Showing papers by "Herbert Budka published in 1990"

Loss of neurons in the frontal cortex in AIDS brains.

Abstract: Neurons of Area 11 in the fronto-orbital cortex of 18 unselected AIDS brains are analyzed by means of stereology. Neurological abnormalities including dementing symptoms were described in eight patients. Neuropathology diagnosed human immunodeficiency virus (HIV)-specific changes in four, and diffuse poliodystrophy in eight brains. The majority (71.4%) of these brains was immunoreactive for HIV antigens when tested by immunocytochemistry. A significant loss of neurons is found as compared to normal controls. Neuronal density in AIDS brains is reduced by 18%, and the perikaryon volume fractions is reduced by 31%. Although only speculation on pathogenesis of this neuronal loss is possible at present, it may represent a part of the pathomorphological substrate of AIDS-related dementia. Moreover, it confirms by quantitative means damage to the cerebral cortex in AIDS which has been described only qualitatively as diffuse poliodystrophy.

Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation.

Abstract: Cryostat sections of 12 gliomas and of 3 peritumoral brain tissue samples were investigated for mononuclear cell infiltration by immunohistochemistry, concentrating on cells expressing monocyte/macrophage markers. Only low numbers of T cells were detected in the tumors, whereas in average 20%–30% of all cells present in the samples were recognized by various macrophage markers. These cells carried surface epitopes with known function, like Fc-γ (Fcg) and complement receptors. Microglial cells, in comparison to typical debris laden macrophages, were only recognized by a restricted panel of macrophages markers (anti-Fcg receptors 1, 2, 3, complement receptor CR3, HLA DR, common leucocyte antigen CD45 and the monocyte marker RM3/1). In peritumoral tissue mainly dendritic, microglia-like cells were present, which revealed decreased expression of antigens CD4, RM3/1 and Fcg receptors in comparison to those in gliomas. A significant positive correlation was found between the number of RM3/1 or CR3 (CD11b)-positive cells and the proliferation rate of the tumors as documented by the number of bromodeoxyuridine-positive or Ki-67+ cells.

Human immunodeficiency virus (HIV) envelope and core proteins in CNS tissues of patients with the acquired immune deficiency syndrome (AIDS)

Abstract: Frequency, cellular tropism and relation to pathology of productive infection with human immunodeficiency virus (HIV) in human central nervous system (CNS) were studied. Serial sections of formolfixed and paraffin-embedded CNS tissues from 70 patients (69 with acquired immune deficiency syndrome, AIDS) were immunolabeled with monoclonal antibodies against HIV antigens (Ags) p17, p24, and gp41. Additional and double (immuno)stains were used to identify cell types and opportunistic infectious agents. HIV Ags were detected in 52 cases; they were restricted to cells with characteristics of microglia or macrophages. Anti-gp41, anti-p24, and anti-p17 labeled 50, 33, and 15 cases, respectively. Immunoreactivity for core proteins predominated in mature macrophages and microglia of fully developed lesions; additional immunoreactivity for gp41 was seen in microglia adjacent to, or unassociated with, histopathological lesions. Multifocal and/or diffuse lesions previously suggested as HIV induced because of characteristic histopathology, consistently contained large numbers of cells with HIV Ags (33 cases), confirming their HIV specificity. Isolated labeled microglia without associated pathology, found in seven brains, presumably represent the earliest stage of productive CNS infection by HIV. Lesions of opportunistic infections contained no (34 cases), few (16 cases), or many (4 cases) cells with HIV Ags. These data do not suggest transactivation of local HIV production by opportunistic agents as a frequent event in vivo. Development of specific HIV histopathology appears correlated with the number of productively infected cells.

Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignany and proliferation indices

Abstract: Proliferation indices and mean number of silver-stained nucleolar organizer region-associated proteins (Ag-NORs) are compared in 65 brain tumors, including 34 gliomas, 8 meningiomas, 17 metastatic tumors, and 6 other tumors. Immunocytochemical investigations include labeling with the monoclonal antibody Ki-67 which identifies the whole growth fraction, and with a monoclonal antibody against bromodeoxyuridine (BrdUrd) which detects cells in the S phase of the cell cycle after in vitro incubation with BrdUrd. When all types of tumors are collectively considered, mean numbers of Ag-NORs did not correlate with Ki-67 and Brd-Urd labeling indices (LIs) and mitotic index. Among tumor subtypes, only meningiomas showed significant correlations between Ag-NOR counts, LIs, and malignancy. Mean number of Ag-NORs did not correlate with proliferation indices and tumor grade in low-grade and high-grade gliomas. However, recurrent high-grade gliomas showed a tendency to higher Ag-NOR counts than primary tumors. This study indicates that counting of Ag-NORs in paraffin sections is of limited value in tumor neuropathology. Correlations found in meningeal tumors should be substantiated in larger series.

Progressive multifocal leukoencephalopathy (PML) in AIDS and in the pre-AIDS era. A neuropathological comparison using immunocytochemistry and in situ DNA hybridization for virus detection.

Abstract: Twenty-five brains with definite, and three brains with possible, progressive multifocal leukoencephalopathy (PML), including six brains of AIDS patients, were studied with special regard to the detection of papovaviruses. Formalin-fixed serial paraffin sections were immunostained with monospecific anti-JC virus (JCV) and genus-specific anti-simian virus (SV) 40 antisera, and hybridized in situ with DNA probes for JCV and SV 40, respectively. Immunocytochemistry (ICC) and in situ hybridization (ISH) were similarly sensitive in detecting virus in classical PML lesions. In all but one definite PML cases at least one method detected virus (96%). Possible PML tissue was never labeled. Labeling patterns were generally similar in ICC and ISH: mainly oligodendroglia and, less frequently, astroglia harbored virus, whereas labeling of neurons and endothelia was absent. Bizarre giant astrocytes were occasionally labeled by ICC and ISH. Burnt-out lesions harbored JCV DNA but not virus antigens. SV 40 DNA was never detectable. PML morphology in AIDS cases did not usually differ from the disease process seen in the pre-AIDS era. However, two AIDS brains presented extremely extended and, in one case, unusually necrotizing PML damage; in the latter case, PML lesions contained large amounts not only of JCV, but also of human immunodeficiency virus (HIV) antigens. We conclude that ICC and ISH are methods of comparable sensitivity for detection of papovavirus in flourishing PML lesions. In burnt-out PML lesions only ISH may detect virus. The possibility of an exceptional non-JCV (e.g., SV 40) etiology of PML could be neither confirmed for disproved. In AIDS, massive coinfection by HIV of PML lesions may increase damage to tissue, resulting in unusually extended and necrotizing PML.

Multifocal vacuolar leucoencephalopathy: a distinct HIV-associated lesion of the brain.

Abstract: A 20-year-old male AIDS patient developed rapidly progressive dementia for more than 3 months prior to death. Autopsy showed, in addition to adrenal cytomegalovirus (CMV) infection and focal cerebral necrosis due to toxoplasmosis, multifocal subcortical white matter lesions of the brain which were strikingly similar to the histopathology of vacuolar myelopathy in AIDS. These distinct lesions contained macrophages which were rarely multinucleated and expressed HIV antigens by immunocytochemistry. The distribution of lesions mimics extrapontine myelinolysis and progressive multifocal leucoencephalopathy (PML); PML was excluded by the absence of papovaviruses by immunocytochemistry and by in situ DNA hybridization. Tissue damage in multifocal vacuolar leucoencephalopathy is different from hitherto characterized HIV-specific neuropathology such as HIV encephalitis and HIV leucoencephalopathy, and should be included in the list of conditions with damage of the brain white matter in AIDS.