Complement profile in microscopic polyangiitis and granulomatosis with polyangiitis: analysis using sera from a nationwide prospective cohort study.

OBJECTIVE: The complement cascade, especially the alternative pathway of complement, has been shown in basic research to be associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). We aimed to elucidate relationships between serum complement components and clinical characteristics in AAV. METHOD: In a nationwide prospective cohort study (RemIT-JAV-RPGN), we measured the serum levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, mannose-binding lectin, and properdin in 52 patients with microscopic polyangiitis (MPA) and 39 patients with granulomatosis with polyangiitis (GPA). RESULTS: The properdin level of MPA and GPA was significantly lower than that of healthy donors. The properdin level was negatively correlated with the Birmingham Vasculitis Activity Score (BVAS) (ρ = -0.2148, p = 0.0409). The factor D level at 6 months was significantly positively correlated with the Vasculitis Damage Index (VDI) at 6, 12, and 24 months (ρ = 0.4207, 0.4132, and 0.3115, respectively). Patients with a higher ratio of C5a to C5 had higher neutrophil percentage and serum immunoglobulin G levels, and significantly lower creatinine levels. Cluster analysis divided the MPA and GPA patients into three subgroups. A principal component (PC) analysis aggregated 15 types of complements into alternative pathway-related PC 1 and complement classical pathway and common pathway-related PC 2. CONCLUSIONS: The serum levels of properdin and factor D were correlated with the BVAS and the VDI in MPA and GPA, respectively. Our analyses suggested the pathological heterogeneity of MPA and GPA from the aspect of complement components.

Laser-Beam-Patterned Topological Insulating States on Thin Semiconducting MoS_{2}.

Identifying the two-dimensional (2D) topological insulating (TI) state in new materials and its control are crucial aspects towards the development of voltage-controlled spintronic devices with low-power dissipation. Members of the 2D transition metal dichalcogenides have been recently predicted and experimentally reported as a new class of 2D TI materials, but in most cases edge conduction seems fragile and limited to the monolayer phase fabricated on specified substrates. Here, we realize the controlled patterning of the 1T^{'} phase embedded into the 2H phase of thin semiconducting molybdenum-disulfide by laser beam irradiation. Integer fractions of the quantum of resistance, the dependence on laser-irradiation conditions, magnetic field, and temperature, as well as the bulk gap observation by scanning tunneling spectroscopy and theoretical calculations indicate the presence of the quantum spin Hall phase in our patterned 1T^{'} phases.

Pulsed laser deposition with rapid beam deflection by a galvanometer mirror scanner.

A pulsed laser deposition system with rapid beam deflection (RBD-PLD) by a galvanometer mirror scanner has been developed for alternating ablation of multiple targets with a single laser instrument. In this system, the alternating deposition of different target materials is carried out by scanning the laser beam between the positionally fixed targets with a galvanometer mirror instead of mechanically switching the target positions on a fixed optical path of the laser beam as is done in conventional pulsed laser deposition (PLD) systems. Thus, the "wait" time required for switching target materials to be deposited, which typically takes several seconds in a conventional system, can be made as short as a few milliseconds. We demonstrate some of the advantages of this PLD system in several technologically important aspects of thin film synthesis: (1) fast fabrication of binary alloy films, (2) preparation of natural composition spread libraries, (3) effect of the target switching time on the deposition of volatile compounds, (4) control of the degree of mixing of two different materials in a film, and (5) efficient growth of compositionally graded thin films.

Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma.

OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Serum αKlotho as a Predictor of Graft Dysfunction After Kidney Transplantation.

OBJECTIVE: To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. METHODS: Plasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). RESULTS: The median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. CONCLUSION: Measurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.

Advancement of magma fragmentation by inhomogeneous bubble distribution.

Decompression times reported in previous studies suggest that thoroughly brittle fragmentation is unlikely in actual explosive volcanic eruptions. What occurs in practice is brittle-like fragmentation, which is defined as the solid-like fracture of a material whose bulk rheological properties are close to those of a fluid. Through laboratory experiments and numerical simulation, the link between the inhomogeneous structure of bubbles and the development of cracks that may lead to brittle-like fragmentation was clearly demonstrated here. A rapid decompression test was conducted to simulate the fragmentation of a specimen whose pore morphology was revealed by X-ray microtomography. The dynamic response during decompression was observed by high-speed photography. Large variation was observed in the responses of the specimens even among specimens with equal bulk rheological properties. The stress fields of the specimens under decompression computed by finite element analysis shows that the presence of satellite bubbles beneath a large bubble induced the stress concentration. On the basis of the obtained results, a new mechanism for brittle-like fragmentation is proposed. In the proposed scenario, the second nucleation of bubbles near the fragmentation surface is an essential process for the advancement of fragmentation in an upward magma flow in a volcanic conduit.

Molecular survey of Bartonella henselae and Bartonella clarridgeiae in pet cats across Japan by species-specific nested-PCR.

Cats are known to be the main reservoir for Bartonella henselae and Bartonella clarridgeiae, which are the agents of 'cat-scratch disease' in humans. In the present study, we investigated the prevalence of the two Bartonella species on 1754 cat bloods collected from all prefectures in Japan during 2007-2008 by a nested-polymerase chain reaction (PCR) targeting the 16S-23S rRNA internal transcribed spacer region. Overall, Bartonella DNA was detected in 4·6% (80/1754) of the cats examined. The nested-PCR showed that 48·8% (39/80) of the positive cats were infected with B. henselae mono-infection, 33·8% (27/80) with B. clarridgeiae mono-infection and 17·5% (14/80) were infected with both species. The prevalence (5·9%; 65/1103) of Bartonella infection in the western part of Japan was significantly higher than that (2·3%; 15/651) of eastern Japan (P < 0·001). Statistical analysis of the cats examined suggested a significant association between Bartonella infection and FeLV infection (OR = 1·9; 95% CI = 1·1-3·4), but not with FIV infection (OR = 1·6; 95% CI = 1·0-2·6).

Expression of neprilysin in periodontitis-affected gingival tissues.

OBJECTIVE: Although the pathogeneses of Alzheimer's disease (AD) and periodontal diseases have overlapping features, including ageing and chronic inflammation, the association between AD and periodontitis remains unclear. To explore the pathogenesis of periodontitis, a comprehensive gene expression/transcriptome analysis in periodontitis-affected gingival tissues found that the AD pathway was significantly up-regulated in periodontitis-affected gingival tissues. AD-related genes, amyloid beta precursor protein (APP), interleukin-1 beta and compliment 1QA, were significantly elevated in periodontitis. In the present study, balance between mRNA expression of APP and a potent amyloid degradation enzyme, neprilysin (NEP), as well as protein localisation of APP and NEP were analysed. DESIGN: Eighteen periodontitis-affected and 18 clinically healthy control gingival tissues were taken from patients with severe chronic periodontitis or undergoing tooth extraction. Total RNA was purified and used for quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR). The localisation of APP and NEP was analysed by immunohistochemistry (IHC). RESULTS: Both APP and NEP genes were up-regulated in periodontitis-affected gingival tissues. APP-expressing macrophages and NEP-expressing neutrophils and fibroblasts, reflecting inflammatory stages, were detected in inflamed gingival tissues by IHC. CONCLUSION: The up-regulation of APP and NEP mRNA levels in periodontitis-affected gingival tissues compared with healthy controls was confirmed by qRT-PCR analyses. Since NEP is one of the primary enzymes that degrades amyloid beta, increased NEP mRNA levels in periodontitis may act as an inhibitor of amyloid beta accumulation in gingival tissues, balancing increased APP mRNA expression. However, NEP has several effects including degradation of vasoactive substances; therefore, further sresearch is needed.

Morphology dependence of the thermal transport properties of single-walled carbon nanotube thin films.

The thermal transport properties of random network, single-walled carbon nanotube (SWNT) films were assessed using Raman spectroscopy. Two types of SWNT films were investigated: single-layer and stacked. The single-layer films were fabricated by aerosol chemical vapour deposition and subsequent direct dry deposition, while the stacked films were prepared by placing the single-layer films on top of one another. The anisotropy of the network structures of each of these films was evaluated based on the angular dependence of the optical absorbance spectra. The results show that the anisotropy of the films decreases with increasing film thickness in the case of the single-layer films, and that the film anisotropy is preserved during the stacking process. The sheet thermal conductance is proportional to the SWNT area density in the case of stacked films, but is reduced with increasing thickness in the case of single-layer films. This effect is explained by a change in the network morphology from a two-dimensional anisotropic structure to the more isotropic structure. This work demonstrates the fabrication of low-density films with high sheet thermal conductance through the stacking of thin SWNT films.

Calcineurin Inhibitor-Induced Pain Syndrome in ABO-Incompatible Living Kidney Transplantation: A Case Report.

BACKGROUND: Calcineurin-inhibitor-induced pain syndrome (CIPS) was used as a reference in the literature as reflex sympathetic dystrophy syndrome related to calcineurin inhibitors. Much of the literature describes CIPS that occurred after kidney and bone marrow transplantation. We describe a rare case of CIPS in induction immunosuppression before kidney transplantation, under administration of an anti-rheumatoid drug. METHODS: A 53-year-old woman had pre-status of ABO-incompatible living kidney transplantation. The patient had rheumatoid arthritis, but that was well-controlled with salazosulfapyridine as an anti-rheumatoid drug. Fourteen days before transplantation, she received induction immunosuppressive therapy consisting of tacrolimus (TAC) and mycophenolate mofetil (MMF) and she stopped taking salazosulfapyridine. The third day after that treatment, she had a high fever, fatigue, and joint pains of the knees, elbows, and wrists. RESULTS: When the patient stopped taking TAC and MMF and started taking salazosulfapyridine again, she soon recovered. Next, we challenged same induction immunosuppression therapy with administration of salazosulfapyridine; however, the patient had the same symptom. We considered that the symptom was caused by TAC or MMF, and we did not challenge-test each drug. We found that taking only TAC caused the same symptom for the patient. Also, we challenged cyclosporine (CsA) with MMF and confirmed that she did not have the symptom. CONCLUSIONS: We decided that drugs of the induction immunosuppression therapy were CsA, MMF, prednisolone, and basiliximab. The patient received induction therapy with plasmapheresis and rituximab in addition to the above-mentioned drugs, and we performed ABO-incompatible kidney transplantation for her. The post-surgical course was good, without acute rejection, and she had no pain.

Structural study of epitaxial LiCoO2 films grown by pulsed laser deposition on single crystal SrTiO3 substrates.

Epitaxial LiCoO2 (LCO) thin films of different orientations were fabricated by pulsed laser deposition (PLD) in order to model single-crystal behavior of intercalation cathodes during electrochemical reactions. This paper demonstrates that (1) epitaxial growth of LCO on a single crystal Nb-doped SrTiO3 (Nb:STO) of different orientations occurs with a single orientation relationship; (2) surface morphology of the LCO films is established by the morphology of coalescing grains during island growth mode, whereas morphology of the grains can be visualized as different cuts from a cube with low-energy {104}R-LCO surfaces; (3) the films consist of predominately trigonal R-LiCoO2 phase, with a small fraction of the occasionally present cubic c-LixCoO2 phase; (4) cyclic voltammetry measurements have determined rectification at interface between LCO and Nb:STO causing bias on the oxidation part of cycling, thus preventing full cycling.

Anomalous magnetoresistance in the spinel superconductor LiTi2O4.

LiTi2O4 is a unique compound in that it is the only known spinel oxide superconductor. The lack of high quality single crystals has thus far prevented systematic investigations of its transport properties. Here we report a careful study of transport and tunnelling spectroscopy in epitaxial LiTi2O4 thin films. An unusual magnetoresistance is observed which changes from nearly isotropic negative to prominently anisotropic positive as the temperature is decreased. We present evidence that shows that the negative magnetoresistance likely stems from the suppression of local spin fluctuations or spin-orbit scattering centres. The positive magnetoresistance suggests the presence of an orbital-related state, also supported by the fact that the superconducting energy gap decreases as a quadratic function of magnetic field. These observations indicate that the spin-orbital fluctuations play an important role in LiTi2O4 in a manner similar to high-temperature superconductors.

Ultrasound-guided percutaneous aspiration of hyperreactio luteinalis avoids laparoscopic untwisting of ovarian torsion.

Hyperreactio luteinalis (HL) is characterized by multicystic bilateral enlargement of the ovaries and is a self-limiting benign condition associated with pregnancy or trophoblastic disease. Since HL regresses spontaneously over time, it should be managed conservatively as long as the patient's condition permits; torsion of the enlarged ovaries is believed to be the only exception that mandates surgical intervention. Here, we describe a case of HL complicated by ovarian torsion that was treated successfully without surgical intervention. A 33-year-old woman was admitted to our hospital owing to acute abdomen. Nine days previously, she had had a stillbirth caused by hydrops fetalis at 24 weeks' gestation. The characteristic findings observed on magnetic resonance imaging (MRI) led to the diagnosis of HL complicated by torsion of the enlarged left ovary. Emergency laparoscopic detorsion of the ischemic left ovary was planned. Aiming to reduce the risk of cystic injury and bleeding at the trocar insertion site, volume reduction of the left ovarian cyst was performed by percutaneous aspiration. The patient's pain diminished rapidly and laparoscopic surgery was deferred. Subsequent MRI revealed that gadolinium enhancement of the left ovarian tumor had been restored, indicating spontaneous detorsion of the left ovary. The patient remained asymptomatic and was discharged from the hospital 12 days after aspiration of the cyst. From this experience, we propose that, in cases of ovarian torsion occurring in large functional cysts, including HL, volume reduction by percutaneous cyst aspiration should be considered before performing emergency laparoscopic surgery.

Deterministic arbitrary switching of polarization in a ferroelectric thin film.

Ferroelectrics have been used as memory storage devices, with an upper bound on the total possible memory levels generally dictated by the number of degenerate states allowed by the symmetry of the ferroelectric phase. Here, we introduce a new concept for storage wherein the polarization can be rotated arbitrarily, effectively decoupling it from the crystallographic symmetry of the ferroelectric phase on the mesoscale. By using a Bi5Ti3FeO15-CoFe2O4 film and via Band-Excitation Piezoresponse Force Microscopy, we show the ability to arbitrarily rotate polarization, create a spectrum of switched states, and suggest the reason for polarization rotation is an abundance of sub-50 nm nanodomains. Transmission electron microscopy-based strain mapping confirms significant local strain undulations imparted on the matrix by the CoFe2O4 inclusions, which causes significant local disorder. These experiments point to controlled tuning of polarization rotation in a standard ferroelectric, and hence the potential to greatly extend the attainable densities for ferroelectric memories.

Amyloid beta (A4) precursor protein expression in human periodontitis-affected gingival tissues.

OBJECTIVE: Periodontitis involves periodontal tissue destruction and is associated with chronic inflammation and ageing. Periodontitis has recently been recognised as a risk factor for Alzheimer's disease (AD). We showed upregulation of molecules in the AD pathway including amyloid beta (A4) precursor protein (APP), a key gene in AD, interleukin-1 beta (IL-1ß), and complement component 1 (q subcomponent, A chain) (C1QA) in periodontitis compared to healthy tissues. Here, we quantitatively analysed the expression levels of APP, IL-1ß, and C1QA and determined the localisation of APP in gingival tissues. DESIGN: Fourteen chronic periodontitis patients and 14 healthy participants were enrolled. Six samples of total RNA from two distinct sites of healthy and periodontitis-affected gingival tissues from three randomly selected patients were used for microarray analyses, and significant biological pathways in periodontitis were identified. Differential gene expression of APP, IL-1ß, and C1QA, which belong to the AD pathway, were analysed with quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR) using samples from these 14 chronic periodontitis patients and 14 healthy controls. APP localisation was analysed with immunohistochemistry. RESULTS: APP, IL-1ß, and C1QA mRNA levels were significantly upregulated in periodontitis-affected gingival tissues. APP was mainly localised in macrophages in gingival connective tissues underneath the epithelial layers. CONCLUSIONS: An association between AD and periodontitis was detected with microarray and computer-aided data mining analyses. qRT-PCR identified differential gene expression in periodontitis-affected gingival tissue that may be related to AD pathogenesis. Elevated APP, IL-1ß, and C1QA transcripts and APP-expressing macrophages in periodontitis-affected gingival tissues were observed, suggesting a relationship between periodontitis and AD pathogenesis.

Plasma CD147 reflects histological features in patients with lupus nephritis.

OBJECTIVE: A glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN. METHODS: Plasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147. RESULTS: In LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, prediction using a single molecule would be quite difficult because of the complex pathogenesis of LN. The diagnostic accuracy of multiplex parameters indicated that the combination including plasma CD147 might yield excellent diagnostic abilities for guiding ideal LN therapy. CONCLUSION: Plasma CD147 levels might offer useful insights into disease activity as a crucial biomarker in patients with LN.

Three-dimensional continuation study of convection in a tilted rectangular enclosure.

A continuation method developed from a three-dimensional spectral finite element code is used to study natural convection in a tilted rectangular cavity. The cavity has its length equal to two times the side of its square cross section and it contains a fluid with a Prandtl number Pr = 1. A detailed bifurcation diagram is first obtained in the case without inclination in order to get the sequence of the different branches of solutions and determine the stable solutions. The focus is then put on the stable solutions in the inclined cavity, when the tilt occurs around its longest axis. The subtle changes induced by the tilt on the convective system are clarified. Three different stable solutions are obtained: the longitudinal roll L- solution (with the same sense of rotation as the inclination angle), which develops smoothly from zero Rayleigh number on the leading branch; the longitudinal roll L+ solution (with a sense of rotation opposite to the inclination angle), which is on a disconnected branch and is stabilized beyond a secondary bifurcation point; the oblique roll O ± solutions (corresponding to transverse roll solutions perturbed by the longitudinal flow induced by the tilt), which quickly appear beyond saddle-node points on new disconnected branches. The domain of existence of these stable solutions is eventually obtained and described in the Rayleigh number-inclination parameter space. Finally, the Nusselt number is determined as a function of the inclination at a constant Rayleigh number for the different stable solutions. The Nusselt number is maximum at an inclination of 49.55° for the leading longitudinal roll L- solution.

π and π + σ plasmon localization in single-walled carbon nanotube meta-materials.

We have investigated the plasmon excitations and interband transitions in nematic nanotube meta-materials with different nanotube mean diameters. While the characteristic optical low-energy transitions give testimony to the differing mean diameters, the full momentum resolved π as well as π + σ plasmon response of the meta-materials is found to be entirely invariant with the nanotube diameters 1 nm < d < 2 nm. We hence demonstrate that plasmons on single-walled carbon nanotubes are fully channeled to be one dimensional in the typical range of nanotube diameters. The internal morphology of the meta-material offers a knob to uniformly tune the plasmon resonances.