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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The autosomal recessive mutations fa (rat) and db (mouse) cause obesity syndromes that develop early and ultimately become severe. Although both fa/fa rats and db/db mice have been studied extensively as models of human obesity and diabetes, the molecular bases of these phenotypes remain unknown. We have mapped fa in 50 fa/fa (obese) offspring of a (13M x Brown Norway) F1 fa/+ intercross relative to two molecular markers, Ifa and Glut-1, which flank db on mouse chromosome 4 and which are located on rat chromosome 5. Ifa and Glut-1 are linked to fa, with a gene order, Ifa-fa-Glut-1, that is identical to that for the region around db in the mouse genome. These results place fa on rat chromosome 5 and suggest that db and fa are mutations in homologous genes.
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PMID:Rat obesity gene fatty (fa) maps to chromosome 5: evidence for homology with the mouse gene diabetes (db). 188 16

Like human kininogens-deficiency, the ureter urine of Brown Norway (B/N) Katholiek rat, a congenitally deficient strain in plasma high molecular weight (HMW)- and low molecular weight (LMW)-kininogen, showed no detectable kinin in the peptide fraction of gel chromatography, whereas normal ureter urine (B/N-Kitasato rat) expressed kinin in the peptide fraction, when assayed by bradykinin enzyme immunoassay (EIA). However there was immunoreactive substance in the higher molecular weight fraction in both strains of rat. The nature of this substance is not known, but it may give rise to a wrong estimate for kinin if rat urine is allowed to immunoassay directly, and peptide fraction of urine is not resolved into its components by gel chromatography. Kinin degrading activity in rat urine is so potent that kinin could be mostly degraded when stored in the bladder, since kinin was found in the peptide fraction of fresh ureter urine but not in that of bladder urine of the normal strain.
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PMID:Differentiation of kinin fractions in ureter urine and bladder urine of normal and kininogen-deficient rats. 268 78

The development of a humoral immune response to the tubular basement membrane (TBM) alloantigen of Brown-Norway (BN) rat kidneys was studied after transplantation of BN rat kidneys into bilaterally nephrectomized Lewis (LEW) rats. The LEW rat recipients consisted of four groups receiving no form of immunosuppression, pretransplantation cyclosporin alone, or pretransplantation donor-specific or donor-nonspecific transfusions combined with cyclosporin. The latter two regimens induce indefinite allograft survival in the majority of recipients. Circulating antibody to collagenase-solubilized BN rat renal basement membrane (CS-BN-RBM) was present in all four groups of transplant recipients within 1 week after transplantation, and no significant differences in antibody levels were noted between rats receiving no immunosuppression (survival of 1-2 weeks) and the groups of rats who received various immunosuppressive regimens and survived longer. Circulating antibody to BN-CS-RBM continued to increase in quantity in the cyclosporin-treated group until the time of death (2-10 weeks post-transplantation). In the much longer lived combined transfusion and cyclosporin-treated groups, circulating antibody to BN-CS-RBM generally attained a maximum at approximately 2 to 4 months post-transplantation and then plateaued or decreased somewhat before the time of death (3-16 months post-transplantation). No correlation was found between quantity of circulating anti-BN-CS-RBM antibody and post-transplantation survival. Comparative study of the quantity of circulating antibody to BN-CS-RBM (the presumed nephritogenic antigen of experimental tubulointerstitial nephritis in the BN rat) in serum from transplant recipients as compared to serum from BN rats with severe experimental tubulointerstitial nephritis (TIN) (as induced by immunization with heterologous TBM antigens) demonstrated a greater quantity of potentially nephritogenic antibody circulating in transplant recipients than in BN rats with experimental TIN. Histologically, the transplanted kidneys in immunomodulated recipients demonstrated focal chronic interstitial inflammatory infiltrates with tubular atrophy and relative sparing of the glomeruli. The development of immune responses to tissue-specific alloantigens may become of clinical significance as graft-survival times are increased.
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PMID:The development of humoral immunity to tissue-specific tubular basement membrane alloantigens after renal transplantation across the major histocompatibility barrier in rats immunomodulated with blood transfusions and cyclosporin. 329 55

The BB rat develops a syndrome of autoimmune diabetes similar to Type I diabetes of man. It also has a severe T cell lymphopenia. As part of an ongoing breeding program to transfer the diabetogenic genes of the BB rat onto inbred rat strain backgrounds, diabetic animals were used in a backcross (BC)- intercross (IC)-backcross breeding scheme with Brown Norway (BN), Lewis (L), and Wistar-Furth (WF) inbred rats. We have used monoclonal antibodies to analyze both lymphopenia and major histocompatibility (MHC) antigens (the RT1 locus in the rat) in relation to the development of diabetes. To examine T cell subsets we used a panel of monoclonal antibodies, in particular W3/25 and OX19 , which discriminate the abnormal phenotype better than W3/13. In our breeding program, at least two independent genes or gene complexes are required for the expression of diabetes. One gene determines the lymphopenia, is inherited by simple autosomal recessive genetics and is not linked to the MHC. The second gene is linked to the MHC. Both genes are necessary, but neither gene is sufficient by itself for the development of diabetes.
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PMID:Two genes required for diabetes in BB rats. Evidence from cyclical intercrosses and backcrosses. 620 17

Tumor necrosis factor (TNF) has been implicated in the pathophysiology of a number of inflammatory diseases of the lung. Using the TNF receptor fusion protein, Ro 45-2081, our study investigated the involvement of TNF in allergic inflammatory responses in the airways of sensitized guinea pigs and Brown-Norway rats. Sensitized guinea pigs exhibited an enhanced airway reactivity to substance P (1-10 micrograms/kg, i.v.) at 6 hr after antigen challenge which was inhibited (P < .05) by Ro 45-2081 (3 mg/kg, i.p.). Treatment with Ro 45-2081 (1-3 mg/kg, i.p.) dose-dependently inhibited (P < .05) the accumulation of neutrophils and total cells in bronchoalveolar lavage fluid in sensitized guinea pigs examined at 6 and 24 hr postchallenge. Ro 45-2081 (3 mg/kg, i.p.) also significantly (P < .05) reduced the number of eosinophils in bronchoalveolar lavage at both time points whereas a lower dose (1 mg/kg, i.p.) had no effect. Ro 45-2081 (1 or 3 mg/kg, i.p.) abolished antigen-induced microvascular leakage (quantified by tissue content of Evans blue dye) in the trachea and main bronchi in sensitized guinea pigs. In the Brown-Norway rat, Ro 45-2081 (1-3 mg/kg, i.p.) caused a dose-dependent inhibition of neutrophil and eosinophil infiltration into bronchoalveolar lavage fluid at 24 hr after antigen challenge. In both guinea pig and Brown-Norway rat models, treatment with dexamethasone (30 mg/kg, i.p., for guinea pig and 0.3 mg/kg, i.p., for Brown-Norway rat) produced virtually identical results to those obtained with Ro 45-2081. The ability of Ro 45-2081 to inhibit antigen-induced responses in sensitized animals suggests that TNF is a mediator of allergic inflammation in the lung.
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PMID:Pharmacological evidence for tumor necrosis factor as a mediator of allergic inflammation in the airways. 876 39

Role of renal kallikrein-kinin system has been studied using mutant Brown-Norway Katholiek (BN-Ka) rats, in which both high- and low-molecular weight kininogens were almost absent in plasma and kinin in urine was mainly not detectable. Mutant BN-Ka rats were very sensitive to increased salt intake, resulting in raised systemic blood pressure that is linked to reduced urinary excretion of sodium, when compared with normal BN-Kitasato (BN-Ki) rats. Consequently, sodium accumulated in erythrocytes and cerebrospinal fluid in mutant BN-Ka rats. Subcutaneous infusion of angiotensin II (20 mg/day/rat) also enhanced the concentration of sodium in erythrocytes and in cerebrospinal fluid and increased the systemic pressure by releasing aldosterone. A 4-day infusion of 0.3 M sodium solution (6 ml/kg/h) to the abdominal aorta of conscious and un-restrained mutant BN-Ka rats increased the pressor responses of the arterioles to norepinephrine and angiotensin II (i.a.) by 30- and 10-fold, respectively. Infusion of ebelactone B, (a selective inhibitor of carboxypeptidase Y-like exopeptidase, a kininase in rat urine), to normal BN-Ki rats during induction of hypertension with DOCA and salt, resulted in the reduction of the raised blood pressure, indicating that a site of action of kinins was at the luminal membrane of the renal tubule cells. Our results support the view that the role of renal kallikrein-kinin system is to excrete 'excess sodium' and a reduction in the generation of renal kinins may be a factor in the development of hypertension as a result of the sodium accumulation in the body.
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PMID:Role of the renal kallikrein-kinin system in the development of hypertension. 922 52

Based on a literature implicating altered calcium homeostasis in brain aging and Alzheimer's Disease (AD) and evidence of decreased vitamin D action in AD subjects, the possibility was tested that calcitriol (1,25(OH)2 vitamin D3), the active form of vitamin D3, might reduce markers of brain aging in rats. Animals were treated 5x weekly for prolonged periods (6-12 months) with either calcitriol in doses sufficient to elevate serum calcium and phosphate (20 ng/rat), calcitonin (1.5 IU/rat) or vehicle, in three separate long-term experiments on aging rats. New stereological methods (physical disector) of cell counting were used to evaluate neuronal density, a reliable biomarker of hippocampal aging in rats. In two experiments utilizing Brown-Norway x F344 hybrid rats (BN x F344), 8 months and 12 months of chronic treatment with calcitriol resulted in a higher density of CA1 neurons in the middle regions of the hippocampus, compared to vehicle or calcitonin treatment. However, one study with aging F344 rats was terminated early because of extensive strain-specific pathology and no effect of calcitriol on neuronal density was observed. These studies suggest that, under some conditions, hormonal treatments that regulate calcium homeostasis can modulate markers of brain aging.
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PMID:Long-term treatment with calcitriol (1,25(OH)2 vit D3) retards a biomarker of hippocampal aging in rats. 988 49

We examined the role of CD8+ T cells in a Brown-Norway rat model of asthma, using a monoclonal antibody to deplete CD8+ T cells. Ovalbumin (OA)-sensitized animals were given anti-CD8 antibody (0.5 mg/rat) intravenously 1 week prior to exposure to 1% OA aerosol and were studied 18-24 hr after aerosol exposure. Following administration of anti-CD8 antibody, CD8+ cells were reduced to <1% of total lymphocytes in whole blood and in spleen. In sensitized animals, OA exposure induced bronchial hyper-responsiveness (BHR), accumulation of eosinophils, lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also an increase in tissue eosinophils and CD2+, CD4+ and CD8+ T cells in airways. Anti-CD8 antibody caused a further increase in allergen-induced BHR (P<0.03, compared with sham-treated animals), together with a significant increase in eosinophil number in BAL fluid (P<0.05). While CD2+ and CD4+ T cells in airways were not affected by anti-CD8 treatment, the level of CD8+ T cells was significantly reduced in sensitized, saline-exposed animals (P<0.04, compared with sham-treated rats), and sensitized and OA-challenged rats (P<0.002, compared with sham-treated rats). Using reverse transcription-polymerase chain reaction, an increase of T helper (Th)2 cytokine [interleukin (IL)-4 and IL-5], and also of Th1 cytokine [interferon-gamma (IFN-gamma) and IL-2], mRNA in the lung of sensitized and OA-exposed animals was found; after CD8+ T-cell depletion, Th1 cytokine expression was significantly reduced (P<0.02), while Th2 cytokine expression was unchanged. CD8+ T cells have a protective role in allergen-induced BHR and eosinophilic inflammation, probably through activation of the Th1 cytokine response.
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PMID:Effect of CD8+ T-cell depletion on bronchial hyper-responsiveness and inflammation in sensitized and allergen-exposed Brown-Norway rats. 1023 23

Chemokines are thought to contribute to the cellular infiltrate characteristic of renal transplant rejection. We show that Met-RANTES, a chemokine receptor antagonist, suppresses recruitment of inflammatory cells into renal allografts. In a renal transplant model (Fisher RT1(lvl) rat kidney into Lewis RT1(l) rat) where no additional immune suppressant was used, Met-RANTES-treated animals showed a significant reduction in vascular injury score (16.10 +/- 5.20 vs. 62.67 +/- 18.64) and tubular damage score (15.70 +/- 5.22 vs. 33.00 +/- 6.44) relative to untreated animals. In a more severe rejection model (Brown-Norway RT1(n) rat kidney into Lewis RT1(1) rat), Met-RANTES significantly augmented low-dose cyclosporin A treatment to reduce all aspects of renal injury including interstitial inflammation (score 71.00 +/- 6.10 vs. 157.30 +/- 21.30). The majority of infiltrating cells in these models (60-70%) consisted of monocytes. Potential mechanisms of action of Met-RANTES were tested using monocyte attachment assays on microvascular endothelium under physiological flow conditions. Preexposure of microvascular endothelium to RANTES resulted in RANTES immobilization and RANTES-induced firm adhesion of monocytes only after prestimulation of the endothelium with IL-1beta. Met-RANTES completely inhibited this RANTES-mediated arrest. Thus, Met-RANTES may counter acute rejection by blocking leukocyte firm adhesion to inflamed endothelium.
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PMID:Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection: blocking monocyte arrest and recruitment. 1042 61

Chemokines contribute to the mononuclear cell infiltrate in vessels and interstitium which is characteristic of renal transplant rejection. By employing the chemokine receptor blocker Met-RANTES it was shown that recruitment of inflammatory cells into renal allografts could be significantly suppressed. In a renal transplant model (Fisher RT1(1v1) rat kidney into Lewis RT1(1) rat) Met-RANTES-treated animals showed a significant reduction in vascular injury score (16.10 +/- 5.20 vs. 62.67 +/- 18.64) and tubular damage score (15.70 +/- 5.22 vs. 33.00 +/- 6.44) relative to untreated animals. In a severe rejection model (Brown-Norway RT1n rat kidney into Lewis RT1(1) rat), Met-RANTES significantly augmented low-dose cyclosporin A treatment to reduce all aspects of renal injury including interstitial inflammation (score 71.00 +/- 6.10 vs. 157.30 +/- 21.30). In a monocyte attachment assay on microvascular endothelium under physiological flow conditions exposure of microvascular endothelium to RANTES resulted in RANTES immobilization and RANTES-induced firm adhesion of monocytes only after prestimulation of the endothelium with IL-1 beta. Met-RANTES completely inhibited this RANTES-mediated arrest. Thus, Met-RANTES can reduce acute rejection by impeding leukocyte arrest to inflamed endothelium.
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PMID:[Reduction of acute kidney transplantation rejection by the chemokine receptor antagonist Met-RANTES]. 1071 11


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