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Biomedical subjects

E R Kern

Publications and source records attributed to E R Kern.

At least 91 records · Page 5Linked to original sources
PubMed1982

Failure of 2-deoxy-D-glucose in the treatment of experimental cutaneous and genital infections due to herpes simplex virus.

The effectiveness of 2-deoxy-D-glucose (2-DG) was evaluated in the treatment of cutaneous infections with herpes simplex virus type 1 (HSV-1) in mice and genital infections with HSV type 2 (HSV-2) in mice and guinea pigs. Groups of mice were inoculated in the lumbosacral or orofacial area with HSV-1 and treated topically three times a day with 0.2% or 0.5% 2-DG solution beginning 3 hr after inoculation. No effect on skin lesions, mortality, or latency was observed. Mice were inoculated intravaginally with HSV-2 and treated intravaginally three times a day with 0.2%-5% 2-DG in solution or suspended in miconazole nitrate cream beginning 6 hr, 24 hr, or 48 hr after inoculation. Replication of HSV-2 in the vagina and final mortality were not affected. Guinea pigs were infected intravaginally with HSV-2 and treated both intravaginally and topically on the external genitalia four times a day with 1% or 5% 2-DG in miconazole nitrate cream. Treatment initiated just prior to development of lesions (on day 3 after inoculation) did not alter vaginal virus replication, lesion development and severity, or virus titers in lesions.

Administration, Topical↗
PubMed1982

Genital herpes in guinea pigs: pathogenesis of the primary infection and description of recurrent disease.

Guinea pigs inoculated intravaginally with herpes simplex virus type 2 (HSV-2) developed a self-limiting infection characterized by vesiculo-ulcerative lesions on the external genital skin, urinary retention, and hindlimb paralysis. Infection rarely resulted in death. Virologic, histologic, and immunoperoxidase data suggested the following scheme for viral pathogenesis: initial replication in the introitus, vagina, and bladder; spread via sensory nerves to the lumbosacral dorsal root ganglia and spinal cord, and transmission via peripheral nerves to the external genital skin to produce the characteristic lesions. After recovery from primary infection, animals developed recurrent vesicular lesions, shed virus from genital sites in the absence of lesions, and harbored latent HSV-2 in dorsal root ganglia. Genital infection in the guinea pig shares many features with genital herpes in humans and provides a model to explore mechanisms of latency and reactivation and to evaluate several methods for control of recurrent disease.

Animals↗
PubMed1982

Typing of herpes simplex virus with type-specific human immunoglobulin M in an indirect immunofluorescence assay.

Sera from nine individuals with suspected primary herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infection were screened to identify those containing HSV type-specific immunoglobulin M (IgM). Selected sera were then utilized in an IgM-specific indirect immunofluorescent-antibody HSV-typing assay (patent pending). To evaluate the procedure, 29 HSV isolates were grown in cultures of continuous human amnion cells, fixed, and used as substrates for indirect immunofluorescence. Determination of virus type was based on intensity of fluorescence of the substrate with HSV-1- and HSV-2-specific antisera after staining with fluorescein-conjugated anti-human IgM. Typing of the isolates by restriction endonuclease digestion showed that of 29, 18 were HSV-2 and 11 were HSV-1. Results by IgM-specific indirect immunofluorescent-antibody assay were identical to those by restriction endonuclease digestion for 27 of the isolates; 2 isolates failed to replicate adequately in the test cells. The IgM-specific indirect immunofluorescent-antibody procedure appears to be a simple, rapid, and accurate technique which could be of use to clinical virology laboratories.

Fluorescent Antibody Technique↗
PubMed1982

Use of viral infections in animal models to assess changes in the immune system.

Viral infections in animal models appear to be ideal systems for determining toxicity to the immune system by environmental substances. Since many viral infections that are utilized in animals produce systemic disease, these models provide an opportunity to evaluate the interaction between virus and components of host resistance. In these infections it is possible to delineate the role of antibody, interferon, cell-mediated immunity, neutrophils and macrophages in response to infection. A change in any of these components responsible for resistance to a particular virus may be correlated with an alteration of mortality an pathogenesis of the viral infection. Three experimental viral infections in mice that are potential candidates for use in determining immunotoxicity are discussed in terms of the response of individual components of resistance to infection and how changes in there components result in alterations of viral pathogenesis. The resistance to encephalomyocarditis virus infection in mice appears to be primarily mediated by antibody and interferon while with herpes simplex virus, infections are mainly controlled through cell-mediated immunity, macrophages, and possible interferon. Cellular immunity also appears to be primarily responsible for resistance to cytomegalovirus infections. Therefore, it is important in the use of these systems for evaluating immunotoxicity to define the pathogenesis of the viral infection and the specific host responses to these infections and to be able to correlate a change in host resistance with an alteration of the viral infection.

Animals↗
PubMed1981

Progressive neurological disease associated with chronic cytomegalovirus infection.

Cytomegalovirus (CMV), the most common infectious cause of nervous system damage in the fetus and newborn infant, generally has been thought to exert its teratogenic effect during early pregnancy, and it has been assumed that clinical or postmortem abnormalities reflect static insults incurred earlier. Over the past two years we have identified two infants who presented with various clinical signs suggesting CMV infection. Serial CT head scans showed mild hydrocephalus progressing to extensive loss of brain substance and hydrocephalus in one and a normal scan going on to polycystic encephalomalacia in the other. Both infants had urine or leukocyte cultures that were repeatedly positive for CMV. These data suggest that CMV can cause progressive central nervous system damage after birth. The findings may account for some unexplained brain malformations and for a portion of the neurodegenerative disorders occurring in babies who appear normal at birth.

Brain Diseases↗
PubMed1981

A comparison of phosphonoacetic acid and phosphonoformic acid activity in genital herpes simplex virus type 1 and type 2 infections of mice.

The activity of phosphonoacetic acid (PAA) and phosphonoformic acid (PFA) against four strains of herpes simplex virus type 1 (HSV-1) and four strains of HSV-2 were compared in tissue culture and in a murine model of genital herpes. In mouse embryo fibroblast cells, both drugs were three-fold more active against the HSV-1 strains than against the HSV-2 strains. In contrast, in the animal model infections, PAA appeared to be more active against the HSV-2 strains, while PFA was equally effective against both HSV types. In mice infected intravaginally with HSV-2 and treated with intravaginal 5% PAA, none of the treated mice became infected, replication of virus in the genital tract was completely inhibited, none of the infected mice died from encephalitis, and latent infection in lumbosacral ganglia of surviving animals was completely prevented. In HSV-1 genital infection treated with PAA, 20-60% of mice became infected, replication of virus in the genital tract was strikingly reduced, none of the infected mice died, and latent infection was completely prevented. In both HSV-2 and HSV-1 genital infections, 20-70% of animals treated with 8% PFA became infected, growth of virus in the genital tract was reduced significantly but not completely suppressed, mortality was variably altered, and there was a trend towards reduction in the frequently of latent infection. These results indicate that HSV-1 strains are more sensitive to PAA and PFA in tissue culture, but the HSV-2 strains are generally more amenable to therapy in the murine model of genital herpes. Although PAA appeared to be more active that PFA in the genital infection, both drugs significantly altered the course of the infection. Since dermal toxicity associated with PAA precludes its use in humans and since PFA is already undergoing trials in patients with recurrent herpes labialis, the current results suggest that topical PFA deserved further evaluation in the treatment of mucocutaneous HSV infections, including genital herpes.

Animals↗
PubMed1981

Differences in neurovirulence among isolates of Herpes simplex virus types 1 and 2 in mice using four routes of infection.

Differences in neurovirulence between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were investigated using recent clinical isolates and laboratory-passaged strains in intravaginal, intranasal, intraperitoneal, and intracerebral infections of mice. The HSV-2 isolates caused higher death rates in all four infections. No differences in death rate were observed between recent and passaged isolates of either HSV-1 or HSV-2. After intravaginal inoculation, HSV-1 isolates replicated to higher titers in the vaginal mucosa, but HSV-2 isolates produced a higher death rate and a greater frequency of latent infection in lumbosacral ganglia of surviving animals. After intranasal inoculation, HSV-2 isolates again produced a higher death rate, but the frequency of latent infection in trigeminal ganglia was higher with HSV-1 isolates. The data suggest that the HSV-2 isolates have an enhanced capacity to enter and replicate in the central nervous system of mice but that latency is influenced by both virus type and route of inoculation.

Animals↗
PubMed1981

Effect of interferon administration on pulmonary osteogenic sarcomas in an experimental murine model.

The iv inoculation of a suspension of osteogenic sarcoma cells induced metastatic tumor nodules in the lungs of C57BL/6 mice. The administration of 50,000-100,000 U of interferon daily for 7 days strikingly reduced the tumor mass in the lung and the number of tumor nodules present in histopathologic sections when the interferon treatment was initiated immediately after tumor cell inoculation. In some animals the development of any detectable metastatic lesion was completely prevented. Extending the therapy form 7 days to 21 days failed to improve the protective effect. Interferon therapy delayed until 7 days after tumor cell inoculation had no effect. These findings indicate the effectiveness of exogenous interferon in this murine osteogenic sarcoma model when interferon treatment is initiated within 1 hour of tumor cell inoculation, but not when it is delayed until tumor nodules are established in the lungs.

Animals↗
PubMed1980

Topical ether and herpes simplex labialis.

In a double-blind, placebo-controlled study, 51 patients with recurrent herpes simplex labialis were treated with topical ether or placebo within 24 hours of onset of a lesion. There was no noteworthy difference between groups given ether and placebo in progression of lesions, healing time, duration or intensity of pain, and duration or quantity of virus excretion. The ether also failed to reduce appreciably lesion virus titer, even when lesions were cultured immediately after topical application. Despite these results, 75% of the patients receiving ether and 77% of those receiving placebo reported effective reduction of the severity and duration of lesions. The marked placebo effect in the treatment of recurrent herpes infection helps to emphasize the need for objective measurements and placebo-controlled studies.

Administration, Topical↗
PubMed1980

Sensitivity of herpes simplex virus types 1 and 2 to three preparations of human interferon.

Ten isolates of herpes simplex virus (HSV) type 1 and nine isolates of HSV type 2 were tested against virus-induced (alpha), fibroblast (beta), and mitogen-induced (gamma) preparations of human interferon (HuIFN). HSV type 2 was slightly more sensitive and HSV type 1 somewhat less sensitive to all three preparations of HuIFN than Sindbis and vesicular stomatitis virus-both considered to be quite sensitive to HuIFN. HSV type 2 was significantly more sensitive than HSV type 1 to each of the HuIFN preparations (P less than 0.01; Mann-Whitney ranksum test). Clinical isolates did not appear to differ from laboratory strains. These results indicate that both HSV types 1 and 1 are sensitive to the three different preparations of HuIFN. HuIFN may have a role in natural recovery from and may have potential as an antriviral chemotherapeutic agent in HSV infections in humans.

Humans↗
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↗
PubMed1979

Clinical and virologic course of herpes simplex genitalis.

The clinical and virologic course of herpes simplex genitalis in women and men was examined in order to identify measurements useful in antiviral trials. Factors influencing the clinical course included initial disease versus recurrent disease, wet-skin versus dry-skin lesions, female versus male sex. Women with initial genital herpes had higher mean peak lesion virus titers than those with recurrent disease (10(4.5) pfu compared with 10(2.5) pfu) and excreted virus longer (13 to 15 days compared with 6 to 8 days). Men with recurrent lesions had higher mean peak virus titers than women (10(4.0) pfu compared with 10(2.5) pfu), but the duration of virus excretion was shorter (three to four days compared with six to eight days). There was pronounced variation in the clinical and virologic course of recurrent lesions among different patients and even within the same patient. These observations indicate several difficulties that must be considered in conducting careful antiviral trials in patients with herpes simplex genitalis.

Adolescent↗
PubMed1978

Effect of treatment with exogenous interferon, polyriboinosinic-polyribocytidylic acid, or polyriboinosinic-polyribocytidylic acid-poly-L-lysine complex on Herpesvirus hominis infections in mice.

The effect of treatment with exogenous interferon was compared with those of two interferon inducers, polyriboinosinic-polyribocytidylic acid [poly(I) . poly(C)] and poly(I) . poly(C)-poly-L-lysine complex [poly(ICLC)], in three model Herpesvirus hominis type 2 infections of mice. After intraperitoneal inoculation of H. hominis type 2, all drugs significantly protected animals against death and increased the mean day of death when administered as late as 48 hr after viral inoculation. With intranasal inoculation of H. hominis type 2, pretreatment with poly (I) . poly (C) and poly (ICLC) increased the mean day of death; however, no drug prevented death. In mice inoculated intravaginally, local treatment with exogenous interferon or poly(I) . poly(C) appeared to reduce the mean titers of virus in genital secretions and resulted in earlier clearance of infection in some animals. Systemic treatment of genital H. hominis type 2 infections with all drugs resulted in significant numbers of infected animals surviving the infection, although the mean titers of virus in genital secretions were unchanged. Therapeutic efficacy varied depending on the route of viral inoculation.

Administration, Intranasal↗
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↗