Inhibition of serum and glucocorticoid regulated kinase-1 as novel therapy for cardiac arrhythmia disorders.

Alterations in sodium flux (I) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel Na1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1).

Maternal and fetal outcomes in pregnant Japanese women with inflammatory bowel disease: our experience with a series of 23 cases.

Background/aims: Our physicians work to expand the possibilities to treat female patients with inflammatory bowel disease (IBD) who wish to become pregnant. Although many drugs, including 5-aminosalicylate (5-ASA), corticosteroids, immunomodulators, and biologics, are used safely during pregnancy, few reports have described the therapeutic regimen throughout pregnancy and the management of patients who relapse during pregnancy precisely. The aim of this study was to assess the management of patients with IBD during pregnancy.

[Perspectives of Individualized Treatment by Genome-Wide Analyses in Ovarian Cancer].

Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective.

Cancer-specific mutations in p53 induce the translation of Δ160p53 promoting tumorigenesis.

Wild-type p53 functions as a tumour suppressor while mutant p53 possesses oncogenic potential. Until now it remains unclear how a single mutation can transform p53 into a functionally distinct gene harbouring a new set of original cellular roles. Here we show that the most common p53 cancer mutants express a larger number and higher levels of shorter p53 protein isoforms that are translated from the mutated full-length p53 mRNA.

[Osteoporosis in chronic obstructive pulmonary disease.].

Chronic Obstructive Pulmonary Disease(COPD)is characterized by persistent airflow limitation that is associated with chronic inflammatory process caused by inhaled noxious particles such as cigarette smoke. COPD involves not only the lungs but also extrapulmonary abnormalities as systemic effects. Osteoporosis is one of major comorbidities in COPD, and is often under-diagnosed.

Patterns of clinical practice for sentinel lymph node biopsy in women with node-negative breast cancer: the results of a national survey in Japan.

Purpose: Sentinel lymph node (SLN) biopsy is now accepted as the standard of care for axillary staging in women with node-negative breast cancer. Currently, dye, radioisotope (RI), and fluorescence indocyanine green (fICG) are tracers available. Importance of these three tracers has been recognized for SLN biopsy but the trend for SLN mapping has not been reported.

Functional joint regeneration is achieved using reintegration mechanism in Xenopus laevis.

A functional joint requires integration of multiple tissues: the apposing skeletal elements should form an interlocking structure, and muscles should insert into skeletal tissues via tendons across the joint. Whereas newts can regenerate functional joints after amputation, Xenopus laevis regenerates a cartilaginous rod without joints, a "spike." Previously we reported that the reintegration mechanism between the remaining and regenerated tissues has a significant effect on regenerating joint morphogenesis during elbow joint regeneration in newt.

RANIBIZUMAB FOR MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION: One Initial Injection Versus Three Monthly Injections.

Purpose: To compare the 12-month-efficacy of 1 initial intravitreal ranibizumab injection (IVR) followed by pro re nata (PRN) dosing with that of three initial monthly IVR followed by PRN dosing in patients with macular edema (ME) after branch retinal vein occlusion.

Design: Prospective, interventional study.

Methods: Of 81 eyes, 42 received 1 initial IVR injection (1+PRN group) and 39 eyes received 3 monthly IVRs (3+PRN).

Dipeptidyl peptidase-4 inhibitor improved exercise capacity and mitochondrial biogenesis in mice with heart failure via activation of glucagon-like peptide-1 receptor signalling.

Aims: Exercise capacity is reduced in heart failure (HF) patients, due mostly to skeletal muscle abnormalities including impaired energy metabolism, mitochondrial dysfunction, fibre type transition, and atrophy. Glucagon-like peptide-1 (GLP-1) has been shown to improve exercise capacity in HF patients. We investigated the effects of the administration of a dipeptidyl peptidase (DPP)-4 inhibitor on the exercise capacity and skeletal muscle abnormalities in an HF mouse model after myocardial infarction (MI).

Mechanisms of fat-induced gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide secretion from K cells.

Gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which are gastrointestinal hormones released in response to nutrient ingestion and potentiate glucose-stimulated insulin secretion. Single fat ingestion stimulates GIP secretion from enteroendocrine K cells; chronic high-fat diet (HFD) loading enhances GIP secretion and induces obesity in mice in a GIP-dependent manner. However, the mechanisms of GIP secretion from K cells in response to fat ingestion and GIP hypersecretion in HFD-induced obesity are not well understood.

Src regulates insulin secretion and glucose metabolism by influencing subcellular localization of glucokinase in pancreatic β-cells.

Aims/introduction: Src, a non-receptor tyrosine kinase, regulates a wide range of cellular functions, and hyperactivity of Src is involved in impaired glucose metabolism in pancreatic β-cells. However, the physiological role of Src in glucose metabolism in normal, unstressed β-cells remains unclear. In the present study, we investigated the role of Src in insulin secretion and glucose metabolism.

Uterine anatomy and function on cine magnetic resonance imaging.

The female reproductive organ undergoes dynamic morphological changes under the influence of hormonal stimuli, and particularly those mediated by estrogen and progesterone. The uterus changes both its morphological appearance and its functional movements in function of these influences. Functionally, the uterus is known to exert two kinds of inherent contractility: sustained uterine contractions and uterine peristalsis.

A case of neurolymphomatosis caused by follicular lymphoma successfully treated with bendamustine.

Currently, there is no standard treatment for neurolymphomatosis because of the scarcity of clinical studies. Here, we report the successful treatment of neurolymphomatosis caused by follicular lymphoma with bendamustine, which could be an effective treatment option for this condition.

A phase II study of neoadjuvant chemotherapy with S-1 and cisplatin for stage III gastric cancer: KUGC03.

Objectives: A multi-center phase II study was conducted to evaluate the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin for advanced gastric cancer.

Methods: The eligibility criteria were clinical T3/T4 or N2, not Stage IV. Patients received two 35-day cycles of S-1 plus cisplatin, and then underwent D2 gastrectomy.

Reversal of c-MET-mediated Resistance to Cytotoxic Anticancer Drugs by a Novel c-MET Inhibitor TAS-115.

Background: The cellular N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) protein is the receptor tyrosine kinase for hepatocyte growth factor. We recently found that c-MET protein expression and activation were enhanced in the majority of small cell lung cancer cell lines with cytotoxic anticancer drug resistance, and that down-regulation of c-MET reduced resistance to these drugs.

Materials And Methods: Expression of c-MET was studied in three non-small cell lung cancer (NSCLC) cell lines, including six resistant cell strains to cytotoxic anticancer drugs.

Circulating Tumor Cells as an Independent Predictor of Survival in Advanced Gastric Cancer.

Background: When the indication for surgery of highly advanced gastric cancer is considered, careful selection of the patients is important. In addition to tumor-node-metastasis factors and peritoneal lavage cytology (CY), which are important predictors of prognosis, detection of circulating tumor cells (CTCs) could be another potential marker.

Methods: This study prospectively evaluated CTCs using a semi-automated immunomagnetic separation system (CellSearch) for 136 patients with advanced gastric cancer to determine the frequency of CTC positivity.

Characteristics and trends of emergency patients with drug overdose in Osaka.

Aim: Drug overdose is an important issue in emergency medicine. However, studies covering overdose patients transported by ambulance have not been sufficiently carried out. We attempted to clarify problems of suspected drug overdose patients transported by ambulance.

Imatinib use immediately before stem cell transplantation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph(+) ALL04.

Incorporation of imatinib into chemotherapeutic regimens has improved the prognosis of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). We investigated a role of imatinib immediately before hematopoietic stem cell transplantation (HSCT). Children with Ph(+) ALL were enrolled on JPLSG Ph(+) ALL 04 Study within 1 week of initiation of treatment for ALL.

Reintegration of the regenerated and the remaining tissues during joint regeneration in the newt Cynops pyrrhogaster.

Urodele amphibians, such as newts, can regenerate a functional limb, including joints, after amputation at any level along the proximal-distal axis of the limb. The blastema can regenerate the limb morphology largely independently of the stump after proximal-distal identity has been established, but the remaining and regenerated tissues must be structurally reintegrated (matched in size and shape). Here we used newt joint regeneration as a model to investigate reintegration, because a functionally interlocking joint requires structural integration between its opposing skeletal elements.

Simple gamete preservation and artificial reproduction of mammals using micro-insemination techniques.

Assisted reproductive technology (ART) has been applied in various procedures as an effective breeding method in experimental, domestic, and wild animals, and for the treatment of human infertility. Micro-insemination techniques such as intracytoplasmic injection of spermatozoa and spermatids are now routinely used ART tools. With these techniques, even immotile and immature sperm cells can be employed as donors for producing the next generation.

Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation.

Expression of truncated PITX3 in the developing lens leads to microphthalmia and aphakia in mice.

Microphthalmia is a severe ocular disorder, and this condition is typically caused by mutations in transcription factors that are involved in eye development. Mice carrying mutations in these transcription factors would be useful tools for defining the mechanisms underlying developmental eye disorders. We discovered a new spontaneous recessive microphthalmos mouse mutant in the Japanese wild-derived inbred strain KOR1/Stm.

[Targeting the PD-1/PD-L1 immune checkpoint signal - a new treatment strategy for cancer].

Recent studies have revealed that tumor cells can acquire several mechanisms to evade host immunity in the tumor microenvironment, called cancer immune escape. One of the most important mechanisms in this system is an immunosuppressive co- signal, called immune checkpoint, in the programmed cell death-1(PD-1)/programmed death-ligand 1(PD-L1)pathway. PD-1 is mainly expressed on activated T cells, while PD-L1 is frequently expressed on tumor cells.