Cerebral Oxygenation Dynamics During Incremental Exercise: Comparison of Arm Cranking and Leg Cycling.

This study aimed to compare cerebral oxyhemoglobin (O2Hb) levels during incremental exercise by cycling vs. arm cranking in 12 healthy adult men aged 20.8 ± 0.2 years old. O2Hb was measured by near-infrared spectroscopy. Regions of interest included the left and right prefrontal cortices (LtPFC and RtPFC, respectively), the left and right premotor cortices (LtPMC and RtPMC, respectively), and the supplementary motor area (SMA) bilaterally. After 4 min of rest, 4 min of warm-up was performed by using ergometer followed by incremental exercise (increasing work rate by 5 W/min for arm cranking and 20 W/min for cycling exercise). All values were averaged every tenth of the participant's exercise time period from beginning of incremental exercise to end point. At the middle exercise intensity (50% exercise time), the averaged O2Hb values obtained at all regions of interest seemed to be higher during arm cranking exercise as compared to cycling; however, there were no significant differences between two types of exercise. At the end point of incremental exercise (100% exercise time), the O2Hb obtained at all regions of interest was significantly higher during arm cranking exercise compared to cycling (LtPFC 0.081 ± 0.019 vs. -0.001 ± 0.013 mM·cm, RtPFC 0.076 ± 0.021 vs. 0.018 ± 0.015 mM·cm, SMA 0.012 ± 0.040 vs. 0.040 ± 0.016 mM·cm; arm cranking vs. cycling; p < 0.05, respectively). We conclude that exercise-induced cerebral oxygenation is greater with arm cranking than with leg cycling.

Effects of 20-Minute Intensive Exercise on Subjects with Different Working Memory Bases.

Continuous moderate-intensity aerobic exercise improves cognitive function including working memory (WM). We aimed to determine the differences in the effects of exercise on WM based on pre-exercise WM function and oxyhemoglobin (O2Hb) changes. We enrolled 12 healthy adult males who, after a 4-min rest and warm-up, performed a 20-min exercise regime at a workload corresponding to 50% of maximal oxygen consumption. They performed a pre- and postexercise two-back test, and the reaction times were recorded. Near-infrared spectroscopy was used to monitor the O2Hb concentration in the left prefrontal cortex during the exercise. Based on the pre-exercise reaction time, the subjects were allocated into either a fast group (FG) or a slow group (SG). The pre- and postexercise changes in the reaction time and time-to-peak O2Hb were compared. Further, we determined the relationship between the change in the reaction time and time-to-peak O2Hb. There was no significant change in the reaction time of the FG; however, that in the SG decreased significantly. The time-to-peak O2Hb in the FG was significantly less than that in the SG. These results showed differences in the changes of reaction time and O2Hb changes between the FG and SG.

Supine Cycling Exercise Enhances Cerebral Oxygenation of Motor-Related Areas in Healthy Male Volunteers.

It has been reported that the cardiovascular response in the supine position is different from that in the sitting position. However, there are few reports on the effects of posture on cerebral oxygenation during exercise. Cycling exercises change oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) levels in motor-related areas. Therefore, this study compared O2Hb levels at motor-related areas during recumbent versus supine cycling. Eleven healthy young male performed a 30-min cycling exercise protocol at 50% of the maximal oxygen uptake (VO2 max) in the recumbent and supine positions. Near-infrared spectroscopy (NIRS) was used to measure exercise-induced O2Hb and HHb changes in the right (R-PMA) and left premotor areas (L-PMA), supplementary motor area (SMA), and primary motor cortex (M1). In R-PMA, L-PMA and SMA, the O2Hb obtained during supine cycling was significantly higher than that during recumbent cycling (R-PMA, 0.031 ± 0.01 vs. 0.693 ± 0.01; L-PMA, 0.027 ± 0.01 vs. 0.085 ± 0.013; SMA, 0.041 ± 0.011 vs. 0.076 ± 0.008 mM·cm, recumbent vs. supine position; p < 0.05). These results suggest that supine cycling exercise increases R-PMA, L-PMA, and SMA O2Hb levels in healthy young men.

Cancer survivors exhibit a different relationship between muscle strength and health-related quality of life/fatigue compared to healthy subjects.

We investigated the difference in relationship between muscle strength and quality of life (QOL)/fatigue in long-term cancer survivors and healthy subjects. Thirty-six cancer survivors and 29 healthy subjects were assessed for body composition and bone status at the calcaneus using the Osteo Sono Assessment Index. Muscle strength was evaluated via handgrip and knee extensor strength. Health-related QOL was assessed using the Medical Outcome Study 36-item Short-Form Health Survey. Fatigue was measured using the brief fatigue inventory. Cancer survivors exhibited lower QOL scores in the physical functioning, physical role function, bodily pain and general health domains (p < .05). Grip and knee extension muscle strength in cancer survivors was positively correlated with the physical function and bodily pain of QOL (p < .05). The usual fatigue subscale score was only significantly higher in cancer survivors than in healthy subjects (p < .05). However, there were no correlations between muscle strength and fatigue in cancer survivors. Our results showed that muscle strength was an important factor for improving QOL in cancer survivors. We believe that the findings of this study will be relevant in the context of planning rehabilitation for cancer survivors.

Clinical and mutational spectrum of Charcot-Marie-Tooth disease type 2Z caused by MORC2 variants in Japan.

BACKGROUND AND PURPOSE: The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot-Marie-Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan. METHODS: We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next-generation sequencing, and samples from 434 mutation-negative patients were subjected to whole-exome sequencing. We extracted MORC2 variants from these whole-exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines. RESULTS: We identified MORC2 variants in 13 patients. As the second most common causative gene of CMT type 2 after MFN2, MORC2 variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length-dependent polyneuropathy, and electrophysiological studies revealed sensory-dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys. CONCLUSIONS: Our study is the largest report of patients harboring MORC2 variants. We revealed a clinical and mutational spectrum of Japanese patients with MORC2 variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.

Relationship of physical activity with physical function and health-related quality of life in patients having undergone allogeneic haematopoietic stem-cell transplantation.

In this study, we investigated the differences in physical activity before and after transplantation, and the relationship between physical activity and physical function and health-related quality of life (QOL) in 30 patients who underwent allogeneic haematopoietic stem cell transplantation (allo-HSCT). Duration and intensity of physical activity were quantified using a three-dimensional accelerometer. Physical function was quantified by handgrip and knee-extensor strength, with the 6-minute walk test (6MWT) used as a measure of exercise capacity. Health-related QOL was assessed using the 36-item Short-Form Health Survey. The proportion of daily activities performed at an intensity >3.0 metabolic equivalents (METs) increased significantly after allo-HSCT (p < .05). Daily activity time performed at an intensity of 1.6-2.9 METs significantly correlated only with left knee strength (p < .05). In contrast, the total number of daily steps and the proportion of activity performed at 1.6-2.9 METs and >3.0 METs were positively correlated with the 6MWT (p < .05). Additionally, physical functioning and general health subscales in health-related QOL positively correlated with daily activities performed at >3.0 METs (p < .05). Physical activity was associated with 6MWT and health-related QOL. These findings have implications for rehabilitation planning for patients undergoing allo-HSCT.

Reduction in radiation and contrast medium dose via optimization of low-kilovoltage CT protocols using a hybrid iterative reconstruction algorithm at 256-slice body CT: phantom study and clinical correlation.

AIM: To optimize low-kilovoltage (kV) computed tomography (CT) protocols using a hybrid iterative reconstruction (HIR) algorithm at 256-detector-row body CT. MATERIALS AND METHODS: Based on preliminary phantom studies, three different tube voltage protocols with an equal contrast-to-noise ratio (CNR) were developed. They were a conventional 120 kV protocol with filtered back-projection (FBP), an 80 kV protocol with HIR (a 160% increase in the tube current-time product and a 40% reduction in the contrast medium dose), and a 100 kV protocol with HIR (a 20% reduction in the tube current-time product and the contrast medium dose). The clinical study included 70 patients (34 women, 36 men; mean age 70.5 ± 9.1 years, range 44-92 years) who had undergone CT at 120 kV a mean of 148 ± 137 days before undergoing low kV contrast-enhanced body CT (80 kV with HIR, n = 35; 100 kV with HIR, n = 35). The estimated effective radiation dose (ED), image noise, and CNR were calculated and the visual image quality was scored on a four-point scale. RESULTS: Mean ED was 12.3, 8.4, and 15.4 mSv for the 80, 100, and 120 kV protocol, respectively, and significantly lower using the low kV protocols. There was no significant difference in the image noise and CNR between the low kV protocols with HIR and the 120 kV protocol with FBP, or in the visual scores among the three protocols. CONCLUSION: Without ensuing image-quality degradation, the radiation and contrast medium dose can be reduced with optimal contrast-enhanced CT protocols using a low kV technique and an HIR algorithm.

Safety and feasibility of physical therapy in cytopenic patients during allogeneic haematopoietic stem cell transplantation.

This study aimed to investigate the safety and feasibility of physical therapy in cytopenic patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to investigate the effect of physical therapy on physiological functions and quality of life (QOL) in allo-HSCT patients. The study cohort included 321 patients who underwent allo-HSCT. To investigate the safety and feasibility of physical therapy during cytopenia, patients were assigned to the physical therapy group (n = 227) or the control group (n = 94). To determine the effects of physical therapy, patients were divided according to the frequency with which they underwent physical therapy (n = 51 per group). Handgrip strength, knee extensor strength and a 6-min walk test were used as measures of physiological function. Short-Form 36 was used to assess QOL. The physical therapy group had higher rate of achieving engraftment and lower death rate than the control group (P < 0.05). After HSCT, the high-frequency physical therapy group showed significantly less decline than the low-frequency physical therapy group with respect to physical functioning of QOL (P < 0.01). Physical therapy is quite beneficial and can be performed safely and feasibly in cytopenic patients during allo-HSCT.

Atomic resolution electron microscopy in a magnetic field free environment.

Atomic-resolution electron microscopes utilize high-power magnetic lenses to produce magnified images of the atomic details of matter. Doing so involves placing samples inside the magnetic objective lens, where magnetic fields of up to a few tesla are always exerted. This can largely alter, or even destroy, the magnetic and physical structures of interest. Here, we describe a newly developed magnetic objective lens system that realizes a magnetic field free environment at the sample position. Combined with a higher-order aberration corrector, we achieve direct, atom-resolved imaging with sub-Å spatial resolution with a residual magnetic field of less than 0.2 mT at the sample position. This capability enables direct atom-resolved imaging of magnetic materials such as silicon steels. Removing the need to subject samples to high magnetic field environments enables a new stage in atomic resolution electron microscopy that realizes direct, atomic-level observation of samples without unwanted high magnetic field effects.

Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor cellularity.

BACKGROUND AND PURPOSE: On diffusion-weighted imaging (DWI), metastatic tumors of the brain may exhibit different signal intensities (SI) depending on their histology and cellularity. The purpose of our study was to verify the hypotheses (1) that SI on DWI predict the histology of metastases and (2) that apparent diffusion coefficient (ADC) values reflect tumor cellularity. MATERIALS AND METHODS: We assessed conventional MR images, DWI, and ADC maps of 26 metastatic brain lesions from 26 patients, 13 of whom underwent surgery after the MR examination. Two radiologists performed qualitative assessment by consensus of the SI on DWI in areas corresponding to their enhancing portions. We measured the contrast-to-noise ratio (CNR) on T2-weighted images and normalized ADC (nADC) values, and compared them with tumor cellularity. RESULTS: The mean SI on DWI and the CNR on T2-weighted images were significantly lower in well differentiated than in poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. The mean nADC value was significantly higher in well differentiated than poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. All 3 small-cell carcinomas and 1 large-cell neuroendocrine carcinoma exhibited high SI on DWI. The nADC value showed a significant inverse correlation with tumor cellularity. There was no significant correlation between the CNR and tumor cellularity. CONCLUSION: The SI on DWI may predict the histology of metastases; well differentiated adenocarcinomas tended to be hypointense, and small- and large-cell neuroendocrine carcinomas showed hyperintensity. Their ADC values reflect tumor cellularity.

BodyMap incorporated PCR-based expression profiling data and a gene ranking system.

BodyMap is a human and mouse gene expression database that is based on site-directed 3'-expressed sequence tags generated at Osaka University. To date, it contains more than 300 000 tag sequences from 64 human and 39 mouse tissues. For the recent release, the precise anatomical expression patterns for more than half of the human gene entries were generated by introduced amplified fragment length polymorphism (iAFLP), which is a PCR-based high-throughput expression profiling method. The iAFLP data incorporated into BodyMap describe the relative contents of more than 12 000 transcripts across 30 tissue RNAs. In addition, a newly developed gene ranking system helps users obtain lists of genes that have desired expression patterns according to their significance. BodyMap supports complete transfer of unique data sets and provides analysis that is accessible through the WWW at http://bodymap.ims.u-tokyo.ac. jp.

Usefulness of multi-detector row computed tomography for accurate preoperative assessment of pancreatic adenocarcinoma: report of a case.

A 74-year-old female underwent surgical treatment for adenocarcinoma of the pancreatic head. Preoperative multi-detector row computed tomography (MD-CT) demonstrated tumor invasion into the accessory right colic vein and the branch of the middle colic artery (MCA), which was not detected by digital subtraction angiography. MD-CT showed anatomical variants in the left hepatic artery arising from the left gastric artery, and the right posterior hepatic artery arising from the superior mesenteric artery. Three-dimensional reconstruction CT generated a clear picture of the anatomy of the region concerned, which is essential for a safe operation. The MD-CT findings were highly consistent with the intraoperative findings. We have demonstrated that MD-CT is an important and highly accurate modality for pancreatic surgery.

Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell.

Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action.

Expression of the cDNA encoding lipocortin-like 39 kDa protein of guinea pig neutrophils in yeast. Purification and biological characterization.

The cDNA encoding lipocortin-like 39 kDa protein in guinea pig neutrophils was cloned into a yeast expression vector and the constructed plasmid was introduced into a yeast. The gene was expressed in an eukaryotic cell, yeast Saccharomyces cerevisiae and the recombinant protein was purified and characterized. The purified protein was identical with the native one with respect to the antigenicity and several biochemical properties, such as inhibitory action against phospholipase A2, Ca2+-dependent binding to acidic-phospholipids and F-actin and availability as a substrate for tyrosine kinase (EGF receptor/kinase) and protein kinase C.

Studies on drug metabolism by use of isotopes. 23. Metabolic study of 1-butyryl-4-cinnamylpiperazine in the rat during development of tolerance by using two kinds of deuterium-labeled forms.

Mass fragmentographic determination of the plasma, brain, and liver levels of 1-butyryl-4-cinnamylpiperazine (I) and its metabolites in tolerant and nontolerant rats was carried out by using two kinds of deuterium-labeled compounds. 1-Butyryl-4-[a-d2]cinnamylpiperazine (I-d2) was used to develop tolerance and 1-butyryl-4-[arom-d5]cinnamylpiperazine (I-d5) to clarify the metabolic fate of I after I-d2 administration. The present method allowed the clarification of the metabolism of I-d2 and I-d5 independently. In tolerant rats, the brain and liver were lower for I-d5 and higher for I-d5 metabolites than in nontolerant rats. There was no significant difference in the plasma levels of I-D5 between tolerant and nontolerant rats. Our data seem to suggest that development of tolerance to I results from a more rapid metabolism of the drug due to hepatic enzyme induction.

Synthesis and hypolipidemic activity of 2-substituted isobutyric acid derivatives.

A series of 2-substituted isobutyric acid derivatives have been synthesized and evaluated as hypolipidemic agents. Compounds 11 and 20 were found to decrease the level of plasma total cholesterol in experimental hyperlipidemic rats to a greater extent than clofibrate (CF) and to increase the level of plasma high-density lipoprotein cholesterol to the same extent as gemfibrozil (GF). Increase in liver weight caused by these compounds were less than those with CF and GF.

Impaired retention of technetium-99m tetrofosmin in hypertrophic cardiomyopathy.

The purpose of this study was to determine whether myocardial imaging using technetium-99m tetrofosmin can noninvasively identify myocardial damage in hypertrophic cardiomyopathy (HC). The study consisted of 10 patients with apical HC, 10 with asymmetric septal HC (ASH) group, 5 with dilated cardiomyopathy (DC)-like group, and 20 healthy subjects. With use of a bull's-eye map of single-photon emission computed tomographic imaging, the total defect score of tetrofosmin and the washout rate were assessed in 5 segments (septum, and anterior, lateral, and inferior walls, and apex) of the left ventricle. A localized increase in defect score and washout rate was observed in the hypertrophied region in the group with apical HC. An increased washout rate was observed in the ASH group regardless of hypertrophy, suggesting that tetrofosmin retention by the mitochondria was impaired in the entire left ventricular wall. The washout rate was further increased at all segments in the DC-like group versus the ASH group. Tetrofosmin retention by mitochondria was impaired in the entire left ventricular wall in the ASH group and was increased further in the DC-like group. The dysfunction of myocardial cells was limited to the hypertrophied region in the apical HC group.

Introduction of p21(Waf1/Cip1) gene into a carcinoma cell line of the uterine cervix with inactivated p53.

In carcinomas of the uterine cervix of which p53 is frequently inactivated by papilloma viruses, gene transfer of p21, effector of p53, is an alternative tool to suppress cell growth. We introduced the p21 gene into HeLa cells. The transfectant with p21 showed a significant growth retardation by blockage of G1 to S transfer of the cell cycle. This cell line showed significantly reduced anchorage-independent growth as well as attenuated telomerase activity. These data suggest that gene transfer of p21 is an effective tool to lead carcinoma cells with inactivated p53 into less malignant phenotype.

Rare occurrence of p53 and ras gene mutations in preneoplastic and neoplastic mouse endometrial lesions induced by N-methyl-N-nitrosourea and 17 beta-estradiol.

To examine K-, H-, or N-ras and p53 gene mutations in mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17 beta-estradiol, we performed polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in 13 adenocarcinomas and 11 other preneoplastic lesions. A significant shifted band in exon 5 of p53 using PCR-SSCP was detected in one of 13 adenocarcinomas. Direct sequencing showed that the mutation was TCA-to-TGA (Ser-to-End) transition. These results suggest that ras gene mutations were not related to carcinogenesis and inactivation of p53 may occur with low frequency during the mouse endometrial carcinogenesis in this model.