tbuckley/cabot-search huggingface dataset:
Anticoagulation in patients with liver cirrhosis: complication or therapeutic opportunity?
Authors: Vipul Jairath, Andrew K Burroughs
Journal: Gut (2013)

Like many physiological systems, the coagulation cascade is dependent upon a dynamic interplay, which is between multiple opposing procoagulant and anticoagulant drivers so as to maintain physiological haemostasis and prevent unwanted episodes of bleeding or thrombosis. The end product of this proteolytic cascade is the generation of thrombin, which cleaves soluble fibrinogen into fibrin to form a blood clot.1 This process occurs in several phases. Briefly, the initiation phase occurs when tissue factor exposed on cellular surfaces of vascular injury binds circulating factor VIIa,2 which leads to small amounts of thrombin production through activated factor X (Xa). At this stage there is insufficient thrombin to activate fibrinogen, therefore a series of feedback loops through an amplification stage leads to further thrombin generation which is maintained by the propagation phase through generation of large quantities of activated factor X. Soluble fibrin monomers are formed which are cross-linked by activated factor XIII to form a stable fibrin meshwork. To prevent pathological clot formation, thrombin generation is regulated by the anticoagulant system, including proteins C, S and antithrombin. Finally, clot dissolution occurs via activation of the fibrinolytic cascade.

Healthy people have sufficient quantities of coagulation factors, regulatory proteins and platelets to maintain haemostasis, thus preventing bleeding or thrombotic complications. Patients with cirrhosis of the liver have multiple defects in components of the aforementioned pathways, including deficiencies in both procoagulant and anticoagulant factors,3 anaemia,4 thrombocytopenia,5 hypofibrinogenaemia and dysfibrinogenaemia6 as well as evidence of hyperfibrinolysis.7 These derangements, reflected in conventional coagulation indices and haemorrhagic complications seen with cirrhosis, have led to cirrhosis being regarded as a prototypical haemorrhagic disorder.

However, in recent years this interpretation has been challenged,8 leading to a paradigm shift in understanding, owing to increasing evidence of the thrombotic complications associated with cirrhosis,9 …
Altered Immunoregulation in Waldenström's macroglobulinemia. I. The absence of con A‐induced and spontaneous T suppressor cell activity in a patient and his kindred
Authors: Robert H. Keller, Eric Feldman, Joseph A. Libnoch
Journal: American Journal of Hematology (1983)

Abstract In vitro lymphocyte functions in a patient with Waldenström's macroglobulinemia and his kindred were examined. The percentage and number of total peripheral blood T cells and the absolute number of FCγ bearing T cells were decreased in the patient and family members compared to controls but the B cells and monocytes were normal. In addition, PHA and PWM stimulated proliferation were decreased. Decreased responsiveness to PWM was abrogated by preculturing PBMC in media alone before PWM stimulation. Decreased responsiveness to PHA was not reversed by a similar period of preculture. To further define the above abnormalities in immunoregulation we examined mononuclear subpopulations. In controls, adding purified T cells or Con A activated lymphocytes to autologous cultures which had been stimulated with PHA and PWM significantly decreased proliferative activity. No such suppressive activity of T cells or Con A activated cells from the patient or family members was noted. These data demonstrate an absent or functionally inactive spontaneous and Con A activated T suppressor cells in the family of a patient with Waldenström's macroglobulinemia.
Faith Healers and Physicians — Teaching Pseudoscience by Mandate
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2005)

In the 1939 movie The Wizard of Oz, Frank Morgan plays five roles. In one of them, he is a flimflam hawker of trivia traveling across the plains of Kansas in a horse-drawn wagon. In another, he is the wizard who, concealed by a curtain, manipulates a machine that controls all of Oz. Now, more than 65 years later, another pitchman is rolling across Kansas, but unlike Morgan's bumbling peddler of trinkets and dreams, the new one has no interest in such trifles. It is an articulate and sophisticated anti-evolution movement called “intelligent design.” At its core is the . . .
Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms
Authors: H. Slevogt, L. Maqami, K. Vardarowa, W. Beermann, A. C. Hocke, J. Eitel, B. Schmeck, A. Weimann, B. Opitz, S. Hippenstiel, N. Suttorp, P. D. N'Guessan
Journal: European Respiratory Journal (2008)

<i>Moraxella catarrhalis</i> is a major cause of infectious exacerbations of chronic obstructive lung disease. In pulmonary epithelial cells, <i>M. catarrhalis</i> induces release of the pro-inflammatory cytokine interleukin (IL)-8, which plays a pivotal role in orchestrating airway inflammation. The present study demonstrated that protein kinase (PK)C was activated by Moraxella infection and positively regulated <i>M. catarrhalis</i>-triggered nuclear factor (NF)-κB activation and subsequent IL-8 release. Activation of the PKC/NF-κB signalling pathway was found to be dependent on expression of the Moraxella-specific ubiquitous surface protein A2. In addition, it was shown that specific isoforms of PKC play differential roles in the fine-tuning of the <i>M. catarrhalis</i>-induced NF-κB-dependent gene expression through controlling <i>il8</i> promoter activity. Inhibition of PKCα and ϵ with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKC<i>θ</i> increased, the <i>M. catarrhalis</i>-induced IL-8 transcription and cytokine release. In conclusion, it was shown that <i>Moraxella catarrhalis</i> infection activates protein kinase C and its isoforms α, ϵ and <i>θ</i>, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.
Advances in the genetics of endometriosis
Authors: Erica C Dun, Robert N Taylor, Fritz Wieser
Journal: Genome Medicine (2010)

Endometriosis is a gynecological disease characterized by implantation of endometrial tissue outside of the uterus. Early familial aggregation and twin studies noted a higher risk of endometriosis among relatives. Studies on the roles of the environment, genetics and aberrant regulation in the endometrium and endometriotic lesions of women with endometriosis suggest that endometriosis arises from the interplay between genetic variants and environmental factors. Elucidating the hereditary component has proven difficult because multiple genes seem to produce a susceptibility to developing endometriosis. Molecular techniques, including linkage and genome-wide analysis, have identified candidate genes located near known loci related to development and regulation of the female reproductive tract. As new candidate genes are discovered and hereditary pathways identified using technologies such as genome-wide analysis, the possibility of prevention and treatment becomes more tangible for millions of women affected by endometriosis. Here, we discuss the advances of genetic research in endometriosis and describe technologies that have contributed to the current understanding of the genetic variability in endometriosis, variability that includes regulatory polymorphisms in key genes.
Metabolism of bradykinin by the rat coronary vascular bed
Authors: Marie-Josée Dumoulin, Albert Adam, Charles Blais, Daniel Lamontagne
Journal: Cardiovascular Research (1998)

Objective: To study the metabolism of bradykinin (BK) after a single passage through the coronary bed in isolated Langendorff rat hearts. Methods: BK was infused into the aortic flow line to obtain a final concentration of 10 nM, and the coronary effluent was collected to quantify BK and des-Arg9-BK by competitive enzyme immunoassay. The nature of immunoreactive material was confirmed by immunograms after HPLC separation. The experiments were performed with hearts perfused at either one of the following coronary flow rates: 1, 5 or 10 ml/min. Results: BK recovery without inhibitors was 86.3±2.9, 60.8±6.3, and 29.6±6.8% at 10, 5, and 1 ml/min, respectively. The Vmax/Km ratios at these coronary flow rates were 2.19±0.72, 4.81±0.64, and 2.59±0.33 min−1 g−1, respectively. The angiotensin-converting enzyme (ACE) inhibitor, enalaprilat (130 nM), reduced BK degradation at all flow rates. Inhibition of neutral endopeptidase with retrothiorphan (25 nM) had no effect on BK degradation. However, the combined treatment with enalaprilat and retrothiorphan reduced BK degradation to lower values than enalaprilat alone. The effect of enzyme inhibitors on BK recovery was inversely related to coronary flow: inhibiting BK degradation markedly increased BK recovery at 1 ml/min, but had no effect at 10 ml/min. The kininase I metabolite of BK, des-Arg9-BK, could not be detected under these experimental conditions. Conclusions: ACE is the major enzyme responsible for BK degradation during a single passage through the coronary bed. Neutral endopeptidase contributes to BK degradation only when ACE activity is impaired. The effect of enzyme inhibitors on the coronary concentration of BK is highly dependent on coronary flow rate.
MICRONUTRIENT MALNUTRITION: Policies and Programs for Control and Their Implications
Authors: Barbara A. Underwood, Suttilak Smitasiri
Journal: Annual Review of Nutrition (1999)

Global progress in social and economic development is occurring, although slowly, in the most needy parts of the nonindustrialized world, where nutritional deficiencies, including micronutrients, remain significant public health problems. Until empowering benefits accrue from development spin-offs, policy guidance for purposeful public health actions can help reduce the unconscionable toll on health and quality of life from micronutrient malnutrition and can interrupt its intergenerational debilitating effects on national development. Narrowly focused control programs including homestead production, plant breeding, fortification, and supplementation are in effect, but in general, they have not been holistically planned and integrated into overall development programs. Such integration is needed to ensure sustainability into the next century. A new paradigm is needed, including a new way of thinking by nutrition scientists and program implementers that includes partnerships with the poor in all aspects of program planning and implementation.
Delivering Value: Provider Efforts to Improve the Quality and Reduce the Cost of Health Care
Authors: Jonathan E. Gordon, Joan M. Leiman, Emme Levin Deland, Herbert Pardes
Journal: Annual Review of Medicine (2013)

Growing concern regarding costs of care and health outcomes in the United States has led to widespread calls to address the issue of health care spending. Today, providers across the country are working both to improve the quality and to reduce the cost of health care. These activities span multiple care delivery settings and include care standardization and redesign, shared decision making, palliative care, care coordination, readmission reduction, patient engagement, predictive modeling, and direct cost reduction. These efforts differ from those undertaken in the past because of the availability of information technology tools to collect and analyze data, and because of the emphasis on cost reduction in conjunction with quality improvement. Although the available literature reflects only a small fraction of the provider activities currently in progress, there is cause for hope for achieving a sustainable, innovative, and value-driven health care system.
A major advance in ex vivo intestinal organ culture
Authors: Manon E Wildenberg, Gijs R van den Brink
Journal: Gut (2012)

Important advances are being made in our understanding of the composition and function of the large amount of commensal bacteria that the human intestine has long been known to contain. Metagenomic sequencing has shown that the microbiome of healthy individuals is different from that of patients with inflammatory bowel disease (IBD) and that the microbial composition of patients with Crohn's disease is distinct from ulcerative colitis.1 Whether such microbial alterations in patients with IBD are the cause or consequence of the disease remains to be determined.

Attempts to modulate intestinal disease with bacteria started with the treatment of acute gastrointestinal infections by Alfred Nissle with a strain of Escherichia coli in 1917. Bacterial treatments have been attempted for a large variety of indications, mainly with different Lactococcal and Bifidobacterial species. In general, the better designed trials have shown modest if any clinical effects for most diseases in humans, with the exception of some indications in ulcerative colitis and pouchitis.2 Perhaps the emerging insight into the composition of our microbiota in health and disease will lead to more rational bacterial modulation and open up truly new therapeutic avenues. The development of such disease-modifying microbiotic treatments for …
Screening for lung cancer: we still need to know more
Authors: Stephen G Spiro
Journal: Thorax (2012)

The holy grail for a screening test is that it discovers more cancers in the screened arm than in the control; that those cancers are of an earlier stage and there is, as a consequence, a stage shift towards lower stage cancers compared with the control group; that the test is acceptable to, basically, healthy individuals with low risks of serious side effects resulting from tests following a positive screen; and that the cost of a life saved, or a quality-adjusted life-year (QALY) is acceptable to the economy of the day.

Published in Thorax there is an end-of-screening report on a Danish CT-based study.1 They entered 4104 men and women, (of which 45% were women, unusually high) aged between 50 and 70 years, a 20 pack-year smoking history; lung function was recorded but was not used as an inclusion criterion. The screened group underwent five annual CTs and the control group nothing, but were seen every year. It was not stated why, or what was done to this latter group. At the end of the study period 69 cancers were found in the screened arm and 24 in the control. There were more early stage (stages I and IIB) cancers found in the screened arm than in the control arm: 48 versus 21. However, the number of advanced stage cases (IIIB and IV, and extensive disease small cell) were similar: 21 versus 16, ie, no stage shift effect. There was also a large preponderance of adenocarcinomas and bronchoalveolar cell tumours, typical of screened populations. Also, of 611 participants followed for 5 years, 1404 non-calcified nodules (NCN) were identified, another enduring problem in CT-based trials. Evaluating all deaths by the end of the study, there were 61 in the screen arm of which 15 were from lung cancer, compared with 42 deaths …
Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
Authors: Tamara Matysiak-Budnik, Ivan Cruz Moura, Michelle Arcos-Fajardo, Corinne Lebreton, Sandrine Ménard, Céline Candalh, Karima Ben-Khalifa, Christophe Dugave, Houda Tamouza, Guillaume van Niel, Yoram Bouhnik, Dominique Lamarque, Stanislas Chaussade, Georgia Malamut, Christophe Cellier, Nadine Cerf-Bensussan, Renato C. Monteiro, Martine Heyman
Journal: The Journal of Experimental Medicine (2007)

Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD.
New impact factor reflects increased quality
Authors: W. K. A. Yung
Journal: Neuro-Oncology (2012)

Neuro-Oncology is delighted to report that our 2011 Impact Factor is 5.723, a notable increase from last year's 5.483.

The Impact Factor, a metric used to assess journal quality, is calculated by dividing the number of articles published in the previous 2 years into the number of citations of those articles in the reported year (i.e., the 2011 number was determined by dividing the number of 2011 citations of articles published in 2009 and 2010 by the total number of articles published in 2009 and 2010). The formula used for Neuro-Oncology for 2011 was 1156 citations / 202 articles = 5.723. The Impact Factor is published annually by Thomson Reuters in Journal Citation Reports.


The journal is now ranked 15th of 191 clinical neurology journals (top 8%) and 22nd of 194 oncology journals (top 11%); both of these rankings are higher than last year's. 


	Year	Impact Factor	Rank
			Oncology	Clinical neurology
2011	5.723	22 of 194	15 of 191	
2010	5.483	24 of 184	15 of 185	
2009	4.984	26 of 165	17 of 167	
2008	5.000	25 of 141	15 of 156	
2007	5.806	16 of 132	6 of 146	


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Neuro-Oncology increased its publication frequency from quarterly to bimonthly in 2008 and to monthly in 2010, so we are excited to see that our rapid growth has been accompanied by sustained (and even increased) quality. Additional changes, such as requiring structured abstracts in 2012 and cell line validation statements in 2013, should further improve the journal's quality.


We thank all of you—our authors, reviewers, editors, and readers—for your contributions during the past year; we look forward to working with you to ensure that Neuro-Oncology remains the top journal in its field.
Sphingosine-1-phosphate induces contraction of valvular interstitial cells from porcine aortic valves
Authors: Wolfgang Witt, Anett Jannasch, Daniela Burkhard, Torsten Christ, Ursula Ravens, Coy Brunssen, Anja Leuner, Henning Morawietz, Klaus Matschke, Thomas Waldow
Journal: Cardiovascular Research (2012)

Sphingosine-1-phosphate (S1P) has emerged as a potent bioactive lipid with multiple functions in cardiovascular pathophysiology. Potential roles of S1P in heart valve diseases and expression of relevant receptors (S1P1, S1P2, or S1P3) in valve tissue and in valvular interstitial cells (VICs), the major cell population with essential functions in maintenance of valvular structure, are currently unknown. Exposure to S1P (62–2000 nM) of cultured VICs from porcine aortic valves on cell culture polystyrene resulted in contraction and nodule formation. The S1P-dependent contraction was completely inhibited by blockers of S1P2, RhoA, and RhoA-associated protein kinase (ROCK). Activated RhoA was clearly increased after S1P treatment, whereas activated Rac1 was only slightly reduced. In addition, exposure to S1P induced a transient increase in cytosolic Ca2+. Application of channel blockers and other effectors of Ca2+ homeostasis showed that the S1P effect is largely caused by Ca2+ release from internal stores. However, resistance to blocking S1P2, different kinetics, as well as concentration dependence exclude a major role of Ca2+ influx in S1P-induced nodule formation. In order to verify the effects in situ, contractions of valve tissue slices were measured. The S1P-induced isometric contraction of valve leaflets was of similar force amplitude as observed with adrenaline. The effect was fully reversed by blocking S1P2. The results suggest that S1P induces contraction of VICs from porcine aortic valves by signalling via S1P2, RhoA, and ROCK. In this way, S1P may contribute to regulation of tissue tension in aortic valves.
Balloon gastrostomy migration leading to acute pancreatitis
Authors: J Periselneris, R England, M Hull
Journal: Gut (2006)

A 57 year old woman with cerebrovascular disease had a 16 Fr Corflo percutaneous endoscopic gastrostomy (Merck Gastroenterology, West Drayton, Middlesex, UK) exchanged for a 20 Fr replacement Corflo balloon gastrostomy (volume 5 ml) as a bridge to eventual insertion of a permanent 20 Fr Corflo-cuBBy “button” gastrostomy. Four weeks later she presented with a seven day history of abdominal pain and vomiting. Initial investigations revealed a serum alanine transaminase level of 54 IU/l (normal range (NR) 0–35), serum alkaline phosphatase level of 491 IU/l (NR 70–300), serum bilirubin level of …
Does damage cause inflammation? Revisiting the link between joint damage and inflammation
Authors: J S Smolen, D Aletaha, G Steiner
Journal: Annals of the Rheumatic Diseases (2009)

Rheumatoid arthritis (RA) is characterised by both inflammation, as manifested by pain and swelling, and destruction of the joints. Unequivocal evidence indicates that disease activity, and thus the inflammatory response, is linked to joint damage. From this viewpoint we suggest that, vice versa, joint damage might be a cause of the active disease process, thus leading to a vicious cycle of events. The background to this notion stems from the known autoimmune response in RA, the potential of cartilage and bone breakdown products to elicit inflammation and notions that in joints that have undergone surgery with cartilage removal RA does not flare. However, the clinical evidence for this relationship is still to be provided as proof of the concept.
Radiographic stereoplotting. A new technique and its application to the study of the spine.
Authors: R K Jacoby, H Sims-Williams, M I Jayson, H Baddley
Journal: Annals of the Rheumatic Diseases (1976)

Radiographic stereoplotting is a method for taking three-dimensional measurements from a pair of x-ray films. The x-ray technique is described, as is the stereoplotter. Using this machine it is possible to locate any point within the patient and measure the distance between that point and any other point. From this information it is possible to compute areas, volumes, and angles with great accuracy, which hitherto has been impossible using noninvasive techniques. It is planned to take measurements of the spinal canal in normal backs and in patients with nonspecific back pain, in order to try to define some of these syndromes on a structural basis. It is likely that stereoplotting has some useful application in most branches of clinical medicine, since the x-ray technology is available in any diagnostic x-ray department.