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Biomedical subjects

N Nathanson

Publications and source records attributed to N Nathanson.

At least 19 recordsLinked to original sources
PubMed1992

Neurovirulence tests of type 3 oral poliovirus vaccine manufactured by Lederle Laboratories, 1964-1988.

Oral poliovirus vaccine (OPV) is tested for safety by evaluation of neurovirulence in rhesus and cynomolgus macaques. After intraspinal or intrathalamic injection of varying doses of vaccine, monkeys are followed for 17-21 days, killed, and a histopathological evaluation is made of the severity of poliomyelitis lesions in the spinal cord and brainstem. Each production lot of vaccine is compared with a type 1 OPV reference virus tested by the same method. Records of neurovirulence tests on production lots of type 3 OPV manufactured by Lederle Laboratories, during the period 1964-1988, have recently become available, together with the corresponding tests on type 1 reference vaccine. The cumulative data were collated, using a system under which each monkey was given a single grade according to the severity and spread of neuropathological poliomyelitis lesions. These raw data were assembled into frequency distributions ('neurovirulence profiles'), and used to compare type 3 OPV with the reference vaccine. These comparisons included monkeys injected by intraspinal injection (three vaccine dose levels) and intrathalamic injection (one vaccine dose level), and comprised independent tests conducted by the Food and Drug Administration and by the vaccine manufacturer. A total of 13 different comparisons were made, each one consisting of a pair of profiles, on type 3 OPV and reference vaccine, respectively. In total, these comparisons represented tests on more than 12,000 monkeys. Based on these neurovirulence profiles, the type 3 OPV appeared to be no more virulent than the reference vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1.

We isolated and molecularly cloned a human immunodeficiency virus type 1 (HIV-1) strain (89.6) which is unusual because it is both macrophage-tropic and extremely cytopathic in lymphocytes. Moreover, this is the first well-characterized infectious molecularly cloned macrophage-tropic HIV-1 strain derived from peripheral blood. HIV-1 89.6 differs markedly from other macrophage-tropic isolates within the envelope V3 region, which is important in determining cell tropism and cytopathicity. HIV-1 89.6 may thus represent a transitional isolate between noncytopathic macrophage-tropic viruses and cytopathic lymphocyte-tropic viruses.

Amino Acid Sequence↗
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.

Animals↗
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.

Animals↗
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.

Animals↗
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.

Animals↗
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.

Animals↗
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.

Animals↗
PubMed1977

Rabies: recent advances in pathogenesis and control.

Current knowledge of rabies is reviewed, with emphasis on recent developments in virology, immunology, pathogenesis, treatment, and prophylaxis. Although only a few cases of human rabies occur annually in the United States, the infection is enzootic in wildlife, and an estimated 30,000 possible exposures requiring treatment occur each year. Rabies belongs to the family rhabdovirus, and its molecular anatomy and biochemistry of replication have been described in some detail. There have been advances in measurement of antirabies antibodies, and techniques for measuring cellular immune response have recently been developed. Early stages of infection are more fully understood, with a hypothesis to explain peripheral sequestration of virus during prolonged incubation periods. Rabies was once thought to be uniformly f fatal, but a few patients have survived with aggressive supportive measures. A newly developed vaccine (soon to be licensed in the United States) has been shown highly potent for preexposure immunization and promises to be very effective for postexposure prophylaxis. Current Public Health Service recommendations for postexposure treatment are summarized. Recent research has suggested a novel approach to control of wildlife rabies through oral immunization.

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