Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-3 (IL-3) is an important mediator of physiological and pathophysiological processes affecting the central nervous system (CNS). It stimulates the proliferation and activation of microglia and can enhance differentiation of cholinergic and sensory neurons. To examine the role of IL-3 in the CNS, we utilized transgenic mice expressing a murine antisense IL-3 (AS-IL-3) RNA under the control of the T cell B19 promoter so that expression is limited to hematopoietic cells. The AS-IL-3 transgenic mice develop either a progressive neurologic dysfunction, which includes ataxia, bradykinesia, and paralysis, or a lymphoproliferative syndrome. Histopathology demonstrated accumulations of reactive astrocytes in the cerebellum, brain stem, and spinal cord, accompanied by activated microglia. Partial loss of cerebellar nuclei neurons as well as neurons in the cranial nerve nuclei and spinal cord motor neurons is seen. Despite depletion of IL-3 peripherally, expression of IL-3 mRNA and protein is turned on in the CNS of the transgenic mice. Astrocytes cultured from the AS-IL-3 mice contain IL-3 mRNA and may thus be responsible for the activation of the microglia. This model should provide important insights into the role of cytokines in neurological disorders.
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PMID:CNS interleukin-3 (IL-3) expression and neurological syndrome in antisense-IL-3 transgenic mice. 1033 36

Human parvovirus B19 generally causes erythema infectiosum in childhood, but it can be associated with unusual findings, particularly in immunocompromised patients. This is a report about an immunocompetent 4-year-old female child affected with acute encephalitis by parvovirus B19, documented by polymerase chain reaction performed on cerebrospinal fluid, who was treated with intravenous immunoglobulins and dexamethasone and who developed a cerebellar syndrome with ataxia, dysmetria, and dysarthria. To the best of the authors' knowledge, this may be the first report of human parvovirus B19 encephalitis complicated by severe ataxia in childhood.
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PMID:Severe ataxia as a complication of human parvovirus B19 acute encephalitis in a child. 1848 17

We previously reported in a large cohort (N = 104) of post-mortem tissues the detection of both the non-pathogenic adeno-associated virus (AAV2) in approximately 13% and the pathogenic human parvovirus B19 (B19) in approximately 42% of human brains, particularly the dorsolateral prefrontal cortex. Multiple animal parvoviruses target the developing cerebellum (CBLM) resulting in hypoplasia and ataxia, but very little is known about the human parvoviruses and their ability to infect or cause disease in the CBLM. We have now confirmed in the above cohort the presence of AAV2 and B19 sequences in the CBLM. Our results show that approximately 27% and approximately 70% of human CBLM are positive by nested polymerase chain reaction for AAV2 and B19 sequences, respectively. We also document in a second cohort (N = 10) the presence of AAV2 (50%) and B19 (100%) sequences in the CBLM and correlate our results for B19 with studies from matched sera. Eighty percent (80%) of this cohort was positive for anti-B19 IgG, while none were IgM+, suggesting that most individuals had been previously infected with B19 but none acutely. To our knowledge, this study is the first to demonstrate that both AAV2 and B19 sequences are present at relatively high frequencies in the CBLM and are likely due to persistent rather than acute infection. Further studies will lead to insights into AAV2- and/or B19-CBLM interactions including mechanisms of infection, persistence, and possibly neuropathology, including cerebellar hypoplasia and ataxia.
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PMID:Persistent adeno-associated virus 2 and parvovirus B19 sequences in post-mortem human cerebellum. 1958 79

Human parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells of the human bone marrow. Although the mechanism by which the B19V genome replicates in these cells has not been studied in great detail, accumulating evidence has implicated involvement of the cellular DNA damage machinery in this process. Here, we report that, in ex vivo-expanded human erythroid progenitor cells, B19V infection induces a broad range of DNA damage responses by triggering phosphorylation of all the upstream kinases of each of three repair pathways: ATM (ataxia-telangiectasi mutated), ATR (ATM and Rad3 related), and DNA-PKcs (DNA-dependent protein kinase catalytic subunit). We found that phosphorylated ATM, ATR, and DNA-PKcs, and also their downstream substrates and components (Chk2, Chk1, and Ku70/Ku80 complex, respectively), localized within the B19V replication center. Notably, inhibition of kinase phosphorylation (through treatment with either kinase-specific inhibitors or kinase-specific shRNAs) revealed requirements for signaling of ATR and DNA-PKcs, but not ATM, in virus replication. Inhibition of the ATR substrate Chk1 led to similar levels of decreased virus replication, indicating that signaling via the ATR-Chk1 pathway is critical to B19V replication. Notably, the cell cycle arrest characteristic of B19V infection was not rescued by interference with the activity of any of the three repair pathway kinases.
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PMID:Parvovirus B19 infection of human primary erythroid progenitor cells triggers ATR-Chk1 signaling, which promotes B19 virus replication. 2168 May 29