Transmission of simian acquired immunodeficiency syndrome (SAIDS) with blood or filtered plasma.

Simian acquired immunodeficiency syndrome (SAIDS), a disease clinically and pathologically similar to acquired immunodeficiency syndrome in humans, was transmitted from diseased rhesus monkeys (Macaca mulatta) to normal monkeys by inoculation with heparinized whole blood or plasma that had been passed through filters of 0.45 micrometer pore size. This suggests that the causative agent is small and most probably a virus. No viruses, however, were isolated by standard cell culture techniques from the blood or filtered plasma which caused SAIDS. Both cellular and humoral immunity were markedly depressed in animals with advanced SAIDS.

Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus).

Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.

Focal neurological deficits and West Nile virus infection.

Our experience with West Nile virus infection revealed that 54% of 28 patients had a focal neurological deficit at presentation. A meningitis or encephalitis syndrome was absent in 47% of patients with focal deficits. Details of the variety of deficits, the time to development of deficits, and the associated radiological and laboratory findings are also discussed in the present report.

A rapid method for in situ hybridization for viral DNA in brain biopsies from patients with AIDS.

Brain biopsy is often necessary in the diagnosis of neurological complications found in AIDS patients. We describe here a rapid method of tissue preparation and in situ DNA hybridization for detecting JC virus DNA in frozen brain biopsy sections which allows the diagnosis of progressive multifocal leukoencephalopathy to be established on the day of surgery. Once the diagnosis is established, therapeutic and management decisions can be made more easily. The commercial availability of biotinylated probes for several of the DNA viruses most frequently encountered in brain infections of AIDS patients will provide wide application of these techniques to patient management.

Echovirus meningomyeloencephalitis with administration of intrathecal immunoglobulin.

Echovirus meningomyeloencephalitis was treated with cerebral intraventricular immunoglobulin. This case includes a complete examination of the central nervous system (CNS) supported by viral culture studies, immunoperoxidase staining and electron microscopy. Neuronal loss was most severe in the cerebellum and spinal cord. This may lead to the ataxia and a poliomyelitis-like syndrome often seen in cases of echovirus meningomyeloencephalitis. Focal encephalitic lesions, antigen-antibody reactions and live virus were found at numerous levels of the CNS in spite of intrathecal and intravenous immunoglobulin therapy. This mode of therapy and the electron microscopic features noted in echovirus infections are discussed.

Subacute sclerosing panencephalitis in only one of identical twins. A seven-year follow-up.

We report a seven-year follow-up of identical twins, in one of whom subacute sclerosing panencephalitis (SSPE) developed. Primary measles infection occurred simultaneous in both twins at age 4. The affected twin sustained a grade 1 closed head injury within six months of her primary measles infection. At age 13, SSPE was diagnosed following the onset of personality change and myoclonic seizures. Measles antibody level was elevated in the serum and CSF. After remaining in stage 2 for five years, rapid mental and neurological deterioration occurred. Measles antibody level remained elevated, and oligoclonal IgG was present in both serum and CSF. Results of neurological examination as well as virological and immunological tests were normal in the unaffected twin. Besides the occurrence of head injury, factors known to be associated with SSPE were not obviously different in the twins. We have been unable to determine a difference that would easily explain the occurrence of SSPE in only one of two identical twins.

Coronavirus antibodies in sera from patients with multiple sclerosis and matched controls.

Sera from patients with multiple sclerosis and carefully matched controls were tested for antibodies to three strains of coronavirus. There was no significant difference in the levels of antibody in the patients vs the controls. We conclude that unless the strains of coronaviruses recently reported to have been isolated from patients with multiple sclerosis express important serological differences from those used in these studies, coronaviruses are not associated with the cause of multiple sclerosis.

Measles and canine distemper antibody. Presence in sera from patients with multiple sclerosis and matched control subjects.

Antibody to measles virus and canine distemper virus (CDV) was demonstrated in sera from patients with multiple sclerosis (MS) and from carefully matched control subjects. Elevated measles and CDV antibody titers were found in patients with MS when compared with the matched control subjects. The correlation between the measles and CDV antibody titers was quite high, suggesting that the antibody levels between the two viruses are very closely related. Based on the results of our study and a review of the literature, our conclusion is that the CDV antibody levels in patients with MS and matched control subjects are associated with occurrence of measles virus antibodies.

Chlordecone intoxication in man. I. Clinical observations.

Industrial overexposure to chlordecone, an organochlorine insecticide, caused tremor in 76 of 148 exposed workers. Chlordecone was absorbed through oral, respiratory, and dermal routes, the last possibly the most significant. Epidemiology of this incident disclosed low-level, widespread environmental exposure of man to chlordecone. In 23 workers with chronic chlordecone intoxication, tremor was associated with opsoclonus, pleuritic pain and arthralgia. No seizures were reported. The site of action of chlordecone on the central nervous system is unknown. It concentrates in human adipose and hepatic tissue but is not biodegradable, either in humans or elsewhere in nature.

Chlordecone intoxication in man. II. Ultrastructure of peripheral nerves and skeletal muscle.

Tremors, mental changes, opsoclonus, muscle weakness, gait ataxia, incoordination, and slurred speech developed in several employees in a Virginia chemical plant during the summer of 1974. Epidemiologic and clinical studies suggested that the chlorinated insecticide chlordecone (Kepone) was responsible. Severity of symptoms seemed directly related to dose and duration of exposure. Five sural nerve and six muscle biopsy specimens were examined by light microscopy and electronmicroscopy. The sural nerves were also evaluated by computerized morphometry, which showed considerable decrease in the number of unmyelinated fibers and lesser abnormalities of myelinated fibers. Compared with the nerves of the control subjects, those of patients may have had an increase in Reich and Elzholz bodies, and a modest increase in endoneurial collagen. There were occasional "collagen pockets," stacks of Schwann cell cytoplasmic membranes, redundant Schwann cell cytoplasmic folds, and fewer unmyelinated axons. The skeletal muscles contained increased amounts of lipofuscin and lipidlike droplets in subsarcolemmal areas and within intermyofibrillary spaces; the significance of this is unknown. Fiber size variability, type I predominance, and type grouping were present in three cases. All results strongly suggest that chlordecone is a neurotoxic agent predominantly affecting Schwann cells and unmyelinated fibers of peripheral nerves.

Suppressor cell activity in multiple sclerosis.

Patients with multiple sclerosis and matched controls were tested for lymphocyte stimulation response and induction of suppressor cell activity in response to concanavalin A (Con A) and antigens from axolemma or myelin. Of 17 stable patients, 6 failed to have a suppressor cell response activated by one of these brain cell antigens. Among the patients who lacked these suppressor responses, five had lymphocyte stimulation responses to the same antigens. All matched controls except for one had suppressor cell responses to these antigens and none responded with a positive cellular immune reaction. We found no difference in lymphoproliferative responses to Con A in patients and controls. The level of suppressor cell activity induced by Con A in the stable MS patients varied but did not differ significantly from that of controls.

CSF "monoclonal" bands in chronic relapsing polyneuropathy.

The characteristics and temporal profiles of cerebrospinal fluid (CSF) and serum immunoglobulin patterns on agarose gel electrophoresis were studied in 47 patients with acute idiopathic polyneuropathy (AIP) and 15 patients with chronic relapsing polyneuropathy (CRP). Nineteen of 47 patients with AIP had transient oligoclonal IgG bands, which disappeared when the neurologic signs subsided. By contrast, 14 of 15 patients with CRP had a "monoclonal" (single) IgG band, which (1) was unchanged on repeated CSF examinations over 18 months, (2) was unaffected by corticosteroid therapy, and (3) did not correlate with the severity or chronicity of the disease. Serum protein patterns and in situ central nervous system IGG synthesis and IgG:albumin index were normal in the CRP patients. The origin of the band and the nature of the putative antigen(s) that the band may be directed against were not identified. Our findings suggest that different immunopathogenic mechanisms may be operating in CRP, compared with AIP. The stable IgG band in CRP may reflect response to a persisting antigenic stimulation and, with further experience, may prove to be of prognostic significance by furnishing early in the illness: (1) a clue to the subsequent course of the disease, and (2) possible guidance on therapeutic decisions.

Glial cells of the human developing brain and B cells of the immune system share a common DNA binding factor for recognition of the regulatory sequences of the human polyomavirus, JCV.

Cells of the nervous system and the immune system perform highly specialized functions which reflect the tissue-specific regulation of their genes. However there are some functions between these two cell systems such as antigen presentation, cytokine release, and expression of MHC molecules which suggest a common mechanism for regulation of certain genes. We present data that extend this observation to include the recognition of specific neurotropic viral DNA sequences by glial cells and B cells. The experiments here provide evidence that both human glial cells and B cells possess nuclear DNA binding proteins that interact with nucleotide sequences on the regulatory region of the JC viral genome. These DNA binding proteins are present in human lymphoma B cell lines and fetal glial cultures. The fetal glial cultures are characterized as astrocytes by unique cDNA expression and the presence of GFAP. Data are also presented that demonstrate the presence of JCV infected B cells in brain tissue derived from progressive multifocal leucoencephalopathy, the demyelinating disease caused by JCV infection. The possibility that the glial and B cell protein factor(s) responsible for recognition of the JCV genome belong to a family of proteins similar to known transcriptional control elements such as the Octamer binding proteins or Nuclear Factor-1 is discussed.