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)

A 60-year-old woman with chronic active hepatitis C was treated with 6 million units of rIFN-alpha 2b daily for two weeks and subsequently three times weekly for several months. Histological examination proved a severe form of chronic active hepatitis C unexpectedly complicated with primary biliary cirrhosis (PBC). Before treatment, levels of serum alkaline phosphatase (ALP) or gammaglutamyltranspeptidase (GGT) had remained within normal limits over six months, although anti-mitochondrial antibody (AMA) was shown to be positive. After eight weeks of therapy, the daily dose of rIFN was reduced to 3 million units because of a marked increase of ALP and GGT, although the serum alanine aminotransferase (ALT) was normalized. Four months later, IFN treatment was suspended because of continuous elevation of the ALP and GGT levels, and administration of ursodeoxycholic acid was substituted. Two months later, the ALP and GGT levels returned to the normal range, although ALT was not normalized and HCV-RNA remained positive. This is the first report case that demonstrates IFN treatment potentially exacerbates PBC associated with chronic active hepatitis C. It is important for treating physicians to keep this association in mind.
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PMID:Exacerbation of primary biliary cirrhosis during interferon-alpha 2b therapy for chronic active hepatitis C. 778 37

Human interferon-alpha 2c (IFN-alpha 2c) was produced in Escherichia coli under the control of the alkaline phosphatase promoter using a periplasmic expression system. Compared with other leader sequences, the heat-stable enterotoxin II leader of E. coli (STII) resulted in the highest rate of correct processing as judged by Western-blot analysis. The fermentation was designed as a batch-fed process in order to obtain a high yield of biomass. The processing rate of IFN-alpha 2c could be increased from 25% to more than 50% by shifting the fermentation pH from 7.0 to 6.7. IFN-alpha 2c extracted from the periplasm was purified by a new four-step chromatographic procedure. Whereas cytoplasmically produced IFN-alpha 2c does not have its full native structure, IFN-alpha 2c extracted from the periplasm was found to be correctly folded, as shown by c.d. spectroscopy. Peptide-map analysis in combination with m.s. revealed the correct formation of disulphide bridges. N-terminal sequence analysis showed complete removal of the leader sequence, creating the authentic N-terminus starting with cysteine.
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PMID:Periplasmic expression of human interferon-alpha 2c in Escherichia coli results in a correctly folded molecule. 814 88

We adopted the nonradioactive method used for blot hybridization for the detection of inducible mRNA for HLA-DR alpha by the in situ hybridization. Unstimulated and interferon gamma stimulated MonoMac6 and U937 human monocytic cell lines were used as target cells. Sulphonation of plasmid pBR322 with HLA-DR alpha cDNA insert (2 x 700 bp, in Pstl restriction site) was performed according to the manufacturer's procedure (SulfoProbe Kit, Sigma). The hybridization signals were detected with mouse monoclonal, anti-sulphonated DNA antibody, followed by immunovisualization with anti-mouse IgG-alkaline phosphatase conjugates. Unstimulated MonoMac6 and U937 cells showed few granular reaction products only in small percentage of cells (1-5%), while in IFN gamma stimulated cells the fine granular immunoenzymatic reaction was observed in the cytoplasm of majority of cells (> 80%). This method seems to be easy and rapid to perform, making it applicable for routine diagnostic purposes in tissue sections and biopsies.
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PMID:Detection, by in situ hybridization using sulphonated cDNA probe, the specific mRNA for HLA-DR alpha induced in monocyte cell lines by recombinant interferon gamma. 823 22

Three assays of murine IFN gamma are compared in terms of sensitivity, intra- and inter-assay variability, specificity and simplicity. The widely used viral inhibition assay requires 48 hours, necessitates continuous maintenance and optimization of fibroblast growth, and exhibits the lowest sensitivity. Inhibition of WEHI-279 B cell [3H]thymidine incorporation requires 48-60 hours to quantitate IFN gamma production, can be subject to non-specific inhibition, and is also labor intensive. In both bioassays, specificity must be determined by the analysis of duplicate samples in the presence of neutralizing, IFN gamma-specific mAb. In contrast, a 24 hour, dual mAb ELISA, in which IFN gamma is captured by immobilized, purified rat IgG1 XMG 1.2 mAb and identified with biotinylated mAb R4-6A2 and streptavidin-alkaline phosphatase detects IFN gamma production > 0.05 U/ml. The quantitative range in this assay is typically from 1-100 U/ml. In addition to providing the greatest specificity and shortest duration, this ELISA exhibits the lowest coefficient of variation of the three assays compared. Collectively, assay characteristics such as sensitivity, absence of interference by other proteins, reproducibility, speed and simplicity support the conclusion that this dual mAb based sandwich ELISA represents a substantial improvement over inhibition of viral cytopathic effect or inhibition of WEHI-279 bioassays for characterization of antigen- or mitogen-driven IFN gamma production.
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PMID:A simple, sensitive, dual mAb based ELISA for murine gamma interferon determination: comparison with two common bioassays. 835 16

Interferons have been used to treat chronic hepatitis owing to their antiviral properties. However, now interferons are recognized to inhibit collagen production. Because fibrosis has been associated with liver damage and dysfunction, the effects of interferon-alpha 2b on biliary obstruction-induced cirrhosis were investigated. Obstructive jaundice was induced in male Wistar rats (ca. 200 g) by double ligation and division of the common bile duct. Control rats were sham operated. Interferon-alpha 2b (IFN-alpha; 1000 000 IU per rat) was administered subcutaneously daily after surgery. The animals were sacrificed after 4 weeks of bile duct ligation (BDL) or sham operation. Bilirubins and serum enzyme activities of alkaline phosphatase and gamma-glutamyl transpeptidase (determined as markers of liver damage) increased several-fold after BDL. Erythrocyte and hepatocyte plasma membrane Na+/K+- and Ca2+-ATPase activities decreased significantly in the BDL group. Administration of IFN-alpha to BDL rats resulted in a partial normalization of serum markers of liver damage. The normal activity of both ATPases on erythrocyte and hepatocyte plasma membranes was completely preserved by IFN-alpha. It is concluded that interferons possess interesting hepatoprotective effects not related to their antiviral properties but probably associated with their antifibrogenic effect.
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PMID:Interferon-alpha preserves erythrocyte and hepatocyte ATPase activities from liver damage induced by prolonged bile duct ligation in the rat. 860 32

We have developed an enzyme-linked immunosorbent assay (ELISA) for the sequential analysis of multiple cytokines in limited volumes of biological fluids, including gingival crevicular fluid (GCF) and fibroblast culture supernatants (CS). GCF and CS samples were assayed for multiple cytokines, including IL-1 beta, IL-6, IL-8, GM-CSF and IFN gamma. Immulon 3 microplates were coated with a monoclonal antibody, and a rabbit polyclonal antibody was used to detect the cytokine of interest. Biological samples (200 microL) were added to an anti-IL-1 beta-coated plate and incubated, and 175 microL of each sample were replicate transferred to an anti-IFN gamma-coated plate containing 25 microL/well of diluent. This was repeated in an identical fashion with sequential replicate transfers to an anti-IL-8-coated and finally an anti-IL-6-coated plate. The cytokine standard was a pooled combination of the recombinant human cytokines that were included in the sequence. The plates were developed using an alkaline phosphatase-conjugated goat anti-rabbit IgG and NPP as the substrate. Individual ELISAs ranged in sensitivity from 30 to 2 pg/0.2 mL, with cross-reactivity between these cytokines of < 1%. Additionally, when the same samples were tested in the sequence ELISA vs. the individual ELISA, there was > 85% correlation between the two assays.
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PMID:Sequential ELISA for cytokine levels in limited volumes of biological fluids. 887 92

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

Treatment of the acute promyelocytic (APL) cell line NB4 with interferon alpha (IFN(alpha)), as well as IFN(beta) and gamma, results in an increased expression of the transcripts coding for retinoic-acid receptor type alpha (RAR(alpha)) and the leukemia-specific retinoic acid receptor PML-RAR. Transcriptional induction of the RAR(alpha) and PML-RAR mRNAs is rapid and it is parallelled by an increase in the corresponding proteins. Up-regulation of RAR(alpha) and PML-RAR gene expression by IFN(alpha) is accompanied by a strong potentiation in the induction of 2 retinoid-dependent granulocytic markers, i.e., granulocyte-colony-stimulating factor receptor mRNA and leukocyte alkaline phosphatase. However, IFN(alpha) does not have any effects on the retinoid-dependent regulation of the myeloid surface markers CD11b and CD33. The IFN-dependent increase in RAR(alpha) levels and the enhancing effect of the cytokine on retinoid-dependent granulocytic markers expression may be a characteristic of PML-RAR positive cells, since the phenomena are not observed in HL-60 promyelocytes. Interferons as well as retinoids inhibit the growth of NB4 cells, although the 2 classes of compounds do not significantly interact in terms of anti-proliferative activity. These results suggest the possible use of combinations between IFNs and retinoic acid in the cyto-differentiating treatment of APL patients.
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PMID:Interferons induce normal and aberrant retinoic-acid receptors type alpha in acute promyelocytic leukemia cells: potentiation of the induction of retinoid-dependent differentiation markers. 889 44

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.
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PMID:Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities. 914 69

Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that modulates the cellular functions of both osteoblastic and osteoclastic lineages. It remains unclear whether IFN-alpha regulates the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor, which is a major target molecule regulating skeletal metabolism. In this study, we examined the effect of IFN-alpha on the expression of PTH/PTHrP receptor in human osteoblastic cells (Saos-2). IFN-alpha inhibited the expression of PTH/PTHrP receptor gene in both a time- and dose-dependent manner. The mRNA level was decreased to 61.1% of that of the untreated control by 48 h treatment with 6000 U/mL of IFN-alpha. IFN-alpha also decreased cAMP response to PTH(1-34) in a dose-dependent manner and significantly depressed expression of the receptor protein. However, IFN-alpha did not exert any effect on other osteoblastic markers, such as alkaline phosphatase (ALP) activity, cAMP response to prostaglandin E2 (PGE2), and secretion of bone gla-protein (BGP) and bone sialoprotein (BSP). Finally, IFN-alpha decreased PTH/PTHrP receptor mRNA to 60.7% that of control in the presence of actinomycin D. These data suggest that IFN-alpha downregulates the expression of PTH/PTHrP receptor and its signaling without affecting other osteoblastic markers, and that IFN-alpha regulates its gene expression mainly by decreasing the stability of its mRNA.
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PMID:Lymphoblastoid interferon-alpha downregulates parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor expression in human osteoblastic cells (Saos-2). 973 42


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