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)

A severely anaemic, but asymptomatic patient, who is a heterozygous carrier of haemoglobin Hammersmith (beta42 (CD1) phenylalanine - Serine), has been studied to elucidate the mechanisms resulting in physiological compensation for the anaemia. Four factors have been investigated: the oxygen affinity of her blood, the cardiac output at rest and during exercise, the blood gas indices, and pulmonary function. It was found that due to the presence of Heinz bodies within the erythrocytes, the level of functional, haemoglobin was considerably less (50 g/l) than that measured by standard methods (87 g/l). In addition a moderate degree of arterial hypoxaemia (arterial oxygen tension = 10.7 kPa (80.4 mmHg) was present which could not be explained on the basis of abnormal pulmonary function. Both of these factors would result in tissue hypoxia, but the finding of consistently normal oxygen tensions ('mixed' venous oxygen tension = 5.4 kPa (40.3 mmHg) in blood obtained from the right atrium, suggested that hypoxia was not present. This was explained by a decreased whole blood oxygen affinity (P50 = 4.6 kPa (34.5 mmHg) at pH 7.4) and an increase in the cardiac index (5.3 L.min.-1m-2). The latter was the result of an increased stroke volume (125 - 135 ml), the heart rate being normal (63/min.). During moderate exercise, further increases at cardiac output were brought about by a change in heart rate alone. It has been calculated that the decrease in whole blood oxygen per se could not account for adequate tissue oxygenation. This is confirmed by the finding of an increased cardiac output in this patient. It is suggested that in any severe haemolytic anaemia, even if the whole blood oxygen affinity is low, cardiac output is probably increased to achieve complete physiological compensation.
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PMID:Compensatory mechanisms for the severe anaemia caused by haemoglobin Hammersmith. 93 44

A severe hemolytic crisis was observed in a 34-yr-old female of English-Irish extraction following a viral illness treated with acetaminophen. Heinz bodies and heat instability were present only during a transient hemolytic event. A challenge dose of acetaminophen caused no detectable hematologic abnormality. Structural studies of the hemoglobin during hemolysis and again after complete recovery localized the abnormality to tryptic peptide beta Tp-5, and automated sequencing of I 125-labeled beta chains indicated a replacement of phenylalanine (C7) beta 41 by tyrosine. Substitution of the next residue, phenylalanine (CD1) beta 42 by serine (Hb Hammersmith), has resulted in chronic severe Heinz body hemolytic anemia. The lack of chronic anemia in the present disorder may reflect the different relationships of beta41 and beta 42 and/or the similarities in volume and hydrophobicity of tyrosine and phenylalanine. It is suggested that substitution of tyrosine for phenylalanine in Hb Mequon may disturb the critical environment around the heme group and render it susceptible to oxidative denaturation in the presence of infections and/or drugs.
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PMID:Hemoglobin M equon beta 41 (C7) phenylalanine leads to tyrosine. 97 62

The concentrations of unbound amino acids in erythrocytes and in plasma from 7 normal individuals, 11 patients with various types of aregeneratory anaemia, and 4 patients with hereditary haemolytic anaemias were determined on a Technicon Amino Acid Analyzer (Perry et al 1970). Most amino acids were normally found in higher concentrations in plasma than intracellularly. Cystine, methionine and trypotophan were almost exclusively present in plasma. Aspartic acid, however, was mainly found in erythrocytes, and glutathione only in erythrocytes. Glutamic acid and ornithine were more concentrated in the cells, while glycine and asparagine showed approximately the same concentrations in erythrocytes as in plasma. In the patients, plasma amino acids showed little deviations from normal, but in the erythrocytes there were striking changes. Erythrocyte glutamic acid concentrations were moderately to markedly elevated in all patients studied, and glycine concentrations in 13 out of 15 patients. In addition, the following amino acids were increased intracellularly in more than one patient: glutamine (8 patients), serine (7), asparagine (5), threonine (4), taurine (3), alanine (2), valine (2), ornithine (2), lysine (2), citrulline (2). Aspartic acid was decreased in erythrocytes from 4 patients with aregeneratory and 1 with haemolytic anaemia.
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PMID:Amino acid concentrations in plasma and erythrocytes in aregeneratory and haemolytic anaemias. 119 60

Biochemical disturbances common to vitamin B12 and folate deficiency were investigated in leukocytes from patients with cobalamin deficiency. The investigations focused on the only two human metabolic pathways known to require vitamin B12. In the propionate pathway, deoxyadenosylcobalamin is required for isomerization of methylmalonyl-CoA to succinyl-CoA. Leukocyte oxidation of 14C-propionate to 14CO2 was markedly decreased in 9 patients with Addisonian cobalamin deficiency and 2 patients with low serum cobalamin associated with folate deficiency, whereas 14C-succinate oxidation was normal. Three of the Addisonian patients had only minimal anemia. Within 4 days after one injection of 1,000 mug of cyanocobalamin, in 7 out of 8 patients studied, leukocyte propionate oxidation increased to normal levels. In folate-mediated one-carbon metabolism, as measured by serine biosynthesis from formate, methylcobalamin is required for conversion of methyl-folate to tetrahydrofolate. Leukocyte formation of 14C-serine from 14C-formate was significantly depressed in 5 patients with low serum cobalamin, little or no anemia, and only marginally low total red cell folate, the low serum cobalamin in 2 of these patients was associated with folate deficiency. After 1,000 mug of cyanocobalamin, in 2 of 3 patients, leukocyte serine biosynthesis increased to the normal range. These observations demonstrated that these two metabolic pathways in leukocytes were sensitive to cobalamin deficiency, and responsive to cobalamin therapy. Although there was no correlation between either of these metabolic activities and the serum cobalamin, red cell folate, or hematocrit, there was a striking correlation between impairment of leukocyte propionate oxidation and of leukocyte serine biosynthesis in 5 patients who were minimally anemic. The remarkably close correspondence between effects of low cobalamin on these two metabolic pathways, in nonanemic patients, must be a direct consequence of their common requirements for a cobalamin co-enzyme. These findings emphasize the importance of cobalamin in folate metabolism, and are consistent with the hypothesis that folate is "trapped" as methyl-folate in cobalamin deficiency, but do not exclude the possibility that this "trapping" is caused by a third metabolic function of cobalamin which might mediate transport of folate into cells.
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PMID:Defective leukocyte metabolism in human cobalamin deficiency: impaired propionate oxidation and serine biosynthesis reversible by cyanocobalamin therapy. 124 86

We found that an abnormal hemoglobin with a very low oxygen affinity was responsible for overt cyanosis in an otherwise healthy adolescent. Hemoglobin Beth Israel, in which serine replaces the asparagine residue normally present at position 102 (G4) of the beta-polypeptide chain, was associated with normal blood counts and no apparent exercise intolerance in the heterozygous carrier. Cyanosis resulted from a drastically right-shifted oxygen dissociation curve, whose position and shape could account for the absence of "physiologic" anemia. The whole-blood oxygen tension at 50 per cent oxygen saturation was 88 mm Hg (normally 26 +/- 1 mm Hg), and the arterial blood was only 63 per cent saturated with oxygen despite a normal oxygen tension of 97 mm Hg. The hemolysate showed a low oxygen affinity but normal Bohr effect. Unexplained cyanosis, particularly in association with normal arterial oxygen tension should prompt a search for an abnormal hemoglobin, which may obviate the need for invasive diagnostic procedures.
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PMID:Hemoglobin Beth Israel. A mutant causing clinically apparent cyanosis. 127 28

Limited tryptic digestion of spectrin (Sp) from seven related individuals manifesting hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP) phenotypes revealed the presence of a novel peptide with a molecular weight of 78 Kd and a concomitant decrease in the alpha I domain (80-Kd peptide), which is the domain involved in the dimer self-association process. Sp from the normal members of this white family exhibited a normal peptide pattern, as compared with controls. The abnormal peptide pattern was associated with a decreased ability of Sp dimer to self-associate. In this kindred in which three generations were available for study, the clinical manifestations were quite variable and ranged from the asymptomatic HE carrier state to hemolytic HE or to severe anemia requiring splenectomy. The severity of the disease appeared to be correlated both with the amount of mutant spectrin (31% to 69%) and with the excess of the Sp dimer found in the membrane (26% to 60%, compared with a normal value of 5.6% +/- 2.2%). Partial amino acid sequencing showed that the alpha I/78-Kd peptide resulted from cleavage at lysine residue 10 of the alpha I/80-Kd domain. Knowledge of the exon/intron structure of cloned genomic DNA encoding the alpha I domain allowed us to amplify in vitro a DNA fragment containing the third exon of the alpha-spectrin gene. The amplified fragment was subcloned and sequenced. A G to T transversion was found in the 39th codon (AGT for AGG), which changed the normal arginine to a serine. Hybridization of amplified DNAs with allele-specific oligonucleotides corresponding to the normal and mutant sequences confirmed the presence of the mutation in three other HE members of the family (the propositus mother, brother, and sister).
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PMID:Sp alpha I/78: a mutation of the alpha I spectrin domain in a white kindred with HE and HPP phenotypes. 256 62

We assessed the effect of correction of anemia with recombinant human erythropoietin (rhEPO) on plasma amino acid levels in maintenance hemodialysis patients. The plasma amino acid pattern was estimated by high performance liquid chromatography in 18 healthy persons and 14 hemodialysis patients before and up to 12 weeks after rhEPO therapy. There was a correction of the plasma serine values (67 +/- 16 to 87 +/- 22; P less than 0.05) and a corresponding decrease in the serine precursors, glycine (317 +/- 113 to 228 +/- 56; P less than 0.05) and hydroxyproline (26 +/- 21 to 15 +/- 13; P less than 0.10). The low plasma branched-chain amino acids, valine (137 +/- 33 to 154 +/- 50; P less than 0.10) and leucine (72 +/- 22 to 80 +/- 27; P less than 0.20), also were corrected. The elevated values of ornithine (78 +/- 16 to 62 +/- 19; P less than 0.1) and arginine (94 +/- 14 to 72 +/- 14; P less than 0.1) fell. The diminished glutamine values (470 +/- 125 to 563 +/- 115; P less than 0.1) and the decreased tyrosine/phenylalanine ratio (0.78 +/- 0.17 to 0.98 +/- 0.21; P less than 0.05) rose. Thus, the administration of rhEPO not only affects erythropoiesis, but also corrects the plasma amino acid pattern towards normal.
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PMID:Correction of amino acid metabolism by recombinant human erythropoietin therapy in hemodialysis patients. 263 62

Hb Mississippi was discovered in a 6-year-old Chinese girl with chronic anemia and thalassemia intermedia. Family studies revealed that she had inherited the Hb Mississippi from her father as well as inheriting a gene for beta+-thalassemia from her mother. Electrophoretic analyses of the hemolysate of the father of the father and the proband on polyacrylamide gels at pH 8.6 showed that the abnormal hemoglobin had three distinct mobilities. A similar pattern was also observed by isoelectricfocusing. In addition, multiple abnormal peaks were observed by high performance liquid chromatographic hemoglobin separations as well as high performance liquid chromatographic globin chain separation. Structural analysis of the abnormal hemoglobin demonstrated a single abnormality; the substitution of serine to cysteine at position 44 (CD3) of the beta-globin chain. Since CD3 is on the surface of the beta-globin chain, it was thought that polymerization of the abnormal hemoglobin by disulfide linkages might have been responsible for the anomalous behavior on electrophoresis and high performance liquid chromatography. Gel filtration chromatography on G-200 Sephadex confirmed this supposition and demonstrated that the abnormal globin chain polymerized with itself as well as with other globin chains.
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PMID:Hb Mississippi [beta 44(CD3)Ser----Arg]: a new variant with anomalous properties. 342 43

Toxic shock syndrome toxin 1 (TSST-1) was purified to apparent homogeneity by chromatofocusing and affinity chromatography. The amino acid composition of the toxin was very similar to that reported for TSST-1 by other investigators. The amino-terminal amino acid was serine. A partial specific volume of 0.73 ml/g was calculated for the toxin from the amino acid data, and a molecular weight of 19,200 +/- 1,300 was determined by hydrodynamic methods. New Zealand white rabbits of both sexes were equally susceptible to the lethal effects of the toxin; however, older rabbits (greater than 12 months) were far more susceptible than young adults or weanlings. The 50% lethal dose of TSST-1 in older rabbits was 50 to 60 micrograms/kg when injected subcutaneously and 20 to 30 micrograms/kg when injected intravenously. Enhancement of lethal endotoxin shock by TSST-1 could not be demonstrated when both toxins were injected subcutaneously; however, lethal shock did occur when endotoxin (10 micrograms/kg) was injected intravenously after TSST-1 had been injected by either the subcutaneous (50 to 60 micrograms/kg) or the intravenous (20 to 30 micrograms/kg) route. Endotoxin alone was not lethal at a dose of 500 micrograms/kg of body weight when injected subcutaneously. When injected intravenously, endotoxin at a dose of 500 micrograms/kg was not lethal in weanling males or in females in any age group; however, young (6 to 7 months) and adult (greater than 12 months) males were killed by endotoxin doses as low as 45 to 50 micrograms/kg. Histopathologic studies of rabbits by both sexes which died as a result of TSST-1 alone or in combination with endotoxin showed extensive damage to organs rich in lymphoid and mononuclear phagocytic cells such as the thymus, mesenteric lymph nodes, liver, and spleen. Severe congestion of these organs as well as erythrophagocytosis and lymphoid depletion in the spleen and mesenteric lymph nodes were noted. Congestion and hemorrhage were also found in the heart, lungs, trachea, and thymus. The systemic pathology produced by TSST-1 was strikingly similar to that seen in humans who had died of toxic shock syndrome and in rabbits with subcutaneous chamber inoculated with toxic shock case strains of Staphylococcus aureus. Rabbits that were not killed by the toxin suffered a very rapid and severe leukopenia followed by leukocytosis with a left shift. Lymphopenia was also noted as was a mild but persistent anemia. With the exception of the early leukopenia, very similar hematologic findings have been noted in humans with toxic shock syndrome.
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PMID:Affinity purification of staphylococcal toxic shock syndrome toxin 1 and its pathologic effects in rabbits. 394 96

We describe procedures for the large-scale production of equine infectious anemia virus (EIAV) and for the isolation of the four major non-glycosylated virion proteins, designated p26, p15, p11, and p9. Comparisons of the purified proteins by peptide mapping procedures and by enzyme-linked immunosorbent assays demonstrated the unrelatedness of the four proteins. The characteristic properties of each purified protein were examined by determining isoelectric points and amino acid compositions. We found that EIAV p26 and p9 focus at pI values of 6.2 and 5.0, respectively, and that these proteins contain no unusual amino acids. In contrast, EIAV p15 reproducibly displayed a heterogeneous isoelectric focusing pattern, with major pI values ranging from 5.7 to 8.3. This charge variation evidently correlated with different levels of phosphorylated serine or threonine or both, which could be detected by an amino acid analysis of purified p15. EIAV p11 apparently focused at a pI of greater than 10, reflecting its high content of basic amino acids. Moreover, localization experiments indicated that all four nonglycosylated proteins constitute the internal components of the virus, with all of the virion p11 closely associated with the viral RNA genome. Thus, our results demonstrated that EIAV, a lentivirus, contains structural polypeptides which are analogous to the structural polypeptides described previously in prototype C oncoviruses.
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PMID:Isolation and comparative biochemical properties of the major internal polypeptides of equine infectious anemia virus. 617 43


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