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)

P-glycoprotein is an adenosine triphosphate-dependent drug-efflux pump that extrudes drugs from cells and causes drug-resistance. P-glycoprotein is believed to mediate drug-resistance in a wide variety of tumors. In this study, we developed two P-glycoprotein-positive, murine osteosarcoma cell lines that were resistant to Adriamycin (doxorubicin) (MOS/ADR1 and MOS/ADR2). We created the cell lines by short-term pulse exposures of the parent cell line to Adriamycin followed by single-cell cloning. The MOS/ADR1 and MOS/ADR2 cells were sevenfold and eighteenfold more resistant to Adriamycin than the cells from the parent line. Expression of P-glycoprotein, as examined with an immunofluorescence method, was detected in most of the MOS/ADR1 and MOS/ADR2 cells but not in the parent cells. After the cells had been incubated with Adriamycin for one hour, there was less accumulation of the drug in the resistant cell lines than in the parent cell line. The reduced accumulation was due to the increased efflux of Adriamycin. The Adriamycin-resistant cell lines demonstrated greater alkaline phosphatase activity than the parent cell line and produced more differentiated osteoblastic sarcomas in mice. Dose survival studies with use of a tetrazolium colorimetric assay showed that the MOS/ADR1 cells were cross-resistant to vincristine, vinblastine, etoposide, bleomycin, mitomycin C, and actinomycin D but not to dacarbazine, cisplatin, carboplatin, cytosine arabinoside, carmustine, cyclophosphamide, ifosfamide, methotrexate, and 5-fluorouracil. Although the MOS/ADR2 cells exhibited a similar spectrum of cross-resistance, they were more resistant than the MOS/ADR1 cells. We also tested the effect of three different resistance-modifying agents on the reversal of resistance to Adriamycin. We found that verapamil and trifluoperazine substantially reversed resistance to Adriamycin in the P-glycoprotein positive cell lines, whereas cyclosporin A was relatively ineffective. Because these cell lines retain the histological and biochemical features of bone-producing sarcomas and display the multidrug-resistant phenotype, they may be useful models for additional investigations of drug resistance in osteosarcoma.
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PMID:Experimental models for the study of drug resistance in osteosarcoma: P-glycoprotein-positive, murine osteosarcoma cell lines. 861 43

Idiopathic myelofibrosis (IMF), or agnogenic myeloid metaplasia, was diagnosed in a sexually mature male marmoset (Callithrix jacchus) based on the results of hematology and histopathologic evaluation of the bone marrow. The hematologic changes included pancytopenia, leukoerythroblastosis, anisocytosis, poikilocytosis, and giant platelets. Histopathologic evaluation of the bone marrow showed marked widespread fibrosis replacing hematopoietic cells and the presence of atypical megakaryocytes. In addition, slight multifocal osteolysis with an increase in serum alkaline phosphatase activity was observed. We believe this is the first report of IMF in a nonhuman primate species.
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PMID:Idiopathic myelofibrosis (agnogenic myeloid metaplasia) in a marmoset (Callithrix jacchus): hematologic and histopathologic changes. 924 Aug 43

One of the classic histologic forms of renal osteodystrophy is osteitis fibrosa, and its distinguishing characteristic is bone marrow (BM) fibrosis, caused by the activation of marrow parenchymal cells. A bone biopsy must be performed in order to establish the diagnosis of renal osteodystrophy. The clinical use of bone biopsy is restricted, however, due to the invasiveness of the procedure. In recent studies, bone scans have provided information useful for the differential diagnosis between osteomalacia and osteitis fibrosa. However, bone scans can not provide information on the bone marrow status. Bone marrow immunoscintigraphy (BMIS) using Tc-99m anti-granulocyte antibody (AGA), a highly sensitive test for the detection of bone marrow abnormalities which is also a noninvasive method, has rarely been reported in chronic renal failure (CRF). BMIS can provide information in patients with myelofibrosis. The purpose of this study was to evaluate the usefulness of BMIS in CRF patients with special regards to biochemical parameters. Nineteen CRF patients (13 men, 6 women; mean age: 48 +/- 11 years) in whom bone scintigraphy using Tc-99m MDP (methylene diphosphonate) showed the so-called superscan pattern were included in the study. Their primary renal diseases were chronic glomerulonephritis (n = 14), diabetes (n = 4), and polycystic kidney disease (n = 1). Modes of therapies were continuous ambulatory peritoneal dialysis (CAPD) (n = 13; mean duration: 9.5 months), HD (n = 5; mean duration: 7.8 months), and conservative treatment (n = 1). BMIS using Tc-99m labeled anti-granulocyte monoclonal mouse antibody BW250/183 was performed, and the results were compared with the biochemical parameters of the patients. According to the presence of BM expansion, which may represent marrow fibrosis, the 19 patients were divided into two groups: Group I (n = 7) with BM expansion and Group II (n = 12) with normal marrow distribution. The biochemical parameters and bone markers of Group I were compared with those of Group II. There was no significant difference in biochemical parameters (blood hemoglobin, serum ferritin, erythropoietin, BUN, creatinine) between the two groups. There were no significants difference in serum calcium, phosphorus, tartate-resistant acid phosphatase (TRAP), and intact parathyroid hormone (iPTH) between the two groups. Serum alkaline phosphatase (ALP) and osteocalcin were significantly (P < 0.05) higher in Group I than in Group II. These results suggest that patients with bone marrow expansion in BMIS have increased levels of ALP and osteocalcin, indicating an increased osteoblastic activity. BMIS may be useful for the detection of bone marrow expansion due to marrow fibrosis in renal osteodystrophy, and for the evaluation of the extent of bone marrow fibrosis.
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PMID:Bone marrow immunoscintigraphy (BMIS): a new and important tool for the assessment of marrow fibrosis in renal osteodystrophy? 1064 20

A 28-year-old Japanese woman with suspected essential thrombocythemia (ET) had marked thrombocytosis, mild leukocytosis with normal neutrophil alkaline phosphatase activity, and no anemia. She was monitored without being given any medication. Eleven years later, complete blood counts showed no remarkable changes but some non-lobulated mononuclear megakaryocytes were found in the bone marrow. Cytogenetic analysis revealed deletion of the long arm of chromosome 5 (5q-). Subsequently, hemoglobin and platelet counts decreased gradually, splenomegaly appeared and progressed, after which myelofibrosis developed. Acute leukemia developed 16 years after the first documentation of thrombocytosis. 5q- syndrome is known to be a myelodysplastic syndrome (MDS) with unique clinical features and cases with this syndrome presenting with thrombocytosis of more than 1,000 x 10(9)/L but without anemia are rare. Furthermore, it is noteworthy that in this patient transition to acute leukemia occurred following development of myelofibrosis and marked splenomegaly, which are generally observed in blastic crises resulting from chronic myeloproliferative disorders (CMPD). The patient showed features indicative of CMPD rather than of MDS in spite of presenting with 5q- chromosomal abnormality. This case supports the concept of "mixed myelodysplastic and myeloproliferative syndromes" and suggests the possibility of the appearance of CMPD-like manifestations in 5q- syndrome.
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PMID:5q- syndrome presenting chronic myeloproliferative disorders-like manifestation: a case report. 1081 92

Idiopathic myelofibrosis (IMF) is generally characterized by bone marrow (BM) fibrosis, anemia, splenomegaly and a leuko-erythroblastic blood picture. Although, histopathology is in keeping with the assumption of a stepwise evolution of the disease, little hematological data are available for patients with prefibrotic and early stages of disease. Therefore a clinicopathological study was performed that included firstly an exploratory sample of 68 patients with minor supportive therapy in whom BM biopsies during follow-up (41 +/- 32 months) revealed an evolution of a prefibrotic or very early fibrotic lesion into overt IMF. The validation sample consisted of 556 patients with pretreatment marrow specimens on admission. Diagnostic features and BM lesions were identical compared with the patients of the exploratory sample at their first examination. BM biopsies were processed by routine stainings including silver impregnation (reticulin fibers) and frequently also by immunohistochemistry to identify megakaryocytes and erythroid precursor cells more properly. Apart from minor hemorrhage and peripheral thrombosis patients with early stage IMF presented with non-specific symptoms including varying degrees of leukocytosis (51%), anemia (38%), a platelet count exceeding 600 x 10(9)/l (86%), splenomegaly (15%) and increase in leukocyte alkaline phosphatase (LAP) (24%) and serum lactate dehydrogenase (LDH) (20%). BM histology confirmed a moderate increase in hematopoiesis with a mixed granulocytic and megakaryocytic myeloproliferation, a reduction of erythroid precursors and significant megakaryocytic abnormalities. In keeping with the first BM examination of the exploratory sample no or only a borderline to slight increase in reticulin fibers was detectable, however, in 68 of 134 patients follow-up biopsies revealed a transition into overt IMF (intervals about three years). Median survival of this cohort with early-stage IMF was 129 months thus contrasting manifest IMF with an usually more unfavorable prognosis. Recognition of early stage IMF certainly alters the generally applied diagnostic criteria of this disorder. Regarding patients with associated thrombocytosis, differentiation from essential thrombocythemia is recommended. Moreover, characterization of early stage IMF probably exerts an impact on survival and may influence the decision to perform a BM transplantation.
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PMID:Early-stage idiopathic (primary) myelofibrosis--current issues of diagnostic features. 1214 83

In this paper we describe the establishment and characterization of a transplantable cell line derived from a spontaneously occurring chondroblastic osteosarcoma in a C57BL/6J mouse. The tumor line, MOS-J, forms solid tumors when injected intramuscularly into immunocompetent syngeneic hosts, mimicking endochondral bone development. These transplantable tumors have the capacity to destroy and invade existing bone and invade vessels in close proximity to the tumor. In culture, MOS-J cells form layers of pleomorphic cells with high mitotic activity. These cells have marked alkaline phosphatase activity and form calcified foci in vitro that stain with alizarin red. MOS-J cells also promote osteoclast development in vitro from normal bone marrow cells. These characteristics indicate the potential utility of the MOS-J osteosarcoma cell line as a model for studies of human osteosarcoma and bone biology.
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PMID:Establishment and characterization of a new osteogenic cell line (MOS-J) from a spontaneous C57BL/6J mouse osteosarcoma. 1222 30

The various hemopoietic and supportive cells of the marrow may proliferate beyond physiologic boundaries in response to a number of stimuli. In certain instances, the stimuli are known, and upon their removal the myeloproliferation returns to normal boundaries. These, the reactive myeloproliferations, are best represented by the leukemoid states and the secondary polycythemias. In other cases, the stimuli responsible for the myeloproliferation remain unknown and the clinical disease ends fatally. These, the neoplastic myeloproliferations, include the granulocytic, monocytic and red cell leukemias, as well as the polycythemia vera and myelofibrosis syndrome. In clinical practice it is important to identify the various myeloproliferative syndromes. This task has been facilitated by cytochemical tests that have recently become available, among which the estimation of the leukocyte alkaline phosphatase (LAP) in peripheral blood is a technically simple and extremely useful example. The LAP is normal in secondary polycythemias and decidedly elevated in polycythemia vera, myelofibrosis and leukemoid states. It is greatly decreased in the granulocytic leukemias.
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PMID:The myeloproliferative disorders. Current clinical and laboratory considerations. 1401 Feb 93

Chronic Neutrophilic Leukemia (CNL) is a rare myeloproliferative disorder characterized by a persistent increase of mature peripheral neutrophils, myeloid hyperplasia in bone marrow, hepatosplenomegaly, elevated neutrophil alkaline phosphatase (NAP) and absence of Philadelphia chromosome, with no evidence of infection or malignancy sufficient to mimic a leukemoid reaction. CNL has been associated with multiple myelomas in many reported cases, but transition of Polycythemia Vera (PV) to CNL is very rare. An 81-year-old female patient, who had undergone intermittent phlebotomy following the diagnosis of PV 8 years previously, was admitted to our hospital due to lower back pain. A physical examination showed a splenomegaly 2 cm below the costal margin, with tenderness of the thoracic and lumbar spine area. A peripheral blood examination showed a WBC count of 91,800/microL (neutrophil 88%) with a rare immature form, hemoglobin of 9.1 g/dL and a platelet count of 1,661,000/microL. Her NAP score was 58. The bone marrow examination showed 95% cellularity, with an M:E ratio of 10:1, increased megakaryocytes with normal morphology and the absence of myelofibrosis. Chromosomal studies showed no Philadelphia chromosome. A radiological examination showed compression fractures of the vertebrae and spinal cord compression. No underlying disease causing a leukemoid reaction was detected. With iron replacement, the hemoglobin level failed to increase over 12 g/dL. Therefore, it was concluded to be a transition of PV to CNL. After administration of hydroxyurea and vertebroplasty, the symptom improved and the WBC count was sustained below 40,000/microL.
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PMID:A case of transition of polycythemia vera to chronic neutrophilic leukemia. 1568 21

We conducted the first nationwide survey to clarify the clinical features, treatment methods, and prognoses for polycythemia vera (PV) and essential thrombocythemia (ET). A 1-page questionnaire was mailed to members of the Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG). Surveys on 647 patients (PV, 266 patients; ET, 381 patients) were returned and analyzed. Thrombotic events at diagnosis and during follow-up occurred at rates of 15.4% and 8.5%, respectively, in PV cases and 17.6% and 8.7% in ET cases. Splenomegaly was observed in only 28.8% of PV patients and 10.8% of ET patients. The leukocyte alkaline phosphatase score was elevated in only 46.2% of PV patients. The incidences of abnormal karyotypes were less than 10% in both PV and ET cases. The rates of transformation to myelofibrosis were 2.6% in both PV and ET cases, and acute leukemia was noted in 1.1% of PV patients and 2.9% of ET patients. Prognostic factors were thrombotic history for PV and thrombotic history and age (>or=60 years) for ET. The present study clearly demonstrated clinical differences between Japanese and Western patients for PV and ET. Concerning the treatment of PV and ET, the study revealed considerable variation among Japanese hematologists. These results suggest the necessity of developing treatment guidelines according to risk stratification that are suitable for Japanese PV and ET patients.
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PMID:Clinical features of polycythemia vera and essential thrombocythemia in Japan: retrospective analysis of a nationwide survey by the Japanese Elderly Leukemia and Lymphoma Study Group. 1678 77

The determination of leukocyte alkaline phosphatase (LAP) is used as an aid to diagnose many diseases in the laboratory. For example, it can be used to distinguish chronic myeloid leukemia (CML) from other myeloproliferative disorders (particularly myelofibrosis and polycythemia) and leukemoid reactions (LR). Traditionally, this test is performed with the use of subjective cytochemical assays that assign a score to the level of LAP. Here we present a nonsubjective, quantitative, sensitive, and inexpensive chemiluminescent technique that determines LAP based on the commercial reagent Immulite (AMPPD). To validate this methodology, intact leukocytes obtained from 32 healthy subjects, nine CML patients, and nine LR patients were submitted to the optimized protocol. By measuring the light emission elicited by four concentrations of neutrophils, we were able to estimate the activity of LAP per cell (the slope of the curve obtained by linear regression). A high linear correlation was found between the chemiluminescent result (slope) and the cytochemical score. The slope for healthy individuals ranged between 0.61 and 8.49 (10(-5) mV.s/cell), with a median of 2.04 (10(-5) mV.s/cell). These results were statistically different from those of CML patients (range=0.07-1.75, median=0.79) and LR patients (range= 3.84-47.24, median=9.58; P<0.05).
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PMID:Chemiluminescent determination of leukocyte alkaline phosphatase: an advantageous alternative to the cytochemical assay. 1738 76


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