Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The R-type vitamin B12-binding protein (cobalophilin) in plasma and serum of patients with myeloproliferative diseases and leukocytosis was studied by gel filtration and isoelectric focusing. The isoproteins composing the cobalophilin were mainly the same in these disorders as in plasma of health subjects. In half the patients with chronic myelogenous leukaemia and a few of those with leukocytosis some of the isoproteins were more acid than those found in healthy subjects. In chronic myelogenous leukaemia the high unsaturated vitamin B12-binding capacity of plasma was due to an increase in the fairly acid isoproteins, whereas in polycythaemia vera and in most cases of leukocytosis there was an increase in the least acid isoproteins.
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PMID:Characterization of R-type vitamin B12-binding proteins by isoelectric focusing. III. Cobalophilin (R protein) in myeloproliferative states and leukocytosis. 105 18

A gradient was developed for isoelectric focusing in the pH range 2-5. Cobalophilin (earlier called R proteins or vitamin B12-binding proteins of R-type) was isolated from saliva and amniotic fluid in homogeneous form. It was found to be a glycoprotein with a molecular weight of 59,300-69,100. The preparation from amniotic fluid contained 33% carbohydrate. Cobalophilin variants in plasma, serum, granulocytes, platelets, amniotic fluid, milk, saliva and gastric juice were characterized by isoelectric focusing. Most fluids and cells contained the same isoproteins, with pI values between 2.3 and 5.0. Isoproteins of presumably myelogenic origin (e.g. those in granulocytes and plasma) had pI values below 4.2, whereas those of glandular origin (in milk and saliva) had a pI range of 4.0-5.0. Serum contained more cobalophilin than plasma, owing to release of this protein from granulocytes during clotting. This phenomenon also changed the isoprotein pattern. Plasma and serum from newborn infants and from patients with leucocytosis, polycythaemia vera and chronic myelogenous leukaemia contained the same isoproteins as were found in plasma from healthy subjects. In addition to these, isoproteins with lower than 'normal' pI values were often found in chronic myelogenous leukaemia and occasionally in leucocytosis. It is concluded that cobalophilin from different fluids and cells is a single microheterogeneous protein with a variable carbohydrate composition. The distribution of cobalophilin in different body fluids and cells supports the suggestion that cobalophilin is an antimicrobial protein (Gullberg 1972) like lactoferrin and lysozyme.
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PMID:Vitamin B12-binding proteins of r-type, cobalophilin. 105 22

The unsaturated vitamin B12 binding capacity of whole serum (UBBC) and of the three transcobalamins (TC) has been studied in patients with various haematological diseases including myeloproliferative disorders (MPD) and acute leukaemia. The binding capacity of TC I and TC III was increased in MPD; TC I being particularly high in chronic granulocytic leukaemia (CGL) and TC III especially raised in polycythaemia rubra vera (PRV) and in infectious leucocytosis. The binding capacity of both TC I and TC III correlated with blood neutrophil count and the ratio TC III/TC I was low in CGL and increased in PRV. TC II was increased in acute myelogenous leukaemia, during remission and blast cell crisis of CGL and in refractory anaemia with excess of myeloblasts but not in acute lymphoblastic leukaemia (ALL). TC II correlated inversely with blood neutrophil count. There is an inverse ratio between TC II and TC I at least in myelogenous leukaemia. These abnormalities are discussed in relation to granulocyte kinetics. TC III and TC I reflect probably the total body granulocyte pool and share some biochemical and immunological properties supporting the view that they have a common origin in the more mature stages of the granulocyte cell line while TC II probably originates partly in more primitive granulocytes.
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PMID:The three transcobalamins in myeloproliferative disorders and acute leukaemia. 105 79

During studies that showed the presence of fetal antigens on the surface of human malignant melanoma tumor cells, polyvalent antisera specific for human fetal tissues of varying ages were developed. These reagents demonstrated varying patterns of expression of fetal antigens at different ages in various tissues of the human fetus. The possibility that nonneoplastic adult cells showing either maturation arrest or excessive proliferation also might express fetal antigens led to studies of human bone marrow. Although normal bone marrow cells expressed low levels of fetal antigens, large amounts were seen on bone marrow cells of patients with anemias due to iron, B12, or folic acid deficiencies, as well as on those with leukemia. Moreover, normal adult tissues adapted to long-term culture also expressed fetal antigens. After 3 weeks in organ culture adult human skin showed morphological changes similar to those seen in fetal periderm and strongly expressed fetal antigens. In addition, lymphoblasts in long-term cultured human lymphoid cell lines established from normal donors also carried surface fetal antigens. These latter antigens were shared with neoplastic B-cells (chronic lymphocytic leukemia) but not with T-cells. Their expression varied with the cell cycle. The reexpression of fetal antigens on malignant cells is thought to signal a basic derangement in the control of differentiation which is considered to be peculiar to neoplasia. However, these studies indicate that normal adult cells also may reexpress fetal antigens under circumstances unrelated to neoplasia but associated with either maturation arrest or rapid and excessive proliferation.
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PMID:Fetal antigens in nonneoplastic conditions. 108 33

We have investigated proliferation in bone marrow trephine biopsies from 32 patients with normal or abnormal haemopoiesis, using the monoclonal antibody PC10, which detects proliferating cell nuclear antigen (PCNA), together with immunohistochemical markers of haemopoietic cell lineage. PCNA immunostaining revealed the pattern of proliferation within individual haemopoietic lineages in normal marrow. Two unexpected observations were made: of erythroid cells, only pro-erythroblasts and occasional early normoblasts reacted, and positivity of megakaryocytes was unrelated to nuclear lobulation or CD61 expression. The pathological cases represented conditions in which haemopoiesis is increased (reactive hyperplasia, chronic granulocytic leukaemia, myeloproliferative and myelodysplastic syndromes, megaloblastic anaemia). Increases in the number, and disturbances of the spatial organization, of PCNA-expressing cells were present to a variable extent in all cases. Sheets of PCNA-positive megaloblastoid erythrocytes were frequently found in myelodysplastic and myeloproliferative tissue, associated with marked disturbances in the spatial organization of all haemopoietic lineages. Cases of megaloblastic anaemia due to vitamin B12/folate deficiency also demonstrated greatly increased erythroid PCNA expression, with positivity in some giant metamyelocytes. In addition to reflecting increased proliferation, elevated PCNA expression in some bone marrow pathologies may be due to altered kinetics of the protein induced by disturbances in growth factor production.
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PMID:A study of cell proliferation in formalin-fixed, wax-embedded bone marrow trephine biopsies using the monoclonal antibody PC10, reactive with proliferating cell nuclear antigen (PCNA). 134 81

A 36-year-old male was admitted to the Ehime University Hospital with anemia, eosinophilia and hepatosplenomegaly. Peripheral blood examination demonstrated severe anemia (Hb 7.1g/dl), thrombocytopenia (Plt 6.8 x 10(4)/microliters) and increase of peripheral leukocyte counts (53,000/microliters) with 32.0% of eosinophils which had lobulated nuclei, abnormal distribution of eosinophilic granules and a few vacuoles. The level of serum IgE was low (< 5IU/ml), while that of serum vitamin B12 was elevated. A diagnosis of eosinophilic leukemia was made. He was noted to have spontaneous fluctuations in his eosinophil and total leukocyte counts. To analyze the mechanism of cyclic eosinophilic leukocytosis, we examined eosinophil colony stimulating activity of the serum and plasma of the patient. These examination showed that eosinophil colony-stimulating activity was not found in his serum and plasma, and cyclic eosinophilic leukocytosis was due to the hemopoietic stem cell disorder.
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PMID:[Eosinophilic leukemia with cyclic eosinophilic leukocytosis]. 147 3

A 76 year old female with atypical leukemia complicated by vitamin B12 deficiency demonstrated marked fluctuation in blast percentage and hemopoiesis over 8 month period. She underwent surgical removal of pancreas head cancer 5.5 years ago. In January 1989 severe pancytopenia and mild increase of bone marrow blast were found. Blood transfusions and inadvertent administration of Vitamin B12 resulted in alleviation of pancytopenia and decrease in blast percentage. Several months later her bone marrow blast exceeded 30%, when serum B12 concentration was below 90 pg/ml. B12 injection and blood transfusion resulted in significant improvement in her hematological condition, but shortly thereafter she died of fulminant hepatitis. Her bone marrow cells showed a polyclonal constitution, as assessed by the RFLP-methylation technique using the PGK gene as a probe. The coexistence of leukemic- and normal clones under Vitamin B12 deficiency conditions and the differing behavior of such clones to B12 supplementation may explain the unusual clinical course observed in this patient.
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PMID:[Atypical leukemia accompanied by vitamin B12 deficiency]. 160 9

Histocompatibility antigen (HLA) frequencies in chronic lymphatic leukaemia (CLL) patients and control subjects were compared with respect to disease susceptibility and prognosis. Additionally, HLA and full blood count data were compared in relatives of 25 patients and 31 controls. We found no association of HLA with susceptibility although the presence of HLA B12, alone or in combination with HLA A2, indicated better prognosis. Relatives HLA identical with the patients showed no evidence of white cell disorder when compared with haplo- or non-identical relatives, or controls. As a group, however, relatives of patients had fewer lymphocytes than relatives of controls.
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PMID:Chronic lymphatic leukaemia: an investigation of HLA antigen frequencies and white cell differential counts in patients, relatives and controls. 190 41

Both thymidine kinase (TK) and DNA polymerase (DNAp) are present in measurable amounts in human serum. Even though the use of TK as a clinical marker is rapidly increasing there has been no attempt to characterize the serum TK in a wider extent, i.e.; with respect to Mw or other biochemical parameters. Therefore sera with high TK or DNAp activities derived from patients with cytomegalovirus (CMV) infection, B12-deficiency and leukaemia were fractionated by gel exclusion chromatography. The TK activity eluted as two peaks, one major TK activity with an apparent molecular weight (Mw) or 730 kD and one minor TK activity corresponding to a Mw of 58 kD. The amount of TK activity at 58 kD varied between 7 and 23% of total activity, depending on the serum fractionated. The DNAp activity in sera from patients with malignant disease and B12 deficiency eluted as a single peak corresponding to a Mw of 240 kD. A DNAp with a different Mw (greater than 1000 kD) was recovered from 1 of 3 investigated immunosuppressed patients with CMV infection. A similar pattern of enzyme forms was observed when sera were separated by glycerol gradient centrifugation. The effect of high salt and various reaction solution components on the enzymes were studied. The only condition found that affected the molecular forms of TK was the state of reduction. Incubation of sera with high concentrations of dithioerythritol (DTE) (400 mM) prior to separation transferred all serum TK to the 58 kD form, it also converted most of the serum DNAp from the 240 kD form to a smaller form (56 kD) without affecting the total recovery of enzymatic activity. The reaction product from both TK forms was exclusively monophosphate and none of the TK forms could efficiently utilize cytidine triphosphate as phosphate donor. The substrate kinetics of the small serum TK fraction was identical with those of an enzyme with similar size purified from proliferating HeLa cells, indicating that both serum TK activities are forms of TK 1, the proliferation associated cellular isozyme.
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PMID:Molecular forms in human serum of enzymes synthesizing DNA precursors and DNA. 215 79

The administration of nitrous oxide rapidly inactivates the vitamin B12-dependent enzyme methionine synthase. This inactivation disrupts the normal interrelationships between vitamin B12 and folic acid, and results in altered levels of folic acid derivatives and certain amino acids and their metabolites. Attempts have been made to use the antifolate properties of nitrous oxide to treat patients with leukemia. Although transient improvements may be observed in patients with leukemia who are given nitrous oxide, prolonged administration of nitrous oxide is highly toxic and causes marked hematological and neurological abnormalities. Animal and in vitro studies suggest that the action of nitrous oxide may be tumor selective, and that nitrous oxide may interact with and enhance the therapeutic effect of other antitumor agents. However, there is a delicate balance between the possible beneficial and harmful effects of nitrous oxide, and the conditions for which nitrous oxide may prove useful as a chemotherapeutic adjuvant remain to be defined. Concern has also been raised that nitrous oxide may have carcinogenic potential, especially in operating room and dental personnel who are chronically exposed to trace concentrations of this gas. However, there is no convincing evidence to date that nitrous oxide causes cancer in either animals or humans.
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PMID:Nitrous oxide: a cause of cancer or chemotherapeutic adjuvant? 218 94


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