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)

This contribution presents data from the literature as well as our own results concerning the mechanisms of hepatic encephalopathy (HE). 1. Blood chemistry: In patients with liver cirrhosis, the plasma levels of ammonia, phenylalanine, tyrosine, phenolic acids, and octopamine correlated with the stages of HE. Methionine and free tryptophan concentrations were increased only in stages 2-4. Further, branched chain amino acids were below the normal range. Experimental findings in animals elucidated some mechanisms of these changes. 2. Effects of administered substances: With ammonia, methionine, methanethiol, tryptophan, phenolic substances, and fatty acids central nervous disturbances were observed. 3. Interactions: Anemia, methanethiol, and fatty acids favored ammonia toxicity. Alkalosis diminished cerebral symptoms. 4. Neurotransmitters: HE was accompanied by an enhanced turnover of serotonin and by increased amounts of false neurotransmitters (like octopamine) in the brain. 5. Oxydative brain metabolism: Disorders of cerebral oxygen and glucose utilization were mainly documented in cases of long term HE with EEG alterations. 6. Structural changes of the brain: Most of them are irreversible.
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PMID:[Pathogenesis of hepatic encephalopathy (author's transl)]. 1 66

1. Twelve patients who were treated twice eight hours a week for at least one year were admitted to a dialysis plan of twice seven hours a week and fourteen patients who were dialysed twice eight hours a week for at least one year were dialysed thrice four hours a week. The patients were dialysed with a spool dialysator with cuprophan membrane of a surface of 1 m2. Blood flow was 200--250 ml/min., dialysate flow 500 ml/min. After 3, 6, 10, and 12 months the clinical picture, hydratation, protein katabolism, degree of anaemia and renal osteodystrophy as well as number of complications, degree of rehabilitation, concentration of the medium-molecular substances and of phenylalanine and the glucose tolerance were compared and the opinion of the patients concerning different types of the plan of dialysis was inquired. 2. The plan of dialysis of thrice four hours a week with a conventional dialysator is sufficient for a good state of the most patients. In none of the parameters investigated by us we could establish noticeable differences between the dialysis plan twice eight hours and twice seven hours and thrice four hours a week. The patients themselves clearly preferred a plan of dialysis of thrice four hours a week. 3. The concentration of medium-molecular substances in the blood is no sufficiently sensitive indicator for the determination of the quality of a permanent dialysis treatment in a good clinical state of the patient.
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PMID:[Short-term dialyses using a conventional hemodialyzer]. 67 37

The unstable haemoglobin, Tb Torino (alpha43(CD1)Phe replaced by Val), has been found for the second time in a family from the Treviso region of Italy. The haemoglobin has a slightly lower oxygen affinity than normal. In both cases, the abnormal haemoglobin is associated with inclusion body anaemia but the course of the disorder in the present case is much less severe than that previously reported. The oxygen affinity of the haemolysate has been measured and been found lower than normal.
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PMID:A drug-induced haemolytic anaemia due to Hb Torino (alpha43(CD1)Phe replaced by Val). second finding in an Italian family. 82 80

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

We studied the long-term in vivo effects of recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte functions in nine patients with myelodysplastic syndrome (MDS). The treatment schedule consisted of a 14 d course of rhGM-CSF (250 micrograms/m2/d s.c.) for patients with refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS), while patients with refractory anaemia with excess of blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEBt) received a 14 d combination course of rhGM-CSF (250 micrograms/m2 s.c.) and low dose cytosine arabinoside (20 mg/m2 s.c.). rhGM-CSF increased the mean neutrophil count from 3.9 x 10(9)/l to 44 x 10(9)/l. Significant increases of myeloperoxidase content in granulocytes occurred during treatment (P = 0.003). Phagocytosis and killing of Staph. aureus by granulocytes was markedly enhanced during treatment. Microbicidal capacity normalized in four out of six patients during GM-CSF therapy. However, chemotaxis in response to zymosan-activated serum (ZAS) and f-Met-Leu-Phe (f-MLP), was further impaired on the last day of treatment, which was associated with a marked increase in the expression of the granulocyte adhesion receptors CD11a (P = 0.01), CD11b (P = 0.002), CD11c (P = 0.00015) and CD18 (P = 0.0014). GM-CSF therapy did not cause significant changes in hexose monophosphate (HMP)-shunt activity, chemiluminescence, nor superoxide production. The present results show that in vivo administration of GM-CSF is able to repair at least in part the neutrophil anomalies in patients with myelodysplastic syndrome (MDS), which might be useful in modulating host response to infections. However, increased adherence and impaired chemotaxis may explain some toxicities observed during treatment with GM-CSF.
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PMID:In vivo administration of granulocyte-macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes. 195 74

A significant correlation between MCV and RBCC in intact rats was discovered (r = -0.868, p much less than 0.001, slope = -6.756). Anaemia was induced and the changes in this relationship were studied. Slopes of regression lines (from +1.813 to -118.398) depended on the time which elapsed after strong PHZ-induced haemolytic event: first they changed to positive values, subsequently (during deepest anaemia) to the normal state and to more negative values during the recovery from anaemia. Emergence of MCV values from the regression curve began after weak haemolytic stress from repeated loading of PHE but the values observed did not exceed the prediction interval for individual MCVs.
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PMID:Relationship between erythrocyte volume and count after experimental induction of anaemia in laboratory rats. 243 74

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

As part of our continuing search for new agents which might be useful for the treatment of sickle-cell anemia, we have synthesized two cyclic tetrapeptide homologs, cyclo(-Val-Glu[-Thr-Pro-]-OH) (1a) and cyclo(-Phe-Glu[-Thr-Pro-]-OH (1b), and a tetrapeptide lactone homolog cyclo(H-Thr-Pro-Val-Glu-OH) (2). The intent was that these peptides would mimic a tetrapeptide region around the mutation site of HbS and thus be able to bind at the acceptor site of HbS and thereby inhibit polymerization. The synthesis of the linear peptides was accomplished in solution using both the polymeric reagent (PHBT) and DCC/HOBT methods; cyclization was accomplished by an improved method. 13C-n.m.r. studies were performed which allowed us to assign the conformation about the Thr-Pro bond in 1a and 2 as trans. The cyclic peptides were tested for their ability to increase the solubility of HbS under deoxygenating conditions, but only 1a had any antigelling activity, albeit low.
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PMID:Design, synthesis, and testing of potential antisickling agents. 9. Cyclic tetrapeptide homologs as mimics of the mutation site of hemoglobin S. 359 2

Severe copper deficiency was induced in rats by rearing nursing dams and their offsprings on a semisynthetic diet comprising all the requisite nutrients and trace metals except copper. The copper-deprived rats exhibited growth retardation, severe anaemia, loss of caeruloplasmin, decrease of cytochrome oxidase, accumulation of salt-soluble collagen and a drastic decrease in iron in plasma and liver. Apart from these characteristic signs of deficiency, a marked inhibition of protein synthesis was found to occur both in vivo and in cell-free liver preparations. The curtailed ability to carry out endogenously coded amino acid incorporation into protein contrasted with the unimpaired poly(U)-acid-directed phenylalanine polymerization. This inhibition pattern, as well as the attendant disaggregation of the liver polyribosomes, suggested that the primary biosynthetic lesion was located at the stage of peptide-chain initiation. Concurrently with this alteration there was a pronounced depletion of the hepatic ATP content, associated with a parallel depression of mitochondrial respiration and an enhancement of ATPase activity. Supplementation of the copper-deficient diet with a 2-4-fold excess of iron (relative to the standard diet) prevented growth retardation and anaemia and restored normal energy metabolism, as well as unimpaired protein-synthesizing capacity. The conclusion that these disturbances were primarily determined by the secondary iron deficiency was also borne out by the finding that similar alterations occurred in rats maintained on a copper-sufficient but iron-deficient diet. On the other hand, the iron-fortified diet failed to reverse the other signs of copper deficiency, namely the loss of caeruloplasmin, the diminished rate of cytochrome oxidase and the increase of soluble collagen. The interrelations between the various biochemical lesions induced by deprivation of copper or iron are discussed and the possible role of ATP depletion in determining the derangement of protein synthesis is considered.
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PMID:Biochemical lesions in copper-deficient rats caused by secondary iron deficiency. Derangement of protein synthesis and impairment of energy metabolism. 625 58


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