Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemically detectable erythropoietin-like substance(Epo) in granular convoluted tubule(GCT) cells of submandibular glands (SMG's) was examined in mice in which hemolytic anemia had been induced by phenylhydrazine (ph), and in mice subjected to hypoxia, nephrectomy, or testosterone (TP) injections. Staining for Epo was negative in GCT cells of SMG's in normal mice, while positive staining occurred in GCT cells of the anemic mice and mice subjected to hypoxia or nephrectomy. A positive Epo reaction was also revealed at the luminal borders of distal tubules, and in cells of proximal and distal tubules in the kidney, and in some hepatic and spleen cells, of mice that had received combination regimens producing anemia and hypoxia, or had been nephrectomized. Increased staining of Epo was found in GCT cells of SMG's, and in proximal and distal kidney tubules of mice given the combination treatment plus TP injections. The detection of Epo in GCT cells suggests these extrarenal cells to be sites of accumulation or biosynthesis of the protein under certain specific conditions such as hemolytic anemia and hypoxia.
Cell Mol Biol 1991
PMID:Erythropoietin expressed in granular convoluted tubule cells of mice submandibular glands under hypoxia, anemia, and nephrectomy. 193 6

A new variant of human glucose 6-phosphate dehydrogenase (G6PD), provisionally designated G6PD Harilaou, was observed in a Greek boy affected by severe hemolytic anemia. G6PD Harilaou was associated with very severe deficiency of enzyme activity, which measured about 1% of normal in the patient's fibroblasts. By fusion of Harilaou fibroblasts with a similarly enzyme-deficient mutant CHO cell line, we have isolated a hybrid cell line that has a G6PD activity 5-10 times higher than either of the parental cells. By electrophoretic analysis we show that most of this activity is associated with a hybrid dimeric G6PD molecule consisting of one hamster and one human subunit. We suggest that this heterologous quasi-interallelic complementation is effected by a catalytically abnormal hamster subunit stabilizing a catalytically abnormal and unstable Harilaou subunit. This approach may be useful for the study of dimer formation and stability in human G6PD.
Somat Cell Mol Genet 1990 Mar
PMID:Intragenic interspecific complementation of glucose 6-phosphate dehydrogenase in human-hamster cell hybrids. 215 98

The reaction of oxyhemoglobin with phenylhydrazine has received considerable attention for many decades. The basis for this interest stems from the ability of phenylhydrazine and hydrazine-based drugs to induce hemolytic anemia. Considerable evidence obtained from in vitro ESR experiments implicates free radicals in the events leading to red blood cell hemolysis. However, until this report, no corroborating ESR evidence for in vivo free radical formation has been presented. We have successfully employed ESR to detect the formation of a radical adduct in the blood of rats which received an intragastric dose of phenylhydrazine followed by an intraperitoneal injection of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). An immobilized radical adduct was detected by ESR when phenylhydrazine was administered in a dosage comparable to that prescribed for currently employed hydrazine-based drugs. We were also able to detect this immobilized DMPO adduct when hydrazine was employed in place of phenylhydrazine in the rat studies. The results of a series of experiments led us to ascribe this DMPO radical adduct to the trapping of a hemoglobin-derived thiyl free radical.
Mol Pharmacol 1988 Mar
PMID:In vivo rat hemoglobin thiyl free radical formation following phenylhydrazine administration. 283 22

Among glycolytic enzyme defects, hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1; HK) deficiency is a very rare disease where the predominant clinical effect is nonspherocytic hemolytic anemia. Here we report the characterization at molecular level of the HK type I cDNA from a patient with hemolytic anemia due to hexokinase deficiency. PCR amplification and sequence of the cDNA revealed the presence of a deletion and of a single nucleotide substitution, both in heterozygous form. In particular, the deletion, 96 bp long, concerns nucleotides 577 to 672 in the HK cDNA sequence and was never found in the cDNAs of 14 unrelated normal subjects. The sequence of the HK allele without deletion showed a single nucleotide substitution from T to C at position 1667 which causes the amino acid change from Leu529 to Ser. This heterozygous mutation at nt 1667 was confirmed by direct sequencing of the patient genomic DNA, but when DNAs from 10 normal controls were examined by this technique the substitution at nt 1667 was never found. From these results we concluded that the patient is carrying a point mutation at nt 1667 of one HK allele and a 96 nt deletion in the other allele. In normal subjects two differences from the published cDNA sequence were documented.
Blood Cells Mol Dis 1995
PMID:Hexokinase mutations that produce nonspherocytic hemolytic anemia. 765 56

Glycol ethers produce both hemato- and testicular toxicity in animals, which is dependent on both the alkyl chain length and animal species used. Ethylene glycol monobutyl ether (2-butoxyethanol, BE) causes hemolytic anemia in rats but not in guinea pigs, and red blood cells from both guinea pigs and humans are minimally affected in vitro by the active metabolite 2-butoxyacetic acid. This demonstrates the importance of animal species selection for assessing human risk to BE exposure. 2-Methoxyethanol (ME) produces testicular lesions in rats characterized primarily by the degeneration of spermatocytes undergoing meiotic division with minimal or no hemolytic changes. Because of the differential hemolytic response to BE between rats and guinea pigs, the present study addressed whether the testicular response to ME was similarly dichotomous. Adult rats or guinea pigs were given a single dose of either 200 or 300 mg ME/kg by gavage, and testicular and hemolytic changes were assessed 24 hr after treatment. Testis histology in rats showed dose-dependent degeneration of dividing spermatocytes in stage XIV tubules as expected, with only minimal hemolytic changes, also as expected. In contrast, no testicular or hemolytic effects were observed in guinea pigs 24 hr after either single ME dose. In a subsequent study, a single dose or multiple (3 daily) doses of 200 mg ME/kg were given, and animals were examined at 4 days after the start of treatment. Testes from rats given both single and multiple ME doses showed, as expected, tubules depleted of spermatocytes and early spermatids. In guinea pigs, spermatocyte degeneration was observed in stage III/IV tubules for both dosing schemes, but was much less severe and widespread and differed from rats in morphological characteristics, specifically in the appearance of nuclear chromatin degeneration. In the rat, degenerating spermatocytes showed uniformly condensed and dispersed chromatin, while in the guinea pig they showed marked chromatin condensation at the nuclear periphery. No hemolytic changes were observed in either species or dosing scheme. In summary, although ME-associated testicular lesions were observed in both species, they differed significantly in onset, characteristics, and severity. Both the nature of the differential testicular response to ME and a comparison to the in vitro human testicular response to the active metabolite 2-methoxyacetic acid are subjects of future study.
Exp Mol Pathol 1994 Oct
PMID:Comparison of the testicular effects of 2-methoxyethanol (ME) in rats and guinea pigs. 785 28

Hemoglobinopathies responsible for hemolytic anemias may be divided into two groups. The first one corresponds to thalassemias and the second to the presence of a structurally abnormal hemoglobin (Hb). In thalassemia, the primary biochemical abnormality is a quantitative defect in the biosynthesis of one type of Hb chain. This defect leads to an overall deficit of Hb accumulation in the erythrocyte (hypochromia) together with the presence of an excess of the normally synthesized chains. The unpaired subunits which are less soluble than HbA precipitate, bind to the membrane and ultimately lead to hemolysis. In the second group, the hemolytic anemia is a direct consequence of the physicochemical properties of the structurally abnormal Hb. This molecule may polymerize, precipitate or crystallize within the red blood cell (RBC) leading to membrane alterations and to the destruction of the cell. This chapter will emphasize several examples of structurally abnormal Hbs, such as sickle cell disease and congenital Heinz body hemolytic anemia (CHBHA).
Mol Aspects Med 1996 Apr
PMID:Hemolytic anemias due to hemoglobinopathies. 881 15

A 44-year-old women was treated for hyperparathyroidism resulting from parathyroid hyperplasia. Several months later, following a flu-like episode, she developed fever, confusion, abdominal pain, and diffuse petechiae, with severe thrombocytopenia and hemolytic anemia. She died on the 11th day of hospitalization. At autopsy she had multiple endocrine neoplasia type I, with two islet cell tumors, adrenal adenoma, pituitary adenoma, and bronchial carcinoid with liver metastasis. Florid visceral microthrombi involved arterioles and capillaries of the heart, including the conduction system. Brain, kidney, pancreas, adrenal, and portal areas of the liver were also heavily involved, but thrombi were rare in the liver sinusoids and the lungs. PAS-positive subendothelial deposits were demonstrated. In spite of the disseminated malignancy, the morphologic and laboratory findings were inconsistent with disseminated intravascular coagulation (DIC), and supported the clinical diagnosis of TTP. To the best of our knowledge this is the first report association of TTP with MEN and raises the question of a genetic linkage and/or hormonal interaction.
Hematopathol Mol Hematol 1996
PMID:Fatal thrombotic thrombocytopenic purpura (TTP) presenting concurrently with metastatic multiple endocrine neoplasia (MEN) type I. 887 34

Hydroxylamine is a direct-acting hematotoxic agent leading to hemolytic anemia in animals and man. The effect of hydroxylamine on the morphology, sulfhydryl status and membrane skeletal proteins of human erythrocytes were studied. Loss of reduced glutathione (GSH) from the red blood cells was directly proportional to the hydroxylamine concentration used. This loss of GSH was larger than the sum of the increase in the amounts of extracellular glutathione and intracellular oxidized glutathione (GSSG). The extracellular glutathione is mainly present as GSSG, which is in agreement with the fact that only GSSG is exported from the erythrocytes by membrane bound ATPases. Lack of GSSG export was not limited by decreased ATP levels in the erythrocytes and we concluded that the GSH that disappeared did not become available as intracellular GSSG. After reduction of the erythrocyte incubates the lost GSH was almost completely recovered indicating that the lost GSH is present in the cell as protein-glutathione mixed disulfides. Glutathione thus stored within the cell can be quickly recovered by combined thioltransferase and glutathione reductase activity when conditions become more favorable again. SDS-polyacrylamide gel electrophoresis of membrane ghosts from human red cells revealed changes in skeletal proteins with a smearing of bands 1, 2 and 3 to the higher molecular weight end of the gel and the appearance of new monomeric and dimeric hemoglobin bands at about 16 and 30 kD. The observed alterations are probably a consequence of disulfide bridge formation between cellular proteins (mainly hemoglobin) and skeletal proteins as well as between hemoglobin monomers. Exposure of hydroxylamine to erythrocytes caused severe Heinz body formation but the outside morphology of the cells was only marginally altered. The described changes in sulfhydryl status of the red blood cells are likely to play a major role in the premature splenic sequestration of hydroxylamine-damaged erythrocytes.
Blood Cells Mol Dis 1997 Dec
PMID:Hydroxylamine treatment increases glutathione-protein and protein-protein binding in human erythrocytes. 939 34

Five unrelated patients with hereditary glucosephosphate isomerase (GPI) deficiency resulting in nonspherocytic hemolytic anemia were studied. Three new mutations were found in the coding region of the GPI gene: two patients were heterozygous for 223 A-->G (R75G) and 898 G-->C(R300P), respectively and one was homozygous for 1415G-->A(R472H). Surprisingly, 2 previously reported mutations, 286 C-->T and 1039 C-->T, were found in 2 and 3 patients respectively. Until now only 4 of 18 GPI mutations had been found more than once in unrelated patients and these 4 in only 2 patients each. Eleven of the 20 known point mutations have occurred at CpG "hot spots" and the 286 C-->T and 1039 C-->T are among these. The 489 G/A polymorphism in the GPI coding region was used to demonstrate unequivocally that the 1039 C-->T mutation occurred in both haplotypes and therefore probably originated more than once. Because no common GPI mutation has been found we suggest that heterozygosity for GPI confers little if any selective advantage.
Blood Cells Mol Dis 1997 Dec
PMID:Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA). 944 54

A 34-year-old male acutely presented with widely disseminated malignant melanoma, a microangiopathic hemolytic anemia, and disseminated intravascular coagulation. Although the patient had a history of intense childhood exposure to ultraviolet light and an occupational exposure to organic dyes, he had no history of a precursor skin lesion. The histopathology of the patient's bone marrow revealed sheets of malignant cells immunoreactive with S-100, HMB-45, and vimentin and also staining positively for melanin. A bone marrow aspirate revealed myeloid precursors filled with melanin-bearing vacuoles. Immunophenotypic analysis of the patient's bone marrow by flow cytometry revealed a paucity of hematopoietic cells. A karyotypic analysis of the patient's tumor cells demonstrated an abnormal hypertriploid composite clone characterized by multiple numerical and structural abnormalities. Although the patient was treated aggressively with transfusional support, heparin, and chemotherapy, he expired 3 weeks after diagnosis. This is the first recognized case of metastatic melanoma occurring in association with a microangiopathic hemolytic anemia.
Hematopathol Mol Hematol 1998
PMID:Fulminant metastatic melanoma complicated by a microangiopathic hemolytic anemia. 960 58


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