Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric units in the glandular epithelium of the mouse stomach contain several types of continuously renewing epithelial cells. Acid-producing parietal cells are derived from a multipotent stem cell that also gives rise to mucus-producing pit cells and pepsinogen- and intrinsic factor-producing zymogenic cells. We used nucleotides -1035 to +24 of the mouse H+/K(+)-ATPase beta subunit gene (H+/K(+)-ATPase beta subunit-1035 to +24) to examine the consequences of expressing simian virus 40 T antigen (SV 40 TAg) in the normally rare, nonproliferating, short-lived pre-parietal cell progenitor. Light and electron microscopic morphologic studies plus multilabel immunohistochemical analyses of postnatal day (P) 14-80-day transgenic mice revealed that SV40 TAg produces a 50-70-fold amplification of pre-parietal cells which become the predominant cell type in gastric units. Differentiation to mature parietal cells is blocked, resulting in hypochlorhydria and an associated systemic iron deficiency. SV40 TAg-induced pre-parietal proliferation is accompanied by apoptosis. Examination of adult transgenic mice homozygous for p53 wild type or p53 null alleles established that the apoptosis occurs through a p53-independent pathway. H+/K(+)-ATPase beta subunit -1035 to +24/SV40 Tag is not expressed during differentiation of the zymogenic lineage. Nonetheless, P28-P80 transgenic mice exhibit an apparent block in the conversion of pre-zymogenic to zymogenic cells. This block appears to be quite specific: conversion of preneck to neck cells and neck to pre-zymogenic cells is not affected. Comparison of normal and transgenic mice that are p53+/+ or p53-/- confirmed that the loss of mature zymogenic cells is not dependent upon p53. Although H+/K(+)-ATPase beta subunit -1035 to +24 is not active in pit cell progenitors or their differentiated descendants, there is a 2-3-fold increase in mature pit cells in transgenic animals. Our findings (i) demonstrate an approach for amplifying and characterizing pre-parietal or other progenitor cell populations in gastric units, (ii) reveal an SV40 TAg-inducible, p53-independent apoptotic mechanism that operates in a committed epithelial progenitor cell, and (iii) provide a transgenic mouse model for defining factors that may mediate progression through specific points in the differentiation programs of the parietal and zymogenic cell lineages or that may influence decisions about allocation to the pit cell lineage.
 ...
PMID:Simian virus 40 T antigen-induced amplification of pre-parietal cells in transgenic mice. Effects on other gastric epithelial cell lineages and evidence for a p53-independent apoptotic mechanism that operates in a committed progenitor. 779 80

Pernicious anemia (PA) is a macrocytic anemia that is caused by vitamin B(12) deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis (ABG), whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling's test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are useful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weakness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease (40%) and other autoimmune disorders, such as diabetes mellitus (10%), as part of the autoimmune polyendocrine syndrome. PA is the end-stage of ABG. Long-standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
 ...
PMID:Pernicious anemia: new insights from a gastroenterological point of view. 2127 87