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)

Cyclosporine metabolites (CM) were compared with cyclosporine for their in vitro and in vivo immunosuppressive, nephrotoxic, and hepatotoxic effects using (A) in vitro mixed lymphocyte induction of monocyte/macrophage procoagulant activity (PCA), an accurate marker of allograft rejection; (B) in vitro toxic effects on renal cells in culture; and (C) a unidirectional rejection model of rat small intestinal transplantation (SIT). CM were composed of OL1, OL17, OL18, and two additional peaks C and H, (peak C: mass = 1235, 15.3% of total CM, peak H: mass = 1205, 6.3% of total CM). In vitro, CM fully suppressed the one-way mixed lymphocyte culture-induced PCA from 52.5 +/- 8.2 mU/10(6) PBM to the basal level 22.3 +/- 6.6 mU/10(6) PBM (P less than 0.01), which was comparable to CsA (21.3 +/- 5.5 mU/10(6) PBM). Lewis rats that had received Lewis-Brown Norway F1 hybrid intestinal allografts when treated with CM, demonstrated near-normal histology with minimal signs of rejection as compared with the fulminant clinical and histological rejection observed in the control (untreated and Cremaphor/NaCl treated) animals. PCA was markedly elevated in the control animals, 278 +/- 172 (untreated) and 160 +/- 98 mU/10(6) PBM (Cremaphor/normal saline treated), whereas CsA-treated allogeneic transplants expressed only basal levels of PCA (14.0 +/- 4 mU/10(6) PBM) (P less than 0.01), associated with normal histology. CM-treated animals expressed PCA levels of 27.0 +/- 10 mU/10(6) PBM, which was significantly different from both control and CsA-treated animals (P less than 0.01). In contrast to CsA-treated animals, CM-treated allogeneic transplants demonstrated no apparent renal or hepatic toxicity, as measured by blood urea nitrogen (25.3 +/- 9.5 vs. 10.0 +/- 5.3 mg/dl), alkaline phosphatase (160.7 +/- 29.3 vs. 100.3 +/- 19.5 U/L), and aspartate transaminase (96.7 +/- 23.7 vs. 61.7 +/- 11.7 U/L) (P less than 0.01). Similarly, in contrast to CsA, CM had minimal or no toxicity in renal epithelial and mesangial cells in culture, as measured by minimal or no inhibition of DNA, RNA, and protein synthesis. These results suggest that CM have potent immunosuppressive properties with no apparent nephrotoxicity and hepatotoxicity in vitro and in vivo.
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PMID:The effects of cyclosporine and cyclosporine metabolites in experimental small intestinal transplantation. 236 Feb 47

A study was conducted to investigate nephritogenic tubular basement membrane antigens common to human and rat kidneys. Brown Norway (BN) rats were immunized with human renal basement membrane in complete Freund's adjuvant simultaneously with Bordetella pertussis vaccine. The immunized rats developed polyuria and increased levels of serum creatinine one week after the second immunization. Renal histology at this time revealed marked, acute tubulointerstitial nephritis with linear deposition of IgG and C3 along the tubular basement membrane and Bowman's capsule, but not along the glomerular basement membrane. Rats with this tubulointerstitial nephritis rapidly developed antibodies against renal antigens from normal BN rats such as tubular basement membrane and proximal tubule brush border, however antibodies to glomerular basement membrane appeared later. Western blotting using the same rat sera detected a 145-kDa antigen from 8 M urea-solubilized human renal basement membrane and 120-kDa, 135-kDa and 145-kDa antigens from 8 M urea-solubilized BN rat renal basement membrane. This suggests that renal basement membranes of human and rat origin have common antigens involved in the pathogenesis of tubulointerstitial nephritis.
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PMID:Induction of interstitial nephritis in rats by basement membrane of human origin. 268 56

Inhibition of red cell water transport by the sulfhydryl reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) has been reported by Naccache and Sha'afi ((1974) J. Cell Physiol. 84, 449-456) but other investigators have not been able to confirm this observation. Brown et al. ((1975) Nature 254, 523-525) have shown that, under appropriate conditions, DTNB binds only to band 3 in the red cell membrane. We have made a detailed investigation of DTNB binding to red cell membranes that had been treated with the sulfhydryl reagent N-ethylmaleimide (NEM), and our results confirm the observation of Brown et al. Since this covalent binding site does not react with either N-ethylmaleimide or the sulfhydryl reagent pCMBS (p-chloromercuribenzenesulfonate), its presence has not previously been reported. This covalent site does not inhibit water transport nor does it affect any transport process we have studied. There is an additional low-affinity (non-covalent) DTNB site that Reithmeier ((1983) Biochim. Biophys. Acta 732, 122-125) has shown to inhibit anion transport. In N-ethylmaleimide-treated red cells, we have found that this binding site inhibits water transport and that the inhibition can be partially reversed by the specific stilbene anion exchange transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS), thus linking water transport to anion exchange. DTNB binding to this low-affinity site also inhibits ethylene glycol and methyl urea transport with the same KI as that for water inhibition, thus linking these transport systems to that for water and anions. These results support the view that band 3 is a principal constituent of the red cell aqueous channel, through which urea and ethylene glycol also enter the cell.
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PMID:Binding of DTNB to band 3 in the human red cell membrane. 299 87

Pancreaticoduodenal (PD) allografts (Brown Norway-alloxan-diabetic rats, n = 190) were treated with cyclosporin A (Cy-A) 10 mg/kg/daily and compared with nondiabetics with Cy-A treatment (n = 55), diabetics (n = 50), and diabetics with Cy-A treatment (n = 45). Body weight, blood sugar, blood insulin, blood urea nitrogen (BUN), and creatinine were monitored periodically; there were marked elevations of BUN and creatinine levels, indicating probably nephrotoxicity of Cy-A at this dosage. Some islet cell atrophy in the PD allografts was noted at the conclusion of the study. With respect to the immunosuppressive effect of Cy-A in alloxan diabetic rats, Brown Norway PD transplants into Lewis rats were successful and free of rejection for as long as 15 months post-transplantation. The body weight of these PD transplanted rats, however, never approached values representative of the nondiabetic rats. In our experience, the PD allograft model is acceptable in the clinical situation, particularly in children if the microsurgical technique is mastered and if the Cy-A regimen is used in combination with other immunosuppressant(s).
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PMID:Long-term studies of pancreas allotransplantation in experimental diabetes mellitus. 305 15

Nephrotoxicity has limited the effectiveness of cyclosporine in transplantation therapy and has precipitated the need to develop a new immunosuppressive agent that lacks this nephrotoxicity or has a higher therapeutic index. Prior studies have suggested that cyclosporin G may be equally effective immunosuppressively, but less nephrotoxic than cyclosporine. To compare the immunosuppressive effects of the two agents, graft survival was analyzed in Lewis-Brown Norway rats, which received heterotopic ACl heart allografts and were treated orally with cyclosporin G or cyclosporine at 5 and 10 mg/kg/day. To compare nephrotoxicity the group of rats that had transplantations and an additional group of surgically intact Lewis-Brown Norway rats, treated orally with cyclosporin G or cyclosporine at dosages ranging from 10 to 50 mg/kg/day and for durations ranging from 50 to 180 days, were analyzed in terms of kidney morphology (fibrosis, glomerular damage, interstitial infiltrate, and tubular dilation) and kidney function (blood urea nitrogen and serum creatinine levels) in this model cyclosporin G was significantly less effective than cyclosporine in prolonging graft survival at 5 mg/kg/day but equally effective at 10 mg/kg/day. In addition, cyclosporin G was substantially less nephrotoxic both morphologically and functionally at low (10 mg/kg/day) and high (50 mg/kg/day) dosages. Further studies are indicated to determine the therapeutic index of cyclosporin G and to evaluate its use in combination with other immunosuppressive agents.
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PMID:Analysis of the immunosuppressive and nephrotoxic effects of cyclosporin G. 328 81

Two Brown Swiss and two Holstein steers, average weight of 226 kg, were fasted 8 d. Two days before the fast, jugular vein catheters were installed. Blood samples were collected every 15 min from 0800 to 1400 h on d 0, 2, 5 and 8 of fasting. Plasma from each sample was analyzed for concentrations of growth hormone, and from selected samples for insulin, glucagon, glucose, beta-hydroxybutyrate, free fatty acids, urea N and glycerol. Both growth hormone and insulin concentrations decreased by d 2 of the fast and remained at that concentration. Glucagon, however, remained constant. From d 0 to 2, concentrations of beta-hydroxybutyrate, free fatty acids and glycerol increased but then changed little for d 5 and 8. From d 0 to 2, glucose decreased and urea N increased. In contrast to the other metabolites, glucose and urea N concentrations stabilized between 3 and 5 d of fasting. The ratio of growth hormone to insulin decreased threefold and the ratio of glucagon to insulin decreased fivefold from d 0 to 2; both ratios remained constant during the rest of the fast. The data indicate that fasting cattle adapt by decreasing concentrations in plasma of growth hormone and insulin but not glucagon. These endocrine changes, therefore, seem responsible for greater rates of free fatty acid mobilization and glucose sparing during an energy deficit.
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PMID:Changes in hormone and metabolite concentrations in plasma of steers during a prolonged fast. 390 37

Rat renal allograft survival was enhanced by active immunization with donor strain RT1.B (Ia) antigens. Lewis (LEW) rats (16) were immunized with Brown Norway (BN) lymphocyte extracts containing RT1.B, but not RT1.A antigens, prior to receiving (LEW X BN)F1 renal allografts. Group 1 (8 rats) was immunized with lymphocyte membrane fragments group 2(8 rats) was primed with lymphocyte supernatant extract. Longterm survivors (greater than 60 days; 12 animals) had a mean blood urea nitrogen of 75 +/- 31 mg% and serum creatinine of 2.0 +/- 0.8 mg% at one month. Death occurred in 90% of control allograft recipients within 10 days. Anti-BN RT1.B but not RT1.A antibodies were detected in sera from actively enhanced rats following immunization and at day 7 posttransplantation. We conclude that preimmunization with cell extracts containing donor RT1.B antigens has a protective effect on the allograft, and that the phenomenon of active immunologic enhancement can be produced without immunization to RT1.A antigens.
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PMID:Long-term renal allograft survival in rats preimmunized with donor strain RT1.B antigens. 622 Apr 93

In 915 records of cows of the breeds German Simmental and German Brown the relationships between fertility parameters and milk urea as well as acetone content were analysed with linear models regarding systematic effects of herd, month, lactation number and breed-Brown-Swiss blood proportion. Milk urea concentration showed significant curvilinear associations to following fertility parameters: days open, days between first and last breeding as well as number of inseminations per service period, conception rate at first insemination after calving and lactational incidence of endometritis. The reproductive traits showed an optimum at a milk urea concentration between 15 and 25 mg/dl. The regression of the fertility parameters on acetone content in milk was nearly linearly decreasing and with the exception of days to first breeding after calving significantly different from zero. An increase of milk acetone by 0.01 mmol/l lead to a prolongation of days from first to last breeding in the service period by more than one day, and to a decrease of conception rate at first insemination by nearly one percent. An approach was developed which is suitable to quantify the influence of milk constituents on fertility traits. The model developed can consider nonlinear relationships, more than one metabolic parameter and systematic effects. Thresholds for milk parameters are no longer needed as the negative effects of the metabolic influences caused by nutritional factors are quantified in terms of fertility parameters.
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PMID:[Urea and acetone content in milk as indicators for nutritionally caused fertility disorders of dairy cows]. 820 67

Fibronectin heterogeneity is, in part, the result of post-translational modifications. In these experiments, cartilage fibronectins were purified by anion exchange chromatography, followed by gelatin affinity chromatography or immunoprecipitation, and, finally, sodium dodecyl sulfate--polyacrylamide gel electrophoresis (NaDodSO4 PAGE). A substantial, although variable, portion of the fibronectins from canine and equine cartilages of all ages required salt concentrations from 0.2 to 1.0 M for elution from DEAE-cellulose. This was in contrast to plasma fibronectin which eluted with 0.1 M NaCl, but these results were consistent with observations made on human cartilage by Brown and Jones (1990 J. Rheumatol. 17, 65-72). When cartilage explants were incubated with Na2 35SO4=, the cartilage fibronectins were sulfated and the fibronectins which eluted with high salt contained from 5- to 50-fold more radiosulfate than the fibronectins which eluted with 0.1 M NaCl. A fraction of the 35SO4= which copurified with the cartilage fibronectin and comigrated with it in NaDodSO4-PAGE could be removed by digestion with chondroitinase ABC. This suggested that a percentage of cartilage fibronectins are covalently linked to a chondroitin sulfate or dermatan sulfate chain and thus might also appropriately be called proteoglycans. Alternatively, there is a proteoglycan which binds so tightly to fibronectin that separation is not achieved even in the presence of urea, sodium dodecyl sulfate, and mercaptoethanol.
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PMID:Evidence for a glycosaminoglycan chain on a portion of articular cartilage fibronectins. 821 30

In total, records of 915 cows of the breed German Simmental and German Brown were available to investigate the influences of herd, month, lactation number, stage of lactation, milk production, diseases at calving, breed-Brown-Swiss blood proportion and additive-genetic effect of the cow on milk urea and acetone content. Significant differences between herds, months and lactation numbers could be shown for milk urea and acetone content. Acetone content decreased significantly in the first 100 days post partum by 0.06 mmol/l. Milk fat content was significantly correlated with milk urea and acetone. The heritabilities for milk urea were estimated in German Simmental cows as h2 = 0.06 +/- 0.04 and in German Brown cows as h2 = 0.25 +/- 0.11. Using milk samples up to 50 days post partum, heritability estimates were between h2 = 0.10 +/- 0.09 and h2 = 0.17 +/- 0.12 in German Simmental cows.
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PMID:[Analysis of environmental and genetic influences on the urea and acetone content in milk from the breeds German spotted cattle and German brown cattle]. 826 8


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