Transforming growth factor beta family expression at the bovine feto-maternal interface

<p>Abstract</p> <p>Background</p> <p>Endometrial remodelling is necessary for implantation in all mammalian species. The TGF beta super-family plays a crucial role in this event in humans and mice. However, the role of TGF beta super-family members during implantation is still unclear in ruminants. In the present study, the spacio-temporal expression of TGF beta super-family members including activin was explored in bovine trophoblasts and endometrial tissue during the peri-implantation period in order to elucidate whether it is essential for promoting cell proliferation at the implantation site.</p> <p>Methods</p> <p>Gene expression in the fetal membrane and endometrium of the gravid and non-gravid horn around Day 35 of gestation were analyzed with a custom-made oligo-microarray in cattle. The expression of activin and its related genes was also analyzed with quantitative RT-PCR. Activin-like activity in trophoblastic tissue and BT-1 cells was examined using a fibroblast cell proliferation test and Western blotting.</p> <p>Results</p> <p>The expression of various TGF beta super-family related genes including activin was detected in trophoblasts and the endometrium in cattle. The most intensive activin expression was found in the gravid horn endometrium, and rather intense expression was detected in the non-gravid trophoblastic tissue. Extracts from the fetal membrane including trophoblasts and purified activin both stimulated fibroblast proliferation effectively, and activin was immunologically detected in BT-1 cells, which have trophoblastic features.</p> <p>Conclusions</p> <p>Specific expression of the activin gene (gene name: inhibin beta A) was found in the gravid horn endometrium during peri-implantation. An activin-like molecule, which was derived from the endometrium and trophoblasts, stimulated the proliferation of fibroblast cells. These results suggested that as in other species, the activity of TGF beta super-family members including activin-like molecules plays a pivotal role in endometrial remodelling, which is an essential process in implantation and placentogenesis during the peri-implantation period in cattle.</p

Impact of Gender on In-hospital Mortality in Patients with Acute Myocardial Infarction in Nagasaki

Acute myocardial infarction (AMI) is one of the leading causes of death in Japan. Immediate reperfusion therapy, includingcoronary intervention, improves patient prognosis. Despite this, females are said to be more prone to poor prognosis. A regional AMI registry in Nagasaki prefecture has been instituted recently that will evaluate whether female gender might predict short-term in-hospital death. Seventeen regional AMI centers enrolled all AMI patients from September 2014 through March 2016. A propensity score (PS) was derived using logistic regression to model the probability of females as a total function of the potential confounding covariates. Two types of PS techniques were used: PS matching and PS stratification. The consistency of in-hospital death was determined between PS matched patients of both genders. Based on PS, patients were ranked and stratified into five groups for the PS stratification. Out of 996 patients, 67 (6.7%) died during hospitalization: 31 (10.4%) out of 298 females and 36 (5.2%) out of 698 males (p < 0.0025). The proportion of cardiac and non-cardiac related death was almost same between genders (25 and 6 in female, 29 and 7 in male, respectively). Among 196 PS matched patients, there was a consistency between genders regarding in-hospital deaths (McNemar test, p = 0.6698). The 717 propensity scored patients had no significant differences between genders among propensity quintiles (Cochran-Mantel-Heanszel test, p = 0.7117). We found that gender alone is not an indicator of short-term in-hospital death in acute myocardial infarction patients

Seizures and Syncope Due to Complete Atrioventricular Block in a Patient with Acute Myocarditis with a Normal Left Ventricular Systolic Function

A 43-year-old man was admitted to our hospital presenting with seizures and syncope. He had a history of a cold with a fever of 39°C occurring three days earlier. Electrocardiography (ECG) showed complete atrioventricular block (AV block) with a maximum pause of 32 seconds, for which temporary pacing was performed. Echocardiography showed mild hypertrophy of the left ventricle (LV) with a normal ejection fraction of 61%. Coronary angiography showed normal coronary arteries. Then, an endomyocardial biopsy was performed, the results of which indicated a diagnosis of acute myocarditis. After admission, the complete atrioventricular block disappeared together with normalization of the LV wall thickness

Bendamustine suppresses MM cells <i>in vivo</i>.

<p><b>A.</b> Serum levels of human IgE. Human IgE levels in the serum of NOG mice 4 weeks after treatment with bendamustine were analyzed by ELISA. Non-treated mice were injected with PBS (n = 5, mean ± SD). The experiment was performed three times with similar results. <b>B.</b> Histological studies of the thoracic vertebrae of NOG mice 4 weeks after treatment with bendamustine (right panel) or non-treatment (left panel). Massive infiltration of U266-EGFP cells was observed in non-treated mice. However, an overall reduction of U266-EGFP cells and maintenance of normal hematopoiesis were observed in bendamustine-treated mice. HE staining: T, tumor; m, marrow; arrow, megakaryocyte. Representative data from five fields from the BM of five mice per group from two independent experiments are shown. Upper panel bars = 200 µm. Lower panel bars = 100 µm. <b>C.</b> FACS analysis of U266-EGFP cells at 4 weeks after treatment in bendamustine-treated or non-treated mice (n = 5, mean ± SD). Representative FACS plots of at least 10 mice from two independent experiments are shown.</p

Bendamustine induces p53-dependent apoptosis.

<p>Human CD138⁺ mouse CD45⁻ MM cells from non-treated or bendamustine-treated mice were sorted and immunocytochemistry was performed to analyze cleaved caspase-3 (<b>A, B</b>), p53 (<b>C, D</b>), phosphorylated-p53 (<b>E, F</b>), Bax (<b>G, H</b>), and p21 (<b>I, J</b>). Each group of MM cells was stained with DAPI and anti-fibronectin antibody, anti-p53 antibody, anti-phosphorylated-p53 antibody, anti-Bax antibody, or anti-p21 antibody. At least 100 cells/sample were counted (mean ± SD, n = 10). Bars = 50 µm.</p

Interaction between multiple myeloma cells and the niche in an <i>in vivo</i> human myeloma model.

<p><b>A.</b> Study design of the NOG-hMM model. Two million EGFP⁺ U266 myeloma (U266-EGFP) cells were intravenously inoculated into 2.4 Gy irradiated NOG (NOD/SCID/g_c^null) mice. Two to six weeks after transplantation, mice were sacrificed for analysis. <b>B.</b> Representative clinical manifestation (upper panel) and radiologic examination (lower panel) of mice 4 weeks after transplantation. All mice showed hind leg paralyses (left) associated with spinal compression fractures (left; arrow). This clinical manifestation was observed in more than 20 mice. <b>C.</b> Representative FACS plot of U266-EGFP cell-transplanted NOG mice. Bone marrow of NOG mice was analyzed by FACS 4 weeks after U266-EGFP cell transplantation using anti-human CD138 antibody and anti-murine CD45 antibody. The experiment was performed in more than forty mice with similar results. <b>D.</b> Serum levels of human IgE. Human IgE levels in the serum of NOG mice at 0 (non-transplanted, non-irradiated mice), 5 or 35 days after transplantation with U266-EGFP cells were analyzed by ELISA (n = 3–5, mean±SD). The experiment was performed twice with similar results. <b>E.</b> Double immunohistochemistry (IHC) of EGFP (green) and TOTO3 (blue) of the BM (upper panels), spleen or liver (lower panels) at 2 weeks after transplantation. U266-EGFP cells engrafted only in the BM. Representative data from 10 to 20 fields from the BM of two mice from three independent experiments are shown. Bars = 200 µm. <b>F.</b> Immunohistochemical (IHC) analysis of EGFP (green) and TOTO3 (blue) at the anatomical region of long bones at the early stage. Representative data from 10 to 20 fields from the BM of two mice from three independent experiments are shown. Bars = 200 µm. <b>G.</b> Quantification of U266-EGFP cells at the diaphysis and the metaphysis of the long bones. U266-EGFP at the metaphysis regions is represented relative to the diaphysis region (diaphysis = 100, n = 3, mean ± SEM). The experiment was performed twice with similar results.</p