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Biomedical subjects

L A Glasgow

Publications and source records attributed to L A Glasgow.

At least 37 records · Page 2Linked to original sources
PubMed1977

Synergistic infection with murine cytomegalovirus and Candida albicans in mice.

A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 20% lethal inoculation of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (80%-100%) after an intravenous injection of a 0-20% lethal inoculum of Candida albicans. The current study revealed that mice infected with murine CMV alone had high titers of virus in spleen, liver, lung, and kidney from days 3 through 20, whereas those inoculated with C. albicans alone had a self-limited fungal infection involving only the kidney. In the combined murine CMV-C. albicans infection, the titers of murine CMV in tissues were changed very little. In contrast, C. albicans was recovered from multiple organs, and a progressive renal infection developed. This altered pathogenesis of the candida infection in murine CMV-infected mice resembled that produced by a 100% lethal inoculum of C. albicans alone. These results indicate that the murine CMV infection enhanced the susceptibility of mice to infection with C. albicans and suggest that death was due to progressive fungal infection of the kidney.

Animals↗
PubMed1977

Alteration of host defense mechanisms by murine cytomegalovirus infection.

An animal model of a sublethal infection, utilizing murine cytomegalovirus (MCMV), was developed to determine whether immunological factors could contribute to the establishment of a persistent viral infection. Adult female C3H mice inoculated intraperitoneally with 10(5) plaque-forming units of MCMV developed splenomegaly 5 to 12 days after infection. Virus replicated to peak titers (10(3) to 10(6) plaque-forming units per g of tissue) in liver, spleen, lung, kidney, and salivary gland tissue during the acute phase of the infection (3 to 12 days); it then decreased to undetectable levels in all tissues except salivary gland. Serum interferon was detected as early as 12 h after infection, peaked at 36 h (1,093 U/ml), and was undetectable by 4 days after infection. MCMV-infected animals were hyporeactive to interferon induction with New castle disease virus on days 5 to 9 of the infection. Splenic lymphocyte reactivity to phytohemagglutinin and lipopolysaccharide was normal early during the course of the infection, was suppressed during the acute phase of the infection, and had returned to normal by day 18. These data indicate that several parameters of host defense are transiently suppressed during the course of a MCMV infection. The capacity of cytomegaloviruses to alter host resistance may be one factor that contributes to the establishment of a persistent infection.

Animals↗
PubMed1977

Evaluation of central nervous system vaccinia antibody synthesis in multiple sclerosis patients.

A serum/cerebrospinal fluid (CSF) ratio method was used to determine whether elevated CSF vaccinia antibody titers in some patients with multiple sclerosis are the result of central nervous system antibody synthesis or of a leak in the blood-brain barrier. Nine of 20 multiple sclerosis patients were noted to have a depressed serum/CSF vaccinia antibody ratio and a normal ratio for poliovirus-I, an agent thought not to be involved in the pathogenesis of multiple sclerosis. These data suggest central nervous system synthesis of vaccinia neutralizing antibody. Vaccinia virus antigens may play an important direct or indirect role in the pathogenesis of multiple sclerosis.

Adult↗
PubMed1977

Effect of interferon on systemic herpesvirus infections.

The studies reviewed here are encouraging in that HSV is moderately sensitive to the action of interferon and that infections in experimental animals clearly may be altered by exogenous interferon and interferon inducers. On the other hand it is apparent that the potential of this approach to treatment of herpesvirus infections is limited by the levels of interferon that can be passively administered or induced, the development of hyporeactivity which prevents maintaining high levels of interferon in infected animals after inoculation of inducers, and the failure to alter the course of HSV infection once the virus is established in target organs.

Animals↗
PubMed1976

Nursery outbreak of scalded-skin syndrome. Scarlatiniform rash due to phage group I Staphylococcus aureus.

From Aug 6 to 14, 1973, scariatiniform eruptions that were considered to be mild forms of the staphylococcal scalded-skin syndrome developed in four neonates. One infant had mild epidermal peeling. All had generalized, finely papular erythema that cleared rapidly after treatment with antibiotics. Cultures from the umbilical stumps or anterior nares of three of the infants yielded colonies of group I Staphylococcus aureus, phage type 29/52/79/86/D11/81, that were able to produce epidermal exfoliation in suckling mice. These data indicate that the nursery outbreak was caused by phage group I staphylococci rather than group II organisms previously associated with staphylococcal scalded-skin syndrome. The demonstration that a group I Staphylococcus can produce exfoliative toxin suggests that the same mechanism for toxin production may exist for phage groups I and II staphylococci.

Cross Infection↗
PubMed1976

Effective antiviral chemotherapy in cytomegalovirus infection of mice.

Both murine and human strains of cytomegalovirus were shown to be sensitive to the antiviral effects of adenine arabinoside and phosphonoacetic acid in tissue culture. In mice with lethal cytomegalovirus infections, treatment with adenine arabinoside (either 500 mg/kg intraperitoneally once daily or 250 mg/kg intraperitoneally twice daily for seven days) failed to reduce the mortality rate or to decrease the mean number of days until death. In contrast, treatment with the same dosage regimen of phosphonoacetic acid significantly reduced the mortality rate and decreased the mean number of days until death even when therapy was delayed for 24 hr. Although early treatment with phosphonoacetic acid resulted in a marked reduction in viral titers in the brains and lungs of infected mice, the major reason for efficacy appeared to be complete inhibition of viral replication in the liver. The observation that titers of complement-requiring neutralizing antibody were significantly lower in treated animals than in untreated controls is further evidence of successful therapy. Treatment of a nonlethal cytomegalovirus infection with phosphonoacetic acid beginning 48 hr after viral challenge resulted in elimination of clinical signs of illness and reduction in viral titers in tissues. These results indicate that phosphonoacetic acid is successful in the treatment of murine infections with cytomegalovirus; they suggest that this drug should be considered for potential use in serious cytomegalovirus infections in humans.

Acetates↗
PubMed1976

Advantages and limitations of animal models in the evaluation of antiviral substances.

Since many antiviral substances with potential for use in humans are in various phases of evaluation, criteria must be developed for selection of those compoinds with the greatest probability of efficacy and least toxicity. We lack background experience in evaluation of antivirals to permit extrapolation from in vitro tests to use in humans; it is of critical importance, therefore, to develop animal models for evaluation of antiviral substances before trials in humans and to establish guidelines for the relative predictive reliability of in vitro screening and evaluation in animal models. The complexity of drug-host and virus-host interaction and other factors may limit the predictive value of some or all experimental systems. Although the use of animal models is an important phase in the evaluation of antiviral chemotherapeutic agents, the models must be carefully studied and the interaction of drug and virus in the experimental animal specifically defined if optimal guidelines for the predictive value of model systems are to be developed. These guidelines must then be modified as experience is gained with antiviral substances that reach human trials.

Amantadine↗
PubMed1976

Effect of treatment with exogenous interferon, polyinosinic acid-polyctyidylic acid or polyinosinic acid-polycytidylic acid-poly-L-lysine complex on encephalomyocarditis virus infections in mice.

The effect of treatment with exogenous interferon was compared with two interferon inducers, polyinosinic acid-polycytidylic acid [poly(I:C)] and [poly(I:C)]-poly-l-lysine complex (P-L-L complex), in two model encephalomyocarditis virus infections of mice. Although both inducers stimulated the production of interferon, the peak serum levels induced by P-L-L complex were five- to eightfold greater than those induced with poly(I:C). When encephalomyocarditis virus was inoculated by either the intraperitoneal or the intranasal route, interferon and both of the inducers protected mice against mortality and prolonged the mean day of death when the compounds were given prior to or immediately after viral challenge. In general, treatment with interferon was not as successful as treatment with poly(I:C) or P-L-L complex. In these infections, P-L-L complex appeared to be the most effective agent in that successful treatment resulted when drug therapy was initiated as late as 48 h after virus inoculation. An examination of the effect of treatment on the pathogenesis of the infection indicated that protection was associated with the prevention of viremia and subsequent seeding of target organs, particularly the central nervous system.

Animals↗
PubMed1976

Antiviral activity of BL-3849A, a low-molecular-weight oral interferon inducer.

Oral administration of BL-3849A to adult mice resulted in peak serum interferon titers of 4,000 units from 15 to 30 h after administration, with detectable levels persisting until 48 h. After intraperitoneal (i.p.) inoculation, peak serum interferon titers of 1,000 to 3,000 units were noted between 9 and 18 h. Multiple injections of the inducer by either route resulted in a marked decrease in the interferon response with each successive dose. In mice infected intranasally with the Rochester mouse virus strain of encephalomyocarditis virus, oral treatment with BL-3849A reduced mortality when initiated either 18 h before or 1 h after infection. In contrast, administration of drug by the i.p. route decreased mortality only if begun before infection. In mice inoculated i.p. with encephalomyocarditis virus, treatment by both the oral and the i.p. route decreased the mortality whether initiated 18 h before or 1 h after infection. Treatment by the oral, but not the i.p., route reduced mortality of mice inoculated i.p. with Semliki forest virus or Herpesvirus hominis type 2. BL-3849A appeared to be as effective as tilorone hydrochloride, but less effective than polyriboinosinic-polyribocytidylic acid, in the treatment of these viral infections of mice.

Aminoquinolines↗
PubMed1976

Effect of cytosine arabinoside and 5-iodo-2'-deoxyuridine on a cytomegalovirus infection in newborn mice.

Murine cytomegalovirus was inhibited by 0.6 to 1.2 mug of cytosine arabinoside per ml and by 0.3 to 0.6 mug of 5-iodo-2'-deoxyuridine in mouse embryo fibroblast cells. Human cytomegalovirus was inhibited by similar concentrations of the two drugs in WI-38 cells. Intraperitoneal inoculation of suckling mice with 10(4.5) plaque-forming units of murine cytomegalovirus provides a model for disseminated human cytomegalovirus infection in human newborn infants and is characterized by a widespread infection involving the liver, spleen, lung, kidney, and brain with a 70 to 90% mortality in 7 to 9 days. Treatment with 12.5 mg of cytosine arabinoside per kg or 25 mg of 5-iodo-2'-deoxyuridine per kg twice daily for 8 days had no effect on final mortality or the pathogenesis of the infection with the exception of reduced viral titers in the spleen of 5-iodo-2'-deoxyuridine-treated animals. These data indicate that neither cytosine arabinoside nor 5-iodo-2'-deoxyuridine are effective in the treatment of murine cytomegalovirus infections in suckling mice and suggest that they may be of limited value in the treatment of severe cytomegalovirus infections in human neonates.

Animals↗
PubMed1976

Phage group II staphylococcal strains with chromosomal and extrachromosomal genes for exfoliative toxin production.

Staphylococcal phage group 2 strain UT0007 was previously shown to contain a high-molecular-weight plasmid containing genes for exfoliative toxin (ET) and bacteriocin production. Phage group 2 strains UT0002 and UT0003 (Tox+Bac-) underwent a twofold and ninefold loss of ET activity, respectively, after growth at 44 C for 18 h. Strain UT0002 also lost total bacteriocin activity. Both strains contained (i) a 56S plasmid that was lost from those substrains showing reduced ET activity and (ii) a 21S plasmid with a gene for cadmium resistance that could be transduced into two recipient strains. Since the ET plasmid-negative substrains still made ET, it was postulated that this residual toxin was made from chromosomal genes. In characterizing the plasmid species from strains UT0002 and UT0003, the 21S but little or no 56S plasmid deoxyribonucleic acid could be isolated after centrifugation of cleared lysates from these strains on dye-buoyant density gradients. Treatment of cleared lysates from strain UT0002 with ethidium bromide, Pronase, or sodium dodecyl sulfate, but not heat at 60 C, induced conversion of the 56S closed circular ET plasmid to a 38S open circular form as determined after centrifugation on 5 to 20% neutral sucrose gradients.

Cadmium↗
PubMed1976

Staphylococcal scalded-skin syndrome: development of a primary binding assay for human antibody to the exfoliative toxin.

Exfoliative toxin (ET) from a phage group II Staphylococcus aureus strain causing staphylococcal scalded-skin syndrome was purified by electrofocusing. Ampholytes and salts were removed from the final product by column chromatography on G-50 Sephadex. Sodium dodecyl sulfate-polyacrylamide gels of the final product yielded a single band upon gel electrophoresis, even when 60 mug of protein was placed in the gels. Radiolabeling of the purified toxin with 125I yielded a product that still caused exfoliation of suckling mice, indicating that the toxin was still biologically active. A radioimmunobinding assay was developed and used to test rabbit and human sera for antibodies to exfoliative toxin. Although the maximum percentage of binding was not as high as expected (approximately 40%), it was postulated that either iodination had not been sufficiently vigorous or the toxin had sustained immunological damage. The assay was reproducible and more sensitive than the existing neutralization method and readily applicable to the testing of human sera for exfoliative toxin antibodies.

Animals↗
PubMed1976

Fetal and adult bovine interferon production during bovine viral diarrhea virus infection.

Levels of interferon in adult bovine serum and in fetal bovine serum and tissues were examined during the course of transplacental bovine viral diarrhea virus infection. The cows produced circulating interferon between 2 and 9 days after viral inoculation, with mean peak levels in the serum on day 4. Interferon could be routinely detected in fetal tissues (e.g., thymus, spleen, and kidney) between days 4 and 21 after viral inoculation of the cows at 149 to 150 days of gestation (mid-second trimester) and in fetal serum from day 13 through day 21. Interferon was also detectable in the serum and tissues of fetuses from dams infected at day 95 of gestation (the beginning of the second trimester). In general, no differences were found between the ability of the adult and fetus to produce interferon. Fetal lamb kidney cells were more sensitive to the antiviral effects of bovine interferon than were fetal bovine kidney cells. The antiviral substance from the fetal and adult animals was characterized as interferon by standard criteria.

Age Factors↗
PubMed1976

Synergistic effect on mortality in mice with murine cytomegalovirus and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections.

A synergistic effect on mortality was demonstrated in a combined infection of mice with murine cytomegalovirus (MCMV) and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans. Mice infected intraperitoneally with a 0 to 20% lethal dose inoculum of MCMV 3 days prior to the intravenous injection of a 0 to 20% lethal dose inoculum of either the bacteria or fungus demonstrated a striking enhancement of mortality. MCMV-infected mice given Pseudomonas or Staphylococcus exhibited a 90 to 100% mortality within 24 to 48 h, whereas 80% of viral-infected animals injected with Candida died in 5 days. Injection of the bacteria or fungus at various times during the MCMV infection resulted in enhanced mortality on days 0,1,2, and 3 of the viral infection. Greatest synergism was observed on day 3, with a progressive decline in death rates thereafter. Immunization with MCMV abrogated the synergistic effect on mortality in all three combined infections. Immunization with Pseudomonas reduced mortality in the combined MCMV-Pseudomonas infection. These results indicate that mice exhibit a markedly enhanced susceptibility to bacterial and fungal infections during the course of the MCMV infection and suggest that the enhancement may be related to viral-induced alterations in host resistance.

Animals↗
PubMed1975

Effect of Corynebacterium acnes on interferon production in mouse peritoneal exudate cells.

Corynebacterium acnes, an organism closely related to C. parvum, has been recognized to have a striking effect on the reticuloendothelial system, as well as on both humoral and cellular immunity. In mice previously exposed to C. acnes, serum interferon levels induced by injection of Newcastle disease virus (NDV), Chikungunya virus (CV), and polyinosinic-polycytidylic acid are suppressed. When peritoneal macrophages and lymphocytes from animals exposed to C. acnes were cultivated in vitro, their capacity to produce interferon in response to NDV and CV was reduced. Furthermore, the interferon-producing capacity of these cells in tissue culture was inhibited after exposure to C. acnes to vitro. Exposure of separated populations of peritoneal macrophages and lymphocytes to C. acnes in vitro demonstrated that the interferon response to NDV by both cell types is inhibited. Peritoneal macrophages appear to be the major contributor to the interferon response in this system. Finally, this inhibitory effect was shown to occur after exposure to a purified cell wall preparation of C. acnes organisms, as well as a lipid extract of this preparation.

Animals↗
PubMed1975

Genital herpesvirus hominis infection in mice. I. Development of an experimental model.

Pregnant female mice, after intravaginal inoculation with Herpesvirus hominis (HVH) type 2, developed vaginitis on days 5 to 7 after virus challenge, followed by hunching and hind limb paralysis on days 7 to 9 and death from encephalitis on days 9 to 11. After initial replication in the mucous membranes of the genital tract, virus spread to the spinal cord and ascended to involve the brain. Viremia or replication of H. hominis type 2 in the liver or spleen was not detected. Virus was cleared from vaginal secretions by days 8 to 10 after infection. Pregnant mice were more susceptible to the infection than nonpregnant mice. This experimental infection in female mice provides a model for genital herpesvirus infection and for herpesvirus infection and for herpesvirus encephalitis in which one can evaluate potentially promising antiviral chemotherapeutic agents.

Animals↗