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)

Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon (3 X 10(6) units/day) from the 3rd through 23rd day of the menstrual cycle, and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle. Concentrations of cytosol and nuclear estrogen receptors (ERC and ERN, respectively) and progestin receptors (PRC and PRN) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle. In addition, an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed. Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle, suggesting that interferon interacts in vivo with the function of both FSH and LH. No significant changes were observed in the serum peptide hormone concentrations measured (FSH, LH, prolactin, insulin, growth hormone and TSH); neither were the levels of endometrial ERC, ERN, PRC and PRN affected by interferon administration. As expected, interferon administration resulted in decreased leukocyte counts. Moreover, an increasing tendency in the activities of serum alkaline phosphatase and gamma-glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function. These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds.
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PMID:Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon. 617 89

A technique is described for measurement of the antiviral activity of interferon by an immunoenzymatic assay for viral proteins. Cells treated by tested samples of interferon (IFN) are infected with vesicular stomatitis virus (VSV) and following the development of viral cytopathy are lysed by the addition of deoxycholate and then transferred into ELISA microplates. The viral proteins bind effectively to the microplates proportionally to their level in the culture and may be measured by incubating the plates sequentially with (1) rabbit antiserum against VSV, (2) a conjugate of alkaline phosphatase either to protein A or to an antibody against rabbit IgG and (3) p-nitrophenylphosphate. This procedure may be further simplified by using antibodies against VSV to which alkaline phosphatase has been directly conjugated. We found this immunoenzyme assay to be superior to the 'cytopathic effect inhibition' assay in precision and sensitivity and in being independent of the effectiveness of viral cytopathy.
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PMID:An immunoenzyme quantitative assay for the antiviral effect of interferons. 620 98

In accord with previous studies, (I)n . (C)n, a potent inhibitor of the cell-free protein-synthesizing system of interferon-treated L cells, stimulates incorporation of 32P from [gamma-32P]ATP into the 67,000-dalton protein, P1. The double-stranded RNA (I)n . (br5C)n, which is inactive as an inhibitory of protein synthesis, does not stimulate phosphorylation of P1 under conditions approximating those of protein synthesis. However, we have found conditions under which (I)n . (br5C)n is approximately as effective as (I)n . (C)n in stimulating incorporation of label from [gamma-32P]ATP into 67,000-dalton protein. Upon transfer of labeled P1 from these conditions to those compatible with protein synthesis, there is a time-dependent decrease in label in the 67,000-dalton protein. This decrease is more rapid in the presence of (I)n . (br5C)n than in the presence of (I)n . (C)n. This differential decrease is also observed when 32P-labeled extracts are diluted into buffer containing 10 mM ATP, hexokinase and 1 and M glucose, or Escherichia coli alkaline phosphatase. A partial proteolytic digest of P1 labeled in the absence of double-stranded RNA or in the presence of (I)n . (C)n or (I)n . (br5C)n gives rise to similar peptide patterns. These results suggest that dephosphorylation as well as phosphorylation determines the net incorporation of 32P into P1. Moreover, these results suggest the existence of a phosphatase activity that may be inhibited more strongly by (I)n . (C)n than by (I)n . (br5C)n.
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PMID:Double-stranded RNA inhibits a phosphoprotein phosphatase present in interferon-treated cells. 624 37

A rapid and convenient assay for adenylyl(2' leads to 5')adenosine(A2'p5'A) or adenylyl(3' leads to 5')adenosine(A3'p5'A) phosphodiesterase activities is described. The dinucleotides A3'p5'A and A2'p5'A were labeled to a high specific activity by means of a catalytic-exchange procedure. Degradation studies of each of these labeled dinucleotides showed an asymmetrical distribution of label between the two adenine bases. Enzymatic degradation of [3H]A3'p5'A or [3H]A2'p5'A could be quantitated by first digesting the reaction products with bacterial alkaline phosphatase and then adding a slurry of DEAE-Sephadex. Under conditions described, adenosine did not adsorb to the resin, whereas dinucleotides as well as AMP did adsorb. As a consequence, when liquid scintillation fluid was added to the DEAE-Sephadex reaction mixture slurry, the radioactivity of the dinucleotides and AMP was severely quenched. This permitted a direct estimation of the amount of adenosine liberated during the phosphodiesterase degradation and subsequent alkaline phosphatase digestion. This method was applied to the measurement of A2'p5'A degrading activities in extracts of mouse L cells. Extracts from control mouse L cells were as active in degrading A2'p5'A as extracts from interferon pretreated cells.
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PMID:Assay of 2',5'-oligoadenylate phosphodiesterase activity in mouse L-cell extracts. 630 30

Preliminary results of comparative characterization of the functional activity of leukocytes by cytochemical, virologic, immunologic, and clinical methods of examinations in institutionalized young infants are summarized. The observations covered 100 infants varying in ages from 1 to 3 years with frequent and rare incidence of respiratory diseases. The diagnosis of influenza had been confirmed by serological methods: CFT and ELISA. Infants with positive serodiagnosis were selected for further studies. The functional status of leukocytes was determined by the interferon leukocyte test (ILT), alkaline phosphatase and myeloperoxidase activities. The results presented in the Tables have shown the infants frequently suffering from ARVD to have low values of ILT and higher values of alkaline phosphatase activity but low myeloperoxidase activity. More resistant infants with rare incidence of ARVD had high ILT, high myeloperoxidase activity and low alkaline activity. It is suggested that alkaline activity of leukocytes alone may be of informative value.
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PMID:[Leukocyte function as one of the indices of resistance to influenza in children]. 630 26

(2'-5')Oligoadenylate synthetase [(2'-5')A synthetase], which synthesizes a series of oligoadenylates ppp-(A2'p)n5'A [collectively referred to as (2'-5')A], has been described previously in rat liver cells, where its concentration varied with the growth status of this organ--i.e., it decreased during the early phase of rat liver regeneration after partial hepatectomy. Because double-stranded RNA, the only known activator of this enzyme, has been detected in rat liver nuclei, (2'-5')A synthesis could occur in this tissue in vivo. Analysis of rat liver cell extract after HPLC by the endonuclease-based radiobinding assay revealed several components with retention times similar to (2'-5')A trimer- and tetramer-like material. A further characterization of these compounds by their susceptibility to alkaline phosphatase and snake venom phosphodiesterase, their resistance to micrococcal nuclease, and their ability to activate an endonuclease indicated the natural occurrence of oligonucleotides indistinguishable from authentic (2'-5')A in rat liver cells. Using the combination of the radiobinding assay and a simplified (2'-5')A extraction procedure that does not involve HPLC, we further show that the early drop of (2'-5')A synthetase activity during rat liver regeneration was accompanied by a similar decrease in intracellular (2'-5')A concentration. The three characteristic phases of the (2'-5')A synthetase kinetics during the first 40 hr of liver regeneration were mimicked by the kinetics of the synthesis of the (2'-5')A oligonucleotides themselves: between 6 and 20 hr after hepatectomy, there was a sharp decrease in (2'-5')A concentration; between 20 and 24 hr, the concentration of (2'-5')A reached a minimum; at 36 hr or after the first wave of DNA synthesis (the major event of liver regeneration), the (2'-5')A concentration returned to normal. In this characterization of the (2'-5')A oligonucleotide family in a functional tissue of an animal that had not been previously treated with interferon or infected with virus, the data are compatible with a physiological role of the (2'-5')A system acting as an intracellular component of the regulatory mechanisms leading to cell proliferation or differentiation.
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PMID:(2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy. 630 30

2',5'-oligoadenylates can be assayed sensitively in cell extracts by use of an antiserum having maximum specificity for any compound containing the moiety -pA2'pA2'pA-. These compounds reached high concentrations (25-2000 nM) in monkey CV-1 cells after infection with simian virus 40 (SV40) and treatment with human leukocyte interferon. The levels were highest late in infection and increased in parallel with the accumulation of SV40 late messenger RNAs. Alone, neither interferon nor SV40 caused the 2',5'-oligoadenylate concentrations to increase above the levels present in untreated CV-1 cells, 3 nM or less. Analyses by high performance liquid chromatography revealed little or no (p)pp(A2'p)2A or (p)pp(A2'p)3A, and the extracts showed only very low activity in functional assays with ppp(A2'p)nA-dependent nucleases, equivalent to 3 nM ppp(A2'p)3A or less. Some of the 2',5'-oligoadenylates eluted in the positions of the nonphosphorylated "cores," (A2'p)nA, and a substantial fraction was found in several peaks intermediate between ppp(A2'p)3A and cores. The positions of most of these peaks did not change when digestion with alkaline phosphatase was performed before chromatography, indicating that most of the 2',5'-oligoadenylates lack exposed phosphate groups. In contrast to the effects of infection with SV40, addition of poly(I) X poly(C) to interferon-treated CV-1 cells led to accumulation of high levels (up to 3000 nM) of 2',5'-oligoadenylate-5'-di- or triphosphates capable of activating the ppp(A2'p)nA-dependent ribonuclease.
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PMID:Simian virus 40-infected, interferon-treated cells contain 2',5'-oligoadenylates which do not activate cleavage of RNA. 631 8

A phase I study of human lymphoblastoid interferon (IFN-alpha) was undertaken in patients with acute leukaemia and other malignancies. The pharmacokinetics of intravenous IFN-alpha were also investigated. IFN-alpha was administered to two patients by intravenous (IV) bolus injection at a dose of 5 X 10(6) U/m2; and to a further 37 patients (40 cycles) by continuous intravenous infusion (IVI) for 5, 7, or 10 days at doses ranging from 5 to 200 X 10(6) U/m2/day. Pyrexia, general malaise, anorexia, and rigors were observed at all dose levels; three patients became hypotensive. Myelosuppression occurred in all patients, including seven without bone marrow infiltration. Transient rises in alkaline phosphatase and transaminases (SGOT) were observed in patients receiving daily doses greater than 30 X 10(6) U/m2. Dose-limiting central nervous system toxicity, hyperkalaemia, and hypocalcaemia were encountered at 200 X 10(6) U/m2. In six patients with acute leukaemia there was a fall in the number of circulating leukaemic blasts and in one patient with acute myelogenous leukaemia (AML) the degree of bone marrow infiltration decreased from 99% to less than 5% with cellularity returning to normal. Serum levels of IFN above 1,000 U/ml were achieved with daily doses above 30 X 10(6) U/m2 given by IVI. The maximum safely tolerated daily dose, 100 X 10(6) U/m2 administered for 7 days, is appreciably higher than that used in most previous studies, although even at this level considerable toxicity may be encountered.
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PMID:A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion. 717 12

Data of 100 selected CGL patients were considered. There were 50 male and 50 female patients with an average 38.1 and 41.5 years of age, respectively. Seventy nine patients were in stable, chronic and 21 patients were in accelerated phase. Patients first admitted in blastic phase were excluded. Twenty two patients were subjected to bone marrow transplantation. Characteristically low levels of neutrophil alkaline phosphatase were absent in about 10 to 25% of early cases. It was considered that the level of positive cells could eventually point to the extent of normal population. In the group of the accelerated patients the neutrophil alkaline phosphatase scores were regularly high and the serum cholesterol values lower than those among stable-phase patients. The role of G-CSF (granulocyte colony stimulating factor) was considered. Secondary myelofibrosis was frequently associated with low serum cholesterol. Average survival time was 41 month among non-transplanted and 63+ months among identically-transplanted patients. In accordance with the literature, authors point out that in the presence of any factor not permitting transplantation, prolonged high-dose interferon-therapy could be the first choice, because unlike chemotherapeutic agents used till now, it prolongs survival. Apart from this autotransplantation with marrow or with circulating blood derived stem cells should be considered.
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PMID:[Survey of one hundred patients with chronic granulocytic leukemia from the view of recent developments]. 753 45

The plasma myeloperoxidase (MPO) level was evaluated using a specific radio-immunoassay (RIA) for MPO in alpha 2b-interferon (IFN)-treated patients with chronic viral hepatitis. The plasma MPO was checked before and after the initial 2 weeks use of IFN at a dose of 6 x 10(6) U/day. The mean concentration of plasma MPO was found to be markedly higher after IFN therapy than that before the therapy (421.7 +/- 34.3 vs 242.9 +/- 23.0 ng/mL, P < 0.001). The plasma MPO negatively correlated with the granulocyte count (r = -0.37, P < 0.02) and the platelet count (r = 0.49, P < 0.01, while it positively correlated with serum alkaline phosphatase (ALP; r = 0.41, P < 0.03). The plasma MPO also showed a strong correlation with plasma polymorphonuclear granulocyte elastase (PMN elastase; r = 0.73, P < 0.001). Our study thus suggests that the increased release of MPO from destroyed granulocytes is responsible for the high concentrations of the plasma MPO in patients during IFN therapy, because the plasma MPO, PMN elastase and ALP abundant in granulocytes all increased in spite of a decrease in the granulocyte count. Granulocytopenia during IFN therapy may therefore be due to the increased destruction of granulocytes in addition to a direct suppression of the bone marrow by IFN.
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PMID:Rise of plasma myeloperoxidase during interferon therapy. 754 3


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