Effects of Arterial Stiffness on Cerebral WM Integrity in Older Adults: A Neurite Orientation Dispersion and Density Imaging and Magnetization Transfer Saturation Imaging Study.

BACKGROUND AND PURPOSE: Arterial stiffness is reported to be able to cause axonal demyelination or degeneration. The present study aimed to use advanced MR imaging techniques to examine the effect of arterial stiffness on the WM microstructure among older adults. MATERIALS AND METHODS: Arterial stiffness was measured using the cardio-ankle vascular elasticity index (CAVI). The high-CAVI (mean CAVI ≥ 9 points) and the low-CAVI groups (mean CAVI < 9 points) were created. The neuronal fiber integrity of the WM was evaluated by neurite orientation dispersion and density imaging and magnetization transfer saturation imaging. Tract-Based Spatial Statistics and the tracts-of-interest analysis were performed. Specific WM regions (corpus callosum, internal capsule, anterior thalamic radiation, corona radiata, superior longitudinal fasciculus, forceps minor, and inferior fronto-occipital fasciculus) were selected in the tracts-of-interest analysis. RESULTS: In Tract-Based Spatial Statistics, the high-CAVI group showed a significantly lower myelin volume fraction value in the broad WM and significantly higher radial diffusivity and isotropic volume fraction values in the corpus callosum, forceps minor, inferior fronto-occipital fasciculus, internal capsule, corona radiata, and anterior thalamic radiation than the low-CAVI group. In tracts-of-interest analysis using multivariate linear regression, significant associations were found between the mean CAVI and radial diffusivity in the anterior thalamic radiation and the corona radiata; isotropic volume fraction in the anterior thalamic radiation and the corona radiata; and myelin volume fraction in the superior longitudinal fasciculus (P < .05). Additionally, partial correlation coefficients were observed for the significant associations of executive function with radial diffusivity and myelin volume fraction (P < .05). CONCLUSIONS: Arterial stiffness could be associated with demyelination rather than axonal degeneration.

Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer.

BACKGROUND: Atrial fibrillation is common after oesophageal surgery. The aim of this study was to evaluate whether landiolol hydrochloride was effective and safe in the prevention of atrial fibrillation after oesophagectomy, and to see whether a reduction in incidence of atrial fibrillation would reduce other postoperative complications. METHODS: This single-centre study enrolled patients scheduled for transthoracic oesophagectomy in a randomized, double-blind, placebo-controlled trial between March 2013 and January 2016. Enrolled patients were randomized with a 1 : 1 parallel allocation ratio to either landiolol prophylaxis or placebo. The primary endpoint was the occurrence of atrial fibrillation after oesophagectomy. Secondary endpoints were incidence of postoperative complications, and effects on haemodynamic and inflammatory indices. RESULTS: One hundred patients were enrolled, 50 in each group. Postoperative atrial fibrillation occurred in 15 patients (30 per cent) receiving placebo versus five (10 per cent) receiving landiolol (P = 0·012). The overall incidence of postoperative complications was significantly lower in the landiolol group (P = 0·046). In the landiolol group, postoperative heart rate was suppressed effectively, but the decrease in BP was not harmful. The interleukin 6 level was significantly lower on days 3 and 5 after surgery in the landiolol group (P = 0·001 and P = 0·002 respectively). CONCLUSION: Landiolol was effective and safe in preventing atrial fibrillation after oesophagectomy. Registration number: UMIN000010648 (http://www.umin.ac.jp/ctr/).

Visualizing septin and cell dynamics in mammalian brain slices.

Correct neuronal migration is crucial for the brain architecture and function. During brain development, excitatory and inhibitory neurons generated in the ventricular zone (VZ) of the dorsal telencephalon and ganglionic medial eminence, respectively, move to their final destinations in tightly regulated spatiotemporal manners. While a variety of morphological methods have been applied to neurobiology, in utero electroporation (IUE) technique is one of the most powerful tools for rapid gain- and loss-of-function studies of brain development. This method enables us to introduce genes of interest into VZ progenitor and stem cells of rodent embryos, and to observe resulting phenotypes such as proliferation, migration, and cell morphology at later stages. In this chapter, we first summarize basic immunohistochemistry methods that are foundations for any advanced methods and showed data on the distribution of Sept6, Sept9, and Sept14 as examples. Then, IUE method is described where functional analyses of Sept14 during brain development are used as examples. We subsequently refer to the in vivo electroporation (IVE)-mediated gene transfer, which is conceptually the same method as IUE, into granule cells of hippocampal dentate gyrus in neonatal mice. Finally, an IUE-based time-lapse imaging method is explained as an advanced technique for the analyses of cortical neuron migration. IUE and IVE methods and the application would contribute greatly to the morphological analyses of septins as well as other molecules to elucidate their neuronal functions and pathophysiological roles in various neurological and psychiatric disorders.

Optical dynamics of energy-transfer from a CdZnO quantum well to a proximal Ag nanostructure.

We studied photoluminescence (PL) and energy-transfer dynamics in a hybrid structure comprising a Cd(0.08)Zn(0.92)O quantum well (QW) and an Ag nanostructure. The observed PL quenching was dependent on the electronic states in the QW. Quenching occurred at low temperature where excited carriers recombined radiatively because of excitonic localization, which disappeared with increasing temperature due to delocalization of excitons. Furthermore, nanostructured Ag surfaces produced local surface plasmon (LSP) absorption that was resonant with the PL peak energy of the QW emission. These results indicate that the recombination energy of excitons transfers nonradiatively to induce LSP excitation, which was revealed using time-resolved PL measurements.

Hydrogen sensing properties of protective-layer-coated single-walled carbon nanotubes with palladium nanoparticle decoration.

Protective-layer-coated single-walled carbon nanotubes (SWNTs) with palladium nanoparticle decoration (Pd-SiO(2)-SWNTs) were fabricated and their sensing properties for hydrogen (H(2)) were investigated. SWNTs were coated with a 3-4 nm thick SiO(2) layer by pulsed laser deposition and subsequently decorated with Pd nanoparticles by electron beam evaporation. Even though the SWNTs were completely surrounded by a protective layer, Pd-SiO(2)-SWNTs responded to H(2) down to a concentration of 1 part per million. Compared with the Pd nanoparticle-decorated SWNTs without a protective layer (Pd-SWNTs), Pd-SiO(2)-SWNTs exhibited highly stable sensor responses with variations of less than 20%; Pd-SWNTs showed a variation of 80%. The density of the Pd-SWNTs significantly decreased after the sensing test, while that of the Pd-SiO(2)-SWNTs with the netlike structure remained unchanged. The hydrogen sensing mechanism of the Pd-SiO(2)-SWNTs was attributed to the chemical gating effect on the SWNTs due to dipole layer formation by hydrogen atoms trapped at the Pd-SiO(2) interface. Moreover, the relationship between H(2) concentration and sensor response can be described by the Langmuir isotherm for dissociative adsorption.

Inhibition of N-methyl-D-aspartate receptor activity resulted in aberrant neuronal migration caused by delayed morphological development in the mouse neocortex.

Embryonic and neonatal neocortical neurons already express functional N-methyl-D-aspartate (NMDA) receptors before they form synapses. To elucidate the role of NMDA receptors in neuronal migration in the developing neocortex, we visualized radially migrating neurons by transferring the enhanced green fluorescent protein (EGFP) gene into the ventricular zone (VZ) of the mouse neocortex using in utero electroporation at E15.5. Two days later, we prepared neocortical slices and examined the EGFP-positive cells using time-lapse imaging in the presence of the NMDA receptor antagonist Cerestat. The EGFP-positive cells generated in the VZ in the control slices exhibited a multipolar morphology, but within several hours they became bipolar (with a leading process and an axon-like process) and migrated toward the pial surface. By contrast, many of the multipolar cells in the Cerestat-treated slices failed to extend either process and become bipolar, and frequently changed direction, although they ultimately reached their destination even after Cerestat-treatment. To identify the molecules responding for mediating NMDA signaling during neuronal migration and the changes in morphology observed above, we here focused on Src family kinases (SFKs), which mediate a variety of neuronal functions including migration and neurite extension. We discovered that the activity of Src and Fyn was reduced by Cerestat. These findings suggest that NMDA receptors are involved in neuronal migration and morphological changes into a bipolar shape, and in the activation of Src and Fyn in the developing neocortex.

Distribution of optokinetic sensitivity across the retina of mice in relation to eye orientation.

We examined the effects of stimulus size and location on the mouse optokinetic response (OKR). To this end, we recorded initial OKRs elicited by a brief presentation of horizontally moving grating patterns of different vertical widths and locations in the visual field. Large-field stimuli generated large sustained OKRs, whereas visual stimuli of narrower vertical widths elicited weaker sustained responses at the later period (400-500 ms after the onset of stimulus motion). However, even stimuli of only 5 degrees vertical width elicited detectable transient responses at the initial open-loop period (100-200 ms after the onset of stimulus motion). Presenting 5 degrees -width stimuli at different vertical locations (-10 degrees to +35 degrees relative to the horizon) revealed the spatial distribution of optokinetic sensitivity across the retina. The most sensitive part of the visual field was located at +25 degrees . In addition, we examined the vertical orientation of the eye under our stereotaxic set-up. We observed the optic disc using a hand-held fundus camera and determined the ocular orientation. All eye orientations were distributed in the range of +20-30 degrees relative to the horizon (25.2+/-2.5 degrees ). Thus, the direction of the most sensitive visual field matched the angle of eye orientation. These findings indicate that the spatial distribution of visual field sensitivity to optokinetic stimuli coincides with the distribution of retinal ganglion cell density.

Successful therapeutic use of a single-dose of rituximab on relapse in adults with minimal change nephrotic syndrome.

Minimal change nephrotic syndrome (MCNS) usually is considered to have a good renal prognosis, but the frequency of relapses is a therapeutic challenge to physicians. The treatment of patients with multiple relapses remains a matter of controversy, because few controlled studies are available. We report the case of a 25-year-old man who experienced relapses of MCNS. Single-dose rituximab therapy (total dose 500 mg) was given during the fourth relapse. Complete remission occurred 10 days later, when no CD19/20-positive B cells were detected in the blood. This the first report of efficacy of single-dose rituximab therapy to treat multi-relapsing MCNS in an adult patient.

Raman scattering study of multiferroic Ho(3)Fe(5)O(12) thin films.

Ho(3)Fe(5)O(12) crystallizes in a body-centered cubic lattice and shows no ferroelectricity because of its highly symmetric (centrosymmetric) crystal structure. However, in heteroepitaxially grown thin films, Ho(3)Fe(5)O(12) may exhibit ferroelectricity because of lattice strains induced by the substrate. In this work, heteroepitaxial films of Ho(3)Fe(5)O(12) were grown with different thicknesses of 50-160 nm and studied by x-ray diffraction and Raman scattering. The results were compared with those of bulk polycrystals to characterize residual strains. At room temperature, Raman spectra of films revealed a phonon frequency shift from those of bulk samples, showing lattice distortion. There was a difference in the lattice distortion scheme between the thinner and thicker films. Results of x-ray diffraction were well correlated with the Raman data. Raman measurements at 300-800 K showed the existence of lattice strain up to ∼650 K. This suggests a remanent-polarization character of Ho(3)Fe(5)O(12) films up to this temperature. Closeness between the magnetic ordering temperature T(N) = 567 K and T(C)∼650 K may bring us the ideal multiferroic material with an enhanced magnetoelectric effect at room temperature.

Ocular following responses of monkeys to the competing motions of two sinusoidal gratings.

Ocular following responses (OFRs) were elicited in monkeys at short latencies ( approximately 50ms) by applying motion in the form of successive 1/4-wavelength steps to each of two overlapping vertical sine-wave gratings that had different spatial frequencies. In the first experiment, the two sine waves had spatial frequencies in the ratio 3:5 and moved in opposite directions. The initial OFRs showed a highly nonlinear dependence on the relative contrasts of the competing sine waves. On average, when the contrast of one was less than a third of that of the other then the one with the lower contrast became ineffective - as though suppressed - and the OFR was entirely determined by the sine wave of higher contrast: winner-take-all. In a second experiment, the two sine waves had spatial frequencies in the ratio 3:7 and moved in the same direction (though at different speeds). The initial OFRs again showed a highly nonlinear dependence on the relative contrasts of the competing sine waves, with a winner-take-all outcome when the contrasts of the two sine waves were sufficiently different. In both experiments, the nonlinear dependence on the relative contrasts of the competing sine waves was well described by a contrast-weighted-average model with just two free parameters. These findings were very similar to those of [Sheliga, B.M., Kodaka, Y., FitzGibbon, E.J., Miles, F.A., 2006c. Human ocular following initiated by competing image motions: evidence for a winner-take-all mechanism. Vision Res. 46, 2041-2060] on the human OFR, indicating that the monkey is a good animal model for studying the nonlinear interactions that emerge when competing motions are used.

Centripetal bias on preparation for smooth pursuit eye movements based on the anticipation.

It has been reported that a brief perturbation of a stationary target during fixation induces larger eye movement when monkeys anticipate future smooth pursuit than when they do not. Here, we recorded eye movements in human subjects after briefly perturbing a target and the eccentricity of its initial position was changed under three conditions: (1) subjects anticipated saccades for a target that appeared before; (2) they anticipated smooth pursuit for a target that appeared before; and (3) they anticipated smooth pursuit but did not know beforehand where the target started from. We found that in condition 2 substantial eye movements were induced by the perturbation started moving toward the center. However, weak responses were observed in conditions 1 and 3. These results indicate that ocular responses to brief perturbations of the target at eccentric positions are increased with centripetal bias when human subjects prepare for future smooth pursuit.

Combinatorial peptide library for the analysis of antigen recognition by T cells.

Peptides that consist of 19 residues with random sequences (X19) were considered to deliver antigenic stimuli to CD4T cells. When IL-4, IL-7, IL-9, IL-15 and agonistic Ab to CD29 were co-cultured with single peripheral CD4T cells in the presence of X19 and feeder cells, T cells exhibited clonal expansion. These T cell clones showed heterogeneous proliferation patterns against KGXXXXXXXXXGK-based and KGXXXXXXXXXGKGKK-based combinatorial peptide libraries. Pattern-match search on one of the T cell clones resulted in peptide ligand candidates, one of which induced proliferation, as did protein molecules carrying the corresponding sequence. Combinatorial chemistry was useful in determining not only peptide ligands but also peptide superagonists. For this purpose, use of reverse-phase hydrophobic interaction chromatography and mass spectrometry analysis was efficient. Detailed methods are described in the paper.

Helicobacter pylori infection in rheumatoid arthritis: effect of drugs on prevalence and correlation with gastroduodenal lesions.

OBJECTIVE: The aim of this study was to investigate the impact of Helicobacter pylori infection on clinical features in patients with rheumatoid arthritis (RA) under medication with non-steroidal anti-inflammatory drugs. METHODS: One hundred and eighty-four patients with RA were tested for the presence of H. pylori infection. Clinical features and gastroduodenal lesions were compared between H. pylori-positive and -negative patients. RESULTS: One hundred and thirteen patients were positive and 71 patients were negative for H. pylori. The age, severity of RA, prevalence of gastrointestinal symptoms and gastroduodenal lesions and the class of gastroprotective drugs were not different between the two groups. Reflux oesophagitis was less frequent and sulphasalazine was less frequently administered in the H. pylori-positive group. CONCLUSIONS: The severity of RA, prevalence of gastroduodenal lesions other than reflux oesophagitis and the application of gastroprotective drugs do not seem to depend upon H. pylori infection in RA patients. Sulphasalazine may be protective against H. pylori infection.

Difference in degree of mucosal atrophy between elevated and depressed types of gastric epithelial tumors.

BACKGROUND: The significance of atrophy in the background mucosa and Helicobacter pylori infection in the morphogenesis of gastric epithelial tumors has not yet been investigated. METHODS: The degree of mucosal atrophy, as determined by a histological analysis and the serum pepsinogen (PG) levels, and H. pylori status were investigated in patients with elevated adenoma (EA group; n = 40), elevated early cancer of intestinal type (ECI group; n = 30), depressed early cancer of intestinal type (DCI group; n = 37) and depressed early cancer of diffuse type (DCD group; n = 33), and the findings were then compared to those in 91 controls. RESULTS: At all sites of the stomach, the histologic score of atrophy was higher in the EA group and in the ECI group than in the controls. In the DCI group, the histologic score of atrophy in the antrum was higher than in the controls, but no such difference in the score was found in the DCD group. The PG I/II ratios in the EA, ECI and DCI groups were significantly lower than in the controls, and the value was also different between the ECI and DCI groups. While H. pylori prevalence was higher in all groups than in the controls, a logistic regression analysis which included the grade of atrophy as a determinant revealed the infection to be an independent associated factor for the DCD group. CONCLUSIONS: The difference in the background mucosal atrophy seems to contribute to different macroscopic types in gastric epithelial tumors. This seems to be the case especially for cancer of intestinal type.

Sarcoidosis with giant parotomegaly.

We report the case of a 63-year-old man with bilateral parotid gland sarcoidosis. Giant, elastic, hard, subcutaneous tumors had been present on the right parotic and submaxillary regions for 11 years and on the left for 1 year. The patient had had diabetes mellitus for 8 years. Noncaseating epithelioid cell granulomata were revealed histopathologically in the periductal area of the parotid gland. Bilateral hilar lymphadenopathy was noted on chest x-ray studies. Serum levels of lysozyme were increased. Levels of serum angiotensin-converting enzyme were within normal limits. Tuberculin skin reaction was positive. The tumors gradually improved after treatment with oral minocycline. Giant parotomegaly, as it occurred in this case, is very rare.

[A case report of mirror writing with low perfusion of bilateral anterior cerebral arteries].

A 20-year-old female experienced temporary unintentional mirror writing associated with low perfusion of the bilateral anterior cerebral arteries. When she was 17 years old, she had developed multiple idiopathic intracerebral hemorrhages and right hemiparesis. At the age of 20, she had a generalized convulsion for which she was transferred to our department. Computed tomography (CT) and magnetic resonance images of the brain were obtained, but no fresh abnormal lesion could be detected. The following day, after she had recovered from postictal symptoms, she wrote mirror image words, and her mirror writing then gradually improved within one week. Single photon emission CT showed low perfusion of both anterior cerebral arteries. We concluded that bilateral vascular insufficiency to the supplementary motor areas and corpus callosum caused mirror writing in this case.

Efficient in utero gene transfer system to the developing mouse brain using electroporation: visualization of neuronal migration in the developing cortex.

We report a novel gene transfer system using electroporation. We used this technique to introduce a marker gene plasmid containing enhanced green fluorescent protein into mouse brains at embryonic day 12-17 without removing the embryos from the uterus. The embryos were allowed to continue to develop in utero, and more than 80% were born normally expressing the exogenous gene. Enhanced green fluorescent protein driven by the cytomegalovirus promoter was strongly expressed in the ventricular zone, radial fibers and migrating neuroblasts, but not in mature neurons, suggesting that the cytomegalovirus promoter is silenced after the cells differentiate into mature neurons. Since there is still no convenient way of visualizing the migrating neuroblasts, especially of distinguishing them from the surrounding mature neurons in the cortical plate, this system should provide a good tool for analysing neuronal migration. In the postnatal lateral cortex, neuroblasts migrated almost "tangentially" along the obliquely running "radial" fibers beneath the cortical plate, and after entering the cortical plate, turned towards the marginal zone and migrated radially. Neurons with primitive dendrites were observed only along the border between the marginal zone and the cortical plate, and never at other sites, such as in the middle of the cortical plate. These results imply that the neuroblasts do terminate migration and start differentiation to mature neurons when they encounter the marginal zone, as has long been suggested. By contrast, when elongation factor 1alpha promoter was used, prominent fluorescence allowed visualization of the entire mature neurons as well. The labeled neurons were observed to send axons to the contralateral cortex where they arborized extensively.Thus, this system is much easier and more efficient than virus-mediated gene transfer, and is useful for gain-of-function analysis of neural cell fate determination, migration, positioning and axon path-finding in mouse embryos.