Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
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Gallstones are composed principally of cholesterol monohydrate crystals (cholesterol stones) or the acid salt of calcium bilirubinate (pigment stones). Cholesterol stones and the black variety of pigment gallstones form in sterile gallbladder bile whereas brown pigment gallstones form in infected bile. Biliary supersaturation is the principal pathophysiological defect and is hepatic in origin. Supersaturation results from excessive secretion of cholesterol or bilirubin conjugates, the precursors of unconjugated bilirubin, and/or, deficient secretion of bile salt and lecithin, the solubilizers of these otherwise insoluble lipids. As has now being clarified for cholesterol stones, an imbalance in pro- and antinucleating biliary proteins, hypersecretion of gallbladder mucin and gallbladder dysmotility possibly from cholesterol "toxicity" to sarcolemma, all interact to promote nucleation. Crystallisation results in suspension of cholesterol crystals or bilirubinate salts in gallbladder mucin gel and is known as "biliary sludge". It is believed today that this stage is essential for evolution of both cholesterol and pigment stones. Brown pigment gallstones form principally in the bile ducts. These stones result from infection of the biliary tree, most commonly due to obstruction from migrating gallbladder stones. Chemical compositions of brown and black pigment stones are different: In black stones, calcium bilirubinate is polymerized and oxidatively degraded but in brown stones, calcium bilirubinate is present as the unpolymerised salt. Brown stones differ also from black stones in containing calcium fatty acid soaps, a result of bacterial phospholipase A1 hydrolysis of biliary lecithin. Both types of pigment gallstones may contain crystalline inorganic calcium salts especially carbonate (gallbladder stones) and phosphate (bile ducts stones). Since a molecular understanding of the multiple defects that lead to cholesterol and pigment gallstones is becoming a reality, the future holds much promise for gallstone prevention.
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PMID:Pathogenesis of gallstones. 152 52

Genetic polymorphism in a mucin of the human milk fat globule arises from variable numbers of a tandemly repeated amino acid sequence. As a consequence, the gene from each parent expresses a variable-sized protein. This is manifest on SDS gels in the form of either one or, more often, two protein bands, which differ among individuals in mobility. Evidence of such polymorphism in the bovine mucin, PAS-I, was first obtained from Holstein milk samples. The objective of this study was to evaluate the other major dairy breeds for polymorphism of their PAS-I. Milk samples from individual Jerseys, Guernseys, Ayrshires, and Brown Swiss were analyzed by SDS-PAGE. Bands of the mucin varying in number and mobility were seen in samples from all four breeds. In three of the breeds (Ayrshire, Brown Swiss, and Jersey), there was evidence that two alleles for PAS-I may have become predominant, possibly through degeneration in the structure of their tandem repeats, one that gives rise to a faster moving mucin (relative molecular weight 170,000) and the other to a slower form (relative molecular weight 200,000). In contrast, the PAS-I band patterns on SDS gels for both Guernseys and Holsteins were characterized in nearly 50% of samples by two close bands near the 205,000-molecular weight marker. This pattern was never seen in the other three breeds. The findings suggest a genetic kinship among the Ayrshire, Brown Swiss, and Jersey, on the one hand, and between the Holstein and Guernsey, on the other.
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PMID:Genetic polymorphism of the epithelial mucin, PAS-I, in milk samples from the major dairy breeds. 156 76

Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct. Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition. Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones. Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease. The pathogenesis of black stones is probably related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates. At the pH of bile, this results in two monohydrogenated bilirubin anions that precipitate with calcium ions. Bilirubin monoconjugates that are increased in several conditions, such as Gilbert's syndrome and chronic hemolysis, may play a pivotal role in black stone formation as a source of unconjugated monohydrogenated bilirubin and as a possible co-precipitant with calcium. The precipitation of calcium carbonate and phosphate is influenced by local gallbladder factors. Brown pigment stones are formed in bile infected with enteric bacteria that elaborate hydrolytic enzymes: beta-glucuronidase, phospholipase A, and conjugated bile acid hydrolase. The resulting anions of bilirubin and fatty acids form insoluble calcium salts. We used nb/nb mice with a chronic hemolytic anemia as a model of hemolysis-induced black stone disease. The presence of 40% bilirubin monoconjugates in mouse gallstones indicated the importance of this moiety in the pathogenesis of black stones. Other data obtained by marrow transplantation experiments in mice revealed the relative importance of genotype versus the hemolytic anemia on determinants such as biliary bile acid composition and mucin secretory glands in the mouse gallbladder neck. Additional physical chemical studies of the interaction of unconjugated bilirubin in model bile solutions will be helpful in further delineating the pathogenesis of both black and brown pigment gallstones.
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PMID:Pigment gallstone disease. 202 17

The effect of 13-cis-retinoic acid (13-cis-RA) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male, random bred, Sprague-Dawley (S-D) and inbred Wister/Furth (W/Fu) rats and on isograft tumor growth and metastases in a Brown Norwegian (BN) X W/Fu F1 rat was studied. 13-cis-RA (300 mg/kg diet) was administered to S-D rats 1 week before commencing DMH injections and for the duration of the experiment. W/Fu rats received 13-cis-RA (10 mg/kg weight X 5 days) 6 weeks after DMH injection had begun and monthly thereafter. Primary tumors were detected by serial laparotomy under ether anesthesia in both strains. The time to tumor onset was significantly delayed in treated groups, S-D and W/Fu, P = 0.0339 and 0.0322, respectively (Mantel-Haenszel test), compared with placebo-treated controls. 13-cis-RA (15 mg/kg weight) administered 2 days before and for the duration of isograft tumor growth (DMH 2054, a well-differentiated mucin-producing colon adenocarcinoma that spontaneously metastasized to lung) had no effect on tumor growth or metastasis in the BN X W/Fu F1 rat. The findings suggest that the role of 13-cis-RA is in colon cancer prevention and not in its treatment either in an adjuvant or established setting.
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PMID:Effect of 13-cis-retinoic acid on tumor prevention, tumor growth, and metastasis in experimental colon cancer. 348 Mar 91

Electron microscopy of platinum-shadowed preparations of human tracheobronchial mucins showed very flexible filamentous structures that frequently occurred in an intricate random-coiled pattern of filament(s) surrounding a dense core-like domain. The filament(s) associated with cores accounted for 70-80% of the mass of the mucin preparation, the remainder being accounted for by free filaments. On aggregation, the molecules formed a large interwoven network quite different from the massive rope-like structures characteristic of sheep submaxillary mucin aggregates [Rose, Voter, Sage, Brown & Kaufman (1984) J. Biol. Chem. 259, 3167-3172]. Mild sonication resulted in extensive fragmentation of the tracheobronchial mucin molecules and yielded short filaments of various lengths, free cores and some cores associated with short filaments. Mucin glycopeptide fragments obtained by proteolytic digestion were flexible, core-free, filaments. The glycopeptides obtained by Pronase digestion were shorter than those obtained by tryptic digestion. The intricate structures of human tracheobronchial mucin differ markedly from the extended filaments reported for sheep submaxillary and human ovarian-cyst mucins but agree with the roughly spherical expanded model proposed for mucins by Creeth & Knight [(1967) Biochem. J. 105, 1135-1145] on the basis of hydrodynamic measurements.
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PMID:Structural features of human tracheobronchial mucus glycoprotein. 647 21

The present studies were undertaken to evaluate the histologic effects of graft-versus-host disease on the host colon after small bowel transplantation. Graft-versus-host disease was produced in six Lewis x Brown Norway F1 rats by performing vascularized, out-of-continuity small bowel transplants from parental Lewis donors. Host proximal and distal colon were sampled 14 days after operation when signs of graft-versus-host disease, including weight loss and splenomegaly, were present. Tissue was assessed histologically by blinded observer and compared to eight sham-operated controls. Three histologic features were noted to be statistically increased in diseased animals: (1) mucin loss; (2) crypt abscesses; and (3) large lymphoid aggregates in the mucosa and submucosa. These features were more commonly noted in the distal rather than the proximal colon. Another group of five grafted animals treated with cyclosporine A (10 mg/kg/day intramuscularly) still lost weight but did not display overt signs of graft-versus-host disease and had normal-sized spleens. There was normal mucin content and no evidence of crypt abscesses in these treated animals, although large lymphoid aggregates were present. It is concluded that mucin loss, crypt abscesses, and large lymphoid aggregates are characteristics of graft-versus-host disease-induced colonic injury in this model and that these changes are most evident in the distal colon. Cyclosporine A therapy does not completely reverse the histological changes of colonic graft-versus-host disease. This model may be useful in studying the mechanisms by which immune mediated colitides preferentially affect the distal colon.
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PMID:Graft-versus-host disease after small bowel transplantation is associated with host colonic injury. 755 45

The polymorphic epithelial mucin, PAS-I (also known as MUC1), in individual milk samples from 119 Holstein cows was resolved into bands on SDS-gels. Mobility indices established for these bands provided evidence of four and possibly five polymorphic forms. Sialic acid, a major component of the oligosaccharide portion of PAS-I, was removed from the mucin by treatment of milk samples with neurominidase. This reduced the mobility of the mucin bands but did not alter their mobility relationships within a sample or among samples. Consideration of evidence from this and other studies indicates that the four or five polymorphic forms correspond to alleles, which are inherited, one each from sire and dam, and co-dominantly expressed. It appears that the Holstein population may carry several more alleles for PAS-I than do Ayrshire, Jersey or Brown Swiss cattle. In addition to these breed differences, some remarkable molecular differences have been noted between MUC1 (PAS-I) of human and mouse suggesting that research regarding molecular evolution of this mucin could provide another approach to understanding relationships among species.
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PMID:Polymorphic forms of the epithelial mucin, PAS-I (MUC1), in milk of Holstein cows (Bos taurus). 857 21

It is well known that the Brown Norway (BN) rat strain exhibits airway hyperresponsiveness to exposure to allergens or some chemicals. We investigated the histological characteristics of the trachea and lungs of this strain (10-week-old and retired animals) and compared them with those of age-matched Fischer 344 (F344) rat strain. No histological differences between two strains in tracheal epithelial cells were detected, but differences in the distribution and development of submucosal glands were clarified by the observation of serial sections cut at intervals of 100 microns. Submucosal glands of BN strain were larger in the number and better-developed than those of F344 strain, especially in the middle and lower trachea. Similar results were also obtained in scanning electron microscopic observation of resin casts. There were no significant differences between two strains in the lectin histochemical characteristics of the cytoplasm of glandular epithelial cells. No age-related changes in these morphological characteristics in the two strains were observed. These results suggest that mucin from submucosal glands is quantitatively different but qualitatively similar in the two strains. In addition, microgranuloma mainly composed of histiocytes and eosinophils was observed in the lungs of the BN strain rats.
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PMID:Histological characteristics of respiratory system in Brown Norway rat. 914 92

Environmental toxins, infection, and allergens lead to a transient mucous cell hyperplasia (MCH) in airway epithelia; however, the mechanisms for reducing mucous cell numbers during recovery are largely unknown. This study investigated Bcl-2 expression in mucous cells induced by a neutrophilic or eosinophilic inflammatory response. Brown Norway rats intratracheally instilled with lipopolysaccharide (LPS) showed an inflammatory response characterized primarily by neutrophils. Secreted mucin was increased fourfold at 1 day, and the number of mucous cells was increased fivefold 2, 3, and 4 days post-LPS instillation compared with those in noninstilled rats. None of the mucous cells in non- or saline-instilled control animals expressed Bcl-2, whereas 20-30% of mucous cells were Bcl-2 positive 1 and 2 days post-LPS instillation. Brown Norway rats immunized and challenged with ovalbumin (OVA) for 2, 4, and 6 days showed an inflammatory response characterized primarily by eosinophils. Secreted mucin increased fivefold, and mucous cell number increased fivefold after 4 and 6 days of OVA exposure compared with water-immunized control rats challenged with OVA aerosols. Approximately 10-25% of mucous cells were Bcl-2 positive in OVA-immunized and -challenged rats. These data demonstrate Bcl-2 expression in hyperplastic mucous cells of Brown Norway rats regardless of the type of inflammatory response and indicate that apoptotic mechanisms may be involved in the resolution of MCHs.
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PMID:Bcl-2 in LPS- and allergen-induced hyperplastic mucous cells in airway epithelia of Brown Norway rats. 1107 11

Heparins have demonstrated activity in asthma. The effects of bemiparin, a low molecular weight heparin, were examined on antigen-induced responses in sensitized Brown-Norway rats. Inhaled bemiparin (1 mg/ml) reduced the acute bronchospasm produced by aerosol antigen, prevented airway hyperresponsiveness to 5-hydroxytryptamine postantigen exposure, and reduced the eosinophil count (from 0.205+/-0.062 to 0.054+/-0.016 x 10(6) cells/ml in antigen and antigen+bemiparin groups, respectively; P<0.05), eosinophil peroxidase activity, and proteins in the bronchoalveolar lavage fluid (BALF), as well as the transiently augmented mucin Muc5ac expression. Hyperresponsiveness to adenosine was not affected by bemiparin. In similar experiments, inhaled fondaparinux (1 mg/ml) did not affect the antigen-induced responses, while a low-anticoagulant low molecular weight heparin was effective. In conclusion, bemiparin showed beneficial effects in experimental asthma, probably unrelated to its anticoagulant activity, which extends the previous positive findings obtained with other heparins.
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PMID:Effects of bemiparin on airway responses to antigen in sensitized Brown-Norway rats. 1565 17


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