Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007570 (celiac disease)
 13,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to determine the frequency of liver injury in adult coeliac disease (A.C.D.) the case records of 74 consecutive patients were examined. In 13 cases histological sections of the liver were available and in 5 of these there were signs of reactive hepatitis. Histological signs of distinct hepatic injury with cirrhosis and/or chronic active hepatitis were found in 7 other patients. In 5 of these serum-IgA was normal, whereas 16 out of 20 control patients with liver cirrhosis not associated with A.C.D. had raised serum-IgA. Serum-aspartate-aminotransferase and serum-alanine-aminotransferase were determined in 53 patients; 29 had raised concentrations. In 19 patients serum-aminotransferases were repeatedly determined before and during the dietary regimen and there was a significant reduction in enzyme concentrations during treatment. The median concentration of serum-alkaline-phosphatase was also reduced during treatment but not significantly. The histological evidence of liver injury in 16% and the abnormal liver-function tests in 39% of the patients indicate that hepatic injury is common in A.C.D. Since liver-function tests or liver biopsy specimens were available for only about two-thirds of the patients, liver damage in A.C.D. may be more common than indicated by these results. The effect of a gluten-free diet on aminotransferase concentrations indicates that the liver injury may be reversible and suggests that in some A.C.D. patients progressive liver damage may be prevented by suitable treatment. Since A.C.D. is not always recognised, the diagnosis should be considered in patients with liver disease of unknown aetiology.
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PMID:Hepatic injury in adult coeliac disease. 6 80

Bovine brain inositol monophosphatase is rapidly cleaved by endoprotease lys-C at a single site in the absence of SDS. Further sites are revealed only after prolonged incubation with high concentrations of protease. The initial cleavage occurs near one end of the enzyme, generating an N-terminally-derived 36-residue peptide, which is blocked, and a large 28 kDa fragment bearing a free N-terminus. The start sequence of this fragment was found to be Xaa-Ser-Pro-Ala-Asp-Leu-Val, consistent with the cDNA sequence, and Lys-36-Ser-37 was identified as the cleavage site. The activity of the cleaved enzyme was markedly decreased to 3% of that of the native enzyme, although its dimeric structure was preserved. The 36-residue peptide was not covalently associated with the large fragment after proteolytic cleavage, although the possibility of non-covalent association could not be excluded. Finally, the epitope for the inhibitory monoclonal antibody G-2A4 [Gee, Howell, Ryan & Ragan (1989) Biochem J. 264. 793-798] was found to lie proximal to the endoprotease lys-C cleavage site. In vitro mutagenesis further mapped the epitope for monoclonal antibody G-2A4 to residues around Cys-8 of the enzyme. These results suggest that the N-terminal region of the enzyme is important for activity.
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PMID:Limited proteolysis and 'in vitro' mutagenesis of bovine brain inositol monophosphatase identifies an N-terminal region important for activity. 170 24

A peptide of the pancreatic polypeptide (PP) family was isolated in pure form from the pancreas of an elasmobranch fish, Scyliorhinus canicula (European common dogfish). The primary structure of the peptide was established as: Tyr-Pro-Pro-Lys-Pro-Glu-Asn-Pro-Gly-Glu10-Asp-Ala-Pro- Pro-Glu-Glu-Leu-Ala-Lys-Tyr20-Tyr-Ser-Ala-Leu-Arg-His- Tyr-Ile-Asn-Leu30-Ile-Thr-Arg-Gln-Arg-Tyr.NH2. This sequence contains 86% amino acid sequence homology with human neuropeptide Y, and the COOH-terminal region (residues 20-36) has been fully conserved. Bolus injection of a synthetic replicate of the peptide (0.5-4 nmol) into the celiac artery of conscious dogfish resulted in a significant (P less than 0.01) and dose-dependent increase in arterial blood pressure. A maximum rise in mean pressure (67 +/- 11% over mean basal values; n = 6) was elicited by an injection of 2 nmol peptide. Bolus injections of human neuropeptide Y (0.5-4 nmol) also elicited dose-dependent rises in blood pressure, and the effects produced by the dogfish and human peptides were not significantly different at any dose. The data are consistent with a physiological role for neuropeptide Y-related peptide in cardiovascular regulation in elasmobranch fish.
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PMID:Structural characterization and biological activity of a neuropeptide Y-related peptide from the dogfish, Scyliorhinus canicula. 201 51

A double-lumen perfusion technique has been used to study amino acid and peptide absorption in eight normal control subjects, 13 patients with untreated adult coeliac disease, and 16 patients with dermatitis herpetiformis who had varying morphological abnormalities of the small bowel. All subjects were perfused with isotonic solutions containing 10 mM glycyl-L-alanine and 10 mM glycine + 10 mM L-alanine. Patients with adult coeliac disease had impaired absorption of glycine (p < 0.01) and L-alanine (p < 0.05) from the amino acid solution compared with the control subjects. Amino acid uptake from the dipeptide solution was not significantly impaired, although four individual patients had impaired uptake of both amino acids. In contrast to these findings, very few patients with dermatitis herpetiformis had impaired amino acid absorption from either solution. Sodium absorption was impaired from both solutions when the groups of patients with adult coeliac disease and dermatitis herpetiformis with subtotal villous atrophy and partial villous atrophy were studied, and there were patients in each group who secreted sodium and water. The results suggest that malabsorption of dietary protein is unlikely to occur in dermatitis herpetiformis but may occur and contribute to protein deficiency seen in some severe cases of adult coeliac disease. The impairment of sodium and water absorption provides evidence that there may be functional impairment of the jejunal mucosa in dermatitis herpetiformis as well as in adult coeliac disease.
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PMID:Amino acid and peptide absorption in patients with coeliac disease and dermatitis herpetiformis. 482 Jun 29

The usefulness of optimized and newly elaborated histochemical methods for proteinases is illustrated on two selected substances. DAP IV (Gly-Pro-MNA,FBB,pH 7.2) was discovered in 39% and DAP II (Lys-Ala-MNA,FBB,pH 5.5) in 60% of the lymphocytes of human peripheral blood (ly). The reaction product of such ly differs in quality and quantity. On the ultrastructural level, the reaction product of DAP IV (Gly-Pro-MNA,HNF) was found in cell membranes and lysosomes. Enzyme activity in other areas was probably suppressed during the preparation procedure. Although the number of ly revealed with Lys-Pro-MNA and Phe-Pro-MNA at pH 5.5 and with Lys-Pro-MNA at pH 7.2 is high, these substrates do not distinctly discriminate DAP IV and DAP II. DAP IV occurs exclusively in T lymphocytes. The number of DAP IV-positive ly was not decreased in patients with myelofibrosis, plasmacytoma, chronic granulocytic leukemia, or tricholeukemia. It was, however, greatly reduced in chronic lymphatic leukemia (CLL). In patients with malignant lymphomas other than CLL, ly presence is related to the stage of the disease. Decreased values indicate a more severe stage or a relapse. In the majority of patients with gastric cancer DAP IV-positive ly were decreased. They were normal or increased in patients with peptic ulcer. The assessment of the number of DAP IV-positive ly is a simple method that provides information regarding the condition of patients with malignant lymphomas and gastric carcinoma. Neutrophilic leukocytes and their precursors, and to a lesser extent monocytes, are revealed when N-acetyl-Met-I-naphthyl ester (Ac-Met-N) is used as substrate. Membrane-bound lysosomal and cytosol proteinases were investigated together with disaccharidases in jejunal biopsies of patients with malabsorption syndrome. Activities of all enzymes were affected in patients with celiac disease. According to their impairment enzymes could be arranged: Lactase(L). trehalase (T), brush border endopeptidase (BBEP), gamma-glutamyl transferase (GGT), DAP IV, enzyme(s) cleaving Ac-Mer-N, aminopeptidase A, cytosol peptidases and aminopeptidase M. In the propria, DAP IV is decreased or absent, while GGT and, particularly, DAP II are increased. After a gluten-free diet, activities are restored in a reverse order. BBEP and GGT are useful as auxiliary parameters in the assessment of the damage or differentiation degree of enterocytes. DAP IV is a sensitive indicator of the involvement of the propria.
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PMID:Proteinases in pathology. Usefulness of histochemical methods. 701 84

In order to study cell tropism and attenuation of hepatitis A virus (HAV), the genome of HAV wild-type GBM and two cell culture-adapted variants, GBM/FRhK and GBM/HFS, were cloned and sequenced after amplification by reverse transcriptase-PCR. During virus cultivation, the HAV variant GBM/FRhK had a strict host range for FRhK-4 cells, in contrast to GBM/HFS, which can be grown in HFS and FRhK-4 cells. The HAV variant GBM/HFS was shown to be attenuated when inoculated into chimpanzees (B. Flehmig, R. F. Mauler, G. Noll, E. Weinmann, and J. P. Gregerson, p. 87-90, in A. Zuckerman, ed., Viral Hepatitis and Liver Disease, 1988). On the basis of this biological background, the comparison of the nucleotide sequences of these three HAV GBM variants should elucidate differences which may be of importance for cell tropism and attenuation. The comparison of the genome between the GBM wild type and HAV wild types HM175 (J. I. Cohen, J. R. Ticehurst, R. H. Purcell, A. Buckler-White, and B. M. Baroudy, J. Virol. 61:50-59, 1987) and HAV-LA (R. Najarian, O. Caput, W. Gee, S. J. Potter, A. Renard, J. Merryweather, G. Van Nest, and D. Dina, Proc. Natl. Acad. Sci. USA 82:2627-2631, 1985) showed a 92 to 96.3% identity, whereas the identity was 99.3 to 99.6% between the GBM variants. Nucleotide differences between the wild-type and the cell culture-adapted variants, which were identical in both cell culture-adapted GBM variants, were localized in the 5' noncoding region; in 2B, 3B, and 3D; and in the 3' noncoding region. Our result concerning the 2B/2C region confirms a mutation at position 3889 (C-->T, alanine to valine), which had been shown to be of importance for cell culture adaptation (S. U. Emerson, C. McRill, B. Rosenblum, S. M. Feinstone, and R. H. Purcell, J. Virol. 65:4882-4886, 1991; S. U. Emerson, Y. K. Huang, C. McRill, M. Lewis, and R. H. Purcell, J. Virol. 66:650-654, 1992), whereas other mutations differ from published HAV sequence data and may be cell specific. Further comparison of the two cell culture-adapted GBM variants showed cell-specific mutations resulting in deletions of six amino acids in the VP1 region and three amino acids in the 3A region of the GBM variant GBM/FRhK.
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PMID:Nucleotide sequence of wild-type hepatitis A virus GBM in comparison with two cell culture-adapted variants. 825 70

To clarify the physiological role of vagal amino acid sensors in the liver, the effect of hepatic vagotomy and/or celiac vagotomy (sectioning of the hepatic branch and/or the celiac branches of the vagus nerve) on the secretion of insulin and glucagon after intraperitoneal injection of neutral (L-alanine, L-leucine, and L-phenylalanine), acidic (L-glutamate), or nonmetabolized (cycloleucine) acids, was examined in rats. Hepatic vagotomy enhanced both plasma glucose and glucagon concentrations after intraperitoneal injection of alanine more than those in sham-vagotomized (control) rats, while after intraperitoneal injection of leucine, hepatic vagotomy decreased plasma glucose concentrations and enhanced plasma insulin concentrations more than in control animals. These effects, following both alanine and leucine administration, were blocked by celiac vagotomy. Glutamate, phenylalanine, and cycloleucine stimulation in hepatic-vagotomized rats caused no significant differences in plasma glucose, insulin, or glucagon levels as compared to those in sham-vagotomized rats. Celiac vagotomy alone did not affect plasma glucose, insulin, or glucagon concentrations after stimulation by these five amino acids. The physiological role of alanine and leucine sensors may be to prevent amino acid-induced exaggerated pancreatic hormone secretion and to maintain blood glucose homeostasis, while glutamate, phenylalanine, and cycloleucine have no effect on this pancreatic neuroendocrine system.
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PMID:Hepatic vagal amino acid sensors modulate amino acid induced insulin and glucagon secretion in the rat. 845 96

To understand the rules determining peptide binding to the celiac disease and type 1 diabetes mellitus associated HLA-DQ2 molecule, we have studies in detail the binding of a peptide OVA 258-276Y (IINFEKLTEWTSSNVMEERY) which exhibits strong binding to DQ2. First we tested a set of N- and C-terminal truncated variants, and found the core binding region to comprise residues 267-276Y. Single alanine substitution analysis of the OVA 267-276Y peptide revealed that replacements of V272, E275 and the C-terminal Y had negative effects whereas the substitution of N271 had a positive effect. A polyalanine analogue of the OVA 267-276Y peptide with V272, E275 and a C-terminal Y bound at least as well as the original peptide. A variant peptide with a deletion of R276 displayed decreased binding, suggesting that the anchor residues were out of frame in this analogue. To further characterize the residues playing a role in the binding of the OVA 267-276Y peptide to DQ2 we tested the binding of several analogues with substitutions for V272, E275 and the C-terminal Y residue. Our results indicate that peptides binding to DQ2 have anchor residues in relative positions 4, 7 and (P4, P7 and P9). Residues with negatively charged or hydrophobic aliphatic but not positively charged side chains are preferred in P4 and P7, whereas residues with bulky hydrophobic side chains are preferred in P9.
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PMID:Identification of a putative motif for binding of peptides to HLA-DQ2. 867 2

The HXGH motif of CTP:phosphocholine cytidylyltransferase (CCT) is a unifying feature of the cytidylyltransferase family which has been proposed to function in binding of CTP and catalysis [Veitch, D. P. & Cornell, R. B. (1996) Biochemistry 35, 10743-10750]. Substitution of serine for Gly91 in the HXGH motif of CCT implicates this motif in CTP-binding [Park, Y. S., Gee, P., Sanker, S., Schuster, E. J., Zuiderweg, E. R. & Kent, C. (1997) J. Biol. Chem. 272, 15161]. The model for CTP binding involves hydrogen bond contacts between the histidine imidazole and the CTP phosphate oxygens. We have mutated His89 and His92 to Gly or Ala, which eliminate potential hydrogen bonds, and to Asn or Gln, which conserve these interactions. Mutation to Gly or Ala at both positions, and the H89Q mutation resulted in inactive enzymes. The Vmax of [N89]CT was 100-fold lower than that of wild-type CCT, but CTP binding was not perturbed, suggesting an involvement of His89 in transition-state stabilization. The H92N mutation reduced Vmax and increased the Kms for both substrates fivefold. The H92Q mutation had little effect on substrate binding or Vmax. These data suggest that the Gln92 NH2, and not the Asn NH2, is able to substitute for the histidine NH, and implicates the tau nitrogen of His92 in forming contacts with CTP. This work strengthens the hypothesis that the HXGH motif is involved in the binding of CTP and transition-state stabilization.
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PMID:The role of histidine residues in the HXGH site of CTP:phosphocholine cytidylyltransferase in CTP binding and catalysis. 969 23

The effects of [Arg(0),Trp(5),Leu(8)]-BK (cod [Arg(0)]BK) on vascular preparations from branches of the cod celiac artery and on longitudinal smooth muscle preparations from the cod intestine were investigated. Cod [Arg(0)]BK (3 x 10(-8) M) caused a relaxation of the celiac artery precontracted with adrenaline. The relaxation was abolished by the cyclooxygenase inhibitor indomethacin, suggesting that the effect is mediated through the release of prostaglandins, but there was no evidence for the involvement of leukotrienes or nitric oxide in the response. In the intestinal preparations, cod [Arg(0)]BK produced concentration-dependent contractions (pD(2) = 8.28 +/- 0.16). Experiments with N-terminally and C-terminally truncated analogs and with alanine-substituted analogs of cod [Arg(0)]BK demonstrate that the central amino acid Gly(4) and the C-terminal amino acids Leu(8) and Arg(9) are the most important in determining the conformation of the peptide that interacts with the receptor. The results indicate that the ligand binding properties of the cod BK receptor are considerably different from the receptor present in trout tissues and may resemble those of the mammalian B(2) receptor more closely.
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PMID:Effects of cod bradykinin and its analogs on vascular and intestinal smooth muscle of the Atlantic cod, Gadus morhua. 1144 29


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