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Biomedical subjects

J C Overall

Publications and source records attributed to J C Overall.

At least 55 records · Page 3Linked to original sources
PubMed1981

Viral-induced leukocyte interferon in vesicle fluid from lesions of recurrent herpes labialis.

Antiviral activity characterized as human interferon (HuIFN) was demonstrated in vesicle fluid from lesions of recurrent herpes labialis in 18 of 19 otherwise healthy patients. High titers (geometric mean, 29,200 units) were present during the early course of lesion development. Antiviral activity in vesicle fluid was neutralized by antibody to leukocyte (types I) HuIFN (HuIFN-alpha) in the eight patients in whom it was tested. These results indicate that HuIFN-alpha is present in the local lesions of recurrent herpes labialis. HuIFN may have a role in the pathogenesis of recurrent herpesvirus infections.

Adult↗
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

Sequential production of IFN-alpha and immune-specific IFN-gamma by human mononuclear leukocytes exposed to herpes simplex virus.

Both viral-induced interferon (IFN-alpha) and immune interferon (IFN-gamma) were produced in cultures of human peripheral mononuclear leukocytes (PML) exposed to ultraviolet (UV) light-inactivated herpes simplex virus (HSV). Comparable IFN titers (100 to 300 U) were present in supernatant media from PML of HSV-seropositive and -seronegative donors maintained for 2 days in culture. This "early" IFN was not immunologically specific and had the characteristics of IFN-alpha. In contrast, PML from 20 of 21 (95%) seropositive donors, but only 2 of 22 (9%) seronegative subjects, produced IFN in day-5 cultures that had been washed on day 2 followed by the addition of fresh media without UV-HSV (p < 0.0001). In addition,the geometric mean IFN titer of 35 U present in media from day 5 cultures of seropositive donors was significantly higher (p < 0.0001) than those from seronegative subjects (<10 IFN U). This "late" IFN was defined as immunologically specific by virtue of its being present almost exclusively in PML cultures from seropositive donors. Late-appearing, HSV-induced, immunospecific IFN-gamma had antigenic characteristics of both viral-induced IFN-aand mitogen-induced IFN-gamma. A considerable degree of overlapping sensitivity to anti-IFN-alpha and anti-IFN-gamma antibody existed in late IFN, but was not seen in standard, control specimens. The latter finding suggests that the possible existence of an IFN of antigenic character intermediate to IFN-alpha and IFN-gamma. Late IFN was not induced in PML cultures by UV-inactivated Newcastle disease virus (NDV). NDV did, however, induce high titers of early IFN-alpha in PML cultures of both HSV-seropositive and HSV-seronegative donors. HSV-stimulated lymphocyte blastic transformation occurred only in cultures of seropositive individuals, whereas none occurred in response to NDV. Delayed appearance of antiviral activity with the characteristics of IFN-gamma in HSV-stimulated PML cultures is a sensitive and specific measure of the human immune IFN response. Sequential synthesis of IFN-alpha and IFN-gamma in individual PML cultures provides an opportunity to examine regulation of IFN production in response to virus with intrinsic IFN-inducing properties.

Humans↗
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↗
PubMed1980

Rapid, quantitative, semiautomated assay for virus-induced and immune human interferons.

An improved human interferon (IF) assay is described. This procedure is based on the ability of encephalomyocarditis virus to replicate in WISH cell microcultures with the production of discrete plaques in the presence of a liquid tissue culture medium. Performance of 50% plaque reduction endpoint assays in micro-culture required only 0.1 ml of specimen for determinations using duplicate dilutions beginning at 1:3. Semiautomated equipment facilitated simultaneous in situ dilution and distribution of multiple IF samples in cultures containing preformed WISH cell monolayers. An incubation period of 5 to 6 h was adequate for development of maximal antiviral activity by both virus- and immune-induced IF. Sensitivity of the encephalomyocarditis microplaque reduction assay was comparable to that of other commonly used techniques. The method is rapid, can be completed within 30 h from the beginning of the IF assay, and is able to accommodate as many as 40 to 50 samples at a single time. Encephalomyocarditis microplaque reduction is suitable for the quantitation of IF as an antiviral agent or a lymphokine.

Cell Line↗
PubMed1979

Ineffectiveness of topical adenine arabinoside 5'-monophosphate in the treatment of recurrent herpes simplex labialis.

The ability of topical 10 per cent adenine arabinoside 5'-monophosphate to decrease the severity and frequency of recurrent herpes simplex labialis was evaluated in a double-blind, randomized study of 233 patients at three collaborating institutions. Nine clinical and four virologic measurements were used to evaluate drug efficacy during a single episode. No statistically significant improvement in any measurement was seen in the drug-treated patients. Analyses according to institution and age, stage and size of lesion before therapy also indicated no benefit attributable to the drug. There was no effect of the drug on the rate of recurrence of herpes simplex labialis. We conclude that, despite activity against herpes simplex virus infection in tissue culture and in some laboratory animal models, topical use of the drug is ineffective against recurrent herpes simplex labialis. This may be due to failure of the drug to penetrate the skin.

Arabinonucleotides↗
PubMed1979

Infectious mononucleosis and Epstein-Barr virus. 1. Epidemiology, pathogenesis, immune response.

The evidence linking Epstein-Barr virus causally with infectious mononucleosis is compelling. The disease occurs only in persons who lack antibody to this virus, and serologic findings during the acute illness provide almost certain evidence for its etiologic association. Additional evidence is derived from transformation studies using lymphocytes from persons infected with Epstein-Barr virus. Epidemiologic studies have related the need for close contact with salivary secretions to the low communicability of infectious mononucleosis. The clinically relevant antibodies which develop during the disease, other than heterophile antibody, are those against the viral capsid antigen. Part 2 of this article considers the clinical picture, diagnosis, and management and begins on page 95.

Acute Disease↗
PubMed1979

Infectious mononucleosis and Epstein-Barr virus. 2. Clinical picture, diagnosis, management.

The diagnosis of infectious mononucleosis is confirmed by hematologic, biochemical, and serologic data. An absolute increase in peripheral mononuclear cells to at least 4,500/cu mm is an essential feature. The serologic hallmark of the disease is the presence of heterophile antibody. The age of the patient may affect the clinical presentation and laboratory findings. Therapy is largely supportive, with steroids being used only in the presence of certain severe complications.

Adolescent↗
PubMed1979

Treatment of recurrent herpes simplex labialis with levamisole.

Because deficient immune responses may play a contributory role in recurrent herpes simplex labialis, an immunomodulating agent, levamisole, has been advocated for therapy. Forty-two patients with a high frequency of recurrent herpes simplex labialis were followed for a mean of 7.8 months (range 4 to 12) and treated for 3 days at the onset of each episode of herpes with one of three different doses of levamisole or placebo in a randomized, double-blind study. Statistical analysis revealed that as the dosage increased, so did the frequency of recurrences (P = 0.007). Conversely, duration of the lesions and lesion pain decreased with increasing dosage (P = 0.05 and 0.03). These results indicate that levamisole is not an appropriate drug for the management of recurrent herpes simplex labialis. The paradoxical response to an immunomodulator (increased frequency, decreased severity) provides evidence that altered host responses may contribute to the pathogenesis of the disease.

Adult↗
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

Synergistic infection with murine cytomegalovirus and Pseudomonas aeruginosa in mice.

A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 0--20% lethal inoculum of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (90%--100%) within 48 hr after an intravenous injection of a 0--20% lethal inoculum of Pseudomonas aeruginosa. The current study demonstrated that mice infected with murine CMV alone had high titers of virus in multiple organs over a 20-day period, whereas mice injected with P. aeruginosa alone had a self-limited infection confined to the kidney. In the combined murine CMV-P. aeruginosa infection, titers of virus in tissues were changed very little. In contrast, P. aeruginosa was recovered in high concentrations from multiple organs, a finding which demonstrated a progressive systemic infection closely resembling that produced by a 100% lethal inoculum of P. aeruginosa alone in normal mice. An increased mortality rate due to P. aeruginosa in murine CMV-infected mice was dependent on inoculation of live bacteria and could not be explained by enhanced susceptibility to endotoxin. These results indicate that murine CMF markedly enhanced the suceptibility of mice to infection with P. aeruginosa and suggest that the virus altered mechanisms of host resistance important in recovery from bacterial infections.

Animals↗
PubMed1978

Resistance of visna virus to interferon.

Visna is a slow infection of sheep caused by a retrovirus. The persistence of virus despite the immune response of the host is best explained by restricted genetic expression of the virus and consequently prolonged periods of residence inside cells. The purpose of this investigation was to determine whether the restriction in genetic expression of visna virus is mediated by interferon. Sheep interferon induced by polyriboinosinic-polyribocytidylic acid in fetal lambs inhibited the growth of herpes simplex virus, vesicular stomatitis virus, and vaccinia virus, but even highly concentrated interferon did not affect the replication of visna virus in sheep choroid plexus cells. The same results were obtained whether the effects of interferon were assessed in single of multiple cycles of growth and when interferon was added at later times in the growth cycle of the virus. This unusual resistance of visna virus to interferon suggests that restriction of viral expression by the host is probably not mediated in this way.

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↗