tbuckley/cabot-search huggingface dataset:
Soluble E-selectin, ICAM-1 and VCAM-1 levels in systemic and coronary circulation in patients with variant angina
Authors: Kunihisa Miwa, Akihiko Igawa, Hiroshi Inoue
Journal: Cardiovascular Research (1997)

Objective: The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation. Methods: Antecubital venous plasma samples were collected from 33 patients with variant angina, 22 patients with stable effort angina and 20 control subjects. Samples were also collected from the aortic root (AO) and the coronary sinus (CS) in 18 patients with variant angina before and after left coronary spasm induced by intracoronary injection of acetylcholine. The soluble adhesion molecules were assayed by enzyme immunoassay. Results: Antecubital venous plasma soluble E-selectin (P<.05), ICAM-1 (P<.01) and VCAM-1 (NS) levels were higher in the variant angina group than in the control group, respectively. The plasma soluble ICAM-1 level was also higher (P<.01) in the variant angina group than in the stable effort angina group. In the variant angina group, both soluble ICAM-1 (P<.05) and VCAM-1 (P<.01) levels were significantly lower in CS than AO at baseline. In contrast, after the spasm the plasma soluble ICAM-1 level was (P<.05) higher in CS than AO and the CS–AO differences of soluble ICAM-1 (P<.05) and VCAM-1 (P<.05) increased as compared with the baseline, respectively. These values were remained unchanged in the stable effort angina group after rapid atrial pacing and in the control group after administration of acetylcholine. Conclusions: Circulating plasma levels of both soluble E-selectin and ICAM-1 were elevated in patients with variant angina, indicating an association of an inflammatory reaction with coronary spasm. Both soluble ICAM-1 and VCAM-1 appeared to be trapped in the coronary circulation at baseline and released into the coronary circulation following coronary spasm and reperfusion in the patients.
Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up
Authors: Fritz H Schröder, Jonas Hugosson, Monique J Roobol, Teuvo L J Tammela, Marco Zappa, Vera Nelen, Maciej Kwiatkowski, Marcos Lujan, Liisa Määttänen, Hans Lilja, Louis J Denis, Franz Recker, Alvaro Paez, Chris H Bangma, Sigrid Carlsson, Donella Puliti, Arnauld Villers, Xavier Rebillard, Matti Hakama, Ulf-Hakan Stenman, Paula Kujala, Kimmo Taari, Gunnar Aus, Andreas Huber, Theo H van der Kwast, Ron H N van Schaik, Harry J de Koning, Sue M Moss, Anssi Auvinen
Journal: The Lancet (2014)
Myocyte/capillary mismatch in the heart of uremic patients.
Authors: K Amann, M Breitbach, E Ritz, G Mall
Journal: Journal of the American Society of Nephrology (1998)

Experiments indicate that capillary density is reduced in the hypertrophied left ventricle of rats with subtotal nephrectomy compared to control rats with similar BP and left ventricular hypertrophy, suggesting that in uremia, hypertrophying cardiomyocytes outgrow their capillary supply. No information on myocardial capillary supply in humans is currently available. The hearts of nine dialyzed patients, nine patients with essential hypertension, and 10 normotensive control subjects at postmortem were obtained. Subjects with stenosing coronary lesions and left ventricular pump failure were excluded. Special sampling procedures were used to exclude stereologic artefacts. Capillaries were specifically stained with ulex lectin and analyzed by stereologic techniques. Length density of myocardial capillaries (Lv; mm/mm3) was significantly (P < 0.001) lower in dialyzed patients (1483 +/- 238) than in patients with essential hypertension (1872 +/- 243) or in normotensive control patients (2898 +/- 456). In parallel, myocyte diameter and volume density of myocardial interstitial tissue were significantly (P < 0.001) increased in uremic patients compared to patients with essential hypertension and control patients, respectively. Diminished left ventricular capillary supply in renal failure must increase critical oxygen diffusion distance in the myocardium, thus exposing cardiomyocytes to the risk of hypoxia. It is unknown whether such reduced ischemia tolerance can be reversed by increasing oxygen supply (e.g., by reversing anemia).
Molecular Control of Iron Transport
Authors: Tomas Ganz
Journal: Journal of the American Society of Nephrology (2007)

The iron-regulatory hormone hepcidin is a 25-amino acid peptide that is synthesized in hepatocytes. Hepcidin binds to the cellular iron export channel ferroportin and causes its internalization and degradation and thereby decreases iron efflux from iron exporting tissues into plasma. By this mechanism, hepcidin inhibits dietary iron absorption, the efflux of recycled iron from splenic and hepatic macrophages, and the release of iron from storage in hepatocytes. Hepcidin synthesis is stimulated by plasma iron and iron stores and is inhibited by erythropoietic activity, ensuring that extracellular plasma iron concentrations and iron stores remain stable and the erythropoietic demand for iron is met. During inflammation, increased hepcidin concentrations cause iron sequestration in macrophages, resulting in hypoferremia and eventually anemia of inflammation. Hepcidin deficiency plays a central role in most iron overload disorders. The role of hepcidin abnormalities in anemias that are associated with renal disease and in resistance to erythropoietic therapies remains to be elucidated.
Psychosocial Therapies in Diabetes
Authors: Alan M. Delamater, Alan M. Jacobson, Barbara Anderson, Daniel Cox, Lawrence Fisher, Patrick Lustman, Richard Rubin, Timothy Wysocki
Journal: Diabetes Care (2001)

OBJECTIVE—To review key advances in the behavioral science literature related to psychosocial issues and therapies for persons with diabetes, to discuss barriers to research progress, and to make recommendations for future research. RESEARCH DESIGN AND METHODS—Key findings from the literature on psychosocial research in diabetes are reviewed separately for children and adults. Specific issues covered include psychosocial adjustment and psychiatric disorders, neurocognitive functioning, quality of life, and psychosocial therapies. Barriers that must be addressed to allow research in this area to progress are discussed. Recommendations are then made concerning high-priority areas for advancing research in the field. CONCLUSIONS—A substantial amount of behavioral science research has demonstrated that psychosocial factors play an integral role in the management of diabetes in both children and adults. Research has also shown the efficacy of a number of psychosocial therapies that can improve regimen adherence, glycemic control, psychosocial functioning, and quality of life. More research in this area is needed to develop psychosocial intervention programs for specific patient populations and to demonstrate the cost-effectiveness of these approaches.
Artefacts in measuring joint moments may lead to incorrect clinical conclusions: the nexus between science (biomechanics) and sports injury prevention!
Authors: Eirik Kristianslund, Tron Krosshaug, Antonie J van den Bogert
Journal: British Journal of Sports Medicine (2012)

Measuring joint moments at high speed is integral for sports-related research, but substantial artefacts can arise with certain computational methods. This is relevant for BJSM readers as measurement errors can lead to flawed conclusions. Potential settings where errors have the potential to creep in include anterior cruciate ligament (ACL) risk factor studies, running biomechanics analysis and other fields where biomechanists study fast movements. Our recent paper in Journal of Biomechanics demonstrated the effect of different filtering of force and marker data in joint moment calculations.1 This paper explains those findings for the clinical readership of BJSM and highlights the areas where it may be wise to ‘proceed with caution’ when interpreting previous studies that aim to identify key risk factors for injury.

Estimates of joint moments are fundamental in the study of sporting motion. Joint moments calculated in standard motion analysis are net joint moments, the total effect of all structures that produce forces that work across the joint. Joint moments stem from muscle forces, articular contact and ligaments. We are interested in joint moments because, unlike these separate forces, they can be measured. A correct interpretation of joint moments may help us understand which muscles and ligaments are at risk of injury in certain settings.

If biomechanics is not your thing, feel free to skip down to ‘Implications’ below. Joint moments are normally calculated through the process of inverse dynamics, where ground reaction forces (force plate data) and segment accelerations (marker data—the reflective markers attached to the participant) are combined.

In all high-impact movements, such as running and sidestep cutting, it is normal to see an impact peak in ground reaction force that will result in high acceleration of body segments. Unfortunately, due to random noise in the measurement of marker positions, current motion analysis systems cannot reliably …
Five-Year Outcomes in High-Risk Participants in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) Study
Authors: Shanti Bansal, Frans J.Th. Wackers, Silvio E. Inzucchi, Deborah A. Chyun, Janice A. Davey, Lawrence H. Staib, Lawrence H. Young
Journal: Diabetes Care (2010)

To estimate baseline cardiovascular risk of 1,123 participants in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study and to assess cardiac event rates and the effect of screening on outcomes in these higher-risk participants.Baseline cardiovascular risk was assessed using four established methods: Framingham score, UK Prospective Diabetes Study (UKPDS) risk engine, criteria of the French-Speaking Association for the Study of Diabetes and Metabolic Diseases, and the presence or absence of metabolic syndrome. Cardiac events (cardiac death or nonfatal myocardial infarction) were assessed during the 4.8-year follow-up in participants with intermediate/high cardiovascular risk.By various risk-stratification approaches, 53-75% of participants were defined as having intermediate or high cardiovascular risk. The prevalence of inducible ischemia on screening in these individuals ranged from 21 to 24%, similar to lower-risk participants (19-23%). Cardiac event rates were greater in intermediate-/high-risk versus low-risk groups, but this was only significant for the UKPDS risk engine (4.2 vs. 1.2%, P = 0.002). The annual cardiac event rate was <1% in all risk groups, except in the high-risk UKPDS group (∼2% per year). In intermediate-/high-risk participants randomized to screening versus no screening, 4.8-year cardiac event rates were similar (2.5-4.8% vs. 3.1-3.7%).A substantial portion of the DIAD population was defined as having intermediate/high baseline cardiovascular risk. Nevertheless, their annual cardiac event rate was low and not altered by routine screening for inducible ischemia.
The Melanocortin-4 Receptor: Physiology, Pharmacology, and Pathophysiology
Authors: Ya-Xiong Tao
Journal: Endocrine Reviews (2010)

The melanocortin-4 receptor (MC4R) was cloned in 1993 by degenerate PCR; however, its function was unknown. Subsequent studies suggest that the MC4R might be involved in regulating energy homeostasis. This hypothesis was confirmed in 1997 by a series of seminal studies in mice. In 1998, human genetic studies demonstrated that mutations in the MC4R gene can cause monogenic obesity. We now know that mutations in the MC4R are the most common monogenic form of obesity, with more than 150 distinct mutations reported thus far. This review will summarize the studies on the MC4R, from its cloning and tissue distribution to its physiological roles in regulating energy homeostasis, cachexia, cardiovascular function, glucose and lipid homeostasis, reproduction and sexual function, drug abuse, pain perception, brain inflammation, and anxiety. I will then review the studies on the pharmacology of the receptor, including ligand binding and receptor activation, signaling pathways, as well as its regulation. Finally, the pathophysiology of the MC4R in obesity pathogenesis will be reviewed. Functional studies of the mutant MC4Rs and the therapeutic implications, including small molecules in correcting binding and signaling defect, and their potential as pharmacological chaperones in rescuing intracellularly retained mutants, will be highlighted.
Association of SEEK1 and psoriatic arthritis in two distinct Canadian populations
Authors: P Rahman
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To examine the relationship between SNP +39604 in <i>SEEK1</i> and psoriatic arthritis (PsA) in two distinct Canadian populations. <b>Methods:</b> 103 patients with PsA and 105 ethnically matched controls from Newfoundland and 202 patients with PsA and 100 controls from Ontario were studied. Patients and controls were genotyped for SNP +39604 of <i>SEEK1</i> by time of flight mass spectrometry, using the Sequenom platform. Genomic DNA was amplified by the Dynal RELI SSO HLA- Cw* typing kit for HLA-C typing. <b>Results:</b> The frequency of the minor <i>SEEK1</i>(T) allele in subjects with PsA and controls was 48.5% and 32.4%, respectively (odds ratio (OR) = 2.0; p = 0.017), in the Newfoundland population and 46.5% and 38.0%, respectively (OR = 1.4; p = 0.16), in the Ontario population. Although <i>SEEK1</i> is associated with PsA, particularly in the Newfoundland population, multivariate analysis showed that <i>SEEK1</i> does not seem to be a further susceptibility factor if the HLA-Cw*0602 status is already known. No association was noted between <i>SEEK1</i>(T) allele and onset of psoriasis, PsA, or arthritis pattern. <b>Conclusion:</b><i>SEEK1</i> is associated with PsA in the Newfoundland founder population. This association is probably due to linkage disequlibrium between <i>SEEK1</i> and HLA-Cw*0602 in this population.
Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma
Authors: Pieter Sonneveld, Emilie Asselbergs, Sonja Zweegman, Bronno van der Holt, Marie Jose Kersten, Edo Vellenga, Marinus van Marwijk-Kooy, Annemiek Broyl, Okke de Weerdt, Sarah Lonergan, Antonio Palumbo, Henk Lokhorst
Journal: Blood (2014)
Environmental Tobacco Smoke
Authors: Deborah E. Barnes
Journal: JAMA (1995)

To examine the tobacco industry's public and private responses to rising concern over the health effects of environmental tobacco smoke (ETS).Documents from Brown and Williamson Tobacco Corporation (B&W), the British American Tobacco Company (BAT), and other tobacco interests provided by an anonymous source, obtained from Congress, and received from the private papers of a former BAT officer.All available materials, including confidential reports regarding research and internal memoranda exchanged between tobacco industry lawyers.Privately, B&W and BAT began conducting research related to ETS in the mid 1970s. BAT researchers appear to have determined that sidestream smoke produces irritation, that it contains toxic substances including N-nitrosamines, and that it is "biologically active" (eg, carcinogenic) in laboratory tests. During the 1980s, the primary purpose of BAT's research related to ETS was to develop a new cigarette that emitted less irritating and less biologically active sidestream smoke. Publicly, the tobacco industry has denied that exposure to ETS has been proven dangerous to health. It has criticized the methodology of published research on ETS, even when some of its own consultants have privately acknowledged that the research was valid. In addition, the industry has funded scientific research with the stated purpose of anticipating and refuting the evidence against ETS. The tobacco industry's strategy regarding passive smoking has been remarkably similar to its strategy regarding active smoking. It has privately conducted internal research, at least some of which has supported the conclusion that passive smoking is dangerous to health, while it has publicly denied that the hazards have been proven.
Bronchial Smooth Muscle Remodeling in Nonsevere Asthma
Authors: Pierre-Olivier Girodet, Benoit Allard, Matthieu Thumerel, Hugues Begueret, Isabelle Dupin, Olga Ousova, Régis Lassalle, Elise Maurat, Annaig Ozier, Thomas Trian, Roger Marthan, Patrick Berger
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Increased bronchial smooth muscle (BSM) mass is a key feature of airway remodeling that classically distinguishes severe from nonsevere asthma. Proliferation of BSM cells involves a specific mitochondria-dependent pathway in individuals with severe asthma. However, BSM remodeling and mitochondrial biogenesis have not been examined in nonsevere asthma.Objectives: We aimed to assess whether an increase in BSM mass was also implicated in nonsevere asthma and its relationship with mitochondria and clinical outcomes.Methods: We enrolled 34 never-smoker subjects with nonsevere asthma. In addition, we recruited 56 subjects with nonsevere asthma and 19 subjects with severe asthma as comparative groups (COBRA cohort [Cohorte Obstruction Bronchique et Asthme; Bronchial Obstruction and Asthma Cohort; sponsored by the French National Institute of Health and Medical Research, INSERM]). A phenotypic characterization was performed using questionnaires, atopy and pulmonary function testing, exhaled nitric oxide measurement, and blood collection. Bronchial biopsy specimens were processed for immunohistochemistry and electron microscopy analysis. After BSM remodeling assessment, subjects were monitored over a 12-month period.Measurements and Main Results: We identified characteristic features of remodeling (BSM area >26.6%) and increased mitochondrial number within BSM in a subgroup of subjects with nonsevere asthma. The number of BSM mitochondria was positively correlated with BSM area (r = 0.78; P < 0.001). Follow-up analysis showed that subjects with asthma with high BSM had worse asthma control and a higher rate of exacerbations per year compared with subjects with low BSM.Conclusions: This study reveals that BSM remodeling and mitochondrial biogenesis may play a critical role in the natural history of nonsevere asthma (Mitasthme study).Clinical trial registered with www.clinicaltrials.gov (NCT00808730).
Full-Dose Gemcitabine With Concurrent Radiation Therapy in Patients With Nonmetastatic Pancreatic Cancer: A Multicenter Phase II Trial
Authors: William Small, Jordan Berlin, Gary M. Freedman, Theodore Lawrence, Mark S. Talamonti, Mary F. Mulcahy, A. Bapsi Chakravarthy, Andre A. Konski, Mark M. Zalupski, Philip A. Philip, Timothy J. Kinsella, Nipun B. Merchant, John P. Hoffman, Al B. Benson, Steven Nicol, Rong M. Xu, John F. Gill, Cornelius J. McGinn
Journal: Journal of Clinical Oncology (2008)

Gemcitabine is effective in the treatment of pancreatic cancer and is a potent radiosensitizer. This study assessed safety and efficacy of full-dose gemcitabine administered before and during concurrent three-dimensional conformal radiation (3D-CRT) in patients with nonmetastatic pancreatic cancer.During cycles 1 and 3, patients received gemcitabine at 1,000 mg/m(2) on days 1 and 8 of each 21-day cycle. Cycle 2 included the same dose of gemcitabine on days 1, 8, and 15 of a 28-day cycle with concurrent 3D-CRT at 36 Gy, administered in 15 fractions of 2.4 Gy, over 3 weeks. Resectable patients underwent surgery 4 to 6 weeks after treatment. The primary objective was evaluation of toxicity. Tumor response, CA 19-9, and 1-year survival were also assessed.Forty-one patients enrolled at six institutions between April 2002 and October 2003. Among the 39 treated patients, the most common toxicities were grade 3 neutropenia (12.8%), grade 3 nausea (10.3%), and grade 3 vomiting (10.3%). The response rate was 5.1% and disease control rate was 84.6%. Mean post-treatment CA 19-9 levels (228 +/- 347 U/mL) were significantly (P = .006) reduced compared with pretreatment levels (1,241 +/- 2,124 U/mL). Thirteen (81%) of 16 patients initially judged resectable, three (33%) of nine borderline-resectable patients, and one (7%) of 14 unresectable patients underwent resection after therapy. One-year survival rates were 73% for all patients, 94% for resectable patients, 76% for borderline-resectable patients, and 47% for unresectable patients.Full-dose gemcitabine with concurrent radiotherapy was well tolerated and active. Evaluation of this regimen in a larger, randomized trial for patients with resectable or borderline-resectable disease may be warranted.
Comparative genomics reveals a constant rate of origination and convergent acquisition of functional retrogenes in Drosophila.
Authors: Yongsheng Bai, Claudio Casola, Cédric Feschotte, Esther Betrán
Journal: Genome biology (2007)

Abstract Background Processed copies of genes (retrogenes) are duplicate genes that originated through the reverse-transcription of a host transcript and insertion in the genome. This type of gene duplication, as any other, could be a source of new genes and functions. Using whole genome sequence data for 12 Drosophila species, we dated the origin of 94 retroposition events that gave rise to candidate functional genes in D. melanogaster . Results Based on this analysis, we infer that functional retrogenes have emerged at a fairly constant rate of 0.5 genes per million years per lineage over the last approximately 63 million years of Drosophila evolution. The number of functional retrogenes and the rate at which they are recruited in the D. melanogaster lineage are of the same order of magnitude as those estimated in the human lineage, despite the higher deletion bias in the Drosophila genome. However, unlike primates, the rate of retroposition in Drosophila seems to be fairly constant and no burst of retroposition can be inferred from our analyses. In addition, our data also support an important role for retrogenes as a source of lineage-specific male functions, in agreement with previous hypotheses. Finally, we identified three cases of functional retrogenes in D. melanogaster that have been independently retroposed and recruited in parallel as new genes in other Drosophila lineages. Conclusion Together, these results indicate that retroposition is a persistent mechanism and a recurrent pathway for the emergence of new genes in Drosophila .