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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiviral, antiproliferative, and natural killer (NK) cell activation by recombinant human interferon-consensus (IFN-Con1) has been compared with that of two other type I IFNs: IFN-alpha 2a (Roferon) and IFN-alpha 2b (Intron A). The specific activity (antiviral units/mg) of IFN-Con1 was 10-fold higher than that of the other two IFNs in the vesicular stomatitis virus (VSV)-HeLa antiviral assay. The antiproliferative activity on a molar basis of IFN-Con1 on Daudi cells and Eskol (a human leukemic hairy cell-like cell line) was significantly greater than that of IFN-alpha 2a and IFN-alpha 2b. IFN-Con1 also enhanced or induced NK cell killing of target cells to a greater extent than that of IFN-alpha 2a and IFN-alpha 2b. However, on antiviral unit basis, the activities were similar. These results would suggest that IFN-Con1 may be more effective at lower protein concentrations in clinical applications than other available IFNs.
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PMID:A comparison of interferon-Con1 with natural recombinant interferons-alpha: antiviral, antiproliferative, and natural killer-inducing activities. 157 83

The early events that occur after treatment of the highly interferon alpha (IFN-alpha)-sensitive human lymphoblastoid Daudi cell line with human leukocyte IFN-alpha have been examined. IFN-alpha treatment of Daudi cells results in a rapid and transient increase in the cellular content of diacylglycerol, which occurs in the absence of inositol phospholipid turnover, or an increase in intracellular calcium concentration. Furthermore, IFN-alpha treatment results in a selective, time-dependent activation of the Ca(2+)-independent epsilon isoform of protein kinase C (PKC), while the alpha isoform is unaffected by IFN-alpha treatment. In contrast, IFN-alpha treatment of an IFN-resistant subclone of Daudi cells had no effect on the diacylglycerol content of cells and on the activation of PKC-epsilon. The selective PKC inhibitor staurosporine blocked the transcriptional activation of IFN-alpha-stimulated genes, the cytoplasmic accumulation of mRNAs for these genes, and the induction of antiviral activity by IFN-alpha against vesicular stomatitis virus in IFN-sensitive cells. These observations suggest that transmembrane signaling of IFN-alpha involves diacylglycerol production and activation of PKC-epsilon in Daudi cells.
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PMID:Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells. 183 72

Recombinant interleukin-2 (rIL-2) (NSC# 600664; Hoffmann-La Roche, Inc., Nutley, NJ) was studied in a phase I clinical trial in 33 patients with advanced, measureable cancer of the colon or malignant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status O-1, and no prior chemotherapy or radiotherapy. The goal of the study was to identify a dose and schedule of IL-2 to generate maximal immune modulation with tolerable toxicity. Such a regimen might allow the addition of other treatment modalities and/or prolonged treatment duration in later trials. Each patient received IL-2 as a continuous 24-hour infusion once weekly for 4 weeks and then twice weekly for 4 weeks. Five treatment groups received from 10(3) U/m2 to 3 x 10(7) U/m2 per 24-hour infusion. The maximal tolerated dose was 3 x 10(7) U/m2/d twice weekly. Patients treated twice weekly at 1 x 10(7) and 3 x 10(7) U/m2/d had immune modulation in terms of lymphocytosis, eosinophilia, increased natural killer (NK) activity, and elevated numbers of peripheral blood mononuclear cells expressing CD16, OKT10/Leu-17, and Leu-19 surface markers. Endogenous generation of peripheral blood lymphokine-activated killer (LAK) activity was demonstrated by lysis of NK-resistant Daudi targets, in patients treated at 3 x 10(7) U/m2/d. Biochemical and hematological abnormalities were moderate and reversible. Clinical toxicity included hypotension, myalgia, arthralgia, stomatitis, fever, fatigue, nausea, headache, chills, diarrhea, and oliguria at high doses. Cardiovascular toxicity was tolerable for most patients and reversed after IL-2 was stopped. Two of six melanoma patients at 3 x 10(7) U/m2/d achieved partial responses by the end of the eighth week. This IL-2 schedule appears to produce potentially clinically useful immune enhancement with tolerable toxicity.
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PMID:A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. 278 32

The influence of cimetidine on antiviral activity of leukocyte interferon (IFN-alpha (Le] was studied in plaque-reduction assays using Utrecht (U) amnion cells challenged with vesicular stomatitis virus (VSV) and in CPE inhibition assays using A549 cells challenged with encephalomyocarditis (EMC) virus and WISH cells challenged with VSV. The IFN-alpha (Le)-induced antiviral activity was slightly enhanced in cells treated with cimetidine, whereas cimetidine treatment alone did not show any antiviral effect. The observed titer (OT) was significantly higher (p less than 0.05) in cells treated with cimetidine together with IFN-alpha (Le) compared with the control without cimetidine. The effect of cimetidine on IFN-alpha (Le)-induced cell growth inhibition was studied on Daudi (a Burkitt's lymphoma cell line) and on G361 (a melanoma cell line) cells. The growth of these cells was slightly suppressed by cimetidine alone. When cells were treated with IFN-alpha (Le)/cimetidine, the cell growth inhibition rates were significantly higher (p less than 0.02) than the rates obtained with IFN-alpha (Le) or cimetidine alone. These results indicate that cimetidine can enhance the antiviral as well as the antiproliferative activities of IFN-alpha (Le) in "in vitro" studies.
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PMID:Antiviral and antiproliferative activities of human leukocyte interferon potentiated by cimetidine in vitro. 299 35

The abilities of Escherichia coli-derived human interferon gamma (IFN-gamma) and E. coli-derived human interferon-alpha A (IFN-alpha A) or -alpha 2 (IFN-alpha 2) to augment natural killer (NK) cytotoxicity were compared. When low concentrations (less than 10 antiviral units/ml) of interferons were used, and equal numbers of antiviral units of E. coli-derived IFN-gamma and E. coli-derived IFN-alpha A or IFN-alpha 2 were compared for their ability to augment NK, E. coli-derived IFN-gamma was found to be more active in augmenting NK against the K562 targets, than E. coli-derived IFN-alpha A or IFN-alpha 2. Antiviral units in these experiments were determined by the standard cytopathic effect assay using vesicular stomatitis virus (VSV)-challenged human fibroblasts, trisomic for chromosome 21. However, when these interferons were compared on a weight basis (ng/ml) or on a molar basis, their ability to augment NK against the K562 targets was comparable. These differences in the relative abilities of these interferons (when their concentrations were expressed in antiviral units/ml) to augment NK, were due to an approximately 100-fold difference in their specific activities (antiviral units per mg of interferon). These were 1.8 X 10(6) units/mg for E. coli-derived IFN-gamma, 2.0 X 10(8) units/mg for E. coli-derived IFN-alpha A, and 1.8 X 10(8) units/mg for E. coli-derived IFN-alpha 2. At concentrations higher than 10 units/ml, all these interferons showed a similar ability to augment NK. Studies on the kinetics of the augmentation revealed that in vitro treatment with E. coli-derived IFN-gamma for several hours was necessary for augmentation of NK against targets from haemopoietic human tumour cell lines (K562, Daudi). In contrast, alpha interferons were able to augment NK after treatment in vitro for significantly shorter periods (30 min or less with certain donors). Augmentation of NK cytotoxicity of human peripheral blood mononuclear leucocytes by E. coli-derived IFN-gamma was not accompanied by the induction of interleukin 2 (IL-2) production, suggesting that IL-2 is not involved in the augmentation of NK by IFN-gamma. A monoclonal antibody specific for human IFN-gamma blocked augmentation of NK by E. coli-derived IFN-gamma and natural IFN-gamma, but not by E. coli-derived IFN-alpha A or staphylococcal enterotoxin A (SEA).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of natural killer cytotoxicity by Escherichia coli-derived human interferon gamma. 308 22

A somatic cell hybrid between two human Burkitt's lymphoma cell lines, Raji and Daudi, was infected with either Epstein-Barr virus or vesicular stomatitis virus after interferon treatment. Raji cells are resistant to the antiviral effects of exogenously added interferon, whereas Daudi cells are interferon sensitive. The Raji-Daudi hybrid showed an interferon sensitivity that was intermediary to that of the parental cells against both viruses.
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PMID:Antiviral effects of interferon on a somatic cell hybrid between two Burkitt's lymphoma cell lines of different interferon sensitivities. 617 42

Murine F9 and PCC4 teratoma cells do not express H-2 major transplantation antigens according to virus-specific T-lymphocyte cytotoxic or serological assays. However, such cells can be infected with and readily replicate many types of viruses (coxsackie B 3, mouse hepatitis, Sindbis, Semliki Forest [SFV], lymphocytic choriomeningitis, Pichinde, vesicular stomatitis, herpes simplex type 1) to the same extent as do murine F12 teratoma cells and mouse embryo fibroblasts, all of which express the H-2 determinants. In contrast, F9 and PCC4 cells are not productively infected with murine cytomegalovirus, whereas F12 and mouse embryo fibroblast cells are. In addition to replicating in H-2-negative murine teratoma cells, SFV replicates in H-2-negative murine lymphoblastoid cells. The ability of SFV to infect cells without H-2 antigens and then to effect viral antigenic expression in the cells' cytoplasm and on their surface with similar kinetics and in equivalent amounts as cells with H-2 antigens indicates that the H-2 receptor is not needed for SFV infection. Daudi cells, which lack HLA antigens, block the replication of SFV. This occurs at some point after receptor binding, as demonstrated by diminished viral mRNA. In addition, a possible membrane defect precludes viral exit in Daudi cells transfected with SFV infectious RNA. These results indicate that a cell's possession of H-2 antigens is not a requirement for SFV infection and that major histocompatibility complex antigens are not specific receptors for this virus.
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PMID:Does the major histocompatibility complex serve as a specific receptor for Semliki Forest virus? 737 8

Because alpha-interferon (IFN-alpha) has a number of therapeutic applications in the treatment of various human cancers and diseases of viral origin, an understanding of how this family of proteins interacts with cells to induce their pleiotropic biologic activities is essential. Available data suggest that recombinant IFN-alphas from both natural and synthetic genes bind to a common cell surface receptor and induce antiviral activity in a variety of cell lines. IFN-alphas were found to differ significantly in their abilities to bind to cells; this difference varied with the types of IFN-alpha and cell type used. Consensus interferon (IFN-con1), a nonnaturally occurring synthetic IFN, and IFN-alpha2b competed about equally well for receptor binding sites on Daudi and CaKi cells and were followed by IFN-alpha8 in the ability to compete. Results of affinity cross-linking experiments indicated that all three IFN-alphas interacted similarly with the multichain IFN-alpha receptor. IFN-alpha7, however, competed poorly for binding sites on both cell lines. Each of the IFN-alphas tested displayed discrete biologic differences, which also varied with the assay system used. IFN-con1 and IFN-alpha2b displayed similar antiviral activities on CaKi cells using vesicular stomatitis virus; the viral activities of these IFNs were significantly greater than those of IFN-alpha7 or IFN-alpha8. Studies with murine transfectants demonstrated significant differences in the various IFNs to interact with the IFN-alpha receptor-1 chain of the type I IFN receptor. It is yet to be established, however, that these various in vitro distinctions result in differences in clinical benefit or toxicity between the various subtypes.
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PMID:Biologic activities of natural and synthetic type I interferons. 920 74

The IFN-tau are type I IFN expressed by the early trophoblast of cattle and sheep but have activity on human cells and have been predicted to have potential therapeutic value. We have compared a series of mutant bovine and ovine IFN-tau with regard to their ability to inhibit the proliferation of Daudi cells and to evoke an antiviral (AV) response in WISH cells. Whereas Daudi cell growth was inhibited by Bo-IFN-tau1 in the 1 nM range, WISH cells were much less responsive, requiring exposure to 150 nM for protection against vesicular stomatitis virus. Replacement of lysines at positions 34, 107, 121, and 132 in Bo-IFN-tau, which are in regions predicted to interact with the type I receptor, led to modest but significant alterations in antiproliferative (AP) and AV activities. Replacement of the lysine residues at 160 and 164 had marked effects on biopotency, with K160 being particularly important. The different IFN-tau were able to activate the transcription factors ISGF3 and AAF (GAF) in Daudi cells at concentrations that correlated reasonably well with their AP potencies. Stat activation occurred in WISH cells in response to approximately 2 nM Bo-IFN-tau1, but ISGF3 formation could not be demonstrated even at the 100-fold higher IFN-tau concentrations that gave viral protection. Pretreatment of WISH cells with Hu-IFN-gamma allowed ISGF3 formation to be observed in response to subsequent treatment with Bo-IFN-tau1 or type I human IFN but did not increase the AV responsiveness of the cells. No evidence was found that IFN-tau elicit uniquely different responses on human cells than type I Hu-IFN, except they are much less potent. The data emphasize the importance of a region near the carboxyl terminus for the functional activity of type I IFN, and that although ISFG3 formation may be necessary, its mere presence is not sufficient to provide an antiviral response.
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PMID:The antiproliferative and antiviral activities of IFN-tau variants in human cells. 945 65

Nine interferon-alpha subtypes, IFN-alpha1, IFN-alpha2, IFN-alpha5, IFN-alpha7, IFN-alpha8, IFN-alpha10, IFN-alpha14, IFN-alpha17, and IFN-alpha21, were separated from purified human lymphoblastoid IFN. We tested their inhibitory effects on cell growth and replication of Semliki Forest virus (SFV) and vesicular stomatitis virus (VSV) and their induction of 2',5'-oligoadenylate synthetase (2', 5'-OAS) in ACHN renal cell carcinoma cells. In terms of all three activities, the nine subtypes had similar relative activities, with IFN-alpha10 the most active and IFN-alpha1 the least. Their relative effects on cell growth were similar in two other human cell lines, SK-LU-1 lung cancer cells and KU-2 renal cell carcinoma cells, whereas cells of the Daudi Burkitt lymphoma line behaved quite differently, being highly sensitive to all the nine subtypes. The relative effects with ACHN cells correlated well with their relative binding affinities. However, each of the subtypes bound to both ACHN and Daudi cells to almost the same extent. This suggests that their profound inhibitory effects on the growth of Daudi cells are amplified at some stage in the signal transduction pathway or in the expression of genes that results from binding to the IFN-alpha receptor.
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PMID:Biologic and binding activities of IFN-alpha subtypes in ACHN human renal cell carcinoma cells and Daudi Burkitt's lymphoma cells. 1063 3


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