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Stabilisation splint therapy has long been thought to be effective for the management of temporomandibular disorders (TMD). However, the superiority of stabilisation splint therapy compared to other TMD treatments remains controversial. The aim of this study was to determine the efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for TMD. A total of 181 TMD participants were randomly allocated to a non-splint multimodal therapy (NS) group (n = 85) or a nonsplint multimodal therapy plus stabilisation splint (NS+S) group (n = 96). Non-splint multimodal therapy included self-exercise of the jaw, cognitive--behavioural therapy, self-management education and additional jaw manipulation. Three outcome measurements were used to assess treatment efficacy: mouth-opening limitation, oro-facial pain and temporomandibular joint sounds. A two-factor repeated-measures analysis of variance (ANOVA) was used to evaluate the efficacy of the two treatment modalities (NS vs. NS+S), and Scheffe's multiple comparison test was used to compare the treatment periods. Subgroup analyses were performed to disclose the splint effects for each TMD diagnostic group. All three parameters significantly decreased over time in both groups. However, there were no significant differences between the two treatment groups in the total comparison or subgroup analyses; an exception was the group with degenerative joint disease. No significant difference between the NS and NS+S treatment approaches was revealed in this study. Therefore, we conclude that the additional effects of stabilisation splint are not supported for patients with TMD during the application of multimodal therapy. [ABSTRACT FROM AUTHOR]

Abstract: A disintegrin and metalloproteinase with thrombospondin type 1 motifs, number 13 (ADAMTS13) is a plasma zinc metalloprotease also known as von Willebrand factor (VWF)-cleaving protease. Deficiency of ADAMTS13 activity is known to cause thrombotic thrombocytopenic purpura (TTP) in humans. We isolated the canine ADAMTS13 cDNA, which encodes 1502 amino acids, and expressed the recombinant protein to evaluate VWF-cleaving ability. Although the propeptide domain was longer and the TSP1 repeat domain was shorter than those in other species, the overall structures were similar to human and mouse ADAMTS13. Recombinant canine ADAMTS13 cleaved the 250-kDa VWF monomer into two fragments of 150kDa and 120kDa. Furthermore, high molecular weight VWF multimers were abolished based on the activity of ADAMTS13. These results could facilitate research into hemostatic disorders such as TTP in dogs. [Copyright &y& Elsevier]

Objectives: The aim of this prospective study was to elucidate the efficacy of contrast-enhanced three-dimensional (3D) ultrasound with Sonazoid® (GF Healthcare, Oslo, Norway) as a non-invasive tool to discriminate idiopathic portal hypertension (IPH) from cirrhosis by demonstration of portal vein structure. Methods: There were 16 patients: 11 with biopsy-proven cirrhosis and 5 with biopsyproven IPH. Intrahepatic right portal vein images were taken by 3D ultrasound from 1 min after the injection of Sonazoid (0.0075ml kg-1). Portal vein appearances were compared between 3D ultrasound and percutaneous transhepatic portography (PTP) by four independent reviewers. Sensitivity, specificity and area under the receiver operating characteristic curve (Az) of the images were used for the diagnosis of cirrhosis/IPH, and interimaging, inter-reviewer and interoperator agreement were examined. Results: Sensitivity, specificity and Az of PTP for the diagnosis of cirrhosis/IPH were 63.6%/100%, 100% and 0.9 (0.71-1.0) by Reviewer I and 90.9%/100%, 100% and 1.0 by Reviewer III, respectively. Similarly, sensitivity, specificity and Az of 3D ultrasound for diagnosis of cirrhosis/IPH were 54.5%/80%, 100% and 0.96 (0.84-1.0) by Reviewer II and 72.7%/80%, 100% and 0.97 (0.9-1.0) by Reviewer IV, respectively. Diagnostic agreement between PTP and 3D ultrasound was good between Reviewers I and II (κ=0.793) and good between Reviewers III and IV (κ=0.732). Inter-reviewer agreement was good between Reviewers I and III for PTP diagnosis (κ=0.735), and good between Reviewers II and IV for 3D ultrasound diagnosis (κ=0.792). Interoperator agreement of diagnostic results was good (κ=0.740). Conclusion: Non-invasive visualisation of intrahepatic portal vein structure by contrast-enhanced 3D ultrasound with Sonazoid may have the potential to discriminate IPH from cirrhosis. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this prospective study was to elucidate the efficacy of using contrast-enhanced ultrasound to characterise focal hepatic lesions appearing non-hypervascular on contrast-enhanced CT in chronic liver diseases. Methods: The study population included 22 patients with cirrhosis or chronic hepatitis, who between them had 27 focal hepatic lesions smaller than 20mm (mean 13.9±3.4) that appeared non-hypervascular on contrast-enhanced CT. Contrast-enhanced ultrasound with perflubutane microbubble agent (Sonazoid, 0.0075 ml kg-1) was performed prior to ultrasound-guided needle biopsy, and intensity analysis was done for hepatic lesions in the early phase (-60 s) and late phase (600 s post injection). Results: All seven early-phase hyperenhanced lesions were hepatocellular carcinoma (HCC). 20 lesions iso- or hypoenhanced during the early phase consisted of 11 regenerative nodules (RNs) and 9 HCCs. HCC was more frequent in early-phase hyperenhanced lesions than in iso- or hypoenhanced lesions (p=0.0108). Both late-phase hypoenhanced lesions were HCCs, whereas 25 late-phase isoenhanced lesions consisted of 11 RNs and 14 HCCs. The enhancement patterns of the 11 RNs included isoenhanced appearance in both the early and late phases in 8 lesions, and early-phase hypoenhancement combined with late-phase isoenhancement in the remaining 3. Both of these enhancement patterns (i.e. either iso-iso or hypo-iso) were found in 9 malignant lesions, 9 (75%) of the 12 well-differentiated HCCs. Conclusion: Hypervascularity on contrast-enhanced ultrasound with Sonazoid strongly suggested HCC regardless of non-hypervascularity on CT, and late-phase hypoenhancement was another possible finding of HCC. However, characterisation of hepatic lesions with other enhancement patterns was difficult using our technique. [ABSTRACT FROM AUTHOR]

Abstract: Particles are often electrostatically charged by frictional contact during powder-handling operations. This phenomenon is called ‘triboelectric charging’ or ‘contact electrification’. The charged particles cause problems such as particle deposition and adhesion. In addition, if particles are excessively charged, an electrostatic discharge may occur, which can pose a risk of fire and explosion hazards; thus, to mitigate the adverse effects, it is important to elucidate the underlying triboelectric charging mechanisms. The electrostatics is, on the other hand, very useful in a number of applications that have been developed using the principles. In this review, the basic concepts and theories of charge transfer between solid surfaces are summarized, and chemical factors depending on materials and environmental effects are described. To theoretically analyze the process of particle charging, relevant models are discussed. Using the models, particle charging by repeated impacts on a wall is formulated. To experimentally evaluate particle charging, measurement and characterization methods are outlined. Furthermore, important applications and computer simulations are described. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the relationship between the therapeutic effect of balloon-occluded retrograde transvenous obliteration (B-RTO) and haemodynamic features in the short gastric vein (SGV) in patients with gastric fundal varices (GV). The subjects in this retrospective cohort study comprised 34 patients who had moderate- or large-grade GV with the SGV both on retrograde venography and Doppler ultrasound. The diameter, flow velocity and flow volume in the SGV measured by Doppler ultrasound before B-RTO with 1 h balloon occlusion were compared with the therapeutic effect. Embolisation of GV was achieved in 30/34 patients (88.2%): 27 by initial B-RIO and 3 by second B-RIO. Flow velocity and flow volume in the SGV before B-RIO were significantly lower in the 27 patients with a complete effect on initial B-RIO (7.19±2.44 cm s-1, p=0.0246; 189.52±167.66 ml min-1, p=0.002) than in the 7 patients with an incomplete effect (10.41 ± 5.44cm ç1, 492.14±344.94 ml min-1). Neither endoscopy nor contrast-enhanced CT had recurrent findings of GV in the subject during the follow-up period (94-1440 days; mean, 487.2 ±480.5 days). In conclusion, haemodynamic evaluation of the SGV using Doppler ultrasound may be useful for the prediction of the therapeutic effect of B-RIO. [ABSTRACT FROM AUTHOR]

Aldehyde oxidase (AO) is a homodimer with a molecular weight of 300 kDa. To clarify the reasons for the well-known differences in rat strains, we set out to study the relationship between AO activity and the expression levels of its dimer. AO-catalyzed 2-oxidation activity of (S)-RS-8359 was measured in liver cytosols from ten rat strains. The expression levels of AO dimeric protein were evaluated by the native-PAGE/Western blot. Rat strains with low AO activity showed only a monomer, whereas strains with high activity overwhelmingly exhibited a dimer. Exceptionally, one strain in the high AO activity group displayed complex mixed expression patterns of low and high AO activity groups. However, there was a good relationship between AO activity and the expression levels of a dimer, but not of a monomer. The results suggest that rat strains with low AO activity lack the ability to produce a dimer necessary for catalytic activity, and AO differences in rat strains should be discussed in terms of the expression levels of the dimer itself. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of contrast-enhanced ultrasound for the localization of ultrasonically invisible hypervascular lesions in the liver to facilitate percutaneous ultrasound-guided treatment. Materials and methods: Forty patients with 47 ultrasonically invisible hypervascular lesions (5–20mm) diagnosed on contrast-enhanced computed tomography were enrolled in the retrospective study. Contrast-enhanced ultrasound (CEUS) with Levovist was performed to localize the lesions both in the early phase and liver-specific phase. Diagnosis of was confirmed by percutaneous needle biopsy where feasible, and on the basis of on treatment outcomes or changes in computed tomography findings in those not amenable to biopsy. Results: Thirty-two lesions were diagnosed as hepatocellular carcinoma (HCC). Contrast-enhanced ultrasound localized hepatocellular carcinoma in 24/32 (75%) lesions, the mean diameter (15.1±4.9mm), as measured using computed tomography, being significantly larger than that of the remaining eight lesions (10.5±2.1mm). Ultrasound-guided treatment was performed in 19 of the 24 lesions, and transarterial chemoembolization (TACE) was applied for the other five lesions because of difficult percutaneous access. Five of the eight non-visualised lesions were treated by transarterial chemoembolization, and the other three by surgical resection. The beneficial effect of CEUS was significantly greater when the reason for poor initial visualisation was the coarse liver architecture (17/17) than when it was due to adverse location (seven of 15, p <0.005). Fifteen of the CT-detected hypervascular lesions were considered to represent false positives for HCC, based on their behaviour during follow-up. Conclusion: Contrast-enhanced ultrasound with Levovist facilitates the application of percutaneous ultrasound-guided treatment by improving localization of ultrasonically invisible hypervascular hepatocellular carcinomas in the liver. [Copyright &y& Elsevier]

The mechanisms by which pulmonary granuloma formation is caused by administration of mycobacterial glycolipids such as trehalose dimycolate (TDM), lipoarabinomannan (LAM) and phosphatidylinositol mannosides (PIM) were investigated. When peritoneal and alveolar macrophages were stimulated with TDM, LAM and PIM in vitro, TDM exhibited the strongest tumour necrosis factor (TNF)-inducing activity. Responsiveness of macrophages from mice defected Toll-like receptor 4 (TLR4) was much higher than that of the wild-type mice. Although PIM and LAM also had a significant activity, LAM rather than PIM stimulated higher TNF-α production by alveolar macrophage. When mycobacterial glycolipids were injected as water-in-oil-in-water emulsion into mice via the tail vein, development of pulmonary granuloma in response to glycolipids were related closely to their TNF-inducing activity and TDM exhibited the strongest activity. Granuloma formation was observed not only in mice lacking interleukin (IL)-12 signalling but also interferon (IFN)-γ knock-out mice. Granuloma formation caused by glycolipids correlated with TNF-α levels in lungs. Administration of anti-TNF-α monoclonal antibody into TDM-injected IFN-γ knock-out mice decreased in granuloma formation, suggesting that development of pulmonary granuloma by mycobacterial glycolipids such as TDM is due to IFN-γ-independent and TNF-α-dependent pathway. [ABSTRACT FROM AUTHOR]

Abstract: Pressure effects of the magnetic phase transition in DyCo2 were studied by XRD and XMCD. The magnetic transition changes from 1st order to 2nd order in a range of 4–5GPa. The Co K-edge XMCD is insensitive to the pressure, which is interpreted as resulting mainly from the pressure variation of Dy 4f magnetic polarization. [Copyright &y& Elsevier]

Abstract: We have grown high quality single crystals of MgB2 by the encapsulation method. A new method which combines the magnetic torque method and the field modulation method is successfully employed to detect the dHvA oscillation and the AC response of the superconductor down to the fields below Hc2. The AC torque signal indicates that the surface superconductivity develops well above Hc2 and it evolves into the bulk superconductivity with decreasing field. The irreversible torque curve is observed at much higher fields than Hc2 and can be attributed to a pinning effect of the surface vortices. The superconducting transition detected by the AC torque method significantly broadens indicating that the supercondcuting fluctuation is not negligible. It is suggested that both the surface superconductivity and the fluctuation contribute considerably to the broadening of the resistive transition. We have found that the damping of the dHvA signal from the π band is very large around Hc2 due to the superconducting fluctuation and the pinning effect, but the damping rate becomes moderate with further decreasing field, implying that the superconducting gap may be small for the π band near Hc2. [Copyright &y& Elsevier]

In order to clarify the relationship between the electronic states and magnetic properties in rare-earth iron garnet (R-IG), X-ray magnetic circular dichroism (XMCD) spectra have been precisely recorded at Fe K-edge and R L2,3-edges, especially Dy L2,3-edges in Dy3Fe5O12 (Dy-IG). We have paid attention to the Fe electronic states in a polyhedral environment, the compensation phenomenon in an N-type ferrimagnet, and comparison between the experimental and theoretical spectra. As a result, the identification of the R L2,3-edges dichroic structures is nearly complete, and Dy(5d)–Fe(3d) mixing appears to play an indispensable role for the ferrimagnetic ordering. The difference in the Dy(5d) states between insulating Dy-IG and metallic DyAl2 compounds is briefly discussed. [Copyright &y& Elsevier]

We recently developed a novel kidney-targeted gene transfer technique in rats, using the retrograde renal vein injection of naked plasmid DNA. Many animal disease models are created in mice by transgenic or knockout technologies. However, it is much harder to perform renal vein injection in mice than in rats because they have a thin and short vein. Here we transferred the mouse interleukin (IL)-10 gene into mice by retrograde renal vein injection, using an IL-10 and immunoglobulin fusion protein (IL-10/Fc) (96-kDa) expression plasmid, pCAGGS-IL10/Fc. We observed a dose–response relationship between serum IL-10 levels and the amount of injected DNA. The serum IL-10 levels peaked at day 1 and then were sustained for at least 2 weeks. These results demonstrate that the kidney-targeted naked plasmid DNA transfer of mice by retrograde renal vein injection can be achieved, and the kidney serves as a depot organ for the production of large proteins. [Copyright &y& Elsevier]

A high level of plasmid DNA expression in rat liver can be achieved by the rapid injection of a large volume of a naked DNA solution into the tail vein, called the ‘hydrodynamics-based procedure.’ The preparation of PCR-amplified DNA fragments is easier than that of naked DNA. In this paper we evaluated the effects of expressing the erythropoietin (Epo) gene in the rat liver by injecting fCAGGS-Epo, an Epo-expressing PCR-amplified DNA fragment, via the tail vein. After injection of 5 pmol fCAGGS-Epo (10 μg) or pCAGGS-Epo (18.4 μg), plasmid DNA, the serum Epo levels peaked at week 1, then persisted for at least 12 weeks. Transgene-derived Epo secretion resulted in significant erythropoiesis. These results demonstrated that transfer of PCR-amplified DNA fragments into the rat liver via rapid tail vein injection can be achieved. This method may provide a useful means for studying the physiologic function of a putative gene. [Copyright &y& Elsevier]

Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGS-vIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4[SUP+]T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-γ, tumor necrosis factor-α, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis. [ABSTRACT FROM AUTHOR]

The skin is an important target for gene transfer because of its easy accessibility. Using plasmid DNA expressing rat erythropoietin (pCAGGS-Epo) as the vector, we previously demonstrated long-term Epo delivery in rats by muscle-targeted gene transfer using in vivo electroporation. Here we examined whether this electroporation approach could be applied to gene delivery in rat skin. To optimize gene transfer, we tested the efficiency of skin-targeted Epo gene transfer with three types of electrodes at three different electrode voltages. Each rat was injected intradermally with a total of 800 μg of pCAGGS-Epo, in the abdominal area. Plate-and-fork-type electrodes were effective for Epo delivery by skin-targeted gene transfer at Iow voltages (12∼24 V). The vector-derived Epo mRNA was expressed only at the DNA injection site. The Epo gene was expressed in a dose-dependent manner, the expression persisted for 7 weeks, and hematocrit levels were increased for 11 weeks. Skin injection with pCAGGS-lacZ showed lacZ gene expression in the epidermis on day I after injection and in the subcutaneous muscle layer on day 7. Slight skin damage due to the gene transfer procedure was evident on day 1, but absent by day 7. These results demonstrate that skin-targeted pCAGGS-Epo transfer by in vivo electroporation at Iow voltage is a useful procedure for the short-term delivery of Epo. [ABSTRACT FROM AUTHOR]

The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a short-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokinetic study of continuous Epo delivery by this method in normal rats and uremic five-sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 11 weeks. Repeated administration of the plasmid DNA effectively produced erythropoiesis. Similar erythropoiesis was observed in the uremic rats, and persisted for more than 15 weeks. Both normal and uremic rats showed a significant decrease in platelet count. Moreover, the uremic rats showed Epo-induced hypertension, which is the major sideeffect of recombinant human Epo. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the long-term continuous delivery of Epo in both normal and uremic rats. [ABSTRACT FROM AUTHOR]

Investigates the growth of aluminum phosphide layers on silicon (Si)(100) substrates by molecular beam epitaxy (MBE) and migration enhanced epitaxy. Detection of island growth mode from an initial MBE growth stage; Use of Auger electron spectroscopy; Observation of reflection high-energy electron diffraction intensity oscillations.

We have measured x-ray magnetic circular dichroism spectra at the Co and Pt L2,3-edges in Co80Pt20 perpendicular magnetization films, wherein the uniaxial magnetic anisotropy constant, Ku, significantly increases with decreasing film thickness, δ, and reaches 1.7×107 erg/cm3 for δ=3 nm. The anisotropy of the orbital magnetic moment (AOM) was estimated as a function of δ, and the relationship between AOM and Ku is discussed. When the thickness was reduced, the AOM for Pt 5d was nearly constant, whereas a weak increase was observed for Co 3d. Both AOMs are small in contrast to the large Ku, and any proportionality between AOM and Ku was hardly recognized. This result indicates that a large AOM is not always a necessary and sufficient condition for the appearance of perpendicular magnetization. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding anoctamin 10 (ANO10) mutation using exome sequencing in a patient with autosomal recessive spinocerebellar ataxia (ARSCA).

Examines the plasma thrombin-antithrombin complex concentrations in dogs with malignant tumors. Distribution of plasma thrombin-antithrombin complex concentrations in healthy dogs and dogs with malignant tumors; Hemostatic abnormalities in dogs with hemangiosarcoma; Biochemical basis for the hypercoagulable state seen in Cushing syndrome.

Aim: To examine the sonographic features of shunt vessels derived from the splenic vein at splenic hilum (SS), and explore the relationship between the SS pattern and clinical presentations. Materials and methods: This prospective study in cirrhotic patients consisted of study I (n = 15), which compared the anatomical features of SS at ultrasonography versus angiography, and study II (n = 233), which examined the incidence/haemodynamics of SS and SS-related presentations. Results: Study I showed that SS1 (running toward the upper pole of the spleen) corresponded to short gastric veins, and SS2 (running toward the lower pole of the spleen) corresponded to splenorenal/retroperitoneal shunts. In study II, SS were detected in 47.6% of patients (111/233), SS1 in 77.5% (86/111), SS2 in 17.1% (19/111), and SS3 (both SS1 and SS2) in 5.4% (6/111). The incidence of gastric cardia varices was significantly higher in patients with SS2 (6/19) than in those with SS1 (8/86, p = 0.0097), whereas the incidence of gastric fundal varices was significantly higher in patients with SS1 (44/86) than in those with SS2 (1/19, p = 0.00025) or SS3 (0/6, p = 0.015). There was no difference in the incidence of oesophageal varices among the three SS groups. The Child–Pugh score and grade of ascites was significantly worse in patients with SS3 than in those with SS1 (p < 0.0001, p = 0.0009). Hepatic encephalopathy grade was significantly worse in patients with SS2 (p = 0.0047) or SS3 (p < 0.0001) compared to SS1. Conclusion: The SS pattern facilitates estimation of the possible manifestations, indicating the direction of clinical management of cirrhosis patients. Potential poor liver function is noted in patients with SS3. [Copyright &y& Elsevier]

We propose a method for evaluating thermal conductivity of a single carbon nanotube (CNT) using a fluorescent temperature sensor in liquid and air. The CNT is fixed to sensors by photofabrication. The electrode for Joule-heating of the CNT is fabricated on the sensor. Thermal conductivity of the CNT is evaluated through the temperature difference between both ends of the CNT and the heat quantity input to the CNT. In this paper, we evaluated thermal conductivity of the same CNT in air and liquid. Calculated thermal conductivity of the CNT in air (667 ± 38 [W/m·K]) is higher than that of CNT in water (484 ± 72 [W/m·K]). [ABSTRACT FROM AUTHOR]

We studied the relationship between the lattice constant and magnetism of L 1 0 -ordered FePt under high pressure by means of first-principles calculations and synchrotron x-ray measurements. Based on our calculations, we found that the c/a ratio shows a local maximum at ∼20 GPa and that the Pt magnetic moment first remains almost unchanged and is sharply suppressed at ∼60 GPa. As for the c/a, we experimentally verified the local maximum at ∼20 GPa by powder x-ray diffraction. We also measured the x-ray magnetic circular dichroism at the Pt L edge up to ∼20 GPa. Any significant change in the Pt magnetic moment was not observed in agreement with the calculations. These results, thus, indicate that magnetic states, where the magnetization of Fe decreased and that of Pt did not change, can be created in L 1 0 -ordered FePt by lattice deformation under high pressure. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the study "Association of Estrogen Receptor a Gene Polymorphisms and Transcriptional Activity with Alzheimer's Disease." The study will be presented at a joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry which will be organized in Berlin, Germany, from August 8-14, 1999. The study failed to confirm the previously reported association between ERa gene polymorphisms and Alzheimer's Disease.

We have carefully investigated the α-ε transition pathway of iron under quasihydrostatic pressures. For this purpose, combined measurements of extended x-ray absorption fine structure (EXAFS) and x-ray magnetic circular dichroism at the Fe K edge were performed using a helium pressure-transmitting medium. Collapse of the ferromagnetism simultaneously occurs with the α-ε structural transition, which is in contrast to the scenario that the transition is driven by the pressure-induced instability of the ferromagnetism in α phase of iron. We conclude that shear stress is important to initiate the α-ε transition. Our model to fit the EXAFS profile demonstrates that the local atomic arrangement in ε phase is slightly distorted due to unfinished shuffle motion, whereas shear motion finishes at the beginning of the transition. [ABSTRACT FROM AUTHOR]

Abstract: The magnetic torque measurements were performed on two MgB2 single crystals with the different values of upper critical fields H c2 (3.7T and 3.1T at 4.2K). At low temperatures, the irreversible torque-vs-field curves τ(H) in the both samples show the peak effect, accompanied by the field-history dependence, close to H c2 for all the field directions measured. With increasing temperature, the peak in τ(H) becomes less pronounced, and disappears around T =27K. In the sample with smaller H c2, τ(H) curves display diamagnetic steps at the higher temperatures. On the other hand, in the sample with larger H c2, such a step is not observed. Our results suggest that the order–disorder transition around the peak transforms to the first-order melting transition, which is very sensitive to the degree of disorder. [Copyright &y& Elsevier]

A systematic X-ray magnetic circular dichroism (XMCD) study has been performed at the Ho L2,3-edges in Ho6Fe23 through the magnetic compensation transition. The analysis of the Ho L2,3 XMCD spectra shows that these two signals are proportional to the 4f magnetic moment through the whole temperature range. The magnetic moment of 5d shell derived from sum rules analysis is discussed in terms of the 4f influence to the 5d-band magnetism. [Copyright &y& Elsevier]

The magnetocaloric effect of the superparamagnetic nanocomposite composed of magnetite grains isolated by gold was investigated as a function of the size distribution width. The magnetic entropy change ΔS was evaluated by applying Maxwell’s relation to the magnetization data sets measured at various temperature and applied field. The size distribution was evaluated by the TEM observation, showing that the average sizes were from 4.6 to 7.4 nm and the geometric standard deviations σg from 1.32 to 1.59. Thus evaluated ΔS was found to increase with decreasing σg, demonstrating our previous anticipation that the narrow size distribution would much enhance the magnetocaloric effect of the superparamagnetic nanocomposite material. The ΔS was several times larger than that of our previous nanocomposite composed of γ-Fe2O3 and silver. [Copyright &y& Elsevier]

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10[sup4]-10[sup8] PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. β-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing. [ABSTRACT FROM AUTHOR]

Background: Nivolumab, a PD1-specific monoclonal antibody, was approved in Japan on July 2014 for patients with unresectable or metastatic melanoma. Patients: Nivolumab at 2 mg/kg every 3 weeks were initiated to 18 patients with unresectable or metastatic melanoma at University of Tsukuba Hospital. The median age was 71 (range, 39–80) and male:female ratio was 8:10. Of those, 15 patients had primary site at skin and the other 3 had at mucosa. Most of the patients was performance status (PS) score 0 or 1, except 1 patient with PS score 2. Results: Seventeen adverse events (AE) were recorded. Most common AE was thyroid dysfunction and observed in 5 (28%); hyperthyroidism in 2 and hypothyroidism in 3. Whereas no one with hyperthyroidism required treatment, 2 out of 3 with hypothyroidism were symptomatic, such as fatigue and gain weight. However, their symptoms were recovered by replacement of thyroid hormone. No patient required discontinuation of nivolumab due to AEs. Conclusion: According to our study population, using nivolumab was generally safe. Because most of AEs were mild and were manageable, nivolumab seems to be safer than Ipilimumab. However, we should keep in mind that nivolumab might induce thyroid dysfunction. Patients with symptomatic hypothyroidism required hormone replacement therapy. [ABSTRACT FROM AUTHOR]

Transforming growth factor-beta (TGF-β) signaling is dependent on the heterodimerization of the type II TGF-β receptor (TβRII) with the type I TGF-β receptor (TβRI). Activated TβRI then mediates TGF-β signals by inducing the phosphorylation of Smad2 and/or Smad3, which separately hetetorodimerize with Smad4 and translocate to the nucleus. Phosphorylation of Smad2/Smad3 by activated TβRI is inhibited by two newly discovered members of the Smad family, Smad6 and Smad7. We now report that Smad7 mRNA levels are increased in human pancreatic cancer by comparison with the normal pancreas, and that by in situ hybridization, Smad7 is over-expressed in the cancer cells within the tumor mass. Stable transfection of COLO-357 human pancreatic cancer cells with a full-length Smad7 construct leads to complete loss of the growth inhibitory response to TGF-β1, without altering TGF-β1-mediated induction of PAI-I. Furthermore, Smad7 transfected COLO-357 cells display enhanced anchorage-independent growth and accelerated growth in nude mice. These findings point to a previously unrecognized mechanism for selective suppression of TGF-β-mediated growth inhibition in cancer cells that allows for continued activation of the PAI-I promoter by TGF-β1, which may act to enhance the tumorigenicity of certain cancer cells. [ABSTRACT FROM AUTHOR]

We examined the role of Mls antigens in the induction of autoimmune gastritis (AIG) in BALB/c and DBA/2 mice subjected to thymectomy. The prevalence of AIG in Mis1b mice which underwent thymcetomy on day 3 after birth (3d-Tx) was 78% (mean), while in Mls-1a DBA/2 mice it was <6%. Whereas AIG-ncgative 3d-Tx DBA/2 mice produced 2-mercaptoethanol (2-MF)-sensitive antiparietal cell autoantibody. AIG-positive BALB/c mice made 2-ME-resistani anti-parietal cell autoantibody. In addition, the prevalence of AIG in 3d-Tx BALB/c mice which were rendered tolerant to Mis-1a antigens by injection of bone marrow cells from (BALB/c × DBA/2)F1 mice within 24 h after birth was decreased compared with the non-tolerant control mice; the prevalence being 80% in the controls and 30% in the tolerant animals. Thus, the activation of helper T cells, including T cells responding to Mls-1a antigens and including immunoglobulin class switch, appeared to he closely associated with the induction of AIG. Flowcytometric analysis confirmed that CD4-Vβ6 T cells had increased in the regional lymph nodes of the stomach in AIG mice. However, an increase in the number of Vβ11 T cells, which are known lo increase in 3d-Tx mice, occurred in the CD8, but not in the CD4T cell population. Injection of MoAb to L3T4, but not Lyt2, Vβ6-or Vβ8-TCR, into 3d-Tx BALB/c and syngeneic nude mice which had received spleen cells of 3d-Tx BALB/c mice bearing AIG completely abrogated the development of AIG, despite there being remarkable decreases in T cells expressing relevant markers to the injected antibodies in all the mice. These lindings suggest that the increase of Vβ6+ L3T4+ T cells in AIG mice was concomitant with the activation of AIG-inducing Vβ6- L3T4+ T cells. [ABSTRACT FROM AUTHOR]

Summary: Stroke can be a cause of death, while in non‐fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2–6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18–1·31, P < 0·001] and C‐reactive protein (OR = 1·29, 95% CI = 1·10–1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55–6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke. [ABSTRACT FROM AUTHOR]

We present an x-ray magnetic circular dichroism (XMCD) investigation performed at the Fe K edge in the intermetallic Nd[sub 2]Fe[sub 14]BH[sub x] and Y[sub 2]Fe[sub 14]BH[sub x] compounds with controlled hydrogen content. The present study clearly reveals that hydrogen exerts an appreciable influence on the electronic structure of the whole system, and in particular on the rare-earth sublattice. The combined study of both magnetization and XMCD indicates that the magnetic moments of Nd decrease upon hydrogen uptake. [ABSTRACT FROM AUTHOR]

A temperature-dependent x-ray resonant magnetic scattering study through the spin reorientation transition (SRT) that Nd[sub 2]Fe[sub 14]B undergoes below T[sub SRT]=135 K is presented. The experimental results evidence a strong noncollinearity between the magnetic moments of Nd atoms in 4f and 4g crystallographic sites in the low-temperature phase. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We present a systematic x-ray magnetic circular dichroism (XMCD) study performed at the rare-earth (R) L[sub 2,3] edges on the R[sub 2]Fe[sub 14]B series. The identification of multipolar contributions to the signal allows the application of sum rules to the obtained XMCD spectra. The results show that both orbital and spinorial components of the R(5d) magnetic moment are proportional to the 4f ones. Hence, the magnetic moment of 5d shell derived from a sum-rules analysis evidences an important nonquenched orbital contribution. This result is in contradiction with Campbell’s model for R–Fe intermetallic compounds. Consequently, both XMCD sum rules and Campbell’s model have to be revised in the atomic level. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Magnetic circular dichroism (MCD) of X-ray spectroscopy (X-ray absorption, X-ray emission, and X-ray photoemission) for spinel-type ferrites in hard X-ray region were performed to investigate the electronic and magnetic states under resonant conditions. Higher-energy resolution provides an enhancement of MCD at the pre-edge in X-ray absorption and X-ray emission. On the other hand, a resonant effect in the X-ray photoemission spectroscopy is little for the MCD signals near the absorption edge while obvious dichroic signals are observed in both Fe and Co 2 p core-level spectra. Thus, high-energy resolution and high precision provide fine structures and small variations for the X-ray spectra to perform delicate discussion. [ABSTRACT FROM AUTHOR]

Aims Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper-phosphorylated tau protein. Recently, several other molecules, including flotillin-1, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] and cyclin-dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin-1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. Methods We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2-immunopositive material in detail, using super-resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2-immunopositive material and tau kinases through double immunofluorescence analysis. Results Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2-immunopositive small vesicles (approximately 1 μm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase-3 β and spleen tyrosine kinase. Conclusions These observations suggest that clusters of raft-derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase-bearing vesicles are likely involved in the modification of tau protein and in NFT formation. [ABSTRACT FROM AUTHOR]

Deals with a study that focused on the growth of single crystals of the compounds R[sub2]Fe[sub14]B some 1-4 millimeter in size for a study of the anisotropy of the magnetization curves. Factors considered in the analysis of magnetization curves; Condition that influences the decline of molecular field coefficients; Event that gives rise to interesting magnetic behavior.

A letter to the editor is in response to an article "Facial nerve grading system," by J.W. House and D.E. Brackmann in a previous issue is presented.

Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well. [ABSTRACT FROM AUTHOR]

Recently, nano-polycrystalline diamond (NPD) anvils have been widely applied in high pressure research using X-ray absorption spectroscopy (XAS). The nanometer-sized polycrystallization in NPD anvils enables us to obtain glitch-free X-ray absorption spectra. This advantage of NPD anvils drastically improves the experimental conditions of XAS, which has previously used conventional single-crystal diamond (SCD) anvils. Distorted spectra due to the glitches from the SCD anvils have been an inevitable problem of XAS. This paper reviews recent studies of XAS and related spectroscopic techniques using the NPD anvils, which have mainly been performed on BL39XU of SPring-8. We demonstrate how NPD anvils are useful when using XAS for high pressure research. [ABSTRACT FROM PUBLISHER]

Amyotrophic lateral sclerosis (ALS) shows progressive muscle weakness and atrophy caused by neuronal death associate with TAR DNA-binding protein 43 (TDP43). Meanwhile, Awaji and Gold Coast criterion include an electrophysiological aspect to support clinical findings but not a pathological aspect because myopathological findings of ALS are not considered as specific. However, the advantage of the Awaji criteria is less pronounced in patients with spinal-onset ALS. The Gold Coast criteria enables us to diagnose spinal onset ALS patients and needs to allow for a specific diagnosis including a pathological aspect. Here, we aimed to identify and characterize the histopathology of peripheral axons in muscles of ALS patients. The post-mortem study included 10 sporadic ALS (SALS) patients with TDP43 pathology and 12 patients with non-ALS disease. The muscle biopsy cohort considered 450 patients and enrolled 114 as without family history of ALS or other neuromuscular diseases and not diagnosed with muscle diseases at biopsy. They ensure clinical follow-up in minimum one year. Exclusions were as follows: 51 for not screening clinical records after biopsy, 282 diagnosed with muscular diseases, and 3 harboring known causative genes of ALS. Muscle tissues were evaluated by histochemistry and immunohistochemical analysis. Ten SALS patients exhibited axonal phosphorylated TDP43 (pTDP43)-positive accumulations in intramuscular nerve bundles; 12 non-ALS patients did not. Among the muscle biopsy cohort, 71 patients exhibited intramuscular nerve bundles; 43 did not. Of the former, 33 presenting pTDP43-positive nerve bundles were later diagnosed with ALS. The remaining 38 showed no pTDP43-positive bundles and did not develop ALS. Among those without evident nerve bundles, 3 were later diagnosed with ALS. Among ALS patients in the biopsy cohort, 9 having pTDP43-positive bundles showed only lower motor neuron symptoms at biopsy. Axonal pTDP43 accumulations might be characteristic for ALS patients. As such findings precede clinical fulfillment of the Gold Coast criteria, TDP43 in nerve bundles might be a novel diagnostic biomarker for ALS. [ABSTRACT FROM AUTHOR]

One of the most common zoonotic helminth infections is caused by species in the genus Toxocara, particularly Toxocara canis and T. cati ( Syn. T. mystax). However, their relative contribution to toxocarosis in humans remains largely unknown because causative larvae are seldom recovered and uncertainties regarding the validity of existing serological assays. In this study, we used sera from a pig model experimentally infected with T. canis and T. cati to evaluate whether a Western blot could discriminate between the two species. No proteins were observed that could be used as a diagnostic tool. In addition, a heterogenic protein pattern between individual hosts was found, which was most pronounced in the T. cati-infected pigs. There is therefore an urgent need to optimize and validate current methods or develop new species-specific serological methods in order to implement appropriate control measures. [ABSTRACT FROM AUTHOR]

This article focuses on the localization of Neurod1 to rat chromosome 3 band 3q24→q32 and mouse chromosome 2 band 2E2-E3 by in situ hybridization. Human NeuroD was mapped in chromosome 2q32, which was near IDDM7, a human candidate susceptibility locus of insulin dependent diabetes mellitus (IDDM), and a variant of the NeuroD gene which is associated with IDDM. Further mapping of this gene in other species is expected to accelerate the finding of the IDDM susceptibility loci in the rat and mouse IDDM models.