A monoclonal antibody reacting specifically with ganglioside GD1b in human brain.

A mouse monoclonal antibody directed against one of the major human brain gangliosides, GD1b, has been produced. The antibody binds specifically to the carbohydrate structure of GD1b as it does not react with structurally related gangliosides like GM1, GD2, GT1b or Fuc-GM1, or any other ganglioside of human brain. The results further indicate that terminal galactose as well as the disialosyl group linked to the inner galactose moiety are involved in binding to the antibody.

Genital Chlamydia trachomatis infection in women.

Specimens for isolation of Neisseria gonorrhoeae, Chlamydia trachomatis, Candida albicans, and Trichomonas vaginalis were collected from 585 women attending clinics for venereal diseases. The isolation rates in women attending clinics for venereal diseases. The isolation rates in women with and without genitourinary symptoms, the course of untreated chlamydial infection, the occurrence of chlamydial urethritis, and the response to antibiotic treatment were investigated. A 30% incidence of chlamydial amd gonococcal infection was observed. In most cases the gonococcal infection affected both the cervix and the urethra, whereas the chlamydial infection was restricted to either the cervix or the urethra. Sampling of secretions from the urethra revealed chlamydial infections (15%) that otherwise would have remained undetected. In untreated cases chlamydiae persisted for at least 6 weeks. Bacteriologically, chlamydial infections responded equally well to doxycycline, erythromycin, and a combination of trimethoprim and sulfamethoxazole. however, symptoms persisted in 34% of the women.

Separation of herpes simplex virus virions and nucleocapsids on Percoll gradients.

Herpes simplex virus (HSV) virions and nucleocapsids were separated and purified by centrifugation in density gradient of polyvinylpyrrolidone-coated colloidal silica (Percoll). Virions and nucleocapsids banded at densities of 1.07 and 1.03 g/ml, respectively. The distribution in the gradient of virions and nucleocapsids suggested that particles were discriminated according to difference in size rather than in density. The reduction of cell proteins in preparations of purified virions was 1300--2100 times. The recovery of infective virus was approximately 30%.

Herpes simplex virus-induced demyelination. Effects of reinfection and challenge with neuroantigens.

Mice injected into the snout with the F-strain of herpes simplex virus (HSV) showed demyelination in the central part of the trigeminal root and brainstem. In this well characterized model the effect of reinfection with a virulent strain of HSV, and of immunization with UV-light-inactivated HSV and neuroantigens were examined. A marked enhancement of demyelination was found in mice immunized with spinal cord extracts in Freund's adjuvant prior to the HSV infection. Whether this effect is mediated by a general stimulation of inflammatory or immune competent cells or is dependent upon exposure to specific antigens is not known.

Virus infections in infant mice causing persistent impairment of turnover of brain catecholamines.

Newborn mice were inoculated with attenuated Coxsackie type B4 virus. Three-to-4-day old mice were infected with yellow fever virus vaccine. A number of mice survived the acute infections. Some of these demonstrated residual neurological symptoms, some showed recovery from symptoms while others survived the infection without revealing symptoms of disease. Determinations of dopamine, noradrenaline, 5-hydroxytryptamine, homovanillic acid and 5-hydroxyindoleacetic acid in the inoculated brains indicated an imparied turnover of neurotransmitters. Subnormal concentrations of catecholamines and homovanillic acid were encountered in the acutely-infected mice as well as among the survivors. Failure to synthesize catecholamines was observed not only in mice demonstrating symptoms of disease or in animals which recovered from their infection but also among a proportion of the mice which never demonstrated neurological symptoms. In contrast, 6-week-old Swiss albino mice infected with West Nile virus showed no effect on the turnover of brain monoamines either in acutely infected mice or in animals which survived the acute infection. Herpes simplex virus infection of 3-week-old mice induced during the acute infection an increased release of neurotransmitters. When these mice were "cured" of the infection by increasing the environmental temperature the elevated turnover of monoamine metabolism was normalized. Two months later there were no differences in concentrations of catecholamines or homovanillic acid between infected animals or uninfected controls. Thus, persistent impairment of brain monoamine metabolism was induced in mice infected when very young. The possible importance of the observations, in particular the findings of an impaired turnover after subclinical infection, is discussed.

Neuron to neuron transmission of herpes simplex virus. Transport of virus from skin to brainstem nuclei.

Herpes simplex virus (HSV) injection into the snout of mice was followed by the appearance of HSV antigen in neurons in trigeminal ganglia, main sensory and spinal tract trigeminal nuclei, reticular formation including raphe nuclei and locus ceruleus on both sides. The findings indicate that HSV spreads via axons, passes through a series of neurons and in this way can reach vital nuclei in the brainstem including monoaminergic neurons from the primary replication area in the lip.

A monoclonal antibody against HSV type 1 ribonucleotide reductase cross-reacts with the P0 protein of peripheral nerve myelin.

An epitope on peripheral nerve myelin was detected by the use of a mouse monoclonal antibody directed against the 38 kDa subunit of herpes simplex virus (HSV) type 1 ribonucleotide reductase. Immunohistochemistry showed reactivity solely in PNS myelin. In nerve roots there was a sharp border in transitional zones to the negative CNS myelin. The immunoreactivity was found in rat, guinea pig, bovine and human peripheral nerves. Western blot analysis of peripheral nerve myelin as well as purified P0 revealed a distinctly stained band corresponding to a molecular weight of approximately 29 kDa. The present finding of a shared antigenic determinant between HSV ribonucleotide reductase and peripheral nerve P0 may be of pathogenetic relevance in virus induced demyelinating diseases in the peripheral nervous system.

Latent herpes simplex virus trigeminal ganglionic infection in mice and demyelination in the central nervous system.

Mice were inoculated with herpes simplex virus (HSV) type 1 by gently scraping the skin of the nose with a fine needle. About 80% of the animals developed latent inapparent HSV infections in trigeminal ganglia. Virus was demonstrable for at least 6 months post inoculation (p.i.) by cocultivation of ganglionic tissue with GMK cells. Histologically, trigeminal ganglia revealed infiltrations of inflammatory cells even 6 months p.i. In addition, lesions occurred in the brainstem corresponding to the entry of trigeminal roots, trigeminal tracts and nuclei. Inflammatory cell infiltration, disruption of myelin sheaths and macrophages laden with myelin degradation products were observed 7 days p.i. Fourteen to 30 days p.i. electron microscopy demonstrated completely naked axons. In the transitional region of the trigeminal root denuded axons occurred in the central part of the region while the peripheral myelin, bordering the demyelinated central segments, was intact. Small areas of demyelination were still detectable 3 and 6 months p.i. but there were then also signs of remyelination. Possible mechanisms causing the demyelinations are discussed.

Neural spread of herpes simplex virus types 1 and 2 in mice after corneal or subcutaneous (footpad) inoculation.

Twelve herpes simplex virus (HSV) strains, 6 of each type, were inoculated subcutaneously into the left hind foot and into the cornea of the right eye of 12-day-old Swiss albino mice. The neural spread of virus to trigeminal and spinal ganglia and to brain and spinal cord was studied by demonstration of infective virus, histology and electron microscopy. Type 1 and type 2 infections seemed to spread equally well by intra-axonal transport. Using a protein tracer (horseradish peroxidase) injected into the same site as the virus, transport of the tracer to neurons corresponding to those infected with virus was observed. The extensive destruction of CNS tissue in the transitional region of the trigeminal root where CNS and the peripheral nervous system meet is discussed with reference to the pathogenesis of HSV encephalitis.

Herpes simplex virus infection in capsaicin-treated mice.

Following inoculation into the snout herpes simplex virus (HSV) spread to neurons in mouse trigeminal ganglion and subsequently to the brain. Capsaicin treatment of neonatal mice, which causes a loss of unmyelinated sensory neurons, some of which contain substance P, reduced the mortality rate of HSV-infected mice. Moreover, a lower percentage of mice survived the infection with reactivatable virus. There was also an extensive infection of glial cells proximal to the transitional zone in the trigeminal root between the peripheral and central nervous system. Distal to this zone there was an accumulation of substance P immunoreactivity in centrally directed fibres. This amplified degenerative effect on central branches of the substance P containing sensory nerves by glial infection may contribute to the deafferentiation pain syndrome following HSV infection.

Virus-induced demyelination in herpes simplex virus-infected mice.

Herpes simplex virus (HSV) infection of the mouse trigeminal ganglia and the brain stem is associated with demyelination of axons in the central part of the trigeminal root and inflammatory cell infiltration and perivascular demyelination in the brain stem. Cyclophosphamide (CPA) treatment prior to or soon after HSV inoculation caused increased axonal spread of infective virus from the peripheral site of inoculation, more widespread and severe demyelination and increased mortality, suggesting that by CPA the virus invasion of the CNS was facilitated. A direct cytocidal effect of HSV on myelinating cells seemed one plausible explanation for the demyelination. Influence on demyelination at late stages of infection by cytotoxic immune reactions are not excluded by the results reported but seemed not to dominate the picture. Schwann cells from the peripheral part of the nerve root invaded demyelinated areas in the brain stem and remyelinated the axons.

Clinical experiences with phosphonoformate (foscarnet) treatment of viral diseases following renal transplantation.

The effect of the antiviral drug phosphonoformate (Foscarnet) was studied in 32 patients following renal transplantation. Viral diagnosis was verified in 29 of 33 episodes of suspected clinical virosis. The clinical effect of Foscarnet was good in 12 of 14 primary cytomegalovirus infections. In 5 of 7 varicella-zoster virus, in 4 of 6 secondary cytomegalovirus and in 2 herpes simplex virus (type 1; type 2) infections the effect of the treatment was clinically judged as good. The beneficial effect could in these patients be overestimated as the natural courses of the viral infections were unknown. No clinical side effects of Foscarnet were found. Clinically unimportant changes in s-calcium were noted in 6 patients. The dosage of Foscarnet was increased during the study. At present an initial bolus dose followed by 14 days of parenteral infusions can be recommended.