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Biomedical subjects

J C Overall

Publications and source records attributed to J C Overall.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1977

The natural history of recurrent herpes simplex labialis: implications for antiviral therapy.

We performed daily examination of 80 patients with recurrent herpes simplex labialis to define the course of the disease and to identify quantitative and objective measurements for use in monitoring the efficacy of antiviral chemotherapy. Pain, lesion size, mean virus titers from lesion swabs (10(5) plaque-forming units [PFU]) and frequency of virus-positive lesions (89 per cent) were maximal during the first 24 hours and decreased thereafter. Lesion punch-biopsy virus titers increased from a mean of less than 10(1) PFU in the prodromal and erythema stages to a mean of 10(4.7) in the vesicle stage. MEasurements potentially useful in monitoring antiviral efficacy include: time to loss of crust, time to complete healing, intensity and duration of lesion pain, area defined by lesion virus titer and duration of lesion virus excretion, and maximum lesion virus titer after the first visit. Early application of topical antiviral therapy should theoretically be able to alter the course of this disease.

Administration, Topical↗
PubMed1977

Outbreak of meningitis in a newborn intensive care unit caused by a single Escherichia coli K1 serotype.

Three cases of meningitis that occurred during a nine-day period in a newborn intensive care unit were caused by a single E. coli serotype 07:K1:H-. A single organism outbreak was suspected when the three spinal fluid isolates all possessed the same two unusual bacteriologic and biochemical characteristics: nonmotile and ornithine negative. Culture surveillance identified eight infants colonized with the same strain of E. coli; three of these infants are described. Clusters of cases of E. coli meningitis in newborn intensive care units should be evaluated and managed as potential outbreaks.

Cross Infection↗
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

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↗
PubMed1976

Nosocomial infections in a newborn intensive-care unit. Results of forty-one months of surveillance.

We detected a 24.6 per cent nosocomial infection rate (222 infections in 138 infants) among 904 infants hospitalized for over 48 hours in a regional newborn intensive-care during 41 months of surveillance. Surface infections accounted for 40.1 per cent of the total, pneumonia for 29.3 per cent, bacteremia for 14.0 per cent, surgical-wound infection for 8.1 per cent, urinary-tract infection for 4.5 per cent, and meningitis for 4.0 per cent. Staphylococcus aureus (47.3 per cent) and gram-negative enteric bacilli (45.1 per cent) were the most common organisms recovered. Nosocomial infection rates were significantly higher in infants with a birth weight less than 1500 g (P less than 0.001). The mortality rate in infants with any nosocomial infection was 33 per cent in contrast to 14 per cent in non-infected babies (P less than 0.001). Nosocomial infections are a major problem in newborn intensive-care units.

Birth Weight↗
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

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

Induction of interferon in ovine and human lymphocyte cultures by mycoplasmas.

Mycoplasma pneumoniae, Acholeplasma laidlawii, M. arthritidis, and M. pulmonis were shown to induce interferon in the lymphocyte fraction of ovine peripheral blood leukocytes, but not in the polymorphonuclear leukocyte fraction. Human peripheral blood lymphocytes produced significant levels of interferon in response to infection with M. pneumoniae and M. synoviae. The antiviral substance induced by the mycoplasmas in human lymphocytes was characterized as interferon by the usual criteria.

Acholeplasma laidlawii↗
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↗