PubMed Health⌕ Search

Biomedical subjects

D A Stringfellow

Publications and source records attributed to D A Stringfellow.

At least 19 recordsLinked to original sources
PubMed1991

Chemically induced viral resistance in single preimplantation bovine embryos.

Viral mRNA encoding vesicular stomatitis virus glycoprotein sequences was detected and quantitated using a DNA-hybridization dot-blot technique. This assay was employed to determine if the synthetic double-stranded polynucleotide complex of polyriboinosinic-polyribocytidylic acid would elicit viral resistance in vitro in single day 9 bovine embryos. The levels of viral mRNA were assayed in 4 groups of bovine embryos: unexposed, virus-exposed, polynucleotide-treated, and virus plus polynucleotide treated. Reduced quantities of viral mRNA in single polynucleotide treated embryos demonstrated that resistance to viral infection was induced in day 9 bovine embryos.

Animals↗
PubMed1990

Experimental antitumor activity of BMY-28175 a new fermentation derived antitumor agent.

BMY-28175 is a novel antitumor antibiotic produced in fermentation by Actinomadura verrucosospora. The cytotoxic effects of BMY-28175 were determined using murine and human tumor cell lines in vitro. Following 72 hour exposure, the drug had IC50 values 1.5 to 13.5 ng/ml in a microtiter assay. BMY-28175 was evaluated for antitumor activity against several experimental murine and human tumor models. The drug administered ip was active against ip implanted P388 leukemia, L1210 leukemia, B16 melanoma, M109 lung carcinoma, C26 colon carcinoma, M5076 sarcoma and Lewis lung carcinoma. In addition, BMY-28175 administered iv was active against iv implanted P388 and L1210 leukemias. BMY-28175 was active against sc implanted B16 melanoma (increased lifespan and/or inhibition of primary tumor growth) in about 60% of the tests. The growth of sc implanted M109 was inhibited by BMY-28175 in a single experiment. BMY-28175 was also active against the MX-1 human mammary xenograft implanted in the subrenal capsule of nude mice. The optimal dose for BMY-28175 in these various studies ranged from 0.16 micrograms/kg per injection with consecutive daily (qd1-9) administration, to 51.2 micrograms/kg with single dose administration. The results of these studies indicate that BMY-28175 is one of the most potent antitumor agents yet observed, with a broad spectrum of activity against tumors of murine and human origin and activity against tumors located distal to the site of drug administration.

Aminoglycosides↗
PubMed1990

Necrotic oophoritis in heifers vaccinated intravenously with infectious bovine rhinotracheitis virus vaccine during estrus.

Twenty-two Hereford heifers were injected IM with prostaglandin F2 alpha a, 11 days apart to synchronize estrous cycles. Twelve of 14 heifers that had signs of estrus were inoculated IV with 1 of 3 modified-live infectious bovine rhinotracheitis virus vaccines, and 2 were assigned to a nonvaccinated control group. Also, 6 of the 8 anestrous heifers were inoculated IV with 1 of the 3 vaccines on the fourth day after the last prostaglandin injection and the other 2 were assigned to the nonvaccinated group. Vaccine virus was isolated from the blood and nasal and vaginal secretions from the vaccinated heifers on postvaccination days 4, 7, and 9. On postvaccination day 9, all heifers were ovariectomized and ovarian tissues were processed for virus isolation and histologic examination. Vaccine virus was isolation and histologic examination. Vaccine virus was isolated from ovarian tissues of some heifers in each of the vaccine groups. Necrotic oophoritis characterized by multifocal areas of ovarian tissue necrosis, hemorrhage, and mononuclear lymphocytic infiltration was observed. The corpora lutea and surrounding ovarian tissues taken from vaccinated heifers in each group had varying amounts of necrotic and inflammatory change, but the changes appeared to be more severe in 1 group than in the other 2. Virus also was isolated from 2 of the controls; these heifers apparently became infected with vaccine virus that had been excreted from the vaccinated animals.

Animals↗
PubMed1989

Trypsin treatment of bovine ova after in vitro exposure to vesicular stomatitis virus.

Preimplantation bovine ova were exposed in vitro to vesicular stomatitis virus, Indiana serotype, to document adherence of the virus to the zona pellucida. To determine the efficacy of this treatment, some of the ova were treated with trypsin after exposure to the virus. Vesicular stomatitis virus was isolated from 5 of 10 groups of zona pellucida-intact ova after 12 sequential washes without trypsin treatment. Vesicular stomatitis virus was also isolated from 4 of 11 groups of zona pellucida-intact ova after trypsin treatment.

Adhesiveness↗
PubMed1988

Inhibitors of topoisomerase II: structure-activity relationships and mechanism of action of podophyllin congeners.

The specific inhibition of eukaryote DNA topoisomerase II by the anti-cancer drugs VP16, VM26, and 21 other congeners of podophyllotoxin has been extensively studied in this laboratory through the use of alkaline elution and other techniques. A structure-activity relationship has been established for cytotoxicity, single and double strand DNA breakage, and inhibition of the DNA strand passing activity of topoisomerase II. Furthermore, topoisomerase inhibition was measured in four naturally sensitive and resistant human lung carcinoma cells by quantifying the amount of single and double strand DNA breakage produced by VP16 and VM26 in cells and isolated nuclei. A direct correlation between double but not single strand DNA breaks and cytotoxicity was observed for the analogs in A549 human lung adenocarcinoma cells. In fact, some analogs were capable of producing substantial single strand DNA breakage without producing cytotoxicity. A similar correspondence was observed between double strand DNA breaks and cytotoxicity produced by VP16 and VM26 in the naturally sensitive and resistant cell lines. Evidence is also presented suggesting that the association of the drug with enzyme-DNA intermediate complex and the formation of the enzyme-DNA complex alone both reflected equilibrium governed conditions that were readily reversible. These studies support a model based on the proposal that the actual cytotoxic events are genetic alterations caused by possible heterologous subunit exchanges occurring between adjacent enzyme molecules, which result from the stabilization of the intermediate complex, rather than the actual loss of topoisomerase II activity caused by the inhibition. The resistance of normal cells and cells with acquired resistance to the possible clastogenic effects of topoisomerase inhibition may be, in part, related to the low topoisomerase II levels found in such cells. Topoisomerase II may also play a role in gene amplification and tumor cell heterogeneity by serving as a vehicle through which genetic recombination events may occur.

Cell Line↗
PubMed1986

In vitro exposure of preimplantation bovine embryos to vesicular stomatitis virus.

Vesicular stomatitis virus New Jersey serotype (VSV-NJ) adhered to 14 of 20 zonae pellucidae intact (ZP-I) bovine embryos exposed in vitro. The VSV-NJ-exposed ZP-I bovine embryos were washed by a single- or multiple-pipette procedure. The multiple-pipette washing procedure was more efficient in removing unattached virus than the single-pipette procedure, but neither washing procedure was effective in consistently removing attached virus from ZP-I embryos. The virus plaque assay with Vero-MARU cells was more sensitive than was the suckling mouse intracerebral inoculation procedure for detection of VSV-NJ from the sonic extracts of bovine embryos. A maximum of 15 infective VSV-NJ particles were detected adhering to one virus-exposed, washed ZP-I bovine embryo.

Animals↗
PubMed1986

Phase I study of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP), an oral interferon inducer, in cancer patients.

2-Amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) was given to 59 patients in a Phase I study. The agent was selected because it is an interferon inducer and an immunotherapeutic agent in animal tumor models. The study was conducted in two phases. In the first phase, the drug was administered as a single oral dose of 25-2,000 mg/m2. In the second part, the highest tolerated dose reached during part one was used as the initial dose in a multiple-dose scheme of treatment. Patients were treated weekly. The dose was escalated each week, starting with a dose of 2 g/m2 and escalating to 3, 4, and 5 g/m2. No cardiac, hematologic, hepatic, or renal toxicity was observed. The most common toxicity was nausea and vomiting, which occurred in 18% of the patients; others were headache (8%), abdominal pain (8%), and diarrhea (6%). No consistent induction of interferon and no major modification of host defense parameters occurred. One patient with malignant melanoma showed evidence of tumor regression. Pharmacologic studies demonstrated a significant decrease in the bioavailability of the drug as it was administered in this study. Further studies of ABPP with a preparation that has good availability are indicated to determine the potential antitumor activity of this agent or this class of agents in humans.

Adult↗
PubMed1985

Pyrimidinones. 1. 2-Amino-5-halo-6-aryl-4(3H)-pyrimidinones. Interferon-inducing antiviral agents.

Interferon induction and antiviral activity was discovered with 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone. An analogue study incorporating a series of 2-amino-5-substituted-6-arylpyrimidinones revealed that the most potent interferon inducers were mono- and difluorophenyl analogues. These same analogues were also potent antiviral agents against Semliki Forest virus and herpes simplex type 1. In addition the monomethoxyphenyl analogues were potent antiviral agents but weak interferon inducers. Relatively modest structural changes led to dramatic changes in bioactivity. There was a relatively poor correlation between levels of circulating interferons induced and systemic antiviral activity.

Animals↗
PubMed1979

Glass capillary gas chromatography with electron-capture detection. Separation of prostaglandins.

Glass capillary gas chromatography of the prostaglandins was performed on a system including an all-glass, solventless injector; thermostable methylphenyl-polysiloxane glass capillary columns; and a conventional electron-capture detector fitted with a make-up gas tee. The principal stable metabolites of prostaglandin endoperoxide were separated as perfluorinated derivatives in 35 min. Detection limits equal or exceed those obtained for packed column separations and electron capture detection. Prostaglandin endoperoxide metabolic profiles from mammalian cell cultures were obtained using this system. These profiling studies are not possible with other chromatographic methods because of inferior resolution and sensitivity.

Animals↗
PubMed1979

Prostaglandin D2 formation by malignant melanoma cells correlates inversely with cellular metastatic potential.

B16 malignant melanoma cell lines transform arachidonic acid and its transient metabolite, prostaglandin endoperoxide H2, into prostaglandin D2. The highly metastatic line, B16 F10, forms less prostaglandin D2 compared to the moderately metastatic parent line, B16 F1. Since platelet aggregation may be one factor involved in B16 metastasis and since prostaglandin D2 inhibits platelet aggregation, this prostaglandin could affect the outcome of platelet-tumour interactions, which may contribute ultimately to metastasis. Arachidonic acid metabolism may be another one of the intrinsic biochemical properties of tumor cells that affects their metastasis. Our results suggest that quantitative release of unusual prostaglandins must be considered in this context.

Arachidonic Acids↗
PubMed1979

Antiviral and interferon-inducing properties of 1,5-diamino anthraquinones.

A series of anthraquinones with amino substituents at the 1,5 positions were found to induce interferon in mice. A prototype compound, 1,5-bis[(3-morpholinopropyl)amino]-anthraquinone (Ia), was an effective antiviral agent when administered either orally or parenterally. Peak interferon titers were found 12 to 24 h after drug treatment. The minimum oral dose of Ia required to induce serum interferon or to protect mice against a lethal virus infection was 62 mg/kg. Mice tolerated an oral dose of at least 30 times this minimum effective dose. A single dose of Ia given up to 6 days prior to infection had significant protective activity. Biological properties of Ia were compared with those of three other 1,5-diamino anthraquinones, which also induced interferon and demonstrated antiviral activity in mice. The most active compound was 1,5-bis[[2-(diethylamino)ethyl]amino]-anthraquinone (Ib), which protected mice against virus infection at a dose as low as 8 mg/kg (less than 1/60 its maximum tolerated dose). Mice developed hyporeactivity to interferon induction if the same inducer was injected daily, although by alternating between different inducers the loss of interferon responsiveness could be avoided.

Animals↗
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↗