Site-specific different dynamic cerebral autoregulation and cerebrovascular response to carbon dioxide in posterior cerebral circulation during isometric exercise in healthy young men.

Different cerebral blood flow (CBF) responses to exercise between the posterior cerebral artery (PCA) and vertebral artery (VA) have been previously observed, though the physiological mechanisms remain unknown. There is regional heterogeneity in sympathetic innervation between the PCA and VA, which may affect CBF regulation, especially during sympathoexcitation. Thus, in the present study, we hypothesized that different CBF regulatory mechanisms between PCA and VA contribute to heterogeneous CBF responses to isometric exercise. To test this hypothesis, in thirteen healthy young men, dynamic cerebral autoregulation (CA) and cerebrovascular CO2 reactivity (CVR), were identified in each artery during a 2-min isometric handgrip (IHG) exercise at 30% of maximum voluntary contraction. Similar to previous data, PCA cerebrovascular conductance (CVC) index was decreased from rest (P < 0.004), but not VA CVC during IHG exercise (P > 0.084). Dynamic CA in both PCA and VA were unaltered during the IHG exercise (P = 0.129). On the other hand, PCA CVR was increased during the IHG exercise (P < 0.001) while VA CVR was unchanged (P = 0.294). In addition, individual exercise-induced changes in end-tidal partial pressure of CO2 was related to the individual change in PCA blood velocity (P < 0.046), but was not observed for VA blood flow (P > 0.420). Therefore, these exercise-induced differences in CVR between PCA and VA may contribute to exercise-induced heterogeneous CBF response in the posterior cerebral circulation. These findings indicate that the site-specific posterior CBF should be considered in further research for assessing posterior cerebral circulation.

Effects of acute interval handgrip exercise on cognitive performance.

Previous studies have reported that even a single bout of dynamic exercise improves cognitive performance. However, the acute effect of the interval handgrip (HG) exercise protocol, which is effective in reducing resting blood pressure, on cognitive performance is poorly understood. Cognitive performance was assessed in 17 young healthy subjects before and after a resting control (e.g., time control) and the interval HG exercise (Exercise), which consisted of four trials of 2-min HG exercise at 25% of maximum voluntary contraction with 3-min recovery in between each trial. Mean arterial blood pressure (MAP) and middle cerebral artery blood velocity (MCA V) were measured continuously throughout the experiment. Memory recognition and executive function were assessed using memory recognition and Go/No-Go tasks, respectively. During interval HG exercise, MAP and mean MCA V increased from the resting baseline condition (both P < 0.049) and returned to the resting baseline levels during recovery after the interval HG exercise (both P = 1.000). The reaction time and performance accuracy of the memory recognition task did not change in either the time control condition or Exercise condition (P = 0.514 and P = 0.414 respectively). However, the changes in reaction time of Go/No-Go task from the baseline in Exercise condition was significantly shorter than that in time-control condition (P = 0.004) without affecting performance accuracy (P = 0.482). The results of the present study show that an acute interval HG exercise could improve the processing speed in executive function despite no post-exercise improvement in hemodynamic parameters in young healthy subjects. These findings suggest that the interval HG exercise is a useful exercise mode that can be expected to have a positive effect on the processing speed in executive function regardless of cardiovascular adaptation to exercise.

Greater increase in internal carotid artery shear rate during aerobic interval compared to continuous exercise in healthy adult men.

Interval exercise has been determined to be more effective than continuous exercise for achieving improvement in the cardiovascular function of individuals suffering from cardiovascular disease. However, whether interval exercise improves the cerebrovascular function remains unclear. As per our hypothesis, interval exercise induces a higher cerebrovascular shear rate (SR) than continuous exercise. In this study, 11 adult men randomly performed continuous exercise for 12 min or work-equivalent (57.6 kJ/exercise session) interval exercise of semi-recumbent cycling. The SR in the internal carotid artery (ICA) represents an index of the cerebrovascular SR, which was measured during both the exercises using Doppler ultrasonography. Both the aerobic exercise modes increased the ICA SR. Moreover, the average ICA SR of the interval exercise for the final 4 min of exercise or 2 min of recovery was significantly higher than that for continuous exercise (exercise, 351 ± 75 vs. 330 ± 61/s, p = .038; recovery, 327 ± 86 vs. 290 ± 56/s, p = .014). To our knowledge, this is the first study to show that aerobic interval exercise increased the ICA SR more than equivalent work volume of aerobic continuous exercise. Thus, aerobic interval exercise may be more effective at stimulating the cerebrovasculature, resulting in greater improvements in cerebrovascular function as compared to continuous aerobic exercise in healthy adult men. These findings provide some important information that would help enhance exercise therapy programs for patients with arteriosclerosis, especially in the cerebral circulation.

Reconstructed Diaphragm by Fascia Lata: 13 Years In Vivo.

We report a case of resection of a reconstructed diaphragm with fascia lata after 13 years. A 66-year-old man was diagnosed with a solitary fibrous tumor of the pleura. Thirteen years prior, resection for left postoperative pleural dissemination of solitary fibrous tumor with diaphragmatic resection was performed, and left fascia lata was used for diaphragmatic reconstruction. He relapsed, and the diaphragm was re-resected and re-reconstructed with right fascia lata. The resected, reconstructed fascia lata had microvessels in the fibrous stroma, and it was observed that the autologous tissue had become more resistant to infection by obtaining a blood supply.

Successful treatment with endoscopic transpapillary drainage for gallbladder perforation associated with steroid treatment for interstitial pneumonia (with video).

This case report highlights the clinical efficacy of endoscopic transpapillary drainage for gallbladder perforation in a high-risk surgical patient with a history of steroid treatment for interstitial pneumonia. The usefulness of endoscopic transpapillary gallbladder drainage in high-risk surgical patients with acute cholecystitis has not been established. In difficult cases of emergent surgery, such as described here, endoscopic transpapillary drainage is a promising method to manage gallbladder perforation and acute cholecystitis recurrence.

A unique cause of chronic abdominal pain.

The images presented here demonstrated how we arrived at the diagnosis of Ascaris lumbricoides infection in a 54-year-old man with chronic abdominal pain by capsule endoscopy (CE). In this case, computed tomography (CT) images were not representative, and further investigation with CE was required to confirm the diagnosis. The combination of CT and CE was useful for diagnosing Ascaris lumbricoides infection in this patient.

Improved accuracy in high-frequency AC transport measurements in pulsed high magnetic fields.

We show theoretically and experimentally that accurate transport measurements are possible even within the short time provided by pulsed magnetic fields. For this purpose, a new method has been devised, which removes the noise component of a specific frequency from the signal by taking a linear combination of the results of numerical phase detection using multiple integer periods. We also established a method to unambiguously determine the phase rotation angle in AC transport measurements using a frequency range of tens of kilohertz. We revealed that the dominant noise in low-frequency transport measurements in pulsed magnetic fields is the electromagnetic induction caused by mechanical vibrations of wire loops in inhomogeneous magnetic fields. These results strongly suggest that accurate transport measurements in short-pulsed magnets are possible when mechanical vibrations are well suppressed.

Tug-of-war between actomyosin-driven antagonistic forces determines the positioning symmetry in cell-sized confinement.

Symmetric or asymmetric positioning of intracellular structures including the nucleus and mitotic spindle steers various biological processes such as cell migration, division, and embryogenesis. In typical animal cells, both a sparse actomyosin meshwork in the cytoplasm and a dense actomyosin cortex underneath the cell membrane participate in the intracellular positioning. However, it remains unclear how these coexisting actomyosin structures regulate the positioning symmetry. To reveal the potential mechanism, we construct an in vitro model composed of cytoplasmic extracts and nucleus-like clusters confined in droplets. Here we find that periodic centripetal actomyosin waves contract from the droplet boundary push clusters to the center in large droplets, while network percolation of bulk actomyosin pulls clusters to the edge in small droplets. An active gel model quantitatively reproduces molecular perturbation experiments, which reveals that the tug-of-war between two distinct actomyosin networks with different maturation time-scales determines the positioning symmetry.

Detecting quadrupole: a hidden source of magnetic anisotropy for Manganese alloys.

Mn-based alloys exhibit unique properties in the spintronics materials possessing perpendicular magnetic anisotropy (PMA) beyond the Fe and Co-based alloys. It is desired to figure out the quantum physics of PMA inherent to Mn-based alloys, which have never been reported. Here, the origin of PMA in ferrimagnetic Mn3- δ Ga ordered alloys is investigated to resolve antiparallel-coupled Mn sites using x-ray magnetic circular and linear dichroism (XMCD/XMLD) and a first-principles calculation. We found that the contribution of orbital magnetic moments in PMA is small from XMCD and that the finite quadrupole-like orbital distortion through spin-flipped electron hopping is dominant from XMLD and theoretical calculations. These findings suggest that the spin-flipped orbital quadrupole formations originate from the PMA in Mn3- δ Ga and bring the paradigm shift in the researches of PMA materials using x-ray magnetic spectroscopies.

Habitual cigarette smoking attenuates shear-mediated dilation in the brachial artery but not in the carotid artery in young adults.

In the present study, we hypothesized that habitual cigarette smoking attenuates endothelial function in the cerebral circulation as well as that of the peripheral circulation in young adults. To test this hypothesis, we measured cerebrovascular and peripheral flow-mediated dilation (FMD) in young smokers and nonsmokers in the present study. Ten healthy nonsmokers and 10 smokers participated in the study. We measured blood velocity and diameter in the brachial artery and internal carotid artery (ICA) using Doppler ultrasound. We identified shear-mediated dilation in the brachial artery and ICA by the percentage change in peak diameter during hyperemia stimulation (reactive hyperemia and hypercapnia). We measured the baseline diameter and the shear rate area under the curve from the onset of hyperemia to peak dilation in the brachial artery and ICA, finding the measurements of the smokers and those of the nonsmokers did not differ (p > .05). In contrast to brachial FMD (5.07 ± 1.79% vs. 7.92 ± 3.01%; smokers vs. nonsmokers, p = .019), FMD in the ICA was not attenuated in the smokers compared with that of the nonsmokers (5.46 ± 2.32% vs. 4.57 ± 2.70%; p = .442). These findings indicate that in young healthy smokers, cerebral endothelial function was preserved, and the response of cerebral endothelial function to smoking was different from that of peripheral vasculature.

Does respiratory drive modify the cerebral vascular response to changes in end-tidal carbon dioxide?

NEW FINDINGS: What is the central question of this study? There is an interaction between the regulatory systems of respiration and cerebral blood flow, because the mediator (CO2 ) is the same for both physiological systems. We examined whether the traditional method for determining cerebrovascular reactivity to CO2 is modified by changes in respiration. What is the main finding and its importance? Cerebrovascular reactivity was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may result in under- or overestimation of cerebrovascular reactivity determined by traditional methods in healthy adults. ABSTRACT: The cerebral vasculature is sensitive to changes in the arterial partial pressure of CO2 . This physiological mechanism has been well established as a cerebrovascular reactivity to CO2 (CVR). However, arterial CO2 may not be an independent variable in the traditional method for assessment of CVR, because the cerebral blood flow response is also affected by the activation of respiratory drive or higher centres in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, 10 young, healthy subjects performed hyper- or hypoventilation to change end-tidal CO2 ( PET,CO2 ) with different concentrations of CO2 in the inhaled gas (0, 2.0 and 3.5%). We measured middle cerebral artery mean blood flow velocity by transcranial Doppler ultrasonography to identify the cerebral blood flow response to change in PET,CO2 during each set of conditions. In each set of conditions, PET,CO2 was significantly altered by changes in ventilation, and middle cerebral artery mean blood flow velocity changed accordingly. However, the relationship between changes in middle cerebral artery mean blood flow velocity and PET,CO2 as a response curve of CVR was reset upwards and downwards by hypo- and hyperventilation, respectively, compared with CVR during normal ventilation. The findings of the present study suggest the possibility that an alteration in respiration might lead to under- or overestimation of CVR determined by the traditional methods.

Magnetic Tunnel Junctions with a Nearly Zero Moment Manganese Nanolayer with Perpendicular Magnetic Anisotropy.

A magnetic nanolayer with a perpendicular magnetic easy axis and negligible magnetization is demonstrated. Even though a manganese metal is antiferromagnetic in bulk form, a few manganese monolayers grown on a paramagnetic ordered alloy template and capped by an oxide layer exhibit a strong perpendicular magnetic anisotropy field exceeding 19 T as well as a negligible magnetization of 25 kA/m. The nanolayer shows tunnel magnetoresistance. Moreover, the perpendicular magnetic anisotropy for the nanolayer can be reduced by applying an electric voltage. These findings will provide new insight into a creation of new nanolayer magnets.

A case of normotensive incidentally discovered adrenal pheochromocytoma.

Pheochromocytomas are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla. The clinical presentation includes headache, palpitation, and hypertension, but pheochromocytomas are sometimes clinically silent. The present case highlights the importance of biochemical testing for pheochromocytoma in patients with adrenal incidentaloma, even if they are completely normotensive and asymptomatic.

Effect of leg immersion in mild warm carbonated water on skin and muscle blood flow.

Leg immersion in carbonated water improves endothelial-mediated vasodilator function and decreases arterial stiffness but the mechanism underlying this effect remains poorly defined. We hypothesized that carbonated water immersion increases muscle blood flow. To test this hypothesis, 10 men (age 21 ± 0 years; mean ± SD) underwent lower leg immersion in tap or carbonated water at 38°C. We evaluated gastrocnemius muscle oxyhemoglobin concentration and tissue oxygenation index using near-infrared spectroscopy, skin blood flow by laser Doppler flowmetry, and popliteal artery (PA) blood flow by duplex ultrasound. Immersion in carbonated, but not tap water elevated PA (from 38 ± 14 to 83 ± 31 mL/min; P < 0.001) and skin blood flow (by 779 ± 312%, P < 0.001). In contrast, lower leg immersion elevated oxyhemoglobin concentration and tissue oxygenation index with no effect of carbonation (P = 0.529 and P = 0.495). In addition, the change in PA blood flow in response to immersion in carbonated water correlated with those of skin blood flow (P = 0.005) but not oxyhemoglobin concentration (P = 0.765) and tissue oxygenation index (P = 0.136) while no relations was found for tap water immersion. These findings indicate that water carbonation has minimal effect on muscle blood flow. Furthermore, PA blood flow increases in response to lower leg immersion in carbonated water likely due to a large increase in skin blood flow.

Mechanical properties of spindle poles are symmetrically balanced.

The metaphase spindle is organized for accurate chromosome segregation. One of the fundamental features of the spindle across the species is its symmetrical shape; the spindle consists of two polar arrays of microtubules at both ends. Although it has been suggested that the formation of the bipolar shape requires force balance coordination by molecular motors, i.e., kinesins and dyneins, quantitative analysis for the pole mechanics has not been conducted. Here, we demonstrate that it is not only the shape but also the stiffness and microtubule density of the pairs of pole regions are symmetrically balanced in single spindles self-assembled in Xenopus egg extracts. We found that the inhibition of dynein functions dramatically reduced the stiffness and microtubule density in the pole region. By contrast, the inhibition of one of the kinesins, Eg5, which is the antagonistic motor protein of dynein, increased the value of these parameters. Moreover, the inhibition of both dynein and Eg5 recovered these parameter values to those of non-treated spindle poles. We also found that, when one pole structure was held widened with the use of two glass microneedles, the opposite pole structure spontaneously widened, resulting in the formation of the barrel-like shaped spindle. The values of stiffness and microtubule density in the manipulated pole region decreased, following the spontaneous decrement of those in the paired unmanipulated pole region. These results suggest that the spindle possesses a mechanism to dynamically maintain its symmetry in mechanical properties.

Spatial confinement of active microtubule networks induces large-scale rotational cytoplasmic flow.

Collective behaviors of motile units through hydrodynamic interactions induce directed fluid flow on a larger length scale than individual units. In cells, active cytoskeletal systems composed of polar filaments and molecular motors drive fluid flow, a process known as cytoplasmic streaming. The motor-driven elongation of microtubule bundles generates turbulent-like flow in purified systems; however, it remains unclear whether and how microtubule bundles induce large-scale directed flow like the cytoplasmic streaming observed in cells. Here, we adopted Xenopus egg extracts as a model system of the cytoplasm and found that microtubule bundle elongation induces directed flow for which the length scale and timescale depend on the existence of geometrical constraints. At the lower activity of dynein, kinesins bundle and slide microtubules, organizing extensile microtubule bundles. In bulk extracts, the extensile bundles connected with each other and formed a random network, and vortex flows with a length scale comparable to the bundle length continually emerged and persisted for 1 min at multiple places. When the extracts were encapsulated in droplets, the extensile bundles pushed the droplet boundary. This pushing force initiated symmetry breaking of the randomly oriented bundle network, leading to bundles aligning into a rotating vortex structure. This vortex induced rotational cytoplasmic flows on the length scale and timescale that were 10- to 100-fold longer than the vortex flows emerging in bulk extracts. Our results suggest that microtubule systems use not only hydrodynamic interactions but also mechanical interactions to induce large-scale temporally stable cytoplasmic flow.

Lung adenocarcinoma and adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by heterozygous germline mutations in the tumor suppressor gene MEN1, which encodes a nuclear protein, menin. MEN1 is characterized by the combined occurrence of tumors involving the pituitary gland, pancreatic islets, and parathyroid glands. Additionally, patients with MEN1 often exhibit adrenal tumors. Although most MEN1-associated tumors are benign, malignant lesions arising in these endocrine organs have been reported. Additionally, malignant diseases of non-endocrine organs concomitant with MEN1 have also been reported. Here, we report a rare case of a MEN1 patient who exhibited adrenocortical carcinoma (ACC) and lung adenocarcinoma (LAC). A 53-year-old Japanese woman was diagnosed with genetically proven MEN1 that initially manifested as parathyroid, pancreatic, and adrenal tumors. During the course of the disease, she developed LAC harboring the epidermal growth factor receptor gene mutations and cortisol-secreting ACC. Both tumors were surgically resected. The tumor cells were immunohistochemically negative for menin. Studies have suggested a causative link between MEN1 gene mutations and ACC, and menin expression may decrease in MEN1-related ACCs. In contrast, there are few reports suggesting a specific role of MEN1 gene mutations in LAC. Menin is often inactivated in the LACs of patients without MEN1. Thus, our patient's ACC probably occurred as part of MEN1, whereas the latter had no evident etiological association with her LAC. This case demonstrates the need for physicians to consider the potential development of malignant diseases originating from both endocrine and non-endocrine organs in MEN1 patients.

Preparation of a cell line persistently infected with maedi/visna virus and production of viral antigens.

We attempted to prepare a cell line that produces maedi/visna virus (MVV) and is free of contamination by other viruses and mycoplasmas. Three cell lines, which originated from a sheep, goat and bat, were infected with MVV and passaged approximately every 5 days. The cultured cells were then subjected to polymerase chain reaction analysis for MVV provirus. As a result, a cell line persistently infected with MVV was established from ZZ-R cells, which originated from the fetal goat tongue. The 50-fold concentrated culture fluid formed a precipitation line against reference antiserum.

Serum HER2 as an adjunct to assess HER2 status for advanced gastric cancer: A prospective multicenter trial (SHERLOCK).

BACKGROUND: Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity of gastric cancer can be an obstacle to accurate HER2 assessment. Serum HER2, concentrations of the HER2 extracellular domain shed into the bloodstream, has a potential to compensate HER2 immunohistochemistry (IHC) but has not been scrutinized in gastric cancer. This study sought to explore the clinical utility of serum HER2 in gastric cancer. METHODS: We performed a prospective multicenter trial (SHERLOCK trial) involving patients with all-stage gastric or gastro-esophageal junction cancer. Serum HER2 was measured using direct chemiluminescence while tissue HER2 status was determined using IHC and fluorescent in situ hybridization. For stage IV cases, concordance between local and central laboratories in tissue HER2 assessment was also evaluated. RESULTS: Of 224 patients enrolled, both tissue HER2 status and serum HER2 levels were successfully determined in 212 patients and 21% (45/212) were tissue HER2-positive. Serum HER2 levels, ranged from 4.5 to 148.0 ng/ml (median 10.3), correlated with tissue HER2 status (p = 0.003). At a cut-off level of 28.0 ng/ml determined by receiver operating characteristics analysis, sensitivity, specificity, positive and negative predictive values of serum HER2 were 22.6%, 100%, 100% and 82.3%, respectively. All nine cases with elevated serum HER2 were tissue HER2-positive stage IV cases. Among 61 stage IV cases, the agreement rate for IHC scoring between the local and the central laboratories was 82% and tissue HER2 judgment was conflicting in five (8.2%) cases. Of these five cases, four were confirmed as false-negative and two of these four patients demonstrated elevated serum HER2. CONCLUSIONS: Serum HER2 levels correlated with tissue HER2 status in gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be a useful adjunct tool to detect tissue HER2 false-negative gastric cancer.

Magnetoresistance effect in rubrene-based spin valves at room temperature.

We fabricate spin-valve devices with an Fe3O4/AlO/rubrene/Co stacking structure. Their magnetoresistance (MR) effects at room temperature and low temperatures are systemically investigated based on the measurement of MR curves, current-voltage response, etc. A large MR ratio of approximately 6% is achieved at room temperature, which is one of the highest MR ratios reported to date in organic spin valves. With decreasing measurement temperatures, we observe that the MR ratios increase because of decrease in spin scattering, and the width of the MR curves becomes larger owing to increase in the coercivity of the electrodes at low temperature. A nonlinear current-voltage dependence is clearly observed in these organic spin valves. From the measurement of MR curve for the spin valves with different rubrene layer thickness, we observe that the MR ratios monotonously decrease with increasing rubrene-layer thickness. We discuss the spin-dependent transport mechanisms in these devices based on our experimental results and the present theoretical analysis. Moreover, we note that the devices exhibit smaller MR ratios after annealing compared to their counterparts without annealing. On the basis of atomic force microscopy analysis of the organic films and device resistances, we deduce that the increase of interface spin scattering induced by large surface roughness after annealing most probably leads to reduction in the MR ratios.