Biomedical subjects

E R Kern

Publications and source records attributed to E R Kern.

At least 73 records · Page 4Linked to original sources

PubMed1988

Transmission of cytomegalovirus infection in mice by skin graft.

Transmission of infectious disease, including virus, by allogeneic tissue transplants is a major clinical concern. The present study provided evidence for the transfer of murine cytomegalovirus (MCMV) by syngeneic and allogeneic skin grafts transplanted immediately after harvest from acutely infected donor mice. Transfer of MCMV also occurred following skin grafting with cryopreserved syngeneic skin. Recipients of infected skin were first positive for MCMV between 9 and 15 days post transplant, and MCMV was continually detectable through day 30. These results suggest that fresh or banked skin may serve as a source for transmission of cytomegalovirus infections.

Animals↗

PubMed1987

Interferon treatment of experimental Ross River virus polymyositis.

Ross River virus (RRV), an alpha togavirus, causes an inflammatory myopathy in mice, which probably results from direct lytic effects of virus or viral products on myofibers. Administration of recombinant hybrid human leukocyte interferon-alpha A/D (rIFN-alpha A/D) ameliorates clinical illness and reduces mortality from 86 to 42%. Peak concentrations of virus are reduced by 1,000-fold in serum and by 30-fold in muscle, but anti-RRV antibody production is not altered. Treatment with rIFN-alpha A/D dramatically reduces inflammation and necrosis in muscle. Beneficial effects of rIFN-alpha A/D on experimental, RRV-induced polymyositis result in part from inhibition of viral replication and spread, though immunomodulation might also play an important role.

Animals↗

PubMed1986

Acyclovir treatment of disseminated herpes simplex virus type 2 infection in weanling mice: alteration of mortality and pathogenesis.

Intranasal inoculation of weanling mice with herpes simplex virus type 2 (HSV-2) provides an experimental infection that closely resembles disseminated and central nervous system HSV infections of human neonates. Intraperitoneal treatment with acyclovir (ACV) successfully reduced mortality even when therapy was begun as late as 2 days and oral therapy as late as 4 days after viral challenge. Treatment with ACV beginning on day 1 completely inhibited HSV-2 replication in lung, spleen, kidney, olfactory lobe, and cerebrum and decreased viral titers in the pons by 2-3 logs. Comparison of these data with our previous experiments using adenine arabinoside and adenine arabinoside 5' monophosphate indicates that ACV is more effective in the murine model of neonatal disease and suggests that ACV may also be more effective in treating the disease in humans.

Acyclovir↗

PubMed1985

Topical butylated hydroxytoluene treatment of genital herpes simplex virus infections of guinea pigs.

The effect of topical treatment with butylated hydroxytoluene (BHT) was evaluated in primary and recurrent genital herpes simplex virus type 2 (HSV-2) infection of guinea pigs. In the first experiment, treatment with placebo, 5%, 10%, or 15% BHT was initiated 48 h after viral inoculation and continued 4 times daily for 15 days. During primary infection no differences in maximum lesion severity or titers of virus in lesions were observed, however, lesion duration was reduced in BHT-treated animals resulting in a significantly smaller lesion score-day area under the curve. In a second experiment using U.S.P. mineral oil as an additional placebo, BHT placebo and 15% BHT in a double blind trial, similar results were obtained. Treatment of the recurrent infection in either experiment failed to alter the number of recurrent episodes or days with lesions.

Administration, Topical↗

PubMed1985

Synergism between recombinant human interferon and nucleoside antiviral agents against herpes simplex virus: examination with an automated microtiter plate assay.

An automated, quantitative, cytopathic effect (CPE) inhibition assay with human fibroblasts in 96-well microtiter plates was used to examine the combination of recombinant human interferon-alpha (rIFN-alpha A) and acyclovir, vidarabine, or dihydroxypropoxymethyl guanine against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) in vitro. Fifty percent CPE (CPE50) end points, calculated from optical density readings of crystal violet-stained monolayers in an automated spectrophotometer, represented 1.7 log reduction in viral yield (50-fold or 98% decrease). Using CPE50 end points of drugs alone and in combination, we defined synergism, additivism, or antagonism with an isobologram plot and a combination index equation. The combinations of rIFN-alpha A plus acyclovir and rIFN-alpha A plus dihydroxypropoxymethyl guanine were highly synergistic against both HSV-1 and HSV-2, whereas the combination of rIFN-alpha A plus vidarabine was additive to mildly synergistic. Combinations of antiviral agents synergistic in cell cultures should be pursued with further studies in animal models of human viral disease and potentially in clinical trials.

Acyclovir↗

PubMed1985

Recurrent genital herpes simplex virus infection in guinea pigs.

After recovery from initial genital herpes simplex virus (HSV) infections, female guinea pigs developed spontaneous recurrent infections characterized by discrete erythematous or vesicular herpetic lesions on the external genital skin. HSV type 2 (HSV2) caused significantly more recurrent infections in guinea pigs than did HSV type 1 (HSV1). HSV2-infected animals demonstrated a significant decline in frequency of recurrences over time. The viral nature of the recurrent lesions was confirmed by recovery of infectious HSV, detection of HSV antigen, and histologic examination. Latent HSV2 could be demonstrated in dorsal root ganglia and external genital skin after recovery from the primary infection. Recurrent genital HSV infection in the guinea pig shares many features with recurrent genital herpes in humans and provides a model for studying the relationship between latency and recurrences and for exploring methods for control of recurrent disease.

Animals↗

PubMed1984

Experimental murine cytomegalovirus infection of ocular structures.

To study experimental cytomegalovirus (CMV) infection of ocular structures, 3-week-old Swiss-Webster mice were inoculated intraperitoneally with a 0% to 20% lethal inoculum of murine CMV (MCMV). Murine cytomegalovirus was recovered from homogenates of eye tissues on days 3, 5, and 7 after inoculation. Peak virus titers, mean of 2.93 +/- 0.67 log plaque-forming units of MCMV per gram of ocular tissue occurred on day 5. Urine cytomegalovirus was recovered from explant cultures of eye and optic nerve 14, 21, 60, 90, and 120 days after MCMV inoculation. Murine cytomegalovirus also persisted in intraocular fluids for as long as 90 days. Murine cytomegalovirus infection was confirmed by immunofluorescence antibody staining and transmission electron microscopy. These experiments indicate that MCMV infects the ocular tissues of mice during systemic MCMV infection, and persists in ocular tissues for as long as 120 days after infection. These studies may be directly relevant to ocular disorders that occur during acquired CMV infections of humans, and suggest that ocular tissues may be a site of CMV persistence or latency.

Animals↗

PubMed1984

Activity of human recombinant and lymphoblastoid interferons in human and heterologous cell lines.

Three human alpha interferon (HuIFN-alpha) preparations currently being used in clinical trials, rIFN-alpha A, rIFN-alpha 2, and lymphoblastoid IFN (LYM-IFN) had appreciable activity against encephalomyocarditis and vesicular stomatitis viruses (VSV) in guinea pig transformed and guinea pig embryo cells, but not mouse L or rabbit kidney cells. The level of activity in guinea pig cells, compared with human WISH cells, was 182% (range 9%-1,900%). These results suggest that the guinea pig may be useful for testing the antiviral, anticancer, or immunomodulatory activity of Hu alpha IFNs in vivo.

Animals↗

PubMed1984

Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir.

To determine whether topical acyclovir in polyethylene glycol could reduce the severity of herpes simplex labialis if applied immediately after onset of a recurrence, 10% acyclovir in polyethylene glycol ointment or polyethylene glycol alone was prospectively dispensed to 352 patients in a double-blind, randomized trial. Sixty-nine subjects initiated treatment in the prodrome (57%) or erythema (43%) stage and were followed by clinical and virological criteria. The healing time (6.0 days), maximum lesion area (42 mm2), vesicle or ulcer formation (91%), and maximum lesion virus titer (4.8 log10 PFU) in the drug recipients were not reduced in comparison with those who received the vehicle (5.2 days, 30 mm2, 75%, and 4.5 log10 PFU, respectively). Topical acyclovir in polyethylene glycol was ineffective for the treatment of herpes labialis despite an optimum therapeutic opportunity.

Acyclovir↗

PubMed1984

Failure of interferon to inhibit plutonium-induced osteosarcomas in mice.

The injection of murine interferon three times weekly in dose levels of 1,250, 5,000, or 20,000 U produced no significant antitumor effect against primary 239Pu-induced osteosarcomas in C57BL/6J mice. The interferon treatment was begun 94 days after the plutonium injection, which is well before the radiographic or microscopic appearance of neoplasia, and was continued until the moribund state or death. The average radiation dose accumulated by the skeleton at the time of first treatment was approximately 300 rad. The largest dose of interferon studied, 20,000 U/injection, was approximately 3 X 10(6) U/m2 of body surface, or 10(6) U/kg body weight.

Animals↗

PubMed1983

Acyclovir treatment of experimental genital herpes simplex virus infections. I. Topical therapy of type 2 and type 1 infections of mice.

Intravaginal inoculation of mice with herpes simplex virus (HSV) provides a model infection of genital herpes to determine the effectiveness of potential antiviral agents. topical (intravaginal) treatment with 1% or 5% acyclovir (ACV) in an ointment of gel vehicle initiated 3, 6 or 24 h after inoculation with HSV type 2, significantly inhibited viral replication in the genital tract and usually reduced final mortality. Treatment with 5% ACV initiated 48 or 72 h after infection also reduced vaginal virus titers but did not alter final mortality. When mice were inoculated with HSV type 1 treatment with 5% ACV significantly reduced viral replication in the genital tract when begun as late as 72 h. In HSV-2 infected mice, treatment initiated 3 h but not 24 h after infection prevented the establishment of latent infection in sacral ganglie. These results suggest that topical ACV may be effective antiviral agent for primary genital herpes in humans.

Acyclovir↗

PubMed1983

Impaired migratory and chemotactic activity of neutrophils during murine cytomegalovirus infection.

Mice have been shown to have increased susceptibility to bacterial and fungal superinfections between days 1 and 5 of acute murine cytomegalovirus (MCMV) infection. The current study demonstrated that, during the same period of the MCMV infection, migration of neutrophils into a subcutaneous sponge was impaired (1,300-2,000 cells/mm3 in MCMV-infected animals vs 6,000-7,000 cells in controls; P less than 0.01) and chemotaxis of neutrophils harvested from the sponge was decreased (chemotactic index of 1.5-2.1 in infected animals vs 5.4-5.7 in controls; P less than 0.01). The number of neutrophils in peripheral blood was not altered. Infectious MCMV was present in the neutrophil-rich fraction of peripheral white blood cells, suggesting that direct viral infection of neutrophils may contribute to altered function. These studies suggest that abnormalities in neutrophil function during acute cytomegalovirus infection may contribute to the enhanced susceptibility to bacterial and fungal infections that occurs in both experimental animals and humans.

Animals↗

PubMed1982

Acyclovir treatment of experimental genital herpes simplex virus infections.

Genital herpes simplex virus type 2 (HSV-2) infections in mice and guinea pigs were used to determine the effectiveness of acyclovir administered topically, orally, or parenterally. Topical treatment with 1 percent or 5 percent acyclovir begun six or 24 hours and 5 percent acyclovir begun 48 or 72 hours after intravaginal inoculation of mice with HSV-2 significantly inhibited viral replication in the genital tract. Oral administration of acyclovir resulted in a significant reduction in vaginal virus titers when therapy was begun as late as 72 hours after infection. Topical treatment with 5 percent acyclovir initiated 24, 48, or 96 hours after intravaginal inoculation of guinea pigs with HSV-2 significantly altered lesion severity and virus titers but not vaginal HSV titers. Oral acyclovir therapy begun 24 or 48 hours after infection also significantly reduced the mean lesion score and prevented their development in some animals. Lesion and vaginal virus titers were only partially reduced. Intramuscular administration of acyclovir begun on day 2 or day 4 of infection significantly reduced the mean lesion scores but failed to alter lesion or vaginal virus titers.

Acyclovir↗

PubMed1982

Optimal treatment of herpes simplex virus encephalitis in mice with oral acyclovir.

The effect of oral or intraperitoneal administration of acyclovir was evaluated in four experimental models of herpes simplex virus (HSV) encephalitis in mice. Mice were inoculated with HSV-1 or HSV-2 intracerebrally or with HSV-2 intranasally, intraperitoneally, or intravaginally. With all four routes of inoculation, oral acyclovir therapy significantly reduced mortality when started as late as 72 to 96 hours after viral challenge. Intraperitoneal acyclovir was not effective in protecting mice inoculated intravaginally, but was effective if given 24 to 48 hours after intracerebral or intranasal challenge and as late as 96 hours after intraperitoneal infection. Oral acyclovir was more active than intraperitoneal treatment in all four model infections. Levels of acyclovir inhibitory for HSV in cell culture were maintained in plasma and brain tissue throughout oral treatment but lasted only three to six hours after each intraperitoneal treatment. These results suggest that acyclovir may be useful in treating serious HSV infections in humans.

Acyclovir↗

PubMed1982

Effect of acyclovir treatment on acute and chronic murine cytomegalovirus infection.

Murine cytomegalovirus (MCMV) is inhibited in vitro by 1 to 2 microM acyclovir. Therapy of a systemic MCMV infection in weanling mice with acyclovir was only minimally effective when drug was administered intraperitoneally, while oral administration by addition of acyclovir to the drinking water was highly efficacious in mice with disseminated MCMV. Effective therapy was characterized by reduction of virus titers in lung, liver, spleen, and kidney. In mice chronically infected with MCMV, treatment for 30 days with oral acyclovir eliminated or reduced virus titers in all target organs except the salivary gland. Therapeutic efficacy in this model infection using oral administration of acyclovir could be correlated with the achievement of acyclovir levels in the plasma of experimental animals two to 10 times greater than the mean inhibitory concentration for MCMV in vitro throughout treatment. The lack of efficacy observed when drug was administered intraperitoneally was associated with acyclovir levels exceeding 1 microM for one to three hours after each dose.

Acute Disease↗

PubMed1982

Anti-herpesvirus activity of adenine arabinoside analogues in tissue culture and a genital infection of mice and guinea pigs.

Four analogues of adenine arabinoside (ara-A) were compared for activity against herpes simplex virus (HSV) in tissue culture and in a genital infection of mice and guinea pigs. These analogues, 5'-monophosphate (ara-AMP), 5'-valerate ester (ara-AV), 2'3'-diacetate ester (ara-ADA), and 2',3',5'- triacetate ester (ara-ATA) have greater water and lipid solubility and resistance to deamination than ara-A. In mouse embryo fibroblast cells, similar viral inhibitory levels were noted with ara-A, AMP, and ara-Av, while ara-ADA and ara-ATA were 6-10 time less active. In mice infected intravaginally with HSV type 2 (HSV-2), intravaginal treatment with 10% concentrations of each of the compounds beginning 3 h after viral challenge, had no effect on infection rates, titers of virus in vaginal secretions, mortality rates or the mean day of death as compared with placebo-treated controls. In the HSV-2 genital infection of guinea pigs, treatment with 10% vaginal creams or placebo vehicle was initiated 6 or 24 h after viral inoculation. In animals treated at 6 h with ara-A, ara-AMP and ara-AV, there was complete inhibition of viral replication in the vaginal tract and development of external genital lesions. When treatment with these three drugs was delayed 24 h after infection, there was no effect on vaginal virus titers, but lesions severity was reduced by ara-A or ara-AMP therapy. Ara-ATA was ineffective whether begun at 6 or 24 h. The greater solubility in water and lipid as well as the resistance to deamination of ara-AMP and ara-AV did not appear to enhance their antiviral activity over that of ara-A. Additionally, ara-ADA and ara-ATA exhibited less activity both in tissue culture and in the experimental genital infections.

Administration, Topical↗

PubMed1982

Enhanced susceptibility of mice infected with murine cytomegalovirus to intranasal challenge with Escherichia coli: pathogenesis and altered inflammatory response.

Three-week-old mice inoculated intraperitoneally with murine cytomegalovirus (MCMV) and then challenged intranasally with Escherichia coli strain K1 demonstrated enhanced mortality (70%-90%) as compared with control animals infected with either pathogen alone (0-20%, P less than 0.05). Mortality was greatest when animals were challenged with E. coli on days 1 or 3 after MCMV inoculation. On day 3 of infection with MCMV, clearance of E. coli from blood and tissues was impaired, and there was a decreased inflammatory response to an E. coli-inoculated sponge implanted subcutaneously (geometric mean of 830 leukocytes in sponge fluid/mm3 in MCMV-infected animals vs. 8,510 leukocytes/mm3 in controls, P less than 0.01). On days 1 and 3 of MCMV infection, decreased leukocyte counts in sponge fluid correlated with increased levels of bacteremia (P less than 0.05). These results indicate that MCMV enhances susceptibility to an intranasal challenge with E. coli. A decrease in the inflammatory response may be one mechanism by which MCMV increases susceptibility to bacterial infections.

Animals↗

PubMed1982

Treatment of herpes simplex labialis with topical acyclovir in polyethylene glycol.

A double-blind, placebo-controlled trial of topical 5% acyclovir (ACV) in polyethylene glycol (PEG) was carried out among 208 patients who had an episode of herpes simplex labialis. Patients who were treated with ACV had a greater decrease in median titers of virus in lesions between the first and second visits to the clinic than did patients who were treated with placebo (-1.5 log pfu [plaque-forming units] vs. -0.2 log pfu; P = 0.04). The antiviral effect occurred in the subgroup of patients who entered the study 0-8 hr after the onset of lesions. No differences were noted in the remaining patients who began treatment 9-25 hr after onset. An examination of the subgroup who had virus-positive specimens before treatment revealed prominent and more statistically significant virologic differences between treatment groups. No clinical benefit from treatment with ACV was observed; however, the present study describes the first antiviral effect of topical treatment for recurrent herpes labialis and identifies treatment strategies for future studies.

Acyclovir↗