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

Compromised renal function after renal allograft transplantation often results in anemia in the recipient. Molecular mechanisms leading to anemia during acute rejection are not fully understood; inadequate erythropoietin production and iron deficiency have been reported to be the main contributors. To increase our understanding of the molecular events underlying anemia in acute rejection, we analyzed the gene expression profiles of peripheral blood lymphocytes (PBL) from four pediatric renal allograft recipients with acute rejection and concurrent anemia, using DNA microarrays containing 9000 human cDNA clones (representing 7469 unique genes). In these anemic rejecting patients, an 'erythropoiesis cluster' of 11 down-regulated genes was identified, involved in hemoglobin transcription and synthesis, iron and folate binding and transport. Additionally, some alloimmune response genes were simultaneously down-regulated. An independent data set of 36 PBL samples, some with acute rejection and some with concurrence of acute rejection and anemia, were analyzed to support a possible association between acute rejection and anemia. In conclusion, analysis using DNA microarrays has identified a cluster of genes related to hemoglobin synthesis and/or erythropoeisis that was altered in kidneys with renal allograft rejection compared with normal kidneys. The possible relationship between alterations in the expression of this cluster, reduced renal function, the alloimmune process itself, and other influences on the renal transplant awaits further analysis.
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PMID:Molecular profiling of anemia in acute renal allograft rejection using DNA microarrays. 1249 5

Seventy-two healthy infants (37 males, 35 females) attending a private well baby clinic were enrolled in the study. Their mean birthweights and body weights at one year of age were 3,079 grams and 10 kilograms, respectively. Blood samples were drawn approximately on their first birthday for evaluating the iron status. Complete blood count, hemoglobin (Hb) typing and DNA analysis for common carrier status of thalassemia and hemoglobinopathis were also determined. According to the infants of serum ferritin, the patients were classified into 4 groups: group 1, iron deficiency anemia (Hb <11 g/dl and ferritin <12 ng/L) in 1 infants (1.4%); group 2, iron deficiency without anemia (Hb >11 g/dl and ferritin <12 ng/L) in 5 infants (6.9%); group 3, borderline iron depletion (ferritin 12-30 ng/L) in 39 infants (54.2%); group 4, iron sufficiency (ferritin >30 ng/L) in 27 infants (37.5%). The iron deficiency state emerged as 8.3 per cent (6/72). There was no significant difference of levels of Hb and mean corpuscular volume (MCV) among the infants with iron deficiency without anemia, borderline iron depletion and iron sufficiency. The results also revealed that 25 out of 72 (34.7%) infants were carriers of thalassemia and hemoglobinopathies. The carrier infants had significant lower Hb and MCV than those of the non-carrier infants with the p-values of 0.004 and 0.000, respectively; while their serum ferritin levels were not significantly different. Additionally, the association of carrier and iron deficiency state was further evaluated. The Hb and MCV among carrier infants with and without iron deficiency were not significantly different. Six infants with carrier state were found to have slightly decreased levels of Hb ranging from 10.3 to 10.9 g/dl with the ferritin ranging from 18.7 to 382.9 ng/L while the remainders had Hb of >11 g/dl. Therefore, 7 out of 72 (9.2%) infants had anemia (Hb <11 g/dl) which was caused by the carrier state of thalassemia and hemoglobinopathies (n=6) and iron deficiency anemia (n=1). The risk factors of iron deficiency status were associated with feeding regimen including continuation of breast feeding until one year of age without adequate haem iron supplement, exclusive formula feeding, inadequacy of solid food supplement with only one meal per day and excluding haem iron from animal liver without substitution. The infants with risk factors had significantly lower levels of serum ferritin (mean 14.1 +/- 1.7 ng/L) than those without risk factors (mean 31.9 +/- 1.9 ng/L) with a p-value of 0.000. In conclusion, adequate haem iron supplement in 3 meals of solid food is essential for the prevention of iron deficiency status in one-year-old infants.
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PMID:Iron status of one-year-old infants in a well baby clinic. 1254 80

Iron and oxygen are central to terrestrial life. Aqueous iron and oxygen chemistry will produce a ferric ion trillions of times less soluble than cell iron concentrations, along with radical forms of oxygen that are toxic. In the physiological environment, many proteins have evolved to transport iron or modulate the redox chemistry of iron that transforms oxygen in useful biochemical reactions. Only one protein, ferritin, evolved to concentrate iron to levels needed in aerobic metabolism. Reversible formation and dissolution of a solid nanomineral-hydrated, iron oxide is the main function of ferritin, which additionally detoxifies excess iron and possibly dioxygen and reactive oxygen. Ferritin is a large multifunctional, multisubunit protein with eight Fe transport pores, 12 mineral nucleation sites and up to 24 oxidase sites that produce mineral precursors from ferrous iron and oxygen. Regulation of ferritin synthesis in animals uses both DNA and mRNA controls and genes encoding two types of related subunits with: 1) catalytically active (H) or 2) inactive (L) oxidase sites. Ferritin with varying H/L ratios is related to cell-specific iron and oxygen homeostasis. H-ferritin oxidase activity accelerates rates of iron mineralization in ferritins and, in animals, ferritin produces H(2)O(2) as a byproduct. Properties of ferritin mRNA and ferritin protein pore structure are new targets for manipulating iron homeostasis. Recent observations of the high bioavailability of iron in soybean ferritin and efficient utilization of soybean and ferritin iron by iron-deficient animals, and of soybean iron by humans with borderline deficiency, indicate a role for ferritin in managing global iron deficiency in humans.
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PMID:Ferritin: at the crossroads of iron and oxygen metabolism. 1273 Apr 63

The Philadelphia chromosome-negative chronic myeloproliferative disorders (CMPD), polycythemia vera (PV), essential thrombocythemia (ET) and chronic idiopathic myelofibrosis (IMF), have overlapping clinical features but exhibit different natural histories and different therapeutic requirements. Phenotypic mimicry amongst these disorders and between them and nonclonal hematopoietic disorders, lack of clonal diagnostic markers, lack of understanding of their molecular basis and paucity of controlled, prospective therapeutic trials have made the diagnosis and management of PV, ET and IMF difficult. In Section I, Dr. Jerry Spivak introduces current clinical controversies involving the CMPD, in particular the diagnostic challenges. Two new molecular assays may prove useful in the diagnosis and classification of CMPD. In 2000, the overexpression in PV granulocytes of the mRNA for the neutrophil antigen NBI/CD177, a member of the uPAR/Ly6/CD59 family of plasma membrane proteins, was documented. Overexpression of PRV-1 mRNA appeared to be specific for PV since it was not observed in secondary erythrocytosis. At this time, it appears that overexpression of granulocyte PRV-1 in the presence of an elevated red cell mass supports a diagnosis of PV; absence of PRV-1 expression, however, should not be grounds for excluding PV as a diagnostic possibility. Impaired expression of Mpl, the receptor for thrombopoietin, in platelets and megakaryocytes has been first described in PV, but it has also been observed in some patients with ET and IMF. The biologic basis appears to be either alternative splicing of Mpl mRNA or a single nucleotide polymorphism, both of which involve Mpl exon 2 and both of which lead to impaired posttranslational glycosylation and a dominant negative effect on normal Mpl expression. To date, no Mpl DNA structural abnormality or mutation has been identified in PV, ET or IMF. In Section II, Dr. Tiziano Barbui reviews the best clinical evidence for treatment strategy design in PV and ET. Current recommendations for cytoreductive therapy in PV are still largely similar to those at the end of the PVSG era. Phlebotomy to reduce the red cell mass and keep it at a safe level (hematocrit < 45%) remains the cornerstone of treatment. Venesection is an effective and safe therapy and previous concerns about potential side effects, including severe iron deficiency and an increased tendency to thrombosis or myelofibrosis, were erroneous. Many patients require no other therapy for many years. For others, however, poor compliance to phlebotomy or progressive myeloproliferation, as indicated by increasing splenomegaly or very high leukocyte or platelet counts, may call for the introduction of cytoreductive drugs. In ET, the therapeutic trade-off between reducing thrombotic events and increasing the risk of leukemia with the use of cytoreductive drugs should be approached by patient risk stratification. Thrombotic deaths seem very rare in low-risk ET subjects and there are no data indicating that fatalities can be prevented by starting cytoreductive drugs early. Therefore, withholding chemotherapy might be justifiable in young, asymptomatic ET patients with a platelet count below 1500000/mm(3) and with no additional risk factors for thrombosis. If cardiovascular risk factors together with ET are identified (smoking, obesity, hypertension, hyperlipidemia) it is wise to consider platelet-lowering agents on an individual basis. In Section III, Dr. Gianni Tognoni discusses the role of aspirin therapy in PV based on the recently completed European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study, a multi-country, multicenter project aimed at describing the natural history of PV as well as the efficacy of low-dose aspirin. Aspirin treatment lowered the risk of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke (relative risk 0.41 [95% CI 0.15-1.15], P =.0912). Total and cardiovascular mortality were also reduced by 46% and 59%, respectively. Major bleedings were slightly increased nonsignificnsignificantly by aspirin (relative risk 1.62, 95% CI 0.27-9.71). In Section IV, Dr. Giovanni Barosi reviews our current understanding of the pathophysiology of IMF and, in particular, the contributions of anomalous megakaryocyte proliferation, neoangiogenesis and abnormal CD34(+) stem cell trafficking to disease pathogenesis. The role of newer therapies, such as low-conditioning stem cell transplantation and thalidomide, is discussed in the context of a general treatment strategy for IMF. The results of a Phase II trial of low-dose thalidomide as a single agent in 63 patients with myelofibrosis with meloid metaplasia (MMM) using a dose-escalation design and an overall low dose of the drug (The European Collaboration on MMM) will be presented. Considering only patients who completed 4 weeks of treatment, 31% had a response: this was mostly due to a beneficial effect of thalidomide on patients with transfusion dependent anemia, 39% of whom abolished transfusions, patients with moderate to severe thrombocytopenia, 28% of whom increased their platelet count by more than 50 x 10(9)/L, and patients with the largest splenomegalies, 42% of whom reduced spleen size of more than 2 cm.
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PMID:Chronic myeloproliferative disorders. 1463 83

Erythropoiesis is the process in which new erythrocytes are produced. These new erythrocytes replace the oldest erythrocytes (normally about one percent) that are phagocytosed and destroyed each day. Folate, vitamin B12, and iron have crucial roles in erythropoiesis. Erythroblasts require folate and vitamin B12 for proliferation during their differentiation. Deficiency of folate or vitamin B12 inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes erythroblast apoptosis, resulting in anemia from ineffective erythropoiesis. Erythroblasts require large amounts of iron for hemoglobin synthesis. Large amounts of iron are recycled daily with hemoglobin breakdown from destroyed old erythrocytes. Many recently identified proteins are involved in absorption, storage, and cellular export of nonheme iron and in erythroblast uptake and utilization of iron. Erythroblast heme levels regulate uptake of iron and globin synthesis such that iron deficiency causes anemia by retarded production rates with smaller, less hemoglobinized erythrocytes.
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PMID:New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. 1518 15

Hereditary sideroblastic anemia is a very rare disease recessive and X-linked that affect heme biosynthesis by deficit or decreased of delta aminolevulinic acid synthase (ALAS) activity. We report a case of a six-month-old boy, admitted in the hospital for anemic syndrome. The hemogram showed anemia (hemoglobin: 4.5 g/dL), frankly hypochronic microcytic and a regenerated (mean corpuscular hemoglobin concentration: 26 g/dL, mean cell volume: 53 fl, reticulocytes: 10 x 10(9)/L) with red cells morphologic disorders in smears (anisopoikylocytosis) without attack of the other lineages; white blood cells: 11 x 10(9)/L (neutrophils: 64% and lymphocytes: 35%); platelets: 350 x 10(9)/L. Examination of bone marrow showed an important erythroid hyperplasia (about 69%) with dyserythropoiesis. Perls stain revealed intense siderosis with 90% of ringed sideroblasts and a large number of siderocytes. Exploration of ALAS2 and ABC7 genes on the DNA of the infant was not found abnormalities. Treatment with pyridoxine corrects moderately the anemia. By the way, we proposed to remind that iron deficiency, inflammatory syndrome and thalassemia are the common microcytic anemia. However, it's mandatory to explore other causes if diagnosis is not solved.
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PMID:[Hereditary sideroblastic anemia: a rare diagnosis]. 1521 71

Heme, the major functional form of iron, is synthesized in the mitochondria. Although disturbed heme metabolism causes mitochondrial decay, oxidative stress, and iron accumulation, all of which are hallmarks of ageing, heme has been little studied in nutritional deficiency, in ageing, or age-related disorders such as Alzheimer's disease (AD). Biosynthesis of heme requires Vitamin B(6), riboflavin, biotin, pantothenic acid, and lipoic acid and the minerals zinc, iron, and copper, micronutrients are essential for the production of succinyl-CoA, the precursor for porphyrins, by the TCA (Krebs) cycle. Only a small fraction of the porphyrins synthesized from succinyl-CoA are converted to heme, the rest are excreted out of the body together with the degradation products of heme (e.g. bilirubin). Therefore, the heme biosynthetic pathway causes a net loss of succinyl-CoA from the TCA cycle. The mitochondrial pool of succinyl-CoA may limit heme biosynthesis in deficiencies for micronutrients (e.g. iron or biotin deficiency). Ageing and AD are also associated with hypometabolism, increase in heme oxygenase-1, loss of complex IV, and iron accumulation. Heme is a common denominator for all these changes, suggesting that heme metabolism maybe altered in age-related disorders. Heme can also be a prooxidant: it converts less reactive oxidants to highly reactive free radicals. Free heme has high affinity for different cell structures (protein, membranes, and DNA), triggering site-directed oxidative damage. This review discusses heme metabolism as related to metabolic changes seen in ageing and age-related disorders and highlights the possible role in iron deficiency.
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PMID:Heme, iron, and the mitochondrial decay of ageing. 1523 Dec 38

Iron deficiency is the most widespread micronutrient deficiency world-wild, and is estimated to affect about 30% of the world population. To increase the iron content of rice in Chinese, the 764 bp cDNA of ferritin gene was cloned from soybean (Phaseolus limensis), and constructed between the 1 353 bp rice glutelin GluB-1 promoter and NOS terminator in a binary vector pCAMIBA1301. The constructed pYF1067 vector was introduced into Agrobacterium strain EHA105, and used for transformation of the primary callus derived from immature embryos of a high-yielding rice ( Oryza sativa L. ssp. japonica) variety Wuxiangjin 9. Under the selection on hygromycin-containing medium, seventeen independent transgenic rice lines, total more than 80 transgenic plants, were finally regenerated, and most of these transgenic rice plants grew normally. PCR and Southern blot analysis of total DNA from primary transformants confirmed that one to three copies of the transgenes integrated into the genome of most of the transgenic plants, and they could be stably transmitted into the progeny of the transgenic rice. Northern blot analysis showed that the ferritin gene could specifically express in the endosperm of transgenic rice with high level, while no or low expression in leaves. The expression level varied among different independent transgenic rice plants. There was a significant effect of the high-expression of ferritin on the increased iron content in transgenic rice, the iron content in the milling rice of transgenic rice was up to 64% higher than that of the untransformed wild-type plant, whereas no significant alteration of the zinc level occurred between these two type rice plants.
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PMID:[Endosperm-specific expression of the ferritin gene in transgenic rice (Oryza sativa L.) results in increased iron content of milling rice]. 1547 15

Although alpha0-thalassemia (thal) defects are not very frequent in the Iranian population, Hb H disease does occur in the country. We have analyzed the alpha gene cluster of 13 patients showing the presence of Hb H to establish the molecular background of this disease in southwest Iran (Shiraz and Hormozgan provinces). Using gap-polymerase chain reaction (gap-PCR) and direct DNA sequencing we have found the --MED-I deletion, the polyadenylation signal (poly A) mutations alphaT-Saudi alpha and alphaT-Turkish alpha and Hb Constant Spring (Hb CS) in association with the common -alpha3.7 deletion. This study has revealed that: 1) at least six genotypes are responsible for Hb H disease in the area: .-alpha3.7/ --MED-I; -alpha3.7/alphaT-Saudi alpha; alphaT-Saudi alpha/alphaT-Saudi alpha; alphaCSalpha/--MED-I; --MED-I/alphaT-Turkish alpha; and the atypical forms of Hb H disease -alpha3.7/alphaCSalpha. 2) The molecular background of Hb H disease in the southwest area of Iran is more similar to the Mediterranean type than to the Southeast Asian. 3) Hb Bart's hydrops fetalis syndrome and mild, intermediate or severe postnatal Hb H disease conditions can be expected, but at a relatively low incidence. 4) The diagnostic flowchart for patients with microcytic hypochromic anemia should include iron deficiency, beta-thal, alpha+- and alpha0-thal analyses.
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PMID:Molecular basis of Hb H disease in southwest Iran. 1576 54

In order to overcome the defects of difficult gene operations in low-copy suicide plasmid pCVD442, Gateway technology was applied in the construction process of recombinant plasmid for gene knockout in this study. With this improved knockout system, we inactivated sitC gene, which is associated with iron transport in Shigella flexneri 2a strain 301, to yield the mutant, MTS. The functional detection of the mutant was performed at the level of culture medium, cell and animal experiment, respectively. The gene expression profiles were compared with DNA microarray between the mutant and the wild type under iron-restricted conditions. The results showed that MTS grew obviously less well than the wild-type strains in L broth containing 150 micromol/L iron chelator DIP (2,2'-dipyridyl). Addition of iron or manganese to the cultures stimulated the growth of MTS to wild-type levels in rich culture medium. In either the experiment on the ability of intracellular multiplication and cell-to-cell spread in HeLa and U937 cell lines, or the experiment on keratoconjunctivitis in guinea pigs, MTS showed no obvious changes in virulence compared with the parental strain Sf301. When 65 micromol/L DIP was added to the cultured HeLa cells, the ability of intracellular multiplication of MTS reduced about 51.6% as compared with that of Sf301. The analysis of expression profiles under iron-limited condition showed that MTS was more sensitive for the change of iron deficiency than Sf301. There are 106 more up-regulated genes in MTS than in wild-type strains, which are involved in membrane transportation, amino acid metabolism and uncategorized function genes, while down-regulated genes are mainly involved in energy and carbohydrate metabolism. Under low iron conditions, the expression levels of known iron-transport associated genes generally increased. Additionally, the number of these genes and their increase amplitude in MTS are more than those in Sf301. Together, these results confirmed that Sit iron-transport system is important for the growth of Shigella.
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PMID:Construction, detection and microarray analysis on the Shigella flexneri 2a sitC mutant. 1609 55


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