トルコ・ケステル湖から得られた柱状堆積物の植物性残存物と脂質の炭素１４年代

In 1992, a 5 m core was recovered from Lake Kestel, which is located on the southern Mediterranean coast of Turkey. Accelerator Mass Spectrometry (AMS) radiocarbon dating and stable carbon isotope (13C/12C) analysis were made on both plant remains and lipids from the core sediments.AMS radiocarbon dates of plant remains showed that the sediment was deposited at a relatively constant rate (0.21 cm/year), suggesting a record of the environmental changes during the last 2000 years. The initial radiocarbon contents (A0) in lipids were in the range of 30-90 percent modern carbon (pMC) and tend to vary inversely as 13C/12C change in lipids. Such a low content of A0 in lipids was introduced by an influx of lipids with less 14C contents from the surrounding soil. Therefore, the A0 in surrounding soil to the lake sediment in the past, possibly relating to hydrological and environmental changes such as precipitation and evaporation

Phenethyl iosothiocyanate activates leptin signaling

Obesity, a principal risk factor for the development of diabetes mellitus, heart disease, and hypertension, is a growing and serious health problem all over the world. Leptin is a weight-reducing hormone produced by adipose tissue, which decreases food intake via hypothalamic leptin receptors (Ob-Rb) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates leptin signaling by dephosphorylating JAK2, and the increased activity of PTP1B is implicated in the pathogenesis of obesity. Hence, inhibition of PTP1B may help prevent and reduce obesity. In this study, we revealed that phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate in certain cruciferous vegetables, potently inhibits recombinant PTP1B by binding to the reactive cysteinyl thiol. Moreover, we found that PEITC causes the ligand-independent phosphorylation of Ob-Rb, JAK2, and STAT3 by inhibiting cellular PTP1B in differentiated human SH-SY5Y neuronal cells. PEITC treatment also induced nuclear accumulation of phosphorylated STAT3, resulting in enhanced anorexigenic POMC expression and suppressed orexigenic NPY/AGRP expression. We demonstrated that oral administration of PEITC to mice significantly reduces food intake, and stimulates hypothalamic leptin signaling. Our results suggest that PEITC might help prevent and improve obesity

Cancer Immunol Immunother

Purpose Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. Materials and Methods Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study. The patients received subcutaneous administration of the peptide as an emulsion form with Montanide ISA-51 VG once a week in a dose-escalation manner (doses of 0.5, 1.0, or 3.0 mg/body, 3 patients for each dose). The primary endpoint was safety, and the secondary endpoints were immunological and clinical responses. Results Vaccinations with HIG2-9-4 peptide could be well tolerated without any serious systemic adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses were detected in eight of the nine patients. Doses of 1.0 or 3.0 mg/body seemed to induce a CTL response better than did a dose of 0.5 mg/body, although the number of patients was too small to draw a firm conclusion. The disease control rate (stable disease for ≥4 months) was 77.8 %, and the median progression-free survival time was 10.3 months. Conclusions HIG2-9-4 peptide vaccine treatment was tolerable and effectively induced peptide-specific CTLs in RCC patients. This novel peptide vaccine therapy for RCC is promising

PREDICTION SYSTEMS FOR BLADDER CANCER THERAPY

The present study established systems to predict the chemo‑sensitivity of muscle invasive bladder cancer (MIBC) for neoadjuvant chemotherapy (NAC) with methotrexate, vinblastine, doxorubicin plus cisplatin (M‑VAC) and carboplatin plus gemcitabine (CaG) by analyzing microarray data. The primary aim of the study was to investigate whether the clinical response would increase by combining these prediction systems. Treatment of each MIBC case was allocated into M‑VAC NAC, CaG NAC, surgery, or radiation therapy groups by their prediction score (PS), which was calculated using the designed chemo‑sensitivity prediction system. The therapeutic effect of the present study was compared with the results of historical controls (n=76 patients) whose treatments were not allocated using the chemo‑sensitivity prediction system. In addition, the overall survival between the predicted to be responder (positive PS) group and predicted to be non‑responder (negative PS) group was investigated in the present study. Of the 33 patients with MIBC, 25 cases were positive PS and 8 were negative PS. Among the 25 positive PS cases, 7 were allocated to receive M‑VAC NAC and 18 were allocated to receive CaG NAC according to the results of the prediction systems. Of the 8 negative PS cases, 3 received CaG NAC, 1 received surgery without NAC and 4 received radiation therapy. The total clinical response to NAC was 88.0% (22/25), which was significantly increased compared with the historical controls [56.6% (43/76) P=0.0041]. Overall survival of the positive PS group in the study was significantly increased compared with the negative PS group (P=0.027). In conclusion, the combination of the two prediction systems may increase the treatment efficacy for patients with MIBC by proposing the optimal NAC regimen. In addition, the positive PS group would have a better prognosis compared with the negative PS group. These results suggest that the two prediction systems may lead to the achievement of ‘precision medicine’

A novel locally operated master-slave robot system for single-incision laparoscopic surgery

Purpose: Single-incision laparoscopic surgery (SILS) provides more cosmetic benefits than conventional laparoscopic surgery but presents operational difficulties. To overcome this technical problem, we have developed a locally operated master-slave robot system that provides operability and a visual field similar to conventional laparoscopic surgery. Material and methods: A surgeon grasps the master device with the left hand, which is placed above the abdominal wall, and holds a normal instrument with the right hand. A laparoscope, a slave robot, and the right-sided instrument are inserted through one incision. The slave robot is bent in the body cavity and its length, pose, and tip angle are changed by manipulating the master device; thus the surgeon has almost the same operability as with normal laparoscopic surgery. To evaluate our proposed system, we conducted a basic task and an ex vivo experiment. Results: In basic task experiments, the average object-passing task time was 9.50 sec (SILS cross), 22.25 sec (SILS parallel), and 7.23 sec (proposed SILS). The average number of instrument collisions was 3.67 (SILS cross), 14 (SILS parallel), and 0.33 (proposed SILS). In the ex vivo experiment, we confirmed the applicability of our system for single-port laparoscopic cholecystectomy. Conclusion: We demonstrated that our proposed robot system is useful for single-incision laparoscopic surgery.ArticleMINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES. 23(6):326-332 (2014)journal articl

呼気筋トレーニングが在宅要介護認定者の呼吸指標および嚥下機能に与える効果

Expiratory muscle training（EMT） for improving cough function and prevention of aspiration pneumonia in healthy elderly individuals as well as patients with neurological disorders has received recent attention. Although 2 studies elucidated its effects on swallowing function in a small population of patients with Parkinson’s disease, its overall efficacy remains uncertain. The purpose of this study was to examine the effects of EMT on respiratory indices and swallowing function in elderly individuals receiving home care. The subjects were 22 community-dwelling elderly individuals receiving home care. An EMT training device（Threthold IMT） was applied with reversed use and the training period was 4 weeks. The loading pressure was 30% of baseline MEP and the training sessions were performed for 15 minutes twice a day. Each training session was monitored by a family member and recorded. Respiratory function［forced-vital capacity（FVC） and %FVC］ and respiratory muscle strength ［maximal expiratory pressure （MEP） and maximal inspiratory pressure （MIP）］ were measured at baseline and after 1, 2, 3 and 4 weeks of EMT, while swallowing function ［repetitive saliva swallowing test （RSST）］ was measured at baseline and after 4 weeks. Two-way ANOVA was performed with the factors of ADL score and measurement week. Statistical analysis showed that both factors had effects, though there was no correlation between them. MEP was significantly improved at 3 and 4 weeks after EMT as compared to the baseline, whereas other respiratory indices and RSST were unchanged after EMT. Our findings indicate that EMT can strengthen expiratory muscles and suggest the need for higher expiratory loading pressure. Further research should define the target population more clearly and establish an effective EMT protocol to improve swallowing function