Spinocerebellar ataxia type 8 (SCA8) is a rare hereditary cerebellar ataxia showing mainly pure cerebellar ataxia. We herein report cases of SCA8 in Japanese monozygotic twins that presented with ...nystagmus, dysarthria, and limb and truncal ataxia. Their ATXN8OS CTA/CTG repeats were 25/97. They showed similar manifestations, clinical courses, and cerebellar atrophy on magnetic resonance imaging. Some of their pedigrees had nystagmus but not ataxia. These are the first monozygotic twins with SCA8 to be reported anywhere in the world. Although not all subjects with the ATXN8OS CTG expansion develop cerebellar ataxia, these cases suggest the pathogenesis of ATXN8OS repeat expansions in hereditary cerebellar ataxia.
The suppression of gene expression of vascular endothelial growth factor (VEGF) which regulates tumor angiogenesis
in vivo and is an important factor in tumor growth represents a novel approach to ...cancer treatment. Although small interfering RNA (siRNA) has rapidly become a major tool in gene therapy and is a key inhibitory factor of gene expression, its effect is temporary. The present study investigates the preparation of long-term sustained release poly (
dl-lactic/glycolic acid) (PLGA) microspheres encapsulating anti-VEGF siRNA with a carrier (arginine or branched polyethylenimine) using the w/o/w in-water drying method and their anti-tumor activities. The ratio (%) of encapsulated siRNA increased when arginine or PEI was added to the inner water phase during preparation. The release of siRNA from microspheres in phosphate buffer (pH 7.4) was sustained for over one month. The anti-tumor effects of microspheres
in vivo were evaluated in mice bearing S-180 tumors. An intra-tumor injection of microspheres with encapsulated siRNA obviously suppressed tumor growth. These results indicate that the microspheres of anti-VEGF siRNA with a transfection agent (carrier) have achieved a higher and sustained suppressive effect on VEGF gene expression and should be a practically useful preparation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Head CT, which includes the facial region, can visualize faces using 3D reconstruction, raising concern that individuals may be identified. We developed a new de-identification technique that ...distorts the faces of head CT images. Head CT images that were distorted were labeled as "original images" and the others as "reference images." Reconstructed face models of both were created, with 400 control points on the facial surfaces. All voxel positions in the original image were moved and deformed according to the deformation vectors required to move to corresponding control points on the reference image. Three face detection and identification programs were used to determine face detection rates and match confidence scores. Intracranial volume equivalence tests were performed before and after deformation, and correlation coefficients between intracranial pixel value histograms were calculated. Output accuracy of the deep learning model for intracranial segmentation was determined using Dice Similarity Coefficient before and after deformation. The face detection rate was 100%, and match confidence scores were < 90. Equivalence testing of the intracranial volume revealed statistical equivalence before and after deformation. The median correlation coefficient between intracranial pixel value histograms before and after deformation was 0.9965, indicating high similarity. Dice Similarity Coefficient values of original and deformed images were statistically equivalent. We developed a technique to de-identify head CT images while maintaining the accuracy of deep-learning models. The technique involves deforming images to prevent face identification, with minimal changes to the original information.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chemical modification has been performed on an orally bioavailable and potent CCR5 antagonist, sulfoxide compound 4, mainly focusing on replacement of the 6,7-fused 1-benzazepine nucleus. We ...designed, synthesized, and evaluated the biological activities of ring-expanded 6,8-, 6,9-, and 6,10-fused compounds containing S-sulfoxide moieties, which led to the discovery of 1-benzazocine and 1-benzazonine compounds that exhibited potent inhibitory activities (equivalent to compound 4) in a binding assay. In addition, 1-benzazocine compounds possessing the S-sulfoxide moiety (( S )-(−)-5a,b,d,e) showed greater potency than compound 4 in a fusion assay. From further investigation in a multi-round infection assay, it was found that 1-isobutyl-1-benzazocine compound ( S )-(−)-5b, containing the S-{(1-propyl-1H-imidazol)-5-ylmethyl}sulfinyl group, showed the most potent anti-HIV-1 activity (IC90 = 0.81 nM, in MOLT4/CCR5 cells). Compound ( S )-(−)-5b (TAK-652) also inhibited the replication of six macrophage-tropic (CCR5-using or R5) HIV-1 clinical isolates in peripheral blood mononuclear cells (PBMCs) (mean IC90 = 0.25 nM). It was also absorbed after oral administration in rats, dogs, and monkeys and was thus selected as a clinical candidate. The synthesis and biological activity of the 1-benzazocine compound ( S )-(−)-5b and its related derivatives are described.
Spinocerebellar ataxia type 8 (SCA8) is a rare hereditary cerebellar ataxia showing mainly pure cerebellar ataxia. We herein report cases of SCA8 in Japanese monozygotic twins that presented with ...nystagmus, dysarthria, and limb and truncal ataxia. Their ATXN8OS CTA/CTG repeats were 25/97. They showed similar manifestations, clinical courses, and cerebellar atrophy on magnetic resonance imaging. Some of their pedigrees had nystagmus but not ataxia. These are the first monozygotic twins with SCA8 to be reported anywhere in the world. Although not all subjects with the ATXN8OS CTG expansion develop cerebellar ataxia, these cases suggest the pathogenesis of ATXN8OS repeat expansions in hereditary cerebellar ataxia.
In the present study, in order to reveal novel adverse effects of ultrafine particles (UFP) on the central nervous system, the effects of nanoparticle-rich diesel exhaust particles (NRDEP; count mode ...diameter, 21.45 nm) on emotional behavior, learning capability and brain neurotransmitter levels were studied in rats by intranasal instillation (iNI). NRDEP (10 and 50 µg/rat) was instilled into 2-week old infant, male rats once a week for 4 weeks. Spontaneous motor activity measured was observed to be inverse to the dose level. In active avoidance tests using a shuttle box, NRDEP-treated animals showed a lower avoidance performance than control animals given air-instillation. The levels of dopamine and its metabolite (DOPAC) in the medial mammillary nucleus of the brain tended to be lower in the NRDEP-treated animals. From these results, although the effects of NRDEP by iNI on the emotionality and the brain neurotransmitter levels were not fully clear, the results obtained by avoidance testing suggested involvement of UFP in learning capability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK