PubMed Health⌕ Search

Biomedical subjects

L A Glasgow

Publications and source records attributed to L A Glasgow.

At least 19 recordsLinked to original sources
PubMed1979

Activation of reticuloendothelial cells following infection with murine cytomegalovirus.

Macrophage and reticuloendothelial system function was investigated in adult, female C3H mice during the course of a nonlethal infection with murine cytomegalovirus (MCMV). Peritoneal macrophages harvested from mice infected three to 21 days previously were tumoricidal in vitro for a syngeneic mammary tumor cell line and showed antiviral activity by suppressing replication of vaccinia virus in a fibroblast monolayer. In addition, macrophages harvested from animals on days 7 and 14 after MCMV infection manifested augmented phagocytosis of yeast particles in vitro. Furthermore, enhanced levels of chemiluminescence were emitted during phagocytosis of zymosan particles by macrophages harvested on days 3 and 7 after MCMV infection. Finally, enhanced protection against Listeria monocytogenes was demonstrated in mice on days 7, 14, and 21 after MCMV infection. These findings support the concept of activation of the reticuloendothelial system during viral infection.

Animals↗
PubMed1979

Enhancement of resistance to murine osteogenic sarcoma in vivo by an extract of Brucella abortus (Bru-Pel): association with activation of reticuloendothelial system macrophages.

The administration of an aqueous-ether extracted residue of Brucella abortus (Bru-Pel) inhibits development of transplanted osteogenic sarcomas in mice as evidenced by a decrease in mortality. At least one mechanism through which Bru-Pel modulates host resistance is activation of macrophages of the reticuloendothelial system. Peritoneal macrophages harvested from mice receiving Bru-Pel were cytotoxic for osteogenic sarcoma cells in vitro, limited the replication of vaccinia virus in cell cultures, and demonstrated enhanced emittance of chemiluminescence during phagocytosis of zymosan particles of Candida albicans. The concept of reticuloendothelial system activation was further supported by the evidence that administration of Bru-Pel enhanced resistance of mice to challenge with a lethal inoculum of Listeria monocytogenes. These observation support the hypothesis that Bru-Pel shares a number of characteristics with recognized immunomodulating agents and that one mechanism by which it modulates host resistance to tumors, to virus infections, and to challenge with L. monocytogenes is through activation of macrophages.

Animals↗
PubMed1978

Resistance of visna virus to interferon.

Visna is a slow infection of sheep caused by a retrovirus. The persistence of virus despite the immune response of the host is best explained by restricted genetic expression of the virus and consequently prolonged periods of residence inside cells. The purpose of this investigation was to determine whether the restriction in genetic expression of visna virus is mediated by interferon. Sheep interferon induced by polyriboinosinic-polyribocytidylic acid in fetal lambs inhibited the growth of herpes simplex virus, vesicular stomatitis virus, and vaccinia virus, but even highly concentrated interferon did not affect the replication of visna virus in sheep choroid plexus cells. The same results were obtained whether the effects of interferon were assessed in single of multiple cycles of growth and when interferon was added at later times in the growth cycle of the virus. This unusual resistance of visna virus to interferon suggests that restriction of viral expression by the host is probably not mediated in this way.

Animals↗
PubMed1978

Antitumor activity of interferon against murine osteogenic sarcoma cells in vitro.

Murine interferon inhibited the growth of a continuous line of osteogenic sarcoma (OGS) cells in tissue culture. Inhibition of tumor cell growth by interferon was demonstrated by: a) decreased colony formation in soft agar, b) suppression of clone formation in liquid medium, and c) reduction of tumor cell counts in monolayer cultures. This inhibition of cell growth was further documented by suppression of [3H]thymidine uptake by OGS cells exposed to interferon, which suggested inhibition of DNA synthesis of tumor cells. Exposure of tumor cells for 4 hours, 24 hours, and 2,3,4,6, and 8 days demonstrated greater activity with prolonged exposure to interferon. Inhibition of cell growth was significantly greater for OGS cells than for normal mouse embryo fibroblasts. Finally, the antitumor activity of the interferon preparation could be reversed by anti-interferon antibody.

Animals↗
PubMed1978

Alteration of mortality and pathogenesis of three experimental Herpesvirus hominis infections of mice with adenine arabinoside 5'-monophosphate, adenine arabinoside, and phosphonoacetic acid.

The therapeutic effectiveness of adenine arabinoside 5'-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with H. hominis, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain.

Animals↗
PubMed1978

Treatment of experimental herpesvirus infections with phosphonoformate and some comparisons with phosphonoacetate.

Phosphonoformate (PF) at a concentration of 5 to 10 mug/ml inhibited the growth of type 1 strains of herpes simplex virus (HSV) in tissue culture, whereas 20 to 30 mug/ml was required for inhibition of type 2 strains and about 50 mug/ml was required for murine cytomegalovirus. In mice inoculated intraperitoneally or intracerebrally with HSV or intraperitoneally with murine cytomegalovirus, treatment with 250 to 400 mg of PF per kg twice daily for 5 days had only minimal effectiveness. When mice were inoculated intravaginally (i.vg.) with HSV type 2 and treated i.vg. with 10% PF beginning 3 h after viral inoculation, treatment was effective in completely inhibiting viral replication in the genital tract. If i.vg. therapy was initiated 24 h after infection, when the mice had a mean virus titer of 10(5) plaque-forming units in vaginal secretions, a significant reduction in the mean virus titer was observed on days 3, 5, and 7 after infection as compared with control animals. In guinea pigs treated i.vg. with 10% PF beginning 6 h after i.vg. inoculation with HSV type 2 there was also complete inhibition of viral replication in the genital tract, and no extenal lesions developed. When therapy was initiated 24 h after infection there was a 4 to 5-log decrease in viral titers on days 3, 5, and 7 of the infection and a slight delay in the development of external lesions.

Animals↗
PubMed1978

Variable effect of encephalomyocarditis virus on host defense mechanisms.

A number of viruses have been shown to suppress a variety of host defense mechanisms. To further define the effect of a viral infection on host resistance, a number of parameters were examined during the course of a lethal encephalomyocarditis virus infection of mice. The peripheral lymphocyte count, the induction of interferon in spleen cells by Newcastle disease virus, and the proportion of B cells in the spleen were all decreased or suppressed. In contrast, the responsiveness of spleen lymphocytes to phytohemagglutinin, the delayed-type skin hypersensitivity to dinitrofluorobenzene, and the proportion of T cells in the spleen remained normal. These results indicate that a viral infection may have divergent effects on different parameters of host resistance and emphasize the need to examine several functions before drawing conclusions about the effect of viral infections on host defense mechanisms.

Animals↗
PubMed1978

Peritoneal macrophage activation indicated by enhanced chemiluminescence.

A number of studies have demonstrated the ability of various bacterial preparations, protozoa, and chemicals to activate macrophages and concomitantly to enhance host resistance to both tumors and infections. Recently, viral infections have been shown to have a similar effect upon macrophage function. To better define the metabolic state of activated macrophages, we have evaluated the ability of peritoneal cells (PC) from vaccinia virus- or murine cytomegalovirus-infected or Corynebacterium parvum-treated mice to emit chemiluminescence (CL) during phagocytosis of zymosan particles or yeasts. PC from C. parvum-treated mice (1,400 microgram intraperitoneally) emitted enhanced CL over controls on days 3, 6, 14, and 21 after treatment, thereby establishing the emission of CL as a correlate of metabolic activation. Previous evidence for activation of PC from vaccinia virus-infected mice (10(8) plaque-forming units) was confirmed by demonstration of enhanced levels of CL on days 3, 6, and 13 after murine infection. Likewise, PC from mice infected with murine cytomegalovirus (10(5) plaque-forming units) 3, 6, or 13 days previously demonstrated augmented levels of CL over controls. Opsonized virus particles (vaccinia virus or murine cytomegalovirus) failed to induce the emission of CL with PC from mice infected with the isologous virus. Our data further demonstrate the immunomodulationinduced by virus infections and suggest that the detection of CL is an easily quantitated correlate of macrophage activation which may be helpful in defining metabolic alterations induced during activation.

Animals↗
PubMed1978

Inhibition of murine osteogenic sarcomas by treatment with type I or type II interferon.

Interferon was used to treat C57BL/6 female mice inoculated with a continuous line of murine osteogenic sarcoma cells. A short 7-day course of 30,000--60,000 U/day of tpe I interferon either completely inhibited or delayed the appearance of tumors in experimental animals. The therapeutic efficacy of type I interferon was compared with murine serum that contained type II interferon as well as other lymphokine activity. Tumor development was strikingly inhibited in animals treated for 7 days with serum containing only 600 U of type II interferon. Inhibition of tumor development was thus achieved with 100-fold less interferon than that required with type I preparation.

Animals↗
PubMed1978

Antitumor activity of interferon against murine osteogenic sarcoma in vitro and in vivo.

Murine interferon inhibited the growth of a continuous line of osteogenic sarcoma cells in tissue culture. Inhibition of tumor cell growth was documented by decreased clone formation in liquid medium, decreased tumor cell counts in monolayer cultures, suppression of colony formation in semi-solid agar, and decreased uptake of 3H-thymidine by the osteogenic sarcoma cells in culture. The capacity of anti-interferon antibody to block the tumor cell growth inhibitory activity of the interferon preparation suggested that interferon itself is the biologically active component of the interferon preparations. In vivo, a 7-day course of 30,000-60,000 units/day of type I interferon prepared in cell cultures either completely inhibited or delayed the appearance of tumors in experimental animals inoculated with osteogenic sarcoma cells by the sc route. The therapeutic efficacy of a preparation of murine sera containing type II interferon as well as other lymphokine activity was compared with the type I interferon preparation. Animals treated with 600 units of type II interferon were protected against tumor development as effectively as with 60,000 units/day of type I.

Animals↗
PubMed1978

Activation of reticuloendothelial system macrophages and enhancement of host resistance to a transplantable osteogenic sarcoma in mice by an extract of Brucella abortus.

An aqueous-ether extract of Brucella abortus, Bru-Pel, enhanced resistance of mice to a transplantable osteogenic sarcoma (OGS). The results presented in this report suggest that Bru-Pel is an effective immunomodulator and that one mechanism through which it enhances host resistance is activation of phagocytic cells of the reticuloendothelial system. Peritoneal macrophages from mice inoculated with Bru-Pel 14 days previously were cytotoxic for OGS cells in vitro, limited the multiplication of vaccinia virus in cell cultures, and demonstrated increased chemiluminescence during phagocytosis. Furthermore, Bru-Pel enhanced host resistance to Listeria monocytogenes, in addition to viral infections and a transplantable tumor. These results support the hypothesis that Bru-Pel shares a number of characteristics with other recognized immunomodulating agents and suggest that further studies are warranted to better define the potential of Bru-Pel for immunotherapeutic regimens in man.

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

Genital Herpesvirus homonis infection in mice. II. Treatment with phosphonoacetic acid, adenine arabinoside, and adenine arabinoside 5'-monophosphate.

Genital infection of mice with Herpesvirus hominis type 2 provides an experimental model for screening potential antiviral chemotherapeutic agents before clinical trials in humans. Intravaginal treatment with phosphonoacetic acid (at a dose of 500 mg/kg in saline or as a 5% cream) initiated 3 hr after inoculation with H. hominis type 2 completely inhibited viral replication in the genital tract and prevented subsequent mortality. Although therapy initiated 24-72 hr after infection significantly reduced titers of virus in vaginal secretions from three- to 100-fold, most mice eventually died of encephalitis. Topical treatment with either adenine arabinoside or adenine arabinoside 5'-monophosphate at a dose of 500 mg/kg in saline or as a 10% cream failed to alter viral replication in the genital tract or to protect the mice from death due to encephalitis. Treatment by the intraperitoneal route with any of these three agents had no effect on local viral replication or final mortality.

Adenosine Monophosphate↗
PubMed1977

Immunomodulation of host resistance to experimental viral infections in mice: effects of Corynebacterium acnes, Corynebacterium parvum, and Bacille calmette-guérin.

Resistance to a representative group of experimental virual infections in mice was significantly enhanced by nonspecific modulation of host defense mechanisms. Corynebacterium acnes, Corynebacterium parvum, and bacille Calmette-Guérin were effective in enhancing host resistance. Animals treated seven to 10 days before inoculation of virus were protected against a lethal infection with Herpesvirus hominis type 2, encephalomyocarditis virus, murine cytomegalovirus, or Semliki Forest virus. The protection of experimental animals against encephalomyocarditis virus infection intitiated by either the intraperitoneal or the respiratory route indicated that C. acnes exerted a systemic, rather than local, effect. A maturation process was required for host defense mechanisms stimulated by C. acnes, as indicated by the failure to enhance resistance in suckling animals. Involvement of cells of the lymphoreticular system was demonstrated by transfer of enhanced resistance against H. hominis type 2 to recipient animals with peritoneal exudate cells harvested from mice pretreated with C. acnes. Finally, these same cells inhibited the progression of herpetic infection in tissue culture. The data suggest that immunomodulation, possibly through activation of macrophages, may offer a method for enhancement of host resistance to viral infections.

Animals↗