Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the mouse blastocyst.

The first lineage choice in mammalian embryogenesis is that between the trophectoderm, which gives rise to the trophoblast of the placenta, and the inner cell mass, from which is derived the embryo proper and the yolk sac. The establishment of these lineages is preceded by the inside-versus-outside positioning of cells in the early embryo and stochastic expression of key transcription factors, which is then resolved into lineage-restricted expression. The regulatory inputs that drive this restriction and how they relate to cell position are largely unknown.

Effect of rebamipide ophthalmic suspension on signs and symptoms of keratoconjunctivitis sicca in Sjögren syndrome patients with or without punctal occlusions.

Purpose: The aim of this study was to investigate the efficacy of 2% rebamipide suspension in treatment of keratoconjunctivitis sicca (KCS) in patients with Sjögren syndrome (SS) with or without punctal occlusions.

Methods: Thirty patients with SS, diagnosed based on the presence of autoantibodies and/or focus score >1 on lip biopsies, with corneal fluorescein staining scores (FSS) >3, and conjunctival lissamine green-staining scores (LSS) >3, were treated 4 times daily for 4 weeks with 2% rebamipide ocular suspension. Ocular examinations were performed before treatment and 2 and 4 weeks after treatment to evaluate FSS (0-9), LSS (0-6), and tear film break-up time (BUT).

[Liver injury and hepatic encephalopathy induced by the herbal medicine Hochuekkito].

A 57-year-old man was admitted with pruritus and jaundice following treatment for fatigue with the herbal medicine Hochuekkito. The patient was prescribed prednisolone and ursodeoxycholic acid, but he developed progressive cholestasis that required intravenous methylprednisolone pulse therapy. After treatment with plasma exchange for prolonged prothrombin time, the patient recovered; however, his liver function deteriorated because of liver injury induced by trimethoprim-sulfamethoxazole for pneumocystis pneumonia.

Pulmonary metastases after low-dose-rate brachytherapy for localized prostate cancer.

Purpose: To analyze unusual events and focus discussion on pulmonary metastasis in particular after low-dose-rate brachytherapy (LDR-BT) for prostate cancer (PCa).

Materials And Methods: A total of 616 consecutive patients who had undergone LDR-BT for clinically localized PCa at Jikei University Hospital between October 2003 and April 2010 were enrolled in this study. Follow-up information was summarized, and patterns of biochemical recurrence and clinical outcome were investigated.

The role of angiomotin phosphorylation in the Hippo pathway during preimplantation mouse development.

The Hippo signaling pathway regulates a number of cellular events, including the control of cell fates in preimplantation mouse embryos. The inner and outer cells of the embryo show high and low levels of Hippo signaling, respectively. This position-dependent Hippo signaling promotes the specification of distinct cell fates.

Gemcitabine as a molecular targeting agent that blocks the Akt cascade in platinum-resistant ovarian cancer.

Background: Gemcitabine (2', 2' -difluorodeoxycytidine) is one of many nonplatinum drugs that exhibit activity in recurrent, platinum-resistant ovarian cancer. However, the molecular mechanisms by which Gemcitabine treatment inhibits the proliferation of platinum-resistant ovarian cancer cells still remain unclear. We investigated whether Gemcitabine increases the efficacy of Cisplatin in platinum-resistant ovarian cancer models in vitro and in vivo.

Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos.

Mammalian embryos develop in coordination with extraembryonic tissues, which support embryonic development by implanting embryos into the uterus, supplying nutrition, providing a confined niche, and also providing patterning signals to embryos. Here, we show that in mouse embryos, the expansion of the amniotic cavity (AC), which is formed between embryonic and extraembryonic tissues, provides the mechanical forces required for a type of morphogenetic movement of the notochord known as convergent extension (CE) in which the cells converge to the midline and the tissue elongates along the antero-posterior (AP) axis. The notochord is stretched along the AP axis, and the expansion of the AC is required for CE.

Laparoscopic diagnosis of adenocarcinoma of the appendix mimicking serous papillary adenocarcinoma of the peritoneum.

Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery.

Salvage partial brachytherapy for prostate cancer recurrence after primary brachytherapy.

Objectives: To characterize local recurrence of prostate cancer and to assess the effect of salvage partial brachytherapy after primary 125-iodine low-dose rate brachytherapy with or without external beam radiotherapy in Japanese men.

Methods: Between 2003 and 2010, a total of 616 consecutive patients underwent low-dose rate brachytherapy-based therapy for clinically localized prostate cancer at Jikei University Hospital in Tokyo, Japan. Biochemical recurrence occurred in 45 (7.

Analysis of prognostic factors in localized high-risk prostate cancer patients treated with HDR brachytherapy, hypofractionated 3D-CRT and neoadjuvant/adjuvant androgen deprivation therapy (trimodality therapy).

Trimodality therapy consisting of high dose rate (HDR) brachytherapy combined with external beam radiation therapy (EBRT), neoadjuvant hormonal therapy (NHT) and adjuvant hormonal therapy (AHT) has been used to treat localized high-risk prostate cancer. In this study, an analysis of patients receiving the trimodality therapy was performed to identify prognostic factors of biochemical relapse-free survival (bRFS). Between May 2005 and November 2008, 123 high-risk prostate cancer patients (D'Amico classification) were treated with NHT prior to HDR brachytherapy combined with hypofractionated EBRT.

Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells.

Recapitulating three-dimensional (3D) structures of complex organs, such as the kidney, from pluripotent stem cells (PSCs) is a major challenge. Here, we define the developmental origins of the metanephric mesenchyme (MM), which generates most kidney components. Unexpectedly, we find that posteriorly located T(+) MM precursors are developmentally distinct from Osr1(+) ureteric bud progenitors during the postgastrulation stage, and we identify phasic Wnt stimulation and stage-specific growth factor addition as molecular cues that promote their development into the MM.

Mid-term outcome of permanent prostate iodine-125 brachytherapy in Japanese patients.

Objectives: To analyze mid-term oncological outcomes of low-dose rate brachytherapy in Japanese patients.

Methods: Between 2003 and 2010, 604 consecutive patients with clinically localized prostate cancer were treated with low-dose rate brachytherapy at Jikei University Hospital in Tokyo, Japan. Median follow up was 48 months.

Pre-clinical validation of orthotopically-implanted pulmonary tumor by imaging with 18F-fluorothymidine-positron emission tomography/computed tomography.

The development of positron-emission tomography (PET) and X-ray computed tomography (CT) imaging has improved the detection of tumor burden and, in turn, pre-clinical drug development and clinical treatment. In pre-clinical drug development, clinically-relevant murine cancer models, such as orthotopic models of lung cancer, have provided an accurate representation of tumor burden in humans. However, evidence demonstrating the capability of imaging-guided evaluation of these clinically-relevant models is limited.

Total laparoscopic modified radical hysterectomy with lymphadenectomy for endometrial cancer compared with laparotomy.

Aim: This is the first report to determine the feasibility and safety of total laparoscopic modified radical hysterectomy (TLMRH) in the treatment of presumed stage I endometrial cancer.

Methods: This was a retrospective study of 132 consecutive patients who underwent surgery for early endometrial cancer. Thirty-nine patients underwent TLMRH and bilateral salpingo-oophorectomy (BSO), and 93 had a total abdominal extrafascial hysterectomy and BSO.

Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee arthroplasty.

Purpose: Patients undergoing total knee arthroplasty (TKA) are at high risk of venous thromboembolism, manifesting as deep vein thrombosis (DVT) or pulmonary embolism. The purpose of this study is to evaluate the efficacy and safety of edoxaban 15 mg once daily (o.d.

[A questionnaire survey of indication for cataract surgery].

Purpose: Advances in cataract surgery merits changes in its indication as well as related preoperative eye examinations. This, however, has not been reported in Japan. We performed a questionnaire survey to provide data for these changes.

Effects of combined therapy of alendronate and low-intensity pulsed ultrasound on metaphyseal bone repair after osteotomy in the proximal tibia of aged rats.

Bisphosphonates and low-intensity pulsed ultrasound (LIPUS) are both known to maintain or promote callus formation during diaphyseal fracture healing. However, the effect of these treatments on the repair of metaphyseal fractures has not been elucidated. To evaluate the effects of bisphosphonates and/or LIPUS on cancellous bone healing, an osteotomy was performed on the proximal tibial metaphysis of 9-month-old Sprague-Dawley rats (n = 64).

Dynamic and differential regulation in the microRNA expression in the developing and mature cataractous rat lens.

Recent evidence supports a role for microRNAs (miRNAs) in regulating gene expression, and alterations in gene expression are known to affect cells involved in the development of ageing disorders. Using developing rat lens epithelial cells (LECs), we profiled the expression of miRNAs by a microarray-based approach. Few gene expression changes known to be involved in pathogenesis or cytoprotection were uniquely influenced by miRNA expression.

Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos.

Background: In preimplantation mouse embryos, the first cell fate specification to the trophectoderm or inner cell mass occurs by the early blastocyst stage. The cell fate is controlled by cell position-dependent Hippo signaling, although the mechanisms underlying position-dependent Hippo signaling are unknown.

Results: We show that a combination of cell polarity and cell-cell adhesion establishes position-dependent Hippo signaling, where the outer and inner cells are polar and nonpolar, respectively.

Synaptic plasticity in hippocampal CA1 neurons and learning behavior in transient ischemia-loaded gerbils.

We studied the synaptic plasticity of hippocampal CA1 neurons and spatial learning behavior in gerbils that had been loaded with a transient cerebral ischemia caused by 5 min or 10 min occlusion of the bilateral carotid arteries. The stimulus threshold to elicit the field responses after a transient cerebral ischemia was not different from that in controls, but there was a significant decrease in the magnitude of synaptic responses, which might result from the observed loss of neurons. Long-term potentiation (LTP) and depotentiation after a 10 min cerebral ischemia expressed as a percentage of the pre-tetanus or pre-low frequency stimulation value were almost the same as those in controls, although the actual magnitude of the LTP and depotentiation was lower than in controls.

The structure of brazzein, a sweet-tasting protein from the wild African plant Pentadiplandra brazzeana.

Brazzein is the smallest sweet-tasting protein and was isolated from the wild African plant Pentadiplandra brazzeana. The brazzein molecule consists of 54 amino-acid residues and four disulfide bonds. Here, the first crystal structure of brazzein is reported at 1.