1/6. Adenovirus encephalitis and widespread ependymitis in a child with AIDS.A 4-year-old child with AIDS developed encephalitis 2 months prior to death. Adenovirus was cultured from the cerebrospinal fluid. At autopsy, sections of the brain revealed complete sloughing of the intracranial ependyma, with marked gliosis and edema of the periventricular white matter. cells with large, dark, smudgy intranuclear inclusions, consistent with adenovirus inclusions, were also seen in subependymal locations. in situ hybridization studies confirmed the presence of adenovirus dna in these cells. This represents a case of morphologically proven adenovirus encephalitis in a pediatric AIDS patient.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/6. Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome.The multifunctional cytokine, transforming growth factor beta (TGF-beta), was identified by immunocytochemistry in the brain tissues of four patients with acquired immune deficiency syndrome (AIDS), but not in control brain tissue. The TGF-beta staining was localized to cells of monocytic lineage as well as astrocytes, especially in areas of brain pathology. In addition, the brain tissues from the AIDS patients contained transcripts for human immunodeficiency virus 1 (hiv-1) by in situ hybridization, suggesting a correlation between the presence of hiv-1 in the brain and the expression of TGF-beta. However, the expression of TGF-beta was not limited to hiv-1-positive cells, raising the possibility of alternative mechanisms for the induction of TGF-beta in these AIDS patients' brains. To investigate these mechanisms, purified human monocytes were infected in vitro with hiv-1 and were shown to secrete increased levels of TGF-beta. In addition, hiv-1-infected monocytes released a factor(s) capable of triggering cultured astrocytes that are not infected with hiv-1 to secrete TGF-beta. The release of TGF-beta, which is an extremely potent chemotactic factor, may contribute to the recruitment of hiv-1-infected monocytic cells, enabling viral spread to and within the central nervous system (CNS). Moreover, TGF-beta augments cytokine production, including cytokines known to be neurotoxic. The identification of TGF-beta within the CNS implicates this cytokine in the immunopathologic processes responsible for AIDS-related CNS dysfunction.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/6. Severe encephalitis resulting from coinfections with HIV and jc virus.We observed 3 cases of progressive multifocal leukoencephalopathy (PML) among frozen CNS samples obtained at autopsy from 102 adult AIDS patients. In 2 patients, PML was associated with severe HIV encephalitis. In those 2 cases, the areas of extensive JC-induced demyelination were massively infiltrated by HIV infected macrophages/microglial cells with evidence for localized increase of HIV encephalitis in PML lesions. Using immunohistochemistry and in situ hybridization, we demonstrated that each virus infects, in a latent or productive fashion, different CNS cell populations. Therefore, the extension of HIV encephalitis could not be related to an intracellular transactivation of 1 virus by the other. However, the results are consistent with dissemination of viral infection by the recruitment of HIV-infected macrophages to damaged areas of the brain. This phenomenon might be generalized to other pathogens that are frequently associated with HIV CNS infection. Early detection and treatment of opportunistic CNS lesions could be important to prevent extension of HIV encephalitis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/6. Multifocal vacuolar leucoencephalopathy: a distinct HIV-associated lesion of the brain.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.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/6. In situ amplification and detection of hiv-1 dna in fixed pediatric AIDS brain tissue.To examine whether latent infection by hiv-1 occurs in the central nervous system, we optimized a procedure for amplification and detection of hiv-1 dna in situ, in formalin-fixed brain tissue from a child with severe hiv-1-associated progressive encephalopathy and severe hiv-1 encephalitis. By the use of a two-step technique, which involved polymerase chain reaction with incorporation of digoxigenin-labeled nucleotides followed by in situ hybridization with biotinylated probes, we found infection of numerous mononuclear cells and astrocytes in the cerebral white matter as well as of perineuronal satellite cells in basal ganglia, but not of neurons. Following PCR amplification, nuclear signal was found in 10 to 20 times as many cells as in parallel, control experiments using conventional, unamplified in situ hybridization.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
6/6. Low-grade monoclonal Epstein-Barr virus-associated lymphoproliferative disorder of the brain presenting as human immunodeficiency virus-associated encephalopathy in a child with acquired immunodeficiency syndrome.The association of the Epstein-Barr virus with human immunodeficiency virus-associated primary central nervous system lymphomas is well known. We describe a pediatric patient infected with human immunodeficiency virus who developed a lesion in the central nervous system that appeared to be histologically reactive and that proved to be an Epstein-Barr virus-associated monoclonal B-cell lymphoproliferative disorder by molecular analysis. An 8-year-old girl was diagnosed with vertically transmitted human immunodeficiency virus infection at age 5, for which she was treated empirically with a combination of zidovudine and didanosine. At the age of 7 years, during evaluation for entry into an antiretroviral protocol, a single hypodense frontal lobe lesion was identified by computed tomography. After unsuccessful treatment for presumed toxoplasmosis and progressive neurologic deterioration, a stereotactic brain biopsy was performed. Although the biopsy contained a polymorphic lymphoid infiltrate that appeared to be cytologically reactive, polymerase chain reaction and in situ hybridization studies revealed a monoclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder, which was reminiscent of polymorphic B-cell hyperplasia observed in the setting of immunosuppression following organ transplantation. Postoperative therapy included steroids and antiretroviral therapy. The lesion decreased slightly in size, and the child's neurologic status was relatively unremarkable for 5 months. Subsequently, she developed cytomegalovirus retinitis, progressive encephalopathy, and died with pancytopenia. This case represents a newly described manifestation of Epstein-Barr virus-associated lymphoproliferative disorder, a diagnosis that should be considered in patients with neurologic symptoms and immunodeficiency. In addition, this case exhibited histologic features reminiscent of posttransplant lymphoproliferative disease, a histologic pattern that to our knowledge has not previously been reported in the setting of acquired immunodeficiency syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |