Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
J Neurovirol ; 14(6): 514-21, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19023687

ABSTRACT

Japanese encephalitis (JE) virus is a member of the encephalitic flaviviruses and frequently causes neurological sequelae in a proportion of patients who survive the acute phase of the infection. In the present study, we molecularly identified viral infection in the brain of mice with rigidity of hindlimbs and/or abnormal gait, in which JE virus particles appeared within membrane-bound vacuoles of neurons throughout the central nervous system. Deformation of tight junctions (TJs) shown as dissociation of endothelial cells in capillaries, implying that the integrity of the blood-brain barrier (BBB) has been compromised by JE virus infection. BBB permeability evidently increased in the cerebrum, but not in the cerebellum, of JE virus-infected mice intravenously injected with the tracer of Evans blue dye. This suggests that the permeability of the BBB differentially changed in response to viral infection, leading to the entry of JE virions and/or putatively infected leukocytes from the periphery to the cerebrum as the initial site of infection in the central nervous system (CNS). Theoretically, the virus spread to the cerebellum soon after the cerebrum became infected.


Subject(s)
Blood-Brain Barrier/virology , Cerebrum/virology , Encephalitis Virus, Japanese/physiology , Encephalitis, Japanese/virology , Virus Internalization , Animals , Blood-Brain Barrier/pathology , Cerebrum/blood supply , Cerebrum/pathology , Disease Models, Animal , Encephalitis, Japanese/pathology , Female , Mice , Mice, Inbred ICR , Tight Junctions/virology
2.
J Neurochem ; 103(2): 802-13, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17680984

ABSTRACT

Neuropathological hallmarks of Alzheimer's disease are extracellular senile plaques and intracellular neurofibrillary lesions. The neurofibrillary lesions mainly consist of the hyperphosphorylated microtubule-associated protein Tau predominantly expressed in the axon of CNS neurons. Hyperphosphorylation of Tau negatively affects its binding to tubulin and decreases the capacity to promote microtubule assembly. Among a number of proline-directed kinases capable of phosphorylating paired helical filament-Tau, glycogen synthase kinase 3beta (GSK3beta) was first identified as a Tau protein kinase I and has been demonstrated to phosphorylate Tau both in vivo and in vitro. However, the phosphorylation mechanism of Tau by GSK3beta remained unclear. In this study, we show that the T231 is the primary phosphorylation site for GSK3beta and the Tau227-237 (AVVRTPPKSPS) derived from Tau containing T231P232 motif is identified as the GSK3beta binding site with high affinity of a Kd value 0.82 +/- 0.16 mumol/L. Our results suggest that direct binding and phosphorylation of T231P232 motif by GSK3beta induces conformational change of Tau and consequentially alters the inhibitory activity of its N-terminus that allows the phosphorylation of C-terminus of Tau by GSK3beta. Furthermore, hyperphosphorylation reduces Tau's ability to promote tubulin assembly and to form bundles in N18 cells. T231A mutant completely abolishes Tau phosphorylation by GSK3beta and retains the ability to promote tubulin polymerization and bundle formation. Taken together, these results suggest that phosphorylation of T231 by GSK3beta may play an important role in Tau's hyperphosphorylation and functional regulation.


Subject(s)
Glycogen Synthase Kinase 3/metabolism , Threonine/metabolism , tau Proteins/physiology , Binding Sites , Blotting, Western , Cell Line , Circular Dichroism , Fluorescent Antibody Technique , Glycogen Synthase Kinase 3/physiology , Humans , Immunoprecipitation , Light , Neurofibrillary Tangles/genetics , Neurofibrillary Tangles/pathology , Phosphorylation , Plasmids/genetics , Protein Binding , Protein Conformation , Scattering, Radiation , Thrombin/metabolism , Transfection , Tubulin/biosynthesis , tau Proteins/metabolism
3.
J Pediatr Gastroenterol Nutr ; 44(2): 265-7, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17255842

ABSTRACT

Hepatosplenic T cell lymphoma (HSTCL) are rare cancers ( approximately 100 published cases worldwide) and comprise 5% of peripheral T cell lymphomas. As of October 5, 2006, the FDA's Adverse Event Reporting System has received 8 cases of HSTCL in young patients using infliximab, a tumor necrosis factor-alpha blocking agent, to treat inflammatory bowel disease (6 of the 8 cases had a fatal outcome). All 8 patients were receiving concomitant immunosuppressant therapy (eg, azathioprine, prednisone). It has not been established that infliximab had an exclusive or primary role in the pathogenesis of these HSTCL cases; however, it appears that patients using this product may be at greater risk for developing this rare lymphoma.


Subject(s)
Antibodies, Monoclonal/adverse effects , Gastrointestinal Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Liver Neoplasms/chemically induced , Lymphoma, T-Cell/chemically induced , Splenic Neoplasms/chemically induced , Adolescent , Adult , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Infliximab , Male
4.
Am J Trop Med Hyg ; 69(6): 648-51, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14740883

ABSTRACT

Japanese encephalitis (JE) is an important mosquito-borne viral disease in Southeast Asia. Isolation of JE virus from peripheral blood is usually difficult because of transient and low titer of viremia. An in situ reverse transcriptase-polymerase chain reaction (RT-PCR) method was designed to amplify gene (envelope) fragments of JE virus residing in peripheral blood mononuclear cells (PBMCs) without extraction of RNA. Baby hamster kidney-21 cells infected with the T1P1 strain of JE virus (an isolate from Armigeres subalbatus collected in Taiwan) were fixed with 4% paraformaldehyde and permeabilized with 0.1% Triton X-100. The RT-PCR was then performed in microtubes using digoxigenin-labeled primers. Virus-positive PBMCs were detected in mice at day 1 and day 3, but not day 5, after intravenous inoculation with JE virus, suggesting that detectable virus circulating in the blood of mice is present for only 2-3 days. On examination of mouse brain tissues, viral RNAs were absent until day 3 post-inoculation. This implied that virus migration from the peripheral blood into the central nervous system occurs at or after day 3 post-inoculation. This method is unique in that the reactions can be conducted in tubes; this makes it convenient, accurate, and efficient compared with the conventional in situ RT-PCR on slides.


Subject(s)
Encephalitis Virus, Japanese/isolation & purification , Encephalitis, Japanese/diagnosis , Reverse Transcriptase Polymerase Chain Reaction/standards , Animals , Brain/virology , Cells, Cultured , Cricetinae , DNA Primers , Encephalitis Virus, Japanese/genetics , Female , Humans , Leukocytes, Mononuclear/virology , Mice , Mice, Inbred ICR , RNA, Viral/analysis , RNA, Viral/blood , Sensitivity and Specificity
SELECTION OF CITATIONS
SEARCH DETAIL
...