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Biomedical subjects

J C Overall

Publications and source records attributed to J C Overall.

At least 37 records · Page 2Linked to original sources
PubMed1984

More rapid isolation of herpes simplex virus in a continuous line of mink lung cells than in Vero or human fibroblast cells.

Herpes simplex virus (HSV) was isolated from clinical specimens more rapidly in mink lung (ML) cells, a continuous cell line available from a commercial supplier, than in Vero cells or human fibroblast (HF) cells. Stock strains of HSV type 1 (HSV-1) and HSV-2 titered higher in ML cells than in Vero or HF cells. ML cells were equivalent to rabbit kidney (RK) cells in the isolation of HSV in clinical specimens, but titers of stock HSV strains were lower. ML cells could be employed to type strains of HSV-1 and HSV-2, using the technique of differential susceptibility to bromovinyldeoxyuridine (BVDU). ML cells, therefore, are a convenient and useful cell line for the isolation and typing of HSV in diagnostic virology laboratories.

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↗
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

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

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

Insertion of a small central venous catheter in neonates and young infants.

Total parenteral nutrition (TPN) administered through a central venous catheter in low-birthweight neonates and infants has been complicated by mechanical catheter malfunctions and catheter-associated infections. A retrospective survey of catheter complications 66 infants with 90 pediatric Broviac (1.3 mm o.d.) and large-diameter (French size 3, 4, and 5) Silastic catheters revealed 17 mechanical malfunctions (27%) and 16 cases (26%) of catheter infections. The current study presents our experience using 58 small-diameter (0.635 mm o.d.) Silastic catheters for TPN in 53 neonates and infants. There were 13 episodes (22%) of mechanical problems such as accidental dislodgement, occlusion of the catheter, and perforation of the tubing. Only four cases (7%) of catheter-associated sepsis occurred, a significant reduction (p = 0.008) in this serious problem compared to the previous large catheter study. We have compared clinical features of both large- and small-diameter catheters and suggest specific guidelines for their use. The small-diameter Silastic catheter is safe, easily inserted, and effective in the critically ill, low-birthweight neonate and in young infants weighing less than 6 kg. The pediatric Broviac catheter is recommended for administration of long-term or home TPN to infants and children greater than 6 kg. These catheters are useful for multiple purposes such as blood drawing, chemotherapy, and nutritional support while the small catheter is not as versatile.

Calibration↗
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↗
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

Production of alpha and gamma interferons by spleen cells from cytomegalovirus-infected mice.

Antigen-induced lymphocyte proliferation and the production of a murine immune or type II interferon (MuIFN-gamma) by spleen cells in vitro were used to examine the cellular immune response to a cytomegalovirus infection of mice. Lymphocyte blastogenesis was induced by interaction with cytomegalovirus-infected mouse embryo fibroblasts in spleen cells from mice infected at least 6 days previously with cytomegalovirus. The peak of the blastogenic response occurred after 72 hr in culture with antigen. MuIFN was detected in cultures of cytomegalovirus-infected mouse embryo fibroblasts and spleen cells from both normal and infected mice. The MuIFN produced by spleen cells from normal or infected mice early during the course of the infection (days 1 to 2) was predominantly viral or type I interferon (MuIFN-alpha). Peak titers of MuIFN-alpha were present 24 to 48 h after exposure to antigen in vitro and before the peak of the blastogenic response. In contrast, spleen cells from mice infected at least 6 days previously produced both MuIFN-alpha and MuIFN-gamma in culture with the infected mouse fibroblasts. MuIFN-alpha was present early in the culture, before peak blastogenic activity. Peak levels of MuIFN-gamma were detected as lymphocyte blastogenic activity subsided. These results indicate that the cellular immune system of the murine host is capable of responding to cytomegalovirus infection, the afferent limb by antigen recognition and the efferent limb by the production of the lymphokine MuIFN-gamma.

Animals↗
PubMed1982

Pathogenesis of herpes simplex labialis: correlation of vesicle fluid interferon with lesion age and virus titer.

Of 51 patients with herpes simplex labialis, 50 had detectable interferon (IFN) in samples of lesion vesicle fluid. The median titer of vesicle fluid IFN was 8,200 U. and the range of values was 400 to 63,600 U. The amount of vesicle fluid IFN was correlated with lesion age (r = 0.32, P = 0.024) and vesicle fluid virus titer (r = 0.59, P = 0.00004), but not with the clinical severity of the disease. The presence of vesicle fluid IFN (1,500 to 28,600 U) in 15 lesions less than 12 h old emphasizes the need for early treatment in studies of antiviral agents for herpes simplex labialis.

Adult↗
PubMed1982

Automated, quantitative cytopathic effect reduction assay for interferon.

A rapid, cytopathic effect reduction assay for human interferon (IFN) is described. Dilutions of IFN were made with an automated diluter in 96-well microtiter plates. Total incubation time was 26 h. IFN titers were calculated from optical density readings of crystal violet-stained monolayers in an automated spectrophotometer, which required less than 1 min to read each plate.

Biological Assay↗
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

The histopathologic evolution of recurrent herpes simplex labialis.

In a study of the natural history of recurrent herpes simplex labialis, we examined hematoxylin and eosin-stained sections of biopsies taken from lesions at various clinical stages. The earliest specific findings which could be recognized were changes within the epidermal cell nuclei, including peripheral clumping of chromatin, development of homogeneous "ground glass" appearance, and ballooning of nuclei. Eosinophilic intranuclear inclusion bodies were unusual and occurred in late lesions. Vacuolization was the earliest cytoplasmic alteration within keratinocytes. The herpes-induced changes began focally along the basal cell layer, but the entire epidermis was rapidly altered. Pilosebaceous units were commonly affected. Within the dermis, no cells with typical herpesvirus-induced changes were seen. In early lesions, mononuclear and polymorphonuclear inflammatory cells were equally prominent; in later lesions neutrophils were most numerous. Histopathologic changes of recurrent herpes simplex begin multicentrically within the epidermis and are present prior to the onset of physical findings.

Biopsy↗