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)

According to its immunopharmacological profile, 15-deoxyspergualin (15-DOS) has been investigated as to its disease-modifying activity on HgCl2-induced glomerulonephritis (GN) and on tubulointerstitial nephritis (TIN) in Brown-Norway rats. Both models are induced autoimmune disorders in which afflicted animals display high levels of serum autoantibodies directed against the glomerular or tubular basement membrane (GBM or TBM), respectively. The diseases are manifested by high serum creatinine and urea levels with severe proteinuria. In the model of HgCl2-GN, administration of 15-DOS clearly led to a reduction of proteinuria and decreased the amount of rat IgG attached to the GBM. Furthermore, a therapeutic effect could be demonstrated when 15-DOS was given after the appearance of clinical symptoms. Not only urine-protein values but also anti-laminin antibodies returned to normal levels. Also in the experimental TIN-model, 15-DOS, either given during the induction phase, or even late in the onset of the disease, strongly prevented the proteinuria of this autoimmune disease and inhibited the formation of autoantibodies to TBN.
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PMID:Immunosuppressive therapy of organ-specific nephritic autoimmune diseases with 15-deoxyspergualin. 827 49

In order to further define the enzymatic properties of yeast DNA polymerase delta, the Saccharomyces cerevisiae POL3 gene, whose expression is highly toxic to bacteria in most cloning vectors, was cloned into a new T7 expression vector (W. C. Brown and J. L. Campbell, submitted for publication) which allowed efficient overexpression in bacteria. Fifteen mg of polymerase were obtained from 3 g of cells. Since the protein is produced in insoluble form, to obtain active polymerase, inclusion bodies were solubilized with urea. DNA polymerase delta (124 kDa) was purified in the presence of urea and then renatured by dialysis against buffers containing decreasing concentrations of urea. Optimal protein concentration for refolding was 5 micrograms/ml. By several criteria the enzyme obtained is comparable with that from yeast: specific activity, electrophoretic mobility, template preference, sensitivity to inhibitors, and processivity. The electrophoretic mobility suggests that, unlike DNA polymerase alpha, polymerase delta is not posttranslationally modified in yeast. Polyclonal antibody was raised against the full-length DNA polymerase delta from bacteria and shown to cross-react with the protein purified from yeast on protein blots. The renatured protein also exhibits an exonucleolytic activity. Further examination of this nuclease determined it to be a 3' to 5' exonuclease with the characteristics of a proofreading activity. The presence of this nuclease in the highly purified bacterial polymerase provides biochemical confirmation of earlier genetic evidence (Simon, M., Giot, L., and Faye, G. (1991) EMBO J. 10, 2165-2170) that suggested that DNA polymerase delta's core catalytic subunit contains an intrinsic 3' to 5' exonuclease.
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PMID:Purification and characterization of the Saccharomyces cerevisiae DNA polymerase delta overproduced in Escherichia coli. 838 Apr 19

A wealth of experimental evidence argues that infectious prions are composed largely, if not entirely, of the scrapie isoform of the prion protein. We attempted to restore scrapie infectivity after exposure to protein denaturants including urea, chaotropic salts, and SDS. None of the procedures restored infectivity. Dialysis to remove slowly chaotropic ions and urea failed to restore scrapie infectivity. Attempts to create monomers of the scrapie isoform of the prion protein under nondenaturing conditions using a wide variety of detergents have been unsuccessful, to date, except for one report claiming that scrapie infectivity could be recovered from 12% polyacrylamide gels after SDS/PAGE [Brown, P., Liberski, P. P., Wolff, A. & Gajdusek, D. C. (1990) Proc. Natl. Acad. Sci. USA 87, 7240-7244]. We found that < 0.001% of the infectious prion titer could be recovered from the region of a polyacrylamide gel where the denatured proteinase K-resistant core of the scrapie isoform of the prion protein and other 30-kDa proteins migrate. We conclude that under the denaturing conditions used for SDS/PAGE, the scrapie isoform of the prion protein is denatured and little or no renaturation occurs upon injection of fractions eluted from gels into animals for bioassays.
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PMID:Attempts to restore scrapie prion infectivity after exposure to protein denaturants. 846 92

To characterize some of the physiological features of Japanese beef breeds, plasma concentrations of insulin and metabolites and carcass composition were measured in five Japanese Black, five Japanese Brown, and four Holstein steers (6.2 mo; 164 kg). The steers were raised under typical feeding conditions in Japan until they were slaughtered at 600 to 700 kg BW. Blood samples were collected at 8 mo of age (average BW, 194 kg) and at 300, 400, 500, and 600 kg BW. Plasma insulin concentrations increased with BW in all three breeds and were greater (P < .05) in Japanese Blacks than in the Japanese Browns or Holsteins at 400 and 600 kg BW. The Japanese Blacks exhibited lower (P < .05) plasma glucose levels at 300, 400, and 600 kg BW compared with Holsteins. Regardless of the breed, plasma urea nitrogen (PUN) concentrations increased with BW. The two Japanese breeds had greater (P < .05) PUN levels than Holsteins at 300 and 600 kg BW. Total cholesterol and phospholipid concentrations tended to decrease above 300 kg BW in the Holsteins; however, the concentrations of both metabolites were elevated in the steers of Japanese breeds at 500 and 600 kg BW (P < .05). Breed did not affect the plasma concentrations of albumin, triglycerides, and NEFA. The Japanese breeds had higher (P < .01) dressing percentage, greater (P < .05) carcass fat proportion, and a lower proportion of carcass bone (P < .01) than the Holsteins. These results indicate that there are breed differences in plasma levels of insulin and certain metabolites and carcass composition among Japanese breeds and Holstein.
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PMID:Plasma insulin, metabolite concentrations, and carcass characteristics of Japanese Black, Japanese Brown, and Holstein steers. 942 3

Using Brown Norway (BN) rats, we isolated and characterized the tubular basement membrane (TBM) antigens that are immunologically common to humans. The renal basement membrane (RBM) of BN rat, as an antigen source, was solubilized with 8 M urea instead of collagenase followed by extraction with 0.5 M NaCl. On frozen section-immunohistochemistry, the autoantibody obtained from BN rats, which had been immunized with human RBM and showed tubulointerstitial nephritis, bound to the TBM, the basement membrane of the Bowman's capsule, and the brush border of the proximal tubules, but not to the GBM of the normal BN rat kidney. Nephritogenic antigens were isolated by immunoaffinity chromatography using Sepharose-bound purified autoantibody. By Western blot analysis of the eluate, bands with molecular weight of 200 kDa and 180 kDa were positively reacted to anti-FX1A (brush border antigen) antibody and were apparently different from the major bands with molecular weight of 145 kDa and 130 kDa. The bands with molecular weight of 145 and 130 kDa showed major cross reactivity with antibodies to fibronectin and laminin. In contrast with these high molecular weight (HMW) bands, the major 60 kDa band with three minor bands showed no reactivity with any type of antibody tested. These results indicated that the non-enzymatic solubilization of RBM is one of the possible procedures for isolating the HMW form of antigens. These antigens may be epitopically modified pre-existing constitutions of the basement membrane and may play a role in the induction of tubulointerstitial nephritis.
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PMID:Isolation and characterization of tubular basement membrane antigen common to humans and rats. 985 23

The effects on N use and N volatilization from slurry were investigated in 24 early-lactation Brown Swiss cows (32 kg/d milk) fed four diets with 128, 124, 147 and 175 g/kg DM of crude protein (CP). All diets were supplemented with 0.75 g/kg of rumen-protected Met except for one of the low-protein rations (128 g/kg of CP). The unsupplemented low-protein ration was calculated to be deficient in Met by approximately 20%. No significant treatment effects on performance, water intake and excretion, and slurry quantities were observed. Differences in N intake were closely reflected in the daily excretions of total and urea N via urine, and in urine N as a proportion of total excretory N. These values were higher for the unsupplemented low-protein ration than for the Met-supplemented low-protein ration. The treatment effects on fecal N excretion were generally smaller, and milk N excretion and N balance were not affected. Feed N utilization for milk N excretion increased with decreasing CP content from 27% for the high-protein group to about 35% for the two low-protein groups. Comparing the Met supplemented rations only, ammonia N emission from fresh slurry (excreta:water = 1:0.5) decreased from 231 to 160 and 55 microg/s per square meter of surface with 175, 147 and 124 g/kg of CP, respectively, and the corresponding total N losses during 7 wk of slurry storage declined from 89 to 57 and 25 g/d per cow. Regression analysis demonstrated the basic suitability of milk urea N excretion to estimate urine N excretion and, consequently, potential N emissions.
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PMID:Quantitative effects of feed protein reduction and methionine on nitrogen use by cows and nitrogen emission from slurry. 1113 66

Renal cortical brush-border (BBM), basolateral membrane (BLM), and medullary plasma membrane (mPM) preparations were analyzed to assess the effects of life-long food restriction in aged rats on membrane lipid content. Young male Fischer 344 x Brown-Norway F1 rats consumed food ad libitum (young AL) or were food-restricted (FR, 60% of AL consumption) for either 6 weeks (young FR) or until the age of 30 months old (old FR). Senescent FR rats had 50 per cent decreases in fractional excretion of Na and K (p < 0.001) as compared with the young AL rats. Long-term FR reduced phosphate and titratable acid excretion by 80 per cent (p < 0.001). These values were not significantly different from those observed in young rats during 6 weeks of FR. Food restriction decreased renal Na, K-ATPase activity by 50 per cent (p < 0.001) in both old and young FR animals. Reduction of food intake, in old and young rats, decreased all BBM phospholipid concentrations (phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin) by 50 per cent than in the AL rats (p < 0.001). In BLM, chronic FR resulted only in lower phosphatidylcholine concentration (by 21%, p < 0.05) while phosphatidylethanolamine was increased approximately 80 per cent (p < 0.001). Total phospholipid content in mPM was progressively decreased by 23 per cent (p < 0.05) in the young FR group to be 55 per cent (p < 0.001) in the old FR rats. Cholesterol content was reduced in BBM and mPM by 38 per cent and 25 per cent (p < 0.05), respectively, during long-term FR. Both total phospholipid and cholesterol contents detected in mPM of the old FR rats were significantly lower than those obtained from the young FR animals (by 42%, p < 0.001 and 12%, p < 0.05, respectively). Plasma glucose, blood urea nitrogen, and body weight maintained at significantly lower levels during chronic FR. That life-long FR could prevent renal membrane lipid deposition and could lower renal work may explain the mechanisms that FR can delay the onset and diminish the severity of age-associated renal diseases.
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PMID:Life-long food restriction prevents renal membrane lipid deposition and lowers renal work in rats. 1152 48

This study was designed to test the effects of feed withdrawal and darkening on the performance, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and some blood serum metabolite and mineral concentrations of laying hens reared at high ambient temperatures ranging from 25 to 35 degrees C. Ninety, 16-week-old hens (Ross Brown) were divided into 3 groups, 30 hens each. The first group was used as control. Hens in the second group (feed withdrawal) were subjected to feed removal from 14:00 to 18:00, and hens in the third group (darkening) were subjected to light restriction from 14:00 to 18:00 using black curtains. Liveweight, feed intake, and egg production were higher (P < 0.01) in the feed withdrawal and darkening groups, particularly in the darkening group, than in the control. Water intake was higher in the control group compared with the feed withdrawal and darkening groups (P < 0.01). T3, T4, and TSH concentrations in the serum were higher (P < 0.01), whereas ACTH serum concentration was lower (P < 0.01) in the feed withdrawal and darkening groups compared with the control. The haematocrit was higher in the feed withdrawal and darkening groups compared with the control (P < 0.01). Darkening and feed withdrawal treatments increased serum glucose, urea-N, uric acid, albumin, triglyceride, cholesterol, Ca, P, Na, and K concentrations, also the activities of amylase and alkaline phosphatase, but did not influence the activities of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). The present study found that feed withdrawal and darkening, particularly darkening, at high temperatures during the summer months offer a good management practice to reduce heat stress related depression in feed intake and egg production in laying hens.
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PMID:A simple way to reduce heat stress in laying hens as judged by egg laying, body weight gain and biochemical parameters. 1194 21

The genetic analysis of rodent disease models provides a powerful tool to investigate how modifier loci cause variation in the phenotypic expression of a disease. In order to test the existence of modifier loci influencing polycystic kidney disease (PKD) phenotypes, we derived a backcross between PKD susceptible Han:SPRD(cy/+) and control Brown Norway (BN) rats, and performed a whole-genome scan in 182 PKD affected hybrids showing different grades of disease severity. The genetic dissection of PKD in the cross allowed us to detect a modifier locus, Modpkdr1, on rat chromosome 8 that controls PKD severity, kidney mass and plasma urea concentration. Results from database searches and computational analyses demonstrated that the Modpkdr1 locus shows strong evidence of synteny conservation with human and mouse chromosomal regions controlling kidney diseases, including disease progression of Alport syndrome. Comparative genome mapping also provided an inventory of potential candidate genes for modifier(s) of PKD. Analyses of the coding regions for four strong candidates (Ctsh, Bcl2a1, Trpc1 and Slc21a2) in (cy/+), BN and Lewis rat strains did not reveal sequence variants that could be associated with PKD. The characterization of Modpkdr1 may provide new insights into modulating mechanisms involved in the pathogenesis of PKD that could delay disease progression in humans. It may also have strong implications in the identification of pathophysiological factors common to different renal disorders.
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PMID:Characterization of a major modifier locus for polycystic kidney disease (Modpkdr1) in the Han:SPRD(cy/+) rat in a region conserved with a mouse modifier locus for Alport syndrome. 1218 69

Hatch, M. H. (Brown University, Providence, R.I.) and C. A. Stuart. Urease activity of Proteus species in filtered compared with autoclaved urea media. J. Bacteriol. 83:1119-1123. 1962.-Urease activity of a number of strains of four Proteus species was compared in a filtered medium and an autoclaved medium. Various amounts of saline suspensions of the organisms were used as inocula for the two media. In some experiments Seitz-filtered yeast extract was added to autoclaved basal urea medium. All tests were incubated at 35 C and read 8, 12, 24, and 48 hr after inoculation. The filtered medium appeared superior to the autoclaved medium, particularly when small inocula were employed. Under these conditions, many tests with all four species were negative in the autoclaved medium at 48 hr, in contrast to 100% positive reactions in the filtered medium with all species except P. morganii. The experiments in which Seitz-filtered yeast extract was added to autoclaved basal urea medium suggested that both destruction of growth-promoting substances in the yeast extract and production of conditions inhibitory for growth during autoclaving might be involved in the differences observed between the two media.
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PMID:Urease activity of Proteus species in filtered compared with autoclaved urea media. 1390 16


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