Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Immunosuppressive therapy of organ-specific nephritic autoimmune diseases with 15-deoxyspergualin. 827 49

Serum and urine were taken from healthy dairy cattle from 22 different farms. 214 animals belonged to the Swiss Brown breed and 210 were crossbreds of Simmental-Red Holstein. The animals were given at least 70 g of sodium chloride with their daily feed ration. On 6 farms sodium chloride was offered ad libitum in form of licks, which was presumed to be sufficient for covering their needs. Concentrations of sodium (UR Na), potassium (UR K) and creatinine were analyzed from serum and urine and fractional excretion of Na and K was calculated. Concentrations of sodium and potassium in urine from all cows (mean +/- sd) was 60.9 +/- 44.7 mmol/l and 370.7 +/- 66.9 mmol/l respectively. The FE values were 0.954 +/- 0.939% for sodium and 173.1 +/- 54% for potassium. In 5.5% of the animals values for UR Na < 10 mmol/l were found. There were no significant differences, however, were found in sodium and potassium excretion among farms. Urine samples of at least 10 animals should be analyzed in order to have a reliable estimation of the supply with sodium chloride within a herd. Our results do not support the hypothesis that low sodium excretion would be a predisposing factor for Bovine Dilative Cardiomyopathy in Simmental-Red Holstein cattle.
 ...
PMID:[Investigations on renal excretion of sodium in dairy cattle]. 1002 54

Log-linear models have been shown to be useful for smoothing contingency tables when categorical outcomes are subject to nonignorable nonresponse. A log-linear model can be fit to an augmented data table that includes an indicator variable designating whether subjects are respondents or nonrespondents. Maximum likelihood estimates calculated from the augmented data table are known to suffer from instability due to boundary solutions. Park and Brown (1994, Journal of the American Statistical Association 89, 44-52) and Park (1998, Biometrics 54, 1579-1590) developed empirical Bayes models that tend to smooth estimates away from the boundary. In those approaches, estimates for nonrespondents were calculated using an EM algorithm by maximizing a posterior distribution. As an extension of their earlier work, we develop a Bayesian hierarchical model that incorporates a log-linear model in the prior specification. In addition, due to uncertainty in the variable selection process associated with just one log-linear model, we simultaneously consider a finite number of models using a stochastic search variable selection (SSVS) procedure due to George and McCulloch (1997, Statistica Sinica 7, 339-373). The integration of the SSVS procedure into a Markov chain Monte Carlo (MCMC) sampler is straightforward, and leads to estimates of cell frequencies for the nonrespondents that are averages resulting from several log-linear models. The methods are demonstrated with a data example involving serum creatinine levels of patients who survived renal transplants. A simulation study is conducted to investigate properties of the model.
 ...
PMID:A Bayesian hierarchical model for categorical data with nonignorable nonresponse. 1496 67

Renal epithelial proliferation has previously been found to be a common condition in a colony of Lewis x Brown Norway (BN) F2 hybrid rats. The aim of this study was to investigate the prevalence and clinical consequences of this condition in pure inbred BN and Lewis rats. Renal epithelial proliferation was found in 29 of 49 BN rats (59%) examined and in four of 50 Lewis rats (8%) examined. Serum creatinine and serum corticosterone was not influenced by the condition. Haematuria was more common in BN rats with (74%) than without renal papillary proliferation (35%, P < 0.05), but it may not be used to diagnose renal epithelial proliferation, as we found rats having renal epithelial proliferation without showing haematuria and rats showing haematuria without having renal epithelial proliferation. Haematuria was also common in Lewis rats (16-56% dependent of age and gender), in which renal epithelial proliferation were found in only 8%. Fluctuating asymmetry, which was used as a measure of developmental instability, was found to be increased in rats with renal epithelial proliferation (P < 0.05). Haematuria was also found to be related to the degree of fluctuating asymmetry (P < 0.01). Although the prevalence of renal epithelial proliferation is clearly higher in BN rats than in Lewis rats (P < 0.01), and although in previous reports the condition was found in F2 BN x Lewis hybrids and not in F1 BN x Lewis hybrids it cannot clearly be defined as having been caused by a single Mendelian gene, as we found it in both inbred strains. Futhermore, we found that morphologically the proliferations could be placed on the papillary as well as the medullary wall of the renal pelvis, while previously it has only been described on the papillary wall.
 ...
PMID:Renal epithelial proliferation and its clinical expression in Brown Norway (BN) rats. 1497 93

We studied the effects of mycophenolate mofetil, a specific inhibitor of inosine monophosphate dehydrogenase, on the mercuric chloride induced autoimmune glomerulonephritis in Brown Norway rats and also on the renal contents of adrenomedullin. In the rats with autoimmune glomerulonephritis, plasma and renal tissue adrenomedullin levels were increased significantly. Coadministration of mycophenolate mofetil resulted in prevention of autoimmune glomerulonephritis and also in maintaining of plasma and renal tissue adrenomedullin levels at control levels. Adrenomedullin mRNA expressions in the renal cortex were also higher in the rats with autoimmune glomerulonephritis. Significant positive correlations were found between renal cortical adrenomedullin levels and urinary Na+ and N-acetyl-beta-D-glucosaminidase excretion. A significant negative correlation between renal cortical adrenomedullin levels and creatinine clearance was also found. These results suggest that mycophenolate mofetil suppresses the renal damage in rats with autoimmune glomerulonephritis and renal adrenomedullin may participate in the pathophysiology of autoimmune glomerulonephritis.
 ...
PMID:Mycophenolate mofetil prevents autoimmune glomerulonephritis and alterations of intrarenal adrenomedullin in rats. 1506 64

Linkage analysis studies previously identified genetic loci associated with proteinuria and hypertension on chromosome 1 of fawn-hooded hypertensive (FHH) rats. The present studies were performed on conscious male and female rats to evaluate the influence of transfer of chromosome 1 from the Brown Norway (BN) rat to the FHH genetic background (FHH-1BN). Rats were maintained for 2 wk on 8.0% NaCl chow with NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (12.5 mg/l) to induce hypertension and accelerate the onset of renal disease. Mean arterial blood pressure (MAP) was significantly higher in the male FHH (188 +/- 3 mmHg, n = 13) compared with the BN (121 +/- 3 mmHg, n = 8); MAP in the FHH-1(BN) was midway between the two parental strains (167 +/- 5 mmHg, n = 9). Urinary protein and albumin excretion rates in the male FHH-1(BN) (Uprot = 189 +/- 36 mg/day, Ualb = 69 +/- 16 mg/day, n = 10) were also midway between levels observed in the FHH (Uprot = 485 +/- 54 mg/day; Ualb = 206 +/- 25 mg/day, n = 13) and the BN (Uprot = 32 +/- 5 mg/day, Ualb = 5 +/- 1 mg/day, n = 8). Creatinine clearance was elevated, and the degree of glomerular damage was significantly reduced in the FHH-1BN compared with the FHH. Qualitatively similar results were obtained from female FHH, FHH-1BN, and BN rats. The present results indicate that genes contributing to l-NAME-induced hypertension and renal disease are found on chromosome 1 of the FHH rat.
 ...
PMID:Substitution of chromosome 1 ameliorates L-NAME hypertension and renal disease in the fawn-hooded hypertensive rat. 1564 86

Chronic allograft nephropathy (CAN) is the primary cause for late kidney allograft loss. Carbon monoxide (CO), a product of heme metabolism by heme oxygenases, is known to impart protection against various stresses. We hypothesized that CO could minimize the chronic fibroinflammatory process and protect kidney allografts from CAN. Lewis kidney grafts were orthotopically transplanted into binephrectomized Brown-Norway rats under short-course tacrolimus. Recipients were maintained in room air or exposed to CO at 20 parts/million for 30 days after transplant. Efficacy of inhaled CO was studied at day 30 and day 80. Isografts maintained normal kidney function throughout the experiment with creatinine clearance of approximately 1.5 ml/min. Renal allograft function in air controls progressively deteriorated, and creatinine clearance declined to 0.2 +/- 0.1 ml/min by day 80 with substantial proteinuria. CO-treated animals had significantly better creatinine clearance (1.3 +/- 0.2 ml/min) with minimal proteinuria. Histological examination revealed the development of progressive CAN in air-exposed grafts, whereas CO-treated grafts had minimal tubular atrophy and interstitial fibrosis, with negligible collagen IV deposition. In vitro analyses revealed that CO-treated recipients had significantly less T cell proliferation against donor peptides via the indirect allorecognition pathway and less anti-donor IgG antibodies compared with air controls. Intragraft mRNA levels for chemokines (regulated on activation normal T cell expressed and secreted, macrophage inflammatory protein-1alpha, chemokine receptors (CCR1, CXCR3, CXCR5), IL-2, and intercellular adhesion molecule-1 were significantly decreased in CO-treated than in air-treated allografts. Furthermore, reduction of blood flow in air-treated allografts was prevented with CO. In conclusion, inhaled CO at a low concentration efficiently abrogates chronic fibroinflammatory changes associated with CAN and improves long-term renal allograft function.
 ...
PMID:Low-dose carbon monoxide inhalation prevents development of chronic allograft nephropathy. 1613 50

Killer cell immunoglobulin-like receptors (KIR) on natural killer cells mediate killing by recognizing class I presentation of peptides by infected or oncogenic cells. KIR differences in stem cell transplants have been implicated in increased graft vs host disease. Human leukocyte antigen (HLA)-matched-related kidney recipients have the best graft survival as compared to one haplotype-matched recipients. These HLA-identical transplant pairs may be ideal for studying minor HLA antigens and KIR polymorphic differences and their relation to graft function. We have studied KIR polymorphism in recipients and donor pairs of HLA-matched sibling kidney transplants to demonstrate differences in genotype as related to long-term graft function and/or chronic rejection. We employed a KIR genotyping kit (Dynal, Brown Deer, WI), that uses sequence-specific priming by PCR to identify 19 alleles for genotypes in 12 donor/recipient (D/R) pairs at least 1 year posttransplant. There were two pairs that had different alleles in the recipient that were not found in the donor. One pair had different alleles found in the donor that were not present in the recipient. Two pairs had difference in alleles in both the donor and recipient. Seven of the 12 pairs had the same KIR genotype. Eight of the 12 pairs (both donor and recipient) exhibited a haplotype with 2DL2+ and 2DS2+. Four of the 12 exhibited a haplotype 2DL2- and 2DS2-. Three out of four of these recipients had increased creatinine levels and at least one graded rejection episode. One of these three has lost their graft. In conclusion, the genotyping of HLA-matched sibling kidney transplant D/R pairs demonstrates that there may be an association of higher risk for poor graft function when both genotypes lack 2DL2 and 2DS2.
 ...
PMID:Killer cell immunoglobulin-like receptor polymorphisms in HLA-identical kidney transplant recipients: lack of 2DL2 and 2DS2 may be associated with poor graft function. 1744 84

Oxidative stress is important in the pathogenesis of renal ischemia-reperfusion (IR) injury; however whether imbalances in reactive oxygen production and disposal account for susceptibility to injury is unclear. The purpose of this study was to compare necrosis, apoptosis, and oxidative stress in IR-resistant Brown Norway rats vs. IR-susceptible Sprague-Dawley (SD) rats in an in vivo model of renal IR injury. As superoxide (O (2) (.-) ) interacts with nitric oxide (NO) to form peroxynitrite, inducible NO synthase (iNOS) and nitrotyrosine were also examined. Renal IR was induced in SD and BN rats by bilateral clamping of renal arteries for 45 min followed by reperfusion for 24 h (SD 24 and BN 24, respectively). BN rats were resistant to renal IR injury as evidenced by lower plasma creatinine and decreased acute tubular necrosis. TUNEL staining analysis demonstrated significantly decreased apoptosis in the BN rats vs. SD rats after IR. Following IR, O (2) (.-) levels were also significantly lower in renal tissue of BN rats vs. SD rats (P < 0.05) in conjunction with a preservation of the O (2) (.-) dismutating protein, CuZn superoxide dismutase (CuZn SOD) (P < 0.05). This was accompanied by an overall decrease in 4-hydroxynonenal adducts in the BN but not SD rats after IR. BN rats also displayed lower iNOS expression (P < 0.05) resulting in lower tissue NO levels and decreased nitrotyrosine formation (P < 0.01) following IR. Collectively these results show that the resistance of the BN rat to renal IR injury is associated with a favorable balance of oxidant production vs. oxidant removal.
 ...
PMID:Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury. 1745 15

We developed an improved solution for hypothermic storage (0-4 degrees C) of kidneys. The cold storage solution (HBS) was composed of macromolecules, high-energy cellular substrates, and a mixture of antiproteolytic amino acids, antioxidants, and anti-inflammatory compounds. The objectives in developing this solution were to achieve superior metabolic support of the kidney during cold storage and to protect against ischemic injury. Inbred Brown Norway rats, weighing 225-250 g, were subjected to orthotopic ultrarapid technique for kidney isotransplantation to minimize warm ischemia and to test the preservation process. The kidney was transplanted after 12 h of preservation. The animals were divided into three groups based upon the preservation solution utilized: HBS solution, HTK solution (Custodiol), and UW solution (UWS)(ViaSpan). Among the recipients, each group had two subsets. The first subset of animals was used to assess survival at 7 days as well as the reperfusion damage index (RDI) based on the macroscopic physical characteristics of the kidney at the time of transplantation. The second subset in each group was utilized to measure serum creatinine and blood urea nitrogen at 4 and 7 days, and histology at death or sacrifice. Mean +/- standard deviation (M +/- SD) was used for all parameters studied. The HBS solution showed significantly better protection at 12 h when compared to HTK and UW solutions. The reperfusion damage index (RDI) showed excellent preservation in the HBS (14 +/- 1), good preservation in UWS (13 +/- 1.5), and moderate preservation in the HTK (11 +/- 2) group. Histology was in concordance with the RDI, showing better histological findings with HBS and UW solutions than with the HTK group. Serum creatinine was significantly better in the HBS group when compared to HTK and UWS. Survival was statistically different, with 80% survival at 7 days in the HBS group, 20% survival in the HTK group, and 50% survival in the UWS group (p < .05). The HBS solution offered a new alternative for kidney cold storage with significantly better results when compared to the current gold standards of HTK and UW solutions in Brown Norway rats. This solution warrants further testing in other mammals.
 ...
PMID:Evaluation of a novel cold storage solution (HBs) in a rat kidney transplant model. 1771 Jun 7


<< Previous 1 2 3 4 5 Next >>