The effect of leg hyperthermia using far infrared rays in bedridden subjects with type 2 diabetes mellitus

We examined the effect of leg hyperthermia on oxidative stress in bedridden subjects with type 2 diabetes mellitus using 15-min sessions of far infrared rays over a two-week period. Four subjects (male 1, female 3) incapacitated by a stroke were recruited for this study. All patients were admitted to Takahashi Central Hospital and ate the same hospital meals. Fasting plasma glucose, HbA1c, tumor necrosis factor (TNF)alpha, free fatty acid, leptin, adiponectin and plasma 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) levels as a marker of oxidative stress were measured on admission, just before and 2 weeks after local heating of the leg. Results showed that plasma total 8-epi-PGF2alpha levels were decreased significantly while TNFalpha levels were increased significantly. On the other hand, glucose, HbA1c, free fatty acid, leptin and adiponectin levels were not changed during the study period. These results suggest that repeated leg hyperthermia may protect against oxidative stress.</p

Survival motor neuron (SMN) protein in the spinal anterior horn cells of patients with sporadic amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving mainly the upper and lower motor neurons of adult humans. With regard to the pathomechanism of spinal anterior horn cell (AHC) degeneration in ALS, copy number abnormalities of the survival motor neuron (SMN) genes have been reported in sporadic (s) ALS. SMN protein is the protein responsible for the pathogenesis of spinal muscular atrophy (SMA), an autosomal recessive disease characterized by lower motor neuron loss and muscle atrophy. The disease is caused by deficiency of SMN protein induced by mutation of one of the SMA-associated genes, SMN1. To clarify the role of SMN protein in the degeneration of spinal AHCs in sALS, we examined the amount of cytoplasmic SMN protein in individual AHCs using cytofluorophotometry in 9 patients with sALS and 10 control subjects. It was found that: 1) SMN protein was present in the cytoplasm, nucleus and nucleolus of AHCs and in the nucleus of glial cells, 2) expression of SMN protein in AHCs was significantly associated with cell size in both sALS patients and controls, 3) expression of SMN protein per unit area in AHCs was similar in sALS patients and controls. These findings suggest that: 1) the amount of SMN protein in the cytoplasm of AHCs is strictly controlled in accordance with cell size, in both sALS patients and controls, 2) the amount of SMN protein in the AHCs of sALS patients may be reduced when the AHCs are atrophic, and 3) decrease of SMN protein in the AHCs of sALS patients may be a secondary, and not primary, phenomenon according to their sizes.ArticleBRAIN RESEARCH. 1372:152-159 (2011)journal articl

Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists.</p> <p>Method</p> <p>Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs.</p> <p>Results</p> <p>We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid base fraction, which contained PHS and DHS, or authentic PHS or DHS increased PPAR-dependent transcription. Additionally, phytoceramide stimulated PPARα activity in HepG2 hepatocytes, suggesting that phytoceramide activates genes regulated by PPARα.</p> <p>Conclusions</p> <p>Phytoceramide and yeast-derived sphingoid bases activate PPARs, whereas ceramide and dihydroceramide do not change the PPAR activity. The present findings suggest that phytoceramide acts as a PPAR ligand that would regulate PPAR-targeted genes.</p

Antitumor effects of α-bisabolol against pancreatic cancer.

In the present study, we investigated whether α-bisabolol, a sesquiterpene alcohol present in essential oils derived from a variety of plants, has antitumor effects against pancreatic cancer. α-Bisabolol induced a decrease in cell proliferation and viability in pancreatic cancer cell lines (KLM1, KP4, Panc1, MIA Paca2), but not in pancreatic epithelial cells (ACBRI515). α-Bisabolol treatment induced apoptosis and suppressed Akt activation in pancreatic cancer cell lines. Furthermore, α-bisabolol treatment induced the overexpression of early growth response-1 (EGR1), whereas EGR1 siRNA decreased the α-bisabolol-induced cell death of KLM1 cells. Tumor growth in both subcutaneous and peritoneal xenograft nude mouse models was significantly inhibited by intragastric administration of 1000 mg/kg of α-bisabolol, once a week for three weeks. The results indicate that α-bisabolol could be a novel therapeutic option for the treatment of pancreatic cancer

Inhibitory Effect of 1α-Hydroxyvitamin D3 on N-nitrosobis (2-oxopropyl)Amine-induced Cholangiocarcinogenesis in Syrian Hamsters

Sixty-three male 5-week-old Syrian hamsters received the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) s.c. in 5 weekly injections (the first, 70mg/kg body, and the remaining, 20mg/kg each). The hamsters that received BOP were given intragastric administration of 0.2ml of medium chain triglyceride (MCT) with or without 0.04μg of 1α-hydroxyvitamin D3 [1α(OH)D3] through a feeding tube for 12 weeks. Thus, 3 groups were assigned:Group 1;BOP alone (n＝20), Group 2;BOP＋MCT (n＝18) and Group 3;BOP＋1α(OH)D3 (n＝25). The mean body weight of Group 3 was lower than those of Groups 1 and 2 at the end of the experiment (p＜0.001,Tukey-Kramer HSD test). At the end of week 12, all surviving hamsters were put to sleep. The incidences of liver tumors were 80%, 72% and 32% in Groups 1, 2 and 3, respectively. The incidence of tumors in Group 3 was significantly lower than in Group 1 and Group 2 (p＜0.05, χ2-test). All tumors were cholangiocarcinoma. These results indicated that BOP-induced cholangiocarcinogenesis was suppressed by the supplemental administration of 1α(OH)D3

地球環境変動に伴う海洋音波伝搬減衰の長期変化

発表番号: 15-19 / 海洋音響学会2015年度研究発表会（2015年5月14日～15日, 東京大学） / 海洋音響学会2015年度研究発表会講演論文集から転

地震前後におけるアルゴフロートを用いた海洋物理データ収集の研究

Tohoku region Pacific Ocean earthquake that occurred on March 11, 2011, resulted in extensive damage to vast areas rangingfrom the Tohoku to Kanto. However, at the time of an earthquake occurrence, the research vessel which was researching aboutmarine in earthquake hypocenter area adjacent seas is not confirmed, and ocean physical data like water temperature or salinityincluding ocean sound speed data required for echo sounder etc. cannot be acquired. Therefore, paying attention to the oceanautomatic profiling system (Argo system) in this study. Currently, Argo float has deployed about 3600 units in all the worldocean. Thus, it does not require large-scale observation system by research ship or tethered buoy. And we became able to graspthe marine structure of the scale of the earth immediately and easily.In this study, tried the acquisition of ocean physical data from the Argo data (water temperature, salinity, pressure) which unfolded before and after an earthquake near the focal area. As a result, In this earthquakes associated with the huge tsunami,rapid water temperature change has been confirmed in the vicinity of the sea after the earthquake.In addition, we analyzed about Sumatra offing earthquake accompanied by a similar huge Tsunami. Data was acquired fromtwo Argo floats which was observation in the seismic center area of ocean in 2005. As a result, a few days after the tsunamioccurrence, the thing by which the ocean physical data indicates a profile different from usual was suggested. Thus, to variationsin sudden marine environment, Argo system has been shown to be one of the effective database.SSS02-04発表要旨 / 日本地球惑星科学連合2015年大会（2014年5月24日～5月28日, 幕張メッセ国際会議場） / 日本惑星科学連合の許諾に基づき本文ファイルを掲

Change of Sound Speed Profile in the Epicenter near the Large-scale Undersea Earthquake Observed by Ocean Observation Float

The Tohoku region Pacific Ocean earthquake that occurred on March 11, 2011, resulted in extensive damage in a vast area ranging from the Tohoku to Kanto. However, at the time of the earthquake, no research vessel was confirmed to be investigating marine life in the seas adjacent to epicenter area, so physical data like water temperature and salinity, as well as ocean sound speed data required for the echo sounder, could not be acquired. Therefore, in this study, we compute the sound speed profile from the Argo system data(water temperature, salinity, pressure) that was being deployed near the area of the epicenter both before and after the earthquake, and attempt to detect the change in the sound speed field. In addition, the Tohoku region Pacific Ocean earthquake and the Sumatra earthquake in December 2004, which were accompanied by a giant tsunami, were also investigated. Results showed that in the main temperature front between the central thermocline and deep-sea isothermal layer, water temperature did not change very much. However, we confirmed the tendency for the underwater sound speed to suddenly increase dramatically after an earthquake

Current state of therapeutic development for rare cancers in Japan, and proposals for improvement

This article discusses current obstacles to the rapid development of safe and effective treatments for rare cancers, and considers measures required to overcome these challenges. In order to develop novel clinical options for rare cancers, which tend to remain left out of novel therapeutic development because of their paucity, efficient recruitment of eligible patients, who tend to be widely dispersed across the country and treated at different centers, is necessary. For this purpose, it is important to establish rare cancer registries that are linked with clinical studies, to organize a central pathological diagnosis system and biobanks for rare cancers, and to consolidate patients with rare cancers to facilities that can conduct clinical studies meeting international standards. Establishing an all‐Japan cooperative network is essential. Clinical studies of rare cancers have considerable limitations in study design and sample size as a result of paucity of eligible patients and, as a result, the level of confirmation of the efficacy and safety shown by the studies is relatively low. Therefore, measures to alleviate these weaknesses inherent to external conditions need to be explored. It is also important to reform the current research environment in order to develop world‐leading treatment for rare cancers, including promotion of basic research, collaboration between industry and academia, and improvement of the infrastructure for clinical studies. Collaboration among a wide range of stakeholders is required to promote the clinical development of treatment for rare cancers under a nationwide consensus