tbuckley/cabot-search huggingface dataset:
Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis
Authors: T Kamisawa
Journal: Gut (2003)

Autoimmune pancreatitis is a unique clinical entity proposed recently, and is sometimes associated with inflammation of other organs.To examine the pathophysiology of the pancreas and other organs in patients with autoimmune pancreatitis.We evaluated clinicopathological findings in six resected and one autopsied patient with autoimmune pancreatitis. The pancreas, peripancreatic tissue, bile duct, and gall bladder were examined histologically and immunohistochemically. Biopsied salivary gland and cervical lymph node of one patient were also examined. We also performed similar immunohistochemical examinations in pancreatectomy specimens from 10 patients with alcoholic chronic pancreatitis and biopsied salivary glands from five patients with Sjögren's syndrome.Stenosis of the extrahepatic bile duct was detected in all patients. Histological findings were characterised by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Immunohistochemically, diffusely infiltrating cells consisted predominantly of CD4 or CD8 positive T lymphocytes and IgG4 positive plasma cells. Similar inflammatory processes also involved the peripancreatic tissue, extrahepatic bile duct, gall bladder, and salivary gland. Lymph nodes were swollen with infiltration of IgG4 positive plasma cells. None of these findings was seen in alcoholic chronic pancreatitis or Sjögren's syndrome.The development of the specific inflammations in extensive organs as well as the pancreas in patients with autoimmune pancreatitis strongly suggests a close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.
Different Interleukin-1β Converting Enzyme (ICE) Family Protease Requirements for the Apoptotic Death of T Lymphocytes Triggered by Diverse Stimuli
Authors: Apurva Sarin, Ming-Lei Wu, Pierre A. Henkart
Journal: The Journal of Experimental Medicine (1996)

Two cell permeable peptide fluoromethyl ketone inhibitors of Interleukin-1 beta converting enzyme (ICE) family proteases were tested as inhibitors of apoptotic cell death of T lymphocytes at various stages of differentiation. The CPP-32-like protease activity in apoptotic cell lysates was blocked by both the ICE inhibitor Cbz-Val-Ala-Asp(OMe)-fluoromethyl ketone (ZVAD-FMK) as well as its truncated analog Boc-Asp(OMe)-fluoromethyl ketone (BD-FMK), which failed to block ICE. In vitro apoptotic death in murine thymocytes triggered by the independent agents dexamethasone, etoposide, radiation, anti-Fas, and anti-CD3 was blocked equally well by BD-FMK and ZVAD-FMK, but not by the control reagent Cbz-Phe-Ala-fluoromethyl ketone. In activated T cell blasts, while anti-CD3/ Fas-induced death was almost completely inhibited by both ZVAD-FMK, and BD-FMK, death induced by dexamethasone, etoposide, or irradiation was more sensitive to inhibition by BD-FMK. In the murine T cell line CTLL-2, apoptotic death induced by IL-2 withdrawal, etoposide, or dexamethasone was inhibited by BD-FMK, while ZVAD-FMK was without effect. These data indicate that ICE-family proteases comprise a common functional step in distinct T cell apoptotic death pathways, but suggest that different family members are likely to be critical in various differentiated T cell types, even when triggered by the same stimulus.
Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop.
Authors: Y Kanamori, K Ishimaru, M Nanno, K Maki, K Ikuta, H Nariuchi, H Ishikawa
Journal: The Journal of Experimental Medicine (1996)

We have revealed that about one and a half thousand tiny clusters, filled with one thousand closely packed lymphocytes, can be found throughout the murine small and large intestinal mucosa. They are located in crypt lamina propria (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large fraction of lymphocytes in CP expresses c-kit, IL-7R, Thy1 and a lymphocyte function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR alpha beta-, TCR gamma delta-, sIgM-, and B220-. The population size of IL-2R alpha+, HSA+ and Pgp-1+ subsets is variable (20-50%) and the composition of CD8+, Ly-1+, and CD4+ subsets is smaller but also variable (3-20%). In the small intestine, CP do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CP remain the same in aged mice (&amp;gt; 114 wk) but double after estrogen treatment even though the thymi are attenuated sharply in both conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue level of cellular behavior, neither PP, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina propria of IL-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CP are present in germ-free mice and in athymic (nu/nu), SCID, TCR beta x delta-/-, RAG-2-/-, PP-deficient (aly/aly), stem cell factor (Sl/Sld) and c-kit (W/Wv) mutant mice. Taking all of these results together, CP are the first identification of gut-associated murine lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning.
Should contemporary rheumatoid arthritis clinical trials be more like standard patient care and vice versa?
Authors: T Pincus
Journal: Annals of the Rheumatic Diseases (2004)

The information used by rheumatologists when delivering care to patients with rheumatoid arthritis (RA) is derived mainly from two sources: randomised controlled clinical trials and experience in clinical care. However, these two sources differ significantly because (<i>a</i>) the extensive inclusion and exclusion criteria result in clinical trial participants being recruited from only a minority of patients seen in standard clinical care; (<i>b</i>) assessments in clinical trials are conducted according to standard quantitative measures and indices, while standard clinical care of most patients with RA is generally conducted empirically, without collection of any quantitative data other than laboratory tests to estimate prognosis and document change in status; and (<i>c</i>) although baseline databases of various clinical trials (and observational studies) are 60–90% identical in content, they are not standardised and therefore not amenable to direct comparisons. Strategies to promote similarities between clinical trials and standard clinical care in patients with RA may include: more generalised inclusion criteria; incorporation of quantitative measurement into standard care, easily accomplished by asking each patient to complete a simple questionnaire at each visit to a rheumatologist; and consensus among rheumatologists for databases with standard content and format in clinical care and research involving patients with RA.
Diagnostic misclassification reduces the ability to detect linkage in inflammatory bowel disease genetic studies
Authors: M S Silverberg
Journal: Gut (2001)

<h3>BACKGROUND</h3> Linkage data have now identified several inflammatory bowel disease (IBD) susceptibility loci but these data have not been consistently replicated in independent studies. One potential explanation for this is the possibility that patients enrolled in such studies may have been erroneously classified with respect to their diagnosis. <h3>AIMS</h3> To determine the rate and type of misclassification in a large population of individuals referred for participation in an IBD genetics study and to examine the effect of diagnostic misclassification on the power to detect linkage. <h3>METHODS</h3> The medical records of 1096 patients entered into an IBD genetics programme were reviewed using standardised diagnostic criteria. The original patient reported diagnoses were changed, if necessary, based on review, and the reasons for the change in diagnosis were recorded. To evaluate the effect of misclassification on linkage results, simulations were created with Gensim and analysed using Genehunter to evaluate a model for IBD inheritance. <h3>RESULTS</h3> Sixty eight of 1096 (6.2%) individuals had a change in diagnosis from that originally reported. The majority of changes were patients with either Crohn9s disease or ulcerative colitis who were determined not to have IBD at all. The principal reasons for changes to the original diagnosis were discordance between the patients9 subjective reports of diagnosis and actual clinical history, endoscopic, or pathological results; a change in disease pattern over time; and insufficient information available to confirm the original diagnosis. A 10% misclassification rate resulted in 28.4% and 40.2% loss of power to detect a true linkage when using a statistical model for a presumed IBD locus with λ<sub>s</sub>values of 1.8 and 1.3, respectively. <h3>CONCLUSIONS</h3> Diagnostic misclassification occurs in patients enrolled in IBD genetic studies and frequently involves assigning the diagnosis of IBD to non-affected individuals. Even low rates of diagnostic misclassification can lead to significant loss of power to detect a true linkage, particularly for loci with modest effects as are likely to be found in IBD.
Introducing meta-services for biomedical information extraction
Authors: Florian Leitner, Martin Krallinger, Carlos Rodriguez-Penagos, Jörg Hakenberg, Conrad Plake, Cheng-Ju Kuo, Chun-Nan Hsu, Richard Tzong-Han Tsai, Hsi-Chuan Hung, William W Lau, Calvin A Johnson, Rune Sætre, Kazuhiro Yoshida, Yan Hua Chen, Sun Kim, Soo-Yong Shin, Byoung-Tak Zhang, William A Baumgartner, Lawrence Hunter, Barry Haddow, Michael Matthews, Xinglong Wang, Patrick Ruch, Frédéric Ehrler, Arzucan Özgür, Güneş Erkan, Dragomir R Radev, Michael Krauthammer, ThaiBinh Luong, Robert Hoffmann, Chris Sander, Alfonso Valencia
Journal: Genome biology (2008)

We introduce the first meta-service for information extraction in molecular biology, the BioCreative MetaServer (BCMS; http://bcms.bioinfo.cnio.es/ ). This prototype platform is a joint effort of 13 research groups and provides automatically generated annotations for PubMed/Medline abstracts. Annotation types cover gene names, gene IDs, species, and protein-protein interactions. The annotations are distributed by the meta-server in both human and machine readable formats (HTML/XML). This service is intended to be used by biomedical researchers and database annotators, and in biomedical language processing. The platform allows direct comparison, unified access, and result aggregation of the annotations.
Sequential Systemic Administrations of Combretastatin A4 Phosphate and Radioiodinated Hypericin Exert Synergistic Targeted Theranostic Effects with Prolonged Survival on SCID Mice Carrying Bifocal Tumor Xenografts
Authors: Junjie Li, Marlein Miranda Cona, Feng Chen, Yuanbo Feng, Lin Zhou, Guozhi Zhang, Johan Nuyts, Peter de Witte, Jian Zhang, Jie Yu, Raymond Oyen, Alfons Verbruggen, Yicheng Ni
Journal: Theranostics (2013)

Objectives: Based on the soil-to-seeds principle, we explored the small-molecular sequential dual-targeting theranostic strategy (SMSDTTS) for prolonged survival and imaging detectability in a xenograft tumor model.Materials and Methods: Thirty severe combined immunodeficiency (SCID) mice bearing bilateral radiation-induced fibrosarcoma-1 (RIF-1) subcutaneously were divided into group A of SMSDTTS with sequential intravenous injections of combretastatin A4 phosphate (CA4P) and 131 I-iodohypericin ( 131 I-Hyp) at a 24 h interval; group B of single targeting control with CA4P and vehicle of 131 I-Hyp; and group C of vehicle control (10 mice per group).Tumoricidal events were monitored by in vivo magnetic resonance imaging (MRI) and planar gamma scintiscan, and validated by ex vivo autoradiography and histopathology.Besides, 9 mice received sequential intravenous injections of CA4P and 131 I-Hyp were subjected to biodistribution analysis at 24, 72 and 120 h.Results: Gamma counting revealed fast clearance of 131 I-Hyp from normal organs but intense accumulation in necrotic tumor over 120 h.After only one treatment, significantly prolonged survival (p<0.001) was found in group A compared to group B and C with median survival of 33, 22, and 21 days respectively.Tumor volume on day 15 was 2.0 ± 0.89, 5.66 ± 1.66, and 5.02 ± 1.0 cm 3 with tumor doubling time 7.8 ± 2.8, 4.4 ± 0.67, and 4.5 ± 0.5 days respectively.SMSDTTS treated tumors were visualized as hot spots on gamma scintiscans, and necrosis over tumor ratio remained consistently high on MRI, autoradiography and histology.Conclusion: The synergistic antitumor effects, multifocal targetability, simultaneous theranostic property, and good tolerance of the SMSDTTS were evident in this experiment, which warrants further development for preclinical and clinical applications.
Molecular Evolution of Freshwater Snails with Contrasting Mating Systems
Authors: Concetta Burgarella, Philippe Gayral, Marion Ballenghien, Aurélien Bernard, Patrice David, Philippe Jarne, Ana Correa, Sylvie Hurtrez-Boussès, Juan Escobar, Nicolas Galtier, Sylvain Glémin
Journal: Molecular Biology and Evolution (2015)

Because mating systems affect population genetics and ecology, they are expected to impact the molecular evolution of species. Self-fertilizing species experience reduced effective population size, recombination rates, and heterozygosity, which in turn should decrease the efficacy of natural selection, both adaptive and purifying, and the strength of meiotic drive processes such as GC-biased gene conversion. The empirical evidence is only partly congruent with these predictions, depending on the analyzed species, some, but not all, of the expected effects have been observed. One possible reason is that self-fertilization is an evolutionary dead-end, so that most current selfers recently evolved self-fertilization, and their genome has not yet been strongly impacted by selfing. Here, we investigate the molecular evolution of two groups of freshwater snails in which mating systems have likely been stable for several millions of years. Analyzing coding sequence polymorphism, divergence, and expression levels, we report a strongly reduced genetic diversity, decreased efficacy of purifying selection, slower rate of adaptive evolution, and weakened codon usage bias/GC-biased gene conversion in the selfer Galba compared with the outcrosser Physa, in full agreement with theoretical expectations. Our results demonstrate that self-fertilization, when effective in the long run, is a major driver of population genomic and molecular evolutionary processes. Despite the genomic effects of selfing, Galba truncatula seems to escape the demographic consequences of the genetic load. We suggest that the particular ecology of the species may buffer the negative consequences of selfing, shedding new light on the dead-end hypothesis.
Fibroblast cell behaviour growing into a stiffened three dimensional collagen matrix
Authors: Vanesa Vicens, Susanna Estany, Adai Colom, Jordi Alcaraz, Daniel Navajas, A. Juliana Sanabria, Roger Llatjos, Ignacio Escobar, Pablo V. Romero, Federic Manresa, Jordi Dorca, Maria Molina
Journal: European Respiratory Journal (2011)

Introduction:  Idiopathic Pulmonary Fibrosis is a process that involves abnormal cell behaviour and increased tissue stiffness. The aim of this study was to elaborate a stiffened three-dimensional (3D) collagen I matrix to study cultured human cells inside.   Methods:  3D matrices were elaborated with native collagen I and it was non-enzymathically glycated with ribose at different conditions. Matrix stiffness was measured with Athomic Force Microscope and collagen deposition was evaluated by confocal reflexion microscope. Primary fibroblasts were obtained from normal human lungs. Cellular viability in 3D matrices was evaluated by AlamarBlue fluorescence assay and LIVE/DEAD kit at different time points.   Results:  It was observed that fluorescence AlamarBlue assay requires more time incubation to detect viability in 3D collagen matrices than in 2D cell cultures. An increased stiffness of 3D matrices was achieved with high concentration of collagen and ribose glycation from the second week. Stiff-variability and morphological changes in collagen I fibers was dependent on the media used for the matrix elaboration and the glycation condition. Cell death was detected in higher ribose concentrations. Fibroblasts showed a better-defined morphology and viability in matrices elaborated with lower ribose concentrations and DMEM media.   Conclusion:  The development of this 3D collagen I matrix allows the fibroblast growth inside a modified microenvironment. Cell viability depends on different variables and it dramatically decreases with higher concentrations of ribose. This innovated model could help in the study of cell behaviour and phenotype at different conditions.  Supported by: SEPAR, SOCAP, FUCAP, PS09/01757
Autoimmune liver disease, autoimmunity and liver transplantation
Authors: Marco Carbone, James M. Neuberger
Journal: Journal of Hepatology (2013)

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune process is not clear. In this manuscript, we review novel findings about disease processes and mechanisms that lead to autoimmunity in the liver and their possible involvement in the immune response vs. the graft after LT.
Omalizumab in patients with chronic spontaneous urticaria: a systematic review and <scp>GRADE</scp> assessment
Authors: M.C. Urgert, M.T. Elzen, A.C. Knulst, Z. Fedorowicz, E.J. Zuuren
Journal: British Journal of Dermatology (2015)

Chronic spontaneous urticaria (CSU) is characterized by the occurrence of hives, angio-oedema or both for a period of at least 6 weeks. Many patients remain symptomatic despite treatment with H1 antihistamines, even at higher doses. This systematic review assessed the quality of the evidence for the effects of omalizumab as treatment in patients with CSU. We searched PubMed, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials up to 7 August 2014. Three review authors independently carried out study selection, risk of bias assessment and data extraction. Two review authors analysed the data. Five randomized controlled trials (RCTs), which included 1116 participants, were evaluated. All the RCTs were judged as having a low risk of bias. There was a statistically significant improvement in measures of disease activity and quality of life following treatment with omalizumab when compared with placebo [mean difference (MD) −11·58, 95% confidence interval (CI) −13·39 to −9·77 and MD −13·12, 95% CI −16·30 to −9·95, respectively]. Complete response and partial response were more frequent after treatment with omalizumab [risk ratio (RR) 6·44, 95% CI 3·95–10·49 and RR 4·08, 95% CI 2·98–5·60, respectively]. There was no difference in the proportion of participants reporting adverse events between the omalizumab and placebo treatment groups (RR 1·05, 95% CI 0·96–1·16). There was high-quality evidence to support the effectiveness and safety of omalizumab 300 mg per month for the treatment of CSU for up to 6 months.
Lipid Alterations and Decline in the Incidence of Coronary Heart Disease in the Helsinki Heart Study
Authors: Vesa Manninen
Journal: JAMA (1988)

In the Helsinki Heart Study, a randomized five-year, double-blind trial, a 34% reduction in the incidence of coronary heart disease (CHD) was observed in dyslipidemic men treated with gemfibrozil. Averaged over the five years of the trial, gemfibrozil therapy produced, compared with placebo, mean decreases of 10% in serum total cholesterol level, 14% in non-high-density lipoprotein (HDL) cholesterol level, 11% in low-density lipoprotein (LDL) cholesterol level, 35% in triglyceride level, and a mean increase of 11% in HDL cholesterol level from baseline levels measured prior to treatment. While changes in HDL cholesterol level were similar in all Fredrickson types, the effect on concentrations of total cholesterol and LDL cholesterol was largest in type IIA and on LDL minimal in type IV. The reduction of CHD incidence over placebo was largest in type IIB and smallest in type IIA. The lipid changes were dependent on lipid levels prior to treatment and on compliance with the medication regimen. When risk factors for CHD, including age, blood pressure, smoking and drinking habits, baseline lipid levels, and exercise and relative weight, were controlled by applying the Cox proportional hazards model, the changes in serum HDL and LDL cholesterol levels were both statistically significantly associated with the decline in CHD incidence within the gemfibrozil-treated group. The large decrease in serum triglyceride levels had relatively small effect on CHD incidence. Thus, the results of this study, together with earlier observations, suggest that both elevating HDL and lowering LDL cholesterol levels are effective in the primary prevention of CHD. (<i>JAMA</i>1988;260:641-651)
Book: Virtual University? Educational Environments for the Future
Authors: J. O'N. Roach
Journal: BMJ (2001)

Ed Henk J van der Molen Portland Press Ltd, £75, pp 168 ISBN 1 85578 145 X Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> The driver behind change in learning environments is money. The use of the internet for learning is no exception. While currently that money comes in the form of research grants, entrepreneurs have realised that, in tomorrow's world, online learning may be the biggest web industry yet. This has spawned growing interest in the new concept of “virtual” universities and medical schools. In … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif