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

Genetic linkage analyses in human populations have traditionally combined male and female progeny for determination of quantitative trait loci (QTL). In contrast, most rodent studies have focused primarily on males. This study represents an extensive female-specific linkage analysis in which 236 neuroendocrine, renal, and cardiovascular traits related to arterial pressure (BP) were determined in 99 female F2 rats derived from a cross of Dahl salt-sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/SsNHsdMcwi (BN) rats. We identified 126 QTL for 96 traits on 19 of the 20 autosomal chromosomes of the female progeny. Four chromosomes (3, 6, 7, and 11) were identified as especially important in regulation of arterial pressure and renal function, since aggregates of 8-11 QTL mapped together on these chromosomes. BP QTL in this female population differed considerably from those previously found in male, other female, or mixed sex population linkage analysis studies using SS rats. Kidney weight divided by body weight was identified as an intermediate phenotype that mapped to the same region of the genome as resting diastolic blood pressure and was correlated with that same BP phenotype. Seven other phenotypes were considered as "potential intermediate phenotypes, " which mapped to the same region of the genome as a BP QTL but were not correlated with BP. These included renal vascular responses to ANG II and ACh and indices of baroreceptor responsiveness. Secondary traits were also identified that were likely to be consequences of hypertension (correlated with BP but not mapped to a BP QTL). Seven such traits were found, notably heart rate, plasma cholesterol, and renal glomerular injury. The development of a female rat systems biology map of cardiovascular function represents the first attempt to prioritize those regions of the genome important for development of hypertension and end organ damage in female rats.
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PMID:Genomic map of cardiovascular phenotypes of hypertension in female Dahl S rats. 1453 35

Experiments examined the influence of diet and genetics on hypertension and renal disease in inbred Dahl salt-sensitive (SS/Mcw) rats and consomic rats in which chromosomes 16 (SS.BN16) or 18 (SS.BN18) of the normotensive Brown Norway rat were inserted into the genetic background of the SS/Mcw. Dahl SS/Mcw breeders and offspring were randomly placed on a purified AIN-76A diet or a grain-based diet, and male offspring were screened for cardiovascular and renal phenotypes following 3 wk on a 4.0% NaCl diet. High-salt arterial blood pressure (162 +/- 5 mmHg, n = 10), urinary protein excretion (147 +/- 16 mg/day, n = 14), and albumin excretion (72 +/- 9 mg/day, n = 14) were significantly elevated in the Dahl SS/Mcw maintained on the purified diet compared with rats fed the grain-based diet. Rats fed the purified diet also exhibited significantly more renal glomerular and tubular damage than rats fed the grain diet. Moreover, feeding the purified diet to the parents led to a significant increase in blood pressure in the offspring, regardless of offspring diet. Similar dietary effects were observed in SS.BN16 and SS.BN18 rats. In rats fed the purified diet, substitution of chromosomes 16 or 18 led to a significant decrease in arterial blood pressure, albumin excretion, and protein excretion compared with the SS/Mcw. Chromosomal substitution did not, however, affect albumin or protein excretion in the consomic rats compared with the SS/Mcw when the rats were maintained on the grain diet. These data demonstrate a significant influence of diet composition on salt-induced hypertension and renal disease in the Dahl SS/Mcw rat.
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PMID:Influence of diet and genetics on hypertension and renal disease in Dahl salt-sensitive rats. 1460 Feb 13

Brown seaweeds are interesting materials to be used as biosorbents for heavy metals due to their high binding ability and low cost. The study of the passive biosorption of protons on this kind of materials and its dependency on pH, ionic strength, and medium composition is essential for the practical application of brown algae in wastewater treatment. This work reports the results of the study of the proton binding equilibria of dead biomass from the seaweeds Sargassum muticum, Cystoseira baccata, and Saccorhiza polyschides by potentiometric titration with a glass electrode in the pH range between 2 and 8. Two different salts, NaCl and KNO3, in concentrations ranging from 0.05 to 2 mol x L(-1), were used as background electrolytes. The influence of the ionic strength was accounted for by means of the Donnan model in combination with the master curve approach. Different empirical expressions to describe the swelling behavior of the biosorbent were tested. On the basis of the intrinsic affinity distribution analysis a unimodal Langmuir-Freundlich isotherm was selected to describe the proton binding properties. The results show very little influence of the type of salt. The ionic strength dependency of the proton binding is very similar for the three species, and average empirical expressions of the Donnan volume are proposed. The maximum proton binding capacities obtained ranged between 2.4 and 2.9 mol x kg(-1), with average intrinsic proton affinity constants between 3.1 and 3.3, and heterogeneity parameters of ca. 0.5 for S. muticum and C. baccata, and slightly higher (ca. 0.7) for S. polyschides. The combined Langmuir-Freundlich equation and Donnan model allowed a good description of the experimental charge vs pH curves obtained.
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PMID:Acid-base properties of brown seaweed biomass considered as a Donnan gel. A model reflecting electrostatic effects and chemical heterogeneity. 1465 2

Hydrogels present an attractive alternative to nanoscale block copolymer aggregates and microscale resin beads as potential asystemic serum cholesterol reduction materials. Not only would the oral delivery of these materials be more pleasant than the sand-like bile salt anion sequestrant beads but also the hydrogel preparation is much simpler than the copolymer aggregate analogues [Cameron, N. S.; Eisenberg, A.; Brown, G. R. Biomacromolecules 2002, 3, 116-123. Cameron, N. S.; Eisenberg, A.; Brown, G. R. Biomacromolecules 2002, 3, 124-132]. Our goal was to explore these materials building on our experience with bulk resins and self-assembled copolymers. In this paper, following a brief introduction to hydrogels and their application to hypercholesterolemia, the synthesis, characterization, and preliminary glycocholate binding properties of poly(N,N,N-trimethylammoniumalkyl acrylamide chloride)gel are presented [Cameron, N. S.; Eisenberg, A.; Brown, G. R. Polym. Preprints 2002, 43, 771-772].
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PMID:Poly(N,N,N-trimethylammoniumalkyl acrylamide chloride) based hydrogels for serum cholesterol reduction. 1471 4

This study compared the expression of enzymes and transport and channel proteins involved in the regulation of sodium reabsorption in the kidney of Dahl salt-sensitive (DS) and salt-resistant Brown-Norway (BN) and consomic rats (SS.BN13), in which chromosome 13 from the BN rat has been introgressed into the DS genetic background. The expression of the Na+/K+/2Cl- (BSC-1) cotransporter, Na+/H+ exchanger (NHE3), and Na+-K+-ATPase proteins were similar in the renal cortex of DS, BN, and SS.BN13 rats fed either a low-salt (0.1% NaCl) or a high-salt (8% NaCl) diet. The expression of the BSC-1 and the renal outer medullary K+ channel (ROMK) were higher, whereas the expression of the cytochrome P4504A proteins responsible for the formation of 20-hydroxyeicosatetraenoic (20-HETE) was lower in the outer medulla of the kidney of DS than in BN or SS.BN13 rats fed either a low-salt or a high-salt diet. In addition, the renal formation and excretion of 20-HETE was lower in DS than in BN and SS.BN13 rats. These results suggest that overexpression of ROMK and BSC-1 in the thick ascending limb combined with a deficiency in renal formation of 20-HETE may predispose Dahl S rats fed a high-salt diet to Na+ retention and hypertension.
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PMID:Elevated BSC-1 and ROMK expression in Dahl salt-sensitive rat kidneys. 1496 39

Escherichia coli YjeQ represents a conserved group of bacteria-specific nucleotide-binding proteins of unknown physiological function that have been shown to be essential to the growth of E. coli and Bacillus subtilis. The protein has previously been characterized as possessing a slow steady-state GTP hydrolysis activity (8 h(-1)) (D. M. Daigle, L. Rossi, A. M. Berghuis, L. Aravind, E. V. Koonin, and E. D. Brown, Biochemistry 41: 11109-11117, 2002). In the work reported here, YjeQ from E. coli was found to copurify with ribosomes from cell extracts. The copy number of the protein per cell was nevertheless low relative to the number of ribosomes (ratio of YjeQ copies to ribosomes, 1:200). In vitro, recombinant YjeQ protein interacted strongly with the 30S ribosomal subunit, and the stringency of that interaction, revealed with salt washes, was highest in the presence of the nonhydrolyzable GTP analog 5'-guanylylimidodiphosphate (GMP-PNP). Likewise, association with the 30S subunit resulted in a 160-fold stimulation of YjeQ GTPase activity, which reached a maximum with stoichiometric amounts of ribosomes. N-terminal truncation variants of YjeQ revealed that the predicted OB-fold region was essential for ribosome binding and GTPase stimulation, and they showed that an N-terminal peptide (amino acids 1 to 20 in YjeQ) was necessary for the GMP-PNP-dependent interaction of YjeQ with the 30S subunit. Taken together, these data indicate that the YjeQ protein participates in a guanine nucleotide-dependent interaction with the ribosome and implicate this conserved, essential GTPase as a novel factor in ribosome function.
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PMID:Studies of the interaction of Escherichia coli YjeQ with the ribosome in vitro. 1497 29

Previous studies using reciprocal crosses between the spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY) strain suggested a role for the Y chromosome in the SHR's exaggerated preference for saline solutions. We have reexamined the role of the Y chromosome in the salt preference of the SHR using a consomic strain derived from SHR and Brown Norway (BN-Lx) progenitors. We also studied congenic lines in which regions of BN-Lx chromosomes 8 and 20 had been introgressed into the SHR genome. Animals were given a choice of water and 0.9% saline to drink over a period of 7 days and their total fluid intake (TFI; water plus saline) and saline preference (proportion of the TFI taken as saline) calculated. SHR bearing the BN-Lx Y chromosome had a significantly reduced saline preference when compared to progenitor SHR. Evidence was also found for the existence of a region on chromosome 8, which influences fluid intake in the SHR. The causative genes involved in these effects however remain to be determined.
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PMID:Salt preference of congenic strains derived from the spontaneously hypertensive rat. 1498 94

To evaluate the potential role of impaired renin-angiotensin system (RAS) function in contributing to reduced vascular relaxation in Dahl salt-sensitive (S) rats, responses to ACh (10(-6) mol/l) and hypoxia (Po(2) reduction to 40-45 mmHg) were determined in isolated middle cerebral arteries of Dahl S rats, Brown Norway (BN) rats, and consomic rats having chromosome 13 (containing the renin gene) or chromosome 16 of the BN rat substituted into the Dahl S genetic background (SS-13(BN) and SS-16(BN), respectively). Arteries of BN rats on a low-salt (LS) diet (0.4% NaCl) dilated in response to ACh and hypoxia, whereas dilation in response to these stimuli was absent in Dahl S rats on LS diet. Vasodilation to ACh and hypoxia was restored in SS-13(BN) rats on an LS diet but not in SS-16(BN) rats. High-salt diet (4% NaCl), to suppress ANG II, eliminated vasodilation to hypoxia and ACh in BN and in SS-13(BN) rats. Treatment of SS-13(BN) rats with the AT(1) receptor antagonist losartan also eliminated the restored vasodilation in response to ACh and hypoxia. These studies suggest that restoration of normal RAS regulation in SS-13(BN) consomic rats restores vascular relaxation mechanisms that are impaired in Dahl S rats.
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PMID:Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation. 1503 Nov 25

Brown Norway (BN) and BN Katholiek (BN/Ka) rat strains are both susceptible to develop lesions in the internal elastic lamina (IEL) of the aorta. BN/Ka rats are characterized by a single point mutation in the kininogen gene leading to deficiency in high- and low-molecular-weight kininogen. Recently, a suggestive quantitative trait locus for lesions in the IEL of the abdominal aorta was identified in an F2 intercross between Dahl salt-sensitive (SS) and BN rats, implicating kininogen as a positional candidate gene. Therefore, BN and BN/Ka rat strains represent ideal model organisms with which to study the contribution of kininogen to the genetic predisposition to IEL lesion formation and to characterize the early events underlying vascular remodeling. Here we present data demonstrating that genetic kininogen deficiency promotes the formation of aneurysms in the abdominal aorta but not the development of atherosclerosis upon 12-wk treatment with an atherogenic diet. Aneurysm formation was associated with an enhanced elastolysis, increased expression of MMP-2 and MMP-3, downregulation of TIMP-4, and with FasL- and caspase-3-mediated apoptosis. Kininogen-deficient animals also featured changes in plasma cytokines compatible with apoptotic vascular damage, i.e., upregulation of IFN-gamma and downregulation of GM-CSF and IL-1beta. Finally, in response to atherogenic diet, kininogen-deficient animals developed an increase in HDL/total cholesterol index, pronounced fatty liver and heart degeneration, and lipid depositions in aortic media without atherosclerotic plaque formation. These findings suggest that genetic kininogen deficiency renders vascular tissue prone to aneurysmatic but not to atherosclerotic lesions.
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PMID:Genetic kininogen deficiency contributes to aortic aneurysm formation but not to atherosclerosis. 1523 17

Our previous studies showed that adrenalectomy (ADX) has surprisingly no effect on body weight and fluid intake in the Brown Norway rat strain, suggesting that mineralocorticoid receptor (MR)-mediated effects are present even in absence of corticosteroids in this strain. Moreover, glucocorticoid receptor (GR)-mediated mechanisms are more effective in Brown Norway than in Fischer 344 rats. Such functional differences in corticosteroid receptor pathways between Brown Norway and Fischer 344 rats led us to compare the effect of ADX and MR/GR-mediated actions on sodium and potassium excretion between these two rat strains. To this end, we first measured the effect of an acute high dose of aldosterone on the urinary Na+/K+ concentration ratio in intact and ADX Brown Norway and Fischer 344 rats. Second, to discriminate mineralocorticoid from glucocorticoid actions, we treated chronically ADX rats with increasing doses of aldosterone or RU28362, a pure GR agonist, in the drinking fluid. As sodium homeostasis involves salt appetite regulation, behaviour under mineralocorticoid control, we also measured saline preference in Brown Norway and Fischer 344 rats. Our data illustrate: (1) the very limited effect of ADX on body weight, food and fluid intake, diuresis, natriuresis, kaliuresis and salt appetite in Brown Norway rats, supporting the presence of MR signalling pathways in the absence of adrenal steroids in these rats; (2) the insensitivity of MR to aldosterone in intact Brown Norway rats, and the reduced sensitivity of MR to aldosterone in ADX Brown Norway rats compared with ADX Fischer 344 rats; and (3) the greater sensitivity of GR-related mechanisms to RU28362 in Brown Norway than in Fischer 344 rats in terms of body weight gain and electrolyte excretion. Considering that both MRs and GRs regulate hypothalamic-pituitary-adrenal axis processes, such functional differences in corticosteroid receptors could be at the origin, at least partly, of the strain differences in corticotropic activity/reactivity to stress previously described.
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PMID:Excretion of electrolytes in Brown Norway and Fischer 344 rats: effects of adrenalectomy and of mineralocorticoid and glucocorticoid receptor ligands. 1536 79


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