Herpesvirus hominis: isolation from human trigeminal ganglion.

Herpesvirus hominis was isolated from the trigeminal ganglion obtained at autopsy from 1 of 22 patients with no clinical evidence of active herpetic disease, and from one patient with malignant lymphoma who died with herpes zoster on the abdomen, pulmonary cytomegalic inclusion disease, and possible oral herpes simplex. Virus was isolated by cocultivation of explants of ganglion with monolayers of Vero green monkey kidney cells and required 3 weeks of culture before viral cytopathic effects were evident. These observations support the concept that latent infection of sensory ganglia may be the source of virus in recurrent herpetic disease in man.

Spiroplasma sp. 16S rDNA in Creutzfeldt-Jakob disease and scrapie as shown by PCR and DNA sequence analysis.

The pathogenesis of the transmissible spongiform encephalopathies (TSE), which include Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, remains an enigma. In this paper we present evidence for the association of Spiroplasma sp., a wall-less prokaryote, with TSE. We have shown PCR amplification of Spiroplasma 16S rDNA in TSE-infected brain tissues (13 of 13 CJD cases and 5 of 9 scrapie cases) and not in control brains (0 of 50). Direct sequencing of the amplified PCR products has confirmed the presence of Spiroplasma-like DNA in all 5 of the TSE brains tested. Our evidence is not necessarily in conflict with involvement of a PrPres--a protease-resistant host-derived protein referred to as the prion--in the pathogenesis of TSE, since there is evidence that another factor is involved. We propose a bacterium, namely Spiroplasma, as this associated factor although the role of Spiroplasma in TSE cannot be determined from these experiments. The presence of the nucleic acid sequence of this microbe in all cases of TSE in our laboratory and not in controls provides direct evidence of the association of Spiroplasma sp. with TSE.

Progressive multifocal leukoencephalopathy: failure of response to transfer factor and cytarabine.

A 57-year-old woman with a 2-year history of neurologic symptoms was shown on brain biopsy to have progressive multifocal leukoencephalopathy. Although cell-mediated immune mechanisms were impaired, no underlying disease was found. The administration of transfer factor enhanced cell-mediated immunity, but the neurologic symptoms did not improve. Separate courses of glucocorticoids and cytarabine were associated with rapid neurologic deterioration.

A method for enumeration ot T and B lymphocytes in tissues.

A method for the identification of T and B lymphocytes in tissue specimens is described. A sonication technique results in viable relatively pure lymphocyte populations which are easily classified by their surface markers. This readily reproducible method can become a standard laboratory procedure in the evaluation of disease states which require such information related to the classification of lymphocyte cell origin.

Horseradish peroxidase labeled antisera--a diagnostic method for evaluating the percentages of B lymphocytes in peripheral blood.

Horseradish peroxidase labeled antisera supplied commercially was used to evaluate B lymphocytes in peripheral blood. This technique not only gave comparable results to the conventional fluorescein method, but also proved to be more advantageous.

Effect of trimethoprim/sulphamethoxazole and hyperbaric oxygen on experimental Spiroplasma mirum encephalitis.

This study was undertaken to determine the susceptibility of experimentally induced Spiroplasma mirum infection in the rat to trimethoprim/sulfamethoxazole (TMP/SMX) in combination with hyperbaric oxygen (HBO). One-day-old Fisher 344 rats were intracerebrally inoculated with the GT-48 strain of S. mirum and were exposed to regimens employed combined antibiotic and HBO treatments. The exclusive use of TMP/SMX produced a significant reduction in mortality (P less than 0.0001) and an absence of clinical signs of infection. HBO in combination with TMP/SMX showed similar effect on mortality and no evident clinical disease. The addition of HBO did result in a significant decrease in spiroplasma brain titres but was no more effective in preventing the spiroplasma-induced fatal microcystic encephalopathy than when the antibiotics were used alone. The exclusive use of HBO produced a catastrophic mortality rate in the spiroplasma-infected rats, which is contrary to the effect of HBO on conventional bacterial infections.

Eastern equine encephalomyelitis. Histopathologic and ultrastructural changes with isolation of the virus in a human case.

Enveloped Toga virus particles were demonstrated by means of an electron microscopy in the brain tissues of a 3-year-old girl with acute encephalitis. Areas of demyelinization and necrosis throughout the white matter and brainstem were revealed by light microscopy. These viral particles were identified as eastern equine encephalomyelitis virus in postmortem isolation of the virus utilizing young mice and complement-fixation studies. To the authors' knowledge, this is the first demonstration of eastern equine encephalomyelitis virus particles in human tissues by electron microscopy.

Neurovirulence in an experimental focal herpes encephalitis: relationship to observed seizures.

An animal model of focal herpes simplex encephalitis was used to study several strains of type-1 herpes simplex virus. Rabbits were inoculated in the olfactory bulb by a standardized technique. Virus strains resulting in mortality of greater than 70% produced seizures of 3 types, and all animals that seized became moribund or died. In contrast, a virus strain resulting in a 20% mortality produced no seizures. Administration of 60 mg phenobarbital intramuscularly daily reduced mortality significantly in animals given the epileptogenic viruses. Cultures from temporal and frontal lobes showed viral growth more frequently than did cultures of other brain areas. Microscopic examination of routine and immunoperoxidase-stained brain sections confirmed the focal nature of the infection. Clinical syndromes such as seizures arising from viral brain disease may influence mortality in animal model systems.

Malignant transformation in craniopharyngioma.

Malignant transformation in a craniopharyngioma has not been described previously. A 49-year-old woman presented with recurrence of a suprasellar craniopharyngioma diagnosed 35 years previously. The patient had been treated surgically for recurrence on five occasions. Radiation therapy had been administered 7 years before the final presentation. Tissue obtained from the fifth operation revealed malignant degeneration in a typical craniopharyngioma.

The small midline occipital encephalomeningocele: definition of a syndrome.

An unusual group of encephalomeningoceles is described. Two children were noted at birth to have a raised area of abnormal skin at the occipital midline. Both of these lesions were found to perforate the superior sagittal sinus and to end between the leaves of the falx cerebri, and to contain a small amount of abnormal cerebral tissue with no connection to either occipital lobe. Previous case reports are reviewed; these lesions are true encephalomeningoceles, rather than glial heterotopias. The embryology of such lesions is considered, and likely differs from the much more common occipital encephalocele arising from one or both occipital lobes.

Spiroplasma-like inclusions in Creutzfeldt-Jakob disease.

Spiral membranous inclusions were discovered on electron microscopic study of brain biopsy tissues from a 46-year-old man with Creutzfeldt-Jakob disease (CJD). These replicate coiled membranous configurations measured 850 to 1,000 nm in length and 75 to 137.5 nm in width and were located within axoplasm, primarily in presynaptic terminals. These inclusions closely resemble Spiroplasma, a plant pathogen, and the finding of these structures in CJD suggests the concurrence of Spiroplasma infection with a human chronic degenerative brain disease.

Primitive neuroectodermal tumor in a 57-year-old man.

Primitive neuroectodermal tumors are rare cerebral neoplasms previously described only in children and young adults. This report describes such a tumor arising in the left frontal lobe of a 57-year-old man. After surgical resection and radiation therapy to the primary site, the patient developed extensive central nervous system metastases that led to his death. The histopathologic, radiographic, and clinical features of this case suggest that future therapeutic protocols for primitive neuroectodermal tumor should be similar to those for childhood medulloblastoma or neuroblastoma.

Nonfulminant herpes simplex encephalitis as a cause for mesial temporal sclerosis.

Although mesial temporal sclerosis has been recognized for more than 100 years, its etiology remains unknown. It is proposed that a common infectious agent, herpes simplex virus type-1, may cause this disorder by means of a nonfulminant infection of mesial temporal lobe structures, which is resolved by the immune system and becomes gliotic in the course of healing by the central nervous system. Brain sections from a long-term experiment in a model of herpes simplex encephalitis reveal such a scar, which shows a high concentration of glial fibrillary acidic protein, without any evidence of residual herpes antigen, by immunocytochemistry.

Gliosarcoma developing from an irradiated ependymoma.

A 17-year-old girl was operated for a cystic mass located deep within the left parieto-occipital white matter. Histologically the tumor was an ependymoma with a vascular stroma. In spite of irradiation the tumor recurred locally twice, 1 and 2 years respectively after the original operation. The ependymoma portion of the tumor remained unchanged, but the stroma showed increased vascular hyperplasia at the time of the second operation and transformation into a fibrosarcoma in the third operative specimen. Proliferating cell markers (MIB-1) were positive only in the ependymoma cell nuclei in the first two specimens, but were also extensively present in the nuclei of the fibrosarcoma in the third specimen. In the latter, the fibrosarcoma portion greatly overwhelmed the residual ependymoma islands, but remained sharply delineated from them. This is the first observed case of a gliosarcoma originating from an ependymoma. The histological pattern of this mixed tumor clearly indicates that the source of the sarcomatous portions was the neoplastically transformed fibrovascular stroma of the original tumor, rather than "desmoplastic" alterations of the neoplastic ependymal cells themselves.

Neurotropic response of Spiroplasma mirum following peripheral inoculation in the rat.

Spiroplasma mirum experimentally produces a persistent brain infection in suckling rats when administered intracerebrally. In order to examine spiroplasma infection induced by a more natural route, suckling rats were inoculated both intraperitoneally and subcutaneously with strain GT-48. No mortality was recorded over a 50-day study period. Rats developed localized alopecia and showed a significant reduction in body weight. Minimal pathological alterations were observed in brain tissues, in addition to cataracts, retinal degeneration and panophthalmitis. Spiroplasmas were recovered from brain and spleen on day 2 following peripheral inoculation with highest titres in the spleen. Spleen titres significantly declined (p less than 0.022) during the 50-day study period. On day 50, brain titres exceeded those in the spleen. The attraction of spiroplasma to central nervous system tissues may be related to its nutritional dependence on sterols.

Antiserum to scrapie-associated fibril protein cross-reacts with Spiroplasma mirum fibril proteins.

Protease-resistant fibril proteins purified from Spiroplasma mirum and from Creutzfeldt-Jakob disease-infected brain tissues reacted with antisera to scrapie-associated fibrils on Western immunoblot analysis. These data suggest that there are conformational similarities among spiroplasma proteins and infection-specific proteins of the transmissible spongiform encephalopathies.

Evaluation of [3H]thymidine uptake method for studying growth of spiroplasmas under various conditions.

[3H]thymidine uptake and colony counts are quantitative and inexpensive methods for studying Spiroplasma growth. Using these techniques, we demonstrated subtle effects on the growth of suckling mouse cataract agent of medium alterations, inoculum size, and freezing of cultures. In addition, suckling mouse cataract agent multiplied more actively under aerobic than under anaerobic conditions. These techniques have wide application for the study of Spiroplasma growth and will be useful for the development of a defined medium.