Angle-resolved photoemission study of MX-chain compound [Ni(chxn)2_2Br]Br2_2

We report on the results of angle-resolved photoemission experiments on a quasi-one-dimensional $MX$-chain compound [Ni(chxn)$_2$Br]Br$_2$ (chxn = 1$R$,2$R$-cyclohexanediamine), a one-dimensional Heisenberg system with $S=1/2$ and $J \sim 3600$ K, which shows a gigantic non-linear optical effect. A "band" having about 500 meV energy dispersion is found in the first half of the Brillouin zone $(0\le kb/\pi <1/2)$, but disappears at $kb / \pi \sim 1/2$. Two dispersive features, expected from the spin-charge separation, as have been observed in other quasi-one-dimensional systems like Sr$_2$CuO$_3$, are not detected. These characteristic features are well reproduced by the $d$-$p$ chain model calculations with a small charge-transfer energy $\Delta$ compared with that of one-dimensional Cu-O based compounds. We propose that this smaller $\Delta$ is the origin of the absence of clear spin- and charge-separation in the photoemission spectra and strong non-linear optical effect in [Ni(chxn)$_2$Br]Br$_2$.Comment: 4 pages, 3 figure

Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells

Chondrogenesis is the complex process that leads to the establishment of cartilage and bone formation. Due to their ability to differentiate in vitro and mimic development, embryonic stem cells (ESCs) show great potential for investigating developmental processes. In this study, we used chondrogenic differentiation of ESCs as a model to analyze morphogenetic events during chondrogenesis.ESCs were differentiated into the chondrocyte lineage, forming small cartilaginous aggregates in suspension. Differentiated ESCs showed that chondrogenesis was typically characterized by five overlapping stages. During the first stage, cell condensation and aggregate formation was observed. The second stage was characterized by differentiation into chondrocytes and fibril scaffold formation within spherical aggregates. Deposition of cartilaginous extracellular matrix and cartilage formation were hallmarks of the third stage. Apoptosis of chondrocytes, hypertrophy and/or degradation of cartilage occurred during the fourth stage. Finally, during the fifth stage, bone replacement with membranous calcified tissues took place.We demonstrate that ESCs show the chondrogenic differentiation pathway from the pluripotent stem cell to terminal skeletogenesis through these five stages in vitro. During each stage, morphological changes acquired in preceding stages played an important role in further development as a scaffold or template in subsequent stages. The study of chondrogenesis via ESC differentiation may be informative to our further understanding of skeletal growth and regeneration

Effects of hydrophilic polymer-coated polysulfone membrane dialyzers on intradialytic hypotension in diabetic hemodialysis patients (ATHRITE BP Study) : a pilot study

Background: Intradialytic hypotension (IDH) is a common clinical manifestation associated with poor prognosis in hemodialysis (HD) patients. HD patients who suffer from diabetic nephropathy (DN) are increasing and diabetes is a major cause of IDH. Effective interventional treatments for IDH have yet to be fully evaluated. The aim of this multicenter prospective study is to clarify the effect of biocompatible hydrophilic polymer-coated polysulfone (PS) membrane, TORAYLIGHT® NV (NV) dialyzers on IDH. Methods: This is a prospective stratified-randomized multicenter trial. Forty DN patients undergoing HD and receiving two or more times of treatments for IDH per month were enrolled in this study. They were stratified by the number of treatments for IDH and divided to two groups using NV or conventional PS/polyethersulfone (PES) dialyzers. The number of treatments for IDH and changes in systolic blood pressure (SBP) were monitored for 6 months. Patients’ demographic and clinical characteristics were also collected at enrollment and the last month of the observation period. In order to clarify the patient characteristics that induced preferable effects by using NV dialyzers, responders were defined as the patients whose average SBP falls in 1 month improved from over 30 mmHg to no more than 30 mmHg. Results: The total number of treatments for IDH decreased significantly in NV group, even though pre-dialysis body weight and ultrafiltration volume were similar. In addition, patients using NV had significantly higher post-dialysis SBP and the lowest SBP during HD at sixth month compared as those in PS/PES group. NV responders had valuables suggesting malnutrition and microinflammation, and better lipid profiles than non-responders. However, the representative markers related to nutritional status, arteriosclerosis, and inflammation were not improved by NV treatment. Conclusions: NV had preferable effects on IDH in DN HD patients. Our results suggest the usefulness of NV as a possible method to deal with IDH. Further studies are needed to clarify the mechanism of NV effects on hemodynamic status

High intensity zone in lumbar spine and its correlation with disc degeneration

Purpose ; To investigate the prevalence, clinical significance of high intensity zone (HIZ), and associated disc degeneration. Materials and methods ; We undertook retrospective analysis of 228 patients, aged from 15 to 55 years, who had undergone magnetic resonance (MR) imaging of lumbar spine in outpatient clinic from 2013 to 2014. HIZ was defined as a presence of high intensity signal in the annulus on T2-weighted images. All HIZ positive discs were classified according to Pfirrmann grading system for presence of disc degeneration. Results ; Forty-three patients (18.8%) with 53 intervertebral discs demonstrated HIZ. There was no significant predominance about age and gender for the presence of HIZ. HIZ occurred mainly at L4-5 (43.3%) and L5-S1 (30.2%) levels, infrequently at L3-4 (17%) and rarely at upper levels. The prevalence of disc degenerations with Pfirrmann grade 3, 4, and 5 were significantly higher in HIZ positive patients than in randomly selected 35 HIZ negative patients (64% vs. 46%, respectively). Conclusion ; In this study we identified that the presence of HIZ was directly proportional to increased incidence of disc degeneration in remaining lumbar discs. The prevalence of significant degeneration was significantly higher in HIZ positive patient at lower three lumbar levels

Clinical Significance of High-intensity Zone for Discogenic Low Back Pain : A Review

High-intensity zone (HIZ) was originally described as a high-intensity signal on T2-weighted magnetic resonance (MR) images, located in the posterior annulus fibrosus, clearly separated from the nucleus pulposus. Among symptomatic patients with low back pain, HIZ is present in 28-59% of cases. In morphologically abnormal discs, high sensitivity and specificity of 81% and 79%, respectively, were reported for HIZs and concordant pain during discography. In contrast, another report indicated low rates. Although most papers reported high sensitivity and specificity for this relationship, it remains controversial. Regarding the pathology of HIZs, inflammatory granulation tissues are found at sites showing HIZs. Such inflammatory tissues produce pro-inflammatory cytokines and mediators, which sensitize the nociceptors within the disc and cause pain. An effective treatment for this condition is yet to be established. Recently, minimally invasive surgery using percutaneous endoscopic discectomy (PED) under local anesthesia was introduced. After removal of the degenerated disc material, the HIZ is identified with the endoscope and then coagulated and modulated with a bipolar radio pulse. This technique is called thermal annuloplasty. In conclusion, HIZs is an important sign of painful intervertebral disc disruption, if identified precisely based on factors such as location and intensity

Clinical Application of Computer-Aided Diagnostic System for Harmonious Introduction of Complementary Dialysis Therapy

In chronic peritoneal dialysis (PD) therapy, peritoneal permeability is gradually enhanced over the duration of the therapeutic course, leading to a grave decline in the therapeutic efficiency. In recent years, a novel therapy (CD therapy), which integrates PD therapy with hemodialysis therapy, is being applied to end-stage PD patients to complement the decline of therapeutic efficiency caused by the grave degeneration of the peritoneal tissue. To realize a harmonious introduction of the CD therapy, this study developed a useful index (KAu/c), which evaluates both therapeutic efficiency and degeneration of peritoneal tissue. Using a mathematical model and KAu/c, we were able to validate the therapeutic efficiency in the PD patients, and, in one case, propose a better prescription for the patient by employing the CD therapy. The clinical implementation of this methodology is indispensable with regard to expanding the therapeutic monitoring system for renal replacement therapy

Radiographic changes of cervical destructive spondyloarthropathy in long-term hemodialysis patients : A 9-year longitudinal observational study

Analyses of radiographic changes and clinical symptom of destructive spondyloarthropathy (DSA) on consecutive 42 patients managed with long-term hemodialysis were performed to elucidate radiographic changes of DSA and the factors that influence to the destructive changes. Patients underwent plain radiographs of the cervical spine with 9 years interval. Grading of radiological feature from lateral view was classified into grade 0 to grade 3. Clinical symptom was evaluated using modified Japanese Orthopaedic Association scoring system for cervical myelopathy (mJOA score). Destructive changes were observed in 3 patients at the first examination, and those were observed in 15 patients 9 years after the first examination. There is no statistically significant difference between the duration of hemodialysis and the grade. The mean age at the onset of hemodialysis, however, was significantly higher in patients of grade 2 and 3 than those of grade 1. Older patients with long-term hemodialysis had destructive changes. Destructive changes commonly observed in lower cervical spine. The average numbers of the involved disc level were 1.6 in grade 2 and 1.0 in grade 3. Clinical symptoms were varied in each grade and there was no statistically significant difference in total mJOA score among these grades

Genetic Heterogeneity of Hepatitis C Virus in Association with Antiviral Therapy Determined by Ultra-Deep Sequencing

The hepatitis C virus (HCV) invariably shows wide heterogeneity in infected patients, referred to as a quasispecies population. Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail.Using a newly developed massive-parallel ultra-deep sequencing technique, we investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients receiving peg-interferon (IFN) α2b plus ribavirin therapy.Ultra-deep sequencing determined a total of more than 10 million nucleotides of the HCV genome, corresponding to a mean of more than 1000 clones in each specimen, and unveiled extremely high genetic heterogeneity in the genotype 1b HCV population. There was no significant difference in the level of viral complexity between immediate virologic responders and non-responders at baseline (p = 0.39). Immediate virologic responders (n = 8) showed a significant reduction in the genetic complexity spanning all the viral genetic regions at the early phase of IFN administration (p = 0.037). In contrast, non-virologic responders (n = 8) showed no significant changes in the level of viral quasispecies (p = 0.12), indicating that very few viral clones are sensitive to IFN treatment. We also demonstrated that clones resistant to direct-acting antivirals for HCV, such as viral protease and polymerase inhibitors, preexist with various abundances in all 27 treatment-naïve patients, suggesting the risk of the development of drug resistance against these agents.Use of the ultra-deep sequencing technology revealed massive genetic heterogeneity of HCV, which has important implications regarding the treatment response and outcome of antiviral therapy

Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells

MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1−/− mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1−/− mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1−/− mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1−/− mice. Transplantation of MCP-1−/− bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1−/− mice increased lung metastasis. The primary tumors of MCP-1−/− mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1−/− mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment