Transforming growth factor-beta1 in adult human microglia and its stimulated production by interleukin-1.

Ameboid microglia express human immunodeficiency virus 1 (HIV-1) more frequently than do ramified microglia. These two microglial subtypes might also differ in the frequency with which they express transforming growth factor-beta1 (TGF-beta1), a cytokine that regulates HIV-1 expression in monocytes. Results described here show that ameboid and ramified microglia express TGF-beta1. In brain tissues from HIV-1-infected individuals as compared with seronegative controls, ameboid rather than ramified microglia more frequently expressed TGF-beta1. Ameboid microglia, isolated and cultured from postmortem adult human brain more frequently expressed TGF-beta1 in presence of interleukin-1(IL-1), a cytokine that is elevated in brains of HIV-1-infected individuals when compared with seronegative controls. The stimulation of TGF-beta1 by IL-1 was dose and time dependent, occurring with ameboid microglia isolated from either frontal cortex or globus pallidus but not midbrain pons. Ameboid microglia are similar to the RCA-1-positive cells that form clusters, called microglial nodules, in the brain of HIV-1-infected individuals. Pathologic conditions, such as disseminated microglial nodules, are associated with HIV-1 encephalitis, direct infection of the brain, and moderate to severe neurologic impairment. TGF-beta1 expression in ameboid microglia may play a role in HIV-1 neuropathogenesis.

Control of astrocytosis by interleukin-1 and transforming growth factor-beta 1 in human brain.

Astrocytosis is a common neurocellular manifestation of brain pathology in individuals with a variety of diseases. It is comprised of astrocytic hyperplasia (an increase in number of astrocytes) and astrocytic hypertrophy (an increase in size of astrocytes). The precise cause(s) of astrocytosis remains unknown. We morphometrically measured the relative extent of astrocytosis in brains of 22 individuals who died with seven different diseases. The relative amounts of interleukin-1 (IL-1) and transforming growth factor-beta 1 (TGF-beta 1) immunoreactive products (IRPs) were next assessed in sections serial to those in which astrocytosis was measured because these cytokines were shown in animal and in vitro experiments to be associated with astrocytosis. The data demonstrate that astrocytosis and these cytokines were co-localized in all examined human tissues. Relative increase in density of astrocytes was correlated with the increase in total IL-1 but not TGF-beta 1. In contrast, the increase in size of astrocytes was correlated with TGF-beta 1 associated only with astrocytes but not with total IL-1. Both IL-1 and TGF-beta 1 IRPs were present in GFAP IRP-containing and other cells, as assessed by double label immunocytochemistry. These observations suggest that IL-1 acts on astrocytes by both, paracrine and autocrine mechanisms whereas, TGF-beta 1 only acts by an autocrine mechanism. Because these correlations were statistically significant and also because a change in number and size of astrocytes constitutes the most frequent response of astrocytes to several diseases or injury, we conclude that these cytokines may mediate the most common pathological change in human brain.

Gliosis in human brain: relationship to size but not other properties of astrocytes.

Gliosis is the most frequent and therefore important neurocellular reaction to brain insult occurring in diseases ranging from AIDS to infarction. Neuropathological diagnosis of gliosis is based on morphological changes of brain glial cells. Changes commonly agreed to reflect gliosis are qualitative increases in size, number and glial fibrillary acidic protein (GFAP) immunoreactivity of astrocytes. These parameters were morphometrically quantified in brain tissues of 22 individuals who died with 7 diseases and statistically compared to the extent of gliosis independently determined by 3 qualified observers. The data indicate that the extent of gliosis correlated with the increase in size of astrocytes in white matter (p = 0.67) and this relationship was statistically significant (P = 0.0006). In contrast, the extent of gliosis was not correlated with the density of astrocytes nor the intensity of GFAP staining.

The recognition of mycobacterial infections by intraoperative cytology in patients with acquired immunodeficiency syndrome.

In patients with the acquired immunodeficiency syndrome, mycobacterial lymphadenitis is characterized by the presence of numerous acid-fast bacilli within histiocytes. In Diff-Quik-stained cytologic preparations of such lymph nodes, performed during intraoperative consultations, the presence of mycobacteria is manifested by numerous negatively staining rod-shaped spaces intracellularly within histiocytes, as well as extra-cellularly in the background. Recognition of these characteristic "footprints," or "negative images," of mycobacteria can facilitate early diagnosis and treatment. The morphological characteristics that help to distinguish between Mycobacterium avium-intracellulare and Mycobacterium kansasii are also described.

Thorotrast-associated gliosarcoma. Including comments on thorotrast use and review of sequelae with particular reference to lesions of the central nervous system.

The occurrence of a glioblastoma with sarcoma, a gliosarcoma, in the left frontal-temporal area of a 49-year-old woman with a history of Thorotrast exposure, is described. Thorotrast-laden histiocytes and free Thorotrast material were found in both components of the tumor. An overlying, adherent dural cranial lesion was found to contain massive deposits of Thorotrast embedded in a dense fibrotic and sclerotic stroma with focal calcification. These features are typical of "Thorotrastoma." Thorotrast stains greenish-brown with hematoxylin and eosin and appears as refractile granular particles of relatively uniform size either within histiocytes or as free material. The radioactivity of the deposits was confirmed through the use of a scintillation counter, and 232 thorium was definitively identified though the use of scanning electron microscopy with energy-dispersive X-ray analysis. Immunohistochemical studies of the tumor demonstrated glial fibrillary acid protein (GFAP) immunoreactivity in areas of glioma and focal vimentin and actin immunoreactivity in areas of sarcoma. Thorotrast-associated lesions of the central nervous system (CNS) are infrequently reported, and a Thorotrast-associated gliosarcoma has not yet been reported. The use of Thorotrast, its radiobiology, and sequelae are reviewed with particular emphasis on lesions occurring in the CNS.

Disseminated talc granulomatosis. An unusual finding in a patient with acquired immunodeficiency syndrome and fatal cytomegalovirus infection.

The association of disseminated magnesium silicate talc granulomatosis and acquired immunodeficiency syndrome is reported in a male homosexual who used intravenous drugs and who died of overwhelming cytomegalovirus (CMV) infection. Autopsy findings included widespread deposition of talc crystals in the lungs, liver, lymph nodes, bone marrow, and spleen. Typical CMV inclusions were seen in the lungs, kidneys, adrenal glands, gastrointestinal tract, and right eye. There was no evidence of malignancy. Analysis of peripheral blood neutrophil function revealed impaired chemotaxis and chemokinesis, but opsonophagocytosis had remained normal. The CMV infection in the small bowel was extensive and resulted in severe destruction of the muscularis propria and neural plexi, leading to marked dilatation and persistent diarrhea. The terminal course was marked by intractable hypotension, pneumonitis, and malnutrition, which could be attributed respectively to CMV involvement of the adrenal glands, lungs, and small bowel. The etiology and possible role of systemic talc granulomatosis in the development of immunosuppressive illness is reported herein.

Systemic visceral talc granulomatosis associated with miliary tuberculosis in a drug addict.

Light and scanning electron microscopic study of tissues obtained at biopsy and at autopsy from a 64-year-old male drug addict revealed the presence of foreign body granulomas associated with birefringent crystals in the lungs, liver, bone marrow, spleen, and lymph nodes. Caseating granulomas associated with Mycobacteriaceae tuberculosis were also present. Energy dispersive X-ray analysis identified the crystals as talc. Minute talc crystals were also visualized in urine sediment, by scanning electron microscopy and identified by energy dispersive X-ray analysis.

Aphasia resulting from occlusion of the left anterior cerebral artery. Report of a case with an old infarct in the left Rolandic region.

A 62-year-old right-handed woman was admitted to the hospital with a cerebrovascular accident in the left hemisphere. She was aphasic as well as hemiplegic on the right. She had had a left cerebrovascular accident 18 years earlier that caused weakness in the right hand, but no grossly detectable speech problems. Autopsy disclosed an old infarct along the left Rolandic area, and a recent infarct in the territory of the left anterior cerebral artery. The clinical picture and pathologic changes are discussed in an attempt to relate the findings at autopsy to the recently developed aphasia.

Oculomotor nerve regeneration after aneurysm surgery.

A 57-year-old woman had symptoms of oculomotor nerve palsy first appearing one year before successful surgical ligation of a saccular aneurysm arising from the right posterior cerebral artery. During the subsequent postoperative period of two years, oculomotor nerve functions improved as the result of regeneration. Extensive morphometric evaluation of the regenerated nerve was compared to the normal side at the light microscopic level. The affected nerve showed a reduction in the transverse area (62%), estimated number of fibers (49%), and mean diameter of myelinated axons (23%). The normal g-ratio of axon to total diameter was almost constant at 0.64, but on the regenerated side it increased to 0.73. An increase in unmyelinated axons and connective tissue endoneurium was evident at the ultrastructural level. The significance of these marked quantitative changes was compared to the partial return of oculomotor nerve function.