[HIV encephalopathy and neural stem cell virology].
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AIDS Dementia Complex↗
Biomedical subjects
Yoshiharu Miura
Publications and source records attributed to Yoshiharu Miura.
[Posterior leukoencephalopathy syndrome presenting with bilateral ataxie optique: a case report].
We report a 45 years old right-handed woman who developed acute respiratory distress syndrome (ARDS) after the operation for rupture of an ovarian cyst. One week after the onset of ARDS, she presented visual disturbance and Gerstmann syndrome. MRI T2-weighted images demonstrated abnormal high intensity lesions involving the gray and white matter of the occipital lobes bilaterally extending to the parietal lobes. Based on these findings, she was diagnosed as having posterior leukoencephalopathy syndrome (PLES). Her neurologic symptoms gradually improved, however, she started to complain of difficulty in grasping a cup placed on her peripheral visual fields. Neurological examination revealed no visual disturbance, weakness or cerebellar ataxia. She could easily reach objects presented in the central visual field, however, she could not grasp objects presented peripheral visual fields, while she was looking straight ahead. This disorder was observed both in the right and left visual field, whether she used the right hand or the left hand. We thought she had ataxie optique of Garcin. She was noted to have bilateral both direct and crossed ataxie optique. Ataxie optique is characterized by disturbance in reaching objects presented in the peripheral visual field. The underlying pathophysiologic mechanism is believed to be disconnection of the fibers between the primary visual area and the angular gyrus at the parietooccipital junction. Crossed ataxie optique consisting of difficulty in reaching objects presented in the contralateral visual field believed to be caused by disconnection of crossed pathways of the corpus callosum. Ataxie optique in our patient can be explained by disconnection of both direct and crossed fibers. Ataxie optique is sometimes unrecognized by the patient. Our patient suggests that ataxie optique may well be a symptom of PLES.
Ataxia↗
[HIV encephalopathy].
HIV encephalopathy is one of the complexified viral diseases. In the infected brains, HIV-infection is restricted in macrophages and microglia although its damage extends to neurons and oligodendrocytes. Accumulating evidences have suggested that many viral and host factors are involved in this disease. However, its precise mechanism is still unsolved. To examine the mechanism of the disease, we developed an HIV-1-infected human cell-transplanted mouse model and TNF-related apoptosis-inducing ligand was identified as a neurotoxic host factors in HIV-infected brain. Next, we examined the neurotoxic host factors using co-culture system with macrophage-tropic HIV-1-infected macrophages as followings: Target brain cells are murine neuron/glia mixed culture, murine neurospehre-forming culture and rat brain hippocampus slice culture. In these systems, neurons and neural stem cells were preferentially damaged. On the other hand, we also identified two anti-HIV genes, CD 14 and CD63 (dN), which inhibit HIV-1-induced cytotoxicity using a lentiviral screening system. Because they express on monocyte or activated macrophage and microglia, these results suggest that CXCR4-using HIV-1 cannnot expand inside of brain. We also extended the screening system to identify the host factors which protect against HIV-1-induced encephalopathy. Our study will contibute to development of new therapeutic strategy for HIV encephalopathy as well as other CNS diseases.
AIDS Dementia Complex↗
[A new murine model of HIV-associated encephalopathy].
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AIDS Dementia Complex↗
Molecular evolution of adenylating domain of aminoadipate reductase.
BACKGROUND: Aminoadipate reductase (Lys2) is a fungal-specific protein. This enzyme contains an adenylating domain. A similar primary structure can be found in some bacterial antibiotic/peptide synthetases. In this study, we aimed to determine which bacterial adenylating domain is most closely related to Lys2. In addition, we analyzed the substitution rate of the adenylating domain-encoding region. RESULTS: Some bacterial proteins contain more than two similar sequences to that of the adenylating domain of Lys2. We compared 67 amino acid sequences from 37 bacterial and 10 fungal proteins. Phylogenetic trees revealed that the lys2 genes are monophyletic; on the other hand, bacterial antibiotic/peptide synthase genes were not found to be monophyletic. Comparative phylogenetic studies among closely related fungal lys2 genes showed that the rate of insertion/deletion in these genes was lower and the nucleotide substitution rate was higher than that in the internal transcribed spacer (ITS) regions. CONCLUSIONS: The lys2 gene is one of the most useful tools for revealing the phylogenetic relationships among fungi, due to its low insertion/deletion rate and its high substitution rate. Lys2 is most closely related to certain bacterial antibiotic/peptide synthetases, but a common ancestor of Lys2 and these synthetases evolutionarily branched off in the distant past.
Adenosine↗
Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection.
HIV-1 infection in the brain induces neuronal apoptosis leading to HIV-associated dementia. To explore the underlying mechanism, we developed a murine model by using human peripheral blood mononuclear cell (PBMC)-transplanted nonobese diabetic (NOD)-severe combined immunodeficiency (SCID) (hu-PBMC-NOD-SCID) mice. Administration of lipopolysaccharide (LPS) to HIV-1-infected hu-PBMC-NOD-SCID mice induced infiltration of HIV-1-infected human cells into the perivascular region of the brain and neuronal apoptosis was found in macrophage (M)-tropic but not T cell (T)-tropic HIV-1-infected brains. The apoptotic neurons were frequently colocalized with the HIV-1-infected macrophages that expressed tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Administration of a neutralizing antibody against human TRAIL but not human TNF-alpha or Fas ligand (FasL) blocked the neuronal apoptosis in the HIV-1-infected brain. These results strongly suggest a critical contribution of TRAIL expressed on HIV-1-infected macrophages to neuronal apoptosis.
Animals↗
TNF-related apoptosis-inducing ligand (TRAIL) induces neuronal apoptosis in HIV-encephalopathy.
Neuronal loss is, frequently found in brains of patients with human immunodeficiency virus (HIV)-encephalopathy. Extensive apoptosis of neurons is probably involved in the development of HIV-encephalopathy. The present study was designed to investigate the mechanism of neuronal apoptosis. For this purpose, we examined autopsy brains of two patients with HIV-encephalopathy. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and active forms of caspase-3- and -8-positive cells, including neurons, were found in the perivascular regions of the brains. In these regions, TNF-related apoptosis-inducing ligand (TRAIL)+ macrophages were also observed. We also examined brains of HIV-1-infected mouse model inoculated with human cells. In these brains, TUNEL+ neurons were also found in the perivascular region, the site where infiltrated HIV-1-infected and TRAIL-expressing macrophages were observed. Using an in vitro-culture system, we also demonstrated that the HIV-1-infected monocyte-derived macrophages preferentially expressed TRAIL and that the addition of HIV-1-infected macrophages or human TRAIL-overexpressing mouse cells to cultured mouse primary neurons/glia resulted in neuronal apoptosis. Our results suggest the involvement of TRAIL expressed on HIV-1-infected macrophages in the induction of neuronal apoptosis in infected brain.
AIDS Dementia Complex↗
Aminoadipate reductase gene: a new fungal-specific gene for comparative evolutionary analyses.
BACKGROUND: In fungi, aminoadipate reductase converts 2-aminoadipate to 2-aminoadipate 6-semialdehyde. However, other organisms have no homologue to the aminoadipate reductase gene and this pathway appears to be restricted to fungi. In this study, we designed degenerate primers for polymerase chain reaction (PCR) amplification of a large fragment of the aminoadipate reductase gene for divergent fungi. RESULTS: Using these primers, we amplified DNA fragments from the archiascomycetous yeast Saitoella complicata and the black-koji mold Aspergillus awamori. Based on an alignment of the deduced amino acid sequences, we constructed phylogenetic trees. These trees are consistent with current ascomycete systematics and demonstrate the potential utility of the aminoadipete reductase gene for phylogenetic analyses of fungi. CONCLUSIONS: We believe that the comparison of aminoadipate reductase among species will be useful for molecular ecological and evolutionary studies of fungi, because this enzyme-encoding gene is a fungal-specific gene and generally appears to be single copy.
Aldehyde Oxidoreductases↗
Death ligand-mediated apoptosis in HIV infection.
Apoptosis has been suggested to cause severe CD4+ T cell depletion in patients infected with HIV. This review focuses on the biological events involved in death ligand-induced apoptosis during HIV infection. Among these ligands, TRAIL appears critical in HIV-infection. Death ligand-induced apoptosis might be a major pathogenic event in many virus-induced diseases including AIDS and the clarification of its mechanism will aid in the development of therapeutic strategies.
Apoptosis↗