tbuckley/cabot-search huggingface dataset:
Slug Expression in the E-cadherin Preserved Tumors Is Related to Prognosis in Patients with Esophageal Squamous Cell Carcinoma
Authors: Yasuto Uchikado, Shoji Natsugoe, Hiroshi Okumura, Tetsuro Setoyama, Masataka Matsumoto, Sumiya Ishigami, Takashi Aikou
Journal: Clinical Cancer Research (2005)

The expression of E-cadherin correlates with the development, progression, and metastasis of esophageal squamous cell carcinoma (ESCC). Slug, a member of the snail family of transcriptional factors, is a newly identified suppressive transcriptional factor of E-cadherin. The purpose of the present study was to evaluate the clinical significance of E-cadherin and Slug expression in ESCC.Immunohistochemistry was used to investigate the expression of E-cadherin and Slug proteins in 203 patients with ESCC. The relationships between expression of these proteins and clinicopathologic factors, including prognosis, were analyzed.Positive expression of E-cadherin and Slug was observed in 43% and 48% of cases, respectively. The tumors with reduced E-cadherin expression or positive Slug expression invaded deeper, had more lymph node metastasis, and had more lymphatic invasion than the tumors with preserved E-cadherin expression or negative Slug expression. Slug expression significantly correlated with reduced E-cadherin expression. Sixty-seven of the 98 (68.4%) tumors with positive Slug expression had reduced E-cadherin expression (P = 0.0011). Patients with reduced E-cadherin expression or positive Slug expression had poor clinical outcomes. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were negative for Slug expression than for those who were positive for Slug expression (P = 0.035). Multivariate analysis indicated that E-cadherin expression and Slug expression were not independent prognostic factors.Evaluation of not only the expression of E-cadherin but also the co-expression of E-cadherin and Slug in preserved E-cadherin group is useful for predicting malignant properties of ESCC.
TCT-177 Long-term follow-up after interventional left atrial appendage occlusion in a real world collective: Data from the ALSTER-LAA Registry and comparison with results from the ARISTOTLE trial
Authors: Felix Meincke, Lukas Krebs, Felix Kreidel, Tobias Spangenberg, Maximilian Schmidt-Salzmann, Karl-Heinz Kuck, Martin W. Bergmann
Journal: Journal of the American College of Cardiology (2014)
A Central Role of Perforin in Cytolysis?
Authors: E R Podack, H Hengartner, M G Lichtenheld
Journal: Annual Review of Immunology (1991)

Studies on the gene structure, on the transcript, and on perforin protein are reviewed, including intracellular trafficking. Perforin transcription is tightly regulated and specific for CTL and NK. Two independent pathways for perforin induction exist, only one of them being IL-2 independent. Perforin expression in vitro and in vivo correlates with the functional expression of cytotoxicity in viral infection, transplant and tumor rejection, and in autoimmunity. Perforin together with granzymes is localized in cytolytic granules. However, the trafficking of those two proteins is quite different. Since the properties of perforin containing granules encompass the characteristics of secretory granules and of lyzosomes, the term granulosomes is used to describe this unique organelle. Evidence is reviewed to refute the concept that the homologous restriction factors of complement also restrict the lysis of homologous cells by perforin.
Somatic Mutation in Human T-Cell Leukemia Virus Type 1 Provirus and Flanking Cellular Sequences During Clonal Expansion In Vivo
Authors: F. Mortreux, I. Leclercq, A.-S. Gabet, A. Leroy, E. Westhof, A. Gessain, S. Wain-Hobson, E. Wattel
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia/lymphoma, shows intrapatient genetic variability. Although HTLV-1 can replicate via the reverse transcription of virion RNA to a double-stranded DNA provirus (the conventional manner for retroviruses), its predominant mode of replication is via the clonal expansion (mitosis) of the infected cell. This expansion is achieved by the viral oncoprotein Tax, which keeps the infected CD4 T lymphocyte cycling. Because Tax also interferes with cellular DNA repair pathways, we investigated whether somatic mutations of the provirus that occur during the division of infected cells could account for HTLV-1 genetic variability. Methods: An inverse polymerase chain reaction strategy was designed to distinguish somatic mutations from reverse transcription-associated substitutions. This strategy allows the proviral sequences to be isolated together with flanking cellular sequences. Using this method, we sequenced 208 HTLV-1 provirus 3′ segments, together with their integration sites, belonging to 29 distinct circulating cellular clones from infected individuals. Results: For 60% of the clones, 8%–80% of infected cells harbored a mutated HTLV-1 provirus, without evidence of reverse transcription-associated mutations. Mutations within flanking cellular sequences were also identified at a frequency of 2.8 × 10−4 substitution per base pair. Some of these clones carried multiple discrete substitutions or deletions, indicating progressive accumulation of mutations during clonal expansion. The overall frequency of somatic mutations increased with the degree of proliferation of infected T cells. Conclusions: These data indicate that, in vivo, HTLV-1 variation results mainly from postintegration events that consist of somatic mutations of the proviral sequence occurring during clonal expansion. The finding of substitutions in flanking sequences suggests that somatic mutations occurring after integration, presumably coupled with selection, help move the cellular clones toward a transformed phenotype, of which adult T-cell leukemia/lymphoma is the end point.
An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure
Authors: Kevin S. Thorneloe, Mui Cheung, Weike Bao, Hasan Alsaid, Stephen Lenhard, Ming-Yuan Jian, Melissa Costell, Kristeen Maniscalco-Hauk, John A. Krawiec, Alan Olzinski, Earl Gordon, Irina Lozinskaya, Lou Elefante, Pu Qin, Daniel S. Matasic, Chris James, James Tunstead, Brian Donovan, Lorena Kallal, Anna Waszkiewicz, Kalindi Vaidya, Elizabeth A. Davenport, Jonathan Larkin, Mark Burgert, Linda N. Casillas, Robert W. Marquis, Guosen Ye, Hilary S. Eidam, Krista B. Goodman, John R. Toomey, Theresa J. Roethke, Beat M. Jucker, Christine G. Schnackenberg, Mary I. Townsley, John J. Lepore, Robert N. Willette
Journal: Science Translational Medicine (2012)

Transient receptor potential vanilloid 4 (TRPV4) channels are expressed in human heart failure lungs, which can be blocked to prevent and resolve heart failure–induced pulmonary edema.
Indirect recognition by helper cells can induce donor-specific cytotoxic T lymphocytes in vivo.
Authors: R S Lee, M J Grusby, L H Glimcher, H J Winn, H Auchincloss
Journal: The Journal of Experimental Medicine (1994)

In vitro studies have revealed that help for cytotoxic T lymphocyte (CTL) induction can be mediated through several pathways, including direct recognition of allogenic class II antigens by CD4+ cells, direct recognition of allogeneic class I antigens by "CD4-independent" CD8+ cells, and "indirect" recognition of peptides of alloantigens presented in association with self class II molecules. Whereas good evidence for the two direct pathways is available in vivo, there is relatively little evidence to show that indirect recognition can initiate graft rejection. This study examined the role of indirect allorecognition during the generation of CTLs in mice as they rejected major histocompatibility complex (MHC) class II-deficient skin after depletion of CD8+ T cells in vivo. Recipients were depleted of CD8+ T cells by in vivo treatment with anti-CD8 monoclonal antibody and then grafted with allogeneic skin lacking MHC class II antigens. The mice rejected the skin grafts rapidly. Although flow cytometry showed marked depletion of CD8+ T cells in these mice, we found that (a) CD8+ CTLs were generated and sensitized to MHC class I antigens of the donor; (b) the generation of the CD8+ CTLs required the help in vivo of CD4+ cells, as well as priming with the allogeneic skin graft; and (c) the CD4+ T helper cells were sensitized indirectly to donor peptides presented in association with class II antigens on recipient antigen-presenting cells. These results provide evidence that indirect recognition can provide effective help for CTL induction during graft rejection, even when the cytotoxic T cells are sensitized by determinants expressed only on the donor graft.
Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice
Authors: Jane K. Howard, Graham M. Lord, Giuseppe Matarese, Silvia Vendetti, Mohammad A. Ghatei, Mary A. Ritter, Robert I. Lechler, Stephen R. Bloom
Journal: Journal of Clinical Investigation (1999)

Thymic atrophy is a prominent feature of malnutrition. Forty-eight hours' starvation of normal mice reduced the total thymocyte count to 13% of that observed in freely fed controls, predominantly because of a diminution in the cortical CD4+CD8+ thymocyte subpopulation. Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes. The ob/ob mouse, which is unable to produce functional leptin because of a mutation in the obese gene, has impaired cellular immunity together with a marked reduction in the size and cellularity of the thymus. We found that ob/ob mice had a high level of thymocyte apoptosis resulting in a ratio of CD4+CD8+ (cortical) to CD4–CD8– (precursor) thymocytes that was 4-fold lower than that observed in wild-type mice. Peripheral administration of recombinant leptin to ob/ob mice reduced thymocyte apoptosis and substantially increased both thymic cellularity and the CD4+CD8+/CD4–CD8– ratio. In contrast, a comparable weight loss in pair-fed PBS-treated ob/ob mice had no impact on thymocyte number. In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy.
Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism
Authors: Liang Dong, Ji Wen, Eric Pier, Xiao Zhang, Bo Zhang, Fangzheng Dong, Nick Ziegler, Margaret Mysz, Rafael Armenta, Rutao Cui
Journal: Cancer Research (2010)

Melanocyte-stimulating hormone (MSH) reduces UV-induced DNA damage through the induction of pigmentation. In this study, we provide evidence that MSH also enhances DNA repair in skin keratinocytes by modulating the function of DNA repair molecules. Intracutaneous injection of MSH prevented UV-induced DNA damage in human and mouse skin independent of its effects on melanogenesis. In keratinocytes, MSH bound to the melanocyte melanocortin receptor type 1 and activated adenylate cyclase activity, which in turn activated Xeroderma pigmentosum group A (XPA)-binding protein 1 and induced nuclear translocation of XPA, a critical factor controlling nucleotide excision repair signaling pathways. Together, our findings reveal a novel pigmentation-independent mechanism that underlies MSH-mediated DNA repair following UVB irradiation.
Insulin dependent diabetes in childhood and material deprivation in northern England, 1977-86.
Authors: Y J Crow, K G Alberti, J M Parkin
Journal: BMJ (1991)

To determine the incidence of insulin dependent diabetes in the Northern region of England in children less than 16 years old in the period 1977 to 1986 and to relate the incidence data to an index of deprivation.Retrospective analysis of hospital case records identified from the regional health authority's computer; validation of the primary source with hospital clinic registers and community paediatric registers.Northern region, excluding South Cumbria District Health Authority (659,300 children under 16 in 1981).All children diagnosed with insulin dependent diabetes before the age of 16 and resident in the region at time of diagnosis.Incidence rates for the 10 year period and analysis of incidence rates within categories of deprivation.919 incident cases were identified. The validation procedure covered 54% of all cases identified and gave 95% completeness of ascertainment. The average annual incidence over the 10 year period was 14.8/100,000 for girls and 13.4/100,000 for boys. The annual incidence for the most and least deprived areas of the region was 18.7/100,000 (95% confidence interval 16.2 to 21.5) for boys and 7/100,000 (5.6 to 8.8) for girls. There was a highly significant trend (p less than 0.001) of decreasing incidence with decreasing level of deprivation.In the north of England the incidence of childhood diabetes is related to material deprivation.
Dietary modulation of the inflammatory cascade
Authors: Dolphus R. Dawson, Grishondra Branch‐Mays, Octavio A. Gonzalez, Jeffrey L. Ebersole
Journal: Periodontology 2000 (2013)

Abstract Dietary supplementation has traditionally consisted of adding vitamins and/or minerals to correct or prevent a nutritional deficiency. When supplementing the diet with other inflammatory mediators, such as essential fatty acids, there is an adjunctive benefit to the standard therapies used in the control of chronic inflammatory diseases such as Crohn’s disease or rheumatoid arthritis. This review focuses on the strategies utilized for therapeutic modulation of the inflammatory cascade through dietary supplementation with specific biomolecules. Examples of how these biomolecules affect local and systemic immune responses to chronic inflammation are examined. In particular, an overview of the literature identifying the potential to modify the host response to chronic periodontitis is provided.
Gestational Hypertension and Preeclampsia in Living Kidney Donors
Authors: Amit X. Garg, Immaculate F. Nevis, Eric McArthur, Jessica M. Sontrop, John J. Koval, Ngan N. Lam, Ainslie M. Hildebrand, Peter P. Reese, Leroy Storsley, John S. Gill, Dorry L. Segev, Steven Habbous, Ann Bugeja, Greg A. Knoll, Christine Dipchand, Mauricio Monroy-Cuadros, Krista L. Lentine
Journal: New England Journal of Medicine (2014)

Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies.
Cell specific expression of peroxiredoxins in human lung and pulmonary sarcoidosis
Authors: V L Kinnula
Journal: Thorax (2002)

Background: Six proteins of the peroxiredoxin (Prx) family have recently been characterised which have the capacity to decompose hydrogen peroxide in vivo and in vitro. These proteins may have an important role in the protection of human lung against endogenous and exogenous oxidant stress. However, the expression and distribution of these proteins in healthy human lung and diseased lung tissue is unknown. Methods: The cell specific expression of Prxs in healthy lung tissue from four non-smokers and in parenchymal tissue from 10 subjects with pulmonary sarcoidosis was investigated by immunohistochemistry, and expression of these proteins in various cultured lung cells and cells of bronchoalveolar lavage (BAL) fluid of controls and patients with sarcoidosis was assessed by Western blot analysis. Results: All six Prxs could be synthesised in cultured human lung cells. The bronchial epithelium showed moderate to high expression of Prxs I, III, V and VI, the alveolar epithelium expressed mainly Prxs V and VI, and alveolar macrophages expressed mainly Prxs I and III. Granulomas of subjects with sarcoidosis expressed mainly Prxs I and III. Samples of BAL fluid from controls and from subjects with sarcoidosis had very similar findings, except that Prxs II and III had a tendency for increased immunoreactivity in sarcoidosis tissue. Conclusions: Prxs I, III, V, and VI, in particular, have prominent and cell specific expression in human lung tissue. High expression of Prxs I and III in granulomas and alveolar macrophages of sarcoidosis parenchyma may have a significant effect on the oxidant burden and the progression of lung injury in this disease.
Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes
Authors: D Basso
Journal: Gut (2004)

<b>Background and aims:</b> We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. <b>Methods:</b> Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours. <b>Results:</b> Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. <b>Conclusions:</b> Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.
Employers seek 2% rise for doctors and dentists
Authors: A. O'Dowd
Journal: BMJ (2008)

Health service employers want doctors to receive a below inflation pay rise of 2% next year.

The call for an “affordable” pay rise for 2009-10 from NHS Employers, the body that represents NHS organisations, came in its evidence to the doctors’ and dentists’ review body (DDRB) published on Tuesday.

The BMA, which is due to publish its own evidence to the pay review body later this week, would not comment directly on NHS Employers’ recommendations, but said it would be seeking a “fair and appropriate” pay award. …
Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice
Authors: Nariaki Asada, Masayuki Takase, Jin Nakamura, Akiko Oguchi, Misako Asada, Norio Suzuki, Ken-ichi Yamamura, Narihito Nagoshi, Shinsuke Shibata, Tata Nageswara Rao, Hans Joerg Fehling, Atsushi Fukatsu, Naoko Minegishi, Toru Kita, Takeshi Kimura, Hideyuki Okano, Masayuki Yamamoto, Motoko Yanagita
Journal: Journal of Clinical Investigation (2011)

In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced production of fibroblast-derived erythropoietin, a hormone that stimulates erythropoiesis. Despite their importance in chronic kidney disease, the origin and regulatory mechanism of fibroblasts remain unclear. Here, we have demonstrated that the majority of erythropoietin-producing fibroblasts in the healthy kidney originate from myelin protein zero–Cre (P0-Cre) lineage-labeled extrarenal cells, which enter the embryonic kidney at E13.5. In the diseased kidney, P0-Cre lineage-labeled fibroblasts, but not fibroblasts derived from injured tubular epithelial cells through epithelial-mesenchymal transition, transdifferentiated into myofibroblasts and predominantly contributed to fibrosis, with concomitant loss of erythropoietin production. We further demonstrated that attenuated erythropoietin production in transdifferentiated myofibroblasts was restored by the administration of neuroprotective agents, such as dexamethasone and neurotrophins. Moreover, the in vivo administration of tamoxifen, a selective estrogen receptor modulator, restored attenuated erythropoietin production as well as fibrosis in a mouse model of kidney fibrosis. These findings reveal the pathophysiological roles of P0-Cre lineage-labeled fibroblasts in the kidney and clarify the link between renal fibrosis and renal anemia.
Geographic Variation in Breast Cancer Incidence Rates in a Cohort of U.S. Women
Authors: F. Laden, S. E. Hankinson, D. Spiegelman, L. M. Neas, G. A. Colditz, D. J. Hunter, J. E. Manson, C. Byrne, B. A. Rosner, F. E. Speizer
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Breast cancer mortality and incidence rates vary by geographic region in the United States. Previous analytic studies have measured mortality, not incidence, and have used regional prevalences to control for geographic variation in risk factors rather than adjusting for risk factors measured at the level of the individual. We prospectively evaluated regional variation in breast cancer incidence rates in the Nurses' Health Study and assessed the influence of breast cancer risk factors measured at the individual level. Methods: The Nurses' Health Study cohort was established in 1976 when 121 700 female nurses aged 30–55 years living in 11 U.S. states were enrolled. These states represent all four regions of the continental United States. We identified 3603 incident cases of invasive breast cancer through 1992 (1 794 565 person-years of follow-up). We calculated relative risks (RRs) adjusted for age and for age and established risk factors (i.e., multivariateadjusted analysis), comparing California, the Northeast, and the Midwest with the South. Results: For premenopausal women, there was little evidence of regional variation in breast cancer incidence rates, either in age-adjusted or in multivariate-adjusted analyses. For postmenopausal women in California, age-adjusted risk was modestly elevated (RR = 1.24; 95% confidence interval [CI] = 1.05–1.47); after adjusting for age and for established risk factors, the excess rate in California was attenuated by 25% (RR = 1.18; 95% CI = 1.00–1.40). No excess of breast cancer incidence was observed for postmenopausal women in either the Northeast or the Midwest. Conclusions: Little regional variation in age-adjusted breast cancer incidence rates was observed, with the exception of a modest excess for postmenopausal women in California. Adjustment for differences in the distribution of established risk factors explained some of the excess risk in California.
258 HYPOFRACTIONATED CARBON ION THERAPY DELIVERED WITH SCANNED ION BEAMS FOR PATIENTS WITH HEPATOCELLULAR CARCINOMA – FEASIBILITY AND CLINICAL RESPONSE
Authors: D. Habermehl, J. Debus, T. Ganten, M.-K. Ganten, J. Bauer, I.C. Brecht, B. Stephan, T. Haberer, M. Härtig, O. Jäkel, K. Parodi, T. Welzel, S.E. Combs
Journal: Journal of Hepatology (2013)