Colocalization of 14-3-3 Proteins with SOD1 in Lewy Body-Like Hyaline Inclusions in Familial Amyotrophic Lateral Sclerosis Cases and the Animal Model

Background and Purpose: Cu/Zn superoxide dismutase (SOD1) is a major component of Lewy body-like hyaline inclusion (LBHI) found in the postmortem tissue of SOD1-linked familial amyotrophic lateral sclerosis (FALS) patients. In our recent studies, 14-3-3 proteins have been found in the ubiquitinated inclusions inside the anterior horn cells of spinal cords with sporadic amyotrophic lateral sclerosis (ALS). To further investigate the role of 14-3-3 proteins in ALS, we performed immunohistochemical analysis of 14-3-3 proteins and compared their distributions with those of SOD1 in FALS patients and SOD1-overexpressing mice. Methods: We examined the postmortem brains and the spinal cords of three FALS cases (A4V SOD1 mutant). Transgenic mice expressing the G93A mutant human SOD1 (mutant SOD1-Tg mice), transgenic mice expressing the wild-type human SOD1 (wild-type SOD1-Tg mice), and non-Tg wild-type mice were also subjected to the immunohistochemical analysis. Results: In all the FALS patients, LBHIs were observed in the cytoplasm of the anterior horn cells, and these inclusions were immunopositive intensely for pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$. In the mutant SOD1-Tg mice, a high degree of immunoreactivity for misfolded SOD1 (C4F6) was observed in the cytoplasm, with an even greater degree of immunoreactivity present in the cytoplasmic aggregates of the anterior horn cells in the lumbar spinal cord. Furthermore, we have found increased 14-3-3$\beta$ and 14-3-3$\gamma$ immunoreactivities in the mutant SOD1-Tg mice. Double immunofluorescent staining showed that C4F6 and 14-3-3 proteins were partially co-localized in the spinal cord with FALS and the mutant SOD1-Tg mice. In comparison, the wild-type SOD1-Tg and non-Tg wild-type mice showed no or faint immunoreactivity for C4F6 and 14-3-3 proteins (pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$) in any neuronal compartments. Discussion: These results suggest that 14-3-3 proteins may be associated with the formation of SOD1-containing inclusions, in FALS patients and the mutant SOD1-Tg mice.Mathematic

Epsilon Launch Vehicle - First Flight and its Evolutions -

The first Epsilon launch vehicle was successfully launched from Uchinoura Space Center (USC) on September 14th, 2013. Epsilon has achieved full mission success by injecting SPRINT-A into planned orbit with high accuracy. Epsilon is now ready to offer launch opportunities for small payloads to the Low Earth Orbit (LEO) and Sun Synchronous Orbit (SSO). The paper consists of three parts. At first, this paper describes the main features of Epsilon launch vehicle, its mission profile and the brief summary of actual flight data. Secondly, the short-term development plan is presented, as Epsilon has to become more cost effective in order to meet the growing needs for lower cost. Finally a further development plan including design evolutions under study is presented

A laterally-spreading tumor in a colonic interposition treated by endoscopic submucosal dissection

Herein we describe an early colonic carcinoma which developed in a colonic interposition 14 years after surgery for esophageal cancer, which was successfully treated by endoscopic submucosal dissection (ESD). An 80-year-old man underwent colonic interposition between the upper esophagus and stomach after surgery for an early esophageal squamous cell carcinoma in 1994. He received a surveillance endoscopy, and a laterally-spreading tumor of granular type, approximately 20 mm in size, was identified in the colonic interposition. An endoscopic biopsy revealed moderately differentiated adenocarcinoma histologically, however, we diagnosed the lesion as an intramucosal carcinoma based on the endoscopic findings. The lesion was safely and completely removed en bloc by ESD using a bipolar knife. Histologically, the lesion was an intramucosal moderately differentiated adenocarcinoma in a tubular adenoma

Hypoxia Imaging Endoscopy Equipped with Laser Light Source from Preclinical Live Animal Study to First-In-Human Subject Research

<div><p>A goal in next-generation endoscopy is to develop functional imaging techniques to open up new opportunities for cancer diagnosis. Although spatial and temporal information on hypoxia is crucial for understanding cancer physiology and expected to be useful for cancer diagnosis, existing techniques using fluorescent indicators have limitations due to low spatial resolution and invasive administration. To overcome these problems, we developed an imaging technology based on hemoglobin oxygen saturation in both the tumor and surrounding mucosa using a laser endoscope system, and conducted the first human subject research for patients with aero-digestive tract cancer. The oxygen saturation map overlapped the images of cancerous lesions and indicated highly heterogeneous features of oxygen supply in the tumor. The hypoxic region of the tumor surface was found in both early cancer and cancer precursors. This technology illustrates a novel aspect of cancer biology as a potential biomarker and can be widely utilized in cancer diagnosis.</p></div

Clinicopathological findings of the study with gastric cancer patients.

<p>Clinicopathological findings of the study with gastric cancer patients.</p