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

Brown, Ruby L. (North Carolina State College, Raleigh) and James B. Evans. Comparative physiology of antibiotic-resistant strains of Staphylococcus aureus. J. Bacteriol. 85:1409-1412. 1963.-A collection of antibiotic-resistant strains of Staphylococcus aureus isolated from clinical sources was studied with respect to nutritional requirements and common diagnostic tests. Contrary to numerous reports in the literature indicating changes in these characteristics in antibiotic-resistant mutants, the present cultures were typical members of the taxonomic species S. aureus. They were coagulase-positive, fermented both glucose and mannitol under anaerobic conditions, produced acetoin from glucose, grew and produced black colonies on tellurite glycine agar, required both thiamine and nicotinic acid, and did not require other vitamins or purines. It is suggested that in most instances these cultures from clinical sources represent spontaneous mutants having genetic changes limited largely to loci concerned with antibiotic resistance. Most reports of extensive changes in physiology and nutritive requirements by antibiotic-resistant strains of S. aureus are based on studies of resistant strains selected after exposing a large population of the parent sensitive strain to toxic levels of antibiotics, chemical mutagens, or irradiation. Such isolates may have widespread genetic damage at other loci in addition to those concerned with their antibiotic resistance.
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PMID:COMPARATIVE PHYSIOLOGY OF ANTIBIOTIC-RESISTANT STRAINS OF STAPHYLOCOCCUS AUREUS. 1404 37

Sex differences in opioid antinociception have been reported in rodents and monkeys, with opioids being more potent in males than females. In the present study, the influence of rat strain on sex differences in opioid antinociception was examined in a warm water tail-withdrawal procedure. Antinociceptive tests were conducted with the high-efficacy micro-opioid morphine, and the less efficacious opioids buprenorphine, butorphanol and nalbuphine. Baseline nociceptive latencies were consistently higher in males than their female counterparts. Sex differences in opioid antinociception were observed in all strains tested, with the opioids being more potent and/or effective in males. The magnitude of the sex differences was related to the relative efficacy of the opioid, with morphine, buprenorphine, butorphanol and nalbuphine being on average 2.2-, 2.6-, 15.9- and 11.9-fold more potent in males. Sex differences also varied markedly across strains, with large differences consistently obtained in the F344 and F344-Sasco strains, moderate differences in the ACI, DA, Lewis, Sprague Dawley, Wistar and Wistar-Kyoto strains, and small differences in the Long Evans-Blue Spruce, Long Evans, Brown Norway and Holtzman strains. When compared across strains, there was no relationship between sex differences in nociceptive sensitivity and opioid sensitivity. These findings provide strong support for the role of genetic factors in determining sex differences in opioid antinociception, and suggest that the use of low-efficacy opioids, coupled with the use of rat strains that display small and large sex differences in opioid antinociception, may provide a sensitive tool to investigate the mechanisms underlying sex differences in opioid antinociception.
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PMID:Pharmacogenetic analysis of sex differences in opioid antinociception in rats. 1465 21

1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2. Our congenic lines, produced by transferring Dmo1 chromosomal segments from the non-diabetic Brown Norway (BN) rat into the OLETF strain, have confirmed the strong, wide-range therapeutic effects of Dmo1 on dyslipidaemia, obesity and diabetes in the fourth (BC4) and fifth (BC5) generations of congenic animals. Analysis of a relatively small number of BC5 rats (n = 71) suggested that the critical Dmo1 interval lies within a < 4.9 cM region between D1Rat461 and D1Rat459. 3. To confirm the assignment of the Dmo1 critical interval, we intercrossed BC5 animals to produce a larger study population (BC5:F1 males; n = 406). For the present study, we used bodyweight at 18 weeks of age as an index of obesity; this phenotype is representative of the closely associated dyslipidaemia and hyperglycaemia phenotypes. 4. Interval mapping assigned logarithm of odds (LOD) peaks at the D1Rat90 marker (LOD = 9.11). One LOD support interval lies within the < 1.7 cM region between D1Rat461 and D1Rat459. 5. This large intercross study confirms that Dmo1 is likely localized within the interval.
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PMID:A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats. 1475 94

The primary objective of this study was to evaluate the effect of cyclooxygenase (COX) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), in two in vivo models of VEGF-dependent corneal and choroidal angiogenesis and two in vivo models of VEGF-mediated vascular leakage. Non-selective COX inhibitors (the NSAIDs indomethacin and flunixin, p.o. or i.p.), the COX-1 selective inhibitor SC-560 (s.c. or i.p.), and the COX-2 selective inhibitor NS-398 (s.c. or i.p.) were evaluated in four experimental models. Choroidal neovascularization was induced in Brown Norway rats by argon laser photocoagulation and measured after ten days. Corneal neovascularization was induced by alkaline cautery in Sprague-Dawley rats and measured after four days. VEGF protein levels in the cornea were quantified by ELISA. VEGF-induced intradermal extravasation of Evans blue dye (EBD)-albumin was assayed in Hartley guinea pigs. Intravitreal VEGF-induced blood-retinal barrier breakdown was assayed by scanning ocular fluorophotometry in Dutch Belt rabbits. Indomethacin (1 or 3 mg kg(-1) day(-1), p.o.), SC-560 (20 mg kg(-1) day(-1), s.c.), and NS-398 (20 mg kg(-1) day(-1), s.c.) failed to inhibit laser-induced CNV. CNV was inhibited, however, by the corticosteroid dexamethasone (0.5 mg kg(-1) day(-1); p.o. or s.c.; 99% or 90% inhibition; p<0.01 or p<0.001, respectively). In contrast, cautery-induced corneal angiogenesis was inhibited partially by the NSAID indomethacin and the COX-2 selective inhibitor NS-398. Indomethacin, 3.5 or 7 mg kg(-1) day(-1), inhibited corneal neovascularization by 56% (p<0.001) or 68% (p<0.001) respectively. Similar partial inhibition of angiogenesis in the cornea model was observed with NS-398 (10 or 20 mg kg(-1) day(-1), s.c. or i.p.; 54% inhibition, p<0.001), but not with the COX-1 selective SC-560 (10 or 20 mg kg(-1) day(-1), s.c.). In the cornea, VEGF protein is dramatically upregulated 24 and 48 hr after cautery, and both indomethacin and NS-398-but not SC-560-significantly inhibited this VEGF upregulation. In experimental models of VEGF-induced vascular leakage, COX inhibitors had no effect on dermal or retinal vascular responses to VEGF. The NSAIDs indomethacin (7.5 or 20 mg kg(-1), p.o. or i.p.) and flunixin (12.5 mg kg(-1), i.p.) failed to inhibit VEGF-induced dermal extravasation of EBD-albumin in guinea pigs. In contrast, L-NAME (25 or 50 mg kg(-1), p.o.)-an anti-vasodilatory inhibitor of nitric oxide synthase-dose-dependently inhibited up to 64% (p<0.001) of this dermal vascular leakage. VEGF-mediated retinal vascular leakage was not blocked by COX inhibition. Intravitreal VEGF-induced BRB breakdown--which was completely blocked by VEGF neutralizing s-Flt-1/Fc protein (intravitreal co-administration; p<0.001)--was not inhibited by indomethacin (20 mg kg(-1) day(-1), s.c.). Although COX inhibitors were ineffective at blocking experimental CNV, both non-selective and COX-2 selective inhibitors partially blocked severe inflammatory corneal angiogenesis and its concurrent upregulation of VEGF protein. These results suggest that eicosanoids produced by inducible COX-2 are among multiple mediators that modulate VEGF expression as a stimulus in inflammation-associated angiogenesis. The lack of effect with COX inhibitors on either VEGF-mediated dermal extravasation or VEGF-mediated blood-retinal barrier breakdown indicates that COX activity is not required for vascular leakage responses to VEGF.
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PMID:Effect of COX inhibitors on VEGF-induced retinal vascular leakage and experimental corneal and choroidal neovascularization. 1532 74

Extracellular matrix (ECM) molecules such as elastin and collagen provide mechanical support to the vessel wall and are essential for vascular function. Evidence that genetic factors influence aortic ECM composition and organization was concluded from our previous studies showing that the inbred Brown Norway (BN) rat differs significantly from the outbred Long-Evans (LE) and the inbred LOU rat with respect to both thoracic aortic elastin content and internal elastic lamina (IEL) rupture in the abdominal aorta and iliac arteries. Here, we measured aortic elastin and collagen contents as well as factors that may modulate these parameters [insulin growth factor (IGF)-I, transforming growth factor (TGF)-beta(1), and matrix metalloproteinase (MMP)-2] in seven inbred rat strains, including BN and LOU. We also investigated whether IEL ruptures occur in strains other than BN. We showed that LOU, LE, BN, and Fischer 344 (F344) rats were significantly different for aortic elastin content and elastin-to-collagen ratio, whereas LE, Lewis, WAG, and Wistar-Furth (WF) were similar for these parameters. BN and F344 had the lowest values. BN was the only strain to present numerous IEL ruptures, whereas F344, LE, and WF presented a few and the other strains presented none. In addition, IGF-I and TGF-beta(1) levels in the plasma and aorta differed significantly between strains, suggesting genetic control of their production. Because inbred rat strains provide interesting models for quantitative trait locus analysis, our results concerning elastin, collagen, IEL ruptures, and cytokines may provide a basis for the search for candidate genes involved in the control of these phenotypes.
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PMID:Characteristics of the aortic elastic network and related phenotypes in seven inbred rat strains. 1547 77

We examined the alterations in vitamin A metabolism as a result of flupenthixol or cefotiam administration. The impact of these drugs on indices of vitamin A status was evaluated in Brown Norway and Long-Evans rats. Intramuscular drug administration for 28 d resulted in a decline in systemic retinol. Changes in circulating retinol with time for chronic dosing showed drug treatment (P<0.001) and time (P<0.03) to be significant factors, but rat strain (P=0.33) was not a significant factor. Flupenthixol was the most active retinol-lowering compound (P<0.005). At the end of the 28 d period, hepatic retinyl ester hydrolase activity was greater in drug-treated rats than in controls (P<0.05). With regard to effects on liver reserves: (1) flupenthixol treatment resulted in vitamin A depletion (P<0.05); (2) cefotiam treatment stimulated vitamin A accumulation; (3) distinctive patterns of retinol and its esters were seen in response to treatment. It is reasonable to assume that the drugs interfere with vitamin A in at least two ways: (1) lowering of plasma retinol, an early event in the interaction, may be caused by inhibition of hepatic holo-retinol-binding protein secretion or stimulation of clearance, or both; (2) when plasma retinol levels are persistently low, and as the hepatic deposits of the xenobiotics build up, there are changes in the vitamin A pool size and composition of the liver. Candidate enzymes are retinyl ester hydrolase and cytochrome P450. The relationship between these two events will be studied in further detail.
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PMID:Flupenthixol and cefotiam: effects on vitamin A metabolism in rats. 1552 28

1. We have confirmed the Diabetes Mellitus OLETF type I (Dmo1) effect on hyperphagia, dyslipidaemia and obesity in the Otsuka Long-Evans Tokushima Fatty (OLETF) strain. The critical interval was narrowed down to 570 kb between D1Got258 to p162CA1 by segregation analyses using congenic lines. 2. Within the critical 570 kb region of the Dmo1 locus, we identified the G-protein-coupled receptor gene GPR10 as the causative gene mutated in the OLETF strain. The ATG translation initiation codon of GPR10 is changed into ATA in this strain and, so, is unavailable for the initiation of translation. 3. The GPR10 protein has a cognate ligand, namely prolactin-releasing peptide (PrRP). Centrally administered PrRP suppressed the food intake of congenic rats that have a Brown Norway derived Dmo1 region (i.e. with wild-type GPR10), but did not suppress that of the OLETF strain, indicating that GPR10 is without function and could explain hyperphagia in the OLETF strain. 4. Moreover, when restricted in food volume to the same level consumed by the congenic strain, OLETF rats showed few differences in the parameters of dyslipidaemia and obesity compared with congenic strains. 5. Taken together, these results demonstrate that the mutated GPR10 receptor is responsible for the hyperphagia leading to obesity and dyslipidaemia in the obese diabetic strain rat.
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PMID:Mutated G-protein-coupled receptor GPR10 is responsible for the hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat. 1585 42

The total synthesis of the proposed structure of feigrisolide A is reported. Ethyl (S)-3-hydroxybutyrate was the chiral starting material. A Brown asymmetric allylation and an Evans aldol reaction were key steps of the synthesis. The NMR data of the synthetic product are different from those of the natural product. The published structure of feigrisolide A is therefore erroneous. A subsequent comparison of spectral data strongly suggests that feigrisolides A and B are identical with (-)-nonactic acid and (+)-homononactic acid, respectively.
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PMID:Stereoselective synthesis of the published structure of feigrisolide A. Structural revision of feigrisolides A and B. 1683 61

Stereoselective total syntheses of two novel conformationally restrained epothilone analogues are described. Evans asymmetric alkylation, Brown allylation, and a diastereoselective aldol reaction served as the key steps in the stereoselective synthesis of one of the two key fragments of the convergent synthetic approach. Enzyme resolution was employed to obtain the second fragment as a single enantiomer. The molecules were assembled by esterification, followed by ring-closing metathesis. In preliminary cytotoxicity studies, one of the analogues showed strong and selective growth inhibitory activity against two leukemia cell lines over solid human tumor cell lines. The precise biological mechanism of action and high degree of selectivity of this analogue remain to be examined.
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PMID:Total synthesis and selective activity of a new class of conformationally restrained epothilones. 1795 8

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic obesity in which the animals retain the desire to run voluntarily. Running wheels were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary (SED) OLETF rats that were not given access to running wheels served as age-matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to cessation of daily running in Fischer 344 x Brown Norway rats, epididymal fat did not increase during the first 173 h of running cessation in the OLETF runners. Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than SED rats. Oil red O staining for intramyocellular lipid accumulation was not statistically different among groups. However, lipid peroxidation levels, as determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173 rats. mRNA levels of glutathione S-transferase-alpha type 4, an enzyme involved in cellular defense against electrophilic compounds such as 4-HNE, were higher in epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and relative transcript levels for peroxisome proliferator-activated receptor-delta and peroxisome proliferator-activated receptor-gamma coactivator type 1 were surprisingly not different between runners and SED rats. In summary, voluntary running was associated with lower levels of lipid peroxidation in skeletal muscle without significant changes in intramyocellular lipids or mitochondrial markers in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of extreme overeating, daily physical activity promotes improved health of skeletal muscle.
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PMID:Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat. 1807 66


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