tbuckley/cabot-search huggingface dataset:
Association of the tumour necrosis factor α −308 but not the interleukin 10 −627 promoter polymorphism with genetic susceptibility to primary sclerosing cholangitis
Authors: S A Mitchell, J Grove, A Spurkland, K M Boberg, K A Fleming, C P Day, E Schrumpf, R W Chapman
Journal: Gut (2001)

BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology. Abnormalities in immune regulation and genetic associations suggest that PSC is an immune mediated disease. Several polymorphisms within the tumour necrosis factor α (TNF-α) and interleukin 10 (IL-10) promoter genes have been described which influence expression of these cytokines. This study examines the possible association between polymorphisms at the −308 and −627 positions in the TNF-α and IL-10 promoter genes, respectively, and susceptibility to PSC. METHODS TNF-α −308 genotypes were studied by polymerase chain reaction (PCR) in 160 PSC patients from Norway and the UK compared with 145 ethnically matched controls. IL-10 −627 genotypes were studied by PCR in 90 PSC patients compared with 84 ethnically matched controls. RESULTS A total of 16% of Norwegian PSC patients and 12% of British PSC patients were homozygous for the TNF2 allele compared with 3% and 6% of respective controls. The TNF2 allele was present in 60% of PSC patients versus 30% of controls (OR combined data =3.2 (95% confidence intervals (CI) 1.8–4.5); p corr =10 −5 ). The association between the TNF2 allele and susceptibility to PSC was independent of the presence of concurrent inflammatory bowel disease (IBD) in the PSC patients; 61% of PSC patients without IBD had TNF2 compared with 30% of controls (OR combined data =3.2 (95% CI 1.2–9.0); p corr =0.006 ). There was no difference in the −627 IL-10 polymorphism distributions between patients and controls in either population. The increase in TNF2 allele in PSC patients only occurs in the presence of DRB1*0301 (DR3) and B8. In the combined population data, DRB1*0301 showed a stronger association with susceptibility to PSC than both the TNF2 and B8 alleles (OR combined data =3.8, p corr =10 −6 v OR combined data =3.2, p corr =10 −5 v OR combined data =3.41, p corr =10 −4 , respectively). CONCLUSIONS This study identified a significant association between possession of the TNF2 allele, a G→A substitution at position −308 in the TNF-α promoter, and susceptibility to PSC. This association was secondary to the association of PSC with the A1-B8-DRB1*0301-DQA1*0501-DQB1*0201 haplotype. No association was found between the IL-10 −627 promoter polymorphism and PSC.
Pentafecta: A New Concept for Reporting Outcomes of Robot-Assisted Laparoscopic Radical Prostatectomy
Authors: Vipul R. Patel, Ananthakrishnan Sivaraman, Rafael F. Coelho, Sanket Chauhan, Kenneth J. Palmer, Marcelo A. Orvieto, Ignacio Camacho, Geoff Coughlin, Bernardo Rocco
Journal: European Urology (2011)
Environment and invironment in IBDs: partners in crime
Authors: Peter Laszlo Lakatos, Johan Burisch
Journal: Gut (2014)

IBD are chronic inflammatory disorders of the GI tract of unknown aetiology. Crohn's disease (CD) and UC may present with a variable clinical phenotype, and they run a highly variable disease course with a considerable proportion of patients with CD eventually developing penetrating or stricturing complications.1 The key mechanism underlying the pathogenesis of these diseases is assumed to be a dysregulated immune response to commensal flora in a genetically susceptible host.2 Thus, host genetics, the intestinal microbiota (commensal flora and dysbiosis) and external environmental factors are all thought to play an important role in the pathogenesis and in determining subsequent disease behaviour and outcomes. Genetic and recently microbiota research became a success story leading to a revolution in our understanding of the pathogenesis of IBDs and gave insight into the biology leading to new targeted treatment options. It all began with the identification of NOD2/CARD15 and unravelling the importance of innate immunity and defective bacterial sensing in 2001. Since then we have witnessed a rapid acceleration of gene discovery catalysed by the advent of genome-wide association studies, thanks to large collaborations of national and international groups.3 As of today, more than 160 IBD loci have been identified and these risk loci highlight several key pathways including innate immunity, adaptive immune responses, maintenance of intestinal barrier function, pathogen sensing, endoplasmic reticulum stress and response to oxidative stress.4 Of note, some important differences were noted between Europe and Asia (e.g. NOD2 or TNFSF15). In addition, most …
Chromosomal Translocations in Lymphoid Malignancies Reveal Novel Proto-Oncogenes
Authors: S J Korsmeyer
Journal: Annual Review of Immunology (1992)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
[591] IMPACT OF ANEMIA AND ZIDOVUDINE USE ON SUSTAINED VIROLOGICAL RESPONSE IN A TRIAL OF PEGYLATED INTERFERON PLUS RIBAVIRIN IN HIV/HCV-COINFECTED PATIENTS
Authors: M. Nunez, M. Romero, A. Ocampo, K. Aguirrebengoa, M. Cervantes, A. Pascual, S. Echevarria, V. Asensi, P. Barreiro, J. Garcia-Samaniego, V. Soriano
Journal: Journal of Hepatology (2007)
Patient Tolerance to Extended Irradiation in Hodgkin's Disease
Authors: RALPH E. JOHNSON
Journal: Annals of Internal Medicine (1969)

The radiotherapy of patients with Hodgkin's disease clinically limited to lymph nodes and the spleen is reviewed. Each patient was extensively evaluated and classified according to anatomic extent of disease before treatment. Extended irradiation of all major lymph node regions above and below the diaphragm was used on patients with localized as well as widespread lymph node involvement. Recovery of bone marrow function has been observed after irradiation, permitting the effective use of chemotherapy in the majority of patients who have relapsed with radiotherapeutically uncontrolled disease. Definite morbidity has resulted from this type of radical radiotherapy, although the incidence of serious complications has not been prohibitive. Extended irradiation appears to be a practical form of therapy, and the preliminary results are encouraging for selected patients with advanced Hodgkin's disease.
Influence of imatinib interruption and rechallenge on the residual disease in patients with advanced GIST: results of the BFR14 prospective French Sarcoma Group randomised, phase III trial
Authors: A. Patrikidou, S. Chabaud, I. Ray-Coquard, B.N. Bui, A. Adenis, M. Rios, F. Bertucci, F. Duffaud, C. Chevreau, D. Cupissol, J. Domont, D. Pérol, J.Y. Blay, A. Le Cesne
Journal: Annals of Oncology (2012)
Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle
Authors: Kimberly A. Kelly, Jennifer R. Allport, Andrew Tsourkas, Vivek R. Shinde-Patil, Lee Josephson, Ralph Weissleder
Journal: Circulation Research (2005)

Endothelial vascular adhesion molecule-1 (VCAM-1) is a critical component of the leukocyte-endothelial adhesion cascade, and its strict temporal and spatial regulation make it an ideal target for imaging and therapy. The goal of this study was to develop novel VCAM-1-targeted imaging agents detectable by MRI and fluorescence imaging using phage display-derived peptide sequences and multimodal nanoparticles (NPs). We hypothesized that VCAM-1-mediated cell internalization of phage display-selected peptides could be harnessed as an amplification strategy to chaperone and trap imaging agents inside VCAM-1-expressing cells, thus improving target-to-background ratios. To accomplish our goal, iterative phage display was performed on murine endothelium under physiological flow conditions to identify a family of VCAM-1-mediated cell-internalizing peptides. One specific sequence, containing the VHSPNKK motif that has homology to the alpha-chain of very late antigen (a known ligand for VCAM-1), was shown to bind VCAM-1 and block leukocyte-endothelial interactions. Compared with VCAM-1 monoclonal antibody, the peptide showed 12-fold higher target-to-background ratios. A VHSPNKK-modified magnetofluorescent NP (VNP) showed high affinity for endothelial cells expressing VCAM-1 but surprisingly low affinity for macrophages. In contrast, a control NP without VCAM-1-targeting sequences showed no affinity for endothelial cells. In vivo, VNP successfully identified VCAM-1-expressing endothelial cells in a murine tumor necrosis factor-alpha-induced inflammatory model and colocalized with VCAM-1-expressing cells in atherosclerotic lesions present in cholesterol-fed apolipoprotein E apoE-/- mice. These results indicate that: (1) small peptide sequences can significantly alter targeting of NPs, (2) the used amplification strategy of internalization results in high target-to-background ratios, and (3) this technology is useful for in vivo imaging of endothelial markers.
Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor beta.
Authors: Y Vodovotz, C Bogdan, J Paik, Q W Xie, C Nathan
Journal: The Journal of Experimental Medicine (1993)

Activated mouse peritoneal macrophages produce nitric oxide (NO) via a nitric oxide synthase that is inducible by interferon gamma (IFN-gamma): iNOS. We have studied the mechanisms by which transforming growth factor beta 1 (TGF-beta) suppresses IFN-gamma-stimulated NO production. TGF-beta treatment reduced iNOS specific activity and iNOS protein in both cytosolic and particulate fractions as assessed by Western blot with monospecific anti-iNOS immunoglobulin G. TGF-beta reduced iNOS mRNA without affecting the transcription of iNOS by decreasing iNOS mRNA stability. Even after iNOS was already expressed, TGF-beta reduced the amount of iNOS protein. This was due to reduction of iNOS mRNA translation and increased degradation of iNOS protein. The potency of TGF-beta as a deactivator of NO production (50% inhibitory concentration, 5.6 +/- 2 pM) may reflect its ability to suppress iNOS expression by three distinct mechanisms: decreased stability and translation of iNOS mRNA, and increased degradation of iNOS protein. This is the first evidence that iNOS is subject to other than transcriptional regulation.
Screening for Breast Cancer: Time, Travel, and Out-of-Pocket Expenses
Authors: R. H. Secker-Walker, P. M. Vacek, G. J. Hooper, D. A. Plante, A. S. Detsky
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: We estimated the personal costs to women found to have a breast problem (either breast cancer or benign breast disease) in terms of time spent, miles traveled, and cash payments made for detection, diagnosis, initial treatment, and follow-up. METHODS: We analyzed data from personal interviews with 465 women from four communities in Florida. These women were randomly selected from those with a recent breast biopsy (within 6-8 months) that indicated either breast cancer (208 women) or benign breast disease (257 women). One community was the site of a multifaceted intervention to promote breast screening, and the other three communities were comparison sites for evaluation of that intervention. All P values are two-sided. RESULTS: In comparison with time spent and travel distance for women with benign breast disease (13 hours away from home and 56 miles traveled), time spent and travel distance were statistically significantly higher (P<.001) for treatment and follow-up of women with breast cancer (89 hours and 369 miles). Personal financial costs for treatment of women with breast cancer were also statistically significantly higher (breast cancer = $604; benign breast disease = $76; P <.001) but were statistically significantly lower for detection and diagnosis (breast cancer = $170; benign breast disease = $310; P<.001). Among women with breast cancer, time spent for treatment was statistically significantly lower (P = .013) when their breast cancer was detected by screening (68.9 hours) than when it was detected because of symptoms (84.2 hours). Personal cash payments for detection, diagnosis, and treatment were statistically significantly lower among women whose breast problems were detected by screening than among women whose breast problems were detected because of symptoms (screening detected = $453; symptom detected = $749; P = .045). CONCLUSION: There are substantial personal costs for women who are found to have a breast problem, whether the costs are associated with problems identified through screening or because of symptoms.
Adjuvant zoledronic acid in patients with early breast cancer: final efficacy analysis of the AZURE (BIG 01/04) randomised open-label phase 3 trial
Authors: Robert Coleman, David Cameron, David Dodwell, Richard Bell, Caroline Wilson, Emma Rathbone, Maccon Keane, Miguel Gil, Roger Burkinshaw, Robert Grieve, Peter Barrett-Lee, Diana Ritchie, Victoria Liversedge, Samantha Hinsley, Helen Marshall
Journal: The Lancet Oncology (2014)
An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota
Authors: Ian B Jeffery, Paul W O'Toole, Lena Öhman, Marcus J Claesson, Jennifer Deane, Eamonn M M Quigley, Magnus Simrén
Journal: Gut (2011)

<h3>Background and aims</h3> Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that may be triggered by enteric pathogens and has also been linked to alterations in the microbiota and the host immune response. The authors performed a detailed analysis of the faecal microbiota in IBS and control subjects and correlated the findings with key clinical and physiological parameters. <h3>Design</h3> The authors used pyrosequencing to determine faecal microbiota composition in 37 IBS patients (mean age 37 years; 26 female subjects; 15 diarrhoea-predominant IBS, 10 constipation-predominant IBS and 12 alternating-type IBS) and 20 age- and gender-matched controls. Gastrointestinal and psychological symptom severity and quality of life were evaluated with validated questionnaires and colonic transit time and rectal sensitivity were measured. <h3>Results</h3> Associations detected between microbiota composition and clinical or physiological phenotypes included microbial signatures associated with colonic transit and levels of clinically significant depression in the disease. Clustering by microbiota composition revealed subgroups of IBS patients, one of which (n=15) showed normal-like microbiota composition compared with healthy controls. The other IBS samples (n=22) were defined by large microbiota-wide changes characterised by an increase of <i>Firmicutes</i>-associated taxa and a depletion of <i>Bacteroidetes</i>-related taxa. <h3>Conclusions</h3> Detailed microbiota analysis of a well-characterised cohort of IBS patients identified several clear associations with clinical data and a distinct subset of IBS patients with alterations in their microbiota that did not correspond to IBS subtypes, as defined by the Rome II criteria.
Critical Function for Nuclear Envelope Protein TMEM209 in Human Pulmonary Carcinogenesis
Authors: Takashi Fujitomo, Yataro Daigo, Koichi Matsuda, Koji Ueda, Yusuke Nakamura
Journal: Cancer Research (2012)

Therapeutic targets for more effective and less toxic treatments of lung cancer remain important. Here we report the identification of the integral nuclear envelope protein TMEM209 as a critical driver of human lung cancer growth and survival. TMEM209 expression was normally limited to testis, but we found that it was widely expressed in lung cancer, in which it localized to the nuclear envelope, Golgi apparatus, and the cytoplasm of lung cancer cells. Ectopic overexpression of TMEM209 promoted cell growth, whereas TMEM209 attenuation was sufficient to block growth. Mass spectrometric analysis identified the nucleoporin protein NUP205 as a TMEM209-interacting protein, stabilizing NUP205 and increasing the level of c-Myc in the nucleus. Taken together, our findings indicate that TMEM209 overexpression and TMEM209-NUP205 interaction are critical drivers of lung cancer proliferation, suggesting a promising new target for lung cancer therapy.
An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study
Authors: Simon LF Walsh, Athol U Wells, Nicola Sverzellati, Gregory J Keir, Lucio Calandriello, Katerina M Antoniou, Susan J Copley, Anand Devaraj, Toby M Maher, Elizabetta Renzoni, Andrew G Nicholson, David M Hansell
Journal: The Lancet Respiratory Medicine (2014)

BackgroundMortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive and test a staging system for determining prognosis in pulmonary sarcoidosis.MethodsWe identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, including the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers.FindingsThe test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1·04, 95% CI 1·02–1·06, p<0·0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4·24, 2·84–6·33, p<0·0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5·89, 2·68–10·08, p<0·0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians.InterpretationA clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables.FundingNational Institute of Health Research Respiratory Disease Biomedical Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.
Prevalence and Clinical Course of Pleural Effusions at 30 Days after Coronary Artery and Cardiac Surgery
Authors: Richard W. Light, Jeffrey T. Rogers, J. Phillip Moyers, Y. C. Gary Lee, R. Michael Rodriguez, William C. Alford, Stephen K. Ball, George R. Burrus, William H. Coltharp, David M. Glassford, Steven J. Hoff, John W. Lea, Jonathan C. Nesbitt, Michael R. Petracek, Thomas D. Starkey, William S. Stoney, Mark Tedder
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The present prospective study was designed to determine the prevalence of pleural effusion at approximately 28 days after cardiac surgery and their subsequent course. This consecutive case study included 389 patients; 312 had only coronary artery bypass graft surgery (CABG) surgery, 37 had both valve and CABG surgery, and 40 had only valve surgery. Chest radiographs were obtained approximately 28 days postoperatively. Patients were subsequently contacted by telephone 3, 6, and 12 months postoperatively and questioned about the presence of fluid in their chest and related symptoms. The prevalence of pleural effusions in the patients undergoing only CABG surgery (63%) or CABG surgery plus valve surgery (62%) was significantly (p = 0.05) higher than that in the patients undergoing valve surgery only (45%). The prevalence of effusions occupying more than 25% of the hemithorax was 9.7%. The primary symptom associated with these larger effusions was dyspnea. Chest pain and fever were uncommon. Over the 12-month follow-up, the effusions tended to resolve. In conclusion, the prevalence of pleural effusions occupying more than 25% of the hemithorax is approximately 10%, 28 days postoperatively. These larger pleural effusions produce dyspnea but not chest pain or fever, and most of the effusions disappear gradually over the subsequent months.
Which Infants With Eczema Are At Risk Of Food Allergy? Results From A Population Based Study
Authors: Jana K. Eckert, Pamela Martin, Adrian Lowe, Jennifer Koplin, Shyamali Dharmage, Lyle Gurrin, Mimi L.K. Tang, Anne-Louise Ponsonby, Melanie Matheson, David Hill, Katrina Jane Allen
Journal: Journal of Allergy and Clinical Immunology (2014)
Recurrent laryngeal nerve palsy associated with mediastinal amyloidosis
Authors: P. Conaghan
Journal: Thorax (2000)

Amyloidosis affecting peripheral nerves causing isolated nerve palsies is uncommon. Localised amyloidosis occurs less frequently than the reactive or immune related systemic forms, and mediastinal localisation is virtually unknown. We present a case of recurrent laryngeal nerve palsy associated with mediastinal AL amyloidosis in a middle aged man.
The national TB strategy: jointly taking responsibility for TB control?
Authors: O. M. Kon, L. P. Ormerod
Journal: Thorax (2015)

The ‘Collaborative Tuberculosis Strategy for England 2015–2020’1 was recently published on the 19 January 2015 and represents a joint approach by Public Health England (PHE) and the National Health Service of England (NHSE) to tackle the ongoing issue of tuberculosis (TB) in the UK.

Although we saw an encouraging small decrease in the numbers of TB cases in 2013,2 this is in the setting of this disease continuing to be a problem in the UK where we still have one of the highest rates of TB in Western Europe3 and where rates of TB in some high-burden boroughs are comparable to some areas of the Indian subcontinent and South East Asia. Our rates of disease are still almost double that of the preceding two decades. Despite the epidemiological data indicating that the majority of TB cases are in foreign-born individuals, the UK has not yet implemented a systematic programme of latent TB infection (LTBI) detection and prophylactic treatment.4 In addition, there is evidence that ongoing transmission rates are also extremely high in vulnerable groups such as the homeless, those with substance abuse problems and those with a past history of imprisonment.5 The Find & Treat service based in London has been able to provide a targeted approach in this setting, but similar projects are lacking in other high-incidence UK cities.

While the majority of cases and highest rates of disease are centred around the well-recognised ‘hot-spots’ of TB (in conurbations like London, Leicester, Birmingham, Luton, Manchester and Coventry), there is an emerging issue of complex and multi-drug resistant TB (MDR-TB) in areas of low incidence where the local clinical infrastructure may be less well resourced and coordinated. …
Systemic sarcoidosis initially presenting as an orbital tumour
Authors: M Faller, A Purohit, N Kennel, F de Blay, J Sahel, G Pauli
Journal: European Respiratory Journal (1995)

A 73 year old woman presented with redness, itching and painless proptosis of the left eye. Clinical examination and computed tomographic (CT) scan of the orbit revealed a postero-ocular mass, the biopsy of which showed a noncaseating, giant cellular, epithelioid granuloma compatible with sarcoidosis. The patient had no respiratory complaints, but the thoracic CT scan showed multiple bilateral hilar and mediastinal adenopathies. Gallium scan showed increased uptake in both hilar regions, in the left orbit and in the right parotid gland. Multiple bronchial biopsies revealed sarcoid granulomas, with a bronchoalveolar lavage (BAL) cytological pattern of active sarcoidosis. The evolution was favourable with prednisolone given at a dose of 0.5 mg.kg-1 daily. It is suggested that in an unusual presentation of sarcoidosis, a thorough search should be made for localization at other sites, lungs in particular, even in the absence of respiratory complaints.