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Biomedical subjects

D A Stringfellow

Publications and source records attributed to D A Stringfellow.

27 records · Page 2Linked to original sources
PubMed1978

Prostaglandin restoration of the interferon response of hyporeactive animals.

Virus-infected animals and those bearing various types of malignancies progressively lose the ability to respond to interferon inducers. The interferon response of virus-infected animals could be restored to normal levels when inducers were administered with certain prostaglandins. This suggests that prostaglandins may enhance the therapeutic efficacy of interferon inducers as antiviral and antineoplastic agents.

Animals↗
PubMed1978

Prostacyclin biosynthesis in activated, stimulated and normal mouse peritoneal cell populations.

Nonspecific resistance to infectious and neoplastic disease can be enhanced by administration of "immunomodulators". The levels of enhancement can be monitored by following in vitro function of cells of the lympho-reticuloendothelial system. To gain a better understanding of the physiological and biochemical nature of this enhancement, the metabolism of prostaglandin endoperoxide PGH2 was followed in mouse peritoneal cells (PCs). Homogenates of PCs from normal, unstimulated mice yielded primarily prostacyclin (PGI2) when incubated with PGH2. Homogenates of PCs from mice injected with the immunomodulators C. parvum, levamisole HCl, pyran copolymer, or thioglycollate yielded less PGI2. Reductions ranged from 73% for C. parvum to 32% for levamisole. A statistically significant inverse correlation existed between the level of macrophage "activation" and ability of cellular homogenates to produce prostacyclin. The results suggest that prostacyclin may be involved in modulation of nonspecific resistance.

Animals↗
PubMed1977

Suppressed response to interferon inducation in mice infected with encephalomyocarditis virus, Semliki forest virus, influenza A2 virus, Herpesvirus hominis type 2, or murine cytomegalovirus.

Mice infected with encephalomyocarditis virus, Semliki Forest virus, influenza A2 virus, Herpesvirus hominis type 2, or murine cytomegalovirus developed a state of hyporeactivity to interferon induction. In general, the capacity of infected animals to produce interferon in response to inducers became progressively impaired during the course of infection. The severity and time of onset of hyporeactivity, however, were dependent upon the inducer and the nature of the viral infection. During viral infections associated with generalized hyporesponsiveness, a factor that could inhibit interferon production by murine cells in culture was identified in the serum. This serum hyporeactive factor may have mediated the development of hyporeactivity in vivo. Hyporeactivity of the host's interferon response was associated with progression of viral infection and may be partially responsible for the limited effectiveness of interferon inducers in the modification of viral infections, when administered after onset of symptoms.

Animals↗
PubMed1977

Comparation interferon- inducing and antiviral properties of 2-amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), tilorone hydrochloride, and polyinosinic-polycytidylic acid.

2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), polyinosinic acid-polycytidylic acid [poly(I:C)], and tilorone HCl induced high levels of serum interferon in mice. Each consequently protected mice against infection with several viruses. After daily injection of inducer, mice developed a reduced interferon response (hyporeactivity) to each compound. However, hyporeactivity developed more slowly to U-25,166 and poly(I:C) than to tilorone HCl. After onset of hyporeactivity, 5 to 6 days without each inducer were required before normal serum interferon levels could be stimulated. Animals also developed a hyporeactive state as a consequence of Semliki Forest or encephalomyocarditis virus infections. By day 2 of either infection, mice had a suppressed interferon response to tilorone HCl, but remains responsive to poly(I:C) or U-25,166 until day 4. In vivo, poly(I:C) stimulated interferon production in a variety of cells and organs, whereas the tilorone HCl and U-25,166 responses involved a nonlymphoid component of the reticuloendothelial system. In vitro, poly(I:C) induced interferon in a variety of murine cells, U-25,166 was active in murine thymus and spleen organ cultures, and tilorone was inactive. These data indicate that U-25,166 is an interesting low-molecular-weight interferon inducer.

Animals↗
PubMed1977

Production of the interferon protein: hyporesponsiveness.

A number of mechanisms may be responsible for development of hyporeactivity in cells or animals infected with viruses or exposed to interferon inducers. Available evidence, however, has implicated a specific control protein in modulation of interferon production. The precise identity and mechanism by which the repressor molecule modulates interferon production is at present unknown. Development of hyporeactivity to interferon induction as a consequence of repeated doses of an inducer or that develops secondary to virus infection may represent a serious limitation to use of inducers as antiviral agents. However, judicious selection of treatment regimens and inducers may circumvent or limit the severity of hyporeactivity and consequently enhance the therapeutic activity of interferon inducers.

Animals↗
PubMed1977

Feline interferon response to 2-amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166).

U-25,166 induced high serum interferon levels in cats at concentrations at least 40 times less than the maximum tolerated dose. Although certain cats responded to U-25,166 by consistently producing higher interferon levels than did other cats, this relationship was not observed if the same animals were injected with Newcastle disease virus or polyriboinosinic:polyribocytidylic acid (poly I:C). Using a biweekly treatment regimen, cats remained responsive to interferon induction by U-25,166 over an 18-week period in which 9 doses of the compound were given. Cats given the compound daily, however, soon became hyporesponsive to interferon induction. Interferon was induced in cats given U-25,166 orally as a suspension or in capsules, but circulating interferon levels were low in cats given the drug by subcutaneous injection.

Administration, Oral↗
PubMed1976

Murine leukemia: depressed response to interferon induction correlated with a serum hyporeactive factor.

Mice injected by the intraperitoneal route with either L1210 or P388 leukemic cells progressively developed a state of hyporeactivity to interferon induction that was dependent upon inducer and time of administration. A circulating factor was detected in the serum of both L1210 and P388 leukemic mice that could transfer hyporeactivity to normal murine cells in vitro. A direct relationship existed between the concentration of serum factor and development of hyporeactivity to interferon induction in vivo. Characterization of the serum hyporeactive factor from P388 or L1210 leukemic mice indicated that both were similar to a hyporeactive factor previously detected in serum from virus-infected mice. These results suggest a cause-effect relationship between the serum hyporeactive factor and development of hyporeactivity in vivo.

Animals↗
PubMed1975

Hyporeactivity to interferon induction: characterization of a hyporeactive factor in the serum of encephalomyocarditis virus-infected mice.

Mice infected with encephalomyocarditis virus develop a severe state of hyporeactivity to interferon induction. One mechanisms possibly responsibile for development of hyporesponsiveness in these animals is a circulating factor which can be detected in their serum 96 h after encephalomyocarditis virus infection (at the time of peak hyporeactivity in vivo). This report describes some of the physiocochemical characteristics of this serum hyporeactive factor (SHF). SHF is a protein with a molecular weight between 20,000 and 40,000 that was extremely labile at 56 C, losing greater than 90% of its biological activity in 8 min, but stable at 37 c for at least 4 h. Hyporeactive factor was also stable over a pH range of 2 to 11 for 48 h at 4 C. These results suggest that SHF is physicochemically similar to interferon. However, no interferon could be detected in the SHF preparation, and no loss in biological activity was observed when the serum factor was incubated with anti-interferon antibody, suggesting that they are separate substances.

Animals↗