Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of age, gender and phenobarbital treatment on the hepatic cytosolic glutathione S-transferase subunit composition was studied in Brown Norway rats. Affinity chromatography followed by reversed phase HPLC was used in order to separate the various glutathione S-transferase subunits. Corresponding steady-state mRNA levels were measured by Northern Blot analysis using cDNA clones hybridizing to mRNA encoding glutathione S-transferase subunits 1/2, 3/4 and 7, respectively. In all the age groups studied (15, 25, 53, 99, 112 and 136 weeks) the total amount of glutathione S-transferase protein was in untreated rats significantly higher in males (132 micrograms/mg cytosolic protein) than in females (91 micrograms/mg cytosolic protein) and significant gender dependent differences in the subunit composition were demonstrated. Aging seemed to be of minor importance in untreated as well as in phenobarbital treated rats. Under control conditions, the subunit composition of male rats between 15 and 136 weeks old consisted of 28, 12, 11 and 49% of subunits 1, 2, 3 and 4 respectively and of female animals of the same age groups of 38, 26, 7 and 30%, respectively. In all the age groups studied phenobarbital administration (45 mg/kg body weight, i.p., once a day for 7 days) doubled total glutathione S-transferase protein in both genders and affected the subunit composition in a significant way, emphasizing the already existing differences between genders. Subunits 1, 2 and 3, especially, were increased in male rats in comparison to females resulting in the observation that levels of glutathione S-transferase subunits studied became higher in males than in their female counterparts. The HPLC results were confirmed by steady-state mRNA analysis. In untreated rats, higher levels of mRNA encoding glutathione S-transferase subunits 1/2 and 3/4 were present in male than in female livers. Phenobarbital treatment increased mRNA levels in both genders. Subunit 7 was never detected. These effects were demonstrated in both young and old rats.
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PMID:Effect of the aging process on the gender and phenobarbital dependent expression of glutathione S-transferase subunits in brown Norway rat liver. 185 62

Age-associated alterations of hepatic cytosolic glutathione S-transferase activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene were investigated in Brown Norway rats of both sexes (11-144 weeks old), under control conditions and after administration of phenobarbital. With both substrates, small changes in glutathione S-transferase activities are observed for the control rats (15-53 weeks old). For these specific age groups, male glutathione S-transferase activities are significantly higher than those of their female counterparts, with sex-related differences being most pronounced after 1,2-dichloro-4-nitrobenzene conjugation. Using 1-chloro-2,4-dinitrobenzene as a 'general' substrate, the sex-differences tend to decrease from the age of 53 weeks onwards to become non-significant at the age of 112 weeks. Phenobarbital administration significantly increases the total and the isoenzymes 3-3 and 3-4 activities in both sexes, with the highest and the lowest increase being observed in the youngest and oldest animals, respectively. It therefore can be concluded that some age-related variations exist as far as the glutathione S-transferase activity of both control and phenobarbital-treated rats are concerned, but that the changes observed are rather small. On the contrary, the parameters 'Sex' and 'Phenobarbital treatment' are found to be responsible for the major activity changes observed.
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PMID:Hepatic cytosolic glutathione S-transferase activities in ageing brown Norway rats--importance of sex differences and phenobarbital treatment for studies of ageing. 223 11

Coronary vasomotion is an important determinant of myocardial perfusion in patients with angina pectoris, and it influences not only normal but also stenotic coronary arteries. The ability of a stenotic coronary artery to change its size is dependent on the presence of a normal musculo-elastic wall segment within the stenosis (i.e., eccentric stenosis). Coronary vasoconstriction of normal and stenotic coronary arteries has been reported by Brown and coworkers (Circulation 1984; 70: 18-24) during isometric exercise. The effect of dynamic exercise on coronary vasomotion was evaluated in one group of 13 patients with ischaemia-like symptoms and normal coronary arteries (group 1) and in a second group of 12 patients with coronary artery disease with exercise-induced angina pectoris (group 2). Luminal area of a normal and a stenotic vessel segment was determined by biplane quantitative coronary arteriography at rest, during supine bicycle exercise and 5 min after administration of 1.6 mg sublingual nitroglycerin. Coronary sinus blood flow was measured in group 1 at rest and after 0.5 mg kg-1 intravenous dipyridamole using coronary sinus thermodilution. Coronary flow reserve was calculated from coronary sinus flow after dipyridamole divided by coronary sinus flow at rest. In group 1, coronary vasodilation of the large (i.e., proximal) and the small (i.e., distal) coronary arteries was observed during exercise in seven patients (subgroup A). However, in the remaining six patients (subgroup B) coronary vasoconstriction of the small arteries (-24%, P less than 0.001) was found during exercise, whereas the large vessels showed coronary vasodilation (+26%, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary vasomotor tone during static and dynamic exercise. 251 65

Aortocoronary vein bypass surgery might not restore normal maximal coronary flow reserve to bypassed coronary vessels because residual diffuse coronary atherosclerosis might limit maximal hyperemia. To investigate the effect of diffuse atherosclerosis and a focal stenosis at the graft-coronary anastomosis, we measured coronary flow reserve with an extensively validated subselective Doppler catheter in 24 patients with 35 bypass grafts perfusing angiographically normal coronary vessels. The Doppler catheter was positioned in the midportion of the graft, and coronary flow reserve was measured as the peak/resting velocity ratio after selective graft injection of a maximally vasodilating dose of papaverine. Luminal dimensions of the bypass graft, graft-coronary insertion, and bypassed coronary vessel were measured by quantitative coronary angiography (Brown/Dodge method). Measurements of coronary flow reserve and coronary dimensions of vein bypass grafts were compared with similar measurements obtained from 13 patients with normal coronary vessels and normal myocardium. Seventeen of the 35 bypass grafts perfused unobstructed coronary-vein graft anastomoses (less than 50% area stenosis) and normal myocardium. The coronary flow reserve of these 17 bypass grafts was normal (5.0 +/- 0.4, mean +/- SEM) and not significantly different from that measured in normal arteries (5.1 +/- 0.6), even though the cross-sectional area of the native coronary artery just distal to the bypass insertion was 40% smaller than in matched normal vessels. Bypass grafts perfusing hypertrophied (n = 2) or infarcted (n = 6) myocardium had significantly reduced coronary flow reserve compared with normal vessels (2.7 +/- 0.3; p less than .01), even when the infarcted wall had only minimal hypokinesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does coronary artery bypass surgery restore normal maximal coronary flow reserve? The effect of diffuse atherosclerosis and focal obstructive lesions. 295 10

Obliterative bronchiolitis (OB) affects over half of all survivors following lung or heart-lung transplantation. Respiratory epithelial cell injury, peribronchial inflammation, and proliferation of fibrovascular tissue causing airway occlusion characterize the lesion. While peroxynitrite is known to participate in other models of acute lung injury, its role in the evolution of OB is unclear. Using a rat model of experimental OB, tracheas from Brown-Norway or Lewis rats were transplanted into Lewis recipients. Treated animals received FP-15, a peroxynitrite decomposition catalyst, at 1 mg/kg/day intraperitoneal for 14 days. Luminal obstruction, epithelial loss, and inflammatory infiltrate were examined, as was nitrotyrosine staining by immunohistochemistry in explanted tracheas. By postoperative day 14, control allografts demonstrated marked peribronchial inflammation, near complete loss of respiratory epithelium and extensive intraluminal proliferation of fibrovascular connective tissue, with a mean 83% reduction in airway cross-sectional area. Allograft recipients treated with FP-15 showed reduced nitrotyrosine formation, preservation of respiratory epithelium, limited peribronchial inflammation, and only 14% (P <.001) reduction in airway cross-sectional area. Peroxynitrite therefore appears to play a role in the development of obliterative bronchiolitis in rats. The peroxynitrite decomposition catalyst, FP-15, is protective when administered daily and warrants investigation into its potential clinical utility.
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PMID:Enhanced peroxynitrite decomposition protects against experimental obliterative bronchiolitis. 1283 21

Beta chemokines have been implicated in cardiac and renal allograft rejection. This study determined if antibody antagonization of beta chemokines conferred protection against the development of experimental obliterative bronchiolitis (OB) in a heterotopic rat tracheal allograft model. Rat tracheas were transplanted from Brown-Norway or Lewis donors into Lewis recipients. Rats received 200 microg/day of either anti-RANTES or anti-MCP-1 antibody for 14 days. Luminal obstruction and epithelial loss were calculated. Northern blots for MCP-1 and RANTES mRNA expression were performed, and immunohistochemistry for chemokine protein localization. There was a significant increase in airway obstruction in allografts compared to isografts (P < 0.001). Antibody-treated allografts demonstrated an amelioration of airway obstruction from 58% (vehicle allografts) to 26% (anti-RANTES) and 12% (anti-MCP-1), both of which were significant (P < 0.001). Epithelial preservation was increased in both antibody-treated groups (P < 0.001), and increased expression of MCP-1 and RANTES mRNA was present in tracheal allografts by Day 2 and maximal by Day 6. Beta chemokines are expressed during the development of experimental OB, as MCP-1 and RANTES mRNA expression increased with time from transplantation. Both MCP-1 and RANTES are functional in the formation of the fibroproliferative response that characterizes OB in this model, and their antagonization conferred protection against airway obstruction and epithelial loss.
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PMID:The role of the beta chemokines in experimental obliterative bronchiolitis. 1461 12