Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of serum gamma-glutamyl transpeptidase (GGT) and, when appropriate, alkaline phosphatase (AP) and 5'-nucleotidase (NTD) have been measured as a routine in 276 patients with malignant haematological diseases during a 26-month trial period. GGT levels add no prognostic information to the routine haematological surveillance of leukaemia. Polychemotherapy does not appear to be an inducer of liver drug-metabolising microsomal enzymes. Polycythaemia rubra vera, myelofibrosis and chronic lymphocytic leukaemia may cause little change in GGT, AP and NTD levels despite marked hepatomegaly. A raised GGT in Hodgkin's disease and non-Hodgkin lymphoma is generally associated with active and widespread disease, but not necessarily a sign of malignant tissue in the liver. The elevations of GGT in myeloma may be secondary to liver infiltration though this group merits further detailed study.
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PMID:Evaluation of the usefulness of serum gamma-glutamyl transpeptidase levels in the management of haematological neoplasia. 2 19

To determine whether decreased alkaline phosphatase activity in the granules from neutrophils of patients with chronic myelogenous leukemia (CML) was due to an absence of enzyme or the production of defective enzyme, we compared the immunologic properties of granule alkaline phosphatase derived from patients with CML with that of normal subjects and patients with polycythemia vera (PRV). Antisera prepared in rabbits against granule alkaline phosphatase purified from the neutrophils of a patient with PRV produced a single precipitin line of antigenic identity when reacted with extracts of normal, PRV, and CML neutrophil granules. A histochemical stain for alkaline phosphatase activity (alpha-naphthyl acid phosphate coupled with Fast Blue RR) specifically stained the precipitin line. A variety of quantitative precipitin techniques failed to produce satisfactory precipitation of alkaline phosphatase activity. Comparative analyses were therefore performed by affinity chromatography using goat antirabbit-gammaglobulin linked to Sepharose 4B to adsorb alkaline phosphatase complexed with rabbit gamma globulin. With this method, 100% of CML, normal, and PRV alkaline phosphatase could be adsorbed. Using limiting concentrations of antibody, a proportionally smaller fraction of enzyme activity was absorbed as the concentration of PRV alkaline phosphatase or normal alkaline phosphatase was increased. Extracts of CML granules containing comparable amounts of protein but 200-fold less alkaline phosphatase activity per milligram did not specifically reduce adsorption. Thus, in CML, we found no evidence that the granulocytes contained a large amount of antigenically normal but enzymatically defective alkaline phosphatase. Examination of electron micrographs revealed no significant differences in the number or distribution of granules in the granulocytes of normal subjects or patients with PRV or CML. This suggests that the low level of neutrophil alkaline phosphatase in CML granulocytes is the result of decreased enzyme content and not a consequence of synthesis of catalytically defective enzyme.
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PMID:Neutrophil alkaline phosphatase: comparison of enzymes from normal subjects and patients with polycythemia vera and chronic myelogenous leukemia. 4 59

Polycythemia rubra vera and chronic myelogenous leukemia are both myeloproliferative disorders and, as such, share certain clinical features. Although some myeloproliferative disorders may transform into others, conversion of polycythemia rubra vera to chronic myelogenous leukemia has been denied. We report here an elderly man with polycythemia rubra vera and a normal leukocyte alkaline phosphatase who developed chronic myelogenous leukemia with a low leukocyte alkaline phosphatase and a marrow karyotype of 45, X, Ph1-positive. In addition, we have collected evidence of two similar cases and thus conclude that, although uncommon, polycythemia rubra vera may on occasion progress to chronic myelogenous leukemia.
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PMID:Polycythemia rubra vera progressing to Ph1-positive chronic myelogenous leukemia. 106 Mar 94

Polycythemia vera (PV) is one of the myeloproliferative diseases, and, as such, is an example of clonal hematopoiesis. The progeny of a single, abnormal, hematopoietic stem cell gain a growth advantage over their normal counterparts resulting in overproduction of red cells generally accompanied by overproduction of granulocytes and platelets as well. There are a variety of nonspecific symptoms at onset related to the increased red cell mass and hematocrit accompanied by the more specific manifestations of pruritus, erythromelalgia, and hepatic, portal, and mesenteric vein thrombosis. Splenomegaly and hypertension are common. The laboratory hallmark is an increased red cell mass. There is also often an increase in white cell count, platelet count, and leukocyte alkaline phosphatase along with other findings reflecting the increased rate of turnover of hematopoietic cells. The bone marrow biopsy generally displays hypercellularity involving all three cell lines and absent iron stores. The diagnosis of PV depends on excluding spurious polycythemia in which there is a high hematocrit but a normal red cell mass and secondary polycythemia in which there is an increased red cell mass in response to tissue hypoxia or the inappropriate production of erythropoietin, generally by a tumor. In addition, one should try to establish the diagnosis in a positive fashion by a combination of studies of the blood and bone marrow. Phlebotomy and occasionally plateletpheresis should be used as acute therapy. Chronic therapy is guided by the knowledge that patients treated with phlebotomy alone have an increased rate of thrombotic complications particularly in older patients and those with previous thrombotic disease. Myelosuppressive therapy can reduce the incidence of these complications, but is commonly associated with an increased incidence of second malignancies, particularly acute leukemia. At present, hydroxyurea is the myelosuppressive agent of choice. Antiplatelet agents have a limited role except in the palliation of the syndrome of erythromelalgia. Median survival is approximately 10 years. As implied above, the causes of morbidity and mortality vary with the mode of chronic therapy which has been employed, leukemia being more common after myelosuppressive therapy and thrombotic complications being more common after therapy with phlebotomy alone. Ten percent to 50% of patients move into a spent phase followed by postpolycythemic myeloid metaplasia, irrespective of previous therapy employed. Eventually, the major problems may be cytopenias and massive splenomegaly.
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PMID:Polycythemia vera. 158 7

The activity of neutrophil alkaline phosphatase (NAP) has been commonly measured semi-quantitatively by rating the intensity and number of positive granules on cytochemical staining. This method has been widely adopted because of quickness and simplicity. However, the scoring system, in itself, seems to have several demerits that it has poor reproducibility and has limit for expressing enhanced NAP activity. We improved previous methods for measuring biochemical activities of NAP. Our method was as quick and simple as cytochemical measurement and had more excellent reproducibility. Biochemical activities of NAP ("b-NAP"s) in extract from 2 x 10(6) neutrophils of 7 patients with polycythemia vera were about six times as high as those of 7 cases of essential thrombocythemia [144.8 +/- 33.2, 23.1 +/- 9.1 U, respectively], while NAP scores in the former showed only twice the degree of elevation of those in the latter. These observations suggest that our method can represent high NAP activity more exactly than NAP score and may be a potential tool in differentiating polycythemia vera from essential thrombocythemia.
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PMID:[An improved method for biochemical measurement of the activity of neutrophil alkaline phosphatase and its application to myeloproliferative disorders]. 194 23

We observed significantly reduced serum alpha 2-HS glycoprotein concentrations in patients with acute lymphocytic, acute nonlymphocytic, chronic granulocytic and chronic myelomonocytic leukemias, Hodgkin's and non-Hodgkin's lymphomas, myelofibrosis, and multiple myeloma, but not in patients with chronic lymphocytic leukemia and polycythemia vera, as compared with healthy controls. We followed the serum level of the protein for 18 months. Patients with infectious complications, those receiving cytostatic treatment, and those in the preterminal period had further reduced serum alpha 2-HS glycoprotein levels. The reduction of serum alpha 2-HS glycoprotein concentration was primarily due to decreased production caused by infiltration of the liver, a hepatotoxic effect of cytostatic treatment, and, to a lesser degree, to increased consumption. We found statistically significant negative correlations between serum alpha 2-HS glycoprotein concentration and erythrocyte sedimentation rate, serum aspartate aminotransferase and alkaline phosphatase activities, and IgG and IgM concentrations. The determination of the alpha 2-HS glycoprotein concentration is useful for the assessment and follow-up of the clinical status and therapy of patients with hematological malignancies and also has prognostic significance.
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PMID:Serum alpha 2-HS glycoprotein concentration in patients with hematological malignancies. A follow-up study. 195 51

Forty-eight patients with polycythemia vera (PV) were retrospectively studied for incidence of acute leukemia over a 12 year period. Initial clinical features, hemogram, RBC mass, B12 levels, neutrophil alkaline phosphatase (NAP), and therapy given were studied for association with development of acute leukemia. There were 25 males and mean age at diagnosis was 61.4 years. Initial Hg was 18.38 +/- 1.86 g/dl, WBC 16.44 +/- 12.92 (x 1,000/mm3), platelets 632.94 +/- 303.81 (x 1,000/mm3), B12 1,030.93 +/- 445.20 pg/ml, and neutrophil alkaline phosphatase (NAP) score 136.63 +/- 55.14. Twenty-three patients were treated with phlebotomy alone and 25 received additional myelosuppressive therapy as follows--2 received p32 alone, 4 alkylating agents alone, 8 hydroxyurea (HU) alone, and 11 received 2 or more (multiple) of these agents. None of those treated with phlebotomy alone but 6 of 25 (24%) patients given myelosuppressive therapy developed acute leukemia (P = .03) after a mean period of 46.8 months from start of myelosuppressive therapy. Four of the 11 patients (36%) receiving multiple agent therapy developed acute leukemia (P = .019). Initial hemoglobin levels, but not the other clinical parameters, were significantly higher in patients who developed acute leukemia (P = .002), and this difference persisted in various subgroups receiving myelosuppressive therapy. Thus, high initial hemoglobin and use of any myelosuppressive therapy are associated with an increased risk of leukemic transformation in polycythemia vera. This risk becomes substantial with the use of two or more myelosuppressive agents. Since myelosuppressive therapy does not prolong survival, its role in the management of polycythemia vera should be reexamined.
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PMID:Leukemic transformation in polycythemia vera: analysis of risk factors. 232 2

We recently reported the development of several monoclonal antibodies (MoAbs) to native human erythropoietin (Ep). In the present study we have used the two antibodies with highest affinity to develop a two-sided or sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ep in human serum. In this assay Ep is incubated in microtiter wells precoated with the first (IgE) anti-Ep antibody. Assay wells are then incubated with the second (IgG1) anti-Ep antibody, which is labeled noncovalently with the enzyme alkaline phosphatase (AP) by means of bispecific tetrameric antibody complexes consisting of IgG1 anti-Ep cross-linked to IgG1 anti-AP using rat MoAbs specific for mouse IgG1. Application of this noncovalent labeling procedure, in combination with substrate amplification, results in a detection sensitivity of 0.5 to 1.0 mU/sample (5 to 10 mU/mL), which makes this assay suitable for measuring normal serum Ep levels. The validity of this ELISA for quantitating Ep in biological fluids was demonstrated by the parallelism obtained between pure recombinant Ep dose-response curves and those obtained with plasma and serum from healthy donors and patients with various hematologic disorders. Normal plasma Ep levels detected with this ELISA ranged from 9 to 101 mU/mL with a mean of 32 +/- 23 (SD) mU/mL. Ep levels in sera from patients with polycythemia vera were in the low to normal range, whereas Ep levels in sera from patients with secondary polycythemia and patients with aplastic anemia were moderately to strongly elevated. These results demonstrate that the Ep-ELISA is a sensitive, reliable, and nonradioactive immunologic method for quantitating Ep levels and should prove useful in a variety of clinical and laboratory settings.
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PMID:An enzyme-linked immunosorbent assay for erythropoietin using monoclonal antibodies, tetrameric immune complexes, and substrate amplification. 247 3

Phenylhydrazine (PHZ) is a hemolytic agent which has been used in the treatment of polycythemia vera. Recent studies performed in our laboratory have indicated that the PHZ-induced anemia is immuno-hemolytic in etiology, and a prolonged bleeding time was present in some of the rats chronically treated with PHZ. The nature of this bleeding tendency was explored in the present experiment. PHZ was administered to rats once a week for a six week period. During this time, the animals were monitored for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration, and individual coagulation factor levels as well as routine plasma chemistries and blood cell counts. In addition, radioimmunoassays (RIA) for prostacyclin, a platelet aggregation inhibitor, and prostaglandin (PG) E2 were performed. PHZ-treated animals displayed a significant elevation in both PT and APTT when compared with saline injected controls, although plasma fibrinogen levels were not appreciably altered. Further tests revealed a PHZ-induced decrease in prothrombin and factor V levels. In addition, a significant increase in plasma serum glutamate oxaloacetate transaminase (SGOT), lactate dehydrogenase (LDH), and alkaline phosphatase levels was observed as well as a diminution in cholesterol and triglycerides following PHZ administration. PHZ treatment also induced an elevation in prostacyclin levels and transient thrombocytopenia. These findings indicate that several factors may contribute to the prolonged bleeding time in PHZ-treated rats including a drug induced thrombocytopenia possibly associated with enhanced synthesis of autologous immunoglobulin G (IgG) against the senescent red cell antigen, and diminished synthesis of vitamin K-dependent coagulation factors which may be mediated by reduced vitamin K uptake by the hypo-cholesterolemic subjects.
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PMID:Hemostatic alterations associated with phenylhydrazine-induced anemia in the rat. 262 15

The occurrence of polycythemia vera in a father, mother, and two sons is reported. Thirteen kindreds with familial polycythemia vera in 31 members are reviewed. Comprehensive records were available for all four patients as well as other family members, since all were diagnosed and treated at the author's institution over a period of nearly 50 years. The mean age at diagnosis, sex predominance, symptoms, and incidence of chromosomal abnormalities, leukocytosis, thrombocytosis, and elevated leukocyte alkaline phosphatase levels were similar to those of nonfamilial cases. The mean RBC volume at diagnosis and the incidence of splenomegaly appear to be higher in familial than nonfamilial cases. The mode of inheritance is unclear, but genetic factors may be involved in the pathogenesis of this myeloproliferative disorder.
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PMID:Familial polycythemia vera. 269 Nov 18


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