Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a 32-year-old woman with an ulcer that had persisted for more than 13 months despite treatment with the H2 blocker ranitidine, the latter was replaced by the H+K(+)-ATPase inhibitor omeprazole. Treatment with omeprazole also failed to bring about healing of the ulceration which, at times, measured up to 10 cm in diameter. On account of a hemorrhage from the ulcer, a Billroth II resection of the stomach had to be performed. The histological work-up of the surgical specimen confirmed the tentative diagnosis of a secondary ulceration in underlying eosinophilic gastritis established on the basis of the work-up of biopsy material obtained from the ulcer. The reason for the failure of the lesion to respond to the H2 blocker or omeprazole in this case was a diffuse infiltration of the antral wall with eosinophilic granulocytes, and the resulting secondary persistent ischaemic ulceration.
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PMID:Failure of ranitidine and omeprazole treatment in eosinophilic gastritis with ulceration. 176 63

Autoantibodies in the sera of patients with pernicious anemia recognize, in addition to the alpha subunit of the gastric H+/(+)-ATPase, an abundant gastric microsomal glycoprotein of apparent Mr 60,000-90,000. Herein we have colocalized the glycoprotein and the alpha subunit of the gastric H+/K(+)-ATPase to the tubulovesicular membranes of the parietal cell by immunogold electron microscopy. Moreover, the glycoprotein and the alpha subunit were coimmunoprecipitated, and copurified by immunoaffinity chromatography, with an anti-glycoprotein monoclonal antibody. The pig glycoprotein was purified by chromatography on tomato lectin-Sepharose, and five tryptic peptides from the purified glycoprotein were partially sequenced. The complete amino acid sequence, deduced from the nucleotide sequence of overlapping cDNA clones, showed 33% similarity to the sequence of the beta subunit of the pig kidney Na+/K(+)-ATPase. We therefore propose that the 60- to 90-kDa glycoprotein autoantigen is the beta subunit of the gastric H+/K(+)-ATPase and that the alpha and beta subunits of the proton pump are major targets for autoimmunization in autoimmune gastritis.
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PMID:The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a beta subunit of the gastric H+/K(+)-ATPase (proton pump). 197 21

Autoimmune gastritis, induced by day-3 thymectomy of BALB/c mice, is a destructive CD4+ T cell-mediated disease characterized by leukocyte infiltrates in the gastric mucosa, loss of parietal and chief cells and anti-gastric H/K ATPase autoantibodies. Our previous studies have indicated that a T cell response to the H/K ATPase beta subunit is required for the onset of autoimmune gastritis (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419). To determine whether a response to the beta subunit autoantigen is alone sufficient to induce autoimmunity, or whether other tissue-specific factors are required, we have generated transgenic mice expressing the gastric H/K ATPase beta subunit in beta islet cells of the pancreas (RIP-H/K beta). RIP-H/K beta mice developed autoimmune gastritis and insulitis after day-3 thymectomy. Significantly, insulitis, observed as a peri-islet infiltrate, was only detected in thymectomized mice with autoimmune gastritis. There was no apparent immune destruction of the pancreas as insulitis did not progress to invasion of the islets or diabetes. Double transgenic mice, expressing the gastric H/K ATPase beta subunit in the thymus and in the pancreas, were protected from both gastritis and insulitis after day-3 thymectomy. Therefore, insulitis in the RIP-H/K beta mice appears to be dependent on a T cell response to the H/K ATPase beta subunit. This is the first example where an organ-specific initiating autoantigen has been expressed in another peripheral tissue. Autoimmune destruction in the stomach, but not the pancreas, indicates that tissue-specific factors play a fundamental role in the development of organ-specific autoimmunity.
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PMID:Expression of a gastric autoantigen in pancreatic islets results in non-destructive insulitis after neonatal thymectomy. 758 46

Helicobacter pylori is a major cause of gastritis and an important factor in duodenal ulcer relapse. Eradication of H. pylori has usually been achieved by triple therapy, a combination of bismuth salts and two antibiotics. The disadvantage of these regimens is the large number of tablets and the high incidence of side effects. A new H+,K(+)-ATPase inhibitor, lansoprazole (LPZ), has a strong acid inhibitory effect and an anti-H. pylori effect in vitro. These dual effects have an advantage for the eradication of H. pylori by LPZ alone or by a combination of LPZ and antibiotics. In this study, we investigated an anti-H. pylori effect of LPZ alone and LPZ plus low-dose amoxicillin and the relation between the status of H. pylori colonization and the endoscopic healing stage. LPZ monotherapy suppressed H. pylori but did not eradicate it. LPZ plus low-dose amoxicillin dual therapy eradicated H. pylori in 45.5% of patients with gastric ulcer disease. However, this rate is not satisfactory for eradication therapy. The optimal dosage and duration of treatment need to be specified. A high rate of healing to the endoscopic S2 stage was achieved by eradication of H. pylori and the recurrence of gastric ulcer was suppressed in patients in whom H. pylori was eradicated. The eradication of H. pylori may change the natural course of gastric ulcer disease as it does in duodenal ulcer disease.
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PMID:Lansoprazole versus lansoprazole plus amoxicillin treatment for eradication of Helicobacter pylori in patients with gastric ulcer. 759 22

Based on clinical studies, a negative association between Helicobacter pylori and autoimmune corpus gastritis is described. In the present investigation of an unselected population of 1461 adults we can state, however, that there exists a relationship between H. pylori infection and the development of gastric corpus autoimmunity. As confirmation for the gastric autoantibody development through molecular mimicry, a high homology (72% in 25 amino acid overlap) between the beta subunit of H. pylori urease and that of H + K + ATPase, the gastric parietal cell autoantigen, was revealed.
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PMID:Association of Helicobacter pylori and gastric autoimmunity: a population-based study. 759 5

Human sera from autoimmune gastritis patients containing autoantibodies to gastric parietal cells were analyzed by immunological methods. Enzyme linked immuno-sorbent assay demonstrated that all nine sera reacted with pig gastric vesicles enriched in H+/K(+)-ATPase (gastric proton pump). Immunoblotting experiments indicated that the alpha subunit of the H+/K(+)-ATPase was the major antigen in the vesicles with two of the sera reacting strongly. We further characterized the specificity of the antibodies using partial sequences of the pig alpha subunit fused with truncated TrpE (anthranilate synthase). The antibodies from autoimmune gastritis patients reacted differently to the two fusion proteins (Met-1 to Ala-79, and Arg-606 to Ile-964), indicating that each patient sera contains a mixture of autoantibodies recognizing different epitopes with variable contents.
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PMID:Characterization of human autoantibodies reactive to gastric parietal cells. 767 90

Autoimmune gastritis, a CD4+ T cell-mediated organ-specific autoimmune disease, can be induced by thymectomy of neonatal, but not of older, BALB/c mice. Here we have shown that autoimmune gastritis can also be induced in 6-8-week-old BALB/c mice by thymectomy combined with a single dose of cyclophosphamide (300 mg/kg). This treatment reduced the numbers of splenic T and B cells approximately 25-fold. However, by 8 days after treatment, the number of splenic lymphocytes had returned to normal adult levels. Approximately 50% of treated mice developed autoimmune gastritis after 10-12 weeks. These mice had mononuclear cellular infiltrates within the gastric mucosa and serum autoantibodies to the alpha and beta subunits of the gastric H+/K+ ATPase. Transgenic mice, expressing the gastric H+/K+ ATPase beta-subunit in the thymus (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419), did not develop autoimmune gastritis after the adult thymectomy/cyclophosphamide treatment. Thus a T cell response to the H+/K+ ATPase beta-subunit is likely to be required for the onset of gastritis. These observations suggest that pathogenic autoreactive T cells exist in the periphery of normal adult mice and that autoimmunity can be induced by the activation of these autoreactive T cells following transient lymphopenia. Cyclophosphamide-treatment of adult mice without thymectomy did not induce autoimmune gastritis, suggesting thymic regulation of these pathogenic T cells.
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PMID:Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia. 784 36

All available bafilomycins (A1, B1, C1 and D) inhibit and revert macroscopic vacuolization induced by Helicobacter pylori cell-free extracts. Bafilomycin A1 displays the highest activity, followed by bafilomycin B1, C1 and D. The different potency of bafilomycins correlates with their ability to inhibit the vacuolar-type ATPase (V-ATPase) and to dissipate the membrane pH gradient of intracellular acidic organelles. These results suggest that bafilomycins should be considered as possible therapeutic agents in the treatment of gastritis.
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PMID:Cell vacuolization induced by Helicobacter pylori: inhibition by bafilomycins A1, B1, C1 and D. 826 66

A 63-year-old woman was diagnosed as autoimmune gastritis by the presence of serum antibody against alpha-subunit of gastric H+,K(+)-ATPase. The patient did not have pernicious anemia, but showed achlorhydria, marked hypergastrinemia, enterochromaffin-like cell hyperplasia and an extremely high histidine decarboxylase activity in the gastric fundic mucosa. Intragastric acidification by infusion of hydrochloric acid via a nasogastric tube induced a transient reduction of serum gastrin level and fundic mucosal histidine decarboxylase activity. A marked increase in fundic mucosal histidine decarboxylase activity as well as hypergastrinemia appears to be the pathophysiologic response to achlorhydria caused by autoimmunity against gastric H+,K(+)-ATPase.
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PMID:Marked increase in fundic mucosal histidine decarboxylase activity in a patient with H+,K(+)-ATPase antibody-positive autoimmune gastritis. 828 44

Many autoimmune diseases are characterized by autoantibody reactivities to multiple cellular antigens. Autoantigens are commonly defined as targets of the autoimmune B cell response, but the role, if any, of these autoantigens in T cell-mediated autoimmune diseases is generally unknown. Murine experimental autoimmune gastritis is a CD4+ T cell-mediated organ-specific autoimmune disease induced by neonatal thymectomy of BALB/c mice. The murine disease is similar to human autoimmune gastritis and pernicious anemia, and is characterized by parietal and chief cell loss, submucosal mononuclear cell infiltrates, and autoantibodies to the alpha and beta subunits of the gastric H/K ATPase. However, the specificity of T cells that cause the disease is not known. To examine the role of the H/K ATPase in this T cell-mediated disease, transgenic mice were generated that express the beta subunit of the H/K ATPase under the control of the major histocompatibility complex class II I-Ek alpha promoter. We show that transgenic expression of the gastric H/K ATPase beta subunit specifically prevents the onset of autoimmune gastritis after neonatal thymectomy. In addition, thymocyte transfer experiments suggest that tolerance of pathogenic autoreactive T cells is induced within the thymus of the transgenic mice. We conclude that the beta subunit of the gastric H/K ATPase is a major T cell target in autoimmune gastritis and that thymic expression of a single autoantigen can abrogate an autoimmune response to multiple autoantigens.
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PMID:An autoimmune disease with multiple molecular targets abrogated by the transgenic expression of a single autoantigen in the thymus. 839 75


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