Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CHO cell lines that constitutively produce the murine interferon-alpha (IFN-alpha) subspecies alpha 4 and alpha 6 were constructed. The producer cell lines were protected against viral (vesicular stomatitis virus) infection by the IFN species secreted, but were resistant to the growth inhibitory activity of the IFN species. As compared with alpha 4, the alpha 6 protein displayed a high antiproliferative activity when added to normal CHO cells, which correlates completely with the high antiviral activity of alpha 6 on these cells. Three messenger ribonucleic acid (mRNA) species, which are normally induced in CHO cells by IFN treatment (1-8, 2-5A synthetase, and ISG 15) were constitutively present in CHO producer cell lines. The level of another mRNA (ISG 54), however, was very low in the producer cells as compared with its expression in short-term IFN-treated cells. These data indicate that 1-8, 2-5A synthetase and ISG 15 are not involved in the antigrowth activity of IFN in this system, but rather suggest a function of ISG 54 in this respect.
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PMID:Interferon-alpha-(IFN) producing CHO cell lines are resistant to the antiproliferative activity of IFN: a correlation with gene expression. 324 Oct 15

Variant sublines of Friend erythroleukemia cells (FLC) that do not respond to alpha/beta-interferon (IFN-alpha/beta) by developing an antiviral state but respond partially to IFN-gamma with an induced antiviral state, lack the ability to induce the 2',5'-oligoadenylate (2-5A) synthetase pathway. Exposure of wild-type and variant cells to exogenous 2-5A oligomers made permeable with lysolecithin resulted in 50-70% inhibition of protein synthesis. Further, the replication of vesicular stomatitis virus in IFN-resistant 2-5A synthetase-deficient FLC exposed to 2-5A trimer was inhibited to the same extent as in wild-type cells. Last, a significant cleavage of ribosomal RNA was observed in samples of total RNAs extracted from variant and wild-type permeabilized FLC, but only if they were exposed to 2-5A. These data are compatible with the conclusion that (i) the activation of the 2-5A-dependent endoribonuclease is not impaired in the variant cells, and (ii) the uninducibility of 2-5A synthetase can be bypassed by exogenously introducing its products, which leads to the establishment of a bona fide antiviral state.
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PMID:2',5'-Oligoadenylate synthetase-uninducible alpha/beta-interferon-resistant Friend cells develop an antiviral state when permeabilized with lysolecithin and treated with 2',5'-oligoadenylate oligomers. 346 65

Mouse interferon-beta (IFN-beta) cDNA, whose signal sequence had been removed by BAL 31 digestion, was introduced into a Bacillus subtilis secretion vector constructed by using the promoter and signal sequence of the B. subtilis alpha-amylase gene. The resultant chimeric plasmids were transferred into B. subtilis 207-25. Four kanamycin-resistant transformants were selected by both colony hybridization and a new immunoblot method for secretory proteins. They secrete the proteins which cross-react with sheep anti-mouse IFN-beta serum into the culture medium. One of them expressed a high IFN-beta activity as assayed by the L cell and vesicular stomatitis virus system, while the other three showed weak or little IFN activities. Based on our previous study [Ohmura et al., Nucl. Acids Res. 12 (1984) 5307-5319], it was suggested that the secreted IFN molecules are hybrid proteins in which the NH2-terminal region consists of part of the alpha-amylase signal peptide. Nucleotide sequence analysis revealed that plasmid pTUB502, which expressed high IFN activity, is joined to the mouse IFN-beta gene from the codon position 6 of its mature protein. The other three plasmids, pTUB506, pTUB509, and pTUB519, contain the mouse IFN-beta gene from the codon positions 3, 1, and -5, respectively. The NH2-terminal region of the mouse IFN-beta seems to be closely related to its biological activity.
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PMID:Synthesis and secretion of biologically active mouse interferon-beta using a Bacillus subtilis alpha-amylase secretion vector. 392 34

Three human alpha interferon (HuIFN-alpha) preparations currently being used in clinical trials, rIFN-alpha A, rIFN-alpha 2, and lymphoblastoid IFN (LYM-IFN) had appreciable activity against encephalomyocarditis and vesicular stomatitis viruses (VSV) in guinea pig transformed and guinea pig embryo cells, but not mouse L or rabbit kidney cells. The level of activity in guinea pig cells, compared with human WISH cells, was 182% (range 9%-1,900%). These results suggest that the guinea pig may be useful for testing the antiviral, anticancer, or immunomodulatory activity of Hu alpha IFNs in vivo.
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PMID:Activity of human recombinant and lymphoblastoid interferons in human and heterologous cell lines. 609 83

Five human interferon-alpha (leukocyte) subtypes derived from genes cloned in Escherichia coli have been compared for their ability to induce antiviral activity against vesicular stomatitis virus infection of various mammalian cell cultures. These interferons, designated LeIF-A (IFN-alpha 2), -B, -C, -D (IFN-alpha 1) and LeIF-F, show different relative activities when assayed on human, bovine, hamster, mouse, rabbit and monkey cell lines. As with a natural human buffy-coat interferon-alpha preparation, three subtypes (LeIF-B, -C and -D) showed considerable activity on RK-13 rabbit cells, but two (LeIF-D and -F) also showed some activity on mouse L-929 cells. Of the five interferon subtypes examined, LeIF-F demonstrated the highest degree of species specificity.
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PMID:Comparison of the antiviral activities of various cloned human interferon-alpha subtypes in mammalian cell cultures. 617 50

Human peripheral blood mononuclear leukocytes (PBL) cocultured with WISH human amnion cells rapidly produced alpha-type interferon (IFN-alpha) and in an IFN-dependent manner protected the WISH cells against the cytopathic effects caused by vesicular stomatitis virus. When the number of PBL per WISH cell monolayer culture was diluted out using multiple WISH microtiter plate cultures for each PBL dilution, the protection of the WISH cultures appeared as an all-or-none phenomenon. Thus, at one small mean number of PBL per culture, some cultures were protected against the virus, while others were not. Limiting dilution analysis, with plot of the logarithm of the fraction of nonprotected WISH cell cultures at each PBL dilution against the mean number of PBL per culture, yielded straight lines with an intercept on the ordinate close to 1. This indicated a single-hit event due to the function of a single type of limiting "protecting unit". The frequency of this limiting unit in the PBL population could reproducibly be determined for an individual blood donor. For a limited number of different blood donors it ranged from 1/400 to 1/3000. These minimal frequency estimates were considerably increased (40-300%) after 3 h preincubation of PBL with IFN-alpha. Two major alternatives were considered with regard to the nature of the limiting protecting units. They were either IFN-producing cells operating alone, or they were inducer-type cells that possibly used IFN as a mediator to activate protecting cells present in excess in the coculture system. The second possibility was favored, and the relation of the protecting cell type to the natural killer cell system is discussed herein.
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PMID:Limiting dilution analysis of human peripheral blood mononuclear leukocytes that react to human amnion cells and protect these against viral challenge. 617 10

The antiviral activities of recombinant human leukocyte interferons IFN-alpha A and IFN-alpha D as well as five hybrids of these interferons against retroviruses, vesicular stomatitis virus, and encephalomyocarditis virus were studied in feline, human, and murine cells. Although these interferon species had widely different potencies, their activities against these viruses were, in general, proportional. The IFN-alpha A/D (Bgl) hybrid was the most potent species, and the IFN-alpha D/A (Bgl) hybrid was the least potent. However, the latter species did not interfere with the action of the former species. Like natural human leukocyte interferon, each of the seven species of recombinant interferons induced the synthesis of at least five proteins in human fibroblasts, whereas induction of only one such protein was readily detected in a feline fibroblast line in which these interferon species inhibited the replication of all three viruses.
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PMID:Antiviral and protein-inducing activities of recombinant human leukocyte interferons and their hybrids. 620 Jun 7

In contrast to normal clonal cells (A5) derived from NIH/3T3 mouse fibroblasts, another clone (A10) derived from the same source was found to be resistant to the anti-lytic-virus activity of IFN and to be deficient in the induction of (2'-5') oligoadenylate synthetase (2-5A synthetase) by IFN. Following infection of either A5 or A10 cells with Moloney murine sarcoma virus (MSV), a few transformed colonies were isolated, expanded, and tested for their sensitivity to IFN. It is clearly demonstrated that IFN exerts a specific anti-proliferative effect on both MSV-transformed A5 (MA5) and A10 (MA10) cells, as evident by a slower growth rate, a decreased rate of DNA synthesis, and a lower cloning efficiency in its presence. Furthermore, unlike the original A10 cells, the IFN-treated transformed counterpart (MA10 cells), as well as MA5 cells, were protected from the lytic effect of either mengovirus or vesicular stomatitis virus (VSV). In addition, IFN treatment inhibited the release of retroviral particles from the transformed cells. The level of 2-5A synthetase activity in the various transformed cell lines was then determined. Whereas in A10 cells an induction of less than twofold in the enzymatic activity was detected following IFN treatment, a four- to fivefold increase in this activity could be seen in MA10 cells.
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PMID:Transformation by murine sarcoma virus alters the sensitivity of clonal cells derived from NIH/3T3 mouse fibroblasts to interferon. 620 44

A sensitive enzyme immunoassay (EIA) for determining the biological activity of human interferon was developed. Green monkey kidney (Vero) cells and human embryonic lung (HEL) cells were grown in microtitre plates, treated with leukocyte interferon (IFN alpha) and infected with vesicular stomatitis virus (VSV). Cells were fixed with paraformaldehyde and permeabilized with Triton X-100. Viral antigen synthesis was measured by labelling the cells with VSV antiserum followed sequentially by protein A horseradish peroxidase conjugate and o-phenylenediamine. Interferon activity was detected as a lowering of the absorbance value from that of the virus control wells, reflecting the inhibition of virus protein synthesis by interferon. The minimum amount of interferon producing statistically significant (P less than 0.01) decrease of absorbance in Vero cells was 1-5 international units (I.U.)/ml as in the standard plaque reduction test the detection limit was 7.5 I.U./ml or more. In HEL cells the detection limit was 1 I.U./ml measured by EIA. The EIA for interferon activity is at least as sensitive as the traditional plaque reduction test. It is reproducible, easy to automatise and requires 7-10 times less cell culture materials than the plaque reduction test. We find it preferential especially when large numbers of specimens with limited volumes are to be analysed for interferon activity.
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PMID:Sensitive interferon assay based on immunoenzymatic quantification of viral antigen synthesis. 629 74

Dose responses of the NIH standard IFN-alpha and IFN-beta preparations were compared with recombinant DNA-derived IFN-beta (IFN-beta 1) and various IFN-alpha subtypes, molecular hybrids and mixtures. Cytopathic effect assays were employed using vesicular stomatitis virus on human HeLa and bovine MDBK cells. A natural peripheral blood lymphocyte and recombinant DNA-derived IFN-gamma were also included in the comparisons. Two-tailed t-tests between slopes showed no significant differences in any pair-wise comparison using crude or highly purified preparations.
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PMID:Comparisons of dose-response data for various standard and recombinant DNA-derived human interferons. 629 67


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