高機能自閉症者のパニック軽減についての一考察 : 事例Kを通じて

Autistic children and adults easily panic when they cannot handle a particular situation. Resulting panic behaviors repulse surrounding people such as classmates and neighbors, which may lead to isolation of the autistic individual. Therefore, reducing an autistic person's panic behaviors has the potential to make him or her more acceptable to society. As one method to reduce panic behaviors we chose to improve communication by introducing a cellular phone capable of e-mail communication. The case was a 26-year autistic man, who had graduated from high school. He had a high level of language skill although his conversational skill was quite limited (referred to as "K" hereafter). When K had trouble in crowd of people, he loudly asked for help if somebody who he knew was nearby. When K could not communicate well, he repeated the same words or question many times. In a panic situation K swung his arms widely and sometimes waved his hand so vigorously that the fingers bounced against one another and made a loud tapping sound. ((His therapists could do nothing but patiently listen to his explanation about these behaviors after he had calmed down.)) We arranged for K to use a cellular phone to communicate with his mother through e-meil when he had trouble or could not select among available items in a choice situation such as in a store. Six months later he began to communicate with his previous and current therapists, and his e-mail messages gradually became more comprehensible. Over one and half years after he started using the cellular phone, the following changes were noted : 1) Reduced incidence of panic behaviors, 2) More willing to talk or send e-mails about the cause of his panic behaviors, 3) Improved verbal and e-mail expression of feelings and emotional upset and 4) Increased frequency of approaching people using phrases such as "Would you like to・・・" or "I think it will be fun to・・・." Thus, we demonstrated that e-mail communication using a cellular phone may reduce panic behaviors and enrich language expression in high functioning autistic adults

Importin-β and the small guanosine triphosphatase Ran mediate chromosome loading of the human chromokinesin Kid

Nucleocytoplasmic transport factors mediate various cellular processes, including nuclear transport, spindle assembly, and nuclear envelope/pore formation. In this paper, we identify the chromokinesin human kinesin-like DNA binding protein (hKid) as an import cargo of the importin-α/β transport pathway and determine its nuclear localization signals (NLSs). Upon the loss of its functional NLSs, hKid exhibited reduced interactions with the mitotic chromosomes of living cells. In digitonin-permeabilized mitotic cells, hKid was bound only to the spindle and not to the chromosomes themselves. Surprisingly, hKid bound to importin-α/β was efficiently targeted to mitotic chromosomes. The addition of Ran–guanosine diphosphate and an energy source, which generates Ran–guanosine triphosphate (GTP) locally at mitotic chromosomes, enhanced the importin-β–mediated chromosome loading of hKid. Our results indicate that the association of importin-β and -α with hKid triggers the initial targeting of hKid to mitotic chromosomes and that local Ran-GTP–mediated cargo release promotes the accumulation of hKid on chromosomes. Thus, this study demonstrates a novel nucleocytoplasmic transport factor–mediated mechanism for targeting proteins to mitotic chromosomes

Outcomes of definitive chemoradiotherapy for stage iva (T4b vs. n4) esophageal squamous cell carcinoma based on the japanese classification system: A retrospective single-center study

The differences in prognoses or progression patterns between T4b non-N4 and non-T4b N4 esophageal squamous cell carcinoma post chemoradiotherapy (CRT) is unclear. This study compared the outcomes of CRT for stage IVa esophageal squamous cell carcinoma according to T/N factors. We retrospectively identified 66 patients with stage IVa esophageal squamous cell carcinoma who underwent definitive CRT at our center between January 2009 and March 2013. The treatment outcomes, i.e., progression patterns, prognostic factors, and toxicities based on version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events, were studied. The patients (56 men and 10 women) had a median age of 67 (range: 37–87) years. The T/N classifications were T4b non-N4 (28/66), non-T4b N4 (24/66), and T4b N4 (14/66). Objective response was achieved in 57 patients (86.4%, (95% confidence interval, 74.6–94.1%)). There were no significant differences between the T/N groups in terms of overall survival, progression-free survival, and progression pattern. We found no significant differences in prognoses or progression patterns among patients with T4b non-N4, non-T4b N4, and T4b N4 esophageal squamous cell carcinoma. Thus, it seems impractical to modify CRT regimens based on T/N factors

Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system: a study using green fluorescent protein transgenic zebrafish

Nitro-fatty acids are electrophilic fatty acids produced in vivo from nitrogen peroxide that have many physiological activities. We recently demonstrated that nitro-fatty acids activate the Keap1-Nrf2 system, which protects cells from damage owing to electrophilic or oxidative stresses via transactivating an array of cytoprotective genes, although the molecular mechanism how they activate Nrf2 is unclear. A number of chemical compounds with different structures have been reported to activate the Keap1-Nrf2 system, which can be categorized into at least six classes based on their sensing pathways. In this study, we showed that nitro-oleic acid (OA-NO2), one of major nitro-fatty acids, activates Nrf2 in the same manner that of a cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) using transgenic zebrafish that expresses green fluorescent protein (GFP) in response to Nrf2 activators. In transgenic embryos, GFP was induced in the whole body by treatment with OA-NO2, 15d-PGJ2 or diethylmaleate (DEM), but not with hydrogen peroxide (H2O2), when exogenous Nrf2 and Keap1 were co-overexpressed. Induction by OA-NO2 or 15d-PGJ2 but not DEM was observed, even when a C151S mutation was introduced in Keap1. Our results support the contention that OA-NO2 and 15d-PGJ2 share an analogous cysteine code as electrophiles and also have similar anti-inflammatory roles