379 results on '"Brown PA"'
Search Results
252. TEMPONE reduces renal dysfunction and injury mediated by oxidative stress of the rat kidney.
- Author
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Patel NS, Chatterjee PK, Chatterjee BE, Cuzzocrea S, Serraino I, Brown PA, Stewart KN, Mota-Filipe H, and Thiemermann C
- Subjects
- Animals, Coloring Agents pharmacology, Dose-Response Relationship, Drug, Hydrogen Peroxide pharmacology, Immunohistochemistry, Kidney drug effects, Kidney metabolism, Kidney physiology, Kidney Diseases drug therapy, Male, Mice, Nitrogen chemistry, Poly Adenosine Diphosphate Ribose chemistry, Poly(ADP-ribose) Polymerases chemistry, Rats, Rats, Wistar, Reactive Oxygen Species, Reperfusion Injury, Tetrazolium Salts pharmacology, Thiazoles pharmacology, Tyrosine chemistry, Urine, Kidney pathology, Kidney Diseases pathology, Oxidative Stress, Triacetoneamine-N-Oxyl pharmacology, Tyrosine analogs & derivatives
- Abstract
Here we investigate the effects of the stable, water-soluble nitroxyl radical, TEMPONE, on renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the rat kidney in vivo. TEMPONE significantly improved both glomerular and tubular function (serum urea, creatinine, creatinine clearance, and fractional excretion of Na(+)) in a dose-dependent manner and significantly attenuated the reperfusion-injury associated with I/R (urinary N-acetyl-beta-D-glucosaminidase, aspartate aminotransferase, assessment of renal histology). TEMPONE also markedly reduced the immunohistochemical evidence of the formation of nitrotyrosine and poly(ADP-ribose), indicating reduction of nitrosative and oxidative stress, respectively. The latter was reflected in vitro, where TEMPONE significantly reduced cellular injury of primary cultures of rat renal proximal tubular (PT) cells caused by hydrogen peroxide in a dose-dependent manner. Importantly, in contrast to its in vivo metabolite TEMPOL (which also provided protective effects against renal I/R and oxidative stress of PT cells), TEMPONE reduced renal dysfunction and injury without causing a significant reduction in blood pressure upon administration. These results suggest, for the first time, that TEMPONE can reduce the renal dysfunction and injury caused by I/R and the injury caused to PT cells by oxidative stress without producing the adverse cardiovascular effects observed when using other nitroxyl radicals.
- Published
- 2002
- Full Text
- View/download PDF
253. Agonists of peroxisome-proliferator activated receptor-alpha (clofibrate and WY14643) reduce renal ischemia/reperfusion injury in the rat.
- Author
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Sivarajah A, Chatterjee PK, Hattori Y, Brown PA, Stewart KN, Todorovic Z, Mota-Filipe H, and Thiemermann C
- Subjects
- Animals, Gene Expression, Intercellular Adhesion Molecule-1 genetics, Kidney blood supply, Kidney physiopathology, Male, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear genetics, Reperfusion Injury genetics, Reperfusion Injury physiopathology, Transcription Factors genetics, Clofibrate pharmacology, Kidney drug effects, Kidney injuries, Pyrimidines pharmacology, Receptors, Cytoplasmic and Nuclear agonists, Reperfusion Injury prevention & control, Transcription Factors agonists
- Abstract
Background: The aim of this study was to investigate the effects of peroxisome-proliferator activated receptor-alpha (PPAR-alpha) agonists, clofibrate and WY14643 on the renal dysfunction and injury caused by bilateral ischemia/reperfusion (I/R) of rat kidneys in vivo., Material/methods: Male Wistar rats were anesthetized with sodium thiopentone (120 mg/kg i.v.) and subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary biochemical indicators of renal dysfunction and injury were measured; serum creatinine (sCr, glomerular dysfunction), fractional excretion of Na+ (FENa, tubular dysfunction), and urinary N-acetyl-b-D-glucosaminidase (uNAG, tubular injury). Additionally, renal sections were used for histological grading of renal injury and for RT-PCR analysis of the expression of PPAR-isoforms in kidneys obtained from rats prior to or after I/R. In addition, expression of intercellular adhesion molecule-1 (ICAM-1) was determined using Northern blot analysis., Results: Using RT-PCR, we document here the expression of PPAR-alpha, PPAR-beta and PPAR-gamma1 (but not PPAR-gamma2) in the kidney of the rat. I/R resulted in the down-regulation of PPAR-alpha without modulation of any other PPAR. Clofibrate and WY14643 significantly reduced the increases in sCr, FENa and uNAG caused by renal I/R, indicating attenuation of renal dysfunction and injury. Expression of ICAM-1 caused by I/R of the kidney was not modulated by PPAR-alpha agonists., Conclusions: We show here that (i) renal I/R results in the down-regulation of PPAR-alpha in the kidney, and (ii) that the PPAR-alpha agonists clofibrate and WY14643 reduce the renal dysfunction and injury associated with I/R of the kidney.
- Published
- 2002
254. Bone-marrow-derived macrophages genetically modified to produce IL-10 reduce injury in experimental glomerulonephritis.
- Author
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Wilson HM, Stewart KN, Brown PA, Anegon I, Chettibi S, Rees AJ, and Kluth DC
- Subjects
- Albuminuria immunology, Albuminuria therapy, Animals, Glomerulonephritis immunology, Glomerulonephritis pathology, Immunotherapy methods, Interferon-gamma metabolism, Interleukin-10 genetics, Interleukin-10 therapeutic use, Kidney pathology, Macrophages immunology, Macrophages transplantation, Male, Rats, Rats, Sprague-Dawley, Transduction, Genetic, Tumor Necrosis Factor-alpha metabolism, Bone Marrow Cells cytology, Cell- and Tissue-Based Therapy methods, Glomerulonephritis genetics, Glomerulonephritis therapy, Interleukin-10 metabolism, Macrophages cytology, Macrophages metabolism
- Abstract
Macrophages are intimately involved in the development of immune-mediated inflammation, including glomerulonephritis. We have transduced primary cultures of macrophages to express IL-10 and tested the ability of these cells to control rat nephrotoxic nephritis (NTN), a model of human glomerulonephritis. Ad-IL-10-transduced bone-marrow-derived macrophages (BMDM) produced large amounts of IL-10 in culture, and their TNF-alpha production was decreased in response to interferon-gamma and LPS. Transduced macrophages were injected into the renal artery of rats, 6 h after the induction of NTN, where they localized efficiently to inflamed rat glomeruli. Delivery of IL-10-expressing macrophages to nephritic rats produced a marked reduction in albuminuria compared with unmodified NTN or injection of Ad-null-transduced BMDM. IL-10 treatment decreased the number of glomerular ED1- and ED3-positive cells, MHC class II expression, and the number of fibrinoid lesions. Interestingly, anti-inflammatory changes in the Ad-IL-10-injected kidney were mirrored by changes in the contralateral kidney. These results highlight that Ad-IL-10-transduced macrophages infiltrate inflamed glomeruli and reduce the severity of glomerular inflammation, emphasizing the value of local delivery of genetically modified macrophages in the manipulation of inflammatory disease.
- Published
- 2002
- Full Text
- View/download PDF
255. Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.
- Author
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Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, and Driscoll M
- Subjects
- Aging genetics, Aging pathology, Animals, Biomarkers analysis, Caenorhabditis elegans physiology, Caenorhabditis elegans Proteins genetics, Cellular Senescence genetics, Gene Expression Regulation, Genes, Helminth, Humans, Locomotion physiology, Longevity genetics, Longevity physiology, Muscles cytology, Muscles pathology, Muscles physiology, Mutation genetics, Nervous System Physiological Phenomena, Neurons cytology, Neurons physiology, Organ Specificity, Phenotype, Reproduction, Stochastic Processes, Time Factors, Aging physiology, Caenorhabditis elegans cytology, Caenorhabditis elegans genetics, Cellular Senescence physiology, Phosphatidylinositol 3-Kinases
- Abstract
The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages. We report remarkable preservation of the nervous system, even in advanced old age, in contrast to a gradual, progressive deterioration of muscle, resembling human sarcopenia. The age-1(hx546) mutation, which extends lifespan by 60-100%, delayed some, but not all, cellular biomarkers of ageing. Strikingly, we found strong evidence that stochastic as well as genetic factors are significant in C. elegans ageing, with extensive variability both among same-age animals and between cells of the same type within individuals.
- Published
- 2002
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256. Lipoteichoic acid from Staphylococcus aureus reduces renal ischemia/reperfusion injury.
- Author
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Chatterjee PK, Zacharowski K, Cuzzocrea S, Brown PA, Stewart KN, Mota-Filipe H, and Thiemermann C
- Subjects
- Animals, Antioxidants pharmacology, Cyclic N-Oxides pharmacology, Kidney Diseases pathology, Kidney Tubules drug effects, Kidney Tubules metabolism, Kidney Tubules pathology, Male, Malondialdehyde metabolism, Nitric Oxide biosynthesis, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, P-Selectin metabolism, Peroxidase metabolism, Rats, Rats, Wistar, Reperfusion Injury pathology, Spin Labels, Tyrosine metabolism, Kidney Diseases drug therapy, Lipopolysaccharides pharmacology, Reperfusion Injury drug therapy, Staphylococcus aureus chemistry, Teichoic Acids pharmacology, Tyrosine analogs & derivatives
- Abstract
Background: The aim of this study was to investigate whether in vivo administration of a low, sub-lethal dose of lipoteichoic acid (LTA), a bacterial wall-fragment derived from the Gram-positive bacterium Staphylococcus aureus, protects the kidney against the renal dysfunction and injury caused by ischemia/reperfusion (I/R)., Methods: Male Wistar rats were administered LTA from S. aureus (1 mg/kg, IP). After 24 hours, rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary markers were measured for the assessment of renal function, tubular and reperfusion-injury. Renal sections were used for histological grading of renal injury and for immunohistochemical localization of P-selectin, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicative of peroxynitrite formation). Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Nitric oxide (NO) production was determined by measurement of plasma nitrite/nitrate levels., Results: LTA pretreatment significantly reduced renal dysfunction, tubular and reperfusion-injury caused by I/R of the kidney as well as histological evidence of renal injury. LTA also reduced the expression of P-selectin and kidney MPO activity associated with renal I/R. MDA levels were significantly reduced by LTA pretreatment suggesting a reduction in the lipid peroxidation and formation of reactive oxygen species (ROS). LTA pretreatment also markedly reduced both the expression of iNOS and the formation of nitrotyrosine associated with renal I/R. Although LTA significantly reduced plasma nitrite/nitrate levels associated with I/R, nitrite/nitrate levels remained at levels significantly higher than that measured from the plasma obtained from Sham-operated animals., Conclusions: These data suggest, to our knowledge for the first time, that LTA pretreatment for 24 hours significantly reduces renal I/R injury. We propose that the mechanism of the protective effect involves reduction of the production of NO, ROS and peroxynitrite subsequent to reduced P-selectin and iNOS expression and PMN recruitment. However, although LTA pretreatment resulted in a reduction of iNOS expression and NO production, we hypothesize that the remaining significant levels of NO contribute to the beneficial actions provided by LTA.
- Published
- 2002
- Full Text
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257. Electrical enhancement of formulated plasmid delivery in animals.
- Author
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Draghia-Akli R, Khan AS, Cummings KK, Parghi D, Carpenter RH, and Brown PA
- Subjects
- Alkaline Phosphatase blood, Alkaline Phosphatase metabolism, Animals, Body Weight, DNA metabolism, Dogs, Dose-Response Relationship, Drug, Embryo, Mammalian metabolism, Genetic Vectors, Injections, Intramuscular, Mice, Polyglutamic Acid metabolism, Swine, Time Factors, Electroporation, Gene Transfer Techniques, Plasmids metabolism
- Abstract
Electroporation has been shown to significantly increase plasmid transfer to the skeletal muscle, but this procedure is also implicated in muscle damage. We are reporting a highly efficient in vivo transfer of a plasmid formulated with poly-(L-glutamate) (PLG) into murine, canine and porcine muscle fibers using electric pulses of low field intensity. In mice and pigs, the use of secreted embryonic alkaline phosphatase (SEAP) as the indicator gene caused increased PLG expression by 2-3 fold compared to naked plasmid; while delivery of a PLG-plasmid formulation to dogs showed a 10-fold increase in serum SEAP levels compared to plasmid alone. Muscle lesions were reduced by the protective PLG. Thus, PLG may constitute a useful adjuvant for increased expression and reduced muscle trauma to plasmid DNA delivered by electroporation.
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- 2002
- Full Text
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258. Blood contrast enhancement with a novel, non-gaseous nanoparticle contrast agent.
- Author
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Wickline SA, Hughes M, Ngo FC, Hall CS, Marsh JN, Brown PA, Allen JS, McLean MD, Scott MJ, Fuhrhop RW, and Lanza GM
- Subjects
- Animals, Dogs, Emulsions, Injections, Intravenous, Nanotechnology, Particle Size, Phantoms, Imaging, Contrast Media chemistry, Fluorocarbons chemistry, Ultrasonography, Doppler, Color methods
- Published
- 2002
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259. Renal injury in apolipoprotein E-deficient mice.
- Author
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Wen M, Segerer S, Dantas M, Brown PA, Hudkins KL, Goodpaster T, Kirk E, LeBoeuf RC, and Alpers CE
- Subjects
- Animals, Antigens, Differentiation biosynthesis, Apolipoproteins E genetics, Galectin 3, Immunohistochemistry, Kidney metabolism, Kidney pathology, Kidney Glomerulus pathology, Mice, Mice, Knockout, Apolipoproteins E deficiency, Hyperlipidemias physiopathology, Kidney physiopathology
- Abstract
Hyperlipidemia is thought to accelerate the progression of renal diseases, but the mechanisms by which hyperlipidemia exerts its deleterious effect is still poorly understood. The aim of this study was to describe the renal pathology in a hyperlipidemic mouse strain, the apolipoprotein E-deficient mice (apoE-/-). Renal specimens from a total of 34 mice were studied, including 19 apoE-/- females at the age of 36 weeks, 9 apoE-/- females at the age of 24 weeks, and 6 wild-type females (C57BL/6) as controls. Kidneys were evaluated by histologic examination, immunohistochemistry, and electron microscopy. Immunohistochemistry was used to detect MAC-2-expressing monocyte/macrophages, and the proliferation marker PCNA. Glomerular cell number, glomerular matrix area, and glomerular area were quantified by morphometry. Glomerular lesions in apoE-/- mice were characterized by macrophage accumulation, commonly with foam cell appearance, deposition of extracellular matrix, glomerular hyperplasia, and at times prominent mesangiolysis associated with capillary microaneurysms. Some cases demonstrated lipid deposits filling glomerular capillaries. Arterioles of the vascular pole demonstrated a "foamy" degeneration of smooth muscle cells. These lesions related to hyperlipidemia in this well-established mouse strain have not been previously described. Because this mouse strain is among the most widely studied for interventions aimed at altering hyperlipidemia and the progression of atherosclerosis, we believe that our observations may be of major importance for the accurate interpretation of interventional studies in this strain and offer a new opportunity to study mechanisms of hyperlipidemic renal injury.
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- 2002
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260. Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury.
- Author
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Chatterjee PK, Patel NS, Kvale EO, Cuzzocrea S, Brown PA, Stewart KN, Mota-Filipe H, and Thiemermann C
- Subjects
- Animals, Cells, Cultured, Cytokines pharmacology, Kidney Glomerulus drug effects, Kidney Glomerulus physiopathology, Kidney Tubules drug effects, Kidney Tubules pathology, Kidney Tubules physiopathology, Kidney Tubules, Proximal metabolism, Kidney Tubules, Proximal pathology, Male, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type II, Rats, Rats, Wistar, Thiourea analogs & derivatives, Tyrosine biosynthesis, Enzyme Inhibitors pharmacology, Ischemia pathology, Ischemia physiopathology, Lysine analogs & derivatives, Lysine pharmacology, Nitric Oxide Synthase antagonists & inhibitors, Renal Circulation drug effects, Reperfusion Injury pathology, Reperfusion Injury physiopathology, Thiourea pharmacology, Tyrosine analogs & derivatives
- Abstract
Background: Nitric oxide (NO), produced via inducible nitric oxide synthase (iNOS), is implicated in the pathophysiology of renal ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of the iNOS inhibitors L-N6-(1-iminoethyl)lysine (L-NIL) and aminoethyl-isothiourea (AE-ITU) on (a) renal dysfunction and injury mediated by bilateral I/R of rat kidneys in vivo and (b) cytokine-stimulated NO production by primary cultures of rat proximal tubule (PT) cells., Methods: Male Wistar rats subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Rats were administered either L-NIL (3 mg/kg IV bolus 15 min prior to I/R followed by 1 mg/kg/h throughout I/R) or AE-ITU (1 mg/kg IV bolus 15 min prior to I/R followed by 1 mg/kg/h throughout I/R). Serum and urinary biochemical indicators of renal dysfunction and injury were measured; serum creatinine (SCr, glomerular dysfunction), fractional excretion of Na+ (FENa, tubular dysfunction), serum aspartate aminotransferase (sAST, I/R injury) and urinary N-acetyl-beta-d-glucosaminidase (uNAG, tubular injury). Additionally, renal sections were used for histological grading of renal injury and for immunological evidence of nitrotyrosine formation. Nitrate/nitrate levels in plasma were measured using the Griess assay and used as an indicator of NO production. Primary cultures of rat PT cells were incubated with interferon-gamma(IFN-gamma, 100 IU/mL) and lipopolysaccharide (LPS, 10 microg/mL) for 24 h, either in the absence or presence of increasing concentrations of L-NIL or AE-ITU (0.001 to 1 mmol/L) after which nitrite/nitrate levels were measured using the Griess assay., Results: L-NIL and AE-ITU significantly reduced the I/R-mediated increases in SCr, FENa, sAST and uNAG, indicating attenuation of I/R-mediated renal dysfunction and injury. Specifically, L-NIL and AE-ITU reduced the I/R-mediated glomerular and tubular dysfunction and biochemical and histological evidence of tubular injury. Both L-NIL and AE-ITU attenuated the plasma levels of nitrate (indicating reduced NO production) and the immunohistochemical evidence of the formation of nitrotyrosine. In vitro, L-NIL and AE-ITU both significantly reduced cytokine-stimulated NO production by primary cultures of rat PT cells in a dose-dependent manner., Conclusions: These results suggest that L-NIL and AE-ITU reduce the renal dysfunction and injury associated with I/R of the kidney, via inhibition of iNOS activity and subsequent reduction of NO (and peroxynitrite) generation. We propose that selective and specific inhibitors of iNOS activity may be useful against the NO-mediated renal dysfunction and injury associated with I/R of the kidney.
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- 2002
- Full Text
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261. Development of an internet-based rainfall atlas for Alabama.
- Author
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Durrans SR and Brown PA
- Subjects
- Alabama, Data Collection, Reference Values, Environmental Monitoring, Internet, Rain
- Abstract
In the United States, rainfall information needed for intensity-duration-frequency (IDF) curves or design storm hyetographs can be found in TP 40, HYDRO-35, and the NOAA Atlas 2. Additional rainfall data collected since the dates of those publications, and improved methods for statistical treatment of data, have motivated update studies in several regions of the United States. One of the new studies has been performed for the State of Alabama. Results of the Alabama study are embodied in an internet-based graphical user interface, which permits users to interactively point and click on a geographical location of interest, and have IDF curves and/or storm hyetographs returned on demand. Reactions to the internet-based rainfall atlas have been promising, and have led to additional work for the National Weather Service, Office of Hydrologic Development.
- Published
- 2002
262. Traditional versus hazard analysis and critical control point-based inspection: results from a poultry slaughter project.
- Author
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Cates SC, Anderson DW, Karns SA, and Brown PA
- Subjects
- Animals, Chickens, Meat standards, Safety Management, Sanitation standards, Consumer Product Safety, Food Contamination prevention & control, Food Inspection methods, Meat microbiology
- Abstract
Federal meat and poultry inspection has changed little since the Federal Meat Inspection Act was passed in 1906, followed by the Poultry Products Inspection Act of 1957 and related amendments. These acts mandate sensory or organoleptic (sight, smell, and touch) inspection of all carcasses. For several decades, the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS) has been urged by various organizations to move to a scientific, risk-based inspection system. In partial response to these calls, the FSIS has developed new slaughter inspection models that are currently being tested with volunteer plants in the hazard analysis and critical control point (HACCP)-based inspection models project. To evaluate whether plants operating under the new inspection models perform at least as well as they did under the current or traditional system, microbial and organoleptic data are being collected before and after the implementation of the new inspection models. In this article, we describe the baseline and models data collection procedures and present the results of the baseline and models data collection for eight plants that slaughter young chickens. The results from the first eight volunteer plants suggest that inspection under the new models is equivalent and in some ways superior to that of traditional inspection. This pilot project suggests that new slaughter inspection systems, which rely on HACCP principles with FSIS oversight and verification services, can maintain or even improve food safety and other consumer protection conditions relative to traditional hands-on inspection methods.
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- 2001
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263. The application of kudzu as a medium for the adsorption of heavy metals from dilute aqueous wastestreams.
- Author
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Brown PA, Brown JM, and Allen SJ
- Subjects
- Adsorption, Bioreactors, Cadmium isolation & purification, Copper isolation & purification, Models, Theoretical, Waste Disposal, Fluid, Zinc isolation & purification, Metals, Heavy isolation & purification, Rosales, Water Pollutants, Chemical isolation & purification
- Abstract
This study assessed the use of kudzu (Pueraria lobata ohwi) as a medium for the capture of copper, cadmium, and zinc from low concentration solutions. The rate and extent of uptake was studied using a system of standardized batch adsorbers under steady-state and transient-rate conditions. All plant components were tested. Residual metals analyses were performed on an ICP-AES/OES (Optima 3000 DV). The Langmuir, Freundlich, and Redlich-Peterson isotherms were determined; the Langmuir isotherm was found to best represent the data for copper and cadmium uptake. The Redlich-Peterson best represented the data for zinc. Kudzu was determined to be an effective adsorbent for removal of heavy metals. Though its capacity for metals removal is less than commercial grade ion exchange resins, it could be used at much lower cost, and may find application in the treatment of dilute mixed-matrix metal wastestreams, such as urban runoff, where the application of resins would be expensive and subject to premature poisoning by interfering contaminants.
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- 2001
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264. Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat.
- Author
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Chatterjee PK, Brown PA, Cuzzocrea S, Zacharowski K, Stewart KN, Mota-Filipe H, McDonald MC, and Thiemermann C
- Subjects
- Acetylglucosaminidase urine, Acute Kidney Injury metabolism, Acute Kidney Injury pathology, Anesthesia, Animals, Aspartate Aminotransferases blood, Cyclooxygenase 2, Glutathione Transferase urine, Immunohistochemistry, Isoenzymes analysis, Isoenzymes metabolism, Kidney Glomerulus blood supply, Kidney Glomerulus enzymology, Kidney Glomerulus pathology, Male, Malondialdehyde metabolism, NF-kappa B metabolism, Nitric Oxide Synthase analysis, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, Oligopeptides pharmacology, Peroxidase metabolism, Prostaglandin-Endoperoxide Synthases analysis, Prostaglandin-Endoperoxide Synthases metabolism, Rats, Rats, Wistar, Reperfusion Injury metabolism, Reperfusion Injury pathology, Serine Proteinase Inhibitors pharmacology, gamma-Glutamyltransferase blood, Acute Kidney Injury drug therapy, Cysteine Proteinase Inhibitors pharmacology, Glycoproteins pharmacology, Reperfusion Injury drug therapy
- Abstract
Background: Activation of the cysteine protease calpain has been implicated in renal ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of calpain inhibitor-1 (Cal I-1) in an in vivo model of renal I/R injury., Methods: Male Wistar rats were administered Cal I-1 (10 mg/kg, IP) 30 minutes before undergoing bilateral renal ischemia (45 minutes) followed by reperfusion (6 hours). Plasma concentrations of urea, creatinine, Na(+), gamma-glutamyl transferase (gamma GT), aspartate aminotransferase (AST) and urinary Na(+), glutathione S-transferase (GST), and N-acetyl-beta-D-glucosaminidase (NAG) were measured for the assessment of renal dysfunction and I/R injury. Creatinine clearance (C(Cr)) and fractional excretion of Na(+) (FE(Na)) were used as indicators of glomerular and tubular function, respectively. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of neutrophil infiltration and lipid peroxidation, respectively. Renal sections were used for histologic grading of renal injury and for immunohistochemical localization of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)., Results: Cal I-1 significantly reduced I/R-mediated increases in urea, creatinine, gamma GT, AST, NAG, and FE(Na) and significantly improved C(Cr). Cal I-1 also significantly reduced kidney MPO activity and MDA levels. Cal I-1 also reduced histologic evidence of I/R-mediated renal damage and caused a substantial reduction in the expression of iNOS and COX-2, both of which involve activation of nuclear factor-kappa B (NF-kappa B)., Conclusions: : These results suggest that Cal I-1 reduces the renal dysfunction and injury associated with I/R of the kidney. We suggest that the mechanism could involve the inhibition of I/R-mediated activation of NF-kappa B.
- Published
- 2001
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265. Novel approaches to the analysis of the Maillard reaction of proteins.
- Author
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Fayle SE, Healy JP, Brown PA, Reid EA, Gerrard JA, and Ames JM
- Subjects
- Electrophoresis, Gel, Two-Dimensional methods, Electrophoresis, Polyacrylamide Gel methods, Lysine analysis, Food Analysis methods, Maillard Reaction, Proteins analysis
- Abstract
The Maillard reaction comprises a complex network of reactions which has proven to be of great importance in both food science and medicine. The majority of methods developed for studying the Maillard reaction in food have focused on model systems containing amino acids and monosaccharides. In this study, a number of electrophoretic techniques, including two-dimensional gel electrophoresis and capillary electrophoresis, are presented. These have been developed specifically for the analysis of the Maillard reaction of food proteins, and are giving important insights into this complex process.
- Published
- 2001
- Full Text
- View/download PDF
266. Direct and moderating effects of community context on the psychological well-being of African American women.
- Author
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Cutrona CE, Russell DW, Hessling RM, Brown PA, and Murry V
- Subjects
- Adult, Child, Female, Humans, Mothers psychology, Residence Characteristics, Social Support, Adaptation, Psychological, Black or African American psychology, Gender Identity, Social Environment, Social Identification
- Abstract
The effects of community characteristics on well-being were examined among 709 African American women. Direct and moderating effects of neighborhood characteristics on distress were tested. Aggregate-level ratings of neighborhood cohesion and disorder were significantly related to distress, although the relation between cohesion and distress became nonsignificant when individual risk factors were statistically controlled. Aggregate-level neighborhood variables interacted significantly with individual risk and resource variables in the prediction of distress, consistent with trait-situation interaction theories (D. Magnusson & N. S. Endler, 1977). Community cohesion intensified the benefits of a positive life outlook. Community disorder intensified both the benefits of personal resources and the detrimental effects of personal risk factors. Results showed evidence of resilience among African American women.
- Published
- 2000
- Full Text
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267. Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat.
- Author
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Chatterjee PK, Cuzzocrea S, Brown PA, Zacharowski K, Stewart KN, Mota-Filipe H, and Thiemermann C
- Subjects
- Acute Kidney Injury metabolism, Acute Kidney Injury pathology, Animals, Cell Membrane Permeability, Cell Separation, Cells, Cultured, Chelating Agents pharmacology, Deferoxamine pharmacology, Disease Models, Animal, Hydrogen Peroxide pharmacology, Kidney Glomerulus blood supply, Kidney Glomerulus enzymology, Kidney Glomerulus pathology, Kidney Tubules, Proximal enzymology, Kidney Tubules, Proximal pathology, Male, Malondialdehyde metabolism, Necrosis, Oxidants pharmacology, Peroxidase metabolism, Poly(ADP-ribose) Polymerases analysis, Poly(ADP-ribose) Polymerases biosynthesis, Rats, Rats, Wistar, Reperfusion Injury metabolism, Reperfusion Injury pathology, Spin Labels, Tyrosine analogs & derivatives, Tyrosine analysis, Acute Kidney Injury drug therapy, Cyclic N-Oxides pharmacology, Free Radical Scavengers pharmacology, Oxidative Stress drug effects, Reperfusion Injury drug therapy
- Abstract
Background: The generation of reactive oxygen species (ROS) contributes to the pathogenesis of renal ischemia-reperfusion injury. The aim of this study was to investigate the effects of tempol in (1) an in vivo rat model of renal ischemia/reperfusion injury and on (2) cellular injury and death of rat renal proximal tubular (PT) cells exposed to oxidant stress in the form of hydrogen peroxide (H2O2)., Methods: Male Wistar rats underwent bilateral renal pedicle clamping for 45 minutes followed by reperfusion for six hours. Tempol (30 mg/kg/h), desferrioxamine (DEF; 40 mg/kg/h), or a combination of tempol (30 mg/kg/h) and DEF (40 mg/kg/h) were administered prior to and throughout reperfusion. Plasma concentrations of urea, creatinine, Na+, gamma-glutamyl transferase (gammaGT), aspartate aminotransferase (AST), and urinary Na+ and N-acetyl-beta-D-glucosaminidase (NAG) were measured for the assessment of renal function and reperfusion injury. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Renal sections were used for histologic grading of renal injury and for immunohistochemical localization of nitrotyrosine and poly(ADP-ribose) synthetase (PARS). Primary cultures of rat PT cells were incubated with H2O2 (1 mmol/L for 4 h) either in the absence or presence of increasing concentrations of tempol (0.03 to 10 mmol/L), DEF (0.03 to 10 mmol/L), or a combination of tempol (3 mmol/L) or DEF (3 mmol/L). PT cell injury and death were determined by evaluating mitochondrial respiration and lactate dehydrogenase (LDH) release, respectively., Results: In vivo, tempol significantly reduced the increase in urea, creatinine, gammaGT, AST, NAG, and FENa produced by renal ischemia/reperfusion, suggesting an improvement in both renal function and injury. Tempol also significantly reduced kidney MPO activity and MDA levels, indicating a reduction in PMN infiltration and lipid peroxidation, respectively. Tempol reduced the histologic evidence of renal damage associated with ischemia/reperfusion and caused a substantial reduction in the staining for nitrotyrosine and PARS, suggesting reduced nitrosative and oxidative stress. In vitro, tempol significantly attenuated H2O2-mediated decrease in mitochondrial respiration and increase in LDH release from rat PT cells, indicating a reduction in cell injury and death. Both in vivo and in vitro, the beneficial actions of tempol were similar to those obtained using the Fe2+ chelator DEF. However, coadministration of DEF and tempol did not produce any additional beneficial actions against renal ischemia/reperfusion injury or against oxidative stress-mediated PT cell injury/death., Conclusion: Our results suggest that the membrane-permeable radical scavenger, tempol, reduces the renal dysfunction and injury associated with ischemia/reperfusion of the kidney.
- Published
- 2000
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268. Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis.
- Author
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Wilson HM, Minto AW, Brown PA, Erwig LP, and Rees AJ
- Subjects
- Animals, Infusion Pumps, Kidney drug effects, Kidney pathology, Nephritis pathology, Nephritis physiopathology, Neutrophils metabolism, Protein Isoforms metabolism, Protein Isoforms pharmacology, Rats, Rats, Sprague-Dawley, Reference Values, Tissue Distribution, Transforming Growth Factor beta pharmacology, Kidney metabolism, Nephritis metabolism, Transforming Growth Factor beta metabolism
- Abstract
Background: Transforming growth factor-beta has three main isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) that have distinct but overlapping functions in immunity, inflammation, and tissue repair. TGF-beta1 has been implicated in progressive renal scarring, but the roles of TGF-beta2 and TGF-beta3 are less clear. The purpose of this study was to characterize the expression of all three isoforms in nephrotoxic nephritis (NTN) in rats and to determine the effect of TGF-beta3 infusions on injury because of its reported combined anti-inflammatory and antifibrotic effects., Methods: TGF-beta1, TGF-beta2, and TGF-beta3 expression was analyzed by immunohistochemistry and RNase protection assays. TGF-beta3 was administered by osmotic minipumps at 2 microg/day, a dose shown to alter glomerular macrophage function in vivo. Injury was assessed morphologically and functionally., Results: The three TGF-beta isoforms showed a different distribution in normal rats and after the induction of nephritis. TGF-beta1 was only detected in glomeruli of the most severely nephritic rats. TGF-beta2 was found in glomerular neutrophils, whereas damaged podocytes expressed TGF-beta3. Infusions of TGF-beta3 did not reduce proteinuria over seven days after the induction of nephritis. They did, however, have a profound effect on glomerular macrophage number (7.76 +/- 4.1 in treated rats vs. 14.4 +/- 4.7 in controls, P < 0.02). The numbers of class II-positive macrophages were similar in the two groups, whereas class II-negative macrophages infiltrating glomeruli were significantly decreased (4.06 +/- 3.1 vs. 9.1 +/- 4.4, P < 0.02). TGF-beta did not influence the amount of glomerular matrix., Conclusions: TGF-beta isoforms have different expressions and presumptively different roles in NTN. The infusion of pharmacological doses of TGF-beta3 has profound effects on macrophages infiltrating nephritic glomeruli and reveals marked heterogeneity of infiltrating macrophages.
- Published
- 2000
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269. The cyclin kinase inhibitor p21WAF1/CIP1 is required for glomerular hypertrophy in experimental diabetic nephropathy.
- Author
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Al-Douahji M, Brugarolas J, Brown PA, Stehman-Breen CO, Alpers CE, and Shankland SJ
- Subjects
- Animals, Blood Glucose analysis, Cyclin-Dependent Kinase Inhibitor p21, Cyclins genetics, DNA biosynthesis, Hypertrophy, Kidney Tubules metabolism, Mice, Mice, Knockout, Proteinuria etiology, RNA, Messenger analysis, Streptozocin, Transforming Growth Factor beta genetics, Cyclins physiology, Diabetes Mellitus, Experimental pathology, Diabetic Nephropathies pathology, Kidney Glomerulus pathology
- Abstract
Background: Diabetic nephropathy is characterized by glomerular hypertrophy. We have recently shown that experimental diabetes mellitus is associated with an increase in glomerular expression of the cyclin kinase inhibitor p21WAF1/CIP1 (p21). Furthermore, in vitro glucose-induced mesangial cell hypertrophy is also associated with an up-regulated expression of p21. In this study, we tested the hypothesis that p21 mediates diabetic glomerular hypertrophy in vivo., Methods: Experimental diabetes mellitus was induced by streptozotocin in mice in which p21 was genetically deleted (p21 -/-) and in wild-type mice (p21 +/+). Kidney biopsies were obtained from diabetic and control (citrate injected) p21 +/+ and p21 -/- mice at day 60. The tissue was used for morphologic studies of glomerular size (measured by computer image-analysis system), glomerular cellularity (cell count), glomerular matrix expansion (silver stain), apoptosis (TUNEL), and expression of transforming growth factor-beta1 (TGF-beta1) by in situ hybridization., Results: The glomerular tuft area increased 11.21% in diabetic p21 +/+ mice at day 60 compared with control (3329.98 +/- 244.05 micrometer(2) vs. 2994. 39 +/- 176.22 micrometer(2), P = 0.03), and the glomerular cell count did not change in diabetic p21 +/+ mice at day 60 compared with the control. These findings are consistent with glomerular hypertrophy. In contrast, the glomerular tuft area did not increase in diabetic p21 -/- mice at day 60 compared with the control (3544.15 +/- 826.49 vs. 3449.15 +/- 109.65, P = 0.82), nor was there an increase in glomerular cell count (41.41 +/- 13.18 vs. 46.95 +/- 3.00, P = 0.43). Diabetic p21 +/+ mice, but not p21 -/- mice, developed an increase in proteinuria at day 60 compared with the control. Tubular cell proliferation, measured by proliferating cell nuclear antigen immunostaining, was increased in both diabetic p21 +/+ (2.1-fold) and p21 -/- (7.61-fold) mice compared with controls. Glomerular cell apoptosis did not increase in diabetic mice. Although glomerular TGF-beta1 mRNA levels increased in both strains of diabetic mice at day 60, the glomerular matrix did not expand., Conclusions: Hyperglycemia was associated with glomerular hypertrophy in p21 +/+ mice. Despite the increase in TGF-beta1 mRNA, diabetic p21 -/- mice did not develop glomerular hypertrophy, providing evidence that the cyclin kinase inhibitor p21 may be required for diabetic glomerular hypertrophy induced by TGF-beta1. The loss of p21 increases tubular but not glomerular cell proliferation in diabetic nephropathy. The absence of glomerular hypertrophy appears protective of renal function in diabetic mice.
- Published
- 1999
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270. Right heart failure as the dominant clinical picture in a case of primary amyloidosis affecting the pulmonary vasculature.
- Author
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Chapman AD, Brown PA, and Kerr KM
- Subjects
- Aged, Aged, 80 and over, Fatal Outcome, Female, Humans, Pulmonary Heart Disease pathology, Amyloidosis complications, Amyloidosis pathology, Hypertension, Pulmonary complications, Pulmonary Heart Disease etiology, Ventricular Dysfunction, Right pathology
- Abstract
A 91-year-old female patient died of right heart failure and pulmonary hypertension. The autopsy revealed multi-organ vascular amyloidosis and pulmonary alveolar septal amyloidosis with no evidence of parenchymal myocardial amyloid deposition. This is a rare example of cor pulmonale secondary to pulmonary amyloidosis.
- Published
- 1999
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271. Psychology as a theoretical foundation for health education in nursing: empowerment or social control?
- Author
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Piper SM and Brown PA
- Subjects
- Health Knowledge, Attitudes, Practice, Humanism, Humans, Nursing Education Research, Patient Participation, Health Education methods, Models, Nursing, Models, Psychological, Power, Psychological, Psychology, Educational, Social Control, Formal
- Abstract
This article explores the relationship between psychology and health education and illustrates how ostensibly 'neutral' models and theories of psychology can be used by conflicting health education philosophies and ideologies. We contend both that health education is an intrinsic element of nursing (which, for the purpose of this article, also includes health visiting and midwifery) and that psychology legitimately underpins practice. Our concern in this article is in the potential application of models and theories of health-related behaviour such as the health belief model (Rosenstock et al 1988), the theory of reasoned action (Fishbein & Ajzen 1985) and the stages of change model (Prochaska & DiClemente 1982) to the health education elements of nursing practice without an awareness and scrutiny of their particular ideological standpoint, and contrasting relationships to power, and thus an understanding of the potential ambiguity regarding their role and function.
- Published
- 1998
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272. Upregulation and co-localization of connexin43 and cellular adhesion molecules in inflammatory renal disease.
- Author
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Hillis GS, Duthie LA, Brown PA, Simpson JG, MacLeod AM, and Haites NE
- Subjects
- Adult, Aged, Cell Adhesion Molecules analysis, Connexin 43 analysis, E-Selectin analysis, E-Selectin metabolism, Female, Granulomatosis with Polyangiitis metabolism, Humans, Immunohistochemistry, Intercellular Adhesion Molecule-1 analysis, Intercellular Adhesion Molecule-1 metabolism, Kidney chemistry, Lupus Erythematosus, Systemic metabolism, Male, Middle Aged, Vascular Cell Adhesion Molecule-1 analysis, Vascular Cell Adhesion Molecule-1 metabolism, Cell Adhesion Molecules metabolism, Connexin 43 metabolism, Glomerulonephritis metabolism, Kidney metabolism
- Abstract
Connexin43 (Cx43) is a major component of gap junctions. These are widely distributed in the human kidney and are thought to be involved in the inflammatory response and in the regulation of cell growth. Cellular adhesion molecules (CAMs) are also thought to be important in these processes, where they possibly facilitate gap junction formation. The aims of the current study were to define for the first time the expression of Cx43 in inflammatory glomerulonephritis and to compare the localization of this connexin with that of the intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Human renal biopsies and control sections of normal human kidney were stained using the alkaline phosphatase/anti-alkaline phosphatase immunohistochemical technique, demonstrating that Cx43 was strongly expressed on inflammatory cells, on damaged tubular cells, and on interstitial cells. This pattern of expression was paralleled closely by that of ICAM-1 and, to a lesser extent, by that of VCAM-1. Cx43 is therefore primarily implicated in tubulointerstitial inflammation.
- Published
- 1997
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273. Expression of beta 1 integrins in IgA nephropathy.
- Author
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Hillis GS, Roy-Chaudhury P, Duthie LA, Stewart KN, Brown PA, Simpson JG, and MacLeod AM
- Subjects
- Antibodies, Monoclonal, Humans, Immunohistochemistry, Kidney immunology, Kidney Glomerulus immunology, Kidney Tubules immunology, Glomerulonephritis, IGA immunology, Integrin beta1 analysis
- Abstract
Aim: To compare the expression of beta 1 integrins in renal biopsies from patients with IgA nephropathy with that found in normal human kidney., Methods: Thirty renal biopsies from patients with IgA disease plus six control specimens were stained with monoclonal antibodies directed against the alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, and beta 1 integrin chains using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. The intensity of integrin expression was graded semiquantitatively by a pathologist unaware of the antibody used., Results: Glomerular crescents stained strongly for alpha 3, alpha v, and beta 1, but integrin expression was greatly reduced or absent in fibrotic glomeruli. There were no alterations in the intensity of mesangial cell staining for any of the integrins tested. There was accentuated staining for the alpha 2, alpha 5, alpha v, and beta 1 chains in areas of interstitial scarring plus alpha 2, alpha 3, alpha v, and beta 1 on damaged tubules. Inflammatory cells expressed alpha 4, alpha 5, and beta 1., Conclusions: In IgA nephropathy the interstitium is the main site of altered beta 1 integrin expression. Glomerular crescents also express several beta 1 integrins, but we found no differences in the intensity of integrin expression on mesangial cells. Altered beta 1 integrin expression may play a role in tubulointerstitial scarring in IgA disease. Thus modulation of integrin expression might attenuate this process.
- Published
- 1997
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274. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo.
- Author
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Lewis EJ, Bishop J, Bottomley KM, Bradshaw D, Brewster M, Broadhurst MJ, Brown PA, Budd JM, Elliott L, Greenham AK, Johnson WH, Nixon JS, Rose F, Sutton B, and Wilson K
- Subjects
- Administration, Oral, Animals, Arthritis, Experimental drug therapy, Cartilage metabolism, Cattle, Humans, Imidazoles pharmacokinetics, Male, Protease Inhibitors pharmacokinetics, Rats, Rats, Sprague-Dawley, Cartilage drug effects, Imidazoles pharmacology, Matrix Metalloproteinase Inhibitors, Protease Inhibitors pharmacology
- Abstract
1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.
- Published
- 1997
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275. Inhibition of bovine nasal cartilage degradation by selective matrix metalloproteinase inhibitors.
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Bottomley KM, Borkakoti N, Bradshaw D, Brown PA, Broadhurst MJ, Budd JM, Elliott L, Eyers P, Hallam TJ, Handa BK, Hill CH, James M, Lahm HW, Lawton G, Merritt JE, Nixon JS, Röthlisberger U, Whittle A, and Johnson WH
- Subjects
- Aggrecans, Animals, Cattle, Chondroitin Sulfate Proteoglycans chemistry, Collagen metabolism, Humans, Interleukin-1 pharmacology, Lectins, C-Type, Matrix Metalloproteinase 1, Matrix Metalloproteinase 9, Matrix Metalloproteinase Inhibitors, Peptide Mapping, Proteoglycans chemistry, Chondroitin Sulfate Proteoglycans metabolism, Enzyme Inhibitors metabolism, Extracellular Matrix Proteins, Metalloendopeptidases antagonists & inhibitors, Nasal Septum metabolism, Proteoglycans metabolism
- Abstract
N-terminal analysis of aggrecan fragments lost from bovine nasal cartilage cultured in the presence of recombinant human interleukin 1alpha revealed a predominant ARGSVIL sequence with an additional ADLEX sequence. Production of the ARGSVIL-containing fragments has been attributed to the action of a putative proteinase, aggrecanase. The minor sequence (ADLEX) corresponds to a new reported cleavage product; comparison of this sequence with the available partial sequence of bovine aggrecan indicates that this is the product of a cleavage occurring towards the C-terminus of the protein. Matrix metalloproteinase (MMP) inhibitors inhibited aggrecan loss from bovine nasal explants incubated in the presence of recombinant human interleukin 1alpha. A strong correlation between inhibition of aggrecan metabolism and inhibition of stromelysin 1 (MMP 3) (r=0.93) suggests a role for stromelysin or a stromelysin-like enzyme in cartilage aggrecan metabolism. However, the compounds were approx. 1/1000 as potent in inhibiting aggrecan loss from the cartilage explants as they were in inhibiting stromelysin. There was little or no correlation between inhibition of aggrecan metabolism and inhibition of gelatinase B (MMP 9) or inhibition of collagenase 1 (MMP 1). Studies with collagenase inhibitors with a range of potencies showed a correlation between inhibition of collagenase activity and inhibition of collagen degradation in the cartilage explant assay. This indicates that in interleukin 1alpha-driven bovine nasal cartilage destruction, stromelysin (or a closely related enzyme) is involved in aggrecan metabolism, whereas collagenase is principally responsible for collagen degradation.
- Published
- 1997
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276. A pilot study in medical education using interactive television.
- Author
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Brebner EM, Brebner JA, Norman JN, Brown PA, Ruddick-Bracken H, and Lanphear JH
- Subjects
- Feasibility Studies, Humans, Male, Pilot Projects, Scotland, United Arab Emirates, Autopsy, Education, Medical, Undergraduate methods, Telecommunications
- Abstract
Medical students in the United Arab Emirates do not receive postmortem teaching. This is because postmortems are not normally carried out, for cultural reasons. In order to address this problem a collaborative project was established between the medical schools of Aberdeen University and the United Arab Emirates University to evaluate the feasibility, acceptability and effectiveness of telepathology teaching. A videoconferencing link was established between the UK and the Middle East using ISDN at a transmission speed of 384 kbit/s. Although some technical problems relating to line continuity were encountered, the results relating to feasibility, acceptability and effectiveness were very positive. Although expensive, this form of teaching may still be cost-effective in relation to the benefits.
- Published
- 1997
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277. Intercontinental postmortem studies using interactive television.
- Author
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Brebner EM, Brebner JA, Norman JN, Brown PA, Ruddick-Bracken H, and Lanphear JH
- Subjects
- Humans, Scotland, Telecommunications, United Arab Emirates, Autopsy, Education, Medical methods, Telepathology
- Abstract
For cultural reasons, medical students in the United Arab Emirates (UAE) are not offered postmortem studies. In a collaborative project between the medical schools of Aberdeen University and the UAE University the feasibility, acceptability and effectiveness of telepathology teaching were evaluated. The transmission of postmortem video images at a quality high enough for teaching purposes was achieved at a data transmission speed of 384 kbit/s. Videoconferencing as a method of presentation was viewed by the students as both interesting and useful. All students participating in the telepathology teaching sessions exceeded the minimum acceptable score of 60% in a multiple-choice examination. Although international videoconferencing at 384 kbit/s is expensive, the costs involved in the telepathology project were small in relation to the educational benefits.
- Published
- 1997
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278. The relationship between enzymuria and kidney enzyme activities in experimental gentamicin nephrotoxicity.
- Author
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Whiting PH and Brown PA
- Subjects
- Acetylglucosaminidase urine, Analysis of Variance, Animals, Anti-Bacterial Agents pharmacology, CD13 Antigens urine, Gentamicins pharmacology, Kidney Function Tests, Male, Rats, Rats, Sprague-Dawley, Reference Values, gamma-Glutamyltransferase urine, Acetylglucosaminidase metabolism, Anti-Bacterial Agents toxicity, CD13 Antigens metabolism, Gentamicins toxicity, Kidney drug effects, Kidney enzymology, Kidney Tubules, Proximal enzymology, gamma-Glutamyltransferase metabolism
- Abstract
The aim of this study was to investigate the relationship between the urine excretion and kidney activities of enzymes predominantly located in the proximal renal tubule, viz. the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase (NAG) and the predominantly brush border enzymes alanine aminopeptidase (AAP) and gamma-glutamyltransferase (GGT) in an experimental model of gentamicin nephrotoxicity. Groups of six animals received either gentamicin (50 mg/ kg/day by intraperitoneal injection) or saline daily and were killed after 4, 7, 10, or 14 days of treatment. Gentamicin nephrotoxicity was characterized by reduced creatinine clearance rates and increased urinary flow rate and glycosuria, but only on day 14. Structural changes included a similar degree of vacuolation of the renal proximal convoluted tubules (PCT) in all animals sacrificed on days 11 and 14, some evidence of PCT brush border loss, and the presence of protein casts on day 14. Following gentamicin treatment, increased NAG, AAP, and GGT enzymuria were noted at all time points tested. However, while the increases in urine AAP and GGT activity were paralleled by decreased total renal activity, total kidney NAG activity increased on days 4, 7, and 11 before falling back to pretreatment values on day 14. Interestingly, NAG enzymuria was highest in those animals with protein casts in the lumen of the PCT. The results suggest that increased AAP and GGT enzymuria reflect loss of brush border integrity while increased NAG enzymuria is consistent with the autophagic response of the kidney to acute injury.
- Published
- 1996
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279. Histoplasmosis--a ten year follow-up.
- Author
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Johnston AW, Brown PA, and Ewen SW
- Subjects
- Aged, Follow-Up Studies, Humans, Male, Time Factors, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Histoplasmosis drug therapy
- Abstract
A patient with chronic disseminated histoplasmosis was followed after successful treatment with amphotericin B for 10 years until his death from chronic obstructive airways disease. Necropsy showed that Histoplasma organisms could still be identified in the adrenal and pancreatic abscesses, though none appeared viable on electron microscopy. Excision of such abscesses should be considered in view of their potential as a reservoir of organisms.
- Published
- 1996
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280. Proteins of the fibrinolytic system in human thrombi.
- Author
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Robbie LA, Bennett B, Croll AM, Brown PA, and Booth NA
- Subjects
- Humans, Immunohistochemistry, In Vitro Techniques, Blood Proteins metabolism, Fibrinolysis physiology, Plasminogen Activator Inhibitor 1 blood, Plasminogen Activators blood, Thrombosis blood
- Abstract
The proteins of fibrinolysis have been quantified in human thrombi, to assess the balance between plasminogen activators and their major inhibitor PAI-1. The relative roles of PAI-1 and alpha 2-AP were also examined since we have previously shown that both platelet PAI-1 and plasma alpha 2-AP are important determinants of clot lysis in vitro. Extracts and sections were prepared from human thrombi for quantitative immunoassay and immunohistochemical staining respectively. PAI-1 and alpha 2-AP were present at high concentrations. Levels of t-PA and t-PA-PAI-1 complex were relatively low. Staining confirmed the presence of abundant PAI-1, associated primarily with platelet material within the thrombus and also with fibrin. Staining for alpha 2-AP was also intense and demonstrated strong association with fibrin. The alpha 2-AP concentration was similar to its high plasma concentration, whereas PAI-1 levels were up to 30 times greater than that in circulating blood, suggesting that active recruitment of platelets contributes to the high PAI-1 concentration in thrombi.
- Published
- 1996
281. Creatine kinase MB isoforms: a potential predictor of acute cardiac allograft rejection.
- Author
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Anderson JR, Hossein-Nia M, Brown PA, Corbishley C, Murday AJ, and Holt DW
- Subjects
- Adolescent, Adult, Biopsy, Cardiomyopathies diagnosis, Cardiomyopathies enzymology, Cardiomyopathies pathology, Endocardium pathology, Female, Follow-Up Studies, Graft Rejection enzymology, Graft Rejection pathology, Heart Transplantation pathology, Humans, Immunosuppressive Agents therapeutic use, Isoenzymes, Male, Middle Aged, Myocardial Ischemia diagnosis, Myocardial Ischemia enzymology, Myocardial Ischemia pathology, Myocardium pathology, Predictive Value of Tests, Prospective Studies, Creatine Kinase blood, Graft Rejection diagnosis, Heart Transplantation immunology
- Abstract
Background: Noninvasive studies to detect or predict acute allograft rejection after heart transplantation have failed to be sufficiently reliable to substitute for endomyocardial biopsy. Isoforms of creatine kinase MB isoenzyme (MB2 and MB1) are extremely sensitive markers of ischemic myocardial damage and, in theory, may be elevated in cardiac allograft rejection when myocardial necrosis is visible on microscopy (International Society for Heart and Lung Transplantation grade 2 or greater)., Methods: We examined, prospectively, the endomyocardial biopsy specimens (n = 256) of 50 consecutive patients undergoing orthotopic heart transplantation. Blood samples for creatine kinase MB isoforms (n = 527) were taken immediately before endomyocardial biopsy and at intervals between biopsies., Results: The median ratio of MB2/MB1 in plasma samples taken at the time of biopsy for grades 2 and 3 was not significantly different from the ratio from biopsy specimens graded 0 and 1 (1.65 versus 1.33; p = Not significant). The sensitivity for diagnosing a moderately severe rejection was 47% with a specificity of 58%. However, in patients with significant acute rejection (grades 2 and 3) in whom consecutive samples were collected, the MB2/MB1 ratio was significantly increased before histologic changes seen on biopsy in 13 of 16 rejection episodes by a mean of 14 days. The sensitivity for predicting rejection (grade 2 or 3) before endomyocardial biopsy was 60% with a specificity of 71% (positive predictive value 43%, negative predictive value 86%)., Conclusions: Creatine kinase MB isoforms may predict the occurrence of acute rejection before histologic evidence seen on endomyocardial biopsy.
- Published
- 1995
282. Integrin distribution in normal kidney and cultured human glomerular cells.
- Author
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Stewart KN, Hillis G, Roy-Chaudhury P, Brown PA, Simpson JG, and MacLeod AM
- Subjects
- Antibodies, Monoclonal, Cells, Cultured, Epithelium metabolism, Glomerular Mesangium metabolism, Humans, Immunohistochemistry, Kidney Glomerulus metabolism, Tissue Distribution, Kidney metabolism, Receptors, Very Late Antigen metabolism
- Published
- 1995
283. Creatine kinase MB2 isoform release as a marker of perioperative myocardial damage during cardiac transplantation.
- Author
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Hossein-Nia M, Kallis P, Brown PA, Murday AJ, Treasure T, and Holt DW
- Subjects
- Adolescent, Adult, Biomarkers blood, Female, Humans, Intraoperative Period, Isoenzymes, Male, Middle Aged, Organ Preservation, Time Factors, Tissue Donors, Creatine Kinase blood, Heart Transplantation, Myocardial Ischemia enzymology
- Published
- 1994
- Full Text
- View/download PDF
284. Laparoscopic approaches to abdominal malignancy.
- Author
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Greene FL and Brown PA
- Subjects
- Abdominal Neoplasms surgery, Contraindications, Hodgkin Disease pathology, Humans, Laparoscopes, Lymph Nodes pathology, Lymphoma, Non-Hodgkin pathology, Neoplasm Staging, Patient Selection, Reoperation, Abdominal Neoplasms pathology, Laparoscopy adverse effects
- Abstract
The use of laparoscopy for diagnosis and staging of intra-abdominal malignancies is not an exclusive procedure. It is another modality in the armamentarium of caring for the patient. The selection of the appropriate patients is discussed in detail and must include a determination of the long-range plans for intervention. The technical issues include problems of previous abdominal surgery, adhesions, ability to tolerate general endotracheal anesthesia, and ability to properly position the patient for an adequate examination. The endoscopic surgeon must be able to differentiate between the benign and malignant process during endoscopic examination and must be skilled in obtaining appropriate biopsies. In the staging of lymphoma, laparoscopy has virtually replaced the open celiotomy technique. Laparoscopic removal of appropriate lymph nodes is essential. The role of laparoscopy in a second-look operation is discussed as well as contraindications and complications of the procedure.
- Published
- 1994
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- View/download PDF
285. Creatine kinase MB isoforms: sensitive markers of ischemic myocardial damage.
- Author
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Hossein-Nia M, Kallis P, Brown PA, Chester MR, Kaski JC, Murday AJ, Treasure T, and Holt DW
- Subjects
- Adolescent, Adult, Aged, Angina Pectoris enzymology, Angina Pectoris therapy, Angioplasty, Balloon, Coronary, Coronary Angiography, Coronary Artery Bypass, Female, Humans, Isoenzymes, Kinetics, Male, Middle Aged, Thoracotomy, Creatine Kinase blood, Myocardial Ischemia enzymology
- Abstract
We investigated the use of creatine kinase (CK) MB isoforms as a marker of myocardial cell injury in a preliminary study of 16 patients with chronic stable angina after successful percutaneous transluminal coronary angioplasty (PTCA) and 25 patients after coronary artery bypass grafting (CABG). Three control groups were studied: apparently healthy volunteers (n = 31), patients undergoing thoracotomy (n = 10), and patients undergoing routine coronary angiography (n = 9). Patients in the PTCA group showed an association between ischemic ST segment changes lasting > 3 min and a transient increase in the MB2/MB1 ratio; however, all had total CK-MB activity within normal limits. Routine coronary angiography subjects had no significant change in MB2/MB1. In the CABG patients, MB2/MB1 peaked within 1 h after the cross-clamp release and returned to baseline by 24 h postoperatively. The median time to peak MM3/MM1 and total CK-MB activity was 2 and 8 h after reperfusion, respectively, returning to baseline values by 2 and 5 days, respectively. After thoracotomy, MB2/MB1 was increased only in elderly patients (n = 5) with risk factors for ischemic heart disease; total CK-MB activity was increased in only three of these. Apparently, CK-MB isoforms can detect myocardial damage in clinical settings with less overt damage than myocardial infarction.
- Published
- 1994
286. The relationship between total kidney cyclosporin A concentrations, trough drug levels and renal function in the rat following withdrawal of treatment.
- Author
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Mead JC, Brown PA, and Whiting PH
- Subjects
- Animals, Cyclosporine blood, Male, Rats, Rats, Sprague-Dawley, Cyclosporine pharmacokinetics, Cyclosporine toxicity, Kidney drug effects, Kidney metabolism
- Abstract
Groups of 6 male rats received cyclosporin A (CsA: 20 mg kg-1 day-1) by gavage for either 4, 7, 10 or 14 days and were sacrificed 24 hours later. CsA nephrotoxicity was characterised functionally by decreased creatinine clearance rates and increased enzymuria. A significant correlation (r2 = 0.980; P < 0.01) was observed between the CsA concentration in renal tissue (4.88 +/- 2.16, 13.54 +/- 3.68, 25.71 +/- 6.59 and 36.64 +/- 6.797 micrograms g-1 kidney wet weight, [mean +/- SD] on days 4, 7, 10 and 14 respectively) and trough whole blood (TWB) CsA concentrations (0.86 +/- 0.18, 1.82 +/- 0.59, 3.35 +/- 0.52 and 3.70 +/- 1.12 micrograms ml-1, respectively) was observed. Furthermore, an apparent relationship between both renal tissue and TWB CsA concentration, the degree of renal microcalcification (MC) at the cortico-medullary junction and magnitude of the renal dysfunction was observed. In a second experiment, treatment was withdrawn after 14 days at 20 mg kg-1 day-1. Following withdrawal of treatment for 1, 4, 7, 10 or 14 days, renal tissue and whole blood CsA concentrations fell progressively from 32.23 +/- 11.23 and 3.01 +/- 0.96 (micrograms g-1 wet weight and micrograms ml-1, respectively) to 25.66 +/- 9.77 and 2.12 +/- 0.66, 10.42 +/- 0.65 and 0.78 +/- 0.23, 4.35 +/- 1.2 and 0.51 +/- 0.16, 3.98 +/- 3.76 and 0.27 +/- 0.03, and 2.58 +/- 1.56 and not detected.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
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- View/download PDF
287. Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid.
- Author
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Rice GC, Brown PA, Nelson RJ, Bianco JA, Singer JW, and Bursten S
- Subjects
- Acyltransferases antagonists & inhibitors, Animals, Female, Lysophospholipids metabolism, Membrane Lipids metabolism, Mice, Mice, Inbred BALB C, Pentoxifylline analogs & derivatives, Pentoxifylline pharmacology, Second Messenger Systems, Phosphatidic Acids antagonists & inhibitors, Shock, Septic prevention & control
- Abstract
Certain phosphatidic/plasmanic/plasmenic acid (PA) species function as lipid intermediates in cell activation and may function directly as intracellular signaling molecules. PA can also be dephosphorylated to 1,2-diradyl-sn-glycerol by phosphatidate phosphohydrolase. Treatment of various cell types, including murine P388 monocytic leukemia cells, with bacterial lipopolysaccharide rapidly stimulates large increases in PA and PA-derived diradylglycerol. Pentoxifylline, 1-(5-oxohexyl)-3,7-dimethylxanthine, inhibits lipopolysaccharide-stimulated formation of PA in P388 cells at high concentrations (IC50 = 500 microM). Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] is a unique metabolite of pentoxifylline in humans and is > 800-fold more active as an inhibitor of PA formation than pentoxifylline (IC50 = 0.6 microM). Lisofylline does not inhibit lipopolysaccharide-induced activation of phosphatidylinositol-specific phospholipase C and generation of phosphatidylinositol-derived diradylglycerol. Lisofylline but not pentoxifylline protects BALB/c mice from endotoxin lethality when administered 4 hr after lipopolysaccharide. This protective effect is independent of either agent's effect on suppression of plasma tumor necrosis factor alpha. These data suggest that inhibitors of PA formation may have significant clinical potential in the treatment of sepsis and septic shock.
- Published
- 1994
- Full Text
- View/download PDF
288. Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.
- Author
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Borkakoti N, Winkler FK, Williams DH, D'Arcy A, Broadhurst MJ, Brown PA, Johnson WH, and Murray EJ
- Subjects
- Amino Acid Sequence, Arthritis, Rheumatoid metabolism, Binding Sites, Cartilage metabolism, Catalysis, Collagen chemistry, Collagen metabolism, Collagenases genetics, Fibroblasts enzymology, Humans, In Vitro Techniques, Metalloendopeptidases antagonists & inhibitors, Metalloendopeptidases chemistry, Metalloendopeptidases genetics, Models, Molecular, Molecular Sequence Data, Molecular Structure, Osteoarthritis metabolism, Protein Conformation, Protein Folding, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins chemistry, Recombinant Proteins genetics, Zinc chemistry, Collagenases chemistry, Matrix Metalloproteinase Inhibitors
- Abstract
In rheumatoid and osteoarthritis, degradation of articular cartilage is mediated by the matrix metalloproteinases collagenase, stromelysin and gelatinase. The key event in this process is the cleavage of triple helical collagen by collagenase. We have determined the crystal structure of the catalytic domain of human recombinant fibroblast collagenase complexed with a synthetic inhibitor at 2.2 A resolution. The protein fold is similar to the amino termini of the zinc endopeptidases astacin thermolysin and elastase despite a lack of primary sequence homology. The conformation of the bound inhibitor provides a molecular basis for the design of inhibitors of collagenase and other matrix metalloproteinases. Such inhibitors should be useful in the treatment of a variety of diseases including arthritis and cancer.
- Published
- 1994
- Full Text
- View/download PDF
289. Urokinase-plasminogen activator is synthesized in vitro by human glomerular epithelial cells but not by mesangial cells.
- Author
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Brown PA, Wilson HM, Reid FJ, Booth NA, Simpson JG, Morrison L, Power DA, and Haites NE
- Subjects
- Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Epithelium metabolism, Glomerular Mesangium cytology, Humans, In Situ Hybridization, Kidney Glomerulus cytology, RNA, Messenger metabolism, Tissue Distribution, Urokinase-Type Plasminogen Activator genetics, Glomerular Mesangium metabolism, Kidney Glomerulus metabolism, Urokinase-Type Plasminogen Activator biosynthesis
- Abstract
The plasmin protease system may have a role in maintaining the patency of renal tubules and in regulating matrix degradation within the glomerulus. Urokinase-plasminogen activator (u-PA) is a serine protease which plays an important part in the regulation of plasmin production from plasminogen. The synthesis of u-PA by cultured human glomerular cells, in particular mesangial cells, is controversial. The present study describes the presence of u-PA in supernatants of pure cultures of human glomerular epithelial cells (EC), cocultures of EC and human mesangial cells (MC) and whole glomeruli, but not within pure cultures of MC. To confirm the synthesis of u-PA mRNA in glomerular EC, cocultures of EC and MC were tested by in situ hybridization with u-PA antisense and sense digoxigenin-labeled RNA probes. Cytoplasmic localization of u-PA mRNA was demonstrated only in the EC, thus confirming the absence of synthesis of u-PA by human mesangial cells in culture.
- Published
- 1994
- Full Text
- View/download PDF
290. Alleviation of experimental cyclosporin A nephrotoxicity by low dose aspirin in the rat.
- Author
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Adams KE, Brown PA, Heys SD, and Whiting PH
- Subjects
- 6-Ketoprostaglandin F1 alpha urine, Animals, Aspirin administration & dosage, Creatinine blood, Kidney Diseases chemically induced, Kidney Diseases urine, Male, Rats, Rats, Sprague-Dawley, Thromboxane A2 urine, Urea blood, Aspirin pharmacology, Cyclosporine toxicity, Kidney Diseases prevention & control
- Abstract
Groups of male Sprague-Dawley rats received either cyclosporin A (CsA; 25 mg/kg by gavage), low dose aspirin (ASP; 20 mg/kg by gavage), a combination of both, or the appropriate drug vehicles daily for 14 days. Renal structure and function were assessed on day 0 (pretreatment) and on days 7 and 14. Compared to pretreatment results, CsA nephrotoxicity was characterized by increased plasma urea and creatinine concentrations and by moderate to severe microcalcification (MC) at the corticomedullary junction by day 14. The development of nephrotoxicity was also associated with a 5-fold increase in urine thromboxane B2 (TxB2) excretion by day 10, while that of 6-ketoprostaglandin F1 alpha remained relatively constant. Although both ASP and saline (ASP vehicle) -cotreated animals demonstrated significantly lower plasma urea and creatinine concentrations compared to treatment with CsA alone, the severity of MC observed on day 14, was reduced only in the ASP cotreatment group. Though whole blood CsA concentrations were similar at around 2400 ng/mL in all experimental groups. In addition, although a 2-fold increase in urine TxB2 excretion was observed on days 7 and 10 following treatment with CsA/ASP, levels were significantly reduced compared to treatment with either CsA alone or CsA/saline (both P < 0.05).
- Published
- 1993
- Full Text
- View/download PDF
291. Effect of transforming growth factor-beta 1 on plasminogen activators and plasminogen activator inhibitor-1 in renal glomerular cells.
- Author
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Wilson HM, Reid FJ, Brown PA, Power DA, Haites NE, and Booth NA
- Subjects
- Epithelial Cells, Epithelium metabolism, Humans, Kidney Glomerulus cytology, Plasminogen Activator Inhibitor 1 genetics, RNA, Messenger metabolism, Tissue Plasminogen Activator metabolism, Urokinase-Type Plasminogen Activator metabolism, Kidney Glomerulus metabolism, Plasminogen Activator Inhibitor 1 metabolism, Plasminogen Activators metabolism, Transforming Growth Factor beta pharmacology
- Abstract
Recent evidence suggests that the balance between serine proteases and their inhibitors is central to the maintenance of the glomerular extracellular matrix. We have characterised the urokinase type and the tissue type plasminogen activators (PA) and their inhibitor, PAI-1, secreted from glomerular epithelial and mesangial cells as well as their co-cultures and have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) on the production of such species. Similar data were derived from whole glomeruli suspensions. TGF-beta 1 increased PAI-1 production significantly in epithelial and mesangial cells as well as in whole glomeruli, while PA production was decreased; platelet-derived growth factor had no effect. These effects are consistent with a possible decrease in matrix proteolysis, suggesting a mechanism by which TGF-beta 1 may enhance mesangial matrix accumulation, a characteristic of many forms of glomerular disease.
- Published
- 1993
292. Inflammatory pseudotumour of the urinary bladder.
- Author
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N'Dow J, Brown PA, McClinton S, Moffat LE, and Grieve JH
- Subjects
- Adolescent, Diagnosis, Differential, Female, Granuloma, Plasma Cell diagnosis, Humans, Urinary Bladder Diseases diagnosis, Urinary Bladder Neoplasms diagnosis, Granuloma, Plasma Cell pathology, Urinary Bladder pathology, Urinary Bladder Diseases pathology
- Published
- 1993
- Full Text
- View/download PDF
293. Chronic cyclosporin A (CsA) nephrotoxicity in the rat: the effect of calcium blockade with verapamil.
- Author
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Shaikh MG, Heys SD, Brown PA, and Whiting PH
- Subjects
- Animals, Blood Glucose analysis, Body Weight, Kidney pathology, Kidney Diseases pathology, Male, Rats, Rats, Sprague-Dawley, Cyclosporine toxicity, Kidney drug effects, Kidney Diseases chemically induced, Verapamil pharmacology
- Abstract
Renal structure and function were assessed in groups of male Sprague-Dawley rats, either surgically intact (SI) or nephrectomized (N), treated with either CsA alone (20 mg/kg, p.o.) or in combination with verapamil (VER; 10 mg/kg/day, i.p.) daily for up to 28 days. Compared to vehicle treated controls, reduced creatinine clearance rates (CCR, mean +/- s.e.m.) were noted following CsA treatment in Sl animals on days 21 and 28 (279 +/- 4 vs 196 +/- 20 and 296 +/- 13 vs 122 +/- 13 ml/h/kg, respectively, both P < 0.05). However, CCR was around 60% of pretreatment values in all N animals from day 7 onwards. A two to three-fold elevation in urinary N-acetyl-beta-D-glucosaminidase activity was noted from day 7 to 28 in all CsA treated animals. In addition, a similar severity of both renal tubular basophilia and corticomedullary microcalcification (but not proximal tubular vacuolation), was noted at all time points in animals receiving CsA alone. Co-treatment with VER reduced the severity of microcalcification in CsA groups, particularly N animals, increased CCR on day 14 in the Sl (196 +/- 23 vs 391 +/- 64) and days 21 and 28 in N (141 +/- 14 vs 357 +/- 32 and 152 +/- 28 vs 261 +/- 20) groups, respectively but had no effect on the magnitude of enzymuria, despite significantly increased trough whole blood CsA levels (20-30%) in both Sl and N groups. These results indicate that calcium blockade reduces both structural and functional features of chronic CsA nephrotoxicity.
- Published
- 1993
294. Urinary excretion of deuterium-labeled folate and the metabolite p-aminobenzoylglutamate in humans.
- Author
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Kownacki-Brown PA, Wang C, Bailey LB, Toth JP, and Gregory JF 3rd
- Subjects
- Adult, Chromatography, High Pressure Liquid, Deuterium, Folic Acid administration & dosage, Gas Chromatography-Mass Spectrometry, Humans, Male, Folic Acid urine, Glutamates urine
- Abstract
Stable isotopic methods were employed to determine the proportion of ingested folate excreted as the metabolite p-aminobenzoylglutamate (pABG, free and N-acetyl) in urine. Adult male subjects (n = 7) were maintained on a 4.54 mumol/d (2 mg/d) folate saturation regimen. After 7 d, subjects were given a mixed oral dose containing 0.67 mumol (300 micrograms) each of bideuterofolic acid (d2) and tetradeutero-folic acid (d4). Urine was collected for the following 48 h and analyzed for folate and pABG. The extent of deuterium labeling of urinary folate and pABG was determined by gas chromatography-mass spectrometry. Urinary total pABG excretion increased less than twofold as a result of the folate saturation, whereas urinary folate increased over 10-fold. Urinary d2 and d4 folates each contained 14-15% of the respective oral doses of labeled compounds, whereas urinary d2 and d4 pABG comprised only 0.98-1.15% of the labeled doses. Molar ratios (d2/d4) of excreted folate and pABG indicated that there was no in vivo isotopic discrimination between the labeled folates. Urinary pABG accounted for 5.1 +/- 0.6% of total ingested folate, whereas labeled pABG was about 6.7-7.6% of the excretion of labeled compounds (i.e., labeled folate + pABG). This study indicated that pABG is not a major excretory product during folate supplementation, but its relative importance may increase in conditions of reduced folate nutriture.
- Published
- 1993
- Full Text
- View/download PDF
295. Skin lesion removal: practice by general practitioners in Grampian Region before and after April 1990.
- Author
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Brown PA, Kernohan NM, Smart LM, Savargaonkar P, Atkinson P, Robinson S, Russell D, and Kerr KM
- Subjects
- Biopsy trends, Health Services Research, Humans, Physician Incentive Plans, Practice Patterns, Physicians' trends, Retrospective Studies, Scotland, Skin Diseases diagnosis, Biopsy statistics & numerical data, Family Practice statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Skin Diseases pathology
- Abstract
The introduction of new GP contracts in April 1990 incorporated a financial incentive to undertake minor surgical procedures. Previous reports have noted large increases in the number of GP-derived skin specimens after April 1990. Our present study intended to address whether similar changes have occurred in Grampian Region as well as, more specifically, noting whether there have been changes in the quality of practice following the 1st April 1990. A retrospective study of skin biopsies removed by general practitioners in Grampian Region was undertaken. Cases were selected from four periods of six months (1st April to end of September) in 1987, 1988, 1989 and 1990. All skin specimens sent by general practitioners to the Department of Pathology, Aberdeen Royal Infirmary, were included. Following April 1990 there was a two-fold increase in skin specimen numbers--an increase significantly greater than increases observed over previous years (p < 0.01). Of particular note was the contribution made to this increase by Aberdeen City GPs whose contribution rose five-fold (p < 0.0001). Non-benign lesions (ie malignant plus carcinoma-in-situ-) represented 6% of lesions excised. A non-benign clinical diagnosis or an indication of suspicion was written on only one third of request forms for histopathologically diagnosed non-benign lesions. The proportion of histologically incompletely excised lesions rose over the four years (p < 0.01); moreover the increase in total numbers of lesions resulted in a striking increase in the actual numbers of incompletely excised lesions after April 1990.
- Published
- 1992
- Full Text
- View/download PDF
296. Skin lesion excision in general practice.
- Author
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Brown PA, Kernohan NM, Smart LM, Atkinson P, Robinson S, Russell D, and Kerr KM
- Subjects
- Biopsy, Family Practice, Humans, Minor Surgical Procedures, Skin Neoplasms surgery
- Published
- 1992
297. New postmarketing surveillance regulations affecting the ophthalmic nurse.
- Author
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Brown PA and Amtower PC
- Subjects
- Humans, Legislation, Medical, Equipment and Supplies standards, Nurses, Ophthalmology, Product Surveillance, Postmarketing, Role
- Abstract
A new federal regulation, The Safe Medical Devices Act, mandates that nurses in hospitals, nursing homes, and ambulatory surgery centers report serious problems associated with the use of medical devices to the FDA. Deaths must be reported to the FDA and manufacturer in 10 working days. Serious injuries and illnesses are also to be reported. Summary reports are due to the FDA semi-annually. After August 1995, the FDA may be able to fine the facility up to $15,000 for each violation of the reporting requirements. This article describes ophthalmic nurses' roles and responsibilities pertaining to the new law.
- Published
- 1992
298. Electrochemical enzyme immunoassay for detection of toxic substances.
- Author
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O'Daly JP, Zhao J, Brown PA, and Henkens RW
- Subjects
- Ferrous Compounds chemistry, Lysine analogs & derivatives, Lysine chemistry, Metallocenes, Nitrophenols chemistry, Biosensing Techniques, Hazardous Substances analysis, Immunoenzyme Techniques
- Abstract
Sensors that provide reliable, rapid measurement of toxic substances are needed to solve significant human health and safety problems. We developed a new biosensor design that combines the advantages of immunoassay with electrochemical response. We established that this enzyme-linked immunosensor measures toxic substances in biological samples. The biosensor consists of two major elements: (1) an electrical conducting layer having immobilized enzyme, polyclonal or monoclonal antibodies, and other necessary reagents, and (2) the electronic components used in the signal readout. The result is an amperometric immunoassay based on coupling the immunochemical reaction to the enzyme electrode response by using a soluble, electrochemically active mediator. The specific question addressed was: Does the system's immunochemical detection reliably respond at sufficiently low analyte concentrations? We present our results in these areas: (1) enzyme immobilization on colloidal gold; (2) colloidal gold-enzyme deposition on the electrode surface; (3) mediator-antigen conjugate synthesis; (4) antibody incorporation at the electrode surface; (5) bioelectrode characterization and optimization; and (6) immunosensor demonstration to detect antigen. Sensors that employ immunochemical detection will have broad applicability to detect/diagnose toxic substances in biological samples such as blood and urine and in environmental samples such as wastewater and drinking water.
- Published
- 1992
- Full Text
- View/download PDF
299. Clinical evaluation of cats with lower urinary tract disease.
- Author
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Kruger JM, Osborne CA, Goyal SM, Wickstrom SL, Johnston GR, Fletcher TF, and Brown PA
- Subjects
- Animals, Antibodies, Viral blood, Cats, Female, Fluorescent Antibody Technique, Hematuria diagnosis, Herpesviridae immunology, Herpesviridae Infections diagnosis, Herpesviridae Infections veterinary, Male, Prospective Studies, Pyuria diagnosis, Pyuria veterinary, Sex Factors, Urethral Obstruction diagnosis, Urinary Calculi diagnosis, Urinary Calculi veterinary, Urinary Tract Infections diagnosis, Urinary Tract Infections veterinary, Urination Disorders diagnosis, Cat Diseases diagnosis, Hematuria veterinary, Urethral Obstruction veterinary, Urination Disorders veterinary
- Abstract
In a prospective study, 141 cats with hematuria, dysuria, urethral obstruction, or combinations of these signs were evaluated by contemporary diagnostic methods and compared with 26 clinically normal cats (controls). Specific diagnosis was established in 45% (64/141) of cats affected with lower urinary tract disease (LUTD). Crystalline matrix plug-induced urethral obstruction was diagnosed in 21% (30/141) of affected cats, uroliths were identified in 21% (30/141) of affected cats, uroliths with concomitant bacterial urinary tract infection (UTI) were identified in less than 2% (2/141) of affected cats, and bacterial UTI alone was identified in less than 2% (2/141) of cats with LUTD. Viruses, mycoplasmas, and ureaplasmas were not isolated from urine samples collected from affected or control cats. Bovine herpesvirus 4 (BHV-4)-neutralizing antibodies were not detected in any serum sample obtained from cats with LUTD or from control cats. In contrast, BHV-4 antibodies were detected by an indirect immunofluorescent antibody (IFA) test in sera obtained from 31% (44/141) of cats with LUTD and 23% (6/26) of control cats. The prevalence of positive BHV-4 IFA test results in affected cats was not significantly different from that observed in control cats. Significant association was not apparent between positive BHV-4 IFA test results and clinical diagnosis, abnormal laboratory findings, or cat age. However, the number of male cats with BHV-4 IFA titer was significantly (P less than 0.02, chi 2 test) greater than that of female cats. Detection of BHV-4 antibodies in approximately 30% of affected and control cats indicates prior virus exposure. Further investigations are warranted to clarify the specific role of BHV-4 in cats with naturally acquired LUTD.
- Published
- 1991
300. Educating homeless children and youth.
- Author
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Brown PA
- Subjects
- Adolescent, Child, Humans, Public Policy, United States, Child Welfare, Education standards, Ill-Housed Persons
- Published
- 1991
- Full Text
- View/download PDF
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