Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess biological response, therapeutic activity, and side effects, a randomized, double-blind trial of two doses of interferon-beta ser (IFN-beta ser), differing by 20-fold 4.5 and 90 x 10(6) units), was undertaken in 64 patients with metastatic renal carcinoma. Patients were treated intravenously with injections daily for 10 days with an 11-day rest before treatment was reinitiated. The trial confirmed the relatively good toleration of IFN-beta ser; in the first cycle only 4/63 patients had anorexia of moderate or greater severity. Median weight change over the duration on study was -1.5 kg; in the first cycle only 7% of patients had performance status decline greater than 1 level. Statistically significant changes (p less than 0.05) occurred in granulocytes, lymphocytes, calcium, cholesterol, alkaline phosphatase, and aspartate transferase (AST); however, except for AST, overall clinical differences in the two doses were not great. Of 60 patients evaluated, 1 developed neutralizing antibody. When assessed 24 h after IFN-beta ser at 4.5 x 10(6) units, significant (p less than 0.05) augmentation had occurred in beta 2-microglobulin, HLA-DR, and HLA-DQ expression on monocytes, 2',5'-oligoadenylate (2-5A) synthetase in peripheral mononuclear cells, and natural killer (NK) and K cells functional activity. Although the 90 x 10(6) unit dose also resulted in stimulation of these responses, little additional augmentation of biological response occurred at the higher dose. Except for a decline in monocyte HLA-DR expression, biological responses remained increased at both doses over the 10-day period of treatment. However, no objective regressions of metastatic disease occurred. In view of objective responses in metastatic renal carcinoma in other trials with IFN-beta ser, consideration should be given to alternative schedules.
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PMID:Biological and clinical effects of interferon-beta ser at two doses. 208 72

This study examines the effect of cytosine arabinoside (Ara-C) on CFU-GM progenitor cells grown in methylcellulose culture from normal and myelodysplastic subjects and patients with acute non-lymphoblastic leukaemia. Light density marrow cells were incubated during culture with Ara-C concentrations ranging from 10(-4) M to 10(-12) M. After counting, colonies were cytospun and cells within the colonies examined for alkaline phosphatase positivity and expression of HLA-DR antigen, as indices of differentiation. Monocytes/macrophages were also enumerated in colonies using the monoclonal antibody CD14. In all subjects, 10(-4) M to 10(-6) M Ara-C caused significant reduction in CFU-GM colony formation compared with control (no Ara-C). In no instance did colony numbers increase. Ara-C across the dose curve had no effect on myeloid differentiation markers in any of the groups studied. Similarly, percentages of CD14 positive cells in colonies were not altered by exposure to Ara-C. Using this clonogenic model, these data suggest that Ara-C does not induce differentiation of CFU-GM stem cells in normal subjects or patients with myelodysplasia/acute non lymphoblastic leukemia.
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PMID:Cytosine arabinoside does not cause differentiation in vitro of CFU-GM in marrow from normal, myelodysplastic or ANLL subjects. 231 14

We have studied the effect of maturation to small intestinal-like epithelial cells of the human colonic carcinoma cell line HT29 on the lateral mobility of different representative membrane components (lipid, proteins), as assessed with fluorescence recovery after photobleaching (FRAP). Maturation was induced in vitro in the HT29 cells by replacing glucose (Glu) with galactose (Gal) in the growth medium (DMEM) during a 21-day period. Scanning electron microscopy revealed an increased number of microvilli in the apical cell membrane, and enzyme analyses (alkaline phosphatase, aminopeptidase) in combination with aqueous countercurrent distribution, indicated that maturation was induced with DMEM-Gal. In comparison to control cells grown in DMEM-Glu medium, the more small intestinal-like cells grown in DMEM-Gal displayed no alteration of the lateral mobility of either cholera toxin (B subunit)-labelled ganglioside GM1 (diffusion coefficient, D [x 10(8)] = 0.8-0.9 cm2s-1; mobile fraction, R = 50-60%) or antibody-stained Class 2 histocompatibility (HLA-DR) antigen (D [x 10(9)] = 2 cm2s-1; R = 60-70%). However, antibody-labelled beta 2-microglobulin of HLA Class 1 antigen displayed increased mobility in HT29-Gal cells; D was x 1.4 and R x 1.8 larger in the HT29-Gal cells. By contrast, the mobility of a neoplastic antigen was reduced; D and R were x0.60 and x0.69 of the values seen in HT29-Glu cells. It is thus concluded that DMEM-Gal-induced differentiation in confluent HT29 cells is accompanied by specific rather than general effects on the lateral mobility of different membrane components.
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PMID:Small intestinal differentiation in human colon carcinoma HT29 cells has distinct effects on the lateral diffusion of lipids (ganglioside GM1) and proteins (HLA class 1, HLA class 2, and neoplastic epithelial antigens) in the apical cell membrane. 233 58

The antigenic properties of S-100 beta-positive human T-lymphocytes (S-100 beta+ T-cells) were investigated by a double immunostaining technique employing an indirect immunoperoxidase method for cytoplasmic S-100 beta subunit and an immunoalkaline phosphatase method for cell surface antigens detected by various monoclonal antibodies to human lymphocytes. S-100 beta+ T-cells recognized by their diffuse intracytoplasmic immunoperoxidase reaction, also expressed CD2, CD3, CD8 antigens demonstrated by surface blue alkaline phosphatase reactivity, but not CD4, CD1, CD25 (interleukin-2 receptor), or HLA-DR antigens. However, they displayed a blastic change to T-cell mitogens, such as Concanavalin A(Con-A) and PHA, followed by the expression of CD25 and HLA-DR antigens. Under normal conditions, S-100 beta+ T-cells comprised approximately 5-22.8% of CD8+ cells amongst human peripheral blood mononuclear cells.
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PMID:Immunocytochemical characterization of S-100 beta-positive human T-lymphocytes by a double immunostaining method. 244 20

Human Peyers patches (PP) were studied by immunohistochemistry to characterize functional properties of the follicle-associated epithelium (FAE) including the "membrane" (M) cells. The FAE had no transporting capacity for polymeric IgA (pIgA) because it did not express the secretory component (SC) which acts as a pIgA receptor. However, it expressed MHC class II (HLA-DR) determinants, except for the M cells (which were tentatively identified by absence of brush border alkaline phosphatase). It is possible, therefore, that the FAE generally performs class II-restricted transport and presentation to T cells of antigens which have been adequately processed in the gut lumen. The function of M cells may be limited to transport of particulate or undegraded antigens to subjacent macrophages for processing and subsequent presentation. There were significantly more intra- and subepithelial T cells in PP than in distant villi, and the T cells were concentrated adjacent to M cells. The proportion of the CD4+ phenotype (putative helper T cells) was much higher in FAE (approximately 40%) than in villous epithelium where the CD8+ (putative suppressor) phenotype predominated strikingly (approximately 90%). This disparity might reflect differences in capacity for positive and negative immune regulation at the two sites. The B cells terminating with Ig production in PP and adjacent to solitary lymphoid follicles apparently belonged to relatively mature memory clones as they showed a large proportion of IgG immunocytes and reduced J-chain expression. Conversely, both IgG and IgA immunocytes in lamina propria (LP) showed a high percentage of J-chain positivity (80-100%); such positivity was also considerable (45-60%) in mesenteric lymph nodes (MLN) in contrast to peripheral lymph nodes (PLN) and palatine tonsils (PT). Moreover, there was a decreasing percentage of IgA2 immunocytes in the order of PP (52%), distant ileal LP (40%), MLN (32%), PLN (11%), and PT (5%). Taken together, our results suggested that dissemination of relatively immature memory B-cell clones with high J-chain expression takes place from PP through MLN and that preferential settlement of such clones occurs in LP.
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PMID:Human Peyer's patches: lympho-epithelial relationships and characteristics of immunoglobulin-producing cells. 249 34

Ultrastructural, enzyme histochemical and immunohistochemical studies were performed on tissue obtained from eight cases of malignant fibrous histiocytoma (MFH) and five cases of sacral decubitus ulcer. The MFH was composed of two major tumour cell types: fibroblast-like and histiocyte-like cells. Both cell types demonstrated abundant branching, fragmented rough endoplasmic reticulum (rER), many free ribosomes, occasional small mitochondria, an oval, elliptical or irregularly shaped nucleus with one or two prominent nucleoli and often a few dense bodies. However, pseudopodial projections, multivesicular bodies and phagosomes, common histiocyte organelles, were not seen. With little difference between cases or selection sites, the MFH cells reacted to acid phosphatase (AcP) and alpha-naphtyl butyrate esterase (ANBE) by enzyme histochemistry and with ferritin (Fer), alpha 1-antitrypsin (AT), alpha 1-antichymotrypsin (ACT), fibronectin (FN), HLA-DR, HLA-DP, Leu 10 and OKT 9 in immunohistochemical studies. MFH tumour cells did not immunostain with monocyte/macrophage markers (Leu M1, Leu M3, Mo 1, Mo 2 and Macrophage) although non-neoplastic histiocytes did react to these markers. In addition, granulation tissue, such as that found in sacral decubitus ulcers, was examined and the existence of a specific cell type called the "fibrohistiocytoid (FH) cell" was documented. The FH cell was short, spindle shaped and elliptical. Ultrastructurally, it had fragmented rER distributed in a branching pattern, dispersed free ribosomes, small mitochondria and a few dense bodies, but lacked diverse fused lysosomes and distinct pseudopodial cytoplasmic extensions. The FH cells reacted with AcP, alkaline phosphatase and ANBE but not with peroxidase using enzyme histochemistry and with Fer, AT, ACT, FN, HLA-DR, HLA-DP, Leu 10 and OKT 9 but not with monocyte/macrophage markers, C3d receptor, C3bi receptor in immunohistochemical studies. The FH cells had morphological, enzyme histochemical and immunohistochemical characteristics intermediate between fibroblasts and histiocytes. Similarities between MFH cells and the FH cells seen in chronic inflammation are discussed.
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PMID:Malignant fibrous histiocytoma: similarities to the "fibrohistiocytoid cells" in chronic inflammation. 254 May 88

Recently, great interest has been shown in the histological identification of small cell tumours of childhood--nephroblastoma (Wilms' tumour), neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma--using immunohistochemical methods. However, several antigens operationally specific for leucocyte typing in blood and marrow are also expressed on cells of epithelial and neural origin. We undertook phenotypic characterization of 17 non-haemopoietic small cell tumours of childhood using a panel of 30 monoclonal antibodies to leucocyte, epithelial and cytoskeletal antigens using a sensitive alkaline phosphatase-anti-alkaline phosphatase technique on cryostat sections of fresh tumour. Our results demonstrated frequent expression of the leucocyte-associated antigens CD10 (CALLA), CD9 (p24) and CDw32 (FcRII) in these small cell tumours and occasional expression of MHC class II (HLA-DR) and HNK-1 antigens. However, the leucocyte-associated antigens CD45 (leucocyte common), CD22 (pan B-cell), CD11b (C3bi receptor), CD15 (Lewisx) or CDw42 (platelet gp Ib) were not detected on any tumour. Aberrant expression of desmin, neurofilament and UJ13A antigen was found in nephroblastoma and of epithelial-associated markers (CIBr17 and 43-9F) in neuroblastoma. Our results also demonstrated broad reactivity in frozen section with two monoclonal antibodies specific for melanoma (NKI/C-3) or epithelial cells (OM-1) in paraffin sections. Hence, it is necessary to include monoclonal antibodies to CD45 and pan-epithelial antigens, e.g. LP34 (cytokeratin) or HEA125 for the precise immunohistochemical identification of small round cell malignancies of childhood.
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PMID:Phenotypic characterization of non-haemopoietic small cell tumours of childhood with monoclonal antibodies to leucocytes, epithelial cells and cytoskeletal proteins. 254

Using monoclonal antibodies (MAB) in combination with the alkaline phosphatase anti-alkaline phosphatase technique, 20 meningiomas were examined for the expression of major histocompatibility complex (MHC) antigens. Most of the tumor cells were labeled with the MAB for class I MHC antigens. In addition, class I reactivity was seen in the tumor blood vessels, presumably reflecting labeling of the endothelial cells. Tumor cells and endothelium were not labeled with the MAB for class II MHC antigen HLA-DR. Occasionally a staining of periendothelial cells was detected. The presence of MHC antigens supports the assumption that endothelial cells play a role in antigen presentation, perhaps relevant to the initiation of an immune response, and that meningioma cells can be a target of T cell-mediated immune reactions.
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PMID:Monoclonal antibody analysis of major histocompatibility complex expression in human meningiomas. 258 94

Sixteen specimens excised from apical granulation tissue were examined for immunocompetent T lymphocytes, mononuclear phagocytes, and HLA-DR-determined cells. Light microscopic visualization of the cells was performed using monoclonal antibodies and the immunocytochemical alkaline phosphatase anti-alkaline phosphatase technique. Quantitative assessment of the biopsy specimens showed that in five diagnosed cysts, eight granulomas, and three specimens taken from scar tissue, macrophages represented the dominating inflammatory cell fraction, followed by T lymphocytes. In the latter group, helper/inducer T cells were most frequent. Cysts showed a statistically significant increase in cell populations of helper/inducer, suppressor/cytotoxic T cells, macrophages, and HLA-DR-coded cells. There were only a few activated T lymphocytes.
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PMID:Differentiation of T lymphocyte subpopulations, macrophages, and HLA-DR-restricted cells of apical granulation tissue. 260 72

The expression of HLA class I and II antigens was analysed in 30 primary gastric carcinomas, 27 autologous lymph node metastases and 25 autologous gastric mucosae. We used an immune alkaline phosphatase technique on cryostatic sections and mAbs directed against HLA class I monomorphic determinants, HLA-B locus-specific products and HLA-DR, -DP and -DQ molecules. In addition HLA class I genes were analysed in tumour tissue and compared by Southern blots with the RFLP from autologous mucosa using locus-specific HLA probes. Finally the infiltrating mononuclear cells were studied on gastric tumours and adjacent mucosa with mAbs defining CD4, CD8 and CD11b differentiation antigens. The results obtained showed that three out of 27 primary gastric carcinomas completely lack HLA-ABC antigens (10%). In addition, two primary tumours presented a variable expression. The remaining 22 tumours presented a homogeneous positive HLA class I expression. Interestingly, when the autologous mucosa was analysed, only 12 out 25 specimens were homogeneously stained with mAbs against HLA class I antigens, suggesting that this tissue may lack the expression of HLA antigens before becoming malignant. Indeed, the majority of the gastric carcinomas studied presented a higher HLA-ABC antigenic expression than autologous mucosa. Finally, the HLA expression observed in the primary tumour was similar to that observed in autologous metastases. As a second part of the study we have found a direct relationship between the expression of HLA-DR antigens in mucosa and the intensity of inflammatory infiltration. This relationship was not maintained in the tumour tissue. In the mucosa the CD4-positive T cell was the predominant lymphocyte, while it was CD8 in the HLA-DR-positive tumours. Finally the RFLP of class I genes did not show any differences in any of the cases when compared with autologous mucosa. We included in these studies DNAs from HLA class I-negative tumours, HLA positive and HLA-B-negative ones.
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PMID:MHC class I and II antigens on gastric carcinomas and autologous mucosa. 263 12


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