Biomedical subjects

D P Byington

Publications and source records attributed to D P Byington.

16 recordsLinked to original sources

PubMed1977

Virological and immunological studies in experimental SSPE.

Subacute sclerosing panencephalitis (SSPE) is a progressive, fatal inclusion cell encephalitis of children and adolescents caused by persistent measles virus within the central nervous system (CNS). Because studies in man have failed to elucidate the pathogenesis of this condition, animal studies are necessary. Persistent infection of the hamster CNS can be achieved with a hamster adapted SSPE agent. Animals inoculated intracerebrally with this virus raise antibodies to all known antigens of measles virus and some display clinical signs and pathological changes similar to those noted in human SSPE. Persistent CNS infection occurs only if the hamster is inoculated at a critical age (18 to 25 days of life) or if adults are given transient immunosuppression during acute infection. The biological behavior of the virus isolated from hamster CNS appears to change from a complete to a defective state coincidents with the appearance of serum antibodies to measles virus. Adult hamsters from whom the thymus was removed in the newborn period develop a subacute, uniformly fatal infection when exposed to the SSPE agent. These studies suggest that SSPE may develop in man when measles virus invades the immature CNS at a critical age or when the immune system is uncompletely developed or is inhibited. The finding that transient immunosuppression allows development of persistent CNS infection in adults suggest that immunological malfunction is the significant factor. Of interest, antibody appears to alter viral behavior to a defective, intracellular state thus enhancing viral survival in the host. Once a defective, CNS infection is achieved, lack of, or inhibition of the host cellular immunes response allows it to persist. Methods of therapy in light of these findings will be discussed.

Adolescent↗

PubMed1977

Experimental subacute sclerosing panencephalitis in the hamster: ultrastructure of the chronic disease.

Central nervous system (CNS) lesions were studied from weanling hamsters inoculated with the HBS strain of subacute sclerosing panencephalitis (SSPE) virus. The animals showed clincial signs of acute encephalitis between 8 and 18 days post-inoculation (PI), but all survivors were clinically recovered by day 21 PI. Nevertheless, 13 of 14 hamster brains examined by light and electron microscopy between days 21 and 59 PI had chronic lesions which contained morphologic evidence of persistent viral infection. The lesions developed preferentially in the subependymal areas of the lateral and fourth ventricles and involved degeneration of ependyma with subsequent damage to adjacent parenchyma. All CNS cell types were involved in degeneration. Viral inclusions occurred in both CNS parenchymal cells and in inflammatory cells. Giant cells were particularly common. No budding virus was seen in chronically infected animals, a finding in accord with previous studies. Demyelination was a common constituent of most lesions. It occurred in the presence of inflammatory cells and macrophages, and in later lesions, some remyelination was seen. It is suggested that the damage to myelin is a secondary phenomenon and is not a cellular immune reaction. The possible reasons underlying the latent nature of the virus and the similarities between this condition, canine distemper encephalomyelitis and human SSPE are discussed. It is concluded that the experimental chronic disease is a valid model for the study of human SSPE and may have usefulness in the understanding of other chronic CNS conditions of man, e.g. multiple sclerosis. Additional Key Words: Latent infection; Paramyxovirus; Slow Viruses; Demyelination; Inmmunologic defects; Multiple Sclerosis.

Animals↗

PubMed1975

Effect of neonatal thymectomy on experimental subacute sclerosing panencephalitis in adult hamsters.

Syrian golden hamsters were thymectomized in the first 48 h of life, raised, and then inoculated intracerebrally with the HBS strain of hamster-adapted subacute sclerosing panencephalitis virus when over 12 weeks old. Two groups soon become apparent; one group showed progressive neurological susmptoms and the other group remained healthy. The sick hamsters became moribund between days 8 and 17 postinoculation, and they had large amounts of complete virus in their brains, no antibodies to measles virus in their sera, and a demonstrated lack of thymus tissue. Pathological changes in the central nervous system included marked focal necrosis, numerous giant and inclusion-bearing cells, and slight inflammation. The healthy animals, killed at day 22 or 35 postinoculation, contained no central nervous system virus, moderate amounts of measles antibody in their sera, minimal or absent central nervous system pathology, and histologically identifiable remnants of thymus tissue. These studeis indicate that, in the hamster, the immune system is essential in recovering from central nervous system measles infection and that the antibody response to measles probably requires helper T lymphocytes to develop. Im the absence of antibody to measles, the virus did not undergo modification to a cell-associated state, as noted in previous hamster studies and in human subacute aclerosing panencephalitis. This model system may be useful for passive transfer studies to further clarify the effect of the n vivo immune response to acute and persistent central nervous system measles virus infections9

Aging↗

PubMed1975

Subacute sclerosing panencephalitis virus in immunosuppressed adult hamster.

A hamster-adapted subacute sclerosing panencephalitis agent (HBS virus) produced a subclinical, nonlethal, and cell-associated encephalitis after intracerebral inoculation of adult hamsters. When adult hamsters were immunosuppressed by intraperitoneal injections of rabbit origin anti-hamster lymphocyte serum for varying periods of time before and after intracerebral challenge with HBS virus, more than 50 per cent died in all experiments. Large titers of cell-free virus developed acutely in all animals and were maintained in continuously immunosuppressed hamsters, all but one of which died within 21 days. When animals were given transient anti-hamster lymphocyte serum treatment, those surviving for 21 to 54 days always displayed serum measles antibodies, and, from such animals, highly cell-associated virus could often be isolated from the brain. In such animals and in some others from which no virus could be isolated, the presence of measles antigen or inclusion cell pathology was noted in the brain. The neuropathology was characterized early by focal necrosis; small, multinucleated, ependymal giant cells; and minimal inflammatory reactions. Chronically, it was represented by mild perivascular inflammation, plasma cell accumulations, and inclusion-bearing cells. These studies indicate that it is the host immune response, rather than intrinsic central nervous system resistance to virus infection, which changes with age and thereby increases the chance of survival. The results suggest that antibodies modify the virus, making it more cell-associated or defective and thus enhancing its persistence in the immune host.

Animals↗

PubMed1975

Subacute sclerosing panencephalitis in the hamster. Ultrastructure of the acute disease in newborns and weanlings.

Acute subacute sclerosing panencephalitis has been investigated in both newborn and weanling hamsters intracerebrally inoculated with a human subacute sclerosing panencephalitis isolate (HBS) adapted to grow in hamster central nervous system (CNS) tissue. Newborn animals developed a disease which was fatal in approximately 1 week whereas most weanlings showed signs of an acute disease after day 8, from which a significant number recovered. Ultrastructurally, the human subacute sclerosing panencephalitis isolate (HBS) replicated rapidly in the CNS of newborn hamsters in the absence of an immune response. Giant cells developed from neurons and some demyelination was evident, most probably due to oligodendrocytic damage. Virus replication involved the proliferation of both typical measles virions and morphologically defective particles. Intracytoplasmic viral nucleocapsids were seen, but none were found within nuclei during the acute disease in newborns. Weanling hamsters developed a demonstrable immune response approximately 6 days after inoculation. Virions were seen and the majority appeared morphologically defective, lacking the associated nucleocapsids beneath the viral envelope. Abundant intranuclear, as well as intracytoplasmic, viral inclusions were seen. The results are of significance in the examination of myxoviruses (a group frequently linked to a number of chronic diseases of the CNS), in terms of viral replication in the CNS, in the response of different CNS cell types to infection, and in the influence of age and immune status upon the course of CNS disease.

Animals↗

PubMed1974