Functional evaluation of an artificial anal sphincter using shape memory alloys

This article describes an implantable artificial anal sphincter using shape memory alloys and its in vivo assessment in porcine models. The new design was developed as a low invasive prosthesis with a simple structure to solve the problem of severe fecal incontinence in patients with hypoplastic sphincters or without anal sphincters and especially for ostomates. The artificial anal sphincter consists of two shape memory alloy (SMA) plates as the main functional parts to perform two basic functions when the SMA artificial sphincter is fitted around intestines (i.e., an occlusion at body temperature and an opening function on heating). Our previous assessments with short-term animal experiments revealed promising properties with the occlusion function of the device, although some complications, such as overpressure induced ischemia, heat burn, and infections, remained. This article addresses the concerns related to the practical use of the device, the power supplement to drive the actuator, and overheating protection of the device inside bodies. Results of chronic animal experiments of up to 4 weeks suggested great potential for the improved device.     

Dominant expression of interleukin-10 and transforming growth factor-beta genes in activated T-cells of chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus (EBV) infection is a chronic mononucleosis syndrome associated with clonal proliferation of EBV-carrying T-/natural killer (NK)-cells. High levels of circulating EBV and activated T-cells are sustained during the prolonged disease course, whereas it is not clear how ectopic EBV infection in T-/NK-cells has been established and maintained. To assess the biological role of activated T-cells in chronic active EBV infection (CAEBV), EBV DNA and cellular gene expressions in peripheral T-cells were quantified in CAEBV and infectious mononucleosis (IM) patients. In CAEBV, HLA-DR(+) T-cells had higher viral load and larger amounts of IFN gamma, IL-10, transforming growth factor-beta (TGF beta), and cytotoxic T lymphocyte antigen-4 (CTLA4) mRNA than HLA-DR(-)T-cells. HLA-DR(+) T cells of IM patients transcribed more IFN gamma and IL-10 than their HLA-DR(-)T cells. Expression levels of IFN gamma and forkhead box p3 (Foxp3) in CAEBV HLA-DR(+) T-cells were higher than in IM HLA-DR(+) T-cells. The effective variables to discriminate the positivity of HLA-DR were IL-10, IFN gamma, CTLA4, TGF beta, and IL-2 in the order of statistical weight. EBV load in CAEBV T-cells correlated with the expression levels of only IL-10 and TGF beta. These results suggest that CAEBV T-cells are activated to transcribe IFN gamma, IL-10, and TGF beta excessively, and the latter two genes are expressed preferentially in the EBV-infected subsets. The dominant expression of regulatory cytokines in T-cells may imply a viral evasion mechanism in the disease.     

Genetic polymorphisms of the major histocompatibility complex-encoded antigen-processing genes TAP and LMP in sarcoidosis

Sarcoidosis is a granulomatous disease showing a significant increase in the HLA-DR5, -DR6, and -DR8 associated alleles in Japanese. To investigate whether the class I antigen-processing genes, encoded within the MHC class II region between the HLA-DP and -DQ loci, are involved in determining the susceptibility to Sarcoidosis, TAP1, TAP2, and LMP2 alleles were analyzed by the PCR-RFLP method in 85 Japanese patients with Sarcoidosis and 91 healthy controls.

There were no significant differences in the distribution of TAP1 and LMP2 alleles between the subgroups of the patients and controls positive or negative for DR5, DR6, and DR8. A significant decrease in the frequency of TAP2*0201 was found among the patients negative for DR5, DR6, and DR8 as compared to the DR-matched controls (p < 0.05), but this could be explained by its linkage disequilibrium to the negatively associated allele DR1. These findings suggest that the TAP or LMP2 gene is not primarily involved in the susceptibility to Sarcoidosis. In the course of this study, a linkage disequilibrium was observed in the Japanese population between TAP1 and TAP2 alleles, TAP1*0201 and TAP2*0102.     

A perfusable microfluidic device with on-chip total internal reflection fluorescence microscopy (TIRFM) for in situ and real-time monitoring of live cells

A microfluidic device integrated with a Total Internal Reflection (TIR)-based chip for cell observation and analysis was developed. This integrated device enables in situ Total Internal Reflection Fluorescence Microscopy (TIRFM) on adherent cells cultured under continuous medium perfusion. This TIR-based chip, allows TIRFM to be easily performed on cells without the assembly of complicated optical components and cell culture chambers. The integrated device was evaluated by tracking the movement of fluorescent beads and monitoring the location of insulin granules in mouse pancreatic β-cells. This system offers higher signal-to-noise (S/N) ratio than epi-fluorescence microscopy (EPIFM), and comparable image quality to commercial TIRFM systems when imaging insulin granules. We also detected repetitive changes in intracellular Ca(2+) concentration in MIN6-m9 cells stimulated with KCl, which demonstrates quick perfusion for cell analysis while maintaining high S/N ratio.     

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type arising in the pleura with pleural fibrous plaques in a lathe worker

Our patient was an 86-year-old man who had worked as a lathe operator for 40 years. He had no history of tuberculosis, pyothorax, or autoimmune disease. He had not been exposed to asbestos. He was asymptomatic, but an imaging study showed gradually increasing pleural plaques. A biopsy specimen of a pleural lesion showed sclerosis of the pleura and diffuse infiltration of small- to medium-sized B lymphocytes. Polymerase chain reaction-based analysis detected monoclonal rearrangement of immunoglobulin heavy-chain genes. Histologic diagnosis was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). The lymphoma was negative for Epstein-Barr virus. We report a rare case of a metal worker with MALT lymphoma arising in the pleura with pleural fibrous plaques. It is speculated that MALT lymphoma might develop in the background of pneumoconiosis. Inflammatory and/or immunologic reactions to metal particles might contribute to the oncogenesis of this tumor.     

A thermoreversible hydrogel as a biosynthetic bandage for corneal wound repair

Ocular trauma and disorders that lead to corneal blindness account for over 2 million new cases of monocular blindness every year. A popular ocular surface reconstruction therapy, amniotic membrane transplantation, has been shown to aid corneal wound repair. However, the success rates of the procedure are variable. Here, we proposed to bioengineer a novel synthetic material that would serve as a biomimetic corneal bandage. The PLGA-PEG-PLGA triblock copolymer was synthesised via ring-opening polymerisation. Thermoreversible gelation behaviour was investigated at different polymer concentrations (23%, 30%, 35%, 40%, 45%, w/v) at temperatures ranging between 5 and 60 degrees C. Viscoelastic properties were studied in dynamic mechanical analysis with 1 degrees C/min temperature ramp. Cryo-SEM revealed a porous hydrogel with interconnecting networks. No adverse cytotoxicity was observed with an in vitro scratch-wound assay and in in vivo biocompatibility tests. We have demonstrated that the PLGA-PEG-PLGA hydrogel possessed a suitable gelling profile and, for the first time, the biocompatibility properties for this application as a potential bandage for corneal wound repair.     

Analysis of capturing skin antigens in the steady state using milk fat globule EGF factor 8-deficient skin-hyperpigmented mice

Dendritic cells (DCs) can capture apoptotic cells and present them to immune competent cells as self-antigens (Ags). Langerhans cells (LCs), DCs in the epidermis, are capable of presenting tissue-associated Ags in the steady state, suggesting that LCs may also capture apoptotic cells and transport them to skin regional lymph nodes (LNs). However, to what extent LCs utilize apoptotic cells as self-Ags in vivo is still unclear. To clarify this point, we examined the contribution of milk fat globule EGF factor 8 (MFG-E8), a secreted glycoprotein, to capturing skin Ags. MFG-E8 is expressed in several subsets of macrophages (M phi s) and DCs, including LCs, and crucial for recognizing and engulfing apoptotic cells. Using a skin-hyperpigmented KRT14-Kitl-Tg (Kitl-Tg) mouse system, we measured the accumulation of melanin granules (MGs), a marker of skin Ags, transported from the skin to regional LNs in Mfge8-deficient mice. Unexpectedly, their accumulation in Mfge8-deficient Kitl-Tg mice was comparable to that in Mfge8-heterozygous littermates. Mfge8-deficient DCs engulfed skin-derived MGs efficiently in vitro. The results indicate that MFG-E8 does not contribute critically or functions redundantly to capturing and trafficking of skin Ags in the steady state, and suggest a possibility that LCs may capture skin Ags in forms other than apoptotic cells in vivo.     

Reference dosimetry condition and beam quality correction factor for CyberKnife beam

This article is intended to improve the certainty of the absorbed dose determination for reference dosimetry in CyberKnife beams. The CyberKnife beams do not satisfy some conditions of the standard reference dosimetry protocols because of its unique treatment head structure and beam collimating system. Under the present state of affairs, the reference dosimetry has not been performed under uniform conditions and the beam quality correction factor kQ for an ordinary 6 MV linear accelerator has been temporally substituted for the kQ of the CyberKnife in many sites. Therefore, the reference conditions and kQ as a function of the beam quality index in a new way are required. The dose flatness and the error of dosimeter reading caused by radiation fields and detector size were analyzed to determine the reference conditions. Owing to the absence of beam flattening filter, the dose flatness of the CyberKnife beam was inferior to that of an ordinary 6 MV linear accelerator. And if the absorbed dose is measured with an ionization chamber which has cavity length of 2.4, 1.0 and 0.7 cm in reference dosimetry, the dose at the beam axis for a field of 6.0 cm collimator was underestimated 1.5%, 0.4%, and 0.2% on a calculation. Therefore, the maximum field shaped with a 6.0 cm collimator and ionization chamber which has a cavity length of 1.0 cm or shorter were recommended as the conditions of reference dosimetry. Furthermore, to determine the kQ for the CyberKnife, the realistic energy spectrum of photons and electrons in water was simulated with the BEAMnrc. The absence of beam flattening filter also caused softer photon energy spectrum than that of an ordinary 6 MV linear accelerator. Consequently, the kQ for ionization chambers of a suitable size were determined and tabulated as a function of measurable beam quality indexes in the CyberKnife beam.     

Clinical study of blood purification therapy in critical care in Japan: results from the survey research of the Japan Society for Blood Purification in Critical Care in 2013

To clarify the clinical status of blood purification therapy (BPT) in critical care in Japan, we conducted a cohort study using data from a nationwide registry of the Japan Society for Blood Purification in Critical Care in 2013. We enrolled 2227 patients treated with BPT (female, 39.1%; mean age, 65.5 ± 12.1 years) in the intensive care units of 43 facilities. Patient characteristics, modes of BPT, and survival rate for each disease were investigated. In total, BPT was performed 3053 times. Continuous renal replacement therapy (CRRT) (57.9%) was the most common mode of BPT, followed by intermittent renal replacement therapy (20.2%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX-DHP) (11.5%). Nafamostat mesilate (84.9%) was most frequently used as the anticoagulant. The 28-day survival rate was 56.8% in all patients. The most common mode for acute kidney injury (AKI) and multiple organ failure was CRRT, while PMX-DHP and CRRT were most common for sepsis. There was no significant difference in survival rates among AKI stages 1–3. Survival rate (38.3%) was significantly lower in patients with acute lung injury (ALI) than in those with multiple organ failure (41.8%) and those with sepsis (46.6%). Multivariate regression analysis revealed that the APACHE II score and the presence of acute ALI and acute hepatic failure were significantly associated with death. This large-scale cohort study showed the clinical status of BPT in Japan. Further investigations are required to clarify the efficacy of BPT for critically ill patients.