Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0272170 (SDS)
 50,377 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A minor mucin glycoprotein component (HTM-2) was purified from the tracheobronchial secretions of two cystic fibrosis patients using a protocol established in our laboratory. The secretions were solubilized in 0.1 M Tris-HCl buffer (pH 7.5) containing 0.22 M potassium thiocyanate and fractionated on a Bio-Gel A-5m column, followed by digestion with DNAase, rechromatography on the same column and chromatography on hydroxyapatite which resolved the major mucin (HTM-1) from the minor mucin component (HTM-2). The mucin component HTM-2 was further purified using Superose 6 chromatography. SDS-composite gel (2% polyacrylamide + 0.5% agarose) and 6% polyacrylamide gel electrophoresis showed that the purified HTM-2 was totally free of low-molecular-weight contaminants. Equilibrium density sedimentation centrifugation of purified HTM-2 using CsCl gradients also showed the absence of proteoglycans and other low-molecular-weight proteins. Comparison of carbohydrate and amino acid compositions of the two mucin components indicated that HTM-2 was quite different from the major mucin, HTM-1, reported earlier from our laboratory (Biochemistry, 24, 7334, 1985). This suggested that HTM-2 has a different polypeptide core and is perhaps a different gene product. The effects of 6 M guanidine-HCl and different concentrations of NaCl on the molecular size of HTM-2 and its ability to form aggregates was also investigated using the technique of static light scattering. In buffer containing 6 M guanidine-HCl, HTM-2 had a weight-average molecular weight of approximately 4.5 x 10(6). However, in the presence of buffer containing 0.03, 0.10 or 0.15 M NaCl, the molecular weight of HTM-2 was estimated to be approximately 11 x 10(6). These data suggest aggregation of HTM-2 in the presence of a range of NaCl concentrations. In contrast to HTM-1, which is a more anionic glycoprotein, the apparent molecular size of HTM-2 did not decrease at the higher NaCl concentration.
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PMID:Physicochemical characterization of a minor mucin component from cystic fibrosis tracheobronchial secretions. 202 32

Various studies have demonstrated pronounced systemic IgG response to Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF). However, antibody response to serotype-specific lipopolysaccharides (LPS) has never been studied. ELISA for detection of IgG antibodies to LPS of nine PA-serotypes and to toxin A were performed with serum of 78 CF patients. Anti-LPS profiles of antibodies were confirmed by SDS-PAGE and immunoblotting techniques. The most frequent PA-serotypes found were immunotypes (IT) IT-1 and IT-2, and Habs-3 and Habs-4. Ten patients without PA colonization showed no detectable antibody titers. In patients with chronic PA colonization (n = 46), these antibody titers were significantly (p less than 0.005) higher than in patients with intermittent PA colonization (n = 22). Mean serum antibody titers to LPS of PA IT-1, IT-2, Habs-3, and Habs-4 correlated with duration of PA colonization and with disease severity. Subclass analysis of anti-LPS antibodies revealed elevated levels for all four IgG subclasses and for IgA1. The IgG antibodies to LPS of PA proved to be protective in a murine burn wound sepsis model. We conclude that anti-LPS antibodies to specific PA serotypes in serum may be a sensitive measure of severity and prognosis of CF. Patients with CF show adequate functional immune response to LPS of PA, and it is possible that vaccination against PA before colonization could induce protective immunity.
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PMID:Serotype-specific serum IgG antibodies to lipopolysaccharides of Pseudomonas aeruginosa in cystic fibrosis: correlation to disease, subclass distribution, and experimental protective capacity. 211 7

Diseases of the pancreas in children are often congenital; the genetic basis of some conditions such as cystic fibrosis have been elucidated using molecular biologic techniques. Anatomic abnormalities in childhood that cause symptomatic pancreatic disease are usually treated surgically. The biochemical abnormalities found with enzyme deficiencies, CF, and Shwachman's syndrome are best treated with medical therapy. The most common cause of acute pancreatic injury in children is trauma. Chronic pancreatic insufficiency usually occurs secondary to CF.
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PMID:Disorders of the pancreas in children. 226 27

Absorption of crystalline labeled cobalamin is strongly decreased in cases of cystic fibrosis. In order to determine if this is due to an alteration or a lack of activation of intrinsic factor by proteases, the physicochemical properties and biological activity of intrinsic factor have been studied. Intrinsic factor was purified 800-fold from stimulated gastric juice of cystic fibrosis patients with a yield of 64.2%. Cystic fibrosis intrinsic factor had an estimated Mr of 57,000 in SDS-polyacrylamide gel electrophoresis. Its carbohydrate content resembled that of normal human intrinsic factor, except that the ratio fucose/sialic acid was higher (6.1 and 1.6, respectively) and that the content in N-acetylgalactosamine was decreased. The same alterations in carbohydrate composition were observed for Hc purified from cystic fibrosis saliva. Purified intrinsic factor from cystic fibrosis gastric juice was biologically active in vitro in the presence of ileal solubilized receptor as well as in vivo (Schilling test). The fate of iodinated cystic fibrosis intrinsic factor in guinea pig ileum studied by high-resolution radioautography was similar to that of normal intrinsic factor. In conclusion, despite modifications of the carbohydrate content of the molecule, the biological activity of intrinsic factor is not altered in cases of cystic fibrosis. The malassimilation of crystalline cobalamin observed in cystic fibrosis is due to a mechanism independent from intrinsic factor secretion.
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PMID:Physicochemical characterization and biological activity of intrinsic factor in cystic fibrosis. 232 85

Light scattering has been used to investigate the structure of human tracheobronchial mucin glycoproteins (HTBM) from the sputum of cystic fibrosis patients. The specimen was extracted using 6M guanidinium hydrochloride solution and fractionated by gel exclusion chromatography on Sephacryl S-1000. The fractionated HTBM was purified by density gradient ultracentrifugation. Purity of the resulting material was confirmed by SDS polyacrylamide gel electrophoresis and uv spectroscopy. Light scattering measurements on the fractionated mucins yield weight-average molecular weights Mw, and z-average radii of gyration Rg,z. The native cystic fibrosis HTBM consisted of a high molecular weight fraction with Mw = 9.3 X 10(6) daltons and a lower molecular weight fraction containing partly degraded mucins. After reduction and carboxymethylation of the high molecular weight native fraction, the resulting material was separated into three pools with Mw values of 5.1 X 10(6), 1.6 X 10(6), and 400,000. The derived molecular weights for the protein cores Mp,w, and the experimental radii of gyration are found to be consistent with the Mp,w -Rg relation established previously for submaxillary, cervical, and gastric mucins. These results imply that HTBM has the same extended-coil conformation reported for other mucins and has a molecular structure consisting of subunits, linked into linear chains via covalent (disulfide) bonds.
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PMID:Structural analysis of purified human tracheobronchial mucins. 233 3

Serologically polyagglutinating (PA) and non-typable (NT) strains of Pseudomonas aeruginosa are frequently isolated from cystic fibrosis (CF) patients, but are uncommon in other patients. From serologically typical parent strains, we isolated two variants (one PA, the other NT) which differed from the parent in bacteriophage susceptibility or in sensitivity to the bactericidal action of normal human serum. The PA and NT variants (strains 7/1 and 18S respectively) reacted with antiserum to the parent strains 7 and 18R but did not absorb homologous specific O antibody from antiserum to the parent strains. In contrast the parent strains absorbed anti-PA and anti-NT antibodies from antisera to the variant strains. The yield of lipopolysaccharide (LPS) from acetone-dried cells of the parent strain 7 was similar to that of the PA derivative; but the NT strain 18S yielded only half the LPS of its parent strain. LPS of the variant 7/1 gave a banding profile by SDS-PAGE similar to that of the parent LPS 7, but lacked high-molecular-weight components. LPS of the variant 18S appeared to be grossly different in profile from LPS 18R. Of 533 isolates of P. aeruginosa that were tested with O antisera and with antisera to the two variants, 15% were O-typable and 22% were O-non-typable; 26% reacted with anti-PA serum alone, 10% with anti-NT serum alone, and 27% were agglutinated by both sera. There was a statistically significant correlation between serum sensitivity of CF isolates and their reaction with the PA or NT antisera.
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PMID:Polyagglutinating and non-typable strains of Pseudomonas aeruginosa in cystic fibrosis. 241 63

We have studied both by isoelectric focusing and polyacrylamide gel electrophoresis in the presence of SDS, sera of individuals homozygous (25) and heterozygous (26) for cystic fibrosis and compared them to controls (13). As in our first study [1], the protein with a pI value of 8.4 called 'cystic fibrosis protein' or CFP, was found in about 70% of homozygous and carriers and in 15% of controls. When the same sera were analysed by polyacrylamide gel electrophoresis in the presence of SDS and after staining with Coomassie Blue, an additional protein with a molecular weight close to 12,000 (P12) was present in most of the sera containing CFP, suggesting a close relationship between the two proteins. By increasing the sensitivity of staining by using silver nitrate, P12 was detected with variable intensity in almost all sera of homozygotes and heterozygotes and at the level of traces in all normal sera. These data suggest that P12, like CFP, would be a normal serum protein quantitatively increased in affected subjects.
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PMID:Correlation between the cystic fibrosis protein detected by isoelectric focusing and a protein of 12 kDa detected by SDS-polyacrylamide gel electrophoresis. 244 Jun 20

Urinary excretion of lactulose, mannitol, and 3-0-methylglucose, following oral administration (5 g, 5 g, and 2 g, respectively, in 100 ml H2O; 80 ml/m2), has been measured in subjects with cystic fibrosis (CF) (22), Shwachman syndrome (3), chronic pancreatitis (3), and normal controls (46). Mean lactulose excretion was increased 10-fold in CF (p less than 0.001), and two-fold in other disorders associated with pancreatic insufficiency (PI) (p less than 0.05). Mean mannitol excretion was 1.6 times greater in CF (p less than 0.001), compared with controls, but was reduced in other forms of PI (p less than 0.03). The mean lactulose/mannitol excretion ratio was increased in all types of PI (p less than 0.001). There were no significant differences in 3-0-methylglucose excretion. This study confirms the large increase in lactulose absorption recently reported in CF and also demonstrates increased absorption of mannitol; these changes are different than those in other forms of PI. This study provides further evidence for a specific abnormality of the mucosal barrier to the absorption of passively absorbed, water soluble molecules in CF.
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PMID:Active and passive sugar absorption in pancreatic insufficiency. 249 12

Purified intestinal mucins from eight normal subjects (N) and six patients with cystic fibrosis (CF) were compared for: (1) their content of free thiol groups (-SH) and disulphide bonds (S-S), (2) their immunoreactivity in a specific enzyme-linked immunoassay (ELISA) for the disulphide-bound 118,000 Mr glycoprotein and (3) their content of 118 kDa glycoprotein. Results showed considerable variability in the S-S/-SH content of individual mucin preparations but no differences were observed between N and CF samples. In the ELISA, all mucins were found to have identical antigenic determinants with the same affinity for the anti-118 kDa glycoprotein antibody but marked differences (ranging from 0.2 to 120,000 ng mucin) were observed in their relative immunoreactivities, indicating variable numbers of antigenic determinants. In general, CF mucins appeared to react more strongly in the immunoassay than N mucins. By SDS/polyacrylamide-gel electrophoresis under reducing conditions and densitometric analysis of Coomassie blue-stained gels, differences (up to six-fold) were also detected in the amount of 118 kDa glycoprotein in individual mucin preparations. However, this did not appear to be the cause of the variations in mucin immunoreactivity because not all strongly antigenic mucins contained large amounts of 118 kDa glycoprotein. Thus, accessibility of the 118 kDa glycoprotein to the antibody or the number of functional antigenic determinants within the 118 kDa glycoprotein may vary among different mucin preparations. The greater antigenicity of CF mucins may therefore reflect changes in their macromolecular conformation or in their 118 kDa glycoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disulphide bonds and the 118,000 Mr glycoprotein of human intestinal mucin. 264 11

The mechanism leading to exocrine pancreatic disease in children differs from those encountered in adult patients: I. In acute pancreatitis autodigestion of the gland by proteolytic enzymes may occur and two mechanisms may play a role. 1. Reflux of biliary secretions (e.g. in malformations of the duct system) facilitates activation of trypsinogen by enteropeptidase and leads to the presence of active proteolytic enzymes in the gland (exogenous activation). 2. Lysosomal enzymes may play a role in the intracellular activation of zymogens if inflammation leads to a fusion of lysosomes with zymogen granules (endogenous activation). II. In chronic relapsing and hereditary pancreatitis malformations of the pancreatico-biliary duct system must be sought because surgery may be indicated (common channel syndrome and choledochal cysts). III. Among the hereditary diseases leading to pancreatic insufficiency cystic fibrosis (CF) plays the main role. Haplotype analysis has shown that two genetically different types of CF exists (PS and PI). The pancreas shows manifest insufficiency only in the PI-types which occur in more than 70% of cases but the distribution of haplotypes is different in different ethnic groups. In spite of the recent discovery of the cystic fibrosis gene the exact mechanism leading to exocrine pancreatic dysfunction in CF is not clear, but diminished chloride and bicarbonate secretion, may be the result of a disturbance in the regulation of chloride channels, on acinar or ductular level. In the Shwachman-Diamond syndrome a very severe type of exocrine insufficiency with unknown etiology is encountered at birth.
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PMID:[Physiopathology of the exocrine pancreas in children]. 269 2


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