tbuckley/cabot-search huggingface dataset:
Thousands of NHS staff made redundant have been rehired despite large payoffs
Authors: A. O'Dowd
Journal: BMJ (2013)

The short-term effects of 6-hydroxydopamine (6-OHDA) on the norepinephrine content, <sup>3</sup>H-norepinephrine and <sup>3</sup>H-metaraminol uptake and nerve density of adrenergic nerve terminals have been investigated in mouse heart and iris. The results obtained show that all the parameters investigated were quantitatively reduced to approximately the same degree after all doses and time intervals studied. 6-OHDA administered <i>in vivo</i> thus seems to act on the adrenergic nerves very much in an "all or none" fashion with a complete destruction of norepinephrine uptake-storage mechanisms in a proportion of nerves depending on the dose used, while the remaining nerves are left with more or less intact transmitter mechanisms. Displacement plays a minor role in the depleting action of 6-OHDA. The results obtained furthermore support the view that a destruction of the membrane uptake mechanism of the adrenergic neuron is a very early sign in the degeneration process caused by 6-OHDA.
Treating sleep apnoea is cost effective
Authors: N J Douglas
Journal: Thorax (2002)

<h3>Introduction</h3> SMOC2, a secreted calcium-binding protein of the BM-40/SPARC family was identified from a chondrogenic extract of articular cartilage and is increased in osteoarthritic cartilage. Alterations in bone and cartilage resulting from dysregulated signalling pathways are a hallmark of osteoarthritis. <h3>Objectives</h3> To evaluate the role of SMOC2 in <i>in vitro</i> osteogenesis and chondrogenesis and its interaction with Wnt signalling. <h3>Methods</h3> Wild-type Smoc2 (Smoc2+) or Smoc2 lacking the calcium binding domain (?CaBD) were stably overexpressed and wild-type Smoc2 was silenced (Smoc2-). Alkaline phosphatase (ALP) activity assay and Alizarin Red staining were performed in MC3T3 cells and human periosteal derived cells (hPDCs). Proteoglycan content and mineralization were assessed in ATDC5 micromasses by Alcian blue and Alizarin Red staining. Mice femoral head caps (FHC) were stimulated with recombinant IL-1b and SMOC2. Cartilage loss was evaluated by DMMB assay and Safranin O staining. TCF1 levels were analysed by immunohistochemistry. Human articular chondrocytes (hACs) were stimulated with recombinant SMOC2. Gene expression of osteoblast markers (<i>Opn, Osx, Col1a2</i>), chondrogenic markers (<i>Acan, Col2a1, Col10a1, Mmp13</i>) and canonical Wnt target genes (<i>Axin2, Lef1</i>) were analysed by qPCR and Wnt signalling by Western blot. <h3>Results</h3> Alizarin red staining and ALP activity were reduced in Smoc2 +MC3 T3 cells. Osteoblast gene expression levels were altered in Smoc2 +cells. ?CaBD cells and calcium supplementation to Smoc2 +showed a partial rescue of the effects of Smoc2 +cells. We validated these results in hPDCs. We could not observe an effect on osteogenesis when silencing Smoc2. Smoc2 +ATDC5 micromasses showed reduced chondrogenic gene expression and Alcian blue and Alizarin Red staining intensity. We observed a reverse pattern with an increased chondrogenic gene expression in Smoc2- ATDC5 micromasses. Smoc2 +and Smoc2- ATDC5 cells altered canonical Wnt signalling in opposite directions. SMOC2 also alters protein levels of CamKII. IL-1b triggered cartilage loss was increased and TCF1 levels were reduced in mice FHC stimulated with recombinant SMOC2. In hACs, we observed a negative effect of SMOC2 on chondrocyte markers and canonical Wnt target genes. <h3>Conclusions</h3> Our results suggest an inhibitory role of Smoc2 on mineralization. The inhibitory effects on mineralization are at least partially regulated through interaction with calcium. Moreover, Smoc2 is a regulator of chondrogenic differentiation and cartilage homeostasis by regulating canonical and non-canonical Wnt signalling. <h3>Disclosure of interest</h3> None declared
Fetal cells and cell-free fetal DNA in maternal blood: new insights into pre-eclampsia
Authors: Sinuhe Hahn, Wolfgang Holzgreve
Journal: Human Reproduction Update (2002)

The examination of fetal cells, specifically erythroblasts, and cell-free fetal DNA from the blood of pregnant women is currently the subject of intense research with the aim of developing new risk-free methods for prenatal diagnosis. An unexpected finding made during these studies was that the traffic of fetal erythroblasts into the maternal peripheral circulation was enhanced in pre-eclampsia. Independent prospective studies examining samples collected in the second trimester indicated that this perturbation in fetal cell trafficking occurs early in pregnancy, well before the onset of pre-eclampsia symptoms. The quantitative analysis of cell-free fetal and maternal DNA levels indicated that these concentrations were elevated in a co-ordinate manner in manifest pre-eclampsia, and that these elevations corresponded to disease severity. On the other hand, analysis of prospectively collected samples indicated that only cell-free fetal but not maternal DNA levels were elevated before onset of symptoms in pregnancies which subsequently developed pre-eclampsia. These data support hypotheses suggesting that pre-eclampsia is a multi-step disorder, initiated by a placental lesion that occurs early in pregnancy and which subsequently leads to a systemic maternal inflammatory response and associated endothelial cell damage.
European Guidelines on Upper Tract Urothelial Carcinomas: 2013 Update
Authors: Morgan Rouprêt, Marko Babjuk, Eva Compérat, Richard Zigeuner, Richard Sylvester, Max Burger, Nigel Cowan, Andreas Böhle, Bas W.G. Van Rhijn, Eero Kaasinen, Joan Palou, Shahrokh F. Shariat
Journal: European Urology (2013)
Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn's disease
Authors: S. Vermeire, M. Noman, G. Van Assche, F. Baert, G. D'Haens, P. Rutgeerts
Journal: Gut (2007)

Episodic infliximab (IFX) treatment is associated with the formation of antibodies to IFX (ATIs) in the majority of patients, which can lead to infusion reactions and a shorter duration of response. Concomitant use of immunosuppressives (IS) reduces the risk of ATI formation.To investigate which of the IS-that is, methotrexate (MTX) or azathioprine (AZA)-is most effective at reducing the risk of ATI formation, a multicentre cohort of 174 patients with Crohn's disease, treated with IFX in an on-demand schedule, was prospectively studied. Three groups were studied: no IS (n = 59), concomitant MTX (n = 50) and concomitant AZA (n = 65). ATI and IFX concentrations were measured in a blinded manner at Prometheus Laboratories before and 4 weeks after each infusion.ATIs were detected in 55% (96/174) of the patients. The concomitant use of IS therapy (AZA or MTX) was associated with a lower incidence of ATIs (53/115; 46%) compared with patients not taking concomitant IS therapy (43/59; 73%; p<0.001). The incidence of ATIs was not different for the MTX group (44%) compared with the AZA group (48%). Patients not taking IS therapy had lower IFX levels (median 2.42 microg/ml (interquartile range (IQR) 1-10.8), maximum 21 microg/ml) 4 weeks after any follow-up infusion than patients taking concomitant IS therapy (median 6.45 microg/ml (IQR 3-11.6), maximum 21 microg/ml; p = 0.065), but there was no difference between MTX or AZA. In patients who developed significant ATIs >8 microg/ml during follow-up, the IFX levels 4 weeks after the first infusion were retrospectively found to be significantly lower than in patients who did not develop ATIs on follow-up or had inconclusive ATIs.Concomitant IS therapy reduces ATI formation associated with IFX treatment and improves the pharmacokinetics of IFX. There is no difference between MTX and AZA in reducing these risks. ATI profoundly influences the pharmacokinetics of IFX. The formation of ATIs >8 microg/ml is associated with lower serum levels of IFX already at 4 weeks after its first administration.
Nitric Oxide Production Upregulates Wnt/β-Catenin Signaling by Inhibiting Dickkopf-1
Authors: Qiang Du, Xinglu Zhang, Quan Liu, Xianghong Zhang, Christian E. Bartels, David A. Geller
Journal: Cancer Research (2013)

Abstract Nitric oxide signaling plays complex roles in carcinogenesis, in part, due to incomplete mechanistic understanding. In this study, we investigated our discovery of an inverse correlation in the expression of the inducible nitric oxide synthase (iNOS) and the Wnt/β-catenin regulator Dickkopf-1 (DKK1) in human cancer. In human tumors and animal models, induced nitric oxide synthesis increased Wnt/β-catenin signaling by negatively regulating DKK1 gene expression. Human iNOS (hiNOS) and DKK1 gene expression were inversely correlated in primary human colon and breast cancers, and in intestinal adenomas from Min (Apcmin/+) mice. Nitric oxide production by various routes was sufficient to decrease constitutive DKK1 expression, increasing Wnt/β-catenin signaling in colon and breast cancer cells and primary human hepatocytes, thereby activating the transcription of Wnt target genes. This effect could be reversed by RNA interference-mediated silencing of iNOS or treatment with iNOS inhibitors, which restored DKK1 expression and its inhibitory effect on Wnt signaling. Taken together, our results identify a previously unrecognized mechanism through which the nitric oxide pathway promotes cancer by unleashing Wnt/β-catenin signaling. These findings further the evidence that nitric oxide promotes human cancer and deepens insights in the complex control Wnt/β-catenin signaling during carcinogenesis. Cancer Res; 73(21); 6526–37. ©2013 AACR.
Transient Improvement in Cognitive Function and Synaptic Plasticity in Rats Following Cancer Chemotherapy
Authors: Garrick D. Lee, Dan L. Longo, Yue Wang, Joseph M. Rifkind, Lilanie Abdul-Raman, Jacek A. Mamczarz, Kara B. Duffy, Edward L. Spangler, Dennis D. Taub, Mark P. Mattson, Donald K. Ingram
Journal: Clinical Cancer Research (2006)

Abstract Background: Cancer chemotherapy has been associated with cognitive impairment. Several issues complicate such findings including the patients' health, use of multiple chemotherapeutic agents, and proper assessment of cognition. To control these factors, we conducted cognitive studies in female rats receiving cyclophosphamide or 5-fluorouracil (5FU). Methods: Young (7 months) female Fischer-344 rats received five injections of cyclophosphamide (100 mg/kg), 5FU (150 mg/kg), or saline i.p. every 4 weeks for a total of 18 weeks. Aged (18 months) female Fischer-344 rats were treated with cyclophosphamide (80 mg/kg i.p.) for 16 weeks. After 8 to 10 weeks of recovery, rats were tested in two maze learning tasks, the Morris water maze and the Stone 14-unit T-maze. Neuronal synaptic function was assessed by examining long-term potentiation (LTP) in hippocampal slices obtained from young cyclophosphamide-treated rats. Results: Despite the toxic effects induced by chemotherapy, cyclophosphamide- and 5FU-treated rats showed significantly better maze performance compared with controls. Following 29 to 42 weeks of recovery from chemotherapy, no significant effects were observed on maze performance. In aged rats, cyclophosphamide treatment for 14 weeks also produced toxicity, but no impairment in Stone maze learning after 16 weeks of recovery. When assessed during cyclophosphamide treatment, evidence of impaired LTP emerged; however, with 8 weeks of recovery following five cyclophosphamide treatments, we observed enhanced LTP. Conclusion: Despite toxicity accompanying chemotherapy, no evidence of impaired cognitive performance emerged after recovery. Indeed, following 7 to 9 weeks of recovery, we noted evidence of improved learning and LTP.
Lung function from infancy to preschool in a cohort of children with cystic fibrosis
Authors: Lyndia C. Brumback, Stephanie D. Davis, Gwendolyn S. Kerby, Margaret Kloster, Robin Johnson, Robert Castile, Peter W. Hiatt, Meeghan Hart, Margaret Rosenfeld
Journal: European Respiratory Journal (2012)

This study aimed to describe lung function in a cohort of children with cystic fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool spirometry. Children performed up to four IPFTs (raised volume rapid thoracic compression technique) over 1 yr and five preschool spirometry tests over up to 2 yrs during participation in prospective, multicentre studies of infant and preschool lung function. All lung function data were reviewed centrally for measurement acceptability. 45 children had 252 acceptable measurements (137 IPFTs and 115 preschool spirometries) at ages 0.3–6.5 yrs. The median number of measurements per participant was 6 (range 3–9). Recent Pseudomonas aeruginosa infection was associated with 5.1% (95% CI 0.01–9.9%) lower forced expiratory volume in 0.5 s (FEV 0.5 ) and 16.4% (95% CI 7.0–24.9%) lower forced expiratory flow at 25–25% of forced vital capacity (FEF 25–75% ), after adjustment for length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1–10.1%) lower FEV 0.5 and 10.1% (95% CI 0.6–18.7%) lower FEF 25–75% . Even after accounting for infection status, cough, sex, length, test type and centre, there was significant inter-individual variability in lung function (p&lt;0.01 for each of FEV 0.5 , FEF 25–75% and forced vital capacity). Recent P. aeruginosa infection and cough are associated with lower lung function in children with CF. Significant inter-individual variability in lung function remains to be explained.
Promoter Hypermethylation in Benign Breast Epithelium in Relation to Predicted Breast Cancer Risk
Authors: Cheryl M. Lewis, Leslie R. Cler, Da-Wei Bu, Sabine Zöchbauer-Müller, Sara Milchgrub, Elizabeth Z. Naftalis, A. Marilyn Leitch, John D. Minna, David M. Euhus
Journal: Clinical Cancer Research (2005)

Abstract Introduction: The tumor suppressor genes RASSF1A, APC, H-cadherin, RARβ2, and cyclin D2 are methylated more frequently in breast cancer than in adjacent benign tissue. However, it is unclear whether promoter methylation of tumor suppressor genes in benign breast tissue is associated with an increased risk for breast cancer. Methods: Promoter hypermethylation was measured in benign and malignant breast samples obtained by fine needle aspiration biopsy from 27 breast cancer patients and 55 unaffected women whose risk of breast cancer had been defined using the Gail, Claus, and BRCAPRO models. Results: Cyclin D2 methylation occurred in 57% of tumor samples but not in corresponding benign breast samples and in only one sample from an unaffected patient (P &amp;lt; 0.0001). RARβ2 methylation occurred in 32% of benign breast samples from cancer patients but only 9% of similar samples from unaffected women (P = 0.002). Promoter methylation of RASSF1A and APC occurred more frequently (70% and 56%, respectively) in unaffected women at high-risk for breast cancer as defined by the Gail model than in low/intermediate risk women (29% and 20%, P = 0.04 and P = 0.03). Of the Gail model risk factors, only number of prior breast biopsies was highly correlated with APC and RASSF1A methylation (P = 0.0001 and 0.02, respectively). Conclusions: Since cyclin D2 promoter methylation occurs almost exclusively in tumors, it may be possible to exploit it for the early detection of breast cancer. Promoter methylation of APC, RARβ2, and RASSF1A in benign breast epithelium is associated with epidemiologic markers of increased breast cancer risk.
Pediatric End-of-Life Care for Taiwanese Children Who Died As a Result of Cancer From 2001 Through 2006
Authors: Siew Tzuh Tang, Yen-Ni Hung, Tsang-Wu Liu, Dong-Tsamn Lin, Yueh-Chih Chen, Shiao-Chi Wu, Tsui Hsia Hsu
Journal: Journal of Clinical Oncology (2010)

Purpose Patterns of aggressive end-of-life (EOL) care have not been extensively explored in a pediatric cancer population, especially outside Western countries. The purpose of this population-based study was to examine trends in aggressive pediatric EOL cancer care in Taiwan. Methods Retrospective cohort study that used administrative data among 1,208 pediatric cancer decedents from 2001 through 2006. Results Taiwanese pediatric cancer patients who died in 2001 through 2006 received aggressive EOL care. The majority of these patients in their last month of life continued to receive chemotherapy (52.5%), used intensive care (57.0%), underwent intubation (40.9%), underwent mechanical ventilation (48.2%), or spent greater than 14 days (69.5%) in hospital, and they died in an acute care hospital (78.8%). Of these pediatric cancer patients, one in four received cardiopulmonary resuscitation in the month before they died, and only 7.2% received hospice care. Among those who received hospice care, 21.8% started such care within the last 3 days of life. This pattern of aggressive EOL care did not change over the study period except for significantly decreased intubation in the last month of life. Conclusion Continued chemotherapy and heavy use of life-sustaining treatments in the last month of life coupled with lack of hospice care to support Taiwanese pediatric cancer patients dying at home may lead to multiple unplanned health care encounters, prolonged hospitalization at EOL, and eventual death in an acute care hospital for the majority of these patients. Future research should design interventions that enable Taiwanese pediatric cancer patients to receive EOL care that best meets the individual or the parental needs and preferences.
Tuberculosis Prevention Among Foreign-born Persons in Seattle–King County, Washington
Authors: CHARLES D. WELLS, PATRICK L. F. ZUBER, CHARLES M. NOLAN, NANCY J. BINKIN, STEFAN V. GOLDBERG
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The purpose of this study was to evaluate the outcomes of classified immigrant and refugee (I&R) screening and of contact investigation (CI) of foreign-born TB cases in Seattle–King County (SKC), Washington. We reviewed I&R evaluations from the SKC TB clinic for 1992–1994 and contact evaluation records for 54 randomly selected U.S.-born and foreign-born pulmonary TB patients from 1993. Among 942 I&R evaluated, 693 (74%) had positive tuberculin skin tests (TST). Preventive therapy (PT) was prescribed for 324 (34%) and treatment for 49 (5%). The remaining 377 were dismissed, of whom 96% did not meet American Thoracic Society PT criteria. Contacts of foreign-born cases were more numerous (6.0 versus 3.4 per case, p = 0.04), and significantly more likely to be TST-positive (50% versus 18%) and to be started on PT (40% versus 23%). The large number of I&R eligible for treatment or PT emphasizes the benefit of prompt evaluation of new arrivals. CI provides an excellent opportunity to screen foreign-born persons at high risk for active TB.
Death After Bronchography With a Water-Soluble Iodine-Containing Medium
Authors: O. Frank Agee
Journal: JAMA (1965)

THE HISTORY OF bronchography has largely been that of a search for an "ideal contrast medium,"<sup>1</sup>the properties of which are well established,<sup>2</sup>and include physiologic inertness. Recently, American efforts have been largely in two directions, the investigation of barium suspensions as media and of a new iodine-containing water-soluble mixture (Hytrast), its iodine-containing molecules (not subject to enzymatic hydrolysis) being iopydone and iopydol. These constitute 50% weight per volume combined iodine. To increase viscosity, the suspension contains approximately 0.5% sodium carboxymethylcellulose. It also contains methyl and propyl parabens and monosodium phosphate. The contrast substance satisfies technical radiographic requirements well.<sup>3</sup>Most workers<sup>4</sup>report postbronchographic febrile response with few serious complicatons. There have been reports of histologically verified pneumonia, usually related to an area of alveolar filling (alveolar filling with contrast medium) and there is one published report of death following bronchography with this contrast medium.<sup>5</sup> The
Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk
Authors: Louise A. Brinton, Tim J. Key, Laurence N. Kolonel, Karin B. Michels, Howard D. Sesso, Giske Ursin, Stephen K. Van Den Eeden, Shannon N. Wood, Roni T. Falk, Dominick Parisi, Chantal Guillemette, Patrick Caron, Véronique Turcotte, Laurel A. Habel, Claudine J. Isaacs, Elio Riboli, Elisabete Weiderpass, Michael B. Cook
Journal: Journal of Clinical Oncology (2015)

Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones.
Disparities in Ovarian Cancer Care Quality and Survival According to Race and Socioeconomic Status
Authors: R. E. Bristow, M. A. Powell, N. Al-Hammadi, L. Chen, J. P. Miller, P. Y. Roland, D. G. Mutch, W. A. Cliby
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundThe relationship between racial and socioeconomic status (SES) disparities and the quality of epithelial ovarian cancer care and survival outcome are unclear.
Histocompatibility antigens and genetic control of the immune response in guinea pigs IV. Specific inhibition of lymphocyte proliferation by auto-anti-idiotypic antibodies.
Authors: A F Geczy
Journal: The Journal of Experimental Medicine (1977)

The in vitro T-cell proliferation induced by penicilloylated bovine IgG (BPO-BGG) in sensitized strain 2 guinea pigs could be specifically blocked by the serum of guinea pig (*305) which had been repeatedly immunized with BPO-BGG over a period of 9 mo. The antibodies which appeared in the serum of this animal (*305) were functionally similar to the strain 2 anti-idiotypic antibodies (a strain 2 BPO-BGG) raised by immunizing strain 2 guinea pigs with immuno-adsorbent column-purified BPO-BGG. Animal *305 had no detectable antibodies to BPO-BGG and failed to give a delayed hypersensitivity skin response when challenged with BPO-BGG.
Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis
Authors: Jingang Huang, Christian Beyer, Katrin Palumbo-Zerr, Yun Zhang, Andreas Ramming, Alfiya Distler, Kolja Gelse, Oliver Distler, Georg Schett, Lutz Wollin, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2015)

Nintedanib is a tyrosine kinase inhibitor that has recently been shown to slow disease progression in idiopathic pulmonary fibrosis in two replicate phase III clinical trials. The aim of this study was to analyse the antifibrotic effects of nintedanib in preclinical models of systemic sclerosis (SSc) and to provide a scientific background for clinical trials in SSc.The effects of nintedanib on migration, proliferation, myofibroblast differentiation and release of extracellular matrix of dermal fibroblasts were analysed by microtitre tetrazolium and scratch assays, stress fibre staining, qPCR and SirCol assays. The antifibrotic effects of nintedanib were evaluated in bleomycin-induced skin fibrosis, in a murine sclerodermatous chronic graft-versus-host disease model and in tight-skin-1 mice.Nintedanib dose-dependently reduced platelet-derived growth factor-induced and transforming growth factor-β-induced proliferation and migration as well as myofibroblast differentiation and collagen release of dermal fibroblasts from patients with and healthy individuals. Nintedanib also inhibited the endogenous activation of SSc fibroblasts. Nintedanib prevented bleomycin-induced skin fibrosis in a dose-dependent manner and was also effective in the treatment of established fibrosis. Moreover, treatment with nintedanib ameliorated fibrosis in the chronic graft-versus-host disease model and in tight-skin-1 mice in well-tolerated doses.We demonstrate that nintedanib effectively inhibits the endogenous as well as cytokine-induced activation of SSc fibroblasts and exerts potent antifibrotic effects in different complementary mouse models of SSc. These data have direct translational implications for clinical trials with nintedanib in SSc.