ニューロメジンUはMRGPRX2を介して皮膚マスト細胞の脱顆粒を誘導する

内容の要旨, 審査の要旨広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Effects of expiratory muscle training for elderly patients under long-term care

The purpose of this study was to investigate the effects of an expiratory muscle training （EMT）program on swallowing, tongue pressure and thickness, labial closure force, spirometry, and respiratory pressure in elderly patients under long-term care. The subjects were twenty elderly inpatients without dementia or dysphagia, who were under long-term care at the health facility of a hospital in Tokushima prefecture. They were randomly assigned to one of the two groups, the sham EMT group and the active EMT group. The improvement rates of SVC, %FVC, PEF, %PEF, MEP, %MEP and MIP were significantly different between two groups （p< 0.01）. The EMT program was well-tolerated and led to improvements in respiratory function and muscle strength other than swallowing indices in elderly patients under long-term care. These results may contribute to the prevention and treatment of aspiration pneumonia in elderly individuals under long-term care

Successful paclitaxel-based chemotherapy for an alpha-fetoprotein-producing gastric cancer patient with multiple liver metastases

<p>Abstract</p> <p>Background</p> <p>Alpha-fetoprotein (AFP)-producing gastric cancer is known to frequently cause multiple liver metastases and to have an extremely poor prognosis.</p> <p>Case presentation</p> <p>A 64-year-old Japanese man admitted to our hospital was diagnosed with gastric cancer with liver metastases. He underwent a total gastrectomy with splenectomy, and pathological stage IV disease according to the classification proposed by the Japanese Gastric Cancer Association was assigned. The histological diagnosis was poorly differentiated adenocarcinoma, and tumor production of AFP was confirmed by immunohistochemical staining. Following surgery, the patient received combination chemotherapy consisting of TS-1 and paclitaxel. Initially, AFP levels decreased dramatically and computed tomography (CT) revealed regression of liver metastases. However, multiple new liver metastases appeared and serum AFP levels increased after 5 months. A regimen of 5-FU plus paclitaxel followed by paclitaxel monotherapy was used next. Serum AFP levels once again decreased and CT showed regression or disappearance of liver metastases. The patient currently has a very good quality of life, and is receiving weekly paclitaxel monotherapy as an outpatient. No progression of liver metastases has been observed to date.</p> <p>Conclusion</p> <p>We consider this rare case to have significant value with respect to treatment of AFP-producing gastric cancer with multiple liver metastases, and propose that combining surgery with chemotherapeutic agents such as paclitaxel may lead to a better prognosis in such cases.</p

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2‐mutation carriers

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients

High-Resolution Submillimeter and Near-Infrared Studies of the Transition Disk around Sz 91

To reveal the structures of a transition disk around a young stellar object in Lupus, Sz 91, we have performed aperture synthesis 345 GHz continuum and CO(3--2) observations with the Submillimeter Array (\sim1\arcsec--3\arcsec resolution), and high-resolution imaging of polarized intensity at the $K_s$-band by using the HiCIAO instrument on the Subaru Telescope (0\farcs25 resolution). Our observations successfully resolved the inner and outer radii of the dust disk to be 65 AU and 170 AU, respectively, which indicates that Sz 91 is a transition disk source with one of the largest known inner holes. The model fitting analysis of the spectral energy distribution reveals an H$_2$ mass of $2.4\times10^{-3}$ M_\sun in the cold ($T<$30 K) outer part at $65<r<170$ AU by assuming a canonical gas-to-dust mass ratio of 100, although a small amount ($>3\times10^{-9}$ M_\sun) of hot ($T\sim$180 K) dust possibly remains inside the inner hole of the disk. The structure of the hot component could be interpreted as either an unresolved self-luminous companion body (not directly detected in our observations) or a narrow ring inside the inner hole. Significant CO(3--2) emission with a velocity gradient along the major axis of the dust disk is concentrated on the Sz 91 position, suggesting a rotating gas disk with a radius of 420 AU. The Sz 91 disk is possibly a rare disk in an evolutionary stage immediately after the formation of protoplanets because of the large inner hole and the lower disk mass than other transition disks studied thus far

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

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

開心術前後における身体組成変動

Lean body mass decreases after a major operation such as open-heart surgery, which leads to postoperative complications, as a drastic loss of muscle mass is related to infections and longer hospital stays. The purpose of this study was to examine changes in lean body mass and muscle mass including body composition the perioperative phase until discharge in patients undergoing open-heart surgery. Body fluids, fat and lean body mass in 17 patients were determined before and 1 week after surgery, and at discharge using bioelectrical impedance analysis. In addition, the levels of hemoglobin, albumin, and C-reactive protein in blood were measured. Cardiac rehabilitation consisted of early mobilization and aerobic bicycle exercise was subsequently performed after confirmation of independent walking for 200 meters. Early mobilization after surgery was assisted by physical therapists experienced in cases of cardiovascular surgery. Early mobilization required no more than 3 delayed days and no major complications until discharge in any of the patients. Weight and body mass index were significantly lower at discharge than before and 1 week after surgery, while lean body mass, muscle mass, total body water, intracellular fluid, body protein, and body cell mass values were significantly lower at discharge than before surgery. The changes in body composition seen after cardiac surgery until discharge indicated continuous catabolic reactions in our patients and some cytokines have been suggested to influence this phenomenon. After receiving open-heart surgery, it is important for patients to receive nutritional therapy and begin resistance exercise as soon as possible. Aerobic exercise should produce muscle protein synthesis and increase muscle mass under adequate nutritional support including specific amino acid supplements. Our findings indicate that muscle mass and nutritional status should be monitored after discharge and followed consistently in patients after open-heart surgery

High-Resolution Submillimeter and Near-Infrared Studies of the Transition Disk around Sz 91

To reveal the structures of a transition disk around a young stellar object in Lupus, Sz 91, we have performed aperture synthesis 345 GHz continuum and CO(32) observations with the Submillimeter Array ( 13 resolution), and high-resolution imaging of polarized intensity at the Ks-band by using the Hi-CIAO instrument on the Subaru Telescope (0.25 resolution). Our observations successfully resolved the inner and outer radii of the dust disk to be 65 and 170AU, respectively, which indicates that Sz 91 is a transition disk source with one of the largest known inner holes. The model fitting analysis of the spectral energy distribution reveals an H2 mass of 2.4 103 M in the cold (T 30 K) outer part at 65 r 170 AU by assuming a canonical gas-to-dust mass ratio of 100, although a small amount ( 3109 M) of hot (T 180 K) dust possibly remains inside the inner hole of the disk. The structure of the hot component could be interpreted as either an unresolved self-luminous companion body (not directly detected in our observations) or a narrow ring inside the inner hole. Significant CO(32) emission with a velocity gradient along the major axis of the dust disk is concentrated on the Sz 91 position, suggesting a rotating gas disk with a radius of 420 AU. The Sz 91 disk is possibly a rare disk in an evolutionary stage immediately after the formation of protoplanets because of the large inner hole and the lower disk mass than other transition disks studied thus far