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)

The history of a 45-year-old male type 1 diabetic patient is presented. At the age of 29 years, he was diagnosed to have an autoimmune hepatitis with incipient liver cirrhosis. Five years later, a successful liver/pancreas transplantation was performed. Eighteen months later, however, pancreatic insufficiency occurred due to thrombosis of the pancreatic graft. Besides these conditions, iron deficiency, pernicious anemia, and autoimmune gastritis were also diagnosed. Serum parietal cell antibodies (PCA) and intrinsic factor antibodies (AIF) were positive. At 45, this patient was found to have a gastric carcinoid tumor. The clinical importance of PCA is discussed with regard to chronic atrophic gastritis and pernicious anemia, which both predispose toward gastric carcinoid tumors. Autoimmune type 1 diabetic patients who have a high prevalence of PCA should be screened for gastric autoimmune manifestations and tumors, as the history of this patient illustrates.
 ...
PMID:Autoimmune hepatitis, autoimmune gastritis, and gastric carcinoid in a type 1 diabetic patient: a case report. 1095 74

During the last decades efforts regarding dietary iron supply focused mostly on the prevention of deficiencies, especially during growth and pregnancy. Correspondingly, homeostatic mechanisms increase intestinal iron absorption in iron deficiency, but its downregulation at high intake levels seems insufficient to prevent accumulation of high iron stores at high intake. There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects. Chronic iron excess, e.g. in primary and secondary hemochromatosis, may lead to hepatic fibrosis, diabetes mellitus and cardiac failure. Chronic intake of 50-100 mg Fe/day of highly bioavailable iron with home-brewed beer in sub-Saharan Africans lead to cirrhosis and diabetes. Applying a safety factor of 2 would lead to an upper safe level of 25-50 mg Fe/day for this endpoint of conventional iron toxicity. However, beyond this kind of damage iron is known to catalyze the generation of hydroxyl radicals from superoxide anions and to increase oxidative stress which, in turn, increases free iron concentration. This self-amplifying process may cause damage to lipid membranes and proteins, which relates radical generation and organ damage after ischemia-reperfusion events to available free iron in clinical and experimental settings. Correspondingly, epidemiological studies as well as observations in heterozygotes for hereditary hemochromatosis suggest that the risk of atherosclerosis and acute myocardial infarction is related to body iron stores, though there is conflicting epidemiological evidence as well. The most recent and best controlled studies, however, support the hypothesis that iron stores are related to cardiovascular risk. Iron-amplified oxidative stress may also increase DNA damage, oxidative activation of precancerogens and support tumor cell growth. This is supported by experimental, clinical and epidemiological observations. Due to these mechanisms high iron stores may present a health hazard. Though this has not been finally proven, available evidence strongly recommends not to increase iron intake beyond physiological requirements. To avoid iron deficiency symptoms, on the other hand, care must be taken to meet recommended daily intake.
 ...
PMID:Safety aspects of iron in food. 1142

Pleomorphic adenomas gene-like 2 (PLAGL2) protein containing seven C(2)H(2) zinc finger motifs exhibits DNA binding and transcriptional activation activity and is expressed in response to hypoxia or iron deficiency. To identify the target genes of PLAGL2, we transfected mouse PLAGL2 cDNA into Balb/c3T3 fibroblasts and neuroblastoma Neuro2a cells. Both cells were induced to undergo apoptosis by the expression of PLAGL2 as judged by assays of TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling), DNA fragmentation, propidium iodide staining, and the binding of annexin V to the cell surface. The treatment of the cells with an iron chelator, desferrioxamine, resulted in the induction of apoptosis with a concomitant accumulation of PLAGL2 in the nucleus. The expression of PLAGL2 in Balb/c3T3 cells led to the mRNA expression of a proapoptotic factor, Nip3, which can dimerize with Bcl-2. Nip3 mRNA was also induced in desferrioxamine-treated cells. Furthermore, the Nip3 promoter containing a hypoxia-responsive element was activated by PLAGL2, independent of hypoxia-inducible factor-1 (HIF-1). The transfection of antisense oligonucleotide to mouse Nip3 mRNA into PLAGL2-expressing cells led to a decrease in apoptotic cells compared with sense oligonucleotide-transfected cells. Despite the activation of DNA-HIF-1 binding activity under hypoxic conditions, neither an accumulation of HIF-1 alpha nor the activation of HIF-1 was observed following the expression of PLAGL2. These results indicate that PLAGL2 is located downstream of HIF-1 and suggest that PLAGL2 functions as a tumor suppressor in association with HIF-1.
 ...
PMID:A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis. 1183 86

Endoscopy is indicated for the evaluation of unexplained iron deficiency to rule out neoplasia. Iron deficiency is common in postgastrectomy patients. The endoscopic yield for significant pathology in these patients is unknown but is expected to be lower than for other iron-deficient groups. A retrospective case-control study with 2:1 matching was performed comparing iron-deficient patients (ferritin < or = 50 microg/liter) having prior Billroth I or Billroth II gastrectomy to matched iron-deficient controls with normal gastric anatomy. There were 52 postgastrectomy patients and 113 controls. There were no significant differences between postgastrectomy patient and controls in age, gender ratio, or laboratory test results, with the exception of MCV (88.9 +/- -1.1 vs 86.0 +/- -0.8, mean +/- SEM, P = 0.048) There were no significant differences in the prevalence of upper gastrointestinal pathology (24.5% vs 29.2%), large (>1 cm) colon polyps (8.3% vs 5.2%), or the presence of any adenomatous colon polyp (28.6% vs 18.9%). There were no malignancies. In conclusion, prevalence of clinically significant pathology is similar for postgastrectomy and nonpostgastrectomy iron-deficient patients. Endoscopic evaluation of iron deficiency should not differ in postgastrectomy patients.
 ...
PMID:Endoscopic evaluation of patients with partial gastrectomy and iron deficiency. 1191 53

Iron deficiency is common at presentation in colorectal cancer. Testing for it may complement other screening tests such as faecal occult blood testing and sigmoidoscopy. We therefore examined the feasibility of offering iron deficiency testing to patients in a primary care setting in the UK, offering testing to all 1240 patients aged 55-74 years in one general practice in South Wales, UK. Patients with abnormal results were assessed and offered further investigations. Five hundred and fifty-one people (44.4%) attended for iron deficiency blood tests, of whom 26 patients (4.7%) were iron deficient and offered endoscopic assessment. This identified two cases of benign neoplasia amenable to treatment and no cases of cancer. Iron deficiency testing in a screening context appeared feasible although uptake may be low.
 ...
PMID:Using iron deficiency tests for colorectal cancer screening: a feasibility study in one UK general practice. 1530 48

Ulcerative colitis (UC) patients frequently require iron supplementation to remedy anemia. The impact of systemic iron supplementation (intraperitoneal injection) on UC-associated carcinogenesis was assessed in mice subjected to cyclic dextran sulfate sodium (DSS) treatment and compared with dietary iron enrichment. Systemic iron supplementation, but not a twofold iron diet, remedied iron deficiency as indicated by the histochemical detection of splenic iron stores. A twofold iron diet, but not systemic iron, increased iron accumulation in colonic luminal contents, at the colonic mucosal surface, and in superficial epithelial cells. Colitis-associated colorectal tumor incidence after 15 DSS cycles was not affected by systemic iron (2/28; 7.1%) compared to nonsupplemented controls (4/28; 14.1%) but was significantly increased by the twofold iron diet (24/33; 72.7%) (P < 0.001). Mechanistic study revealed that systemic iron had no effect on DSS-induced inflammation, or colonic iNOS and COX-2 protein levels, compared to controls. Systemic iron supplementation for 16 weeks replenished splenic iron in a spontaneous colitis model (interleukin-2-deficient mice) and significantly reduced colonic inflammation compared to interleukin-2 (-/-) controls without increasing hyperplastic lesions. These results suggest that iron supplemented systemically could be used to remedy anemia in UC patients without exacerbating inflammation or enhancing colon cancer risk. These findings need to be verified in clinical studies.
 ...
PMID:Systemic iron supplementation replenishes iron stores without enhancing colon carcinogenesis in murine models of ulcerative colitis: comparison with iron-enriched diet. 1584 5

Anemia is a frequent reason for seeking medical care in Internal Medicine. It is not a diagnosis, but rather a symptom that needs to be investigated in order to find an etiology. In a retrospective review of 100 cases of anemia, the cause was found in 86 % of cases. The etiologic profile was varied. Iron deficiency remained by far the most frequent cause seen in 47% of case. Other etiologies have been found such as neoplasm in 13 % of cases, chronic renal failure in 8% of cases and endocrinal cause in 5 % of cases. We recommend a diagnostic decision tree that provides a tool for rational and cost effective approach for anemia.
 ...
PMID:[Diagnostic strategy and management of anemia: a consensus from a detailed study of 100 patients followed in internal medicine]. 1588 18

Iron deficiency and tumor bleeding are common causes of anemia in cervical cancer. Anemia has a negative prognostic influence, and its correction is thought to improve prognosis; therefore, most patients are treated with either transfusion and/or erythropoietin. At present little is known about the value of iron stores replenishment to increase hemoglobin levels in this setting. Untreated cervical cancer patients with a hemoglobin <12 g/dL were randomized to intramuscular iron or to transfusion. Iron dose was calculated according to [weight (kg)x(15--actual Hb)x2.4]+500 and administered by injections of 200 mg daily. In both arms, patients who did not achieve at least 10 g/dL hemoglobin before or during chemoradiation were transfused. Patients received standard pelvic radiation plus six weekly doses of cisplatin. Hematic counts were performed before starting chemoradiation and weekly thereafter. Fifteen patients were studied; six were assigned to iron and nine to transfusion. Mean basal hemoglobin levels were 9.9 and 9.5 g/dL respectively. Total iron, saturation index, binding capacity, and ferritin were within normal limits, although there was a high variability among the patients. The mean total dose of iron administered was 1229 mg. Two weeks after randomization, hemoglobin increased to 10.9 and 10.2 g/dL respectively. At wk 1 of treatment and thereafter, levels were higher in the iron arm, in whom the values were close or higher than 12 g/dL (p=0.03). The median number of units transfused were 0 in the iron group and 2 in the transfusion (p=0.02) arm. Parenteral iron seems to be effective to increase hemoglobin in cervical cancer patients.
 ...
PMID:Anemia in cervical cancer patients: implications for iron supplementation therapy. 1596 79

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.
 ...
PMID:Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer. 1930 38

Iron deficiency affects 500 million people, yet the molecular role of iron in gene expression remains poorly characterized. In addition, the alterations in global gene expression after iron chelation remain unclear and are important to assess for understanding the molecular pathology of iron deficiency and the biological effects of chelators. Considering this, we assessed the effect on whole genome gene expression of two iron chelators (desferrioxamine and 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone) that have markedly different permeability properties. Sixteen genes were significantly regulated by both ligands, whereas a further 50 genes were significantly regulated by either compound. Apart from iron-mediated regulation of expression via hypoxia inducible factor-1 alpha, it was noteworthy that the transcription factor p53 was also involved in iron-regulated gene expression. Examining 16 genes regulated by both chelators in normal and neoplastic cells, five genes (APP, GDF15, CITED2, EGR1, and PNRC1) were significantly differentially expressed between the cell types. In view of their functions in tumor suppression, proliferation, and apoptosis, these findings are important for understanding the selective antiproliferative effects of chelators against neoplastic cells. Most of the genes identified have not been described previously to be iron-regulated and are important for understanding the molecular and cellular effects of iron depletion.
 ...
PMID:Iron chelator-mediated alterations in gene expression: identification of novel iron-regulated molecules that are molecular targets of hypoxia-inducible factor-1 alpha and p53. 2002 6


<< Previous 1 2 3 4 5 6 7 Next >>