Biomedical subjects

J T Richards

Publications and source records attributed to J T Richards.

35 records · Page 2Linked to original sources

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↗

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

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↗

PubMed1980

Nanosecond laser photolysis of aqueous carbon monoxy- and oxyhaemoglobin.

The spectra have been measured of the transient species and the final level of absorption observed in nanosecond laser photolysis of aqueous carbon monoxy- and oxyhaemoglobin. These show that the transient absorption change can be interpreted as being due to an ultrafast ligand recombination following the photolysis. The spectra do not support the earlier interpretation (Alpert, B., Banerjee, R. and Lindqvist, L. (1974) Proc. Natl. Acad. Sci. U.S. 71, 558--562) that this was due to a tertiary structural change of the protein.

Carboxyhemoglobin↗

PubMed1978

Interitem structure and the facilitation of simultaneous comparison.

The effects of bilateral display symmetry on simultaneous comparison were examined. Experiment 1 demonstrated that symmetric letter pairs are classified as same more rapidly and accurately than asymmetric letter pairs. Experiments 2 and 3 disentangled the contributions of single-letter and whole-display symmetries (these being confounded in normal letter pairs) and showed that the primary determinant of response facilitation is the presence and registration of interitem relational structure. The last three experiments suggested that this facilitation does not arise from the detection and diagnostic utilization of symmetry. It is concluded that bilateral display symmetry facilitates the normal operations of form comparison. The early operations of field segmentation are discussed as the probable locus for this facilitation effect.

Discrimination, Psychological↗

PubMed1978

Interaction of radical anion probes with glucoamylase I from Aspergillus niger.

The radical anions (SCN)2.- and Br2.- produced during a pulse radiolysis of the respective potassium salts have been used to study the tryptophan residues of the glucoenzyme, glucoamylase I (EC 3.2.1.3.). At neutral pH, Br2.- reacted with the tryptophan residues of glucoamylase I as expected from previous studies of proteins and free amino acids. However, (SCN)2.- at neutral and high pH was surprisingly unreactive towards the native enzyme. Reaction did occur, however, between (SCN)2.- and glucoamylase from which one-third of the covalently bound carbohydrate had been removed, producing a tryptophyl radical. Reaction also occured between (SCN)2.- and glucoamylase I inactivated by treatment with sodium dodecyl sulphate, but the tryptophan residues were not involved. It is concluded from the results that two 'types' of tryptophan residues are found in glucoamylase I; both are attacked by Br2.- but only one type is attacked by (SCN)2.-.

Anions↗

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↗

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