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)

Intestinal blood loss as well as chronic inflammation are regarded as the most important mechanisms in the pathogenesis of anemia in Crohn's disease. In addition, cytokines such as interleukin-6 can suppress erythropoietin production. This study was performed to investigate the importance of iron status, inflammatory activity, and endogenous erythropoietin concentrations for the development of anemia in Crohn's disease. In 49 consecutive patients with Crohn's disease, hemoglobin, inflammatory activity (Crohn's disease activity index, C-reactive protein, alpha 1-acid glycoprotein), iron status (serum iron, transferrin, transferrin saturation, ferritin), and serum erythropoietin levels were studied. Anemic (Hb < 12.0 g/dl; N = 16) vs nonanemic patients (Hb > or = 12 g/dl; N = 33) showed reduced iron compartments (eg, ferritin 28.7 +/- 12.9 micrograms/liter vs 63.2 +/- 15.0 micrograms/liter, transferrin saturation 6.2 +/- 1.4% vs 11.5 +/- 1.3%, P < 0.01) but no differences in inflammatory activity. An inverse correlation between erythropoietin and hemoglobin concentrations was found (r = -0.62; P < 0.001), but the increase in erythropoietin levels was inadequate to the degree of anemia. There was no correlation between erythropoietin and interleukin-6 serum levels. Four of five anemic patients with hemoglobin below 10.5 g/dl and erythropoietin levels within the normal range were treated with parenteral iron (200 mg iron saccharate in 250 ml NaCl, weekly, intravenously). Two of them additionally received recombinant human erythropoietin (150 units/kg, 3x weekly, subcutaneously). After five weeks all patients had a marked increase in hemoglobin. However, the mean increase in erythropoietin-treated patients was 5.0 g/dl compared to 2.0 g/dl in the patients with iron therapy only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anemia in Crohn's disease. Importance of inadequate erythropoietin production and iron deficiency. 808 99

The potential for antibody-dependent enhancement of replication of macrophage/monocyte tropic viruses has posed a significant problem in the development of vaccines for several animal and human viruses and has raised significant concern in the design of potential AIDS vaccines. Using the previously described equine infectious anemia virus/Shetland pony system as a model for HIV-1 vaccine development, we have evaluated the efficacy of a recombinant subunit vaccine containing a baculovirus-expressed envelope surface glycoprotein (gp90) of EIAV. The results of these trials demonstrate not only that the recombinant vaccine failed to protect against infection by standard homologous and heterologous EIAV challenge strains, but that it resulted in a marked enhancement of virus replication and exacerbation of disease in immunized ponies exposed to the heterologous virus strain. Thus, the recombinant EIAV gp90 vaccine provides a novel in vivo model for examining in detail the mechanisms of immune enhancement of a lentivirus infection and for evaluating strategies to avoid the production of deleterious immune responses in AIDS vaccine design.
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PMID:Enhancement of EIAV replication and disease by immunization with a baculovirus-expressed recombinant envelope surface glycoprotein. 811 52

Erythropoietin is the primary growth factor for red blood cells. A glycoprotein hormone synthesized by the kidneys, erythropoietin serves to increase red blood cell production in response to tissue hypoxia. It exerts its effect by increasing the numbers of erythroid progenitor cells in the bone marrow, and by increasing the rate at which their development is accomplished. With the introduction of recombinant erythropoietin in 1987, an important pharmacological agent became available for the manipulation of erythropoiesis. While used primarily for the treatment of the anemia of renal failure, recombinant erythropoietin has also shown usefulness in treating other types of anemias in which the endogenous erythropoietin response is insufficient. Perioperative use of the drug grew as a natural extension of this, and erythropoietin has been applied to correct preoperative anemia, augment autologous blood donation, and improve postoperative red cell recovery. Analysis of these perioperative clinical studies reveals success in these areas, but it also reveals that closer attention to the physiology of the natural response, and to the pharmacology of the recombinant product, might significantly improve results. Such an improvement in efficacy is both desirable and necessary when use of the drug is viewed in the setting of today's changing health care environment. By optimizing dosing schedules and targeting the drug to those most at risk for red cell transfusion, recombinant erythropoietin will likely become an important tool in efforts to achieve the elusive goal of bloodless cardiac surgery.
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PMID:Erythropoietin in cardiac surgery. 821 40

Erythropoietin (EPO) is a prime stimulating factor for red cell production. EPO is a glycoprotein which has a molecular weight of 34,000, and is mainly produced by the kidney. EPO stimulates the differentiation and proliferation of erythroid progenitor cells in the bone marrow. The rate of production of EPO is regulated primarily by renal oxygen availability. Because anemia reduces renal oxygen availability, anemic stress accelerates EPO production in the kidney. Recently, EPO has mainly been determined by radioimmunoassay. Serum EPO titer is usually inversely correlated with hemoglobin concentration, as typically shown in iron deficiency anemia. Serum EPO titers in aplastic anemia are much higher than those in iron deficiency anemia relative to the hemoglobin concentration. Serum EPO titers in anemia caused by malignancies sometimes differ considerably among patients. Serum EPO in renal anemia usually show low titers irrespective of the degree of anemia. Serum EPO titers in untreated polycythemia vera are lower than those in treated polycythemia vera or secondary polycythemia. Determination of serum EPO is useful in differential diagnosis of polycythemia vera. Recombinant human EPO has been used to treat various anemias including renal anemia, refractory anemia, anemia in malignancies and secondary anemia. Determination of serum EPO titers is also valuable in many other situations of clinical medicine.
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PMID:[Erythropoietin determination in clinical medicine]. 835 Apr 98

The red-cell mass is continuously adjusted to the optimal size for its function as an oxygen carrier by messages transmitted to the bone marrow from an oxygen sensor in the kidney. These messages are mediated by the hormone erythropoietin. Erythropoietin is a glycoprotein growth factor synthesized by cells adjacent to the proximal renal tubule in response to signals from a renal oxygen-sensing device, probably a heme protein (1). In the bone marrow, erythropoietin binds to and activates specific receptors on the erythroid progenitor cells (2). In the presence of this erythropoietin-receptor complex the progenitor cells continue their predestined development into mature erythrocytes. Erythropoietin was the first hemopoietic growth factor to be molecularly cloned in 1985 (3). Our understanding of the biology and physiology of erythropoietin has been considerably improved with the advent of recombinant human erythropoietin (rHuEpo). During the past 7 years, rHuEpo has undergone extensive testing in clinical trials. It has been approved for treatment of the anemia of chronic renal failure, both in progressive renal failure and endstage renal failure (ESRD). In these instances, the administration of rHuEpo has been used in effect as a substitutive therapy, since patients' erythropoietin levels are very low despite severe anemia, due to the failure of affected kidneys to produce adequate amounts of the hormone. However, the application of rHuEpo has now moved largely from the primitive indication of renal diseases, and the hormone is currently under study in a number of anemic states of different etiologies, even with relatively high serum erythropoietin levels. Among these, some of the best documented indications are the anemia associated with malignancies, either due to neoplastic bone marrow infiltration or to chemotherapy-related myelosuppression, the anemia of myelodysplastic syndromes and AIDS, the anemia of chronic inflammatory diseases, prematurity, and bone marrow transplantation (4). The purpose of this review is to provide a summary of our present knowledge regarding rHuEpo therapy for the anemia of renal failure. We provide some clues for the correct use of rHuEpo in the treatment of the anemia of chronic inflammatory diseases. In addition, we address a series of new issues in the attempt to better understand the relationship between erythropoietin and liver disease.
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PMID:Erythropoietin and the anemia of chronic diseases. 840 91

A 20-year-old woman from a consanguineous family in the Hunan Province of the People's Republic of China was diagnosed as having Glanzmann's thrombasthenia based on (1) nearly a lifelong history of epistaxis, gum bleeding, petechiae, and purpura; (2) severe menorrhagia resulting in anemia and need for whole-blood transfusion; (3) normal coagulation assays; (4) prolonged bleeding time; (5) absent clot retraction; (6) decreased glass bead retention; (7) absent platelet aggregation in response to adenine diphosphate, epinephrine, and collagen; and (8) normal initial slope of platelet aggregation in response to ristocetin, but with a diminished maximal extent. The patient's platelets had a decreased level of platelet fibrinogen, but the deficiency was not as severe as in other Glanzmann's thrombasthenia patients. As judged by monoclonal antibody binding studies, surface glycoprotein (GP) IIb/IIIa (alpha IIb beta 3) expression was less than 15% of normal and alpha v beta 3 vitronectin receptor expression was 15% to 19% of normal, suggesting that the defect was in GPIIIa (beta 3). Immunoblotting of platelet lysates demonstrated decreased levels of GPIIb (approximately 30% to 35% of normal) and GPIIIa (approximately 10% of normal), and the GPIIb had undergone normal maturational processing into GPIIb heavy and light chains. Sequence analysis of the patient's GPIIIa RNA identified a G to A mutation at nucleotide 1219, predicting a Cys to Tyr substitution at residue 374. The patient's parents, who are first cousins, are asymptomatic and have only minor reductions in platelet aggregation. Direct sequencing of polymerase chain reaction-amplified cDNA and GPIIIa exon VIII indicated that the patient is homozygous and her parents are heterozygous for the mutation. Transient transfection studies in Chinese hamster ovary cells indicated that the mutation results in an 85% to 90% reduction in GPIIb/IIIa surface expression, but these cells retain the ability to mediate adhesion to immobilized fibrinogen. The relative preservation of platelet fibrinogen despite the very low level of platelet surface GPIIb/IIIa expression in this patient raises some interesting questions regarding the mechanism of fibrinogen uptake and the pathophysiology of Glanzmann's thrombasthenia.
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PMID:A Cys374Tyr homozygous mutation of platelet glycoprotein IIIa (beta 3) in a Chinese patient with Glanzmann's thrombasthenia. 878 22

Erythropoietin (Epo) is a glycoprotein produced primarily by the kidney and is the factor regulating the red blood cell production. Unlike most of the hematopoietic growth factors, Epo is principally produced by a single organ, the kidney, and is regulated by a classic feedback control system. Epo acts on the erythroid progenitors after binding to a specific receptor. The gene coding for a 66 Kd chain has been cloned. This chain belongs to the hematopoietic growth factors family. Epo gene was cloned in 1985. The protein coded by this gene is heavily glycosylated. Epo production is regulated by renal tissue hypoxia. Cells producing Epo in the kidney are a subset of peritubular interstitial cells of fibroblastic origin. Epo is now used in clinical applications. Rationale for the use of Epo is based on the serum determination of Epo level. Patients with anemia of chronic renal failure are routinely treated with recombinant Epo. Two other indications are recognized by French authorities: the treatment of anemia of cancer patients receiving platin-derived chemotherapy and the use in autologous blood donation.
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PMID:[Physiology of eryhtropoietin and its therapeutic use]. 888 Nov 1

The understanding of the endocrine regulation of red cell production has been extended greatly since the erythropoietin gene was cloned and recombinant human erythropoietin has become available for experimental and clinical applications. Human erythropoietin is a 30 kDa glycoprotein. It is composed of 165 amino acids and 4 carbohydrate side chains. Studies in rodents have shown that blood-borne erythropoietin originates from peritubular cells, possibly fibroblasts, in the renal cortex and from parenchymal cells in the liver. In addition, erythropoietin mRNA has been demonstrated in spleen, lung and brain. Tissue hypoxia is the main stimulus for erythropoietin synthesis. Erythropoietin gene expression is controlled by DNA-binding proteins, primarily by hypoxia-inducible factor 1. Erythropoietin maintains red cell production by inhibiting apoptosis of erythrocytic progenitors, and by stimulating their proliferation and differentiation into normoblasts. The functional human erythropoietin receptor, a 484-amino acid glycoprotein, is member of the class I cytokine receptor superfamily. Lack of erythropoietin results in anaemia. Recombinant human erythropoietin is efficient for treatment of the anaemia of chronic renal failure. In addition, the drug is increasingly administrated to persons suffering from anaemia of chronic diseases and to surgical patients, thus abolishing the need for homologous red cell transfusion.
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PMID:Erythropoietin in the control of red cell production. 893 50

Trichuris suis is a nematode parasite of swine which can cause serious pathology in infected pigs, such as anorexia, diarrhea, anemia, and death in heavy infections, especially in young animals. Infection with Trichuris suis is difficult to diagnose because much of the pathology occurs when only larval stages are present, and because of sporadic egg production by adult female worms. We have isolated a 20 kDa excretory/secretory (E/S) glycoprotein from culture fluids of adult worms by column chromatography and preparative gel electrophoresis which is diagnostic for Trichuris suis infection in pigs. The antigen did not crossreact in Western blots or enzyme-linked immunosorbent assay with sera from pigs infected with Ascaris suum, Trichinella spiralis, Oesophagostomum dentatum, or Toxoplasma gondii. The antigen was also diagnostic for Trichuris vulpis infection in dogs, and did not crossreact with sera from dogs infected with Toxocara canis, Ancylostoma caninum, or Strongyloides stercoralis. The antigen may be useful in clinical serologic assays for diagnosis of Trichuris infection in pigs and dogs in cases of scouring diarrhea of unknown etiology, and in epidemiological surveys of Trichuris suis infection in swine feeder/finishing operations.
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PMID:A Trichuris specific diagnostic antigen from culture fluids of Trichuris suis adult worms. 906 55

Recombinant human erythropoietin (rhEPO) is an important glycoprotein hormone which has been successfully used in the treatment of anaemia. To facilitate the rapid evaluation of wild-type and mutant forms of rhEPO in structure-function studies, we have developed an expression system in which the recombinant hormone is tagged at the C-terminus with a c-myc peptide. One-step affinity purification of culture supernatants on an anti-myc antibody column yielded proteins which were greater than 50% pure with a specific activity of 300,000 U/mg, in agreement with the value of wild-type protein. We conclude that the additional myc-peptide does not affect receptor binding. The expression system was used to study three mutants in which the N-glycosylation sites were changed to cysteines (Asn24Cys, Asn38Cys and Asn83Cys). Specific activities of these cysteine mutants were significant, but reduced (60%, 22% and 70%, respectively), compared to wild-type. The reduction in specific activity may be due to reduced stability of the mutant proteins.
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PMID:COS-1 cell expression and one-step affinity protein purification and activity of epitope-tagged human erythropoietin and of site-directed mutants. 921 10


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