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[PMID]: 25618838
[Au] Autor:Jones CJ; Choudhury RH; Aplin JD
[Ad] Address:Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester Academic Health Science Centre, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK. Electronic address: carolyn.jones@manchester.ac.uk.
[Ti] Title:Tracking nutrient transfer at the human maternofetal interface from 4 weeks to term.
[So] Source:Placenta;36(4):372-80, 2015 Apr.
[Is] ISSN:1532-3102
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:INTRODUCTION: In this study we have tracked glycogen and glycoprotein flux associated with nutrient uptake into trophoblast in early deciduochorial and later haemochorial placenta. METHODS: α-amylase, glycogen synthase and glycogen phosphorylase were immunohistochemically localised in 6-14 week and term placenta and first trimester decidua. Placentae of 4-18 weeks' gestation and term were also stained with 22 biotinylated lectins. RESULTS: Histochemical data were consistent with glycogenolysis in decidual gland epithelium and placental cyto- and syncytiotrophoblast; α-amylase was present in decidual secretions but absent in placenta. Glycogen and glycogen synthase were both apparent in villous cytotrophoblast cells and columns. Profound changes were observed in placental glycosylation during gestation. Syncytial microvilli were richly glycosylated as were first trimester vacuoles but, by term, syncytiotrophoblast showed little lectin binding except in microvillous and basal membranes. Cytotrophoblast Golgi bodies were active in the first trimester; at term the cells were generally more glycosylated than syncytiotrophoblast. DISCUSSION: We deduce that decidual cell glycogen is broken down for transport into the placenta where the products may be reassembled into glycogen or used for metabolic processes. First trimester histiotrophe is internalised by syncytiotrophoblast, then broken down in apical vacuoles containing lysosomal markers. This process declines after haemotrophic nutrition commences. Transition from histiotrophic to haemotrophic nutrition involves reduced amounts of uterine secretory derivatives reaching the placenta, and reduction in internalisation of glycoprotein by syncytiotrophoblast, presumably reflecting the shift to low molecular weight nutrients. Glycogen accumulates in cytotrophoblast from early pregnancy and is mobilised for utilisation by fetoplacental tissues.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Js] Journal subset:IM
[St] Status:In-Data-Review

  2 / 254581 MEDLINE  
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[PMID]: 25538260
[Au] Autor:Shen Y; Ma J; Yan R; Ling H; Li X; Yang W; Gao J; Huang C; Bu Y; Cao Y; He Y; Wan L; Zu X; Liu J; Huang MC; Stenson WF; Liao DF; Cao D
[Ad] Address:Department of Medical Microbiology, Immunology and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, Illinois....
[Ti] Title:Impaired Self-Renewal and Increased Colitis and Dysplastic Lesions in Colonic Mucosa of AKR1B8-Deficient Mice.
[So] Source:Clin Cancer Res;21(6):1466-76, 2015 Mar 15.
[Is] ISSN:1078-0432
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: Ulcerative colitis and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Aldo-keto reductase 1B10 (AKR1B10) is specifically expressed in the colonic epithelium, but downregulated in colorectal cancer. This study was aimed to investigate the etiopathogenic role of AKR1B10 in ulcerative colitis and CAC. EXPERIMENTAL DESIGN: Ulcerative colitis and CAC biopsies (paraffin-embedded sections) and frozen tissues were collected to examine AKR1B10 expression. Aldo-keto reductase 1B8 (the ortholog of human AKR1B10) knockout (AKR1B8(-/-)) mice were produced to estimate its role in the susceptibility and severity of chronic colitis and associated dysplastic lesions, induced by dextran sulfate sodium (DSS) at a low dose (2%). Genome-wide exome sequencing was used to profile DNA damage in DSS-induced colitis and tumors. RESULTS: AKR1B10 expression was markedly diminished in over 90% of ulcerative colitis and CAC tissues. AKR1B8 deficiency led to reduced lipid synthesis from butyrate and diminished proliferation of colonic epithelial cells. The DSS-treated AKR1B8(-/-) mice demonstrated impaired injury repair of colonic epithelium and more severe bleeding, inflammation, and ulceration. These AKR1B8(-/-) mice had more severe oxidative stress and DNA damage, and dysplasias were more frequent and at a higher grade in the AKR1B8(-/-) mice than in wild-type mice. Palpable masses were seen in the AKR1B8(-/-) mice only, not in wild-type. CONCLUSIONS: AKR1B8 is a critical protein in the proliferation and injury repair of the colonic epithelium and in the pathogenesis of ulcerative colitis and CAC, being a new etiopathogenic factor of these diseases. Clin Cancer Res; 21(6); 1466-76. ©2014 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/1078-0432.CCR-14-2072

  3 / 254581 MEDLINE  
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[PMID]: 25596282
[Au] Autor:Spurgeon ME; Cheng J; Bronson RT; Lambert PF; DeCaprio JA
[Ad] Address:Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin....
[Ti] Title:Tumorigenic activity of merkel cell polyomavirus T antigens expressed in the stratified epithelium of mice.
[So] Source:Cancer Res;75(6):1068-79, 2015 Mar 15.
[Is] ISSN:1538-7445
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Merkel cell polyomavirus (MCPyV) is frequently associated with Merkel cell carcinoma (MCC), a highly aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated copies of the viral genome with persistent expression of the MCPyV large T (LT) and small T (ST) antigen. MCPyV isolated from MCC typically contains wild-type ST but truncated forms of LT that retain the N-terminus but delete the C-terminus and render LT incapable of supporting virus replication. To determine the oncogenic activity of MCC tumor-derived T antigens in vivo, a conditional, tissue-specific mouse model was developed. Keratin 14-mediated Cre recombinase expression induced expression of MCPyV T antigens in stratified squamous epithelial cells and Merkel cells of the skin epidermis. Mice expressing MCPyV T antigens developed hyperplasia, hyperkeratosis, and acanthosis of the skin with additional abnormalities in whisker pads, footpads, and eyes. Nearly half of the mice also developed cutaneous papillomas. Evidence for neoplastic progression within stratified epithelia included increased cellular proliferation, unscheduled DNA synthesis, increased E2F-responsive genes levels, disrupted differentiation, and presence of a DNA damage response. These results indicate that MCPyV T antigens are tumorigenic in vivo, consistent with their suspected etiologic role in human cancer. Cancer Res; 75(6); 1068-79. ©2015 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/0008-5472.CAN-14-2425

  4 / 254581 MEDLINE  
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[PMID]: 25581733
[Au] Autor:Matsushita T; Maruyama R; Ishikawa N; Harada Y; Araki A; Chen D; Tauchi-Nishi P; Yuki T; Kinoshita Y
[Ad] Address:Departments of *Pathology ‡Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Shimane, Japan †Department of Pathology, Queens Medical Center/University of Hawaii, Honolulu, HI.
[Ti] Title:The number and distribution of eosinophils in the adult human gastrointestinal tract: a study and comparison of racial and environmental factors.
[So] Source:Am J Surg Pathol;39(4):521-7, 2015 Apr.
[Is] ISSN:1532-0979
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:There are surprisingly limited data regarding normal counts or distribution of eosinophils in the gastrointestinal tract, despite the increasing incidence of eosinophilic gastrointestinal tract diseases. Moreover, there are no published reports on the eosinophil number throughout the gastrointestinal tract of adults or Asian populations, or those investigating the effect of race on eosinophil count. First, in our study, the number of eosinophils from each portion of the gastrointestinal mucosa was quantified on biopsy slides from a Japanese adult population (132 samples). Next, the surgical resections from Japanese (110 samples), Japanese Americans (64), and Caucasians (57) were used to investigate the racial and environmental effects. Our results with the Japanese biopsy samples showed a significant increase in the number of eosinophils from the esophagus to the right colon (mean±SD/mm: 0.07±0.43 for the esophagus, 12.18±11.39 for the stomach, and 36.59±15.50 for the right colon), compared with a decrease in the left colon (8.53±7.83). Investigation using surgical samples showed that the distribution patterns in the gastrointestinal tract were very similar among the 3 ethnic groups, and there were no significant differences in the number of eosinophils among these groups, except in the esophageal epithelium. This study is the first report on the normal numbers and distribution of eosinophils throughout the gastrointestinal tract not only of an Asian population but also of adults. Our data suggest that a cutoff value for eosinophil counts, when rendering a diagnosis of eosinophilic gastrointestinal tract disease, should be individualized to the different biopsy sites. Interestingly, race and environmental factors did not seem to have a significant effect on eosinophil densities and distributions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1097/PAS.0000000000000370

  5 / 254581 MEDLINE  
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[PMID]: 25517955
[Au] Autor:Morrison JC; Blanco LZ; Vang R; Ronnett BM
[Ad] Address:Departments of *Pathology †Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD.
[Ti] Title:Incidental serous tubal intraepithelial carcinoma and early invasive serous carcinoma in the nonprophylactic setting: analysis of a case series.
[So] Source:Am J Surg Pathol;39(4):442-53, 2015 Apr.
[Is] ISSN:1532-0979
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:A precursor for invasive ovarian/pelvic high-grade serous carcinoma, termed serous tubal intraepithelial carcinoma (STIC), has been identified and characterized through careful analysis of the fallopian tubes in both prophylactic salpingo-oophorectomy specimens obtained from women with either a family history of breast and/or ovarian cancer or germline mutations of BRCA1 and BRCA2 and in cases of pelvic high-grade serous carcinoma. Data on incidental STICs and clinically occult microscopic invasive high-grade serous carcinomas are limited. We analyzed the clinicopathologic features of 22 cases, including 15 pure STICs and 7 STICs associated with microscopic invasive high-grade serous carcinomas, identified incidentally in fallopian tubes removed for nonprophylactic indications. Patient age ranged from 39 to 79 years (mean: 62.7; median: 61), with only 1 patient under the age of 50. No patients were known to carry BRCA1 or BRCA2 mutations. Of the 12 pure STICs for which the location in the fallopian tube could be established, 9 were in the fimbriated portion, 1 was at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. Of the 7 STICs with associated invasive high-grade serous carcinoma, 3 were located in the fimbriated portion, 2 were at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. The invasive components were in the fallopian tube in 6 cases, 4 in subepithelial stroma of tubal mucosa, and 2 as an intramucosal (exophytic) luminal lesion without invasion of underlying subepithelial stroma (size range: 1 to 4 mm). The remaining case had a microscopic focus of high-grade serous carcinoma within the ipsilateral ovary (1.3 mm cortical focus) identified only on deeper sections, without an associated invasive component in the fallopian tube. The preferential finding of atypical epithelium with the cytologic features of high-grade serous carcinoma, namely STIC, in the fallopian tubes rather than the ovaries as an incidental (clinically occult) microscopic lesion in the absence of widespread pelvic carcinoma provides further evidence that STIC is the earliest form of pelvic high-grade serous carcinoma and that the fallopian tube is the site of origin. This study demonstrates the potential for complete examination of the fallopian tubes and ovaries to identify STICs and early invasive serous carcinomas that might be more amenable to the earliest intervention and potential cure.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1097/PAS.0000000000000352

  6 / 254581 MEDLINE  
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[PMID]: 25767927
[Au] Autor:Bernard A; Nickmilder M; Dumont X
[Ad] Address:1 Catholic University of Louvain Brussels, Belgium.
[Ti] Title:Airway Epithelium Defects and Risks of Allergic Diseases: Multiple Associations Revealed by a Biomarker Study among Adolescents.
[So] Source:Am J Respir Crit Care Med;191(6):714-7, 2015 Mar 15.
[Is] ISSN:1535-4970
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.1164/rccm.201409-1748LE

  7 / 254581 MEDLINE  
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[PMID]: 25770259
[Au] Autor:Bach Knudsen KE
[Ad] Address:Department of Animal Science, Aarhus University, Tjele, Denmark knuderik.bachknudsen@agrsci.dk.
[Ti] Title:Microbial degradation of whole-grain complex carbohydrates and impact on short-chain Fatty acids and health.
[So] Source:Adv Nutr;6(2):206-13, 2015 Mar.
[Is] ISSN:2156-5376
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Whole-grain cereals have a complex dietary fiber (DF) composition consisting of oligosaccharides (mostly fructans), resistant starch, and nonstarch polysaccharides (NSPs); the most important are arabinoxylans, mixed-linkage ß(1,3; 1,4)-d-glucan (ß-glucan), and cellulose and the noncarbohydrate polyphenolic ether lignin. The highest concentration of NSPs and lignin is found in the outer cell layers of the grain, and refined flour will consequently be depleted of a large proportion of insoluble DF components. The flow and composition of carbohydrates to the large intestine are directly related to the intake of DF. The type and composition of cereal DF can consequently be used to modulate the microbial composition and activity as well as the production and molar ratios of short-chain fatty acids (SCFAs). Arabinoxylans and ß-glucan in whole-grain cereals and cereal ingredients have been shown to augment SCFA production, with the strongest relative effect on butyrate. When arabinoxylans were provided as a concentrate, the effect was only on total SCFA production. Increased SCFA production in the large intestine was shown by the concentration in the portal vein, whereas the impact on the concentration in peripheral blood was less because the majority of propionate and butyrate is cleared in the liver. Active microbial fermentation with increased SCFA production reduced the exposure of potentially toxic compounds to the epithelium, potentially stimulating anorectic hormones and acting as signaling molecules between the gut and the peripheral tissues. The latter can have implications for insulin sensitivity and glucose homeostasis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3945/an.114.007450

  8 / 254581 MEDLINE  
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[PMID]: 25762925
[Au] Autor:Ito H; Kawaguchi Y; Kawashima Y; Maruno A; Ogawa M; Hirabayashi K; Mine T
[Ad] Address:Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan....
[Ti] Title:A case of pancreatic intraepithelial neoplasia that was difficult to diagnose preoperatively.
[So] Source:Case Rep Oncol;8(1):30-6, 2015 Jan-Apr.
[Is] ISSN:1662-6575
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:A 63-year-old female patient presented to a local physician with pain in her back and epigastric region. An abdominal computed tomography (CT) scan revealed a pancreatic tumor, and the patient was referred to our hospital. Multiple imaging studies that included ultrasonography (US), CT, MRI, and endoscopic US revealed a cystic lesion 3-4 cm in size with node-like projections in the body of the pancreas. The distal main pancreatic duct was also found to be dilated. Endoscopic retrograde pancreatography revealed an irregular stenosis of the main pancreatic duct proximal to the cystic lesion, and malignancy was suspected. The patient was preoperatively diagnosed with pancreatic ductal carcinoma concomitant with intraductal papillary mucinous carcinoma, and a distal pancreatectomy was performed. Rapid pathological diagnosis during surgery revealed positive surgical margins for pancreatic intraepithelial neoplasia (PanIN). Further resection was performed twice, her surgical margin was positive and total pancreatectomy was ultimately conducted. Histopathological findings revealed diffuse microinvasive cancerous lesions corresponding to PanIN-2 (moderate dysplasia) to PanIN-3 (carcinoma in situ) throughout the pancreas. PanIN involves microlesions of the ductal epithelium that may precede pancreatic cancer. Ascertaining changes in PanIN using images provided by diagnostic modalities such as CT and US is challenging. Ductal stenosis and distal cystic lesions resulting from atrophy and fibrosis of pancreatic tissue were noted around PanIN. Considering the possibility of PanIN, a precancerous lesion during differential diagnosis will help to improve early detection and prognosis for patients with pancreatic cancer.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Cu] Class update date: 150314
[Lr] Last revision date:150314
[Da] Date of entry for processing:150312
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1159/000371842

  9 / 254581 MEDLINE  
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[PMID]: 25747723
[Au] Autor:Jia Y; Yu H; Fernandes SM; Wei Y; Gonzalez-Gil A; Motari MG; Vajn K; Stevens WW; Peters AT; Bochner BS; Kern RC; Schleimer RP; Schnaar RL
[Ad] Address:Department of Pharmacology, Third Military Medical University, Chongqing, China; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md....
[Ti] Title:Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells.
[So] Source:J Allergy Clin Immunol;135(3):799-810.e7, 2015 Mar.
[Is] ISSN:1097-6825
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Balanced activation and inhibition of the immune system ensures pathogen clearance while avoiding hyperinflammation. Siglecs, sialic acid-binding proteins found on subsets of immune cells, often inhibit inflammation: Siglec-8 on eosinophils and Siglec-9 on neutrophils engage sialoglycan ligands on airways to diminish ongoing inflammation. The identities of human siglec ligands and their expression during inflammation are largely unknown. OBJECTIVE: The histologic distribution, expression, and molecular characteristics of siglec ligands were explored in healthy and inflamed human upper airways and in a cellular model of airway inflammation. METHODS: Normal and chronically inflamed upper airway tissues were stained for siglec ligands. The ligands were extracted from normal and inflamed tissues and from human Calu-3 cells for quantitative analysis by means of siglec blotting and isolation by means of siglec capture. RESULTS: Siglec-8 ligands were expressed on a subpopulation of submucosal gland cells of human inferior turbinate, whereas Siglec-9 ligands were expressed more broadly (submucosal glands, epithelium, and connective tissue); both were significantly upregulated in patients with chronic rhinosinusitis. Human airway (Calu-3) cells expressed Siglec-9 ligands on mucin 5B (MUC5B) under inflammatory control through the nuclear factor κB pathway, and MUC5B carried sialoglycan ligands of Siglec-9 on human upper airway tissue. CONCLUSION: Inflammation results in upregulation of immune-inhibitory Siglec-8 and Siglec-9 sialoglycan ligands on human airways. Siglec-9 ligands are upregulated through the nuclear factor κB pathway, resulting in their enhanced expression on MUC5B. Siglec sialoglycan ligand expression in inflamed cells and tissues may contribute to the control of airway inflammation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Cu] Class update date: 150314
[Lr] Last revision date:150314
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review

  10 / 254581 MEDLINE  
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[PMID]: 25531207
[Au] Autor:Alekseev O; Limonnik V; Donovan K; Azizkhan-Clifford J
[Ad] Address:Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pa., USA.
[Ti] Title:Activation of checkpoint kinase 2 is critical for herpes simplex virus type 1 replication in corneal epithelium.
[So] Source:Ophthalmic Res;53(2):55-64, 2015.
[Is] ISSN:1423-0259
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:BACKGROUND/AIMS: Herpes simplex virus (HSV) type I keratitis remains a leading cause of corneal morbidity, despite the availability of effective antiviral drugs. Improved understanding of virus-host interactions at the level of the host DNA damage response (DDR), a known factor in the development of HSV-1 keratitis, may shed light on potential new therapeutic targets. This report examines the role of checkpoint kinase 2 (Chk2), a DDR mediator protein, in corneal epithelial HSV-1 infection. METHODS: A small-molecule inhibitor of Chk2 (Chk2 inhibitor II) was applied to HSV-1-infected cultured human corneal epithelial cells (hTCEpi and HCE) as well as to explanted and organotypically cultured human and rabbit corneas. Infection levels were assessed by plaque assay and real-time PCR. RNAi-mediated depletion of Chk2 was performed to confirm the effect of the inhibitor. RESULTS: Inhibition of the Chk2 kinase activity greatly suppresses the cytopathic effect, genome replication and infectious progeny production in vitro and ex vivo. CONCLUSION: This report demonstrates the critical role of Chk2 kinase in the establishment of HSV-1 corneal epithelial infection. These data contribute to our understanding of herpesvirus-host interactions and underscore the significance of DDR activation in HSV-1 keratitis.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1503
[Cu] Class update date: 150314
[Lr] Last revision date:150314
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1159/000366228


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