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)

beta-2 microglobulin levels were measured in stored serum taken at presentation from 262 patients treated with combination chemotherapy for Kiel classification high-grade lymphoma at a single centre over a 15 year period. A significant association was found between elevated levels and advanced (Ann Arbor stage III or IV) disease or hepatic infiltration, but not with other sites of extranodal involvement or bulky disease. Patients with normal levels at presentation had a 70% remission rate with treatment compared to 37% of those with elevated levels (P < 0.001). With median follow up of 6 years duration of remission was significantly greater in patients with normal beta-2 microglobulin at presentation (plateau at 70%, compared to median remission of 19 months in those with raised levels, P < 0.001). Survival overall was also better in the group with normal levels (actuarial median 9 years compared to 1 year, P < 0.001). Multivariate analyses including treatment type, age, sex, B symptoms, stage, bulk, albumin, sodium, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and beta-2 microglobulin, placed beta-2 microglobulin among the three most influential independent variables for prediction of response rate, duration of remission and overall survival.
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PMID:Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas. 847 38

Mutant cell lines defective in the biosynthesis of glycosylphosphatidylinositol (GPI) described to date were isolated by selecting cells which no longer expressed one or more endogenous GPI-anchored proteins on their surface. In this study, a new mutant in this pathway was isolated from ethylmethane-sulphonate-mutagenized Chinese hamster ovary cells stably transfected with human placental alkaline phosphatase (PLAP) as a marker of GPI-anchored proteins. A three-step protocol was employed. In the first step, cells with decreased surface expression of PLAP were selected by four rounds of complement-mediated lysis with an anti-(alkaline phosphatase) antibody. The surviving cells were cloned by limiting dilution and those with low levels of total alkaline phosphatase activity were selected in the second step. Finally, the ability of each clone to synthesize the first three intermediates in GPI biosynthesis in vitro was assessed to determine which cells with low alkaline phosphatase activity harboured a defect in one of these reactions. Of 230 potential mutants, one was defective in the second step of GPI biosynthesis. Microsomes from this mutant, designated G9PLAP.85, were completely unable to deacetylate either endogenous GlcNAc-phosphatidylinositol (PI) synthesized from UDP[6-3H]GlcNAc or exogenous GlcNAc-PI added directly to the membranes. Complementation analysis with the Thy-1-deficient murine lymphoma cells demonstrated that G9PLAP.85 has a molecular defect distinct from these previously described mutants. Therefore, these results suggest that mutants in GPI biosynthesis could be selected from almost any cell line expressing a GPI-anchored marker protein.
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PMID:Isolation and characterization of a Chinese hamster ovary (CHO) mutant defective in the second step of glycosylphosphatidylinositol biosynthesis. 854 92

Patients infected with human immunodeficiency virus (HIV) are at risk for a variety of liver diseases. We undertook a retrospective study of 501 HIV-seropositive patients to assess the yield of percutaneous liver biopsy. The most common indications for liver biopsy were liver test abnormalities (89.5%), fever for 2 weeks (71.9%), and hepatomegaly (52.0%). The most common biopsy-derived diagnosis was Mycobacterium avium complex (MAC), seen in 87 (17.4%) biopsies. Mycobacterium tuberculosis was found in 13 biopsies (2.6%). In 28 biopsies (5.6%) mycobacteria was seen, but speciation of the organism was not possible. Chronic active viral hepatitis was seen in 60 biopsies (12.0%). Opportunistic hepatic infection from other organisms was found in 14 biopsies (2.8%). The most common neoplasm was lymphoma, which was seen in 12 biopsies (2.4%). MAC infection of the liver was associated with elevated alkaline phosphatase (p = 0.01). Among patients with fever for 2 weeks after an extensive negative workup including bone marrow biopsy, 58.2% had a diagnosis by liver biopsy. Overall, 64.3% of liver biopsies yielded a histopathological diagnosis, 45.7% of which were potentially treatable. We could not evaluate whether liver biopsy had a positive effect on patient outcome and survival, nor did we attempt to prove that liver biopsy resulted in a change in treatment or a change in preprocedure clinical diagnosis. Thus, questions about the efficacy of liver biopsy cannot be answered. Liver biopsy may be a helpful diagnostic tool in HIV-positive patients with fever, liver test abnormalities or hepatomegaly.
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PMID:Liver biopsy findings in 501 patients infected with human immunodeficiency virus (HIV). 855 99

We report the first known case of fulminant bone marrow necrosis (BMN) occurring after infusion of fludarabine monophosphate in a patient with recurrent low-grade non-Hodgkin's lymphoma (NHL). Extensive BMN is characterized by the development of fever, bony pain, a leukoerythroblastic peripheral blood film, variable degrees of pancytopenia and elevations in lactate dehydrogenase and alkaline phosphatase. The diagnosis of BMN is rarely entertained ante-mortem. Although the precise role chemotherapy may have played in triggering fatal BMN remains speculative, we alert clinicians to be aware of this entity as more patients with indolent lymphomas and leukemias are treated with this and other potent nucleoside analogs.
Leuk Lymphoma 1995 Sep
PMID:Fatal bone marrow necrosis following fludarabine administration in a patient with indolent lymphoma. 857 66

Search for the new approaches to the diagnosis of lymphoproliferative diseases and transition to the classification scheme "Working Classification of Non-Hodgkin's Lymphomas for Clinical Use" involved assessment of the proliferative status of pathological lymphoid cells by immunocytochemical method with the use of DAKO-PC (Ki-67) monoclonal antibodies. The course and specific features of immunocytochemical reaction with the use of peroxidase-antiperoxidase immune complexes and complexes of alkaline phosphatase and monoclonal antibodies to it on various types of preparations are described in detail, this appreciably extending the potentialities of the use of this method. The studies were carried out with lymphoid cells of different organs of the immune system and peripheral blood of 44 patients with lymphoproliferative diseases and of 5 donors. The results permit considering the developed and tried immunocytochemical method for assessment of the proliferative status of pathological cell populations informative as regards the use of the "Working Classification of Non-Hodgkin's Lymphomas".
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PMID:[Immunocytochemical method of assessment of the proliferative status of lymphoid cells in lymphoproliferative diseases]. 868 60

We have established a human stromal cell line derived from the bone marrow of a patient with chronic myelogenous leukemia in blast crisis. This cell line, designated FS-1, exhibits a fibroblastoid morphology and does not express any hematopoietic cell marker tested. FS-1 is negative for alpha-naphthyl acetate esterase, acetylated LDL, von Willebrand factor, and shows no phagocytosis. This cell line is positive for acid phosphatase, alkaline phosphatase, collagen types I, III, IV, and fibronectin. cDNA from FS-1 cells was subjected to amplification by the polymerase chain reaction to assess the constitutive expression of several cytokine genes. Transcripts for interleukin (IL)-6, IL-7, macrophage colony-stimulating factor (M-CSF), and stem cell factor (SCF) were detected in FS-1 cells. IL-6 and SCF also were detected in the culture supernatants of FS-1 at a concentration of 95 pg/ml and 21.2 pg/ml, respectively. These data show that FS-1, established from a human bone marrow, is a stromal cell line which was not generated using transfection with SV40 T antigen. FS-1 cells may be useful in supporting human hematopoietic cells for experimental manipulation.
Leuk Lymphoma 1996 Jun
PMID:Establishment and characterization of a novel human bone marrow stromal cell line, FS-1. 872 43

A temporary elevation of serum alkaline phosphatase has been described in young children who have no evidence of liver or bone disease. This phenomenon has been termed benign hyperphosphatasemia of infancy. Its occurrence is described in three children undergoing chemotherapy for acute lymphoblastic leukemia and lymphoma. All three children were in remission and in the consolidation or maintenance phase of their therapy when the hyperphosphatasemia occurred. All children were also receiving methotrexate (IM and IV), oral 6-mercaptopurine, and oral sulfamethoxazole/trimethoprim. Although these agents are associated with hepatotoxicity, other liver transaminases (ALT, AST) remained at normal concentrations, and there was an elevation only in the bone isoenzyme of alkaline phosphatase, thus making hepatic toxicity an unlikely etiology for the hyperphosphatasemia. No alteration in chemotherapy was necessary for resolution of the elevated alkaline phosphatase in these children.
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PMID:Benign transient hyperphosphatasemia in children with leukemia and lymphoma. 927 28

Abnormal results of standard biochemical liver tests occur frequently; however, the prevalence of clinically significant liver disease is only about 1% in all patients screened. Thus, development of a rational and cost-effective approach to these patients is important. Liver diseases are generally classified as hepatocellular, cholestatic, and infiltrative. Cholestatic liver disease is further categorized as intrahepatic and extrahepatic. Hepatocellular disease is characterized by transaminase increases greater than 5 times the upper limit of normal, with alkaline phosphatase levels usually increased less than 2 to 3 times the upper limit of normal. Cholestatic disease is characterized by an increase in the alkaline phosphatase level that is 3 to 5 times greater than the upper limit of normal, with only a mild increase of transaminases. The exception to this is cholestasis with cholangitis when the transaminases can be more substantially increased. In infiltrative diseases of the liver such as lymphoma or granulomatous hepatitis, the alkaline phosphatase level is increased disproportionately to that of the bilirubin. Specific etiologic diagnoses cannot usually be based on routine biochemical liver test results, and thus more specialized serum tests are necessary. A liver biopsy is often needed for a precise diagnosis in patients with long-term increases in liver test results. Ultrasonography is the best initial imaging technique for the liver, and if biliary dilatation is noted, endoscopic retrograde cholangiopancreatography is recommended.
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PMID:Clinical approach to the patient with abnormal liver test results. 891 95

Three clonally related T-cell lymphoma lines (PB-1, 2A, and 2B) were examined for expression of IL-2, IL-4, and their receptors. All three lines were derived from a single patient who had an atypical, progressive T-cell lymphoproliferative disorder involving primarily skin (Davis, T.H. et al. 1992, N. Engl. J. Med. 326:1115). The PB-1 cell line was obtained from a relatively early, clinically indolent stage of the cutaneous lymphoma, whereas the 2A and 2B lines were established from a late, aggressive stage of the lymphoma. Reverse-transcriptase PCR performed with primer pairs specific for IL-2 and IL-4 showed that no mRNA coding for these cytokines was present in any of the lines with the exception of IL-4 mRNA in the 2A line. No IL-4 protein, however, was found in any of the cell lines including 2A by immunocytochemical staining with anti-IL-4 mAb. Accordingly, no bioactive IL-4 was present in the supernatants of these lines. In contrast, all three T-cell lymphoma lines contained mRNA for IL-2R alpha, IL-2R beta, IL-4R and common gamma chain. Immunocytochemical analysis revealed that only the PB-1 line stained strongly with mAbs specific for IL-2R alpha, IL-2R beta, and IL-4R whereas the 2A and 2B lines showed only limited staining with these mAbs. In contrast to expression of IL-2R alpha and IL-4R primarily on the cell surface, IL-2R beta was localized mainly in the cell cytoplasm. Testing supernatants of the cell lines by ELISA for the presence of soluble alpha chain of the IL-2R (sIL-2R) has shown that only PB-1 secreted a large amount of sIL-2R, whereas the 2A and 2B lines secreted lesser amounts. Furthermore, the PB-1 cells expressed a relatively large number of IL-4R as determined by IL-4 binding studies using an IL-4-alkaline phosphatase fusion protein. The remaining two lines displayed only limited binding of IL-4. Addition of IL-2 and/or IL-4 to the culture medium did not modulate growth of PB-1 and the other two lines. These findings may indicate that at least some types of T-cell lymphoma evolve from cells which lose the capacity to synthesize T-cell autocrine growth factors such as IL-2 and IL-4, and show progressive loss of receptors for these cytokines.
Leuk Lymphoma 1996 Sep
PMID:Analysis of IL-2, IL-4 and their receptors in clonally-related cell lines derived from a patient with a progressive cutaneous T-cell lymphoproliferative disorder. 902 95

Leukocyte alkaline phosphatase (LAP) is the product of the gene coding for the liver/bone/kidney-type alkaline phosphatase. In the normal hematopoietic system, the only cell type expressing LAP in basal conditions is the post-mitotic neutrophilic granulocyte. Thus LAP represents a specific and restrictive marker for the terminal maturation of the neutrophilic granulocyte. The study of the factors and the molecular mechanisms responsible for the expression of LAP in cells undergoing granulocytic maturation may shed light on this complex biological process. Acute promyelocytic leukemia (APL) represents a unique biological model in which it is possible to investigate neutrophilic differentiation. APL blasts undergo rapid and irreversible maturation towards cells morphologically and biochemically resembling normal mature granulocytes upon in vivo and in vitro challenge with all-trans retinoic acid (ATRA). In this cellular context, we studied the endogenous factors involved in the expression of LAP. The phosphatase is not synthesized in undifferentiated APL blasts and it is expressed only upon treatment with combinations between ATRA and a second cyto-differentiating signal. The second signal may be given by G-CSF, cAMP analogs, IL-6 and to a lesser extent by IL-1 beta. The molecular mechanisms underlying the induction of LAP by combinations of ATRA and G-CSF or cAMP analogs were studied in detail and are the object of this review.
Leuk Lymphoma 1996 Nov
PMID:Leukocyte alkaline phosphatase a specific marker for the post-mitotic neutrophilic granulocyte: regulation in acute promyelocytic leukemia. 903 Oct 80


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