16 results on '"Price PM"'
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2. A role for novel cell-cycle proteins in podocyte biology.
- Author
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Price PM
- Subjects
- Adult, Animals, Cell Cycle Proteins genetics, Cell Differentiation genetics, Cell Division, Humans, Kidney Diseases genetics, Kidney Diseases metabolism, Kidney Glomerulus metabolism, Mice, Mice, Knockout, Proteins genetics, Cell Cycle Proteins metabolism, Kidney metabolism, Podocytes metabolism, Proteins metabolism
- Abstract
Cell-cycle proteins influence almost all aspects of embryogenesis and differentiation. In adults, these proteins control cell division and regeneration after injury. During the past several years, their roles in controlling reaction to stress have been demonstrated in several organ systems. In the kidney, the cell types affected include both tubular and glomerular compartments. Now a novel cell cycle-related protein is shown to influence podocyte biology.
- Published
- 2010
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- View/download PDF
3. The cell cycle and acute kidney injury.
- Author
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Price PM, Safirstein RL, and Megyesi J
- Subjects
- Acute Disease, Animals, Apoptosis, Cyclin-Dependent Kinase Inhibitor p21 physiology, Cyclin-Dependent Kinase Inhibitor p27 physiology, Cyclin-Dependent Kinases physiology, DNA Damage, Humans, Cell Cycle, Kidney pathology
- Abstract
Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute kidney injury.
- Published
- 2009
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4. Diabetes: caught in the Akt?
- Author
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Price PM
- Subjects
- Animals, Cell Cycle, Cell Line, Phosphatidylinositol 3-Kinases drug effects, Proto-Oncogene Proteins c-akt drug effects, Diabetic Nephropathies physiopathology, Glucose pharmacology, Kidney Diseases physiopathology, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism
- Abstract
One complication of diabetes is a pronounced renal cellular hypertrophy, inevitably resulting in chronic fibrotic changes. Chuang and colleagues demonstrate that hypertrophy in vitro is dependent on an increased phosphoinositide 3-kinase (PI3K) activity and is correlated with increased levels of p21(WAF1/Cip1), a cell-cycle regulator that was previously associated with renal fibrosis and sclerosis from nondiabetic causes.
- Published
- 2007
- Full Text
- View/download PDF
5. Cell cycle regulation: repair and regeneration in acute renal failure.
- Author
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Price PM, Megyesi J, and Saf Irstein RL
- Subjects
- Animals, Cyclin-Dependent Kinase Inhibitor p21, Humans, Kidney metabolism, Kidney pathology, Acute Kidney Injury metabolism, Acute Kidney Injury pathology, Cell Cycle Proteins metabolism, Cyclins metabolism
- Abstract
Research into mechanisms of acute renal failure has begun to reveal molecular targets for possible therapeutic intervention. Much useful knowledge into the causes and prevention of this syndrome has been gained by the study of animal models. Most recently, investigation of the effects on acute renal failure of selected gene knock-outs in mice has contributed to our recognition of many previously unappreciated molecular pathways. Particularly, experiments have revealed the protective nature of two highly induced genes whose functions are to inhibit and control the cell cycle after acute renal failure. By use of these models we have started to understand the role of increased cell cycle activity after renal stress, and the role of proteins induced by these stresses that limit this proliferation.
- Published
- 2004
- Full Text
- View/download PDF
6. FDG-PET for response assessment: answers in search of questions.
- Author
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Laking GR and Price PM
- Subjects
- Chemotherapy, Adjuvant, Esophageal Neoplasms pathology, Esophageal Neoplasms therapy, Humans, Radiotherapy, Adjuvant, Remission Induction, Treatment Outcome, Esophageal Neoplasms diagnostic imaging, Fluorodeoxyglucose F18, Radiopharmaceuticals, Tomography, Emission-Computed
- Published
- 2002
- Full Text
- View/download PDF
7. Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure.
- Author
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Megyesi J, Andrade L, Vieira JM Jr, Safirstein RL, and Price PM
- Subjects
- Animals, Cyclin-Dependent Kinase Inhibitor p21, Ischemia pathology, Ischemia physiopathology, Mice, Mice, Knockout genetics, Reperfusion Injury pathology, Survival Analysis, Acute Kidney Injury etiology, Acute Kidney Injury physiopathology, Cyclins genetics, Gene Expression Regulation physiology, Ischemia complications, Renal Circulation
- Abstract
Background: The p21 protein is found in the nucleus of most cells where it modulates cell cycle activity. At low levels, p21 stabilizes interactions between D cyclins and their cyclin-dependent kinases (cdks), but at high levels after induction by several different stress pathways, it causes cell cycle arrest. The p21 mRNA is induced in murine kidney after several types of acute renal failure, including cisplatin administration, ischemia-reperfusion, and ureteral obstruction. We reported that after cisplatin injection, mice with a p21 gene deletion developed much more severe renal damage than wild-type mice. To dissociate the effects of cisplatin-induced DNA damage and subsequent initiation of DNA damage-dependent cell death pathways from effects of acute renal failure, we have now examined mice after ischemia-reperfusion, a model of renal failure not associated with genotoxin-induced DNA damage early after the injury., Methods: Wild-type and p21(-/-) mice were made ischemic by clamping both renal hila for 30 or 50 minutes. At various times after reflow, mortality and parameters of renal function and morphology were quantified. Also, the nuclear proteins p21 and proliferating cell nuclear antigen (PCNA) were localized in kidney sections by immunohistochemistry., Results: Kidney function was more impaired and mortality increased significantly in p21(-/-) mice as compared with p21(+/+) mice. We found more cell cycle activity, indicated by increased number of mitotic cells and nuclear PCNA-positive cells, in kidney of p21(-/-) mice., Conclusions: In this study, p21(-/-) mice were more susceptible to ischemia-induced acute renal failure, with similarly elevated levels of parameters of cell cycle activity. We propose that the increased and inappropriate cell cycle activity in kidney cells is responsible for the increased kidney impairment and mortality.
- Published
- 2001
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8. Two routes to [11C-carbonyl]organo-isocyanates utilizing [11C]phosgene ([11C]organo-isocyanates from [11C]phosgene).
- Author
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Brown GD, Henderson D, Steel C, Luthra S, Price PM, and Brady F
- Subjects
- Chromatography, High Pressure Liquid, Isocyanates chemistry, Isotope Labeling, Phosgene chemistry, Carbon Radioisotopes, Isocyanates chemical synthesis
- Abstract
Two generic radiosynthetic routes for the preparation of [11C-carbonyl]isocyanates have been developed. Reaction of N-organo-sulfinylamines; RNSO, (R = Me, Et, allyl, cyclohexyl and phenyl) with [11C]phosgene gave the corresponding [11C-carbonyl]isocyanates in good radiochemical yield (53-68%) from [11C]phosgene (decay corrected) in ca 16 min from EOB. Alternatively, the reaction of [11C]phosgene with N,N'-organo-ureas; (RNH)(2)CO, (R = Me, Et, Pr and phenyl) also gave the corresponding [11C-carbonyl]isocyanates in moderate radiochemical yield (9-37%) from [11C]phosgene (decay corrected) in ca 16 min from EOB. For identification, the [11C-carbonyl]organo-isocyanates were derivatized with 1-(2-methoxyphenyl)piperazine in situ to [11C-carbonyl]carboxamides and the position of radiolabelling in the carbonyl group confirmed by [11/13C]co-labeling and subsequent carbon-13 NMR spectroscopy.
- Published
- 2001
- Full Text
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9. Modulation of fluorouracil tissue pharmacokinetics by eniluracil: in-vivo imaging of drug action.
- Author
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Saleem A, Yap J, Osman S, Brady F, Suttle B, Lucas SV, Jones T, Price PM, and Aboagye EO
- Subjects
- Administration, Oral, Adult, Aged, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic therapeutic use, Dihydrouracil Dehydrogenase (NADP), Drug Interactions, Enzyme Inhibitors administration & dosage, Female, Fluorouracil administration & dosage, Fluorouracil therapeutic use, Gastrointestinal Neoplasms drug therapy, Half-Life, Humans, Injections, Intravenous, Liver drug effects, Liver metabolism, Male, Middle Aged, Tissue Distribution, Tomography, Emission-Computed, Uracil administration & dosage, Uracil pharmacology, Antimetabolites, Antineoplastic pharmacokinetics, Enzyme Inhibitors pharmacology, Fluorouracil pharmacokinetics, Gastrointestinal Neoplasms metabolism, Oxidoreductases antagonists & inhibitors, Uracil analogs & derivatives
- Abstract
Background: Fluorouracil is widely used for chemotherapy of gastrointestinal cancer, but response rates are poor. Eniluracil is being developed as an inactivator of dihydropyrimidine dehydrogenase, the enzyme that brings about first-pass degradation of fluorouracil. We studied the mechanism of action of eniluracil by measuring with positron emission tomography (PET) the effect of eniluracil on tumour and normal-tissue pharmacokinetics of fluorine-18-labelled fluorouracil., Methods: Six patients with advanced gastrointestinal cancers were studied. PET scanning was done after injection of oxygen-15-labelled water to assess tissue blood flow, followed by 1 mg/m2 18F-fluorouracil. We compared the pharmacokinetics of 18F-fluorouracil when the patients had not received eniluracil, during a 4-day course of oral eniluracil, and during a 28-day course of oral fluorouracil plus eniluracil., Findings: In eniluracil-naïve patients, 18F-fluorouracil localised more strongly (mean 0.0234% [SE 0.0019] of injected activity per mL tissue at 11 min) in liver than in tumours (0.0032% [0.0004]). There was substantial inhibition, after eniluracil administration, of radiotracer uptake and retention in normal liver (mean area under the time versus radioactivity curve 0.927 [SE 0.086] vs 1.857 [0.169] m2 mL(-1) s) and kidneys (1.096 [0.048] vs 5.043 [0.915] m2 mL(-1) s). There was also an increase in plasma uracil and unmetabolised 18F-fluorouracil and an increase in the radiotracer half-life in tumours (2.3 h to >4.0 h)., Interpretation: Two events strongly suggested increased exposure of 18F-fluorouracil and its anabolites in the tumours, consistent with the inactivation of dihydropyrimidine dehydrogenase: a selective decrease in radiotracer exposure in normal liver and kidneys compared with tumours; and an increase in radiotracer half-life in tumours.
- Published
- 2000
- Full Text
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10. DNA synthesis is dissociated from the immediate-early gene response in the post-ischemic kidney.
- Author
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Megyesi J, Di Mari J, Udvarhelyi N, Price PM, and Safirstein R
- Subjects
- Animals, Autoradiography, Cycloheximide pharmacology, Gene Expression, Immunohistochemistry, Male, Proto-Oncogene Proteins c-fos metabolism, Proto-Oncogene Proteins c-jun metabolism, Rats, Rats, Sprague-Dawley, Reperfusion Injury genetics, DNA biosynthesis, Genes, Immediate-Early, Kidney metabolism, Renal Circulation, Reperfusion Injury metabolism
- Abstract
The response of the kidney to ischemic injury includes increased DNA synthesis, which is preceded by rapid and brief expression of the c-fos proto-oncogene. While the timing of these two events would suggest that c-Fos participates in an immediate-early gene program leading to proliferation, no direct test of this hypothesis exists. The purpose of these studies was (1) to determine whether c-fos is expressed as part of a typical immediate-early (IE) gene response, which would require co-expression of c-jun and sensitivity to cycloheximide, and (2) to determine whether the cells expressing c-Fos are the same as those undergoing DNA synthesis. Northern analysis was performed on renal mRNA at different times following release of a 50 minute period of renal hilar clamping. c-jun and c-fos mRNA were rapidly and briefly expressed following renal ischemia and their expression was superinduced by cycloheximide in a manner typical of an immediate-early gene response. 3H-thymidine autoradiography performed on semi-thin sections from intravascularly perfusion fixed kidneys 24 hours following induction of ischemia showed labeled nuclei in cells lining the damaged proximal tubules of the outer stripe of the outer medulla, as well as proximal tubules in the cortex and interstitial cells throughout the kidney. However, immunohistochemical localization of c-Fos and c-Jun protein occurred predominantly in nuclei of the thick ascending limb, distal tubule and collecting duct cells. The studies demonstrate that c-fos and c-jun are expressed following renal ischemia as a typical immediate-early gene response, but they are expressed in cells that do not enter the cell cycle. The failure of the cells to enter the cell cycle may depend on the co-expression of jun-B and jun-D, which suppress the mitogenic activity of c-Jun in other cells. The data suggest that the IE response following renal ischemia is part of the stress response, which is antiproliferative rather than proliferative. The role of the stress response during renal ischemia and the fate of the cells undergoing it are unknown.
- Published
- 1995
- Full Text
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11. Erythroplasia of Queyrat treated with isotretinoin.
- Author
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Harrington KJ, Price PM, Fry L, and Witherow RO
- Subjects
- Administration, Oral, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Erythroplasia drug therapy, Isotretinoin administration & dosage, Penile Neoplasms drug therapy
- Published
- 1993
- Full Text
- View/download PDF
12. Tumour inoculation during laparoscopy.
- Author
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O'Rourke N, Price PM, Kelly S, and Sikora K
- Subjects
- Abdominal Neoplasms secondary, Adenocarcinoma secondary, Aged, Aged, 80 and over, Cecal Neoplasms pathology, Cholecystectomy, Laparoscopic adverse effects, Female, Gallbladder Neoplasms pathology, Humans, Middle Aged, Laparoscopy adverse effects, Neoplasm Seeding
- Published
- 1993
13. Ureteral obstruction decreases renal prepro-epidermal growth factor and Tamm-Horsfall expression.
- Author
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Storch S, Saggi S, Megyesi J, Price PM, and Safirstein R
- Subjects
- Acute Kidney Injury etiology, Acute Kidney Injury genetics, Acute Kidney Injury metabolism, Animals, DNA biosynthesis, DNA genetics, Epidermal Growth Factor genetics, Gene Expression, Male, Mucoproteins genetics, Protein Precursors genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Inbred Strains, Ureteral Obstruction complications, Ureteral Obstruction genetics, Uromodulin, Epidermal Growth Factor biosynthesis, Kidney metabolism, Mucoproteins biosynthesis, Protein Precursors biosynthesis, Ureteral Obstruction metabolism
- Abstract
Northern and dot-blot analysis of polyadenylated RNAs of kidney cortical and outer medullary tissue was performed in male Sprague-Dawley rats at varying times up to 24 hours after bilateral ureteral obstruction (BUO), after 24 hours of unilateral obstruction (UUO) and at varying periods after release of BUO or UUO. Pre-proEGF (preproEGF) and Tamm-Horsfall (TH) mRNA declined by four hours of BUO to virtually undetectable levels at 24 hours of ureteral obstruction. Upon release of BUO or UUO, preproEGF and TH mRNA returned slowly toward normal but remained below control levels up to four days after release of ureteral obstruction. Urinary EGF excretion paralleled these changes in renal preproEGF mRNA. Although these changes are similar to those observed during nephrotoxic and ischemic renal failure, where the expression of the immediate early genes precedes the fall in preproEGF and TH expression, no such increase in the expression of these genes occurred after bilateral ureteral obstruction. These changes in preproEGF and TH expression could also be dissociated from uremia and high rates of DNA synthesis, suggesting that ureteral obstruction itself is a sufficient cause of the reduced expression. The increase in ureteral pressure and its functional and humoral effects may each play a role in reduced preproEGF and TH expression during ureteral obstruction.
- Published
- 1992
- Full Text
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14. Changes in gene expression after temporary renal ischemia.
- Author
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Safirstein R, Price PM, Saggi SJ, and Harris RC
- Subjects
- Animals, Blotting, Northern, Immunoblotting, Male, Rats, Rats, Inbred Strains, Time Factors, DNA biosynthesis, Epidermal Growth Factor genetics, Gene Expression, Ischemia genetics, Kidney blood supply, Protein Precursors genetics, Proto-Oncogenes genetics, RNA, Messenger genetics
- Abstract
Temporary renal ischemia is followed by increased DNA synthesis and cell division as the kidney restores the continuity of the renal epithelium. We sought to characterize some of the changes in proto-oncogene and growth factor expression during this proliferative response. Northern analysis of polyadenylated RNAs of kidney cortical and outer stripe of outer medullary tissue from male Sprague-Dawley rats was performed following release of renal hilar clamping of 50 minutes duration. Ischemia produced an increase in c-fos mRNA that reached a peak at one hour and declined rapidly to control levels by four hours after release of the clamp. A similar rapid increase and decrease in early growth response 1 (Egr 1) mRNA was noted. The response of these immediate early genes was typical of their response to mitogens, suggesting that they served a similar role in renal cell regeneration. Levels of c-Ki-ras and glyceraldehyde phosphate dehydrogenase mRNA were unchanged. Renal preproEGF mRNA decreased at two hours, was virtually absent by 24 hours and remained low for at least four days after ischemia. Urinary excretion of EGF fell immediately after release of ischemia and before the decline in preproEGF mRNA or SNGFR, suggesting post-transcriptional affects of ischemia on renal EGF production. EGF excretion returned to only 50% of control by day 21. Specific 125I-EGF binding increased in membrane fractions of cortex, outer medulla and inner medulla as early as 24 hours after release of the clamp. Cortical 125I-EGF binding increased in the proximal tubule but not in the glomerulus.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1990
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15. Reduced renal prepro-epidermal growth factor mRNA and decreased EGF excretion in ARF.
- Author
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Safirstein R, Zelent AZ, and Price PM
- Subjects
- Acute Kidney Injury etiology, Animals, Blotting, Northern, Cisplatin toxicity, Epidermal Growth Factor genetics, Male, Protein Precursors genetics, Rats, Rats, Inbred Strains, Renal Artery Obstruction complications, Acute Kidney Injury metabolism, Epidermal Growth Factor metabolism, Kidney Cortex metabolism, Protein Precursors metabolism, RNA, Messenger analysis
- Abstract
Levels of prepro epidermal growth factor (EGF) mRNA in renal cortical tissue and urinary EGF excretion have been determined during cisplatin and ischemia-induced acute renal failure in the rat. Northern analysis of polyadenylated RNAs of kidney cortical tissue showed diminished renal preproEGF mRNA in rats injected with cisplatin (5 mg/kg). The decrease in preproEGF mRNA occurred as early as 12 hours in the kidney and persisted for at least three days after cisplatin injection. The submandibular gland, a major site of EGF synthesis, contained normal levels of preproEGF mRNA. Transplatin, a non-nephrotoxic isomer of cisplatin, did not reduce renal preproEGF mRNA levels. Northern analysis of polyadenylated RNAs of kidney cortical tissue 24 hours after a 50 minute period of renal pedicle clamping also showed reduced preproEGF mRNA levels. By contrast, cisplatin increased renal c-fos mRNA. Urinary EGF excretion was also reduced after cisplatin and ischemia and the decrease in EGF excretion correlated significantly with the degree of renal failure. The data show that nephrotoxic and ischemic renal cell injury reduces preproEGF mRNA and urinary EGF excretion. Reduced preproEGF mRNA and diminished EGF excretion may be important in the functional and regenerative responses to renal injury.
- Published
- 1989
- Full Text
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16. Evolutionary significance of persistence of latent oncogenic virus information in vertebrates.
- Author
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Hirschhorn K, Gabelman N, Price PM, and Waxman S
- Subjects
- Animals, Antigens, Neoplasm, Biological Evolution, Cell Transformation, Neoplastic, DNA, Genes, Humans, Hypersensitivity, Delayed immunology, Immune Tolerance, Leukemia Virus, Murine immunology, Leukemia, Experimental immunology, Mice, Neoplasms immunology, RNA, Viral biosynthesis, T-Lymphocytes immunology, Transcription, Genetic, Transformation, Genetic, Virulence, Genetic Code, Oncogenic Viruses immunology
- Published
- 1973
- Full Text
- View/download PDF
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