Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new case of erythrocyte pyruvate kinase deficiency was described. - A 9 year-old male patient was hospitalized because of anaemia, jaundice and splenomegaly. Diagnosis was made primarily on the basis of the erythrocyte enzyme studies. Because the pyruvate kinase of this patient demonstrated certain different characteristics from the other variants described previously, it was tentatively designated PK "Maebashi".
 ...
PMID:A new variant of erythrocyte pyruvate kinase - PK "maebashi". 115 54

Liver disease, particularly alcoholic cirrhosis, is associated with a number of interesting chemical changes which result in structural and metabolic abnormalities of the erythrocyte membrane leading to microscopically observable cell shape changes and hemolytic anemia varying from very mild to potentially lethal. Increase in unesterified serum cholesterol owing to lecithin cholesterol acyl transferase (LCAT) deficiency in cirrhosis leads to expansion of the lipid bilayer and macrocytosis without megaloblastic changes in precursors. Substitutions of phosphatidyl choline (PC) moieties in the erythrocyte lipid bilayer lead to echinocytes (disaturated PC) or to stomatocytes (diunsaturated PC). In some patients, high density lipoprotein (HDL) abnormalities lead to erythrocyte surface changes causing rapid formation of echinocytes. The rapidity and reversibility of these changes suggest blockade of metabolic transport channels critical to the maintenance of erythrocyte membrane shape. Metabolic changes involving vitamin E deficiency leading to lipid peroxidation and pyruvate kinase instability leading to adenosine triphosphate (ATP) reduction have also been invoked to explain hemolysis associated with acute liver damage. The most severe hemolysis in liver disease is associated with acanthocytes (spur cells) and a marked imbalance in cholesterol-phospholipid ratio. These patients usually have hypersplenism, as well as rigid erythrocyte membrane transformations which are irreversible. Any of the other erythrocyte membrane shape changes described appear to be reversible if the liver disease abates, but they too may become irreversible if bits of projecting membrane are repeatedly removed by the macrophages of an enlarged spleen.
 ...
PMID:Mechanisms of hemolysis in liver disease. 218 63

Congenital hemolytic anemia in the Basenji dog resembles pyruvate kinase (PK) deficiency in man as it is characterized by an abbreviated erythrocyte life span, an intense reticulocytosis, type II autohemolysis and splenomegaly. Glucose utilization and lactate production were inadequate with respect to the immature cell population. Analysis of enzymes involved in erythrocyte glycolysis revealed a deficiency of pyruvate kinase.
 ...
PMID:Congenital hemolytic anemia in the Basenji dog due to erythrocyte pyruvate kinase deficiency. 425 18

Ingestion rate of granulocytes in osteomyelofibrosis with splenomegaly, which is still a matter of controversy, was measured in 32 patients. The mean ingestion rate in patients' granulocytes was similar to that of the controls; the results, however, were more dispersed in the patients than in the controls, with very high (three patients) and very low (three patients) ingestion rates. Ingestion alterations were serum-independent. Neutrophil glycolytic enzymes and adenylate-kinase were measured in order to assess: (1) if they could be responsible for the observed abnormalities and (2) if enzyme abnormalities, previously described in red blood cells, also occur in the neutrophils. Major increases in phosphofructoaldolase and in 3-phosphoglycerate kinase activities, contrasting with a decrease in pyruvate kinase activity were observed. These, however, did not correlate with ingestion alterations. In conclusion, we showed that the granulocyte ingestion rate is altered in a few patients only, that the alterations are unrelated to the serum, to adenylate kinase or to glycolytic enzyme abnormalities. The latter, however, are important. The mechanisms of their occurrence are unknown and hypotheses such as those proposed for red blood cells enzyme modifications in myeloproliferative disorders could be applicable.
 ...
PMID:Ingestion rate and glycolytic enzymes in neutrophils of patients with agnogenic osteomyelofibrosis and splenomegaly. 671 65

Trypanosoma brucei EATRO 110 infection in deer mice (Peromyscus maniculatus) produced anemia in 15 of 42 mice between postinoculation days 14 and 70. The infected anemic (IA) mice had significantly higher reticulocyte counts (P less than 0.025), spleen (P less than 0.001) and liver (P less than 0.005) weights, and higher parasitemia than did infected nonanemic (INA) mice. gamma-Globulin concentrations of infected mice were markedly increased, and values for INA mice were 10% higher than values for IA mice. Erythrocyte hexokinase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase, and pyruvate kinase activities were increased in infected mice, whereas phosphofructokinase was only slightly decreased in infected mice. Seemingly, development of anemia was not related to defects in erythrocyte metabolism. Serum iron values of infected mice were similar to those of controls. Storage iron (hemosiderin and ferritin) concentrations were increased in the spleen and to a lesser extent in the liver. The activity of superoxide dismutase, an enzyme that favors conversion of easily mobilized soluble ferritin to poorly mobilized insoluble hemosiderin, was decreased per unit weight of the enlarged spleen, although total activity was increased. The superoxide dismutase activity per unit weight of liver was not altered in infected mice although total liver activities were increased. These findings, as well as the marked reticulocytosis, indicate that lack of iron supply does not have a part in precipitating the anemia of T brucei infection. Leukocytosis was present in infected animals and was associated with lymphocytosis, eosinopenia, basophilia, and monocytosis; these changes were more marked in IA than in INA mice.
 ...
PMID:Pathogenesis of Trypanosoma brucei infection in deer mice (Peromyscus maniculatus): hematologic, erythrocyte biochemical, and iron metabolic aspects. 686 60

Mutant mice with splenomegaly and nonspherocytic hemolytic anemia were found in an inbred colony of the CBA/N (hereafter CBA) strain maintained in the Japan SLC Haruno farm (Shuchi-gun, Shizuoka, Japan). The activity of pyruvate kinase (PK) in red blood cells (RBCs) of the anemic mutants decreased to 16.2% of normal (+/+) CBA mice. Because the mutant CBA mice showed a remarkable reticulocytosis (41.6%) and because the PK activity of reticulocytes is much higher than that of mature RBCs, the PK activity in mature RBCs of the mutant CBA mice was calculated to be 2.8% that of mature RBCs of CBA-(+/+) mice. Because RBC type PK is encoded by the Pk-1 locus of the mouse (chromosome 3), we designated the mutant locus as Pk-1slc. The anemia and PK deficiency of CBA-Pk-1slc/Pk-1slc mice were cured by bone marrow transplantation (BMT) from CBA-(+/+) mice. Prior irradiation was not necessary for the curative BMT. On the other hand, the BMT from CBA-Pk-1slc/Pk-1slc mice to nonirradiated CBA-(+/+) mice did not result in the decrease of RBCs and the reduction of PK activity. The present results indicate that CBA-Pk-1slc/Pk-1slc mice are a potentially useful animal model for studying pathophysiology of PK deficiency and for developing new therapeutic methods to correct PK deficiency.
 ...
PMID:Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the anemia by marrow transplantation without host irradiation. 749 93

Recent progress in the molecular analysis of red cell enzymopathies showed over 160 mutations in the 10 distinct genes which were essential in red cell metabolisms. In addition, since three-dimensional structure of several enzymes including pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G6PD) have been elucidated from X-ray crystallographic studies, the effect of amino acid substitutions on enzyme activity became predictable in some extent. On the contrary, the mechanism of hemolysis remains still unclear. To clarify the pathophysiology of red cell enzymopathies, establishment of an animal model have been long awaited. Recently we discovered the novel mice model of PK deficiency. The mutant mice with splenomegaly and nonspherocytic hemolytic anemia in an inbred colony of the CBA strain were enzymatically diagnosed as PK deficiency. A homozygous missense mutation was identified in the red cell (R)-type PKcDNA sequence of the mutant, and it caused a single amino acid substitution near the substrate binding site of PK. The erythroid-progenitor cell number increased in spleen of the mutant mice to a level approximately 66 times higher than in normal CBA mice, suggesting that compensatory extramedullary erythropoiesis in the spleen of the mutant mice might partly compensate the anemia. The mutant mice will be useful as an experimental model for understanding the pathophysiology of this disorder.
 ...
PMID:[Molecular basis and pathophysiology of red cell enzymopathies]. 889 May 66

In Thailand, the most common cause of chronic hemolytic anemia is thalassemia hemoglobinopathy. We report here a 10-year-old girl with pyruvate kinase (PK) deficiency who was initially diagnosed to have Hb H disease, like her sister. The patient had a history of neonatal jaundice which required blood exchange transfusion twice and phototherapy. She became anemic and regular blood transfusion was required since the age of 2 1/2 months. She was very anemic compared to her sister and was transfusion dependent. Besides, she never had red cell inclusion bodies, thus re-evaluation was performed. The diagnosis of red cell pyruvate kinase deficiency and the exclusion of Hb H disease was achieved after cessation of blood transfusion for 3 months. The family study also confirmed the diagnosis. The patient is now on high transfusion and iron chelation. She is doing well with mild splenomegaly.
 ...
PMID:Pyruvate kinase deficiency in an alpha-thalassemia family: first case report in Thailand. 964 Jun 2

In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.5% and 15% of the normal concentration respectively), a severe glutathione synthetase (GSH-S, EC 6.3.2.3) deficiency was found. One case exhibited a neonatal haemolytic anaemia associated with oxoprolinuria, but without neurological manifestations. The family study revealed GSH-S activity in both parents to be around half the normal level, a finding consistent with the presumed autosomal recessive mode of inheritance of this enzymopathy. Two cases exhibited a well-compensated haemolytic syndrome without anaemia or splenomegaly at steady state. One of these cases was diagnosed after an episode of acute haemolytic anaemia after fava bean ingestion. The remaining patient suffered from moderate to severe chronic non-spherocytic haemolytic anaemia and splenomegaly, and required occasional blood transfusion for a haemolytic crisis associated with drug ingestion. In this patient, the anaemia was corrected by splenectomy. In addition to GSH-S, a panel of 16 other RBC enzyme activities was also studied in all the patients. Hexokinase, aldolase, glucose-6-phosphate dehydrogenase and pyruvate kinase activities all increased; these increases were to be expected, given the rise in the number of circulating reticulocytes. In two patients, the incubation of RBCs with hydrogen peroxide revealed an enhanced production of malonyldialdehyde. DNA analysis showed a homozygous state for 656 A-->G mutation in patients 2 and 3. The GSH-S gene of patient 1, studied elsewhere, revealed an 808 T-->C. The GSH-S gene of patient 4 was not available for study. The present study demonstrates that GSH-S deficiency is also present in Spain and further supports the molecular and clinical heterogeneity of this enzymopathy
 ...
PMID:Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies. 1116 50

A 1-year-old, female Beagle dog with minimal exercise intolerance was found to have a persistent, severe, and highly regenerative anemia, splenomegaly, and progressive osteosclerosis. Despite near-normal in vitro erythrocyte pyruvate kinase (PK) activity, the authors diagnosed PK deficiency by demonstrating a glycolytic block at the PK step, the lack of normal R-type PK isoenzyme, and the presence of M(2)-type PK in the animal's erythrocytes. The dam had half-normal erythrocyte PK activity, which supports an autosomal recessive mode of inheritance. We conclude from our studies that close similarities exist between erythrocyte PK deficiency in Beagle, Basenji, and West Highland White Terrier dogs and that this form of PK deficiency may be more widespread than previously thought.
 ...
PMID:Inherited erythrocyte pyruvate kinase deficiency in a beagle dog. 1267 42


1 2 Next >>