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Biomedical subjects

E R Kern

Publications and source records attributed to E R Kern.

At least 19 recordsLinked to original sources
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↗
PubMed1978

Antiviral activity of extracts from marine algae.

Extracts of two species of marine algae, Constantinea simplex and Farlowia mollis, were tested for antiviral activity in tissue culture and in experimental infections of mice. Treatment of confluent mouse embryo fibroblast cell monolayers with either compound before viral inoculation was effective in inhibiting the replication of herpes simplex virus type 1 and type 2, vaccinia virus, and vesicular stomatitis virus, but not encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus. Prophylactic administration of these extracts was effective in reducing final mortality or prolonging the mean day of death of animals inoculated by the intraperitoneal, intracerebral, or intranasal routes with herpes simplex virus type 2. When therapy was initiated after viral inoculation or at a site other than that of viral inoculation, no significant effect on mortality or on mean day of death was observed. Neither preparation was effective in mice inoculated intraperitoneally with encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus or in animals infected intravaginally with herpes simplex virus type 2. The prophylactic but not therapeutic antiviral activity of these preparations seriously limits their potential use in human herpes simplex virus infections.

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

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

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

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↗