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)

Neuronal transferrin receptor protein expression is highly upregulated widely in CNS following iron deficiency. Using the medial habenular nucleus as a model of neuronal transferrin receptor mRNA expression, the present study examined 17-day-old rats subjected to variations in dietary iron. Changing the iron availability resulted in alterations in plasma and cerebrospinal fluid (CSF) levels of transferrin and iron. The iron-binding capacity of transferrin in CSF was exceeded in normal and iron-overloaded rats. In spite of a lowering of the concentration of brain iron by approximately 22% in iron-deficient rats, neuronal transferrin receptor mRNA was not affected when measured by quantitative densitometry. Brain iron and neuronal transferrin receptor mRNA expression was unaltered in iron overloaded rats. The absence of a rise in transferrin receptor mRNA during iron deficiency suggests that neuronal transferrin receptor mRNA expression is regulated by another mechanism than the post-transcriptional regulation mechanism, which has been attributed to cells of non-neural tissue.
 ...
PMID:Iron-independent neuronal expression of transferrin receptor mRNA in the rat. 1052 82

Reference values for two ferritin assays (Tina-quanta Ferritin, Enzymun, both Roche Diagnostics, Mannheim, Germany) were established (136 males and 139 females). To rule out inflammation as well as iron deficiency in the reference population, subjects with the C-reactive protein concentration < 5 mg/l, and zinc protoporphyrin < 40 micromol/mol heme and the soluble transferrin receptor < 3 mg/l were selected. Taking into account latent iron deficiency as well as hereditary hemochromatosis the 5-95 percentile range was as follows: male, 27-365 microg/l; female, 13-148 microg/l for Tina-quanta and 12-151 microg/l for Enzymun. The Tina-quanta Ferritin assay showed a very good correlation (r > or = 0.990) to Enzymun ferritin, Ferritin Abbott (Abbott Diagnostics, Delkenheim, Germany), N Latex Ferritin (Dade Behring, Marburg, Germany) and the Ferritin Chiron (Chiron Diagnostics, Fernwald, Germany). However, the slopes of the standard principal component method analysis were calculated to be between 1.03 (Enzymun) and 1.41 (N Latex Ferritin). For four assays the median recovery of the 3rd International Recombinant Ferritin Standard (NIBSC 94/572) measured by serial dilution was 89-109%. The N Latex Ferritin assay recovered half of the target values. Because of the good correlation with other assays, a matrix effect is likely. The question arises whether the manufacturers' agreement on the recombinant ferritin standard would harmonize ferritin measurement.
 ...
PMID:Reference values for a homogeneous Ferritin assay and traceability to the 3rd International Recombinant Standard for Ferritin (NIBSC code 94/572). 1053 31

A transfectant HeLa cell clone expressing HFE under the control of a tetracycline-repressible promoter was generated. HFE expression was fully repressed by the presence of doxycycline, while it was strongly induced by growth in the absence of doxycycline. HFE accumulation was accompanied by a large (approximately 10-fold) decrease in H- and L-ferritin levels, by a approximately 3-4-fold increase in transferrin receptor, and a approximately 2-fold increase in iron regulatory protein activity. These indices of cellular iron deficiency were reversed by iron supplementation complexes. The overexpressed HFE immunoprecipitated together with transferrin receptor, indicating a physical association which is the likely cause for the observed approximately 30% decrease in 55Fe-transferrin incorporation after 18 h incubation. In the HFE-expressing cells the reduction in transferrin-mediated iron incorporation was partially compensated by a approximately 30% increase in non-transferrin iron incorporation from 55Fe-NTA, evident after prolonged, 18 h, incubations. The findings indicate that HFE binding to transferrin receptor reduces cellular iron availability and regulates the balance between transferrin-mediated and non-transferrin-mediated cellular iron incorporation.
 ...
PMID:Overexpression of the hereditary hemochromatosis protein, HFE, in HeLa cells induces and iron-deficient phenotype. 1057 Oct 78

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. Liver disease resulting from iron toxicity is the major cause of death in HH. Hepatic iron loading in HH is progressive despite down-regulation of the classical transferrin receptor (TfR). Recently a human cDNA highly homologous to TfR was identified and reported to encode a protein (TfR2) that binds holotransferrin and mediates uptake of transferrin-bound iron. We independently identified a full-length murine EST encoding the mouse orthologue of the human TfR2. Although homologous to murine TfR in the coding region, the TfR2 transcript does not contain the iron-responsive elements found in the 3' untranslated sequence of TfR mRNA. To determine the potential role for TfR2 in iron uptake by liver, we investigated TfR and TfR2 expression in normal mice and murine models of dietary iron overload (2% carbonyl iron), dietary iron deficiency (gastric parietal cell ablation), and HH (HFE -/-). Northern blot analyses demonstrated distinct tissue-specific patterns of expression for TfR and TfR2, with TfR2 expressed highly only in liver where TfR expression is low. In situ hybridization demonstrated abundant TfR2 expression in hepatocytes. In contrast to TfR, TfR2 expression in liver was not increased in iron deficiency. Furthermore, hepatic expression of TfR2 was not down-regulated with dietary iron loading or in the HFE -/- model of HH. From these observations, we propose that TfR2 allows continued uptake of Tf-bound iron by hepatocytes even after TfR has been down-regulated by iron overload, and this uptake contributes to the susceptibility of liver to iron loading in HH.
 ...
PMID:Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. 1068 54

A complete data set (age, weight, diet and recent donation history; venous blood cell count, serum ferritin and soluble transferrin receptor concentrations and transferrin saturation; HFE genotype) was obtained from 113 male and 122 female blood donors. Progressive iron depletion and deficiency - most apparent from serum concentrations of soluble transferrin receptor divided by the logarithm of ferritin concentrations (the TfR-F index) - developed in men donating up to six times in 2 years, although the serum ferritin alone was also informative; however, no prediction could be made for those iron-depleted individuals who will develop iron deficiency after donation. Iron stores in the groups of donors with 'low-normal' haemoglobin (Hb) concentrations were indistinguishable from those in donors with higher Hb values, whereas donors failing the anaemia screen had reduced stores. This supports the UK policy of accepting donations from people whose Hb concentration is up to 0. 5 g/dl below the recommended European threshold. Women eating red meat once a week sustained higher ferritin concentrations, and the iron status of first-time women donors resembled that of men donating twice each year. Homozygosity for either HFE variant allowed greater iron retention in the face of regular donation, but among heterozygotes the findings were inconclusive.
 ...
PMID:A study of the iron and HFE status of blood donors, including a group who failed the initial screen for anaemia. 1069 78

The rat has been widely used as a model for the study of iron deficiency (ID), but the differences in the timing of development of humans and rats must be taken into account to derive appropriate conclusions from the animal model. This study was designed to evaluate the effects of dietary ID and iron excess on rat brain iron and the iron metabolism proteins, transferrin (Tf), transferrin receptor (TfR) and ferritin. The experimental design is developmentally sensitive and permits control of the timing as well as the duration of the nutritional insult. Iron-deficient and iron-supplemented (SU) rats between postnatal day (PND) 10 and 21, PND 21 and 35 and PND 10 and 35 were used to study the effects of early, late, and long-term iron deficiency and supplementation. Some ID rats were iron repleted between PND 21 and 35. These experiments demonstrated several new findings: 1) Early ID/SU (PND 10-21) altered brain iron, TfR, Tf and ferritin concentration in many regions different from those observed in the later period (PND 21-35). 2) Two weeks of iron repletion were adequate for correcting the overall Fe concentration of the brain and of individual brain regions, although larger amounts of iron were necessary to fully normalize iron and its regulatory proteins. 3) Long-term ID/SU resulted accordingly in the continued decrease or increase in brain iron concentration in some brain regions and not others. In conclusion, brain regions regulate their iron concentration in response to local needs when faced with alterations in systemic iron delivery.
 ...
PMID:Variations in dietary iron alter brain iron metabolism in developing rats. 1072 Jan 79

The serum transferrin receptor (sTR) as a marker of iron depletion was evaluated in two groups: 50 normal adults of both sexes living at sea level and 50 iron deficiency anemias (secondary to nutritional, gastrointestinal or gynecologic diseases). Mean values were 16.6 nmol/L (interval of reference 8.8 to 26.2), for controls, without variations related to age and sex, and 66.3 nmol/L (16.1 to 148.8) for anemic patients. Statistical analysis (receiver operating characteristics, ROC) determined an optimal reference interval of 8.8 to 25.8 nmol/L. Predictive values as a diagnostic tool were 97.5%, PV (+) and 97.7%, PV (-); diagnostic efficiency was 97.7%. In both controls and anemics it was observed: 1) an inverse relationship between sTR and serum ferritin (F) (r2 72%; p < 0.001); 2) wide variations of sTR when plasma hemoglobin (Hb) was < 100 g/L (r2 71%; p < 0.001); 3) values for the sTR/logarithm of serum ferritin ratio (sTR/F index) much higher in anemics (75.8) than in controls (9.6). In the former group, iron supplementation normalized sTR levels but did not change ferritin values. We conclude that sTR is a specific and sensitive index of functional iron deficiency and therefore a quick, accurate and non invasive quantitative parameter for the diagnosis of iron deficient erythropoiesis.
 ...
PMID:[Multiparametric analysis for the diagnosis of iron deficiency anemia]. 1075 13

Quality of life and achievements are impaired by unrecognised iron deficiency. The iron requirement of women during their child-bearing age is high and increases in pregnancy. The aim of this study was to determine the prevalence and risk factors for iron deficiency in young mothers under contemporary German life conditions. Between September 1997 and August 1998 the iron status of 507 mothers of one-year old children was assessed. The data was derived from venous blood and questionnaires. Besides conventional methods, the concentration of soluble transferrin receptor was used as leading indicator of iron status. 9.5% had cellular iron deficiency and 2.2% of all mothers had iron deficiency anemia. In addition to absence of school education non-German nationality, a high number of children and vegetarian food are risk factors for iron deficiency. In contrast, high alcohol intake and cigarette smoking are associated with a better iron status. Children of mothers with insufficient iron supply are also at higher risk of iron deficiency.
 ...
PMID:[Prevalence and risk factors of iron deficiency in young mothers]. 1081 46

Dietary copper (Cu) deficiency impairs both innate and acquired branches of immunity. Specific roles of Cu in the activation and effector activities of host-defense cells remain largely unknown. The effects of Cu status on effector activities of a monocytic cell line were investigated as an initial step in the elucidation of specific functions of Cu in phagocytic cells. Exposure of differentiating U937 human promonocytic cells to 5 micromol/L 2,3, 2-tetraamine (tet), a high affinity Cu chelator, for 4 d decreased cellular Cu by 62% without altering cellular Cu,Zn-superoxide dismutase (SOD) activity, Zn content, mitochondrial activity and protein synthesis. In contrast, Cu deficiency suppressed the respiratory burst activity and markedly compromised the ability of U937 cells to kill Salmonella. Similarly, treatment of RAW264.7 murine macrophages with 5 micromol/L tet decreased cell Cu by 78% and Cu,Zn-SOD activity by 15% and increased bacterial survival by 180%. The tet-induced impairment of respiratory burst and bactericidal activities was blocked in cultures supplemented with Cu, but not Zn or Fe. In addition, lipopolysaccharide (LPS)-induced secretion of the inflammatory mediators, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and prostaglandin E(2) (PGE(2)), was decreased by 30-60% in tet-treated U937 cells. Flow cytometric analysis of the surface antigens CD11b and CD71 showed that the suppressed activities of Cu-deficient cells were not due to an attenuation in the degree of differentiation or secondary iron deficiency. These data demonstrate that U937 cells provide a useful model for examining the biochemical roles of Cu in monocyte activity.
 ...
PMID:Copper deficiency suppresses effector activities of differentiated U937 cells. 1082 6

Vitamin A deficiency produces anemia and altered iron status. In this study with rats we tested two hypotheses regarding vitamin A deficiency: (1) that it impairs erythropoiesis, leading to an increased red cell turnover, and (2) that it inhibits the glycosylation of transferrin. Erythropoietic activity was assessed indirectly by determining the myeloid:erythroid ratio in bone marrow smears, the number of erythroid colonies in the red pulp of spleen, the blood reticulocyte index, and zinc protoporphyrin and plasma transferrin receptor concentrations. Transferrin glycosylation was assessed by measuring the sialic acid content of transferrin. The effects of vitamin A deficiency were compared with those of iron deficiency. Iron deficiency produced anemia and low iron levels in organs. Vitamin A deficiency produced low levels of plasma and hepatic retinol, and it induced decreased plasma total iron-binding capacity and raised iron levels in tibia and spleen. Short- but not long-term iron deficiency reduced the number of erythroid colonies in spleen; vitamin A deficiency had no influence. Neither iron nor vitamin A deficiency influenced the myeloid:erythroid ratio in bone marrow smears and the blood reticulocyte production. Plasma transferrin receptor and erythrocyte zinc protoporphyrin concentrations were not affected by vitamin A deficiency but increased with iron deficiency. Vitamin A deficiency did not stimulate erythrocyte breakdown, as indicated by unaltered plasma lactate dehydrogenase activity and reduced plasma total bilirubin levels. Both vitamin A and iron deficiencies raised the proportion of multiple sialylated transferrins in plasma. Thus, we have not found evidence that vitamin A deficiency affects erythropoiesis and erythrocyte turnover. The iron accumulation in spleen and bone marrow may be related to reduced iron transport due to inhibition of transferrin synthesis rather than inhibition of transferrin sialylation.
 ...
PMID:Indicators of erythrocyte formation and degradation in rats with either vitamin A or iron deficiency. 1082 45


<< Previous 1 2 3 4 5 6 7 8 9 10