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Biomedical subjects

H L Lipton

Publications and source records attributed to H L Lipton.

At least 109 records · Page 6Linked to original sources
PubMed1979

Susceptibility of inbred mice to chronic central nervous system infection by Theiler's murine encephalomyelitis virus.

The present study demonstrated that the clinicopathological expression of the late demyelinating disease due to chronic central nervous system infection by Theiler's mouse encephalomyelitis virus was dependent, at least in part, on the strain of mouse used as host. A range of involvement was observed, with late disease being most severe in the SJL strain, intermediate in the CBA and C3H/He strains, and least in C57BL/6 mice. The lack of clinical signs in seven other inbred strains of mice indicates that their response to chronic infection was similar to C57BL/6 mice. SJL, CBA, C3H/He, and C57BL/6 mice all generated similar levels of neutralizing antibody. A correlation between the severity of late disease and central nervous system virus content was not demonstrated, which indirectly suggests an immunopathological rather than a cytolytic mechanism of myelin injury during the late disease period. Finally, in addition to being more extensive, SJL demyelinating lesions contained a disproportionately large number of macrophages compared with those of similar lesions in CBA and C3H/He mice.

Animals↗
PubMed1978

Adult onset of the Dandy-Walker syndrome.

Two patients with the Dandy-Walker malformation first developed neurologic symptoms in adult life. In both patients there was normal motor and intellectual development during childhood, but as adults they had gradual evolution of brain stem and cerebellar signs and obstructive hydrocephalus. Following resection of the fourth ventricular cyst, both patients recovered. A review of the literature disclosed seven additional patients in whom the Dandy-Walker syndrome was first diagnosed in adult life. These cases illustrate that this congenital brain malformation may not only first become symptomatic later in life, but that it is possible for patients to remain asymptomatic.

Adult↗
PubMed1978

Central nervous system immunity in mice infected with theiler's virus. I. Local neutralizing antibody response.

Experimental Theiler's mouse encephalomyelitis virus (TMEV) infection in mice is atypical of most other picornavirus infections because virus persists in the host. It was shown previously that low levels of infectious virus are readily detectable in the central nervous system (CNS) despite the presence of substantial titers of serum neutralizing antibody. In this study antibody assays were performed on CNS tissue homogenates, and neutralizing antibody was regularly found in the CNS of TMEV-infected mice. That neutralization by infected CNS extracts was due to antibody was demonstrated by the specificity of neutralization for TMEV and by elimination or marked reduction of neutralization by in vitro treatment with goat antiserum to mouse IgG. In addition, immunofluorescent staining consistently revealed IgG- but not IgM-containing cells in perivascular cuffs and parenchymal lesions of the brains of infected animals. Evidence of local antibody formation in the CNS was found in the actual reversal of the serum-CNS antibody ratio in about one-third of infected mice after three weeks. In contrast, normal mice had a mean serum-CNS antibody ratio of approximately 100:1 after passive transfer of antibody. Possible reasons for the fact that TMEV is not neutralized by antibody and chronic infection is not aborted include the formation of complexes of infectious virus and antibody in the CNS and the production of antibodies with low affinity for TMEV.

Animals↗
PubMed1978

Characterization of the TO strains of Theiler's mouse encephalomyelitis viruses.

Theiler's mouse encephalomyelitis virus isolates from the central nervous systems of spontaneously paralyzed mice and stools of asymptomatic mice resemble Theiler's original virus isolates. In this study four such strains were adapted by blind subpassage to replicate and to produce cytopathic effect in cell culture. These viruses were then found to be closely related to each other and to GDVII virus by cross-neutralization and to form small plaques. Bovine serum was found to contain cross-reacting antibodies to these viruses.

Animals↗
PubMed1977

Contrasting effects of immunosuppression on Theiler's virus infection in mice.

In the present study, cyclophosphamide and rabbit anti-mouse thymocyte serum were used to immunosuppress SJL/J mice infected with Theiler's mouse encephalomyelitis virus (TMEV) in order to delineate the potential mechanism(s) of virus-induced cellular injury in this infection. Whereas both immunosuppressive agents produced a significant increase in mortality, this treatment had differing effects on the pathological involvement of gray and white-matter structures in the central nervous system. The central nervous system of immunosuppressed TMEV-infected mice had increased microglial cell proliferation and neuronal necrosis, longer maintenance of high virus levels and spread of virus antigen to involve the neocortex and hippocampal complex. These observations indicate that TMEV causes a cytolotic infection of neurons and possibly other cells in gray matter. In contrast, immunosuppression produced a dramatic reduction in mononuclear inflammatory cells in the leptomeninges and spinal cord white matter of infected mice and prevented demyelination. Further, virus antigen was not detected in the leptomeninges and white matter of immunosuppressed and infected mice. These findings suggest that demyelination of TMEV infection is immune mediated.

Animals↗
PubMed1977

A new model of persistent viral infection with primary demyelination.

Theiler's encephalomyelitis virus (TMEV) in mice represents one of the few existing animal models of virus-induced demyelination and may provide further information about the human disease, Multiple Sclerosis. An inbred strain of mice (SJL/j) employed in the present ultrastructural study, develops a life-long neurologic illness characterized by profound spasticity after intracerebral inoculation of TMEV. Anesthetized animals were sacrificed sequentially by total body perfusion with gluteraldehyde from 7 days to 9 months after infection. An intense mononuclear inflammatory infiltrate appeared in the leptomeninges and white matter of spinal cord by 15 days and persisted for as long as one year. These infiltrates contained numerous plasma cells, and perivascular demyelination could be found in almost every 1 micron section. Vesiculation and stripping of myelin by mononuclear cell processes were seen as mechanisms of myelin break-down. However, virions were not found in cells in grey or white matter and the integrity of oligodendrocytes was maintained. At one year, active demyelination was still seen in areas containing naked and remyelinated axons. The relevance of these ultrastructural findings to postulated mechanisms of virus-induced demyelination will be discussed.

Animals↗
PubMed1977

Sources of variation in clinicians' communication to parents about mental retardation.

Sources of variation in clinicians' diagnostic communication to parents of mentally retarded children were identified and examined. Results demonstrated that the nature of clinicians' communication is related to the severity of the child's diagnosis, clinicians' perception of the parents' level of emotional adjustment, whether the clinicians' experienced difficulties in communicating the diagnosis, and their length of clinical experience in the field of developmental disabilities. The dynamics of these relationships were discussed, as were the implications of the findings for future research and for needed changes in the current priority structure of medical education.

Adaptation, Psychological↗
PubMed1976

Theiler's virus-induced demyelination: prevention by immunosuppression.

The effect of immunosuppression with cyclophosphamide and rabbit antiserum to mouse thymocytes on demyelination induced by Theiler's virus in SJL/J mice was ascertained from Epon-embedded sections (1 micrometer) of the central nervous system. Immunosuppression not only eliminated mononuclear cell infiltrates in the spinal cord white matter, but it also prevented the occurrence of demyelination. These results suggest that demyelination in this infection is immune-mediated.

Animals↗
PubMed1976

Chronic neurologic disease in Theiler's virus infection of SJL/J mice.

This study demonstrates that most SJL/J mice inoculated intracerebrally (IC) with 1000 suckling mouse 50% mean lethal doses of Theiler's encephalomyelitis virus (TMEV) develop flaccid paralysis 10-21 days after infection when there is acute spinal cord gray matter involvement (early disease). Surviving mice later develop a distinctive chronic neurologic disorder which is associated with marked mononuclear cell infiltrates and active demyelination in spinal cord white matter (late disease). Moreover, about one-fourth of infected animals only develop signs of late disease which may begin after an incubation period as long as 2 and a half months. Affected mice are less active, incontinent, and have a waddling, spastic gait. Minimal stimulation induces prolonged extensor spasms of all limbs. These late-developing manifestations of chronic TMEV infection are progressive and clinical remissions have not been observed. The effect of persistent CNS infection on general development was monitored by weekly measurement of body weight; however, the growth of chronically-infected mice was found to parallel that of control animals.

Animals↗
PubMed1976

Theiler's virus-induced central nervous system disease in mice.

Theiler's viruses, which are common enteric pathogenes of mice, produce an unusual buphasic disease in the natural host following IC inoculation. There is an early phase of virus growth in CNS gray matter resulting in motor neuron degeneration and microglial proliferation. Since the spinal cord is the principal site of involvement, infected animals develop flaccid limb paralysis (early disease). Immunosuppression of the host during the early phase of infection augments virus growth and pathological lesions in gray matter, suggesting that TV causes a cytocidal infection of neurons. More importantly, surviving mice have persistent infection and pathological change limited to the spinal cord. There is marked mononuclear cell infiltration in the leptomeninges and white matter and concomitant primary demyelination. These changes are associated with a distinctive late-developing neurological disorder characterized by general inactivity, slowed movement, poor righting ability, and stimulus-sensitive extensor spasms. It appears that there are differences in host susceptibility to the development of late disease with the SJL/J inbred strain of mouse regularly showing the most severe clinical manifestations. Both humoral and cell-mediated immunity to TV antigen are delayed, reaching a maximum after 2 months; hence, this temporal sequence of the immune response is atypical of acute virus infections. Certain features of the late disease process favor an immune-mediated mechanism for demyelination, and this possibility is currently under investigation. The cells chronically supporting virus replication and the mechanisms of persistent infection remain to be elucidated.

Acute Disease↗
PubMed1976

Cellular immunity in chronic Theiler's virus central nervous system infection.

After (IC) inoculation of the DA strain of TMEV, SJL/J mice develop chronic CNS infection with marked mononuclear cell infiltration of spinal cord leptomeninges and white matter and concomitant demyelination. In the present study the temporal course of cell-mediated and humoral immune responses to virus were measured in this infection. It was shown that chronic TMEV infection is associated with the development of immunologically specific spleen cell reactivity as judged by in vitro incorporation of 3H-TdR into DNA in response to inactivated TMEV antigen. Spleen cell reactivity is first detectable about 2 months after infection, persists for at least 1 year, and correlates with the temporal development of serum-neutralizing antibody. The late development of sensitized spleen cells is not the result of an immunosuppressive effect of this virus infection since infected mice exhibit normal spleen cell proliferative responses to T cell mitogens and produce normal antibody responses to a heterologous protein antigen, sheep red blood cells. In addition, anti-viral antibody inhibits virus-induced spleen cell reactivity. Finally, the antigen-reactive lymphocyte subpopulation within the spleen responsible for proliferation to TMEV antigen are T cells and not B cells.

Animals↗
PubMed1975

Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination.

An unusual biphasic central nervous system disease developed in 3-week-old Swiss outbred mice after intracerebral inoculation of the DA strain of Theiler's murine encephalomyelitis virus. Nine to 20 days postinfection 86% of mice became paralyzed, and approximately one-half of these animals survived. During this period neuronal necrosis and microglial proliferation were seen in thalamus, brainstem, and spinal cord. There was an initial phase of virus growth in spinal cord followed by persistent infection at a lower concentration. Virus antigen was readily found in the cytoplasm of neurons by immunofluorescent staining early in the course of infection, whereas after 30 days there was a paucity of cells containing virus antigen which were present only in the spinal cord white matter. Between 1 and 5 months, an intense mononuclear inflammatory cell lesion evolved in the spinal cord leptomeninges and white matter, which coincided with a mild gait disturbance in some surviving mice, and patchy demyelination was found in areas of inflammation. The acute gray matter pathology would appear to be the result of direct virus lytic effect. Although the late white matter lesion culminating in demyelination probably represents a cytocidal infection similar to the situation that exists in certain picornavirus carrier culture systems, a virus-induced immunopathological process merits further study.

Animals↗
PubMed1975

Primary demyelination in Theiler's virus infection. An ultrastructural study.

Theiler's virus infection in SJL/J mice was studied ultrastructurally at subsequent intervals after intracerebral inoculation. Extensive spinal cord lesions consisting of leptomeningeal and white matter mononuclear cell infiltrates with concomitant primary demylination were seen by 15 days. Stripping of myelin lamellae by invading mononuclear cell processes and vesicular disruption of myelin were demonstrated to be the patterns of myelin breakdown. Oligodendrocytes in the vicinity of demyelinating lesions never showed degenerative changes, and viral inclusions could not be found in any cells in the central nervous system. Remyelinating axons, first detected 21 days after infections, were more frequently seen in the late phase of the disease when conspicuous gliosis was also present. Active demyelination could still be observed as late as one year after infection at which time inflammation was decreased. However, plasma cells were relatively more numerous at later times after infection. These ultrastructural findings are similar to experimental allergic encephalomyelitis, and suggest an immune-mediated mechanism of demyelination in Theiler's virus infection.

Animals↗