Jedinstveni obrazac djelovanja bisfenola A na ekspresiju gena čimbenika rasta živca embrionske mišje stanične linije N-44 dobivene iz hipotalamusa

We investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf) in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 μmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 μmol L-1 BPA treatment groups compared to controls. However, at 100 to 200 μmol L-1 the Ngf mRNA gradually increased and was significantly higher than control, while the expression of the apoptosis-related genes Caspase 3 and transformation-related protein 73 decreased significantly. These results suggest that in an embryonic hypothalamic cell line the higher doses of BPA induce a unique pattern of Ngf gene expression and that BPA has the potential to suppress apoptosis essential for early-stage brain development.U istraživanju toksičnosti bisfenola A (BPA) utvrđena je ekspresija gena čimbenika rasta živca (eng. nerve growth factor - NGF) embrionske mišje stanične linije mHypoE-N44 dobivene iz hipotalamusa nakon trosatnog izlaganja BPA-u u rasponu doza od 0,02 do 200 μmol L-1. Razine Ngf mRNA snizile su se ovisno o dozi, a značajne razlike od kontrolne skupine zamijećene su za raspon od 2 do 50 μmol L-1. Međutim, počevši od doze od 100 do 200 μmol L-1, razine Ngf mRNA značajno su se povećale u odnosu na kontrolu, a ekspresija gena kaspaze 3 i transformacijskog proteina 73 značajno snizila. Ti rezultati upućuju na to da visoke doze BPA u embrionskoj hipotalamičkoj staničnoj liniji stvaraju jedinstveni obrazac ekspresije gena Ngf te da BPA može suprimirati apoptozu koja je nužna za rani razvoj mozga

Assessment of Gastric Phenotypes Using Magnifying Narrow-Band Imaging for Differentiation of Gastric Carcinomas from Adenomas

Background. Conventional white-light endoscopy and forceps biopsy are insufficient for definitive diagnosis of gastric adenoma. Immunohistochemical studies have reported an obvious phenotypic difference between adenomas and carcinomas. We investigated the utility of narrow-band imaging with magnifying endoscopy (NBI-ME) for mucin phenotypic assessment to differentiate carcinomas from adenomas. Methods. NBI-ME findings were classified into A, B, and AB types, which revealed papillary, tubular pits and groove microstructures, respectively. To investigate A-B classifications retrospectively, 137 patients (155 lesions) that were diagnosed pretherapeutically with adenoma or borderline lesions by biopsy were enrolled. The mucin phenotype was analyzed immunohistochemically in the first 60 lesions. Results. After endoscopic submucosal dissection, A type and AB type lesions were determined histologically as carcinoma (81/82, 99%). B type lesions were adenoma (29/73, 40%) and carcinoma (44/73, 60%). A or AB type correlated to histological carcinomas (sensitivity 65%, specificity 97%, and accuracy 71%). Mucin phenotypes were gastric or gastrointestinal in A type and AB type carcinomas (31/37, 84%) and intestinal in B type adenomas and carcinomas (21/23, 91%). Conclusions. NBI-ME has the advantage of the assessment of mucin phenotypes in gastric carcinomas and adenomas. The proposed A-B classification is useful, especially for differentiation of gastric or gastrointestinal carcinomas from adenomas

Enlargement of accessory spleen subsequent to splenectomy associated with gastrectomy can mimic a solitary tumor : report of a case

We report a case of a 65-year-old woman with an incidental about 20-mm solitary mass between the lateralsegment of the left lobe of the liver and left kidney 5 years after splenectomy associated with total gastrectomy. The mass wassurgically resected, and histological examination revealed it to be an accessory spleen. Small accessory spleens mostly locatednear the splenic hilus, but large accessory spleens are unusual after total gastrectomy with regional lymph nodes resection. Theremaining accessory splenic tissue would undergo compensatory hypertrophy. Hence, the possibility of accessory spleens mustbe considered when an intra-abdominal mass is identified in a patient with splenectomy associated with gastrectomy

Assessment of Gastric Phenotypes Using Magnifying Narrow-Band Imaging for Differentiation of Gastric Carcinomas from Adenomas

Background. Conventional white-light endoscopy and forceps biopsy are insufficient for definitive diagnosis of gastric adenoma. Immunohistochemical studies have reported an obvious phenotypic difference between adenomas and carcinomas. We investigated the utility of narrow-band imaging with magnifying endoscopy (NBI-ME) for mucin phenotypic assessment to differentiate carcinomas from adenomas. Methods. NBI-ME findings were classified into A, B, and AB types, which revealed papillary, tubular pits and groove microstructures, respectively. To investigate A-B classifications retrospectively, 137 patients (155 lesions) that were diagnosed pretherapeutically with adenoma or borderline lesions by biopsy were enrolled. The mucin phenotype was analyzed immunohistochemically in the first 60 lesions. Results. After endoscopic submucosal dissection, A type and AB type lesions were determined histologically as carcinoma (81/82, 99%). B type lesions were adenoma (29/73, 40%) and carcinoma (44/73, 60%). A or AB type correlated to histological carcinomas (sensitivity 65%, specificity 97%, and accuracy 71%). Mucin phenotypes were gastric or gastrointestinal in A type and AB type carcinomas (31/37, 84%) and intestinal in B type adenomas and carcinomas (21/23, 91%). Conclusions. NBI-ME has the advantage of the assessment of mucin phenotypes in gastric carcinomas and adenomas. The proposed A-B classification is useful, especially for differentiation of gastric or gastrointestinal carcinomas from adenomas

Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila

Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity), we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs), Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.This work was supported by grants from the Japan Society for the Promotion of Science and the Japan Ministry of Education, Culture, Sports, Science and Technology to TC and MMi, from the Uehara memorial foundation to TC, from NIH to JWW (DK092640), and from NIH to RLD (2R37 NS19904-30). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Osteoarticular infections in childhood

Objectives : Osteomyelitis (OM) and septic arthritis (SA) in childhood might cause complications, sequelae, or even death if diagnosis and treatment are delayed. Here, we examined the outcomes of OM / SA at a pediatric emergency core hospital in Japan. Methods : This was a single-center, retrospective, observational cohort study at a pediatric emergency core hospital in Japan. Pediatric outpatients who underwent magnetic resonance imaging at the hospital in the period 2012–2020 were recruited. Primary outcomes were sequelae, recurrent symptoms, chronicity, and death. Results : Fifteen OM / SA patients (9 OM, 4 SA, 2 OM+SA) were recruited. The identified major pathogens included methicillin-susceptible Staphylococcus aureus (40.0 %, n = 6) and methicillin-resistant S. aureus (13.3 %, n = 2). Mean time from onset to first hospital visit, hospitalization, and initiation of effective antibiotics was 2 days, 3.9 ± 1.8 days, and 4.9 ± 2.2 days, respectively. All OM / SA patients recovered without complications or sequelae. Conclusions : In this study, all patients with OM / SA showed a good prognosis. Despite the small sample size, this pilot study suggests that the pediatric emergency core system in Japan provides early treatment and a good prognosis for patients diagnosed with OM / SA

Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT

Heterologous expression and characterization of CpI, OcpA, and novel serine-type carboxypeptidase OcpB from Aspergillus oryzae

In the genome of Aspergillus oryzae, 12 genes have been predicted to encode serine-type carboxypeptidases. However, the carboxypeptidase activities of the proteins encoded by these genes have not yet been confirmed experimentally. In this study, we have constructed three of these 12 genes overexpressing strains using Aspergillus nidulans and characterized their overproduced recombinant proteins. Of these three genes, one was previously named cpI; the other two have not been reported yet, and hence, we named them ocpA and ocpB. The recombinant proteins released amino acid residues from the C terminus of peptides, and the activity of the enzymes was inhibited by phenylmethylsulfonyl fluoride, indicating the enzymes to be serine-type carboxypeptidases. Recombinant OcpA, OcpB, and CpI were stable at 45°C, 55°C, and 55°C, respectively, at a low pH. The enzymatic properties of recombinant OcpB were different from those of any reported serine-type carboxypeptidase. On the other hand, recombinant OcpA had similar enzymatic properties to A. oryzae carboxypeptidases O1 and O2. The DNA and N-terminal amino acid sequences of carboxypeptidases O1 and O2 from A. oryzae IAM2640 were similar to those of OcpA. Result of transcriptional analysis of ocpA, ocpB, and cpI suggest differences in transcriptional regulation between these genes