tbuckley/cabot-search huggingface dataset:
Characterisation of autoantibodies to neutrophil granule constituents among patients with reactive arthritis, rheumatoid arthritis, and ulcerative colitis
Authors: H. Locht
Journal: Annals of the Rheumatic Diseases (2000)

To study the frequency and distribution of antineutrophil cytoplasmic autoantibodies (ANCA) among patients with reactive arthritis (ReA), rheumatoid arthritis (RA), and ulcerative colitis (UC) using different immunological methods.Fifty serum samples from patients with reactive arthritis (26 with acute disease and 24 with chronic disease-that is disease of more than one year) were analysed for ANCA with indirect immunofluorescence, enzyme linked immunosorbent assay (ELISA) with six different neutrophil granule proteins as antigens, and immunoblotting on whole neutrophil extract and extracts of azurophil and specific granules. Thirty serum samples from patients with RA and UC served as controls in ELISA and indirect immunofluorescence.Sixteen per cent of patients with ReA were positive in immunofluorescence compared with 30% of patients with RA, and 70% of patients with UC. Thirty two per cent of patients with ReA were positive in ELISA. Antibodies directed against lactoferrin occurred in 20%, antibodies against bactericidal permeability increasing protein (BPI), elastase, cathepsin G, myeloperoxidase, and proteinase 3 were found in 8%, 2%, 2%, 8%, and 6%, respectively. Overall, 50% of RA sera and 53% of UC sera were positive in one or more ELISA assays, the corresponding figures for antibodies against individual antigens were for RA 7%, 3%, 0%, 13%, 47%, 17% and for UC 13%, 20%, 0%, 23%, 10%, and 17%. In immunoblotting, bands corresponding to lactoferrin and BPI were recognised in 44% and 22% of ReA sera.Antibodies against neutrophil granule antigens are often found in patients with ReA, primarily among those with chronic disease. The different methods detect various subsets of antibodies, with immunoblotting being the most and immunofluorescence the least sensitive.
Biodegradable oesophageal stents for refractory benign disease: a case series
Authors: S. Hazeldine, J. Wu, R. Law, R. Przemioslo
Journal: Gut (2011)

<h3>Introduction</h3> Benign oesophageal strictures that are refractory to dilatation are difficult to treat and may require the placement of an oesophageal stent. Biodegradable oesophageal stents (BDOS) are licensed for use in benign oesophageal strictures including achalasia. The biodegradable stent has advantages over metal stents as it negates the need for removal and has few reported local adverse events, the most common being stent migration. We report our experience of BDOS in patients with benign oesophageal strictures refractory to repeated dilatation. <h3>Methods</h3> Patients were considered to have refractory benign oesophageal strictures if histology was negative for malignancy and had undergone at least 3 previous balloon dilatation procedures. Ella BD Polydioxanone stents (UK Medical) were placed under endoscopic and fluoroscopic visualisation with conscious sedation. Stent position and function was checked the following day with a barium swallow. Patients were then followed up clinically, recording dysphagia symptoms, stent migration and complications. <h3>Results</h3> Four patients were identified with refractory benign oesophageal strictures. Mean age 68 (57–87), 3 male and 1 female. Stricture aetiology; 2 achalasia, 1 peptic and 1 postradiotherapy. Follow-up period poststent insertion ranged from 1 to 7 months. On initial inspection all 4 stents were placed correctly. Follow-up barium swallow on day 1 showed one stent had migrated distally (achalasia), this was replaced in the correct position endoscopically. At day 7, dysphagia was not relieved in 1 of 4 patients (achalasia), despite adequate stent patency. At 1 month only 1 of 4 patients had symptom relief (peptic stricture) and was still symptom free at 7 months. Complications included severe odynophagia requiring stent removal (postradiation), food bolus obstruction and aspiration pneumonia (achalasia). <h3>Conclusion</h3> We have experienced variable success in our use of biodegradable stents. In our experience BDOS did not provide significant benefit in those patients with achalasia especially if it was longstanding and there was poor oesophageal motility. Only one patient (peptic stricture) had a prolonged response to dysphagia. Larger case series are required to ascertain the role of BDOS in patients with refractory benign oesophageal strictures.
Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis
Authors: E A M Festen, P Goyette, R Scott, V Annese, A Zhernakova, J Lian, C Lefebvre, S R Brant, J H Cho, M S Silverberg, K D Taylor, D J de Jong, P C Stokkers, D Mcgovern, O Palmieri, J-P Achkar, R J Xavier, M J Daly, R H Duerr, C Wijmenga, R K Weersma, J D Rioux
Journal: Gut (2009)

<h3>Objectives:</h3> Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The <i>IL2/IL21</i> locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the <i>IL2/IL21</i> locus and the IBDs. <h3>Methods:</h3> The four single nucleotide polymorphisms (SNPs) in the <i>IL2/IL21</i> locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran–Mantel–Haenszel test were performed. <h3>Results:</h3> All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35×10<sup>−10</sup>, rs13119723 p = 8.60×10<sup>−8</sup>, rs6840978 p = 3.07×10<sup>−8</sup>, rs6822844 p = 2.77×10<sup>−9</sup>). A moderate association with CD was also found in the pooled analysis (p value range 0.0016–9.86×10<sup>−5</sup>). <h3>Conclusions:</h3> A strong association for the <i>IL2/IL21</i> locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.
Systematic Meta-Analyses and Field Synopsis of Genetic Association Studies in Colorectal Cancer
Authors: E. Theodoratou, Z. Montazeri, S. Hawken, G. C. Allum, J. Gong, V. Tait, I. Kirac, M. Tazari, S. M. Farrington, A. Demarsh, L. Zgaga, D. Landry, H. E. Benson, S. H. Read, I. Rudan, A. Tenesa, M. G. Dunlop, H. Campbell, J. Little
Journal: JNCI Journal of the National Cancer Institute (2012)

Colorectal cancer is a major global public health problem, with approximately 950 000 patients newly diagnosed each year. We report the first comprehensive field synopsis and creation of a parallel publicly available and regularly updated database (CRCgene) that catalogs all genetic association studies on colorectal cancer (http://www.chs.med.ed.ac.uk/CRCgene/). We performed two independent systematic reviews, reviewing 10 145 titles, then collated and extracted data from 635 publications reporting on 445 polymorphisms in 110 different genes. We carried out meta-analyses to derive summary effect estimates for 92 polymorphisms in 64 different genes. For assessing the credibility of associations, we applied the Venice criteria and the Bayesian False Discovery Probability (BFDP) test. We consider 16 independent variants at 13 loci (MUTYH, MTHFR, SMAD7, and common variants tagging the loci 8q24, 8q23.3, 11q23.1, 14q22.2, 1q41, 20p12.3, 20q13.33, 3q26.2, 16q22.1, and 19q13.1) to have the most highly credible associations with colorectal cancer, with all variants except those in MUTYH and 19q13.1 reaching genome-wide statistical significance in at least one meta-analysis model. We identified less-credible (higher heterogeneity, lower statistical power, BFDP >0.2) associations with 23 more variants at 22 loci. The meta-analyses of a further 20 variants for which associations have previously been reported found no evidence to support these as true associations. The CRCgene database provides the context for genetic association data to be interpreted appropriately and helps inform future research direction.
Interleukin-6 in Obese Children and Adolescents With and Without Glucose Intolerance
Authors: Diego Yeste, Joan Vendrell, Rosangela Tomasini, Montse Broch, Miquel Gussinyé, Ana Megia, Antonio Carrascosa
Journal: Diabetes Care (2007)

In recent years, the increased prevalence of obesity in industrialized countries has been accompanied by a parallel rise in the incidence of type 2 diabetes, both in adults and children (1–3). Obese children and adults, after a period of time with obesity (4), may develop type 2 diabetes. Glucose intolerance, an intermediate stage in the progression toward type 2 diabetes, may become apparent in obesity (5,6). Insulin resistance in obese children frequently precedes the development of type 2 diabetes, metabolic syndrome, or both (7,8), and type 2 pre-diabetes has been reported in obese adolescents (9,10). The mechanisms implicated in insulin resistance in obese subjects remain to be fully established. Adipose tissue is the source of a wide variety of molecules involved in the regulation of energy output and carbohydrate metabolism. Among these, proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, in particular, appear to play a role in modulating insulin sensitivity in peripheral tissues and have been associated with the development of insulin resistance in adults (11). Furthermore, glucose induces oxidative stress and increased nuclear factor-κB binding, and it also increases the transcription of nuclear factor-κB–dependent proinflammatory genes (TNF-α and IL-6) (12,13).

Early detection of subjects with obesity-associated metabolic disorders, especially those at risk for glucose intolerance, is …
Binding and Phagocytosis of Apoptotic Vascular Smooth Muscle Cells Is Mediated in Part by Exposure of Phosphatidylserine
Authors: M.R. Bennett, D.F. Gibson, S.M. Schwartz, J.F. Tait
Journal: Circulation Research (1995)

Abstract Apoptosis of vascular smooth muscle cells has recently been demonstrated to occur in vitro and in vivo. Uptake of apoptotic cells into adjacent normal cells appears to be rapid and specific. We have investigated binding and phagocytosis of apoptotic vascular smooth muscle cells by normal smooth muscle cell monolayers. Vascular smooth muscle cells were infected with the proto-oncogene c- myc or the adenovirus E1A gene, induced to undergo apoptosis in low-serum conditions, and then incubated with normal smooth muscle cells. Apoptosis was accompanied by a marked increase in exposure of phosphatidylserine on the outer surface of the cell, which was recognized by binding to annexin V. Liposomes containing phosphatidylserine but not phosphatidylinositol inhibited uptake of apoptotic cells in a dose-dependent manner to a maximum of 50% inhibition; annexin V also inhibited the uptake of apoptotic cells in a dose-dependent and calcium-dependent manner. Binding of apoptotic bodies did not appear to be mediated by endogenous annexin V, as evidenced by the inability of an antibody to annexin V to inhibit uptake. Smooth muscle cells were also able to recognize exposed phosphatidylserine on other cell types, as judged by their ability to bind erythrocytes having a high degree of exposed phosphatidylserine. We conclude that smooth muscle cells express phosphatidylserine during apoptosis, and this exposure partly mediates binding and phagocytosis of dead cells. This mechanism may be important in promoting rapid cell removal in the vessel wall.
INTRACELLULAR FORMS OF MENINGOPNEUMONITIS VIRUS
Authors: William H. Gaylord
Journal: The Journal of Experimental Medicine (1954)

Electron micrographs of intracellular memngopneumonitis virus have shown several types of particles which are presumably representative of different stages of a life cycle. They are: (a) Elementary bodies-dense particles 250 to 300 mmicro in diameter with very dense central granules. (b) Intermediate forms-less dense than elementary bodies and larger. They are 300 to 400 mmicro in diameter, contain a very dense central granule, and often have two or three limiting zones, (c) Circles 400 to 500 mmicro in diameter-homogeneous structures with single membranes and no internal granules. They are often elongated and constricted at the center in the manner of budding yeast cells, (d) Circles 500 to 600 mmicro in diameter with single membranes.mdash;One, two, and three dense granules may be present in some of these structures, (e) "Larger" structures, circular to elliptical, often with discontinuities or ruptures in their membranes. They sometimes seem to have internal septa. It has been inferred from these observations that the virus can multiply by binary fission or by multiple endosporulation and that elementary bodies are a spore-like stage.
Reply to A. Gratwohl
Authors: Henk Lokhorst, Hermann Einsele, David Vesole, Benedetto Bruno, Jesus San Miguel, Jose A. Perez-Simon, Nicolaus Martin Kröger, Philippe Moreau, Gosta C.A. Gahrton, Cristina Gasparetto, Sergio Giralt, William I. Bensinger
Journal: Journal of Clinical Oncology (2011)
Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6·4 years
Authors: B Romanowski, P Colares de Borba, P S Naud, C M Roteli-Martins, N S De Carvalho, J C Teixeira, F Aoki, B Ramjattan, R M Shier, R Somani, S Barbier, M M Blatter, C Chambers, D Ferris, S A Gall, F A Guerra, D M Harper, J A Hedrick, D C Henry, A P Korn, R Kroll, A-B Moscicki, W D Rosenfeld, B J Sullivan, C S Thoming, S K Tyring, C M Wheeler, G Dubin, A Schuind, T Zahaf, Mary Greenacre, An Sgriobhadair
Journal: The Lancet (2009)
Activation and Regulation of Purinergic P2X Receptor Channels
Authors: Claudio Coddou, Zonghe Yan, Tomas Obsil, J. Pablo Huidobro-Toro, Stanko S. Stojilkovic
Journal: Pharmacological Reviews (2011)

Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven possible subunits, denoted P2X1 to P2X7. Each subunit contains a large ectodomain, two transmembrane domains, and intracellular N and C termini. Functional P2XRs are organized as homomeric and heteromeric trimers. This review focuses on the binding sites involved in the activation (orthosteric) and regulation (allosteric) of P2XRs. The ectodomains contain three ATP binding sites, presumably located between neighboring subunits and formed by highly conserved residues. The detection and coordination of three ATP phosphate residues by positively charged amino acids are likely to play a dominant role in determining agonist potency, whereas an AsnPheArg motif may contribute to binding by coordinating the adenine ring. Nonconserved ectodomain histidines provide the binding sites for trace metals, divalent cations, and protons. The transmembrane domains account not only for the formation of the channel pore but also for the binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N- and C- domains provide the structures that determine the kinetics of receptor desensitization and/or pore dilation and are critical for the regulation of receptor functions by intracellular messengers, kinases, reactive oxygen species and mercury. The recent publication of the crystal structure of the zebrafish P2X4.1R in a closed state provides a major advance in the understanding of this family of receptor channels. We will discuss data obtained from numerous site-directed mutagenesis experiments accumulated during the last 15 years with reference to the crystal structure, allowing a structural interpretation of the molecular basis of orthosteric and allosteric ligand actions.
Measuring the quality of screening colonoscopy: moving on from adenoma detection rate
Authors: T. J. W. Lee, C. Nickerson, C. J. Rees, M. D. Rutter
Journal: Gut (2011)

<h3>Introduction</h3> Adenoma detection rate (ADR) is the most widely used metric to assess quality of colonoscopy. Studies have shown ADR to correlate with other measures of colonoscopic performance such as withdrawal time, caecal intubation rate and longer term outcomes such as interval cancer rate. ADR is calculated by dividing the number of procedures in which one or more adenomas are detected by the total number of procedures. It has an inherent limitation in that it does not measure the total number of adenomas detected. The ethos of screening colonoscopy, in addition to detecting cancer, is to detect and remove all adenomas. This abstract examines other measures of adenoma detection in the context of the NHS Bowel Cancer Screening Programme (BCSP). <h3>Methods</h3> Data from all screening colonoscopies in the BCSP performed between August 2006 and August 2009 were analysed. The following measures of adenoma detection were calculated for each colonoscopist who had performed ≤50 procedures: ADR, MAP (mean adenomas per patient−total number of adenomas detected/ number of procedures), MAP+ (mean adenomas per positive procedure−total number of adenomas detected/ number of procedures in which one or more adenoma were detected). Correlation was assessed using Pearson9s correlation coefficient. This abstract examines other measures of adenoma detection in the context of the NHS BCSP. <h3>Results</h3> 31 088 procedures performed by 148 colonoscopists (mean 210 procedures per colonoscopist) were analysed. The mean, range, SD and correlation with ADR of each of the measures of adenoma detection are shown in table 1. 46.5% of patients have one or more adenomas, of these 53% have only one adenoma. For this reason, MAP and ADR correlate closely. However, MAP displays much greater variation than ADR. MAP+ demonstrated less variation and correlates less well with ADR. <h3>Conclusion</h3> MAP reflects the aim of screening colonoscopy to detect and remove all adenomas. MAP may be a more sensitive measure of colonoscopic performance but prospective studies are required to confirm this. MAP+ is a less useful measure of adenoma detection in isolation. It is largely dependent on the ADR but may still be high despite a low ADR. It may be useful as an adjunct to ADR or MAP in colonoscopists with evidence of high colonoscopic performance (ADR greater than the mean of the population). In this group, MAP+ identifies a group of colonoscopists attaining very high adenoma detection.
Familial Renal Tubular Acidosis
Authors: VARDAMAN M. BUCKALEW
Journal: Annals of Internal Medicine (1968)

Editorial Notes1 June 1968Familial Renal Tubular AcidosisVARDAMAN M. BUCKALEW JR., M.D.VARDAMAN M. BUCKALEW JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-6-1367 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is now well-established that the syndrome of renal tubular acidosis (RTA), in which the primary defect is an inability to lower urinary pH normally, occurs as a familial disease in a small percentage of cases. However, the mode of transmission is not entirely clear. In a recent review, Seldin and Wilson (1) summarized the evidence in 14 families suggesting that familial RTA is due to an autosomal dominant gene. The strongest evidence favoring this view is found in the two families originally reported by Pitts, Schulte, and Smith (2) and subsequently by Randall and Taggart (3) and by Schreiner,...References1. SELDIN DW and WILSON JD: Renal tubular acidosis, in The Metabolic Basis of Inherited Disease, 2nd ed., edited by STANBURY, J. B., WYNGAARDEN, J. B., FREDRICKSON, D. S., McGraw-Hill Book Co., Inc., New York, 1966, p. 1230. Google Scholar2. PITTS HH, SCHULTE JW, and SMITH DR: Nephrocalcinosis in a father and three children. J. Urol. 73: 208, 1955. CrossrefMedlineGoogle Scholar3. RANDALL RE and TAGGART WH: Familial renal tubular acidosis. Ann. Intern. Med. 54: 1108, 1961. LinkGoogle Scholar4. SCHREINER GE, SMITH LH, and KYLE LH: Renal hyperchloremic acidosis. Amer. J. Med. 15: 122, 1953. CrossrefMedlineGoogle Scholar5. RANDALL RE: Familial renal tubular acidosis revisited (letters and comments). Ann. Intern. Med. 66: 1024, 1967. LinkGoogle Scholar6. ELKINTON JR, MCCURDY DK, and BUCKALEW VM: Hydrogen ion and the kidney, in Renal Disease, 2nd ed., edited by BLACK, D. A. K., Blackwell Scientific Publications Ltd., Oxford, 1967, p. 110. Google Scholar7. BUCKALEW VM, MCCURDY DK, LUDWIG GD, CHAYKIN LB, and ELKINTON JR: Incomplete renal tubular acidosis. Physiological studies in three patients with a defect in lowering urinary pH. Amer. J. Med.: in press, 1968. MedlineGoogle Scholar8. KUHLENCORDT F, LENZ W, SEEMANN N, and ZUKSCHWERDT L: Renal tubular acidosis and bilateral nephrocalcinosis in uniovular twins. German Med. Monthly 12: 565, 1967. MedlineGoogle Scholar9. WRONG O and DAVIES HE: The excretion of acid in renal disease. Quart. J. Med. 28: 259, 1959. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: VARDAMAN M. BUCKALEWJR., M.D.Affiliations: Department of Medicine Emory University School of Medicine Atlanta, Ga. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAcid-Base Disorders and the Kidney 1 June 1968Volume 68, Issue 6Page: 1367-1368KeywordsRenal diseases ePublished: 1 December 2008 Issue Published: 1 June 1968 PDF downloadLoading ...
Robyn J. Barst, MD
Authors: Lewis J. Rubin
Journal: European Respiratory Journal (2013)

On April 19, 2013, Robyn J. Barst – wife to Sam, mother to Nomi and Lindsey, grandmother to Tobias, physician to many adults and children with pulmonary hypertension, and a friend and colleague of mine for more than 25 years – passed away at her home in Scarsdale, New York after a protracted illness. She was 62 years old.

I can't recall exactly when I first met Robyn, but I will never forget when we last collaborated. It was only a few months ago, in February of this year, at the Fifth World Symposium on Pulmonary Hypertension, held in Nice, France. Robyn had been on the organising committee of the previous four symposia, and we had shared the primary responsibility and workload for the fourth symposium, held in Dana Point, CA, USA, but Robyn was too ill to travel for the most recent meeting. Despite the rapid deterioration in her condition, she organised a teleconference with the two task forces to which she had been assigned, and spent over 8 hours over a 2-day period on the phone with her colleagues, giving her usual insight and providing suggestions for future directions. Everyone in that conference …
A LARGE RENAL CALCULUS
Authors: R. O. Ward
Journal: BMJ (1923)

depends on the relative production of a haemolysin or a neurotoxin.We would suggest a similar genesis in many instances of rheumatoid arthritis by means of a toxin with a special affinity for synovial membrane.However, it must always be remembered that the whole metabolism is upset, and further work is required to inves- tigate other possible factors responsible for the production of the clinical changes observed.Many observers have assigned importance to the isolation of various strains of streptococci from the stools, but the results are so far very variable and no reliable conclusions can be drawn.It is possible that the factor of achlorhydria may have some influence in determining this state of affairs, in view of the work of Billings7 and his collaborators on the variability of streptococcal strains in different media.We wish to thank Dr. Munro,