tbuckley/cabot-search huggingface dataset:
Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer
Authors: B. Glimelius, K. Hoffman, P.-O. Sjödén, G. Jacobsson, H. Sellström, L.-K. Enander, T. Linné, C. Svensson
Journal: Annals of Oncology (1996)

In certain patients with pancreatic and biliary cancer, chemotherapy may relieve tumour-related symptoms, improve quality of life and possibly prolong survival. The extent of these improvements is not completely known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in patients with pancreatic and biliary cancer.Between January 1991 and February 1995, 90 eligible patients with pancreatic or biliary cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was either sequential 5-fluorouracil/leucovorin combined with etoposide (FELv) or, in elderly and poor performance patients, the same regimen without etoposide (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument.Mean scale scores in the QLQ-C30 improved more often/deteriorated less frequently in the chemotherapy group than in the best supportive care group. More patients in the chemotherapy group (36%, 17/49) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (10%, 4/41, P < 0.01). Overall survival was significantly longer in the chemotherapy group (median 6 vs. 2.5 months, P < 0.01). Also, the quality-adjusted survival time was longer for patients randomized to chemotherapy (median 4 vs. 1 months, P < 0.01). The effects were seen both in pancreatic and biliary cancer.The results show that chemotherapy can add to both quantity and quality of life in advanced pancreatic and biliary cancer. The number of patients who benefit from treatment is, however, still limited; for this reason careful selection before, and close monitoring during, treatment are necessary.
Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease
Authors: B R Yacyshyn, W Y Chey, J Goff, B Salzberg, R Baerg, A L Buchman, J Tami, R Yu, E Gibiansky, W R Shanahan
Journal: Gut (2002)

Background and aims: To evaluate the safety and efficacy of the intercellular adhesion molecule 1 (ICAM-1) antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) in Crohn's disease. Methods: Active (Crohn's disease activity index (CDAI) 200–350), steroid dependent (prednisone 10–40 mg) Crohn's patients were randomised into three treatment groups: placebo versus ISIS 2302 (2 mg/kg intravenously three times a week) for two or four weeks. Patients were treated in months 1 and 3, with steroid withdrawal attempted by week 10. The primary end point (steroid free remission) was a CDAI <150 off steroids at the end of week 14. Results: A total of 299 patients were enrolled, with a mean baseline CDAI of 276 and steroid dose of 23 mg/day. Rates of steroid free remission were equivalent for the two and four week ISIS 2302 groups (20.2% and 21.2%) and the placebo group (18.8%). At week 14, steroid withdrawal was successful in more ISIS 2302 patients compared with placebo treated patients (78% v 64%; p=0.032). Steroid free remission was highly correlated with exposure (p=0.0064). Other clinical responses were correlated with exposure, with significant results versus placebo being observed in the highest area under the curve subgroup. CDAI scores decreased by 136 (112) at week 14 versus 52 (107) for placebo (p=0.027) and inflammatory bowel disease score questionnaire improved by 43 (31) versus 15 (36) for placebo (p=0.027). Conclusions: Although the primary outcomes failed to demonstrate efficacy, pharmacodynamic modelling suggests that alicaforsen (ISIS 2302) may be an effective therapy for steroid dependent Crohn's disease.
Systematic literature analysis and review of targeted preventive measures to limit healthcare-associated infections by meticillin-resistant Staphylococcus aureus
Authors: R Köck, K Becker, B Cookson, J E van Gemert-Pijnen, S Harbarth, J Kluytmans, M Mielke, G Peters, R L Skov, M J Struelens, E Tacconelli, W Witte, A W Friedrich
Journal: Eurosurveillance (2014)

Meticillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections in Europe. Many examples have demonstrated that the spread of MRSA within healthcare settings can be reduced by targeted infection control measures. The aim of this systematic literature analysis and review was to summarise the evidence for the use of bacterial cultures for active surveillance the benefit of rapid screening tests, as well as the use of decolonisation therapies and different types of isolation measures. We included 83 studies published between 2000 and 2012. Although the studies reported good evidence supporting the role of active surveillance followed by decolonisation therapy, the effectiveness of single-room isolation was mostly shown in non-controlled studies, which should inspire further research regarding this issue. Overall, this review highlighted that when planning the implementation of preventive interventions, there is a need to consider the prevalence of MRSA, the incidence of infections, the competing effect of standard control measures (e.g. hand hygiene) and the likelihood of transmission in the respective settings of implementation.
QUANTITATIVE STUDIES OF THE PHOTOCHEMICAL DESPECIATION OF HORSE SERUM
Authors: J. P. Henry
Journal: The Journal of Experimental Medicine (1942)

1. Normal horse serum was irradiated for periods of 3 to 4 days, with visible light or with ultraviolet light of known intensity and wave length. The photosensitizer hematoporphyrin was employed in some instances. The serum was exposed to the air in thin layers, and thoroughly agitated throughout irradiation. 2. The irradiated sera were unchanged in color, and over 90 per cent of the original protein content remained precipitable by phosphotungstic acid. 3. Studies of the antigenicity of the sera were carried out on guinea pigs and rabbits. Fresh antigenicities of deviated specificity and of an activity of the order of 1/50th, 1/1,000th, and less than 1/20,000th that of normal horse serum were obtained. The residual content of material having the same antigenic specificity as normal horse serum was estimated as approximately equivalent in activity to dilutions of normal horse serum of 1 cc., 1/10 cc., and less than 1/100 cc. per litre respectively.
MUC1 cell surface mucin is a critical element of the mucosal barrier to infection
Authors: Julie L. McAuley, Sara K. Linden, Chin Wen Png, Rebecca M. King, Helen L. Pennington, Sandra J. Gendler, Timothy H. Florin, Geoff R. Hill, Victoria Korolik, Michael A. McGuckin
Journal: Journal of Clinical Investigation (2007)

Cell surface mucin glycoproteins are highly expressed by all mucosal tissues, yet their physiological role is currently unknown. We hypothesized that cell surface mucins protect mucosal cells from infection. A rapid progressive increase in gastrointestinal expression of mucin 1 (Muc1) cell surface mucin followed infection of mice with the bacterial pathogen Campylobacter jejuni. In the first week following oral infection, C. jejuni was detected in the systemic organs of the vast majority of Muc1–/– mice but never in Muc1+/+ mice. Although C. jejuni entered gastrointestinal epithelial cells of both Muc1–/– and Muc1+/+ mice, small intestinal damage as manifested by increased apoptosis and enucleated and shed villous epithelium was more common in Muc1–/– mice. Using radiation chimeras, we determined that prevention of systemic infection in wild-type mice was due exclusively to epithelial Muc1 rather than Muc1 on hematopoietic cells. Expression of MUC1-enhanced resistance to C. jejuni cytolethal distending toxin (CDT) in vitro and CDT null C. jejuni showed lower gastric colonization in Muc1–/– mice in vivo. We believe this is the first in vivo experimental study to demonstrate that cell surface mucins are a critical component of mucosal defence and that the study provides the foundation for exploration of their contribution to epithelial infectious and inflammatory diseases.
Hypoxia inhibits vasoconstriction induced by metabotropic Ca2+ channel-induced Ca2+ release in mammalian coronary arteries
Authors: Eva Calderón-Sánchez, Miguel Fernández-Tenorio, Antonio Ordóñez, José López-Barneo, Juan Ureña
Journal: Cardiovascular Research (2009)

We have previously described in rat basilar arterial myocytes that in the absence of extracellular Ca2+ influx, activation of L-type Ca2+ channels stimulates a metabotropic cascade leading to Ca2+ release from the sarcoplasmic reticulum (SR) and contraction [a calcium channel-induced Ca2+ release (CCICR) mechanism]. On the other hand, it is known that hypoxia reduces Ca2+ channel activity in coronary myocytes. In the present study, we have investigated whether CCICR is present in coronary arterial myocytes and whether arterial ring contraction induced by CCICR can be inhibited by hypoxia. Isometric force, arterial diameter, cytosolic [Ca2+] and electrical activity were recorded on mammalian (porcine, rat, and human) coronary artery preparations (dispersed myocytes, arterial rings, and intact arterial segments). In the absence of extracellular Ca2+, Ca2+ channel activation increased cytosolic [Ca2+] in isolated myocytes and contracted arterial rings. This contraction was suppressed by antagonists of L-type Ca2+ channels and by inhibiting Ca2+ release from the SR. Hypoxia induced dilatation of coronary arterial rings pre-contracted by activation of Ca2+ channels in the absence of extracellular Ca2+. This effect was present although KATP channels and Rho kinase were blocked by glibenclamide and Y27632, respectively. We show that Ca2+ channel activation can induce metabotropic coronary arterial ring contraction in the absence of extracellular Ca2+ and that this CCICR mechanism is inhibited by hypoxia. Thus, besides reduction of Ca2+ entry through Ca2+ channels, hypoxia seems to induce coronary vasorelaxation by inhibition of metabotropic CCICR.
P-cadherin and the journey to cancer metastasis
Authors: André Filipe Vieira, Joana Paredes
Journal: Molecular Cancer (2015)

P-cadherin is a classical cell-to-cell adhesion molecule with a homeostatic function in several normal tissues. However, its behaviour in the malignant setting is notably dependent on the cellular context. In some tumour models, such as melanoma and oral squamous cell carcinoma, P-cadherin acts as a tumour suppressor, since its absence is associated with a more aggressive cancer cell phenotype; nevertheless, the overexpression of this molecule is linked to significant tumour promoting effects in the breast, ovarian, prostate, endometrial, skin, gastric, pancreas and colon neoplasms. Herein, we review the role of P-cadherin in cancer cell invasion, as well as in loco-regional and distant metastatic dissemination. We focus in P-cadherin signalling pathways that are activated to induce invasion and metastasis, as well as cancer stem cell properties. The signalling network downstream of P-cadherin is notably dependent on the cellular and tissue context and includes the activation of integrin molecules, receptor tyrosine kinases, small molecule GTPases, EMT transcription factors, and crosstalk with other cadherin family members. As new oncogenic molecular pathways mediated by P-cadherin are uncovered, putative therapeutic options can be tested, which will allow for the targeting of invasion or metastatic disease, depending on the tumour model.
Localization of transforming growth factor alpha and its receptor in gastric mucosal cells. Implications for a regulatory role in acid secretion and mucosal renewal.
Authors: R D Beauchamp, J A Barnard, C M McCutchen, J A Cherner, R J Coffey
Journal: Journal of Clinical Investigation (1989)

Transforming growth factor alpha (TGF alpha) shares with epidermal growth factor (EGF) structural homology (35%), a common cell-surface membrane receptor (TGF alpha/EGF receptor), and a nearly identical spectrum of biological activity, including inhibition of gastric acid secretion. Herein, we report expression of TGF alpha mRNA in normal gastric mucosa of the adult guinea pig, rat, and dog. TGF alpha mRNA was also detected in matched surgically resected gastric mucosa and adjacent gastric carcinoma from 10 patients, and in gastric mucosa adjacent to a benign ulcer from an additional patient. TGF alpha protein was quantitated by radioimmunoassay and was present in tumor and adjacent mucosa. TGF alpha/EGF receptor mRNA was also detected in gastric mucosa from all species studied. Localization of TGF alpha and TGF alpha/EGF receptor mRNA expression was examined in samples of unfractionated guinea pig gastric mucosa and from chief cell-enriched and parietal cell-enriched fractions. All samples exhibited TGF alpha and TGF alpha/EGF receptor expression. The TGF alpha signal was greatest in the parietal cell fraction (5.8-fold increase), but was also enhanced in the chief cell fraction (1.9-fold increase) relative to the unfractionated gastric mucosa. Like TGF alpha expression, TGF alpha/EGF receptor mRNA expression was most intense in the parietal cell-enriched fraction (7.8-fold increase), but was also increased in the chief cell-enriched fraction (2.7-fold increase) relative to the unfractionated guinea pig gastric mucosa. We conclude that TGF alpha and TGF alpha/EGF receptor genes are expressed in normal adult mammalian gastric mucosa. These findings, when interpreted in light of described actions of TGF alpha and EGF, provide evidence that local production of TGF alpha could play an important role in the regulation of acid secretion and mucosal renewal in the stomach.
New<i>DNAH11</i>mutations in primary ciliary dyskinesia with normal axonemal ultrastructure: Fig. 1—
Authors: M. Pifferi, A. Michelucci, M. E. Conidi, A. M. Cangiotti, P. Simi, P. Macchia, A. L. Boner
Journal: European Respiratory Journal (2010)

an older age, earlier age at initiation, previous quit attempts) or psychological factors (e.g.stress/anxiety, degree of nicotine dependence) [8, 9].Therefore, besides evaluating a patient's likelihood of smoking resumption, active screening for smoking, both when listed for LTx and during post-LTx follow-up, should be performed.For the patients resuming smoking, a standardised smoking cessation plan should be implemented.Patients' relatives, who most often continue smoking after LTx, must be recommended to stop smoking.At present, however, most LTx centres neither monitor smoking nor perform post-LTx smoking cessation counselling.
Pleuropulmonary changes induced by ergoline drugs
Authors: P Pfitzenmeyer, P Foucher, G Dennewald, B Chevalon, D Debieuvre, P Bensa, F Piard, P Camus
Journal: European Respiratory Journal (1996)

Classic ergolines, such as bromocriptine, methysergide and ergotamine, can induce chronic pleuropneumonitis. We present the cases of eight patients who developed similar changes whilst on other ergolines. In this retrospective case study spanning 1985-1995, clinical data, radiological material, pulmonary function, bronchoalveolar lavage and histopathology were reviewed. Earlier literature on ergoline-induced pleuropulmonary changes was reviewed. Eight middle-aged to elderly individuals of both sexes developed pleuropulmonary changes during long-term therapy with regular dosages of nicergoline (n = 4), dihydroergocristine (n = 3), or dihydroergotamine (n = 1). Bibasilar pleural thickening with or without pleural effusion was present on chest radiographs and computed tomographic (CT) scans in six cases. Increased erythrocyte sedimentation rate was seen in most. Pure interstitial pneumonitis developed in two patients on dihydroergocristine and was reversible in each. Bronchoalveolar lavage was performed in four cases and was abnormal in all, but demonstrated no consistent pattern. Most patients exhibited lung restriction. The outcome was favourable showing slow improvement in all cases following discontinuation of the ergoline. Slight residual pleural thickening was seen in five out of the six cases with pleural involvement. Nicergoline and dihydroergotamine can induce a syndrome of chronic pleural thickening/effusion that slowly improves after drug withdrawal. Dihydroergocristine can induce reversible interstitial pneumonitis.
Genetic Evidence for a Noncanonical Function of Seryl-tRNA Synthetase in Vascular Development
Authors: Wiebke Herzog, Katja Müller, Jan Huisken, Didier Y.R. Stainier
Journal: Circulation Research (2009)

In a recent genetic screen, we identified mutations in genes important for vascular development and maintenance in zebrafish (Jin et al. Dev Biol . 2007;307:29–42). Thirty-two mutations at the adrasteia ( adr ) locus cause a pronounced dilatation of the aortic arch vessels as well as aberrant patterning of the hindbrain capillaries and, to a lesser extent, intersomitic vessels. This dilatation of the aortic arch vessels does not appear to be caused by increased cell proliferation but is dependent on vascular endothelial growth factor (Vegf) signaling. By positional cloning, we isolated seryl-tRNA synthetase ( sars ) as the gene affected by the adr mutations. Small interfering RNA knockdown experiments in human umbilical vein endothelial cell cultures indicate that SARS also regulates endothelial sprouting. These analyses of zebrafish and human endothelial cells reveal a new noncanonical function of Sars in endothelial development.
Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial
Authors: Betty R Kirkwood, Lisa Hurt, Seeba Amenga-Etego, Charlotte Tawiah, Charles Zandoh, Samuel Danso, Chris Hurt, Karen Edmond, Zelee Hill, Guus ten Asbroek, Justin Fenty, Seth Owusu-Agyei, Oona Campbell, Paul Arthur
Journal: The Lancet (2010)
Anal gas evacuation and colonic microbiota in patients with flatulence: effect of diet
Authors: Chaysavanh Manichanh, Anat Eck, Encarna Varela, Joaquim Roca, José C Clemente, Antonio González, Dan Knights, Rob Knight, Sandra Estrella, Carlos Hernandez, Denis Guyonnet, Anna Accarino, Javier Santos, Juan-R Malagelada, Francisco Guarner, Fernando Azpiroz
Journal: Gut (2013)

<h3>Objective</h3> To characterise the influence of diet on abdominal symptoms, anal gas evacuation, intestinal gas distribution and colonic microbiota in patients complaining of flatulence. <h3>Design</h3> Patients complaining of flatulence (n=30) and healthy subjects (n=20) were instructed to follow their usual diet for 3 days (basal phase) and to consume a high-flatulogenic diet for another 3 days (challenge phase). <h3>Results</h3> During basal phase, patients recorded more abdominal symptoms than healthy subjects in daily questionnaires (5.8±0.3 vs 0.4±0.2 mean discomfort/pain score, respectively; p=&lt;0.0001) and more gas evacuations by an event marker (21.9±2.8 vs 7.4±1.0 daytime evacuations, respectively; p=0.0001), without differences in the volume of gas evacuated after a standard meal (262±22 and 265±25 mL, respectively). On flatulogenic diet, both groups recorded more abdominal symptoms (7.9±0.3 and 2.8±0.4 discomfort/pain, respectively), number of gas evacuations (44.4±5.3 and 21.7±2.9 daytime evacuations, respectively) and had more gas production (656±52 and 673±78 mL, respectively; p&lt;0.05 vs basal diet for all). When challenged with flatulogenic diet, patients’ microbiota developed instability in composition, exhibiting variations in the main phyla and reduction of microbial diversity, whereas healthy subjects’ microbiota were stable. Taxa from <i>Bacteroides fragilis</i> or <i>Bilophila wadsworthia</i> correlated with number of gas evacuations or volume of gas evacuated, respectively. <h3>Conclusions</h3> Patients complaining of flatulence have a poor tolerance of intestinal gas, which is associated with instability of the microbial ecosystem.
Human Lymphoma-Lymphoma Hybrids and Lymphoma-Leukemia Hybrids. I. Isolation, Characterization, Cell Surface Markers, and B-Cell Markers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J Zeuthen, G Klein, R Ber, G Masucci, S Bisballe, S Povey, P Terasaki, P Ralph
Journal: JNCI Journal of the National Cancer Institute (1982)

Four new somatic cell hybrids were obtained by fusion of various Burkitt's lymphoma (BL)-derived cell lines that had different selective markers: Raji-P3HR-1, Daudi-Raji, and a P3HR-1-P3HR-1 “autohybrid” derived from two P3HR-1 sublines. In addition, a hybrid was obtained between the Daudi (BL) line and the human leukemia cell line K562. The hybrids were extensively characterized by means of chromosome, isozyme, and HLA surface markers. The phenotypic differences between the parent cell lines allowed some conclusions with respect to the expression of latent Epstein-Barr virus (EBV) genomes, C3 and EBV receptors, and of immunoglobulin and beta 2-microglobulin-HLA expression as well as the influence of the leukemia cell (K562) genome on B-cell properties in the Daudi-K562 hybrid. B-cell and differentiated markers of these hybrids were characterized. High-level expression dominated for the marker C3 and EBV receptors, which showed a good correlation coefficient of 0.84, as was true for Fc receptors and surface immunoglobulin. The Daudi-K562 hybrid showed loss of all B-cell markers but retention of the leukemia cell markers (e.g., hemoglobin synthesis).
Immune-Mediated Antitumor Activity of Reovirus Is Required for Therapy and Is Independent of Direct Viral Oncolysis and Replication
Authors: Robin J. Prestwich, Elizabeth J. Ilett, Fiona Errington, Rosa M. Diaz, Lynette P. Steele, Tim Kottke, Jill Thompson, Feorillo Galivo, Kevin J. Harrington, Hardev S. Pandha, Peter J. Selby, Richard G. Vile, Alan A. Melcher
Journal: Clinical Cancer Research (2009)

Reovirus is a naturally occurring oncolytic virus in clinical trials. Although tumor infection by reovirus can generate adaptive antitumor immunity, its therapeutic importance versus direct viral oncolysis is undefined. This study addresses the requirement for viral oncolysis and replication, and the relative importance of antitumor immunity and direct oncolysis in therapy.Nonantigen specific T cells loaded with reovirus were delivered i.v. to C57BL/6 and severe combined immunodeficient mice bearing lymph node and splenic metastases from the murine melanoma, B16ova, with assessment of viral replication, metastatic clearance by tumor colony outgrowth, and immune priming. Human cytotoxic lymphocyte priming assays were done with dendritic cells loaded with Mel888 cells before the addition of reovirus.B16ova was resistant to direct oncolysis in vitro, and failed to support reovirus replication in vitro or in vivo. Nevertheless, reovirus purged lymph node and splenic metastases in C57BL/6 mice and generated antitumor immunity. In contrast, reovirus failed to reduce tumor burden in severe combined immunodeficient mice bearing either B16ova or reovirus-sensitive B16tk metastases. In the human system, reovirus acted solely as an adjuvant when added to dendritic cells already loaded with Mel888, supporting priming of specific antitumor cytotoxic lymphocyte, in the absence of significant direct tumor oncolysis; UV-treated nonreplicating reovirus was similarly immunogenic.The immune response is critical in mediating the efficacy of reovirus, and does not depend upon direct viral oncolysis or replication. The findings are of direct relevance to fulfilling the potential of this novel anticancer agent.