With the exception of a few granule cells, there was no sign of invasion of other neurons or astrocytes. Massive neuronal infection has been demonstrated in several entities associated with JCV, such as granule cell neuronopathy[21, 32, buy Rucaparib 33]
and fulminant encephalopathy with productive infection of cortical pyramidal neurons. The striking CD8 and microglial perineuronal infiltrates in the pons, may suggest greater sensitivity of the host’s immunological system to recognize early JCV neuronal invasion, than the ability of the immunohistochemical methods to detect the virus at the light microscopic level. PML tends to involve subcortical white matter, mostly in the frontal and parieto-occipital areas.[1-3] Predominantly infratentorial localization of PML in non-AIDS patients is approximately 10 times less common than the cerebral form. Since 1958, when PML was first described, close to 30 case reports of infratentorial PML have been listed in Medline; however, none in RA patients. In view of the increasing array of new and powerful immunomodulators in the treatment of
CX-5461 concentration autoimmune diseases, this case highlights the importance of considering PML in the differential diagnosis for acute or subacute onset of cerebellar or brainstem symptoms in patients with RA on immunosuppressant therapy. Although the frequency of PML with methotrexate use is very low, given the almost uniformly fatal consequences of this infection, patients should be warned of the risk of this complication. Supported in part by NIH grants R56 NS 041198, R01 NS 047029, R01074995 and K24 NS 060950 to IJK. We would like to thank Ms. Bruna Capretta for her help in preparation of the manuscript and Cyprian Estrada for his assistance with photographic documentation. why “
“Drug resistance is one of the most formidable obstacles for treatment of glioma. Eukaryotic initiation factor 4E-binding
protein (4E-BP1), a key component in the rate-limiting step of protein translation initiation, is closely associated with poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is involved in the drug resistance of human glioma. Herein we show that the expression of 4E-BP1 in human SWOZ2-BCNU drug-resistant glioma cells is significantly lower than that of the parent SWOZ2 cell line. Moreover, down-regulation of 4E-BP1 by short interfering RNA significantly impaired the sensitivity of SWOZ2 and U251 cells to carmustine (BCNU). Furthermore, overexpression of 4E-BP1 with plasmid transfection regained this sensitivity. Clinical studies showed that the expression levels of 4E-BP1 in primary glioma tissues were markedly higher than those of recrudescent glioma tissues. Taken together, our results suggest that 4E-BP1 is a novel protein that contributes to acquired drug resistance and it may be a potential target for reversing drug resistance in human glioma.