INTRAOPERATIVE BLEEDING IN ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE STOMACH AND STRATEGY FOR PREVENTION AND TREATMENT

To control intraoperative bleeding is an important key to successful endoscopic submucosal dissection. The distribution of submucosal vessels encountered during the procedure differ in places in the stomach and are roughly categorized into three groups: those located in the antrum, those in the lesser curvature, and those on the anteroposterior corpus wall which consists of oblique muscle layers. Therefore, knowledge of a suitable setting of diathermy and adjusted depth of dissection in the submucosal layer for each site is imperative. The combination of utilizing the distal attachment forced or swift coagulation (trimming with coagulation mode) have enable the treatment with an insulation tipped knife safer.     

Stimulation of tumour necrosis factor-alpha production by recombinant human erythropoietin may contribute to failure of therapy

Although the mechanism of unresponsiveness to recombinant human erythropoietin therapy in dialysis patients has been studied extensively in recent years, many aspects remain unclear. We previously found that administration of erythropoietin induces interleukin-1beta, a cytokine that inhibits erythropoiesis. The present study investigated the involvement of tumour necrosis factor-alpha, another cytokine which inhibits erythropoiesis. Peripheral blood mononuclear cells were obtained from 18 patients on continuous ambulatory peritoneal dialysis, who were being treated with erythropoietin for renal anaemia, and were cultured with various concentrations of erythropoietin (0, 1, 5, 10, and 50 U/ml). Then the tumour necrosis factor-alpha level in the culture supernatant was assayed. The 18 patients were divided into four groups on the basis of the haematocrit after treatment: group A (n = 3), <23.0%; group B (n = 5), 23.0-24.9%; group C (n = 7), 25.0-26.9%; and group D (n = 3), > or =27.0%. In group A, the tumour necrosis factor-alpha level in the culture supernatant was increased by incubation with erythropoietin, while it was not increased in other groups. The tumour necrosis factor-alpha level was significantly higher in group A than in the other groups at erythropoietin concentrations of 5 U/ml. These results suggested that induction of tumour necrosis factor-alpha is one of the reasons for unresponsiveness to recombinant human erythropoietin.     

Efficacy of sitting balance training with delayed visual feedback among patients with stroke: a randomized crossover clinical trial

[Purpose] This study aimed to determine the effect of delayed visual feedback on the center of pressure and sitting balance in patients with stroke. [Participants and Methods] This was a single-blinded, randomized crossover trial. The duration of each intervention in real-time visual feedback and delayed visual feedback conditions while sitting on the platform was five days. We measured the center of pressure, function in sitting test, and functional independence measure for physiotherapy assessment. [Results] Twenty patients with stroke were included in this study. The delayed visual feedback condition improved the center of pressure for lateral distance, function in sitting test, and functional independence measure. The lateral center of pressure deviation increased significantly after 500 ms of intervention. The function in sitting test evaluated the interaction between pre- and post-training, and these conditions revealed that timing and condition factors contributed to the improvement. Sitting balance training affected the functional independence measure. [Conclusion] Sensory-motor and cognitive learning was facilitated through balance training with delayed visual feedback, and the internal model was updated with the efference copy of error correction. Sensory-motor feedback to visual stimulation can improve postural control, balance, and activities of daily living.     

Cytolytic Recombinant Vesicular Stomatitis Viruses Expressing STLV-1 Receptor Specifically Eliminate STLV-1 Env-Expressing Cells in an HTLV-1 Surrogate Model In Vitro

Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo.     

Online reporting system for transfusion-related adverse events to enhance recipient haemovigilance in Japan: A pilot study

BackgroundA surveillance system for transfusion-related adverse reactions and infectious diseases in Japan was started at a national level in 1993, but current reporting of events in recipients is performed on a voluntary basis. A reporting system which can collect information on all transfusion-related events in recipients is required in Japan.MethodsWe have developed an online reporting system for transfusion-related events and performed a pilot study in 12 hospitals from 2007 to 2010.ResultsThe overall incidence of adverse events per transfusion bag was 1.47%. Platelet concentrates gave rise to statistically more adverse events (4.16%) than red blood cells (0.66%) and fresh-frozen plasma (0.93%). In addition, we found that the incidence of adverse events varied between hospitals according to their size and patient characteristics.ConclusionThis online reporting system is useful for collection and analysis of actual adverse events in recipients of blood transfusions and may contribute to enhancement of the existing surveillance system for recipients in Japan.     

Rapid induction of OX40 ligand on primary T cells activated under DNA-damaging conditions

We have previously demonstrated that normal human T cells either long-term repeatedly stimulated or freshly activated in vitro in the presence of TGF-beta express the cell surface T-cell costimulating molecule OX40 ligand (OX40L). To further elucidate the kinetics of OX40L expression by human T cells, we have examined whether cell proliferation was required for the expression of OX40L. Thus, normal fresh peripheral blood mononuclear cells were stimulated with immobilized anti-CD3 antibody in the presence of the DNA synthesis-blocking agents such as mitomycin C, 5-fluorouracil, or X-ray irradiation. Flow cytometric analyses demonstrated that a significant frequency of these DNA-damaged activated primary CD4(+) and CD8(+) T cells became OX40L(+) as early as 1 hour after treatment. The OX40L induction on the DNA-damaged activated T cells was inhibited by treatment with either RNA or protein synthesis inhibitors, actinomycin D, or cycloheximide, respectively. Induced OX40L on T cells was functional because it bound recombinant OX40. These data indicate that human primary T cells are programmed to rapidly express functional OX40L molecules after stimulation under DNA-damaging conditions, demonstrating that the induction of OX40L by T cells is independent of cell proliferation. The clinical implications of these new findings are discussed.     

A genome-wide view of Caenorhabditis elegans base-substitution mutation processes

Knowledge of mutation processes is central to understanding virtually all evolutionary phenomena and the underlying nature of genetic disorders and cancers. However, the limitations of standard molecular mutation detection methods have historically precluded a genome-wide understanding of mutation rates and spectra in the nuclear genomes of multicellular organisms. We applied two high-throughput DNA sequencing technologies to identify and characterize hundreds of spontaneously arising base-substitution mutations in 10 Caenorhabditis elegans mutation-accumulation (MA)-line nuclear genomes. C. elegans mutation rate estimates were similar to previous calculations based on smaller numbers of mutations. Mutations were distributed uniformly within and among chromosomes and were not associated with recombination rate variation in the MA lines, suggesting that intragenomic variation in genetic hitchhiking and/or background selection are primarily responsible for the chromosomal distribution patterns of polymorphic nucleotides in C. elegans natural populations. A strong mutational bias from G/C to A/T nucleotides was detected in the MA lines, implicating oxidative DNA damage as a major endogenous mutagenic force in C. elegans. The observed mutational bias also suggests that the C. elegans nuclear genome cannot be at equilibrium because of mutation alone. Transversions dominate the spectrum of spontaneous mutations observed here, whereas transitions dominate patterns of allegedly neutral polymorphism in natural populations of C. elegans and many other animal species; this observation challenges the assumption that natural patterns of molecular variation in noncoding regions of the nuclear genome accurately reflect underlying mutation processes.