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)

This paper addresses the role of transcriptional regulation in the determination of the levels of expression of different interferon-alpha subtypes secreted from Namalwa cells following infection with Sendai virus. Using RT-PCR to determine the relative abundance of mRNA species coding for the various subtypes, we found a general correlation with corresponding protein levels, indicative of a role for transcriptional control in the determination of levels of individual subtypes. We have used reporter gene constructs to compare the inducibility of the virus-response elements from the IFNA1, A2, A4, and A14 subtype genes cloned upstream of a secreted alkaline phosphatase gene. The inducibility of these reporter gene constructs broadly correlated with the relative mRNA abundances in both transiently and stably transfected Namalwa cells. During work with stable cell lines, we found that G418, the drug used for the selection of transfected cells, inhibited the induction of interferon by both Sendai virus and double-stranded RNA. This inhibition was reversible when G418 was removed from the medium 24 h before the addition of virus.
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PMID:Relative transcriptional inducibility of the human interferon-alpha subtypes conferred by the virus-responsive enhancer sequence. 874 62

A low concentration of differentiation inducers such as dimethylsulphoxide (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate greatly enhanced the antiproliferative effect in vitro and in vivo of interferon alpha (IFN-alpha) to several human lung adenocarcinoma cells. The agents induced morphological changes in the adenocarcinoma cells and the agents together with IFN-alpha-induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-alpha receptor and interferon-stimulated promoter-binding factors. The lung adenocarcinoma cells were not impaired in IFN-alpha receptor and interferon-stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the enhancement of interferon sensitivity in the lung adenocarcinoma cells acts downstream of the activation of ISGF-3.
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PMID:Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents. 876 68

To evaluate the clinical efficacy of alpha-interferon(IFN-alpha) plus cis-platinum in hepatocellular carcinoma(HCC). 56 inoperable patients with HCC were divided into IFN-alpha plus cis-platinum treated group (n = 30) and no antitumor therapy group (n = 26). The survival of IFN-alpha plus cis-platinum treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.001). Median survival time was 33 weeks and 14.0 weeks, respectively. The cumulative estimated survival rates of our IFN-alpha plus cis-platinum treated group (93.5% at 3mo, 75.0% at 6mo) were for longer than that of the no antitumor therapy group (84.6% at 3mo, 57.7% at 6mo). Objective tumor regression, greater than 50% was observed in 13.3% (4 of 30) of patients receiving IFN-alpha plus cis-platinum. By the univariate analysis, the absence of portal vein thrombus (p < 0.05), alkaline phosphatase lesser than 280 U/L (p = 0.001), total bilirubin less than 2.0 mg% (p < 0.05), serum triglyceride less than 155 mg/dl (p < 0.05) were shown to be the factors most significantly favoring a better survival. By the multivariate analysis, using Cox proportional hazards model, IFN-alpha plus cis-platinum treated group (p = 0.0001), alkaline phosphatase less than 280 mg/dl (p = 0.005), the absence of portal vein thrombus (p = 0.020) were independent favorable prognostic factors. We conclude that IFN-alpha plus cis-platinum is useful in patients with inoperable HCC and the above favorable prognostic factors may also be useful in the design and analysis of future clinical trials of systemic chemotherapy for HCC.
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PMID:Combined cis-platinum and alpha interferon therapy of advanced hepatocellular carcinoma. 888 77

Double stranded RNA-dependent protein kinase (PKR) is a double stranded RNA-activated, interferon-induced serine-threonine kinase that participates in both the antiviral and antiproliferative properties of interferon. We previously found that influenza virus inhibited PKR function by recruiting or activating a cellular inhibitor termed P58(IPK). The present study was undertaken to complement our earlier analyses, which demonstrated that P58(IPK) efficiently inhibited PKR autophosphorylation and activity in vitro. We now report that P58(IPK) down-regulates PKR and, in turn, stimulates protein synthetic rates inside the cell. Using transfection analysis, we show that P58(IPK) stimulates translation of secreted embryonic alkaline phosphatase reporter gene mRNA. Furthermore, we found that at least two regions of the P58(IPK) molecule were required for PKR inhibitory activity in COS-1 cells: (i) the DnaJ similarity region at the carboxyl terminus (amino acids 391-504); and (ii) the tetratricopeptide repeat 6 (TPR6) domain (amino acids 222-255) located in the middle of the P58(IPK) protein and within the eukaryotic protein synthesis initiation factor 2alpha homology region. P58(IPK) variants lacking either one of these regions were unable to stimulate secreted embryonic alkaline phosphatase protein synthetic rates. Consistent with this data is the observation that the DeltaTPR6 mutant (the P58(IPK) variant lacking the TPR6 motif) failed to block PKR activity in vitro. Based on these data and our earlier in vitro functional and PKR-P58(IPK) binding analyses, a revised model of PKR regulation by P58(IPK) is presented.
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PMID:The 58-kDa cellular inhibitor of the double stranded RNA-dependent protein kinase requires the tetratricopeptide repeat 6 and DnaJ motifs to stimulate protein synthesis in vivo. 891 May

Interferons have been utilized widely in chronic liver diseases for their antiviral properties. In addition, there is evidence for their antifibrogenic actions. In this work we studied effects of various doses of interferon-alpha 2b on experimental liver fibrosis and cholestasis induced in the rat by biliary obstruction. Collagen was measured as hepatic hydroxyproline content. Cholestasis was determined by serum alkaline phosphatase and gamma-glutamyltranspeptidase activities and by bilirubin content. Glycogen was measured in the liver. Interestingly, the best effects (antifibrotic and anticholestatic) were observed in the group receiving the lowest dose of interferon. These results suggest that interferon-alpha 2b may be used at low doses, thereby decreasing side effects and costs.
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PMID:Dose-response studies of interferon-alpha 2b on liver fibrosis and cholestasis induced by biliary obstruction in rats. 921 63

We have developed an animal model to study human delayed-type hypersensitivity reactions. Previous studies in humans have shown after tuberculin injection the presence of a mononuclear cell infiltration, with almost no eosinophils, associated with a preferential Th-1-type cytokine profile. Human skin graft obtained from tuberculin-reactive donors was grafted onto the back of severe combined immunodeficient mice. After healing, mice were reconstituted intraperitoneally with peripheral mononuclear cells. Tuberculin and diluent were injected intradermally, and skin biopsies were performed 72 hours later. Skin grafts were divided into two parts, one for immunohistochemistry and one for in situ hybridization studies. Immunohistochemistry was performed on cryostat sections using the alkaline phosphatase anti-alkaline phosphatase technique. In the tuberculin-injected sites as compared with the diluent-injected sites, there were significant increases in the number of CD45+ pan leukocytes and CD4+, CD8+, CD45RO+ T cells but not in CD68+ monocytes/macrophages and EG2 or MBP+ eosinophils. The activation markers CD25 and HLA-DR were up-regulated in the tuberculin-injected sites. In situ hybridization was performed using 35S-labeled riboprobes for interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-5. After tuberculin injection, a preferential Th-1-type cytokine profile was observed with significant increases in the numbers of IL-2 and IFN-gamma mRNA-expressing cells. These results are similar to those reported after tuberculin-induced delayed-type hypersensitivity in humans, suggesting that this model might be useful to study cutaneous inflammatory reaction.
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PMID:Tuberculin-induced delayed-type hypersensitivity reaction in a model of hu-PBMC-SCID mice grafted with autologous skin. 962 72

The present study prospectively evaluated the value of liver biopsy in patients with chronic hepatitis B (N=75) and C (N=135) prior to interferon therapy. Biopsy specimens revealed cirrhosis in 26% of patients with hepatitis B and 30% with hepatitis C. Although cirrhosis was not predictable by laboratory values in individual patients mean gamma-GT, alkaline phosphatase, and bilirubin levels were significantly higher in patients with cirrhosis compared to those without. Since cirrhosis significantly impairs the response rate to interferon therapy in hepatitis C but not in hepatitis B, liver biopsy is important for the management of chronic hepatitis C infection. In 88% of patients with serum HBV-DNA, irrespective of the serum HBeAg status, chronic active hepatitis was seen. Similarly, chronic active hepatitis was found in 84% of patients with elevated aminotransferases and hepatitis C antibodies. Thus, chronic active hepatitis was diagnosed in the majority of cases with chronic viral hepatitis, showing that this histopathological diagnosis is of little additional value for the recommendation on interferon treatment in these patients. However, none of the other grading systems of liver biopsy specimens described so far have been evaluated for their ability to predict overall prognosis or response rates to interferon therapy. Therefore, the physician is presently left with the questionable value of a procedure with well-known risks and costs in patients suitable for interferon treatment. Hence, prospective randomized controlled studies to evaluate histopathological grading systems are urgently needed to redefine the necessity of liver biopsy in this routine clinical setting.
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PMID:Value of liver biopsy prior to interferon therapy for chronic viral hepatitis. 969 Mar 95

Interferon (IFN) is the only drug that has been approved by the FDA for therapy of chronic hepatitis C. However, optimal dose and duration of therapy are still controversial. This study compares the effectiveness of treatment of chronic hepatitis C patients with 3 vs. 5 million units (MU) of recombinant alpha-interferon 2-b three times per week. We also evaluated the relapse rate with a shorter 12 week-course of therapy in those patients who had normalization of aminotransferases by week 12. Seventy-five patients were randomized to receive either 3 vs. 5 MU of IFN; seventy-two completed the study. A complete response was seen in 11/35 (31%) of those treated with 5 MU vs. 13/37 (35%) in the 3 MU dose (p = 0.74). Patients were followed after IFN was withdrawn and only 2 had persistently normal aminotransferases. Analysis of multiple variables was done to predict response to IFN and only elevations of GGT, ferritin and alkaline phosphatase were found to be predictors of a poor response. Therefore, we recommend initial therapy with 3 MU of IFN for a longer period than 12 weeks in patients who show a response.
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PMID:Chronic hepatitis C: treatment comparison between 3 and 5 million units of interferon alpha-2b. 988 67

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.
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PMID:The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis. 1035 73

The present studies evaluated the feasibility of establishing a conditionally immortalized osteoprecursor cell line derived from human fetal bone tissue. Primary cultures were transfected with a plasmid in which the Mx-1 promoter drives the expression of SV40 T-antigen when activated by human A/D interferon. Several neomycin (G418)-resistant colonies were characterized for cell growth and alkaline phosphatase (ALP) enzyme activity. The clone, designated OPC1 (osteoblastic precursor cell line 1), which exhibited the highest ALP enzyme activity at passage 10 (P10), was selected for additional osteogenic phenotypic characterization. Reverse transcription-polymerase chain reaction (RT-PCR) phenotyping revealed abundant mRNA for osteocalcin (OC), osteonectin (ON), osteopontin (OP), parathyroid hormone receptor (PTHr), ALP, and procollagen type I (ProI). In addition, the levels of quantitative RT-PCR product of ON, OP, PTHr, and ProI mRNAs exhibited a marked up-regulation when maintained in medium containing an osteogenic supplement (OS). The ability to stimulate osteogenic differentiation was characterized in postconfluent OPC1 cells maintained in tissue culture medium supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2) either with or without an OS. All treatment groups exhibited a striking up-regulation of ALP enzyme activity that coincided with ALP histochemical observations. Postconfluent cells also exhibited the ability to form mineralized nodules under all treatments (confirmed by von Kossa histochemical staining and calcium deposition). An enzyme immunosorbent assay (EIA) was utilized to measure intact human OC from the OPC1 line under the various treatments. Abundant OC was evident in the tissue culture medium indicating de novo sythesis and release from the OPC1 line under appropriate conditions. The clonal human-derived OPC1 line represents a homogeneous osteogenic cell line that not only has maintained a consistent bone phenotype from P10 to at least P30, but has also exhibited the capacity to generate programmed differentiation in the presence of low dose rhBMP-2 (10 ng/ml). Thus, the OPC1 line is a human-derived osteoprecursor that provides a sensitive in vitro cell culture system to evaluate bone development, cell/biomaterial interactions, and may be a useful screen for putative bone differentiating factors.
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PMID:Establishing an immortalized human osteoprecursor cell line: OPC1. 1049 Dec 20


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