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)

To examine arterial mechanical changes during aging, pressure-radius and axial force-radius curves were measured in vivo in carotid arteries from 6- and 23-month-old Brown Norway X Fischer 344 rats. Incremental passive circumferential stiffness (measured at 50, 100, and 200 mm Hg) was higher (P<0.01) in the 23- compared with the 6-month-old rats (14.02+/-1.23 versus 6.58+/-1.51; 2.68+/-0.56 versus 0.99+/-0.34; 1.10+/-0.24 versus 0.69+/-0.15 dyne/mm2x10(3), respectively). Incremental passive axial stiffness was increased (P<0.01) in the 23- compared with the 6-month-old rats (7.95+/-0.70 versus 4.24+/-0.81; 1.91+/-0.10 versus 0.61+/-0.16; 0.58+/-0.09 versus 0.36+/-0.06 dyne/mm2x10(3), respectively). Active incremental circumferential arterial stiffness at 100 and 200 mm Hg was increased (P<0.01) in the older rats. In 6-month-old rats, activation of vascular smooth muscle enhanced (P<0.01) the incremental circumferential and axial stiffness measured at 200 mm Hg. In 23-month-old rats, only active incremental stiffness was increased (P<0.01) at 200 mm Hg. Aging increased (P<0.05) media thickness, collagen content, and the collagen/elastin ratio by 12%, 21%, and 38%, respectively. Elastin density and the number of smooth muscle cell nuclei were decreased by 20% and 31%, respectively, with aging. Thus, structural alterations that occur with aging are associated with changes in both active and passive stiffness. Vascular smooth muscle tone modulates arterial wall anisotropy differently during aging.
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PMID:Large artery remodeling during aging: biaxial passive and active stiffness. 974 Jun 8

Previously we reported that alcohol abuse increases the incidence of the acute respiratory distress syndrome (ARDS) in septic patients, and that chronic ethanol ingestion in rats depletes alveolar epithelial glutathione and increases endotoxin-mediated lung edema. In this study we examined a potential mechanism by which ethanol-induced glutathione depletion could predispose to acute lung injury. We hypothesized that glutathione depletion activates matrix metalloproteinases (MMPs), thereby increasing degradation of the alveolar extracellular matrix (ECM) during sepsis. Ethanol-fed rats (20% vol/vol in water for 6 wk) were given endotoxin (2 mg/kg, intraperitoneally) followed 2 h later by lung isolation and ex vivo perfusion with n-formyl-methionyl-leucyl-phenylalanine (fMLP) (10(-)(7) M). Ethanol ingestion increased (p < 0.05) MMP-9 and MMP-2 activity, as determined by zymography, in the lung tissue and lavage fluid compared with control-fed rats, and increased (p < 0.05) levels of the 7S fragment of type IV collagen in the lung lavage fluid. Ethanol ingestion increased activation, but not production, of the MMP-9 and MMP-2 zymogens. Finally, although concomitant ingestion of N-acetylcysteine had no effect (p > 0.05) on MMP production, it increased (p > 0.05) lung glutathione levels, blocked (p < 0.05) MMP-9 and MMP-2 activation, and decreased (p < 0.05) levels of the 7S fragment of type IV collagen. We conclude that chronic ethanol ingestion, via glutathione depletion, activates MMPs during sepsis, thereby increasing degradation of the alveolar epithelial ECM. Lois M, Brown LAS, Moss IM, Roman J, Guidot DM. Ethanol ingestion increases activation of matrix metalloproteinases in rat lungs during acute endotoxemia.
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PMID:Ethanol ingestion increases activation of matrix metalloproteinases in rat lungs during acute endotoxemia. 1050 28

Chronic inflammation in asthmatic airways can lead to characteristic airway smooth muscle (ASM) thickening and pathological changes within the airway wall. This study assessed the effect of repeated allergen exposure on ASM and epithelial cell deoxyribonucleic acid (DNA) synthesis, cell recruitment and airway wall pathology. Brown-Norway rats were sensitized and then exposed to ovalbumin or saline aerosol every 3 days on six occasions. After the final exposure, rats were administered twice daily for 7 days with the DNA S-phase marker bromodeoxyuridine (BrdU). Using a triple immunohistochemical staining technique, BrdU incorporation into ASM and epithelium was quantified employing computer-assisted image analysis. There were >3-fold mean increases in BrdU incorporation into ASM from 1.3% of cells (95% confidence interval (CI) 1.0-1.6) in saline controls to 4.7% (95% CI 2.6-6.7) after allergen exposure (p<0.001), and in airway epithelium, from 1.3 (95% CI 0.6-2.0) BrdU-positive cells x mm basement membrane(-1) in saline controls to 4.9 (95% CI 3.0-6.7) after allergen exposure (p<0.001). There was increased subepithelial collagen deposition and mucus secretion along with a significant eosinophil and lymphocyte recruitment to the airways. Increased rates of deoxyribonucleic acid synthesis in both airway smooth muscle and epithelial cells along with changes to the airway wall pathology may precede the establishment of smooth muscle thickening and airway remodelling after repeated allergen exposure in rats. This model seems to be appropriate for studying structural changes within the airways as observed in asthma.
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PMID:Repeated allergen exposure of sensitized Brown-Norway rats induces airway cell DNA synthesis and remodelling. 1054 87

Using Brown Norway Katholiek (BNK) rats, which are deficient in kininogen (kinin precursor) due to a mutation in the kininogen gene, we examined the role of endogenous kinins in 1) normal cardiac function; 2) myocardial infarction (MI) caused by coronary artery ligation; 3) cardiac remodeling in the development of heart failure (HF) after MI; and 4) the cardioprotective effect of angiotensin-converting enzyme inhibitors (ACEI) on HF after MI. Two months after MI, rats were randomly treated with vehicle or the ACEI ramipril for 2 mo. Brown Norway rats (BN), which have normal kininogen, were used as controls. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic pressure (EDP), and ejection fraction (EF) as well as myocardial infarct size (IS), interstitial collagen fraction (ICF), cardiomyocyte cross-sectional area (MCA), and oxygen diffusion distance (ODD) were measured. We found that 1) cardiac hemodynamics, function, and histology were the same in sham-ligated BN and BNK rats; 2) IS was similar in BN and BNK; 3) in rats with HF treated with vehicle, the decrease in LVEF and the increase in LVEDV, LVESV, LVEDP, ICF, MCA, and ODD did not differ between BNK and BN; and 4) ACEI increased EF, decreased LVEDV and LVESV, and improved cardiac remodeling in BN-HF rats, and these effects were partially blocked by the bradykinin B(2) receptor antagonist icatibant (HOE-140). In BNK-HF rats, ACEI failed to produce these beneficial cardiac effects. We concluded that in rats, lack of kinins does not influence regulation of normal cardiac function, myocardial infarct size, or development of HF; however, kinins appear to play an important role in the cardioprotective effect of ACEI, since 1) this effect was significantly diminished in kininogen-deficient rats and 2) it was blocked by a B(2) kinin receptor antagonist in BN rats.
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PMID:Role of kinins in chronic heart failure and in the therapeutic effect of ACE inhibitors in kininogen-deficient rats. 1066 82

The pathogenesis and functional consequences of airway remodeling in asthma remain to be fully established. In the present study we evaluated the effect of prolonged allergen exposure on airway function and structure in rats. Sensitized Brown Norway rats were repeatedly exposed for periods of 2, 4, or 12 wk to aerosolized ovalbumin (OA) or phosphate-buffered saline (PBS). OA exposure induced a persistent increase in OA-specific serum IgE and in the number of peribronchial eosinophils. After 2 wk of OA exposure, airway histology revealed goblet-cell hyperplasia, an increase in bromodeoxyuridine-positive cells in airway epithelium, increased fibronectin deposition, and a thickening of the airway inner wall area. This coincided with airway hyperresponsiveness (AHR) to aerosolized carbachol. After OA exposure for 12 wk, increased fibronectin (p < 0.05 versus PBS) and collagen deposition (p < 0.05 versus PBS) were observed in the submucosa. After 12 wk of exposure, neither total nor inner wall area or airway responsiveness to carbachol were any longer significantly different from those of PBS-exposed animals. In conclusion, prolonged OA exposure in rats induces structural airway changes that bear similarities to airway remodeling in asthma. The study data further indicate that depending on the extent and distribution of remodeling, changes in the extracellular matrix can enhance or protect against AHR.
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PMID:Prolonged allergen exposure induces structural airway changes in sensitized rats. 1067 9

Growth performance, carcass and meat quality were determined in 36 fattening Brown Swiss bulls fed with maize silage-hay-concentrate based rations supplemented with fats and various oilseeds. The concentrate diet in the control group contained only barley and soybean meal, while the treated groups included, as partial replacement of the concentrate, rumen-protected crystalline fat, coconut oil, whole crushed rapeseed, sunflower seed or linseed, providing additional 3% fat of total ration dry matter. Animals were housed in groups of six with one representative of each treatment in a monofactorial design and feed was offered using transponder controlled equipment. Daily gains were similar for control, protected fat, rapeseed and linseed treatments (1240 g/d on average), but were lower (P < 0.05) with sunflower seed (1135 g/d) and coconut oil (1038 g/d). Corresponding differences (P < 0.05) in carcass weights were observed. All fat supplemented groups had reduced rumen fluid protozoa counts (P < 0.05). Carcasses tended to be leaner with the fat supplements. Mostly no significant effects on other carcass quality (dressing percentage, conformation score) and meat quality traits (final pH, cooking loss, shear forces) as well as composition (dry matter, fat, collagen) occurred. Consequently, rumen protected fat and some oilseeds can be recommended to be fed to growing cattle as energy sources.
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PMID:Comparative evaluation of rumen-protected fat, coconut oil and various oilseeds supplemented to fattening bulls. 1. Effects on growth, carcass and meat quality. 1083 55

The collagen metabolites hydroxyproline (HYP), deoxypyridinoline (DPD), and the carboxyterminal telopeptide of type I collagen (ICTP) are suitable markers for bone resorption in humans and several animal species. The purpose of this study was to describe the course of bone resorption markers during short-term hypocalcemia induced with disodium ethylenediaminetetraacetic acid (Na2EDTA) and to investigate whether bone resorption is increased in dairy cows under these conditions. EDTA infusions have been used as a model for periparturient paresis in dairy cows and to estimate the calcium mobilization rate from body reserves in ruminants. In this study, hypocalcemia was induced by means of a 5% Na2EDTA infusion (0.55 mg/kg/min Na2EDTA for 5 h = total dose of 100.6 g). Two experiments were conducted: (1) Six 4-11 years-old Brown Swiss cows were infused intravenously with EDTA for 5 h. Blood and urine samples were taken repeatedly from 1 day before until 10 days after infusion. (2) Towards the end of the lactation, the experiment was repeated with the same animals after a 14-day-period of feeding a low calcium diet (26 g/animal per day). The EDTA-infusion induced hypocalcemia and hypophosphatemia. The HYP-, DPD- and ICTP-concentration remained mainly unaffected during both infusions. Only DPD showed an increase during infusion and HYP an increase 2 days after the infusion. In conclusion, the EDTA infusion had little effect on the concentrations of the measured bone markers, which may be due to the fact that the serum calcium pool was refilled by increased absorption of Ca via the gastrointestinal tract. From these results, it can be concluded that bone resorption was not influenced by EDTA infusion.
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PMID:The course of selected bone resorption marker concentrations in response to short-term hypocalcemia experimentally induced with disodium EDTA infusions in dairy cows. 1107 39

Paxillin is a focal adhesion adapter protein involved in the integration of growth factor- and adhesion-mediated signal transduction pathways. Paxillin LD motifs have been demonstrated to bind to several proteins associated with remodeling of the actin cytoskeleton including the focal adhesion kinase, vinculin, and a complex of proteins comprising p95PKL, PIX, and PAK (Turner, C.E., M. C. Brown, J.A. Perrotta, M.C. Riedy, S.N. Nikolopoulos, A.R. McDonald, S. Bagrodia, S. Thomas, and P.S. Leventhal. 1999. J. Cell Biol. 145:851-863). In this study, we report the cloning and initial characterization of a new paxillin LD motif-binding protein, actopaxin. Analysis of the deduced amino acid sequence of actopaxin reveals a 42-kD protein with two calponin homology domains and a paxillin-binding subdomain (PBS). Western blotting identifies actopaxin as a widely expressed protein. Actopaxin binds directly to both F-actin and paxillin LD1 and LD4 motifs. It exhibits robust focal adhesion localization in several cultured cell types but is not found along the length of the associated actin-rich stress fibers. Similar to paxillin, it is absent from actin-rich cell-cell adherens junctions. Also, actopaxin colocalizes with paxillin to rudimentary focal complexes at the leading edge of migrating cells. An actopaxin PBS mutant incapable of binding paxillin in vitro cannot target to focal adhesions when expressed in fibroblasts. In addition, ectopic expression of the PBS mutant and/or the COOH terminus of actopaxin in HeLa cells resulted in substantial reduction in adhesion to collagen. Together, these results suggest an important role for actopaxin in integrin-dependent remodeling of the actin cytoskeleton during cell motility and cell adhesion.
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PMID:Actopaxin, a new focal adhesion protein that binds paxillin LD motifs and actin and regulates cell adhesion. 1113 73

Increased or altered collagen deposition in the airway wall is one of the characteristics of airway remodelling in asthma. The mechanisms underlying this increase, and its functional consequences remain to be established further. Representative in vivo animal models might be useful in this respect. In the present study, collagen deposition after prolonged allergen exposure was characterised in the airway wall of Brown Norway rats. Sensitised rats were repeatedly exposed to ovalbumin (OA) or phosphate-buffered saline during 2 and 12 weeks. The deposition of collagen type I, III, IV, V and VI was not altered in animals exposed to OA for 2 weeks. After 12 weeks of OA exposure, more collagen type I was deposited in the inner and outer airway wall and more type V and VI collagen was observed in the outer airway wall. At 12 weeks the number of vessels, identified via type IV collagen staining was not increased, but the total vessel area was. In conclusion, prolonged allergen exposure in sensitised rats is associated with enhanced deposition of type I, V and VI collagens and increased vascularity. This suggests that some aspects of airway remodelling in asthma could be driven by long-term allergen exposure.
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PMID:Repeated allergen exposure changes collagen composition in airways of sensitised Brown Norway rats. 1221 56

Many cartilage matrix proteins or domains such as collagen types II, IX, and XI, GP39, AG1, VG1, and LP are potential antigens that might induce polyarthritis in susceptible animals (Table 1). Ordinarily, spondylitis is not a feature of polyarthritis induced with collagen types II, IX, and XI, GP39, cartilage matrix protein (matrilin-1) and cartilage LP. It seems that only the proteoglycans aggrecan and versican are capable of inducing sacroiliitis and spondylitis. Both molecules are structural proteins in intervertebral discs. Moreover, the arthritogenic or spondylitogenic epitopes of both molecules have been localized to the homologous N-terminal G1 globular domains. This region of versican and aggrecan is highly conserved, with 52% identity of amino acids. The homology is seen exclusively in the G1 domain and is concentrated between residues 115 and 332 (AG1 numbering) near the natural cleavage DIPEN site of aggrecan [84, 85]. Extra-articular pathology is often seen in rheumatic diseases, especially in AS. Other tissues, such as the sclera of the eye [86] and the media of the arteries [86, 87], also contain type II collagen, AG1, VG1, and LP, and versican is present in the central and peripheral nervous systems. Thus, there is the potential for an immune response against cartilage G1 and LP to be directed against related structures in extra-articular tissues. The presence of versican in the tendon and trochlea of the human superior oblique muscle might account for the occurrence of transient attacks of acquired Brown syndrome in patients with juvenile and adult forms of chronic RA [88]. Thus, it will be interesting to determine whether or not extra-articular expression of these cartilage proteins is closely related to extra-articular pathogenic expression in rheumatic diseases. Uveitis develops in VG1-immunized BALB/c mice, which is not seen in AG1-, and LP-treated animals. There is evidence that aggrecan and LP are also localized at these sites in the eye, but only immunity to versican can induce uveitis. In sacroiliitis and enthesitis of AS patients, the inflammation is associated with chondrometaplasia. In versican-induced sacroiliitis, replacement of cartilage by bone is seen with relatively little inflammation, somewhat resembling the situation in AS (Fig. 2). Versican can also stimulate chondrocyte proliferation [43]. Three conserved domains of human cartilage matrix molecules, namely VG1, AG1, and LP, show considerable homology [77, 79, 80, 89], and each is capable of inducing a unique inflammatory arthritis in BALB/c mice, with VG1 inducing only spondylitis [65], LP inducing peripheral arthritis with no spondylitis [90], and AG1 inducing axial and peripheral arthritis [66, 91]. It remains a mystery why such similar molecules cause different pathology in different target tissues. The exact immunopathogenic mechanisms deserve further study.
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PMID:Animal models of inflammatory spinal and sacroiliac joint diseases. 1295 72


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