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Subcalcaneal bursitis as the initial manifestation of rheumatoid arthritis: ultrasonographic observation of two cases.

In early rheumatoid arthritis (RA), proliferative synovitis sometimes occurs earlier in the tenosynovium or bursal synovium than in the articular synovium. Here we report two patients who presented with subcalcaneal bursitis while progressing from undifferentiated arthritis with high-titer anti-CCP antibodies (ACPA) to a diagnosis of RA. They had initially presented with palindromic transient pain in the hands and the feet. They were strongly positive for ACPA and negative for rheumatoid factor (RF) at the onset of symptoms. A few years later, they developed persistent plantar heel pain and underwent musculoskeletal ultrasonography (MSUS). MSUS revealed subcalcaneal bursitis with synovial proliferation. At that time, they became positive for RF and they were clinically diagnosed and began receiving treatment for RA. They developed overt synovitis in their wrists and fingers several months later. To the best of our knowledge, this is the first report on MSUS-detection of subcalcaneal bursitis with synovial proliferation in patients in the very early phase of RA, although there have been many reports of forefoot bursitis. These cases suggest that MSUS scanning of the plantar surface of the heel may be useful for patients with plantar heel pain who are suspected of having a very early phase of RA, because proliferative synovitis can be detected as subcalcaneal bursitis.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)/GaAs hybrid solar cells with 13% power conversion efficiency using front- and back-surface field.

Planar hybrid solar cells based on bulk GaAs wafers with a background doping density of 10(16) cm(-3) and poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) ( PEDOT: PSS) demonstrated an excellent power conversion efficiency of 8.99%. The efficiency of the cell was enhanced to 9.87% with a back-surface field feature using a molecular beam epitaxially grown n-type GaAs epi-layer. The efficiency and fill factor reach 11.86% and 0.8 when an additional p + GaAs epi-layer is deposited on the surface of the solar cells, which provides a front-surface field. The interface between the high- and low-doped regions in the polymer/GaAs and GaAs formed an electric field that introduced a barrier to minority carriers flow to the substrate and effectively reduced front surface carrier recombination, thereby enhancing light-generated free carrier collection efficiency and open-circuit voltage. Compared with the device without the front- and back-surface field, the fill factor and open-circuit voltage of the hybrid solar cell were improved from 0.76 to 0.8 and from 0.68 V to 0.77V, respectively. The highest efficiency reaches a record 13% when the Zonyl fluorosurfactant-treated PEDOT: PSS is used as a hole-transporting conducting layer for hybrid cells.

Effectiveness of a simulated patient training programme based on trainee response accuracy and appropriateness of feedback.

INTRODUCTION: Simulated patients (SPs) need education and training in required skills to be effective resources in education. This study was conducted to examine the effectiveness of an SP training programme based on the accuracy of trainee responses and the appropriateness of their feedback. METHODS: Thirty-two applicants to the training programme and 35 experienced SPs were included in this study. The experienced SPs served as a reference group. The rate of accurate responses and the rate of appropriate feedback were assessed with pre- and post-training tests, and these two outcome measures were compared with those of the experienced SPs. RESULTS: No significant differences were found in trainee response accuracy or appropriateness of feedback between pre- and post-training tests. The response accuracy rate of the trainees on the pre-training test was significantly lower than that of SPs with 1-2 years of experience, whilst there was no significant difference between these SPs and the trainees on the post-training test. CONCLUSIONS: Although our study suggests that more training is needed to improve the skills of SPs, the training programme may contribute to helping trainees reach a novice level in the skill of providing accurate responses. SP training should be encouraged to contribute to the effectiveness of such teaching and to establish the validity of the assessment.

Single-shot detection of mid-infrared spectra by chirped-pulse upconversion with four-wave difference frequency generation in gases.

Single-shot detection of ultrabroadband mid-infrared spectra was demonstrated by using chirped-pulse upconversion technique with four-wave difference frequency generation in gases. Thanks to the low dispersion of the gas media, the bandwidth of the phase matching condition of the upconversion process becomes very broad and the entire mid-infrared spectrum spanning from 200 to 5500 cm(-1) was upconverted by using a 10 ps chirped pulse to visible wavelength radiation, which was detected with a conventional visible dispersive spectrometer. This method was demonstrated by the successful measurement of infrared absorption spectra of organic polymer films.

PARG dysfunction enhances DNA double strand break formation in S-phase after alkylation DNA damage and augments different cell death pathways.

Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for the degradation of poly(ADP-ribose). PARG dysfunction sensitizes cells to alkylating agents and induces cell death; however, the details of this effect have not been fully elucidated. Here, we investigated the mechanism by which PARG deficiency leads to cell death in different cell types using methylmethanesulfonate (MMS), an alkylating agent, and Parg(-/-) mouse ES cells and human cancer cell lines. Parg(-/-) mouse ES cells showed increased levels of γ-H2AX, a marker of DNA double strand breaks (DSBs), accumulation of poly(ADP-ribose), p53 network activation, and S-phase arrest. Early apoptosis was enhanced in Parg(-/-) mouse ES cells. Parg(-/-) ES cells predominantly underwent caspase-dependent apoptosis. PARG was then knocked down in a p53-defective cell line, MIAPaCa2 cells, a human pancreatic cancer cell line. MIAPaCa2 cells were sensitized to MMS by PARG knockdown. Enhanced necrotic cell death was induced in MIAPaCa2 cells after augmenting γ-H2AX levels and S-phase arrest. Taken together, these data suggest that DSB repair defect causing S-phase arrest, but p53 status was not important for sensitization to alkylation DNA damage by PARG dysfunction, whereas the cell death pathway is dependent on the cell type. This study demonstrates that functional inhibition of PARG may be useful for sensitizing at least particular cancer cells to alkylating agents.

Long-term impact of hypertension on renal allografts.

OBJECTIVE: We assessed the impact of hypertension on renal transplant function and survival in the past decade after introduction of mycophenolate mofetil and rituximab. METHODS: We examined the 184 patients who underwent renal transplantation from March 1982 to September 1999 and presented at our outpatient clinic from 2001 to 2011. They were divided into group 1 with mean systolic blood pressure (mSBP) >130 mm Hg and Group 2 with mSBP <130 mm Hg. We compared mean serum creatinine (sCr) levels for 9 years and 12-year actuarial graft survival rates. Risk factors for graft survival were assessed by Cox regression analysis. RESULTS: There were 75 group 1 and 109 group 2 recipients. The mean sCr level of group 1 was 1.59 ± 0.12 mg/dL and that of group 2 1.54 ± 0.10 mg/dL (P < .0001). Of note was that mean sCr levels of group 1 started to increase about 3 years after transplantation. Although 5-year graft survival rates of both groups were 100%, 9- and 12-year rates among group 1 were 97.3% and 90.5%, respectively, whereas among group 2 they were 99.1% and 98.1%, respectively (P = .0195). Cox univariate and multivariate analyses showed mean SBP to be the only significant risk factor for graft survival (P < .05). CONCLUSIONS: We concluded that the hypertensive group showed deteriorating renal function from around 3 years after transplantation that lowered graft survival afterward, resulting in a clear distinction from the nonhypertensive group at around 10 years after transplantation. Mean SBP was a significant risk factor for graft survival. Hypertension may be a surrogate for a poor renal graft prognosis in the long run.

Renal transplantation in patients with human T-cell lymphotropic virus type 1.

BACKGROUND: Renal transplantation (RTx) in carriers of human T-cell lymphotropic virus type 1 (HTLV-1) has a risk of developing overt leukemia upon immunosuppression. Although there have been a few reports of such cases, it is unclear HTLV-1 carrier if patients on the modern immunosuppressants would develop HTLV-1-associated myelopathy or adult T-cell leukemia lymphoma. METHODS: We retrospectively reviewed the clinical outcomes of RTx in nine HTLV-1 carriers to assess a risk of developing leukemia from 2002 to 2011 using immunosuppression with a calcineurin inhibitor, mycophenolate mofetil (MMF), and steroid. The anti-CD25 monoclonal antibody basiliximab was used for induction. In two cases of ABO-incompatible RTx, the rituximab was also administered before RTx. RESULTS: The ratio of male to female subjects was 2 to 7 with an overall mean recipient age of 54.3 ± 8.1 years. We prescribed cyclosporine (n = 5) or tacrolimus (n = 4). There was only one graft loss due to the death caused by aspiration pneumonia with a functioning graft. No one developed overt leukemia with combined treatment with MMF, basiliximab and rituximab. CONCLUSION: We concluded that RTx in HTLV-1 carriers could be performed using a modern immunosuppressive regimen, without the risk of developing leukemia.

Poly(ADP-ribose) Glycohydrolase deficiency sensitizes mouse ES cells to DNA damaging agents.

Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme for degradation of poly(ADP-ribose) by splitting ribose-ribose bonds. Parg-deficient (Parg(+/-) and Parg(-/-)) mouse ES cell lines have been established by disrupting both alleles of Parg exon 1 through gene-targeting. A transcript encoding a full length isoform of Parg was eliminated and only low amounts of Parg isoforms were detected in Parg(-/-) embryonic stem (ES) cells. Poly(ADP-ribose) degradation activity was decreased to one-tenth of that in Parg(+/+) ES cells. Parg(-/-) ES cells exhibited the same growth rate as Parg(+/+) ES cells in culture. Sensitivity of Parg(-/-) ES cells to various DNA damaging agents, including an alkylating agent dimethyl sulfate, cisplatin, gemcitabine, 5-fluorouracil, camptothecin, and gamma-irradiation was examined by clonogenic survival assay. Parg(-/-) ES cells showed enhanced lethality after treatment with dimethyl sulfate, cisplatin and gamma-irradiation compared with wild-type (Parg(+/+)) ES cells (p<0.05, respectively). In contrast, a sensitization effect by Parg-deficiency was not observed with gemcitabine and camptothecin. These results suggest the possibility that functional inhibition of Parg leads to sensitization of tumor cells to some chemo- and radiation therapies.

PLAP-1/asporin inhibits activation of BMP receptor via its leucine-rich repeat motif.

We previously identified the novel gene, periodontal ligament-associated protein-1 (PLAP-1)/asporin and reported that PLAP-1/asporin inhibited bone morphogenetic protein-2 (BMP-2)-induced cytodifferentiation of periodontal ligament (PDL) cells probably by direct interaction with BMP-2. Here, we elucidated the detailed regulatory mechanism of this protein on BMP-2-induced cytodifferentiation of PDL cells. Recombinant PLAP-1/asporin inhibited BMP-2-induced cytodifferentiation of PDL cells and competitively prevented BMP-2 from binding to the BMP receptor-IB (BMPR-IB), resulting in inhibition of BMP-dependent activation of Smad proteins. The induction of mutation to the leucine-rich repeat (LRR) motif, especially LRR5, within PLAP-1/asporin rescued the inhibitory effect of PLAP-1/asporin on BMP-2. By contrast, a 26-amino acid peptide in the PLAP-1/asporin LRR5 sequence inhibited BMP-2 activity. Our findings indicate that PLAP-1/asporin inhibits BMP-2-induced differentiation of PDL cells resulting from inactivation of the BMP-2 signaling pathway and that LRR, especially LRR5 of PLAP-1/asporin, plays an important role in the PLAP-1/asporin-BMP-2 interaction.

Supramolecular gels formed by amphiphilic low-molecular-weight gelators of N alpha,N epsilon-diacyl-L-lysine derivatives.

Simple L-lysine derivatives, N(alpha)-hexanoyl-N(epsilon)-lauroyl-L-lysine (1), its alkali metal salts (2-4), and two-component compounds that consist of 1 with 2 to 4, were synthesized and their hydrogelation and organogelation properties were studied. Addition of hydrochloric acid to an aqueous solution of the alkali metal salt at room temperature produced a translucent hydrogel. This hydrogelation occurred as a result of a change in nanostructure from micelle-like aggregates to nanofibers, which was induced by partial protonation of the carboxylate to form a carboxylic acid. On the other hand, two-component low-molecular-weight gelators exhibited amphiphilic gelation behavior and functioned as not only hydrogelators, but also as organogelators. FTIR studies revealed that lateral ionic interactions between the carboxylate, alkali metal cation, carboxylic acid, and protons, in addition to hydrogen-bonding and van der Waals interactions play a very important role in hydrogelation. Furthermore, it was found that the water-insoluble carboxylic acid compound underwent a precipitation-dissolution transition with a thermally reversible sol-gel transition in the two-component gelator systems.

Characterization of core promoter elements for ecdysone receptor isoforms of the silkworm, Bombyx mori.

Two ecdysone receptor (EcR) isoforms, EcR-A and EcR-B1, are expressed in a tissue- and stage-specific manner, although the details of their transcription mechanisms are unknown. We determined the transcription start sites of EcR-A and EcR-B1 isoforms of Bombyx mori and found that both core promoter regions consist of initiator (Inr) and downstream promoter elements (DPE) but not TATA boxes. Promoter truncation analysis performed using the luciferase reporter assays and BmN cells showed that, in both isoforms, the regions -296 to -74 for BmEcR-B1, -104 to -61 for BmEcR-A and downstream regions of +1 are essential for basal transcriptional activity. Mutation experiments revealed that both DPE and its 5'-flanking CGCGCG sequence are crucial but DPE of BmEcR-B1 is not important for BmEcR-A transcription. These results indicate that the basal promoter activities differ between the two BmEcR isoforms.

The rotational effect of pronation and supination osteotomies of the forearm in a cadaver model: a comparison of osteotomy sites on the radius and the ulna.

The purpose of this study was to investigate the effect on forearm rotation of rotation osteotomies at the distal and proximal levels of the radius and the ulna. Rotation osteotomies of 15 degrees and 30 degrees were made in the distal and proximal one-third of the radius and the ulna in ten cadaver specimens and changes of forearm arc of rotation were compared after osteotomy at the four sites. This study identifies the proximal ulna as the best of these sites for rotation osteotomy because of the high gain in the rotated direction and minimal loss in the opposite direction.

CLOCK is involved in obesity-induced disordered fibrinolysis in ob/ob mice by regulating PAI-1 gene expression.

BACKGROUND: An increased level of obesity-induced plasma plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular disease. AIM: The present study investigates whether the circadian clock component CLOCK is involved in obesity-induced PAI-1 elevation. METHODS: We examined plasma PAI-1 and mRNA expression levels in tissues from leptin-deficient obese and diabetic ob/ob mice lacking functional CLOCK protein. RESULTS: Our results demonstrated that plasma PAI-1 levels were augmented in a circadian manner in accordance with the mRNA expression levels in ob/ob mice. Surprisingly, a Clock mutation normalized the plasma PAI-1 concentrations in accordance with the mRNA levels in the heart, lung and liver of ob/ob mice, but significantly increased PAI-1 mRNA levels in adipose tissue by inducing adipocyte hypertrophy in ob/ob mice. The Clock mutation also normalized tissue PAI-1 antigen levels in the liver but not in the adipose tissue of ob/ob mice. CONCLUSION: These observations suggest that CLOCK is involved in obesity-induced disordered fibrinolysis by regulating PAI-1 gene expression in a tissue-dependent manner. Furthermore, it appears that obesity-induced PAI-1 production in adipose tissue is not closely related to systemic PAI-1 increases in vivo.

Phthalocyanine-dyed fibers adsorb allergenic proteins.

Phthalocyanine (Pc)-dyed fiber is reported to reduce atopic symptoms in some patients when they use underwear made of the fiber. We investigated the adsorption of allergens on Pc-fiber. Pc-fiber trapped house dust/pollen/food allergens with varied molecular weight and pI. The adsorbed allergens were released in the presence of mild detergent. Pc-fiber did not change the molecular weight or disulfide bonding of the allergens. These observations imply that Pc-fiber is applicable as an "allergen trap" for a wide variety of products.

Measurement of turbulence decorrelation during transport barrier evolution in a high-temperature fusion plasma.

A low power polychromatic beam of microwaves is used to diagnose the behavior of turbulent fluctuations in the core of the JT-60U tokamak during the evolution of the internal transport barrier. A continuous reduction in the size of turbulent structures is observed concomitant with the reduction of the density scale length during the evolution of the internal transport barrier. The density correlation length decreases to the order of the ion gyroradius, in contrast with the much longer scale lengths observed earlier in the discharge, while the density fluctuation level remain similar to the level before transport barrier formation.