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)

A retrospective analysis of 30 patients with chronic myelomonocytic leukemia (CrMML) was performed to define the natural history of the disease and the risk of acute transformation. Our patients fulfilled the following criteria of diagnosis: blood monocytosis over 1 X 10(9)/l, blast cell percentage in bone marrow up to 30, and in peripheral blood less than 5. The most common presenting feature was anemia; seven patients had fever; three patients complained of purpura and bleeding. Anysopoikilocytosis and macrocytosis were frequent. Abnormal granulocyte morphology, defective granulation and abnormal leukocyte alkaline phosphatase were often observed. Blast cells in peripheral blood smears were found in 14 patients. Serum and urine lysozyme levels were increased in 82 per cent and 93 per cent, respectively. Dysplastic changes involving erythroid, granulocytic and megakaryocytic lineages were constant features in all cases. Agranulated blasts above 5 per cent of marrow nucleated cells were seen in 13 patients (43 per cent). Seven of the 20 patients showed non-specific chromosomal abnormalities at diagnosis. Median survival from diagnosis was 18 months (range, 3-112). Evolution into acute myeloid leukemia occurred in 11 patients. No difference in survival was found between patients who developed acute leukemia and patients who did not. A shorter survival has correlated to the following parameters: leukocytes greater than 10 X 10(9)/l, the presence of blasts in peripheral blood and agranulated blasts in the marrow above 5 per cent.
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PMID:Chronic myelomonocytic leukemia: clinical features, cytogenetics, and prognosis in 30 consecutive cases. 386 Apr 66

A factor, termed neutrophil alkaline phosphatase-inducing factor (NAP-IF), that has the capacity to increase the NAP activity of granulocytes was characterized by using two samples: cystic fluid (CF) and conditioned medium of a tumor cell line (T3M5). The molecular weight of NAP-IF was shown to be between 13,000 and 45,000, and its isoelectric point was between 5.5 and 6.2. It was sensitive to heat and proteolytic enzymes, but was resistant to DNase and RNase, suggesting that NAP-IF is an acidic protein or glycoprotein. These characteristics of NAP-IF seem to be similar to those of granulocyte-macrophage colony-stimulating factor (GM-CSF) that is also present in the CF. NAP-IF rich fractions obtained by isoelectric focusing from CF were also found to be rich in a subclass of GM-CSF: granulocyte-CSF (G-CSF). Furthermore, a high correlation was noted between the activities of G-CSF and NAP-IF (gamma = 0.798, P less than 0.005). These results suggest that the two activities, i.e., G-CSF and NAP-IF, may be attributable to an identical macromolecule.
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PMID:Characterization of neutrophil alkaline phosphatase-inducing factor (NAP-IF). 387 40

These data suggest that two types of radioresistant adherent stromal cells are adequate for maintenance of long term hemopoiesis in the Dexter culture system. One cell type appears to be a typical adherent macrophage while the other is an alkaline phosphatase positive epitheloid cell possibly representative of the adventitial reticular cell of the bone marrow. These two cell types seem to be clearly defined by the in-vivo irradiation studies and less clearly defined in the in-vitro irradiation experiments. These data do not exclude other cell types as playing important roles in modulating hemopoiesis but do suggest that these major types are probably playing important roles in maintaining stem cells in long term liquid cultures. In addition, data suggests that the epitheloid cell directly nurtures hemopoietic cells on its surface while the macrophages may serve a separate function. A number of growth factors are produced by these two cell types which appear to include CSF-1, a granulocyte CSA separate from CSF-1 and a megakaryocyte CSA separate from both the GM-CSA and CSF-1 (Table 5). Thus the present data suggest that there are at least three (formula; see text) separate hemopoietic growth factors produced. The FDC-P1 activity produced by irradiated stroma would appear most likely to be GM-CSA-II. The fact that lectins enhanced production of these activities is intriguing but the cell type on which the lectins are acting has not as yet been defined. It appears that lithium also acts upon adherent marrow stromal cells to induce production of myeloid regulatory growth factors. Lithium appears to stimulate both normal and irradiated stroma to produce hemopoietic maintenance and growth factors and the present data suggests that factors active on pre IL-3 cells, HPP-CFC, CFU-D, CFU-meg, and CFU-S are all induced from these stromal cells by lithium. Whether the lithium induced factors and the factors derived from irradiated stroma represent a number of different growth factors or one or two critical regulatory molecules is at present unclear. The synergistic activity derived from the TC-1 cell line is of particular interest in this regard. This CSF-1 dependent activity is capable of acting on a very primitive stem cell to induce impressive proliferation and differentiation. In addition an activity in TC-1 conditioned media which may be synergistic activity appears capable of inducing adherent marrow cell lines which then can subsequently produce more of the same factor, a classic autocrine system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Bone marrow adherent cell hemopoietic growth factor production. 393 Oct 91

In situ studies with the mouse macrophage (M phi)-specific antibody, F4/80, have shown that resident M phi in femoral bone marrow (RBMM) form hematopoietic islands with immature myelomonocytic and erythroid cells (Hume, D. A., et al. 1983. J. Exp. Med. 158: 1522). We have isolated these islands (clusters) by collagenase digestion, purified them from single cells by velocity sedimentation, and analyzed their cellular content. The clusters, ranging from 5- to 100 cells, constituted approximately 7% of the total nucleated cells, and greater than 70% contained at least one strongly staining, F4/80+ central M phi. In comparison, less than 26% showed reactivity for alkaline phosphatase, a marker of fibroblastoid reticulum cells. Compared with the nonclustering population, clusters were enriched with RBMM, fibroblastoid cells, and immature hematopoietic cells, but depleted of mature granulocytes and erythrocytes. The RBMM population was purified from other cells in clusters by selective adherence to glass and was compared with resident peritoneal M phi (RPM) for morphology and the presence of antigens, receptors, and enzymes. RBMM spread more extensively than RPM and frequently extended delicate plasma membrane processes. These and subsequent differences were not attributable to the collagenase treatment. Both M phi populations stained positively with antibodies F4/80 and 2.4G2 (Fc receptor IgG1/2b), bore mannosyl/fucosyl receptors, and showed reactivity for acid phosphatase and nonspecific esterase I. In contrast to RPM, RBMM had no detectable Mac-1 antigen (CR3) or complement receptors, but bore higher levels of Fc receptors (IgG2a and IgG2b) and Ia antigens. In addition, RBMM possessed a novel hemagglutinin activity for unopsonized sheep erythrocytes, which was not present on RPM. RBMM showed no respiratory burst activity in response to zymosan particles, but ingested them avidly. The growth properties of clustering and nonclustered populations were compared by measurement of [3H]thymidine incorporation and progenitor assays. Cells in clusters incorporated three- to fourfold more thymidine than nonclustered cells even in the absence of exogenous growth factors, and autoradiography demonstrated that RBMM made contact with proliferating cells. In contrast, the clusters contained over threefold fewer granulocyte/M phi progenitors compared with nonclustering cells. When clusters were cultivated for up to 3 d, there was rapid outgrowth of monocytes and fibroblastoid cells. These studies demonstrate that RBMM bear a distinct morphology and phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Isolation and characterization of resident stromal macrophages and hematopoietic cell clusters from mouse bone marrow. 403 89

To characterize the biological changes which result in increased granulocyte alkaline p-nitrophenyl phosphatase activity in patients with polycythemia vera, the enzyme was purified from granule fractions of sucrose homogenates made from dextran-sedimented leukocytes of normal subjects and patients with polycythemia vera. Polycythemic blood yielded 3-10 times as much granulocyte alkaline phosphatase per 10(9) leukocytes as did normal blood. Sodium dodecyl sulfate extracts of granules were purified by DEAE-cellulose chromatography and sucrose gradient centrifugation to apparent homogeneity as judged by polycarylamide disk gel electrophoresis. Granulocyte alkaline phosphatase from normal subjects was purified 6910-fold with a 60% yield and a specific activity of 47 U/mg. Granulocyte alkaline phosphatase from polycythemic patients was purified 1.166-fold with a 50% yield and a specific activity of 70 U/mg. The two enzymes did not differ in molecular weight; both appeared to be about 160,000 daltons by sucrose gradient centrifugation. Both appeared to be zinc metalloenzymes, in that they were specifically inhibited by o-phenanthroline. Their elution requirements when adsorbed to DEAE-cellulose suggested they were lipoproteins although the content of phosphorus was below the threshold of detection. The identity of the two enzymes was suggested by immunological studies in which antibody prepared against purified polycythemia vera enzyme gave a precipitation reaction of identity with another polycythemia vera enzyme and two pools of normal enzyme. It is possible to account for the difference in alkaline phosphatase activity between the granulocytes of patients with polycythemia vera and normal subjects by differences in the quantity of enzyme synthesized.
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PMID:Granulocyte alkaline phosphatase. Studies of purified enzymes from normal subjects and patients with polycythemia vera. 473 97

Evidence has been obtained for the humoral mediation of the recently noted tumor-induced rise of the host bone marrow gamma-glutamyltranspeptidase (gamma GT) and alkaline phosphatase (AP) content in vivo: normal rat bone marrow suspensions, if incubated for 18 hr to 3 days with serum from mammary carcinoma hosts, show 2- to 8-fold elevations (per cell) of the same 2 enzymes. The active substance(s) is in the acid-stable, HCI-ethanol-soluble polypeptide fraction of the mammary carcinoma extract, and of the hosts' blood serum. The larger the size of the neoplasm, and the faster its growth rate, the greater the effect of the host serum on the gamma GT and AP of the normal bone marrow cells. In host rats in vivo, this response is followed by increases in the number (as well as the gamma GT and AP content) of circulating granulocytes. Therefore, a positive response on the part of these enzymes in the bone marrow suspension was also sought, and found, upon incubation with preparations which enhance granulocyte colony formation in agar cultures (i.e., colony-stimulating factor and serum from endotoxin-treated rats). The results indicate: (a) that the increase in gamma GT and AP is a necessary prelude to stimulation of granulocyte multiplication by appropriate growth factors; and (b) that measurement of these enzymes in the short-term liquid culture offers a biochemical test for such factors elaborated by cancers or in nonneoplastic conditions.
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PMID:Responses of bone marrow gamma-glutamyltranspeptidase and alkaline phosphatase in vitro to tumor-elaborated granulocytopoietic factors. 614 Oct 2

A number of cytochemical parameters of the hemocytes of larval Galleria mellonella, an insect frequently used as a model by comparative cellular immunologists, are described. Cytochemical methods were used to quantify hemocyte granule-associated components, the results are compared to those obtained for leukocytes from higher animals. Granulocytes contained a population of nonlysosomal granules rich in mucopolysaccharide not seen in plasmatocytes. The numbers and dimensions of these granules showed a positive correlation to cell size, probably reflecting a developmental sequence in granulocyte maturation. Both granulocytes and plasmatocytes had other granules containing the typical lysosomal enzymes, acid phosphatase, beta-glucuronidase, esterase, and lysozyme. The nonlysosomal enzyme alkaline phosphatase was not found in Galleria hemocytes; it is also absent from vertebrate monocytes, macrophages, and immature polymorphonuclear leukocytes. Insect hemocytes appear to lack certain components of antibacterial systems typical of mammalian blood cells, such as H2O2-generating systems, cationic proteins, and myeloperoxidase. The bactericidal mechanisms of hemocytes probably involve lysozyme, as well as other biologically active cellular and humoral factors unique to insects.
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PMID:Observations on the cytochemistry of the hemocytes of an insect, Galleria mellonella. 618 80

In 7 penicillamine-treated patients with generalized scleroderma zinc in serum, erythrocytes and granulocytes, alkaline phosphatase activity in serum and granulocytes, carbonic anhydrase activity in erythrocytes were examined. No significant difference was found between patient and control values, but granulocyte zinc strongly tended to be decreased (0.1 greater than p greater than 0.05). It is our hypothesis that penicillamine may produce a zinc depletion at a cellular level.
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PMID:Zinc and zinc-dependent enzymes in penicillamine-treated patients with generalized scleroderma. 620 23

Fifty-seven patients with refractory acute leukemia were treated with high-dose cytosine arabinoside to establish the maximum tolerated dose and duration and to determine the antileukemic activity. The maximum tolerated regimen was found to be 3 g/sq m every 12 hr for 6 days. At this dose, nonhematologic toxicity was limited to conjunctivitis in approximately half of the patients, and liver toxicity (transient elevations in transaminase, alkaline phosphatase, or bilirubin) was frequently observed, but neither was dose-limiting. Extending the duration of treatment to 8 days resulted in excessive diarrhea and skin toxicity (painful erythema with bullae), while increasing the dose to 4.5 g/sq m q. 12 hr for 6 days resulted in severe cerebellar toxicity. Myelosuppression was severe, but was not related to the intensity of treatment; granulocyte recovery occurred a median of 28 days (range 22-40 days) after initiating therapy, and platelet recovery occurred after a median of 25 days (range 16-41 days). Antileukemic activity was evaluable in the 46 patients who survived at least 3 wk. Complete remissions were obtained in 1 of 6 patients with chronic myelogenous leukemia (CML) in accelerated phase and 1 of 3 acute lymphoblastic leukemia (ALL) patients. A more detailed analysis of response was possible for the 37 evaluable patients with acute nonlymphoblastic leukemia: 70% of these patients responded, with 51% complete remissions. The median unmaintained response was 4 mo (range 2-26+ mo). The complete response rate was higher in patients who received at least 12 doses of high-dose cytosine arabinoside compared to shorter regimens [17/28 (61%) versus 2/9 (22%), p less than 0.05]. Resistance to cytosine arabinoside in conventional doses was documented in 11 patients, 5 of whom responded (2 complete remissions) to high-dose regimens. We conclude that high-dose cytosine arabinoside in the maximally tolerated regimen of 3 g/sq m every 12 hr for 6 days has substantial antileukemic activity in patients refractory to standard therapy. Durable unmaintained remissions can be achieved, even in patients who fail to respond to cytosine arabinoside in conventional doses.
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PMID:High-dose cytosine arabinoside therapy for refractory leukemia. 622 74

Zinc in granulocytes, erythrocytes, serum, urine and zinc-dependent enzymes (alkaline phosphatase in serum and granulocytes, carbonic anhydrase in erythrocytes) were measured in patients with rheumatoid arthritis before and during penicillamine therapy for 6 months. The zinc concentration in serum, urine and erythrocytes increased, while granulocyte zinc decreased. Alkaline phosphatase activity in plasma remained unchanged, while alkaline phosphatase in granulocytes decreased. Carbonic anhydrase activity in erythrocytes decreased. None of the changes could be related to the activity of the disease.
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PMID:Changes in zinc and zinc-dependent enzymes in rheumatoid patients during penicillamine treatment. 643 44


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