One of the worst forms of inequality in the health care field is the inequality suffered by children. In 1996, over 14.5 million children lived in poverty in the United States. Children who live in poverty are less likely to have health insurance and have less access to health care and thus are more likely to suffer negative outcomes in health care. The Congress of the United States in 1997 enacted the State Children's Health Insurance Program (S-CHIP) to expand health insurance coverage for children. This paper examines the major features of the program, actions undertaken by the state governments under this program to expand health insurance coverage for children, and provides some preliminary analysis of the potential positive and negative impact of the program.

Adolescent↗
PubMed2001

Peginterferon alpha-2b: a new approach to improving response in hepatitis C patients.

Chronic hepatitis C infection affects approximately four million Americans. Over the last decade, Type 1 interferons (IFNs) have been the mainstay of therapy for suitable patients. Recently, the combination of IFN plus ribavirin, with enhanced response rates, has replaced IFN monotherapy for treatment of these patients. The addition of a polyethylene glycol (peg) moiety to IFN alpha-2b has provided a drug with reduced clearance whilst retaining biological and antiviral activity. This formulation allows once-weekly dosing and enhances sustained response rates, without significantly changing the safety and tolerability of IFN. Clinical trials indicate a doubling of sustained virological response rates for regimens utilising pegIFN alpha-2b, compared with standard IFN-alpha 2b. The combination of pegIFN alpha-2b and ribavirin further increases the sustained virological response rates to > 50% for suitable patients. Future pegIFN alpha-2b studies will need to examine drug profiles in patients with co-morbid conditions (e.g., renal impairment, liver transplantation), as well as safety and efficacy issues in different ethnic groups. Further clinical trials are also required to determine the benefits of pegIFN alpha-2b in previous non-responders or relapse patients and as maintenance therapy to prevent disease progression. Finally, careful cost effectiveness analyses will need to be performed.

Animals↗