Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells.

Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases.

Molecular pathways governing development of vascular endothelial cells from ES/iPS cells.

Assembly of complex vascular networks occurs in numerous biological systems through morphogenetic processes such as vasculogenesis, angiogenesis and vascular remodeling. Pluripotent stem cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells can differentiate into any cell type, including endothelial cells (ECs), and have been extensively used as in vitro models to analyze molecular mechanisms underlying EC generation and differentiation. The emergence of these promising new approaches suggests that ECs could be used in clinical therapy.

[Combined spinal and epidural anesthesia for cesarean delivery in a patient with a cervical fracture at C2].

There are only a few reports on cesarean section in a patient with cervical fracture without spinal cord injury (SCI). Such patients have high risks for deterioration of SCI following general or regional anesthesia. Here, we present a patient with a fracture of C2 vertebra who underwent cesarean section safely under combined spinal and epidural anesthesia(CSEA).

[Comparison of nine second- and third-generation anti-cyclic citrullinated peptide antibody assays for the diagnosis of rheumatoid arthritis].

The aim of this study was to compare the diagnostic and analytical performances of nine anti-cyclic citrullinated peptide (CCP) antibody assays. Anti-CCP antibody titers were measured in sera from 89 patients with rheumatoid arthritis (RA), 121 with rheumatic diseases other than RA (non-RA), 47 with osteoarthritis (OA), 142 with chronic inflammatory diseases (CID) and 168 healthy subjects. Reproducibility, sensitivity, specificity, correlation and concordance rate of the nine assays were compared.

Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies.

Objective: To examine cancer incidence in patients with systemic sclerosis (SSc) through a meta-analysis of population-based cohort studies.

Methods: Five different databases (Medline, Scopus, CINAHL [Cumulative Index to Nursing and Allied Health Literature], Web of Science, and Cochrane Collaboration) were searched for articles published between January 1966 and May 2012; review articles and the reference lists from the articles that resulted from the search were also evaluated. Population-based cohort studies with data relevant to the determination of cancer risk in patients with SSc were included.

Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes.

Cancer vaccines have yet to yield clinical benefit, despite the measurable induction of humoral and cellular immune responses. As immunosuppression by CD4(+) CD25(+) regulatory T (Treg) cells has been linked to the failure of cancer immunotherapy, blocking suppression is therefore critical for successful clinical strategies. Here, we addressed whether a lyophilized preparation of Streptococcus pyogenes (OK-432), which stimulates Toll-like receptors, could overcome Treg-cell suppression of CD4(+) T-cell responses in vitro and in vivo.

Hemogenic endothelium: a vessel for blood production.

Blood cell production, or hematopoiesis, is critical to the survival of the developing mammalian embryo. The origins of hematopoietic stem cells, capable of giving rise to all blood cell types, are being revealed. During embryogenesis, hematopoietic stem and progenitor cells are generated from a unique population of vascular endothelium termed hemogenic endothelial cells.

Zebrafish erythropoiesis and the utility of fish as models of anemia.

Erythrocytes contain oxygen-carrying hemoglobin to all body cells. Impairments in the generation of erythrocytes, a process known as erythropoiesis, or in hemoglobin synthesis alter cell function because of decreased oxygen supply and lead to anemic diseases. Thus, understanding how erythropoiesis is regulated during embryogenesis and adulthood is important to develop novel therapies for anemia.

Fasting remnant lipoproteins can predict postprandial hyperlipidemia.

Background: Hypertriglyceridemia and postprandial hyperlipidemia is thought to play an important role in atherosclerosis, but to select patients at high-risk for cardiovascular diseases is difficult with triglycerides (TG) alone in these patients.

Methods: To predict postprandial hyperlipidemia without inconvenient test meal loading, we examined lipid concentrations before and after test meal loading and fasting adiponectin, and investigated which of these other than TG were significant during the fasting period in 45 healthy individuals (men: women, 26:19).

Results: TG, remnant-like particle-cholesterol and -triglyceride (RemL-C, RLP-C, and RLP-TG), and TG/apolipoprotein(apo)B were significantly elevated after loading and fasting values significantly and positively correlated with incremental area under the curve (iAUC) (r=0.

TGF-beta-1 up-regulates extra-cellular matrix production in mouse hepatoblasts.

Fetal liver is the major embryonic hematopoietic organ and is extrinsically colonized by circulating hematopoietic stem cells (HSCs). Integrin beta-1 expression on HSCs is crucial for colonization, suggesting that interaction of Integrin beta-1 with extra-cellular matrix (ECM) factors promotes HSC adherence to fetal liver. However, little is known about how ECM production is regulated in fetal liver.

Incidence and aggravation of cervical spine instabilities in rheumatoid arthritis: a prospective minimum 5-year follow-up study of patients initially without cervical involvement.

Study Design: A prospective minimum 5-year follow-up study of the cervical spine in patients with rheumatoid arthritis (RA) initially without cervical involvement.

Objective: To clarify the incidence and aggravation of cervical spine instabilities and their predictive risk factors in patients with RA.

Summary Of Background Data: Many reports have shown the progression of cervical spine involvement in RA.

Does high-sensitivity C-reactive protein or low-density lipoprotein cholesterol show a stronger relationship with the cardio-ankle vascular index in healthy community dwellers?: the KOBE study.

Aim: High-sensitivity C-reactive protein (hs-CRP) identifies individuals at risk for cardiovascular disease (CVD) without an increased level of low-density lipoprotein cholesterol (LDL-C). The present study was performed to compare hs-CRP and LDL-C in association with the cardio-ankle vascular index (CAVI) in Japanese community dwellers considered to be at low risk for atherosclerosis from their level of traditional CVD risk factors.

Methods: A community-based study involving 386 healthy Japanese (261 men and 125 women) without a history of CVD and medications for hypertension, diabetes, and dyslipidemia was performed.

Radiological protection from radioactive waste management in existing exposure situations resulting from a nuclear accident.

In environmental remediation after nuclear accidents, radioactive wastes have to be appropriately managed in existing exposure situations with contamination resulting from the emission of radionuclides by such accidents. In this paper, a framework of radiation protection from radioactive waste management in existing exposure situations for application to the practical and reasonable waste management in contaminated areas, referring to related ICRP recommendations was proposed. In the proposed concept, intermediate reference levels for waste management are adopted gradually according to the progress of the reduction in the existing ambient dose in the environment on the basis of the principles of justification and optimisation by taking into account the practicability of the management of radioactive waste and environmental remediation.

Mesodermal and hematopoietic differentiation from ES and iPS cells.

Embryonic stem (ES) and induced pluripotent stem (iPS) cells can differentiate into any type of tissue when grown in a suitable culture environment and are considered valuable tools for regenerative medicine. In the field of hematology, generation of hematopoietic stem cells (HSCs) and mature hematopoietic cells (HCs) from ES and iPS cells through mesodermal cells, the ancestors of HCs, can facilitate transplantation and transfusion therapy. Several studies report generation of functional HCs from both mouse and human ES and iPS cells.

Intra-aortic clusters undergo endothelial to hematopoietic phenotypic transition during early embryogenesis.

Intra-aortic clusters (IACs) attach to floor of large arteries and are considered to have recently acquired hematopoietic stem cell (HSC)-potential in vertebrate early mid-gestation embryos. The formation and function of IACs is poorly understood. To address this issue, IACs were characterized by immunohistochemistry and flow cytometry in mouse embryos.

Importance of vital signs to the early diagnosis and severity of sepsis: association between vital signs and sequential organ failure assessment score in patients with sepsis.

Objective: While much attention is given to the fifth vital sign, the utility of the 4 classic vital signs (blood pressure, respiratory rate, body temperature, and heart rate) has been neglected. The aim of this study was to assess a possible association between vital signs and the Sequential Organ Failure Assessment (SOFA) score in patients with sepsis.

Methods: We performed a prospective, observational study of 206 patients with sepsis.

Mycophenolate mofetil versus intravenous cyclophosphamide for induction treatment of proliferative lupus nephritis in a Japanese population: a retrospective study.

Objectives: Recent studies have shown that mycophenolate mofetil (MMF) is similar to intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis (LN), but that treatment response may vary according to location and race/ethnicity. Moreover, no studies have been conducted to compare the efficacy of MMF with that of IVC for a Japanese population. We therefore conducted a retrospective study to clarify the efficacy and safety of MMF compared with that of IVC for induction therapy for active LN, classes III and IV, in a Japanese population of 21 patients, 11 of whom received MMF and 10 IVC.

Clarifying the importance of CYP2C19 and PON1 in the mechanism of clopidogrel bioactivation and in vivo antiplatelet response.

Aims: It is thought that clopidogrel bioactivation and antiplatelet response are related to cytochrome P450 2C19 (CYP2C19). However, a recent study challenged this notion by proposing CYP2C19 as wholly irrelevant, while identifying paraoxonase-1 (PON1) and its Q192R polymorphism as the major driver of clopidogrel bioactivation and efficacy. The aim of this study was to systematically elucidate the mechanism and relative contribution of PON1 in comparison to CYP2C19 to clopidogrel bioactivation and antiplatelet response.

In vivo patch-clamp recording from locus coeruleus neurones in the rat brainstem.

Locus coeruleus (LC) neurones extend noradrenergic projections throughout the neuroaxis and are involved in homeostatic functions such as pain modulation, arousal and cardio-respiratory control. To address the cellular mechanisms underlying pain modulation we have developed a patch-clamp recording technique from LC neurones in anaesthetized rats. These recordings showed LC discharge in vivo to be driven by both spontaneous membrane potential oscillations and CNQX-sensitive EPSCs opposed by bicuculine-sensitive IPSCs.

Comparison of reinnervation for preservation of denervated muscle volume with motor and sensory nerve: an experimental study.

Prevention of the atrophy of denervated muscles is essential for a good outcome in facial contouring and oral reconstruction. In this study, we compared the effectiveness of end-to-end and end-to-side neurorrhaphy of the motor nerve, and end-to-end neurorrhaphy of the sensory nerve, all of which are frequently used in such reconstruction for the prevention of muscle atrophy. Wistar rats were divided into four groups: group 1, motor nerve division of semi-membranosus without repair; group 2, motor nerve division and end-to-end coaptation to the saphenous nerve; group 3, motor nerve division and end-to-side coaptation to the sciatic nerve; and group 4, motor nerve division and end-to-end repair.

Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an intractable hematologic malignancy caused by human T-lymphotropic virus type 1 (HTLV-1), which infects approximately 20 million people worldwide. Here, we have explored the possible expression of cancer/testis (CT) antigens by ATLL cells, as CT antigens are widely recognized as ideal targets of cancer immunotherapy against solid tumors. A high percentage (87.

Predicting scores for left ventricular dysfunction in Duchenne muscular dystrophy.

Background: The aim of this study was to predict left ventricular (LV) dysfunction and the timing to perform echocardiography in patients with Duchenne muscular dystrophy (DMD). We developed a scoring system using clinical parameters and examined its efficacy. It is indispensable to utilize echocardiogram for evaluating myocardial damage of DMD patients, but there is no established guideline for determining the clinical conditions which require echocardiographic examination.

SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production.

SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52(low) HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H(2)O(2)- or diamide-induced oxidative stress, IFN-α, IFN-γ and anti-Fas antibody, etoposide, or γ-irradiation.

Embryonic regulation of the mouse hematopoietic niche.

Hematopoietic stem cells (HSCs) can differentiate into several types of hematopoietic cells (HCs) (such as erythrocytes, megakaryocytes, lymphocytes, neutrophils, or macrophages) and also undergo self-renewal to sustain hematopoiesis throughout an organism's lifetime. HSCs are currently used clinically as transplantation therapy in regenerative medicine and are typically obtained from healthy donors or cord blood. However, problems remain in HSC transplantation, such as shortage of cells, donor risks, rejection, and graft-versus-host disease (GVHD).