Blockade of CD80/CD86-CD28 co-stimulation augments the inhibitory function of peptide antigen-specific regulatory T cells.

Mixed lymphocyte culture under the blockade of CD80/CD86-CD28 co-stimulation induces anergic (completely hyporesponsive) T cells with immune suppressive function (inducible suppressing T cells: iTS cells). Previously, iTS cell therapy has demonstrated outstanding benefits in clinical trials for organ transplantation. Here, we examined whether peptide antigen-specific iTS cells are inducible.

CD8 T cell-mediated rejection of allogenic human-induced pluripotent stem cell-derived cardiomyocyte sheets in human PBMC-transferred NOG MHC double knockout mice.

Background: Transplantation of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) has emerged as a promising therapy to treat end-stage heart failure. However, the immunogenicity of hiPS-CMs in transplanted patients has not been fully elucidated. Thus, in vivo models are required to estimate immune responses against hiPS-CMs in transplant recipients.

Analysis of therapeutic potential of monocytic myeloid-derived suppressor cells in cardiac allotransplantation.

Background: Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model.

Methods: We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity.

Retrograde percutaneous coronary intervention for acute myocardial infarction following blunt chest trauma.

A 78-year-old man was admitted to the emergency department because of chest pain following blunt chest trauma. Chest X-ray revealed multiple rib fractures. However, electrocardiogram showed ST elevation in inferior leads suggesting acute myocardial infarction (AMI).

Feasibility of a novel tacking method of securing mesh in transabdominal preperitoneal inguinal hernia repair: Secure tacking against recurrence.

Introduction: Postoperative chronic pain is an important outcome of hernia surgery. In laparoscopic hernia surgery, either fixation outside the trapezoid of disaster or no fixation is recommended to avoid postoperative pain. To avoid recurrence are transabdominal preperitoneal (TAPP) hernia repair, the myopectineal orifice must be covered with mesh during TAPP, but lifting or shrinking of the mesh can lead to recurrence.

Estimation of the Compatibility of Blend Composites of Resins by Measuring the Fluorescent Spectra.

The effects of adding desipramine-containing fluorescence polymer (poly(10,11-dihydro-5-[3-(N-methylamino)propyl]dibenz[b,f]azepine-2,8-diyl-alt-9,9-didodecylfluorene-2,7-diyl, PAzep-Fl) to resins were investigated. When composites were prepared by a reactive blend of poly(lactic acid) (PLA), PAzep-Fl, and diisocyanate, the molecular weight of the obtained composite was larger than that of the composite, which was blended without PAzep-Fl; this suggested that chemical bonding occured between PLA and PAzep-Fl via diisocyanate. The effects of adding PAzep-Fl in two kinds of resins/lysine triisocyanate (LTI) blend were also investigated.

[Anesthetic management of laparoscopic cholecystectomy for a patient with Churg-Strauss syndrome: a case report].

Churg-Strauss syndrome (CSS) is an uncommon disease characterized by bronchial asthma, eosinophilia and systemic vasculitis. Many patients with CSS are suffering from cardiovascular disorders, neurological disorders and/or renal disorders which are associated with systemic vasculitis. Cardiac diseases are considered as the main cause of the death in patients with CSS.

Effects of change in the formulation of lanthanum carbonate on laboratory parameters.

Lanthanum carbonate (LC) is available in the two formulations of chewable tablets and granules. In this study, we changed the formulation of LC from chewable tablet to granules, and compared the laboratory parameters for 3 months before and after changing formulation in 58 hemodialysis (HD) patients. We also surveyed patients about their preferences for the two formulations.

Angiotensin II type 1a receptor signalling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy.

Background And Purpose: Angiotensin II has been implicated in the development of various cardiovascular ailments, including cardiac hypertrophy and heart failure. The fact that inhibiting its signalling reduced the incidences of both sudden cardiac death and heart failure in several large-scale clinical trials suggests that angiotensin II is involved in increased cardiac arrhythmogenicity during the development of heart failure. However, because angiotensin II also promotes structural remodelling, including cardiomyocyte hypertrophy and cardiac fibrosis, it has been difficult to assess its direct contribution to cardiac arrhythmogenicity independently of the structural effects.

[A case of acute renal failure following compartment syndrome after the surgery for femoral neck fracture].

Compartment syndrome is known to develop after a prolonged surgery in the lithotomy position. We experienced acute renal failure following compartment syndrome after the surgery in hemilithotomy position. A 62-year-old man underwent a left hip fixation for femoral neck fracture.

Determination of the B-type natriuretic peptide level as a criterion for abnormalities in Japanese individuals in routine clinical practice: the J-ABS Multi-Center Study (Japan Abnormal BNP Standard).

Objective: The present study was undertaken to establish a useful range for the B-type natriuretic peptide (BNP) level, with the ultimate goal of determining a cut-off BNP level that will make it possible to identify patients with clinically important organic heart disorders among patients encountered in clinical practice.

Methods: A total of 11,967 outpatients were evaluated for this study, and, after applying the exclusion criteria, 361 patients were finally recruited for the analysis. Compared to the factors of gender and body mass index, aging was considered to be an indispensable factor in this analysis.

Induction and enhancement of cardiac cell differentiation from mouse and human induced pluripotent stem cells with cyclosporin-A.

Induced pluripotent stem cells (iPSCs) are novel stem cells derived from adult mouse and human tissues by reprogramming. Elucidation of mechanisms and exploration of efficient methods for their differentiation to functional cardiomyocytes are essential for developing cardiac cell models and future regenerative therapies. We previously established a novel mouse embryonic stem cell (ESC) and iPSC differentiation system in which cardiovascular cells can be systematically induced from Flk1(+) common progenitor cells, and identified highly cardiogenic progenitors as Flk1(+)/CXCR4(+)/VE-cadherin(-) (FCV) cells.

p300 plays a critical role in maintaining cardiac mitochondrial function and cell survival in postnatal hearts.

Rationale: It is known that the transcriptional coactivator p300 is crucially involved in the differentiation and growth of cardiac myocytes during development. However, the physiological function of p300 in the postnatal hearts remains to be characterized.

Objective: We have now investigated the physiological function of p300 in adult hearts.

T-type Ca2+ channel blockade prevents sudden death in mice with heart failure.

Background: Pharmacological interventions for prevention of sudden arrhythmic death in patients with chronic heart failure remain limited. Accumulating evidence suggests increased ventricular expression of T-type Ca(2+) channels contributes to the progression of heart failure. The ability of T-type Ca(2+) channel blockade to prevent lethal arrhythmias associated with heart failure has never been tested, however.

Impact of thymidine phosphorylase-expressing macrophages for surgical margin in partial nephrectomy.

Objectives: We investigated the relationship between the surgical margin in partial nephrectomy (PN) and thymidine phosphorylase (TP)-expressing macrophages in peritumoral tissue of renal cell carcinoma (RCC).

Methods: In 46 patients who underwent radical nephrectomy, we measured TP protein levels in tumor tissue, peritumoral tissue and normal tissue, and conducted immunohistochemical staining for TP and macrophages. In addition, we prospectively conducted PN with a 5-mm margin in 11 patients with pT1a RCC.

Significance of 5-fluorouracil-related enzyme activities in predicting sensitivity to 5-fluorouracil in bladder carcinoma.

Background: The association between 5-fluorouracil (5-FU)-related enzyme activity and the sensitivity of bladder urothelial carcinoma (BUC) to 5-FU were investigated, and methods to improve 5-FU sensitivity were analyzed.

Materials And Methods: Tumor specimens were obtained from 127 patients. Orotate phosphoribosyl transferase (OPRT) activity was analyzed by the paper disc method and thymidine phosphorylase and dihydropyrimidine dehydrogenase (DPD) activities were measured by ELISA.

Guanylyl cyclase-A inhibits angiotensin II type 2 receptor-mediated pro-hypertrophic signaling in the heart.

Angiotensin II plays a key role in the development of cardiac hypertrophy. The contribution of the angiotensin II type 1 receptor (AT1) in angiotensin II-induced cardiac hypertrophy is well established, but the role of AT2 signaling remains controversial. Previously, we have shown that natriuretic peptide receptor/guanylyl cyclase-A (GCA) signaling protects the heart from hypertrophy at least in part by inhibiting AT1-mediated pro-hypertrophic signaling.

Endogenous cardiac natriuretic peptides protect the heart in a mouse model of dilated cardiomyopathy and sudden death.

Ventricular myocytes are known to show increased expression of the cardiac hormones atrial and brain natriuretic peptide (ANP and BNP, respectively) in response to pathological stress on the heart, but their function during the progression of nonischemic dilated cardiomyopathy remains unclear. In this study, we crossed a mouse model of dilated cardiomyopathy and sudden death, which we generated by cardioselectively overexpressing a dominant-negative form of the transcriptional repressor neuron-restrictive silencer factor (dnNRSF Tg mice), with mice lacking guanylyl cyclase-A (GC-A), a common receptor for ANP and BNP, to assess the effects of endogenously expressed natriuretic peptides during progression of the cardiomyopathy seen in dnNRSF Tg mice. We found that dnNRSF Tg;GC-A(-/-) mice were born normally, but then most died within 4 wk.

Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers.

Objectives: The purpose of this study was to determine whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) suppresses coronary spasm.

Background: Coronary spasm is associated with endothelial dysfunction. Statins have been shown to improve endothelial function.

Association of CT dinucleotide repeat polymorphism in the 5'-flanking region of the guanylyl cyclase (GC)-A gene with essential hypertension in the Japanese.

Guanylyl cyclase (GC)-A (natriuretic peptide receptor [NPR]-1), the receptor for atrial and brain natriuretic peptide, is important in the regulation of blood pressure in animal models and, possibly, in humans. In this study, we examined the association between dinucleotide repeat polymorphism within the 5'-flanking region of the GC-A gene and essential hypertension in a group of Japanese subjects. By genotyping 177 hypertensive and 170 normotensive subjects, we identified 5 allele types with 6, 9, 10, 11 and 12 CT dinucleotide repeats, respectively, around position -293, upstream of the ATG codon in the human GC-A gene.

[Preoperative evaluation and anesthetic management of a patient with Brugada syndrome-like ECG].

Brugada syndrome has been known as one of the causes of sudden death due to ventricular fibrillation. We experienced anesthetic management of seven patients with ECG showing Brugada syndrome before surgery, even though they had no symptoms nor family history. All of them showed no problems through-out the operation.

Genetic disruption of angiotensin II type 1a receptor improves long-term survival of mice with chronic severe aortic regurgitation.

Background: Aortic regurgitation (AR) causes left ventricular (LV) volume overload, leading to progressive LV dilatation and dysfunction. In the present study it was examined whether blockade of angiotensin II type 1 receptor (AT1) could improve survival in cases of chronic severe AR.

Methods And Results: AR was induced by puncturing the aortic valves of wild-type (WT) and AT1a knockout (KO) mice.