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Biomedical subjects

N Nathanson

Publications and source records attributed to N Nathanson.

At least 73 records · Page 4Linked to original sources
PubMed1981

Acute rabies death mediated by antibody.

Among inadequately immunized laboratory animals dying of rabies, a small but consistent proportion succumb after an incubation period shorter than that of any of the unvaccinated controls and this phenomenon has been termed 'early death'. It has also been shown that, after immunosuppression either with cyclophosphamide or by thymectomy and irradiation, rabies-infected animals survive longer with decreased incidence of paralysis. It appears that 'early death' also occurs in humans who have been treated (unsuccessfully) with vaccine, with or without accompanying serum therapy, after exposure to rabies. Collectively, these studies suggest that there is a immunopathological component in rabies virus infection. We have therefore investigated a model of lethal rabies infection in immunosuppressed mice and have concluded that B lymphocytes or antibody specific for rabies play a part in the causation of early death. Accordingly the immune response to rabies has a dual role, sometimes favouring survival but sometimes enhancing the disease.

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PubMed1981

Recovery from experimental rabies by adoptive transfer of immune cells.

The transient, sublethal infection produced by intracerebral inoculation of the Flury high egg passage (HEP) strain of rabies virus into adult mice was converted into a lethal one (approx. 80 to 100% mortality) by administering 150 mg/kg cyclophosphamide (CY) 2 days after infection. Immunosuppressed, infected animals showed no immunological response to rabies and died 15 to 20 days after infection. However, mortality was reduced to 12% when suppressed mice were adoptively immunized, 4 days after infection, with an intravenous injection of 60 X 10(6) spleen cells from rabies-immune syngeneic donors. The lymphocytes obtained early after donor immunization (4 to 11 days) reduced mortality, whereas those obtained late (16 to 32 days after immunization) were not effective. The ability of donor cells to protect animals corresponded very closely with donor cytotoxic T lymphocyte (CTL) activity. Within 4 days after immune cell transfer, serum neutralizing antibody and CTL levels in recipients were comparable to those found in virus-infected control animals. Immune donor cells were fractionated into thymus-derived (T-enriched) and bone marrow-derived (B-enriched) subsets. The T and B subsets reduced mortality to 32% and 34% respectively. CTL and serum neutralizing antibody responses could be detected in these animals, although they appeared later than in mice treated with unfractionated immune spleen cells. The present study demonstrates that both B and T lymphocytes are required for optimum clearance of rabies from the central nervous system (CNS) and suggests a functional role for rabies-specific CTL in vivo.

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PubMed1979

An ultrastructural study of the cerebrospinal fluid in visna.

An electron microscopic examination was done on 8 samples of cerebrospinal fluid (CSF) from Icelandic sheep infected by the intracerebral route with visna virus. The specimens were collected 1 month, 2 months, and 4 years after infection. A differentail cell count done on low-power electron micrographs showed that the cellular exudate was composed of mononuclear cells mainly macrophages and lymphocytes with a few plasma cells. Macrophages were with one exception more numerous than lymphocytes and an increased proportion of macrophages showed evidence of phagocytosis with time after infection. Reactive lymphocytes were in general more numerous than small lymphocytes. Various stages in the maturation of plasma cells were observed. The cellular composition in the CSF is compatible with the view that visna is an immunopathological process. Myelin figures and fragments of myelinated axons were observed in two specimens indicating an active myelin-breakdown. The possibility that escape of myelin into the CSF may lead to sensitization to myelin antigens and perpetuation of this chronic neurologic affection is discussed. Visna virions could not be demonstrated.

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PubMed1979

Seasonality and the requirements for perpetuation and eradication of viruses in populations.

Perpetuation of a virus in a population is distinct from the ability to persist in a cell culture or individual host. Parameters which determine perpetuation include: 1) the size of the population; 2) the turnover of the population; 3) the proportion of immunes in the population; 4) the transmissibility of the infection; and 5) the generation time between sequential infections. These parameters may be grouped into two composite factors which most directly affect transmission dynamics and perpetuation: (a) population turnover per generation period, and (b) transmissibility or the fraction of susceptibles infected per existing infection. Perpetuation in small populations usually requires either the ability to persist in individuals or rapid population turnover. Conversely, human viruses which initiate only acute infections require larger populations to persist. Seasonal variation in transmissibility can greatly increase the minimum population size in which persistence is possible, and we argue that the population size of 500,000 for measles persistence (described by Bartlett) is primarily a consequence of seasonal variation. Computer modelling can be used to examine the effect of changes in parameters which determine the seasonal cycle of virus perpetuation and fadeout. Finally, human infections are reviewed to indicate those which have been eradicated (smallpox), are on the threshold of eradication (poliomyelitis), are possibly eradicable (measles), or could be candidates for future efforts (hepatitis A and hepatitis B). In developing a strategy for eradication two points are of great potential utility: first, the seasonal trough should be exploited as a time for effective intervention; and, second, containment efforts should be directed at epidemiologically important population groupings such as schools.

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PubMed1979

Pathogenesis of visna. IV. Spinal fluid studies.

Visna is a persistent retrovirus infection of sheep which produces a chronic progressive paralytic disease after an incubation period lasting from months to years. The cerebrospinal fluid (CSF) was repeatedly sampled in a group of Icelandic sheep which were infected intracerebrally and followed up to 42 months. Minimal levels of infectious virus were isolated from the cerebrospinal fluid (CSF) up to 4 months after infection after which CSF neutralizing antibodies appeared in many sheep. These antibodies varied in titer and in some animals exceeded serum antibody levels which were moderate to high. CSF antibody is apparently produced within the CNS by local proliferation of B cell clones, and is accompanied by the appearance of considerable numbers of plasma cells in the neural parenchyma. Some sheep raised serum antibody to a second serotype of visna virus and in a number of these animals heterotypic antibody was also found in the CSF. An increase in CSF leukocytes often occurs within 1 to 3 months following infection and may then persist or wane. A persistent high level of CSF cells is an indicator of progressive CNS disease and such animals are more likely to yield virus, have higher CSF antibody levels, more severe CNS lesions, and an enhanced risk of clinical illness (progressive paralysis). CSF cells are predominantly macrophages and lymphocytes, with a consistent minority of plasma cells.

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PubMed1978

Multiple sclerosis and canine distemper in Iceland.

Iceland offers a favourable opportunity to examine the suggested relationship between canine distemper and multiple sclerosis. Distemper is not enzootic in Iceland and distemper immunisation is not practised. However, importations result in occasional epizootics, three of which have occurred since 1909. Careful enumeration of multiple sclerosis indicates that there were 129 cases during the period 1946--65. When these cases are subdivided into six regions, by place of birth, regional period-prevalence rates were highest in two regions partially involved by distemper only once in the past 70 years. Also, there was substantial prevalence in a third region, encompassing Reykjavik, where the dog population has been kept very low for over 50 years. The Icelandic experience indicates that multiple sclerosis can occur at high incidence in the virtual absence of canine distemper or in the presence of a very small dog population.

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PubMed1978

The role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells.

The avirulent high egg passage (HEP) strain of rabies virus produces an inapparent infection limited to the central nervous system (CNS) in intracerebrally inoculated adult mice. Heavy chain isotype (anti-mu antiserum) immunosuppression potentiates the infection, with a mortality of about 60% and with elevated virus titers in the brain. Anti-mu-treated mice fail to raise antibody responses to rabies virus although their T cell function is normal when measured by the concanavalin A response of splenic lymphocytes. This indicates that the B cell response plays an important role in clearance of rabies virus from the neuroparenchyma. Treatment with cyclophosphamide or by adult thymectomy, x-irradiation, and bone marrow reconstitution potentiates HEP infection to a greater extent than does isotype suppression. Since these suppressive techniques impair both T and B lymphocyte responses, the data suggest that cellular immune mechanisms may also contribute to host defenses against this central nervous system (CNS) virus infection.

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PubMed1977

The ultrastructure of early visna lesions.

The ultrastructure of visna, a slowly progressive menigo-encephalomyelitis of sheep, was studied in animals sacrificed one month after intracerebral inoculation of visna virus. The major pathological changes, representative of those seen during the first year after infection, consist of inflammation and minor focal destructive lesions of grey and white matter. The inflammatory infiltrates, both subependymal and perivascular as well as of the choroid plexus, were composed mainly of lymphocytes and macrophages with varying numbers of plasma cells. The demyelination seen was of the secondary or Wallerian type. There was no evidence of primary demyelination. Visna virions were not seen in any of the CNS material studied. The ultrastructural findings are compatible with the view that lesions in visna may be induced by a cell-mediated immune response. However, changes characteristic of an autoimmune reaction to myelin antigens were not observed.

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