Shin Yamada

Serum Fucosylated Haptoglobin as a Novel Diagnostic Biomarker for Predicting Hepatocyte Ballooning and Nonalcoholic Steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem around the world. NAFLD patients with nonalcoholic steatohepatitis (NASH) can develop cirrhosis and hepatocellular carcinoma. The ability to distinguish NASH from simple steatosis would be of great clinical significance. Ballooning hepatocytes are characteristic of typical pathological NASH; here, the polarized secretion of proteins is disrupted due to destruction of the cytoskeleton. We previously reported that fucosylated glycoproteins are secreted into bile, but not into sera in normal liver. Therefore, we hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes, and serum fucosylated glycoproteins would increase in NASH patients. To confirm our hypothesis, we evaluated serum fucosylated haptoglobin (Fuc-Hpt) levels in biopsy-proven NAFLD patients (nu200a=u200a126) using a lectin-antibody ELISA kit. Fuc-Hpt levels were significantly increased in NASH patients compared with non-NASH (NAFLD patients without NASH) patients. Interestingly, Fuc-Hpt levels showed a significant stepwise increase with increasing hepatocyte ballooning scores. Multiple logistic regression analysis showed that Fuc-Hpt levels were independent and significant determinants of the presence of ballooning hepatocytes. Moreover, Fuc-Hpt levels were useful in monitoring liver fibrosis staging. Next, to investigate the significance of serum Fuc-Hpt in a larger population, we measured Fuc-Hpt levels in ultrasound-diagnosed NAFLD subjects (nu200a=u200a870) who received a medical health checkup. To evaluate NAFLD disease severity, we used the FIB-4 index (based on age, serum AST and ALT levels, and platelet counts). Fuc-Hpt levels increased stepwise with increasing FIB-4 index. Conclusion Measurement of serum Fuc-Hpt levels can distinguish NASH from non-NASH patients, and predict the presence of ballooning hepatocytes in NAFLD patients with sufficient accuracy. These results support the potential usefulness of measuring Fuc-Hpt levels in clinical practice.

Reevaluation of a lectin antibody ELISA kit for measuring fucosylated haptoglobin in various conditions.

BACKGROUNDnFucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker in a variety of pathological conditions. We previously found that the level of Fuc-Hpt is increased in the sera of patients with pancreatic cancer, and established a lectin antibody ELISA using Aleuria aurantia lectin, which specifically binds to fucosylated residues on oligosaccharides.nnnMETHODSnTo apply this assay system to the clinical detection of several diseases, several assay conditions such as serum dilutions and inhibitory factors were investigated. The Fuc-Hpt kit was available for 25-625 fold serum dilution.nnnRESULTSnWhile the values of Fuc-Hpt assay using sera and plasma were different, they showed positive correlation. The addition of bilirubin and formagine did not influence on Fuc-Hpt assay, but hemoglobin inhibited this assay in a dose-dependent manner.nnnCONCLUSIONSnWe reevaluated this lectin antibody ELISA kit for measuring fucosylated haptoglobin in various conditions in this study.

Cardiorespiratory fitness level correlates inversely with excess post-exercise oxygen consumption after aerobic-type interval training

BackgroundThe purpose of this study was to reveal any association between cardiorespiratory fitness level and excess post-exercise oxygen consumption (EPOC) using three cycling protocols with varying degrees of exercise intensity, i.e., sprint interval training (SIT), high-intensity interval aerobic training (HIAT), and continuous aerobic training (CAT).FindingsTen healthy men, aged 20 to 31 years, attended a cross-over experiment and completed three exercise sessions: SIT consisting of 7 sets of 30-s cycling at 120% VO2max with a 15-s rest between sets; HIAT consisting of 3 sets of 3-min cycling at 80~90% VO2max with a 2-min active rest at 50% VO2max between sets; and CAT consisting of 40 min of cycling at 60~65% VO2max. During each session, resting VO2, exercise VO2, and a 180-min post-exercise VO2 were measured. The net exercise VO2 during the SIT, HIAT, and CAT averaged 14.7 ± 1.5, 31.8 ± 4.1, and 71.1 ± 10.0 L, and the EPOCs averaged 6.8 ± 4.0, 4.5 ± 3.3, and 2.9 ± 2.8 L, respectively. The EPOC with SIT was greater than with CAT (P < 0.01) and HIAT (P = 0.12). Correlation coefficients obtained between subjects’ VO2max and the ratio of EPOC to net exercise VO2 for SIT, HIAT, and CAT were −0.61 (P = 0.06), -0.79 (P < 0.01), and −0.42 (P = 0.23), respectively.ConclusionsOur data suggest that cardiorespiratory fitness level correlates negatively with the magnitude of EPOC, especially when performing aerobic-type interval training.

Development of a short version of the motor FIM for use in long-term care settings.

OBJECTIVEnTo develop a short version of the motor Functional Independence Measure (FIM) for use in long-term care settings.nnnPARTICIPANTSnFor model construction, the participants were 398 community-dwelling persons with disability (mean age 79.3 years (SD 10.3)) who were receiving visiting nurse services. For cross-validation, 169 patients with stroke (mean age 78.0 years (SD 11.2)) in the chronic phase and 187 patients with stroke (mean age 63.4 years (SD 12.7)) in the recovery phase.nnnDESIGNnModel construction and cross-validation study.nnnMAIN OUTCOME MEASURESnThe second power of correlation coefficient (R2) was used for agreement analysis between the short and the full version. Cross-validation of the models was estimated with the intraclass correlation coefficient (ICC).nnnRESULTSnFive to 7 motor FIM items were selected for the models based on Rasch calibration and consideration of internal consistency. Total motor FIM was estimated with the 6-item and 7-item models with regression analysis, which yielded high correlations with the original 13-item motor FIM score (R2>0.95). Regression formulas derived from the models could estimate total motor FIM scores accurately in the 2 cross-validation samples (ICC > 0.98).nnnCONCLUSIONnThe short version of the motor FIM developed is a useful measure of functional status, not only in long-term care but in the recovery phase rehabilitation settings.

An exercise protocol designed to control energy expenditure for long-term space missions.

INTRODUCTIONnAstronauts experience weight loss during spaceflight. Future space missions require a more efficient exercise program not only to maintain work efficiency, but also to control increased energy expenditure (EE). When discussing issues concerning EE incurred through exercise, excess post-exercise energy expenditure (EPEE) must also be considered. The aim of this study was to compare the total EE, including EPEE, induced by two types of interval cycling protocols with the total EE of a traditional, continuous cycling protocol.nnnMETHODSnThere were 10 healthy men, ages 20 to 31 yr, who completed 3 exercise sessions: sprint interval training (SIT) consisting of 7 sets of 30-s cycling at 120% VO2max with a 15-s rest between each bout; high-intensity interval aerobic training (HIAT) consisting of 3 sets of 3-min cycling at 80-90% VO2max with a 2-min active rest at 50% VO2max; and continuous aerobic training (CAT) consisting of 40 min of cycling at 60-65% VO2max. During each session, resting metabolic rate, exercise EE, and a 180-min post-exercise EE were measured.nnnRESULTSnThe EPEEs during the SIT, HIAT, and CAT averaged 32 +/- 19, 21 +/- 16, and 13 +/- 13 kcal, and the total EE for an entire exercise/ rest session averaged 109 +/- 20, 182 +/- 17, and 363 +/- 45 kcal, respectively. While the EPEE after the CAT was significantly less than after the SIT, the total EE with the CAT was the greatest of the three.nnnDISCUSSIONnThe SIT and HIAT would be potential protocols to control energy expenditure for long space missions.

Comprehensive analysis of the skin fungal microbiota of astronauts during a half-year stay at the International Space Station

The International Space Station (ISS) is a huge manned construct located approximately 400 km above the earth and is inhabited by astronauts performing space experiments. Because the station is within a closed microgravity environment, the astronauts are subject to consistent stress. This study analyzed the temporal changes in the skin fungal microbiota of 10 astronauts using pyrosequencing and quantitative PCR assay before, during, and after their stay in the ISS. Lipophilic skin fungi, Malassezia predominated most samples regardless of the collection period, body site (cheek or chest), or subject. During their stay in the ISS, the level of Malassezia colonization changed by 7.6- ± 7.5-fold (mean ± standard deviation) and 9.5- ± 24.2-fold in cheek and chest samples, respectively. At the species level, M. restricta, M. globosa, and M. sympodialis were more abundant. In the chest samples, the ratio of M. restricta to all Malassezia species increased, whereas it did not change considerably in cheek samples. Fungal diversity was reduced, and the ratio of Malassezia to all fungal colonization increased during the astronauts stay at the ISS. The ascomycetous yeast Cyberlindnera jadinii was detected in abundance in the in-flight sample of 5 of the 10 astronauts. The microorganism may have incidentally adhered to the skin during the preflight period and persisted on the skin thereafter. This observation suggests the ability of a specific or uncommon microorganism to proliferate in a closed environment. Our study is the first to reveal temporal changes in the skin fungal microbiota of ISS astronauts. These findings will provide information useful for maintaining the health of astronauts staying in the space environment for long periods and for preventing infection due to the human skin microbiota.

Temporal changes in the skin Malassezia microbiota of members of the Japanese Antarctic Research Expedition (JARE): A case study in Antarctica as a pseudo-space environment.

The International Space Station (ISS) is located approximately 400 km above the Earth. Astronauts staying at the ISS are under microgravity and are thus unable to bathe or shower; instead, they wash their bodies using wet tissues. For astronauts, skin hygiene management is important to maintain the quality of life during long-term stays on the ISS. In Antarctica, members of a Japanese geological investigation team negotiate their way over land using snowmobiles. During their 3-month stay, they are subject to a pseudo-space environment similar to that experienced by ISS astronauts, including the inability to bathe or shower. In this study, temporal changes in the colonization levels of skin lipophilic fungi, Malassezia were investigated in 16 team members. Compared to the levels before their trip to Antarctica, the fold changes in Malassezia colonization levels during the researchers stay in Antarctica were in the range of 3.0 ± 1.9 to 5.3 ± 7.5 in cheek samples, 8.9 ± 10.6 to 22.2 ± 40.0 in anterior chest samples, 6.2 ± 5.4 to 16.9 ± 25.5 in behind-the-ear samples, and 1.7 ± 0.9 to 17.4 ± 33.4 in sole-of-the-foot samples. On the scalp, the level of Malassezia colonization increased dramatically, by 96.7 ± 113.8 to 916.9 ± 1251.5 fold. During their stay in Antarctica, the team members experienced itchy scalps and produced a large number of scales. The relative proportions of Malassezia globosa and M. restricta shifted to seborrheic dermatitis/dandruff types. These results provide useful information for the development of skin hygiene management plans for astronauts staying at the ISS.

Oxygen Uptake during Aerobic Cycling Exercise Simultaneously Combined with Neuromuscular Electrical Stimulation of Antagonists

The purpose of this study was to evaluate oxygen uptake 2 (VO ) uf026 during aerobic exercise with a Hybrid Training System (HTS) at a moderate intensity. Recently it is said that the combined application of electrical stimulation (ES) and Volitional Contractions (VC) is effective. A Hybrid Training System (HTS) has been developed as a resistance exercise method combining ES with VC, and using electrically stimulated eccentric antagonist muscle contractions as a resistance to voluntary agonist muscle contractions. The benefits of combining aerobic exercise and resistance exercise have also been reported. Therefore, we devised an exercise method that combines the resistance exercise of HTS with aerobic cycling exercise. However, the influence of HTS on aerobic exercise has not been confirmed. Outcome measurements of expired gas were compared during conventional ergometer exercise with and without HTS. 11 healthy young men exercised on a cycle ergometer starting at 20 Watts and increasing by 20 Watts every 3 minutes to 100 Watts, with volitional contractions alone (VER) and with HTS (HER). During each VER and HER test, 2 VO uf026 , carbon dioxide output 2 (VCO ) uf026 , expired ventilation (VE) and heart rate (HR) was measured. HR, 22 VO ,VCO uf026uf026 and VE uf026 showed a linear relation with workload during both VER and HER. 2 VO uf026 during HER was significantly higher than during VER at an average of about 21.1% (p<0.001). HER at moderate intensity seems to result in a linear relationship between 2 VO uf026 and the work rate in the same way as conventional aerobic exercise. Furthermore HER resulted in stronger exercise intensity than VER with the same workload. HTS may be a novel exercise technique that could combine resistance exercise with aerobic exercise.

Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

Background Musculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS). We developed the Hybrid Training System (HTS) to maintain an astronaut’s musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system’s orbital operation capability and utility, as well as its preventative effect on an astronaut’s musculoskeletal atrophy. Methods HTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR). 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks) were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance), MRI (muscle volume), and DXA (BMD, lean [muscle] mass, fat mass). Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force) and a measuring tape (upper arm circumference). Results The experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm) changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule) of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts) of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle) mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR. Conclusions These results showed the orbital operation capability and utility, and the preventive effect of HTS for an astronaut’s musculoskeletal atrophy. The initial flight data together with the ground data obtained so far will be utilized in the future planning of human space exploration.

Changes in Mitochondrial Homeostasis and Redox Status in Astronauts Following Long Stays in Space

The effects of long-term exposure to extreme space conditions on astronauts were investigated by analyzing hair samples from ten astronauts who had spent six months on the International Space Station (ISS). Two samples were collected before, during and after their stays in the ISS; hereafter, referred to as Preflight, Inflight and Postflight, respectively. The ratios of mitochondrial (mt) to nuclear (n) DNA and mtRNA to nRNA were analyzed via quantitative PCR. The combined data of Preflight, Inflight and Postflight show a significant reduction in the mtDNA/nDNA in Inflight, and significant reductions in the mtRNA/nRNA ratios in both the Inflight and Postflight samples. The mtRNA/mtDNA ratios were relatively constant, except in the Postflight samples. Using the same samples, the expression of redox and signal transduction related genes, MnSOD, CuZnSOD, Nrf2, Keap1, GPx4 and Catalase was also examined. The results of the combined data from Preflight, Inflight and Postflight show a significant decrease in the expression of all of the redox-related genes in the samples collected Postflight, with the exception of Catalase, which show no change. This decreased expression may contribute to increased oxidative stress Inflight resulting in the mitochondrial damage that is apparent Postflight.