Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth characteristics, survival time, sex differences and hormonal effects, and various biochemical parameters were evaluated in a transplantable Furth/Wistar rat Wilms' tumor model. Survival time was dependent on site of tumor transplant and ranged from a mean of 28 days for intrarenal implantation to 44 days intramusculary. Maximum tumor weight (130 g) was obtained via subcutaneous implant. Lung metastasis was evident in the majority of animals with the exception of those receiving the tumor implant intraperitoneally. The levels of erythropoietin and serum calcium and phosphatase were comparable to control values whereas hematocrit levels declined. Tumor tissue arginase or total protein remained unchanged during tumor growth. In these same tissues DNA, content and 5-alpha-reductase activity significantly and progressively increased with concomitant tumor growths. Measurements of lactic dehydrogenase, alkaline phosphatase, and their isoenzymes indicated patterns of liver involvement which were not macroscopically evident. After 31 days of subcutaneous tumor transplant, male and female rats had tumors of comparable weights. Orchiectomy or estradiol treatment significantly reduced tumor weight in males. In female rats testosterone treatment significantly increased tumor weights. DNA concentration in tumor tissue was unaffected by treatment. Similiarly, although 5-alpha-reductase activity was higher in tumors from males, and arginase higher in females, these enzymes were not affected by surgical or hormonal treatment.
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PMID:Characterization of a Wilms' tumor model. 16 21

A 22-year-old black male presented with erythrocytosis and proteinuria. The erythrocytosis was characterized by increased red cell mass, normal arterial oxygen saturation, and normal hemoglobin electrophoresis and oxygen affinity. There was no splenomegaly, and the white blood cell count, platelet count, serum uric acid concentration, serum B12 levels and leukocyte alkaline phosphatase activity were normal. Tumors of the liver, lung, kidney and cerebellum, which have been associated with erythrocytosis, were not found. The only associated disease was biopsy proven focal glomerulosclerosis. Renal vein thrombosis was excluded by renal venography and arteriography. This case illustrates the rarely reported association of the nephrotic syndrome and erythrocytosis. Other nephrogenic causes of erythrocytosis are mentioned, including renal cysts, tumors, renal artery stenosis and transplantation. The role of the kidney in erythropoietin production and possible mechanisms of nephrogenic erythrocytosis are discussed.
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PMID:Focal glomerulosclerosis and erythrocytosis. 50 18

Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in haemodialyzed patients. Two groups of haemodialyzed patients, each of which comprised 17 subjects, were examined. The first one treated by EPO (EPO group) while the second one did not receive this hormone (NO-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9 and 12 months of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex and age-matched healthy subjects. After EPO therapy an increase of the haematocrit value from 21.8 +/- 0.9% to 32.6 +/- 0.9% was observed which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the NO-EPO group a significant although less marked rise of the haematocrit value (21.4 +/- 0.4% to 24.2 +/- 0.6%) was also noticed. EPO therapy did not change electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose and alkaline phosphatase plasma levels as well as plasma concentrations of calcium related hormones (PTH, calcitonin, 1.25(OH)2D3) and vasopressin (AVP). EPO treatment induced a significant decline of somatotropin (HGH), prolactin (PRO), follitropin (FSH), lutropin (LH), ACTH, cortisol, plasma renin activity, aldosterone, insulin (IRI), glucagon (IR-G), pancreatic polypeptide (PP) and gastrin plasma levels and an increase of plasma estradiol, testosterone and atrial natriuretic peptide (ANP). These EPO induced endocrine alterations were restricted mostly to the first 6 months of EPO administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of long-term erythropoietin therapy on endocrine abnormalities in haemodialyzed patients. 145 6

A sandwich, non-competitive enzyme-linked immunosorbent assay (ELISA) for erythropoietin (EPO) is described. The ELISA utilizes a monospecific, polyclonal antibody raised in rabbits against human recombinant EPO (rhu EPO) and purified over a rhu EPO affinity chromatography column. The ELISA procedure can be summarized as follows: Anti-EPO is coated onto 96-well ELISA microtitre plates; standard EPO or sample is added and left to bind to this catching antibody; this is followed by the addition of the same antibody which has been biotinylated; finally, anti-biotin conjugated to alkaline phosphatase is added and the enzyme reaction developed and read at 405 nm. All parameters of the assay have been optimized. Recombinant human EPO was standardized against the World Health Organization 2nd International Reference Preparation for erythropoietin. The minimal detectable concentration of rhu EPO was 0.3-0.5 mU/ml, which corresponded to 1.2-2 mU/ml of EPO in serum (serum diluted 1:4). No reaction was obtained with a variety of blood components and cytokines, indicating that the anti-EPO antibody did not cross-react with those substances to produce false-positive results. The intra-assay variation ranged from 3% to 10%, while the inter-assay variation ranged from 8.5% to 24%. Serum dose-response curves were parallel to the standard dose-response curve. The assay is easy to use, rapid, reproducible, but above all quantitative, specific and sensitive to measure the EPO content in all serum samples.
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PMID:A sensitive sandwich ELISA for measuring erythropoietin in human serum. 158 Dec 8

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 peroxidase, alkaline phosphatase, acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase activity was assessed using a semiquantitative cytochemical methods in peripheral blood neutrophils from 10 maintenance haemodialysed patients treated with recombinant human erythropoietin (rHu EPO) due to severe anaemia. The examination was performed immediately prior to rHu EPO treatment, after 10 weeks and 32 weeks of therapy. A statistically significant increase in the beta-glucuronidase and N-acetyl-beta-D-glucosaminidase activity was observed after 10 weeks, while all the enzymes studied except peroxidase showed a significant elevation of their activity after 32 weeks of the treatment as compared with the values obtained prior to therapy.
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PMID:[Activity of selected neutrophil enzymes of patients maintained on hemodialysis and treated with erythropoietin (rHu EPO)]. 189 3

The effects of recombinant cytokines on the ploidy of human megakaryocytes derived from megakaryocyte progenitors were studied using serum-free agar cultures. Nonadherent and T cell-depleted marrow cells were cultured for 14 days. Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti-alkaline phosphatase technique, using monoclonal antibody against platelet IIb/IIIa. The ploidy of individual megakaryocytes in colonies was determined by microfluorometry with DAPI (4',6-diamidino-2-phenylindole) staining. Recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner. However, both rhIL-3 and rhGM-CSF had no definite ability to increase the ploidy values. Recombinant human erythropoietin (rhEpo) or recombinant human macrophage colony-stimulating factor (rhM-CSF) by itself did not stimulate the growth of megakaryocyte progenitors. rhEpo or rhM-CSF, however, stimulated increases in the number, size and ploidy values of megakaryocyte colonies in the presence of rhIL-3 or rhGM-CSF. Recombinant human interleukin 6 (rhIL-6) showed no capacity to generate or enhance megakaryocyte colony formation when added to the culture alone or in combination with rhIL-3. rhIL-6, however, increased the ploidy values in colonies when added with rhIL-3. These results show that rhEpo, rhM-CSF and rhIL-6 affect endomitosis and that two factors are required for megakaryocyte development.
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PMID:The effect of cytokines on the ploidy of megakaryocytes. 220 62

The authors reported on a three month long EPREX (human recombinant erythropoietin) therapy of 5 hemodialysis patients for the treatment of their anemia. The drug was administered in bolus form 2 or 3 times a week after dialysis in a dose of 50 to 150 IU/bodyweight increased gradually in every (or every second) week. Hgb ad Htk values were determined once a week while erythrocyte, leukocyte, thrombocyte and reticulocyte count once a month. Serum iron, TIBC, serum ferritin, BUN, serum creatinine, urea, serum ions, liver function assays, serum lipids and amylase were also established. Hgb, Htk levels and reticulocyte count have significantly increased in the 4th week of treatment already, severe anemia ceased with improved appetite, general condition and physical strength. Serum urea and LDH levels significantly increased while SGOT decreased. No significant change in leukocyte and thrombocyte count, serum Na, K, Ca, P, Cl, BUN, creatinine, total protein level, serum albumin, bilirubin, alkaline phosphatase, GGT, GPT, amylase and blood sugar as well as serum lipid level were observed. No adverse reactions occurred during the treatment. After the three gradually decreased and within 6 weeks they had to be transfused again. In three patients the need for transfusion has significantly grown after the treatment. The authors consider EPREX a highly efficient drug in the treatment of anemia in dialysis patients.
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PMID:[Recombinant human erythropoietin in the therapy of anemia in hemodialyzed patients]. 223 36

Human recombinant erythropoietin (r-HuEPO) was given i.v. to rhesus monkeys to compare its safety, erythropoietic effects, and pharmacokinetics in healthy adult and infant animals. Eighteen adult and 18 infant (9- to 15-d-old) monkeys were divided into three groups each of six animals. One group was given 250 U/kg twice weekly, another was given 100 U/kg twice weekly, and a control group was given the drug vehicle for 6 wk. All animals were healthy throughout this period, and for 10 wk after that. Administration of r-HuEPO at these dosages did not produce any changes in leukocytes, platelets, urea nitrogen, bilirubin, creatinine, alkaline phosphatase, alanine amino transferase, gamma-glutamyl transferase, and blood pressure in either age group. At 6 wk, both adult treatment groups had statistically significant increases in Hb concentration. The same dosages that produced these increases in Hb concentration in adults produced no changes in Hb concentration in infant monkeys. Despite active erythropoiesis, as determined by reticulocytosis and increased total body Hb, Hb concentration decreased similarly in the infant treatment and control groups. Pharmacokinetic profiles were obtained at 5 wk of dosing. One h after administration, both doses of r-HuEPO produced significantly lower serum r-HuEPO concentration in the infant monkeys compared with the adults. These differences appeared to be due to a larger volume of distribution of r-HuEPO in the infant monkeys. The t1/2 of r-HuEPO in circulation was the same in both age groups.
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PMID:Age-related differences in erythropoietic response to recombinant human erythropoietin: comparison in adult and infant rhesus monkeys. 228 51

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


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