Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaemia was detected in housed lambs by clinical and haematological investigation. Conjunctival pallor was used as a clinical test for anaemia and the results indicate that this has high specificity (91 per cent to 95 per cent) and low sensitivity (53 per cent to 55 per cent). The haematological results indicated a non-regenerative anaemia with low packed cell volume, red blood cell count and haemoglobin. In a subset of lambs examined biochemically, anaemia was associated with low serum iron concentration and low serum iron binding: cobalt levels were within normal ranges and blood copper levels were slightly raised. At present it is unclear whether this is a primary or secondary iron deficiency.
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PMID:Anaemia in housed lambs. 833 79

Serum erythropoietin (Epo) levels are depressed in anemic AIDS patients relative to controls. The basis for abnormal regulation of Epo has not been defined. The hepatoma cell line Hep3B produces Epo in response to hypoxia and serves as a model for the study of Epo regulation. Hep3B cells are infectible with human immunodeficiency virus-1 (HIV-1) and were used as a model for evaluating potential direct effects of HIV on Epo expression. HIV-1 infected or transfected Hep3B cells produced Epo at significantly lower levels than uninfected Hep3B cells under low O2 conditions or following exposure to cobalt chloride. Epo production induced by hypoxia of HIV-1 infected Hep3B cells was depressed compared with non-HIV containing Hep3B cells when normalized for cell number, total cellular protein or albumin, but not depressed when normalized for alpha-fetoprotein production. The cellular levels of Epo mRNA were not diminished in the HIV-1+ Hep3B cells, indicating a probable posttranscriptional effect of HIV-1 on Epo production. Cellular protein production or secretion rates as measured by precipitable 3H-leucine were not affected by the presence of HIV-1. HIV-1 appeared to depress the production of Epo and some, but not all, other cellular proteins. These results suggest that impaired production of Epo may be a direct effect of HIV-1 infection possibly contributing to anemia in AIDS.
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PMID:HIV-1 suppresses erythropoietin production in vitro. 839 Mar 70

The 5'-flanking region of the human erythropoietin (Epo) gene contains a 0.14-kb sequence that is conserved in the Epo gene from mouse and located within a promoter that is activated under hypoxic conditions such as anemia. Using a fragment containing this sequence in DNA mobility shift assays, we found that specific DNA-binding proteins were induced in mouse kidney nuclei under anemic hypoxia. Using synthetic double-stranded oligonucleotides that contain this sequence, the essential binding site was defined to be the -40 to -20 region upstream of the transcription initiation site in the human Epo gene. By DNA affinity chromatography using a column with the immobilized 5'-flanking sequence, two inducible binding proteins with apparent molecular masses of 55 and 45 kDa were identified in the nuclei of mouse kidney and liver under anemic hypoxia. These binding proteins were also induced during cobalt exposure.
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PMID:Erythropoietin 5'-flanking sequence-binding protein induced during hypoxia and cobalt exposure. 848 13

This study aimed to investigate the influence of different forms of tissue hypoxia on the expression of the endothelin genes in kidneys and livers. Tissue hypoxia in rats was induced by five different manoeuvres, namely hypoxia (8% O2), functional anaemia (0.1% CO), haemorrhage (haematocrit, hct = 0.12), cobalt treatment (60 mg/kg) for 6 h each and renal artery stenosis (0.2-mm clips) for 2 days. Endothelin-1 (ET-1) mRNA levels in the kidneys were increased by 200% with renal artery stenosis, 70% by hypoxia, 50% by anaemia, 30% by CO, but were not changed by cobalt. ET-3 mRNA in the kidneys decreased during renal artery clipping and cobalt treatment and were not significantly changed under the other conditions. ET-2 mRNA was not detected in the kidneys and livers. The abundance of ET-1 in the livers of normoxic animals was about 15% of that found in the kidney. Hypoxia increased ET-1 mRNA by 200%, haemorrhage by 400%, whilst CO and cobalt did not change hepatic ET-1 gene expression. The abundance of ET-3 mRNA in the livers of normoxic animals was about 6% of that found in the kidneys. The expression of the ET-3 gene in the livers was decreased by CO, but was not changed by any of the other experimental conditions used. These findings suggest that hyoxaemia and tissue hypoxia are moderate stimuli for the expression of the ET-1 gene but not for the ET-3 gene in the kidney and more potent stimuli in the liver, whilst cobalt does not activate ET-1 gene expression in the kidneys nor the livers.
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PMID:Influence of hypoxia on hepatic and renal endothelin gene expression. 859 3

Between 1984-1994, 8 cases of MTSI (7 males and one female, between 24-53 years age) have been operated in our Department, representing 2% from all malignant gastrointestinal tumours. The pain as a result of the obstruction, followed by chronic blood loss with anemia and perforation, (4 patients operated in emergency) were the most frequent symptoms, the tumors being localised on jejunum (3) and ileum (5) with a diameter to 3-15 cm. Lymphatic (4), hepatic (2) and peritoneal (I) metastases were present. We performed a wide resection of the bowel and mesentery, including lymph nodes (in 4 cases with radical intention). Histopathological findings: 4 adenocarcinoma, 3 leiomyosarcoma and a lymphoma. Postoperative treatment was selective and consisted in polychemotherapy (PCT) and cobalt therapy (60Co). There was no postoperative mortality, two local recurrences in 6 month. Survival rate at 5 patients was 32 month. At 5 years were in life 2 leiomyosarcoma and 1 adenocarcinoma and at 7 yrs, 1 leiomyosarcoma and 1 adenocarcinoma.
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PMID:[Diagnostic and treatment problems in primary malignant tumors of the small intestine]. 909 Oct 80

The major research accomplishments of the author are described from the time of his PhD thesis work on the mechanism of cobalt polycythemia to the present day. His early work on the quest for the cell that produces erythropoietin (Epo) to his current work on oxygen sensing and signal transduction pathways involved in erythropoietin gene expression are reported. He describes his main research interest in the mechanism of cobalt polycythemia between 1954 and 1962 and his research on how hormones such as the glucocorticoids function in the regulation of erythropoiesis (1956-1962). His major findings during this period were the discovery that hydrocortisone and corticosterone stimulated erythropoiesis (1958) and that cobalt increased erythropoietin production in the isolated perfused dog kidney (1961). He describes how he was led astray in some of his early studies on the cells in the kidney that produce erythropoietin, because of the less-developed technology available to him at that time; and how in situ hybridization and other molecular biology techniques enabled him to confirm some of the earlier work in mice by other investigators that interstitial cells in the kidney were the site of production of erythropoietin in the primate. His work in the controversial area of the mechanism of the anemia of end-stage renal disease is described in detail, as it pertains to Epo deficiency and suppressed erythroid progenitor cell response to Epo. He also discusses his recent work on signal transduction pathways (hypoxia, nitric oxide, adenosine, and C kinase) in oxygen sensing and Epo gene expression.
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PMID:A quest for erythropoietin over nine decades. 959 46

Deficiency of any of the vitamins and minerals essential for normal erythropoiesis (haematinics), including iron, copper, cobalt, vitamins A, B12, B6, C, E, folic acid, riboflavin and nicotinic acid, may be associated with defective erythropoiesis and anaemia. Iron, vitamin B12 and folate are the haematinics for which deficiency states manifest most often clinically and are the focus of this review. The normal absorption of these haematinics and gastrointestinal causes of their deficiency are described. Investigations, including the use of homocysteine metabolite levels and new techniques such as serum transferrin receptor assays, and treatment of haematinic deficiency are discussed in detail.
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PMID:Review article: the diagnosis and treatment of haematinic deficiency in gastrointestinal disease. 1021 44

Our study aimed to investigate the influence of tissue hypo-oxygenation on the adrenomedullin (ADM) system in vivo. For this purpose, male Sprague-Dawley rats were exposed to normobaric hypoxia (8% oxygen) or to functional anemia [0.1% carbon monoxide (CO)] or to cobalt chloride (60 mg/kg) for 6 h. Messenger RNA levels for ADM and its receptor (ADM-R) were assessed in diverse organs by RNase protection assay. Additionally, ADM protein concentrations in these organs, as in plasma, were determined by a RIA. We found that ADM mRNA abundance increased in response to hypoxia and to CO inhalation up to 15-fold in all organs examined. Similarly, ADM-R mRNA abundance increased during hypoxia and CO inhalation in all organs examined with exception of the liver. The effects of hypoxia and of CO inhalation on ADM and ADM-R mRNAs were mimicked by injection of cobaltous chloride. Hypoxia also significantly increased ADM protein content in all organs, and plasma levels of ADM rose twofold in response to hypoxia and CO inhalation. These findings indicate that tissue hypoxia leads to a widespread activation of the ADM system, which comprises a parallel stimulation of ADM and ADM receptor mRNA as enhanced ADM protein synthesis and secretion. The ADM system may, therefore, play a significant role in the physiological response to tissue hypoxia. It appears that ADM and ADM-R belong to the family of classic oxygen-regulated genes, which are activated by a decrease of the pericellular oxygen tension through the same intracellular signaling cascade.
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PMID:Tissue hypoxygenation activates the adrenomedullin system in vivo. 1066 55

Cadmium is a substantial industrial and environmental pollutant which seriously impairs erythropoiesis. Cd has been demonstrated to aggravate anemia by suppressing erythropoietin gene expression in anemic patients. As hypoxic induction of erythropoietin mRNA depends on a transcription factor, hypoxia-inducible factor 1 (HIF-1), we hypothesized that Cd suppresses the hypoxic activation of HIF-1. In hypoxic Hep3B cells, all mRNAs of various genes, which are known to be upregulated by HIF-1 activation under hypoxia, were suppressed by Cd in a dose-dependent manner. Cd inhibited the hypoxia-induced activity of luciferase in 293 cells which was transfected with a reporter plasmid carrying a hypoxia response element. By electrophoretic mobility gel shift assay, Cd inhibited the DNA-binding activity of HIF-1 in hypoxic Hep3B cells. Cd reduced the amount of HIF-1alpha protein in hypoxia, whereas it didn't affect HIF-1 alpha mRNA levels. Moreover, Cd inhibited HIF-1alpha accumulation induced by cobalt and desferrioxamine. Antioxidants and a proteasome inhibitor prevented the HIF-1alpha degradation caused by Cd. The possibility that oxidative stress mediates this action of Cd was examined. Cd didn't affect protein oxidation and reduced glutathione levels in hypoxic cells. These results indicate that Cd triggers a redox/proteasome-dependent degradation of HIF-1alpha protein, reducing HIF-1 activity and in turn suppressing the hypoxic induction of hypoxia-inducible genes.
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PMID:Cadmium blocks hypoxia-inducible factor (HIF)-1-mediated response to hypoxia by stimulating the proteasome-dependent degradation of HIF-1alpha. 1086 24

Both toxic exposure to cadmium and cancer therapy with cisplatin (CDDP) can induce anemia in patients owing to the insufficient production of erythropoietin (EPO). Therefore, the effects of cadmium chloride (Cd) and CDDP in the Hep3B human hepatoma cell line, which up-regulates EPO expression in response to hypoxia and cobalt (Co), were investigated. The induction of binding activity of the HIF-1 transcription factor and EPO mRNA expression and protein production were suppressed by Cd and CDDP in a dose-dependent manner with no apparent cell damage. Mercuric chloride also suppressed hypoxia- and Co-induced EPO production, mRNA expression, and HIF-1 binding in a manner similar to Cd and CDDP, whereas zinc chloride suppressed Co-induced EPO production, mRNA expression, and HIF-1 binding but did not affect hypoxia induction or that observed after simultaneous exposure to hypoxia and Co. In contrast, lead and tin salts had no effect on HIF-1 activation or EPO expression. These results indicate that Cd and CDDP have a strong and specific inhibitory effect on hypoxia- and Co-induced signaling and EPO induction in hepatic cells. It is likely that these agents cause anemia by directly impacting EPO production in the kidney. (Blood. 2000;96:3743-3747)
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PMID:Cadmium and platinum suppression of erythropoietin production in cell culture: clinical implications. 1109 55


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