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Y J Gordon

Publications and source records attributed to Y J Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1990

A herpes simplex type 1 ICPO deletion mutant demonstrates diminished pathogenicity during acute ocular infection in different host animals.

We compared a previously characterized herpes simplex type 1 alpha 0 deletion mutant, dlx3.1, which produced no functional ICP0, with its wild-type parental strain, KOS, during acute ocular infection of different host animals. Acute pathogenicity of the viral strains in NZ rabbits, Balb/c and A/J mice was evaluated by keratitis scores, ocular and trigeminal ganglionic viral titers, and host survival. We found that dlx3.1 was significantly less pathogenic than KOS. Host differences proved very important in the evaluation of acute pathogenicity. A species-dependent enhancement of ocular pathogenicity was demonstrated for dlx3.1 following a larger viral inoculum and host immunosuppression. We conclude that alpha 0 gene function appears to play an important role during acute ocular pathogenicity of HSV-1 in animal models. Furthermore, in vivo pathogenicity studies contribute important information in the evaluation of essential viral gene function.

Acute Disease↗
PubMed1990

A fast, simple reactivation method for the study of HSV-1 latency in the rabbit ocular model.

We developed a simple, fast, economical, and versatile reactivation method for the study of herpes simplex virus type 1 (HSV-1) latency in the rabbit ocular model. Intrastromal injection of sterile, deionized water induced reactivation and ocular shedding of latent HSV-1 in 21 of 27 eyes (78%) in 93% of New Zealand rabbits. Other control groups (eg, anterior chamber injection of sterile, deionized water; topical administration of sterile, deionized water; intrastromal injection of air; and intrastromal needle track), were less efficient in reactivating latent HSV-1. Although the mechanism of reactivation in this model is unknown, the reactivation signal may be related to the relative amount of corneal trauma.

Administration, Topical↗
PubMed1989

Evaluation of immunologic tests for the detection of ocular herpes simplex virus.

Four immunologic tests, Herpchek (HC), latex agglutination (AGG), enzyme immunofiltration (IF), and 1 hour enzyme-linked immunoassay (1EIA), were evaluated for detecting herpes simplex virus (HSV) from ocular specimens. Compared with the standard of HSV-positive cell cultures, 24 (65%) of 37 positive HC tests and 22 (59%) of 37 positive IF tests were significantly more sensitive (P less than 0.0005) than the AGG (3%, 1/37) and 1EIA (26%, 1/34) tests. The HC and IF tests were 100% specific, and easy to interpret. In addition, the clinical diagnosis of HSV infection after a thorough ophthalmologic examination was as sensitive (59%, 22/37) (P = 0.4) as any of the immunologic tests. In conclusion, for definitive diagnosis of HSV, the HC test seems more suitable for a central laboratory that handles a large number of viral specimens, and processes HC-negative tests with follow-up cell culture isolation. The enzyme immunofiltration test seems more suitable for a low-volume viral laboratory which confirms all IF test samples with follow-up cell culture isolation.

Agglutination Tests↗
PubMed1989

Comparison of direct rapid tests for the detection of adenovirus antigen in routine conjunctival specimens.

Two direct rapid tests to detect adenovirus antigen, enzyme immunoassay (EIA) and immunofiltration (IF) were compared with regard to sensitivity, specificity, ease of interpretation, and technical complexity against 75 adenovirus culture-positive and 35 adenovirus culture-negative conjunctival swab specimens. Enzyme immunoassay and IF were equally sensitive (P = 0.5), with sensitivities of 80.6 and 79.0%, respectively, when swab specimens were collected from patients within 7 days of the onset of clinical symptoms of adenovirus infection. After 7 days of clinical onset, IF (46.2%) was more sensitive (P less than 0.01) than EIA (0.0%), and was able to detect residual antigen in three culture-negative specimens. Enzyme immunoassay and IF were equally specific (100%). Both tests were easy to interpret, but IF was more technically complex and is not yet commercially packaged. Enzyme immunoassay could benefit either an office practice or a central laboratory, whereas IF is better suited for the latter.

Adenoviridae Infections↗
PubMed1988

Rapid diagnostic test for ocular adenovirus.

A new, direct, enzyme immunoassay test (Adenoclone, Cambridge BioScience, Hopkinton, MA) was evaluated for the rapid diagnosis of ocular adenovirus infections. In 36 culture-proven cases of adenovirus ocular infection, direct Adenoclone testing of conjunctival swabs was positive in 24 of 31 patients (77%) tested within 1 week of onset of symptoms, and in one of five patients (20%) who presented after 1 week (P less than 0.02). Overall sensitivity was 69%, whereas specificity was 100%. The authors conclude that a positive Adenoclone test is reliable in the rapid diagnosis of early adenovirus ocular infections.

Adenoviridae Infections↗
PubMed1988

RNA complementary to herpes simplex virus type 1 ICP0 gene demonstrated in neurons of human trigeminal ganglia.

Recent studies with mice have demonstrated abundant RNA transcripts which are complementary (antisense) to the herpes alpha gene ICP0 in latently infected ganglia. We investigated the situation in unselected human trigeminal ganglia. Strand-specific 2.7-kilobase herpes simplex virus type 1 (HSV-1) ICP0 RNA probes were prepared, and their sense was determined in productively infected cells. Although in situ hybridization demonstrated ICP0 antisense RNA transcripts in the nuclei of neurons in 46% of the ganglia, ICP0 messenger RNA was not found in any of the ganglia. We conclude that HSV-1 antisense ICP0 RNA is present in humans during ganglionic latency.

Adult↗
PubMed1987

The antiviral effects of rose bengal and fluorescein.

We evaluated the antiviral effects of rose bengal and fluorescein sodium. The direct antiviral activity was determined by an in vitro direct neutralization assay. The 50% inhibitory dose was 16 micrograms/mL for rose bengal and 460 micrograms/mL for fluorescein. The in vivo antiviral effects of these drugs were determined in the mouse herpetic keratitis model. Following topical application, rose bengal reduced surface virus titers (swabs) 1 million-fold, and residual ocular virus (eye homogenates) 32-fold, compared with controls. No infectious virus was recovered by swabbing after topical application of rose bengal. Fluorescein had no significant effect on virus replication. Thus, rose bengal, unlike fluorescein, has significant antiviral activity, and the diagnostic use of rose bengal prior to viral culture may preclude a positive result. Also, the use of rose bengal to grade keratitis in the study of new antiviral agents should be discouraged.

Animals↗
PubMed1987

HSV-1 thymidine kinase negative vaccine: pathogenicity, protection, and perils.

Primary inoculation of mice and rabbits with an avirulent HSV-1 thymidine kinase negative (TK-) mutant reduced keratitis, mortality, and superinfection of the trigeminal ganglion (TG) as measured by cocultivation and iontophoresis-induced ocular shedding following ocular challenge with HSV-1 McKrae and W strains. However species differences were demonstrated; with complete protection in rabbits, and incomplete protection in mice. In mice, BUDR/autoradiography and restriction enzyme analysis identified both HSV-1 McKrae and W strains as having superinfected the TG, established latency and reactivated. Also, the avirulent TK negative inoculating strain was altered to a virulent TK positive strain through possible in vivo selection, mutation &/or host-modification, and possible in vivo recombination with the virulent challenge strains. We conclude that lower species differences require that potential HSV-1 vaccines be tested in non-human primates prior to clinical trials, and that a DNA-free subunit herpes vaccine represents a safer alternative to a live virus vaccine.

Animals↗
PubMed1987

2'-nor-cGMP, a new cyclic derivative of 2'NDG, inhibits HSV-1 replication in vitro and in the mouse keratitis model.

The present study examined the antiherpetic effect of 2'-nor-cGMP, a new cyclic phosphate derivative of 2'NDG, in vitro and in the mouse keratitis model. The 50% inhibitory dose (ID50) was determined with HSV-1 RE strain in Vero cell monolayers for 2'-nor-cGMP (6.9 mcg./ml), 2'NDG (.06 mcg/ml), and trifluridine (F3T) (.72 mcg/ml). Balb C mice underwent bilateral ocular inoculation with HSV-1 RE strain, and then were treated with different therapeutic regimens. The antiviral efficacy of each drug was evaluated by ocular virus titers, clinical grading of epithelial keratitis, and histological evaluation of stromal keratitis. 2'-nor-cGMP was the most effective drug (P = .0001) in reducing ocular viral titers. Both 2'-nor-cGMP and 2'NDG were significantly more effective (P = .0001) than F3T in reducing epithelial keratitis, and as effective as F3T in reducing stromal keratitis.

Acyclovir↗
PubMed1987

HSV-1 latency: thymidine kinase requirement and the round-trip theory.

The present study used the rabbit iontophoresis model to examine the thymidine kinase (TK) requirement for HSV-1 latency, and test the round trip theory of latency with emergent phenotypic mutations of the HSV-1 TK negative (TK-) inoculating strain. The results demonstrated repeated induced ocular shedding of latent HSV-1 in 14-100% of rabbits. The TK phenotype of recovered tear film following spontaneous shedding and repeated iontophoresis induction was thymidine kinase negative in 90% of eyes. Sequential shedding of TK- virus from the same eye over time was demonstrated in 21% of eyes in 33% of rabbits. We conclude that TK is not an absolute requirement for the establishment or reactivation of latent HSV-1 in the rabbit model. The round trip theory of latency was not supported as TK+ isolates and syncytial variants of the TK- inoculating strain which were recovered at the ocular surface after the initial iontophoresis could not be demonstrated following subsequent trials of iontophoresis.

Animals↗
PubMed1987

Timolol promotes reactivation of latent HSV-1 in the mouse iontophoresis model.

The present study examined the effect of topical timolol, a nonspecific beta 1 and beta 2 blocker on reactivation and ocular shedding of latent HSV-1 in an improved mouse iontophoresis model. Latent trigeminal ganglionic infection was established in Balb/C mice following inoculation by corneal scarification with HSV-1 W strain, a clinical isolate, and confirmed by co-cultivation. On day 30, postinfection (pi), the mice were divided into two groups, and treatment begun with coded eye drops (timolol 0.5% or placebo) BID OU for 5 days. On day 31 pi, iontophoresis with 1% 6-hydroxydopamine was performed, and daily treatment with topical epinephrine and 1% prednisolone was administered. Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic effect in Vero cells. Results demonstrated that the timolol-treated group had a significantly greater number of positive eyes, multiple shedding episodes, and total shedding days compared to the control group. We conclude that beta blockade promotes recurrent ocular shedding induced by epinephrine in the mouse iontophoresis latency model.

Animals↗
PubMed1986

Recovery of a latent HSV-1 thymidine kinase negative strain following iontophoresis and co-cultivation in the ocularly-infected rabbit model.

Previous studies in the mouse and guinea pig have reported little or no colonization of sensory ganglia by strains of herpes simplex type 1 failing to express the enzyme, thymidine kinase (TK). The current study in the rabbit demonstrated trigeminal ganglionic colonization and reactivation of a latent thymidine kinase negative strain of HSV-1 by two independent methods: iontophoresis-induced ocular shedding and co-cultivation. Treatment with topical steroids during the acute infection did not enhance the latency rate. Following reactivation, back mutation with phenotypic reversion to thymidine kinase positive was demonstrated in a few recovered isolates. The current study also emphasized the importance of species differences to explain differing experimental results in studies of HSV-1 TK negative latency.

Animals↗
PubMed1986

Efficacy of glycoprotein inhibitors alone and in combination with trifluridine in the treatment of murine herpetic keratitis.

The present study examined the anti-herpetic effect of the glycoprotein inhibitors, hydroxynorvaline and 2-deoxyglucose, alone and in combination with trifluridine on murine ocular herpes. Following ocular inoculation with a large dose of HSV-1 RE strain (10(6) pfu), ICR mice were treated during the acute infection with different therapeutic regimens, and their efficacy was evaluated by ocular virus titers, clinical grading of blepharo-conjunctivitis and histological evaluation of stromal keratitis and iridocyclitis. The results following a large dose HSV-1 inoculum demonstrated that trifluridine was the best single therapeutic agent. Hydroxynorvaline and 2-deoxyglucose had no effect at all. Combination therapy of the glycoprotein inhibitors with trifluridine was no better than trifluridine alone. The mouse HSV-1 keratitis model proved to be an effective, economical alternative to the rabbit model for the evaluation of new antiviral agents.

Animals↗
PubMed1986

The development of an improved murine iontophoresis reactivation model for the study of HSV-1 latency.

The present study reviews the development of an effective murine iontophoresis reactivation model for the study of HSV-1 latency. In a series of experiments, Balb C mice latently infected with HSV-1 McKrae strain were iontophoresed with epinephrine X 3 days (EPI X 3/ION) or 6-hydroxydopamine X 1 day followed by topical epinephrine (6-HD ION/EPI). Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, titration, and neutralization. Additional studies determined the effect of topical ocular steroids on viral recovery rate. The results demonstrated no recovery of McKrae strain in Balb C (0%) with EPI X 3/ION, and no enhancement with topical steroids. 6-HD ION/EPI demonstrated a low recovery rate in mice (8%). However, the recovery rate was significantly increased to 50% by the addition of topical steroids to form the 6-HD ION/EPI/STEROID model, a useful experimental tool. The substitution of a clinical isolate, W strain, for McKrae strain further improved the model. The results demonstrated that, following the acute infection in mice, W strain was associated with a significantly higher (P = .001) survival rate than McKrae strain (81% vs. 52%). There was no statistically significant difference between the two strains, W vs McKrae, in Balb C mice comparing keratitis, establishment of latency (by co-cultivation), spontaneous shedding rate, or induced ocular shedding following iontophoresis. The development of an effective murine iontophoresis model offers an economical method which is uniquely suited for immunological and genetic studies of HSV-1 latency.

Administration, Topical↗
PubMed1984

Herpesvirus inoculation of cornea.

We investigated the effect of primary ocular inoculation with an avirulent herpesvirus type 1 thymidine-kinase-negative mutant on keratitis, survival, and establishment of trigeminal ganglionic latency after ocular challenge with several virulent herpesvirus type 1 thymidine-kinase-positive strains in the murine model. The effect of previous inoculation with the thymidine-kinase-negative mutant was to reduce the severity of keratitis, promote survival, and reduce the frequency of recovery of latent virus compared to the control group for all three superinfecting challenge strains. However, the thymidine-kinase phenotype (negative or positive) of recovered latent ganglionic virus or viruses disclosed incomplete protection from the previous inoculation and recovery of more than one virus strain from the same trigeminal ganglion in several mice. The success of a live, attenuated herpesvirus type 1 vaccine against ocular herpes may be limited in certain individuals by possible superinfection and secondary ganglionic colonization by wild-type herpesvirus capable of producing recurrent ocular disease.

Animals↗
PubMed1984

Evaluation of lithium as an inhibitory agent of herpes simplex virus in cell cultures and during reactivation of latent infection in rabbits.

Lithium carbonate inhibited plaque formation of herpes simplex virus types 1 and 2 in rabbit kidney and Vero cells (50% effective dose, 435.5 to 490 micrograms/ml). Plasma lithium levels of 67 to 134 micrograms/ml were achieved by oral therapy in rabbits. However, neither ocular virus shedding nor virus-positive trigeminal ganglia were reduced after intentional reactivation of latent herpes simplex virus infection.

Animals↗