Hot cross bun" sign in multiple system atrophy with predominant cerebellar ataxia: a comparison between proton density-weighted imaging and T2-weighted imaging.

[Objective]: To investigate whether proton density-weighted imaging can detect the "hot cross bun" sign in the pons in multiple system atrophy with predominant cerebellar ataxia significantly better than T2-weighted imaging at 3T. [Methods]: Sixteen consecutive patients with multiple system atrophy with predominant cerebellar ataxia according to the Consensus Criteria were reviewed. Axial unenhanced proton density-weighted imaging and T2-weighted imaging were obtained using a dual-echo fast spin-echo sequence at 3T. Two neuroradiologists independently evaluated visualisation of the abnormal pontine signal using a 4-point visual grade from Grade 0 (no "hot cross bun" sign) to Grade 3 (prominent "hot cross bun" sign on two or more sequential slices). Differences in grade between proton density-weighted imaging and T2-weighted imaging were statistically analysed using the Wilcoxon signed-rank test. [Results]: In 11 patients (69%), a higher grade was given for proton density-weighted imaging than T2-weighted imaging. In 1 patient (6%), grades were the same (Grade 3) on both images. In the remaining 4 patients (25%), signal abnormalities were not detected on either image (Grade 0). The "hot cross bun" sign was thus observed significantly better on proton density-weighted imaging than on T2-weighted imaging (P = 0.001). [Conclusions]: The "hot cross bun" sign considered diagnostic for multiple system atrophy with predominant cerebellar ataxia is significantly better visualised on proton density-weighted imaging than on T2-weighted imaging at 3T

A two-stage deflection system for the extension of the energy coverage in space plasma three-dimensional measurements

Abstract The in situ measurement of charged particles plays a key role in understanding space plasma physics. Velocity distribution functions of ions and electrons have been acquired with electrostatic analyzers onboard spacecraft. Since conventional energy analyzers (e.g., top-hat electrostatic analyzers) have essentially a two-dimensional field of view, the solid angle coverage is achieved with the aid of spacecraft spin motion or with additional entrance deflection systems in front of the electrostatic analyzer. In the latter case, however, the full angular scan is realized only in the lower energy range (typically only up to 5–15 keV/e), due to the limitation of the electric field applied to the deflector. Here we propose a novel deflection system for extending the energy coverage up to tens of keV. This is especially useful for plasma observations in situations where the anisotropy of the energetic part (> 10 keV) of charged particles plays an essential role in plasma dynamics and hence is of significant interest. Graphical Abstrac

SOD2 protects against oxidation-induced apoptosis in mouse retinal pigment epithelium: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci.

PURPOSE. Oxidative stress from reactive oxygen species (ROS) has been implicated in many diseases, including age-related macular degeneration (AMD), in which the retinal pigment epithelium (RPE) is considered a primary target. Because manganese superoxide dismutase (SOD2), localized in mitochondria, is known to be a key enzyme that protects the cells against oxidative stress, this study was undertaken to examine oxidation-induced apoptosis in cultured RPE cells with various levels of SOD2. METHODS. Primary cultures of RPE cells were established from wild-type (WT), heterozygous Sod2-knockout mouse (HET) and hemizygous Sod2 mice with overexpression of the enzyme (HEMI). Purity of the RPE cell cultures was verified by immunostaining with antibody to RPE65 and quantified by flow cytometry. Oxidative stress was induced in RPE cells by exposing them to H 2 O 2 (0 -500 M) for 1 hour and reculturing them in normal medium for various times (0 -24 hours). Apoptosis in the RPE was examined by TUNEL staining and quantified by cell-death-detection ELISA. Mitochondrial transmembrane potential (MTP) was measured by a cationic dye, and cytochrome c leakage from mitochondria was analyzed by Western blot analysis. RESULTS. More than 95% of the cells in each culture were RPE65 positive, and the relative SOD2 levels in HET, WT, and HEMI cells were 0.6, 1.0, and 3.4, respectively. H 2 O 2 -induced apoptotic cell death was both dose and time dependent, and apoptosis in these cells was related to the cellular SOD2 level. Disruption of MTP and release of cytochrome c were observed to occur before apoptotic cell death, and they correlated with cellular SOD2. CONCLUSIONS. The results demonstrate a critical role of SOD2 in protection against oxidative challenge. Cells from HET mice showed greater apoptotic cell death, whereas in those from HEMI mice, cell death induced by oxidative injury was suppressed. (Invest Ophthalmol Vis Sci. 2005;46:3426 -3434

Targeted Suicide Gene Therapy with Retroviral Replicating Vectors for Experimental Canine Cancers

Cancer in dogs has increased in recent years and is a leading cause of death. We have developed a retroviral replicating vector (RRV) that specifically targets cancer cells for infection and replication. RRV carrying a suicide gene induced synchronized killing of cancer cells when administered with a prodrug after infection. In this study, we evaluated two distinct RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) in canine tumor models both in vitro and in vivo. Despite low infection rates in normal canine cells, both RRVs efficiently infected and replicated within all the canine tumor cells tested. The efficient intratumoral spread of the RRVs after their intratumoral injection was also demonstrated in nude mouse models of subcutaneous canine tumor xenografts. When both RRVs encoded a yeast cytosine deaminase suicide gene, which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil, they caused tumor-cell-specific 5-FC-induced killing of the canine tumor cells in vitro. Furthermore, in the AZACF- and AZACH-cell subcutaneous tumor xenograft models, both RRVs exerted significant antitumor effects. These results suggest that RRV-mediated suicide gene therapy is a novel therapeutic approach to canine cancers

Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate.

Phthalate esters have been used extensively as plasticizers of synthetic polymers. Recent studies have revealed that these esters induce atrophy of the testis, although its pathogenesis remains unknown. The present study describes the possible involvement of oxidative stress in the pathogenesis of atrophy of the rat testis induced by di(2-ethylhexyl)phthalate (DEHP). Biochemical and immunohistochemical analysis revealed that oral administration of DEHP increased the generation of reactive oxygen species, with concomitant decrease in the concentration of glutathione and ascorbic acid in the testis, and selectively induced apoptosis of spermatocytes, thereby causing atrophy of this organ. Oxidative stress was selectively induced in germ cells, but not in Sertoli cells, treated with mono(2-ethylhexyl)phthalate (MEHP), a hydrolysed metabolite of DEHP. Furthermore, MEHP selectively induced the release of cytochrome c from mitochondria of the testis. These results indicate that oxidative stress elicited by MEHP principally injured mitochondrial function and induced the release of cytochrome c, thereby inducing apoptosis of spermatocytes and causing atrophy of the testis