Sera from patients and employees of the Lynchburg Training School and Hospital were tested for Hepatitis B surface antigen by complement fixation test and antibody against Hepatitis B surface antigen by radioimmunoprecipitation test. Hepatitis B surface antigen was detected in 20% of the Down's syndrome patients and 7 percent of the matched other retarded patients. Antibody against Hepatitis B surface antigen was detected in 40% of the Down's syndrome and 57% of the matched other retarded patients. Hepatitis B virus infection as measured by presence of either Hepatitis B surface antigen or antibody was similar in the Down's syndrome patients (59%) and the matched other retarded patients (63%). Male patients had a higher frequency of Hepatitis B surface antigen chronic carriers and a lower frequency of antibodies to Hepatitis B surface antigen than the female patients. No relationship between age at time of first institutionalization and prevalence of Hepatitis B virus infection was demonstrated. However, it was observed that patients institutionalized at an earlier age were more likely to be housed in wards with a high frequency of Hepatitis B surface antigen. Increased length of institutionalization was associated with increased prevalence of Hepatitis B virus infection. Antibody to Hepatitis B surface antigen was detected in 33% of the employees. Employees who worked on wards with a high frequency of Hepatitis B virus infection had a high frequency of Hepatitis B surface antibody (50%) whereas those working on wards with a low frequency of infection had a low frequency of Hepatitis B surface antibody (9%).
Astrocytomas in nonhuman primates following JC virus inoculation provides a model which can be used to evaluate diagnostic and therapeutic techniques used in humans. The CT scan appearance of astrocytomas in nonhuman primates closely resembles that seen in humans. Our studies have shown that tumors may be detected in asymptomatic monkeys. Serial scans have shown astrocytomas to grow rapidly with breakdown of the blood-brain barrier. CT scanning has demonstrated the presence of tumor which was undetectable by gross examination at necropsy but confirmed by light microscopy. Studies are in progress to further define the radiological appearance of gliomas, to evaluate contrast-tagged anti-tumor antibodies as a diagnostic tool in evaluating gliomas by computerized tomography, and to evaluate metabolic parameters of actrocytomas by positron emission tomography.
An increasing number of infectious agents are now recognized to be important causes of perinatal morbidity and mortality. Most of these agents produce asymptomatic or mild infections in the mother; however, some can cause severe or fatal disease in the fetus. In each case, the infectious agent is transmitted from the mother to the child, usually by the transplacental, hematogenous route. The time of maternal infection during gestation frequently influences the chance of fetal infection and severity of fetal disease. The pathogenesis of these infections involves direct infection of the developing fetal tissues. In some cases this infection can interfere with morphogenesis or cause severe tissue destruction. Very late effects are now recognized with some perinatal infection, thus it is important to conduct longitudinal studies of infected children. Fetal disease can be prevented or reduced if prior exposure of the mother has resulted in complete or partial immunity. Immune responses in the fetus, which become detectable at about 20 to 22 weeks gestation, can be used for diagnostic purposes. They also appear to provide some degree of protection of the fetus from severe or fatal disease with certain agents when infection occurs late in gestation. The prevention of fetal damage by perinatal infections can be accomplished by protection of the mother through the appropriate use of vaccines, avoidance of exposure, treatment with immunoglobulins or the use of chemotherapy. Treatment of the child also involves the use of immunoglobulins and chemotherapy.
Owl and squirrel monkeys are susceptible to the oncogenic effects of JCV. These species of New World monkeys can be safely inoculated intracerebrally. Care must be taken with owl monkeys since they have an inherited clotting abnormality. Incubation times for the development of tumors range from 14 to 30 months. Anorexia was the first clinical sign of tumor development. The clinical course is rapid with death within two to three days. This model provides a means for studying diagnostic, virological, immunological and therapeutic techniques which are applicable to human patients with astrocytomas.
Immunofluorescent stains for fibronectin (FN) and glial fibrillary acidic protein (GFAP) were used in conjunction with routine histologic stains to study tumors induced in squirrel and owl monkeys by JC virus from progressive multifocal leukoencephalopathy (PML). Three varieties of glioma were identified. The first and most common variety was a neoplasm similar to grade 4 astrocytoma in humans. The second had thin, normal-appearing FN-positive vessel walls and a vastly expanded neuroectodermal parenchyma which could not be characterized by routine histologic stains. Anti-GFAP revealed the glial nature of the parenchyma. Isolating glial parenchymal cells from divergent FN-positive cells has become important to neurooncology. This type of tumor may be of particular interest for such isolations due to its high ratio of glial cells to divergent cells. The third variety was not a homogeneous neoplasm. It occurred as focal regions within tumors of the first type, and consisted of giant cells with huge nuclei. These cells resemble the cells of a human giant cell glioblastoma and bear a slight similarity to the bizarre glial cells seen in PML. The rare human giant cell glioblastoma might have an association with JC virus or with PML.
