tbuckley/cabot-search huggingface dataset:
Phospholemman Phosphorylation Mediates the Protein Kinase C–Dependent Effects on Na <sup>+</sup> /K <sup>+</sup> Pump Function in Cardiac Myocytes
Authors: Fei Han, Julie Bossuyt, Sanda Despa, Amy L. Tucker, Donald M. Bers
Journal: Circulation Research (2006)

Because phospholemman (PLM) regulates the Na(+)/K(+) pump (NKA) and is a major cardiac phosphorylation target for both protein kinase A (at Ser68) and protein kinase C (PKC) (at both Ser63 and Ser68), we evaluated whether PLM mediates the PKC-dependent regulation of NKA function and protein kinase A/PKC crosstalk in ventricular myocytes. PKC was activated by PDBu (300 nmol/L), and we measured NKA-mediated [Na(+)](i) decline (fluorescence measurements) and current (I(pump)) (voltage clamp). In wild-type mouse myocytes, PDBu increased PLM phosphorylation at Ser63 and Ser68, I(pump) (both at 10 and 100 mmol/L Na(+) in the pipette solution) and maximal NKA-mediated Na(+) extrusion rate (V(max)) from 7.9+/-1.1 to 12.7+/-1.9 mmol.L(-1) per minute without altering NKA affinity for internal Na(+) (K(0.5)). In PLM knockout mice, PDBu had no effect on either V(max) or K(0.5). After pretreatment with isoproterenol (ISO) (1 mumol/L), PDBu still increased the NKA V(max) and PLM phosphorylation at Ser63 and Ser68. Conversely, after pretreatment with PDBu, ISO further increased the Na(+) affinity of NKA and phosphorylation at Ser68, as it did alone without PDBu. The final NKA activity was independent of the application sequence. The NKA activity in PLM knockout myocytes, after normalizing the protein level, was similar to that after PDBu and ISO treatment. We conclude that (1) PLM mediates the PKC-dependent activation of NKA function in cardiac myocytes, (2) PDBu and ISO effects are additive in the mouse (affecting mainly V(max) and K(0.5), respectively), and (3) PDBu and ISO combine to activate NKA in wild-type to the level found in the PLM knockout mouse.
Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial
Authors: John Burn, Anne-Marie Gerdes, Finlay Macrae, Jukka-Pekka Mecklin, Gabriela Moeslein, Sylviane Olschwang, Diane Eccles, D Gareth Evans, Eamonn R Maher, Lucio Bertario, Marie-Luise Bisgaard, Malcolm G Dunlop, Judy WC Ho, Shirley V Hodgson, Annika Lindblom, Jan Lubinski, Patrick J Morrison, Victoria Murday, Raj Ramesar, Lucy Side, Rodney J Scott, Huw JW Thomas, Hans F Vasen, Gail Barker, Gillian Crawford, Faye Elliott, Mohammad Movahedi, Kirsi Pylvanainen, Juul T Wijnen, Riccardo Fodde, Henry T Lynch, John C Mathers, D Timothy Bishop
Journal: The Lancet (2011)
Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist
Authors: M-R. Blanchet, E. Israël-Assayag, Y. Cormier
Journal: European Respiratory Journal (2005)

Nicotinic agonists, including 1,1-dimethyl-4-phenylpiperazinium (DMPP), have anti-inflammatory properties and in some instances smooth muscle relaxing effects. Since inflammation and airway smooth muscle contraction are two major components of asthma, the present authors investigated the effects of DMPP on airway inflammation and airway resistance in a mouse model of asthma. Mice were sensitised and challenged with ovalbumin (OVA) and treated either intraperitoneally or intranasally with DMPP. The effect of DMPP was tested on airway inflammation, airway resistance and on the increase of intracellular calcium in bronchial smooth muscle cells. DMPP given either during sensitisation, OVA challenges or throughout the protocol prevented lung inflammation and decreased the serum level of OVA specific immunoglobulin E. DMPP administration reduced the number of total cells, lymphocytes and eosinophils in the bronchoalveolar lavage (BAL) fluid. Intranasal DMPP administration was as effective as dexamethasone (DEXA) in reducing total cell count and eosinophil counts in BAL fluid. DMPP, but not DEXA, reduced tissue inflammation. Intranasal DMPP, given 10 min before the test, reduced airway responsiveness to metacholine. DMPP also reduced the increase in intracellular calcium in response to bradykinin. In conclusion, these results show that 1,1-dimethyl-4-phenylpiperazinium reduces lung inflammation and prevents airway hyperresponsiveness in the mouse model of asthma.
A PAI-1 Mutant, PAI-1R, Slows Progression of Diabetic Nephropathy
Authors: Yufeng Huang, Wayne A. Border, Ling Yu, Jiandong Zhang, Daniel A. Lawrence, Nancy A. Noble
Journal: Journal of the American Society of Nephrology (2008)

Plasminogen activator inhibitor-1 (PAI-1) has been implicated in renal fibrosis. In vitro, PAI-1 inhibits plasmin generation, and this decreases mesangial extracellular matrix turnover. PAI-1R, a mutant PAI-1, increases glomerular plasmin generation, reverses PAI-1 inhibition of matrix degradation, and reduces disease in experimental glomerulonephritis. This study sought to determine whether short-term administration of PAI-1R could slow the progression of glomerulosclerosis in the db/db mouse, a model of type 2 diabetes in which mesangial matrix accumulation is evident by 20 wk of age. Untreated uninephrectomized db/db mice developed progressive albuminuria and mesangial matrix expansion between weeks 20 and 22, associated with increased renal mRNA encoding alpha1(I) and (IV) collagens and fibronectin. Treatment with PAI-1R prevented these changes without affecting body weight, blood glucose, glycosylated hemoglobin, creatinine, or creatinine clearance; therefore, PAI-1R may prevent progression of glomerulosclerosis in type 2 diabetes.
Role of TBX1 in human del22q11.2 syndrome
Authors: Hisato Yagi, Yoshiyuki Furutani, Hiromichi Hamada, Takashi Sasaki, Shuichi Asakawa, Shinsei Minoshima, Fukiko Ichida, Kunitaka Joo, Misa Kimura, Shin-ichiro Imamura, Naoyuki Kamatani, Kazuo Momma, Atsuyoshi Takao, Makoto Nakazawa, Nobuyoshi Shimizu, Rumiko Matsuoka
Journal: The Lancet (2003)
The AIM2 inflammasome is critical for innate immunity to Francisella tularensis
Authors: Teresa Fernandes-Alnemri, Je-Wook Yu, Christine Juliana, Leobaldo Solorzano, Seokwon Kang, Jianghong Wu, Pinaki Datta, Margaret McCormick, Lan Huang, Erin McDermott, Laurence Eisenlohr, Carlisle P Landel, Emad S Alnemri
Journal: Nature Immunology (2010)
Metabolic Syndrome: A Clinical and Molecular Perspective
Authors: David E. Moller, Keith D. Kaufman
Journal: Annual Review of Medicine (2004)

The metabolic syndrome is a cluster of interrelated common clinical disorders, including obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidemia (hypertriglyceridemia and low HDL cholesterol levels). According to recently defined criteria, the metabolic syndrome is prevalent and is associated with a greater risk of atherosclerotic cardiovascular disease than any of its individual components. Primary defects in energy balance that produce obesity (and visceral adiposity in particular) are sufficient to drive all aspects of the syndrome. Increased free fatty acids and lipid accumulation in certain organs are mediators of insulin resistance. Obesity also leads to a proinflammatory and prothrombotic state that potentiates atherosclerosis. Pathways leading directly from adiposity to the genesis of dyslipidemia and hypertension have been elucidated. Recent knowledge implies a role for fat-derived “adipokines,” including TNFα and adiponectin, as pathogenic contributors or protective factors. Current therapies include diet and exercise as well as agents indicated for the treatment of individual components of the syndrome. Future therapies may accrue from the aggressive pursuit of newer molecular drug targets that have the potential to prevent or treat multiple aspects of the metabolic syndrome.
The dynamics of the lung fluid filtration system in dogs with edema.
Authors: M H Gee, J A Spath
Journal: Circulation Research (1980)

We studied the relationship between pulmonary microvasculature fluid filtration pressures and lung lymph flow rate (Q L ) as filtration pressures increased to determine why lungs with functional lymphatics become edematous and, as filtration pressures decreased, to determine the effect of edema formation on lymphatic function.Edema was induced by rapid intravenous infusion of neutralized Ringer's solution in a volume equivalent to 30% of body weight in seven anesthetized dogs.Pulmonary microvascular pressure (Pmv) and (JL increased to 58 cm H2O and 40 ml/hr, respectively, during the infusion.Initially, QL increased slowly and the estimated net fluid filtration pressure (£p) increased rapidly with infusion.Later in the 30-minute infusion period, small increases in £ P produced greater changes in Q L .Over a 3-hour postinfusion period, Pmv and Q L decreased, but they remained significantly greater than baseline levels.During the postinfusion period, Q L was a linear function of Pmv and a logarithmic function of £P.Extravascular lung water content, measured postmortem, was 70% greater than normal.The relationship between Q L and £P during and after the infusion demonstrated marked hysteresis.These results suggest that extravascular fluid accumulated in the lung in part because the lymphatics responded relatively slowly to rapid increases in £ P .Furthermore, the data suggest that, although the lymphatics may not be a quantitatively important route for removal of edema fluid, the pressure-volume characteristics of the pulmonary interstitium seem to have a major influence on lymphatic function.
High-Dose Immunoglobulin Therapy for Severe IgA Nephropathy and Henoch-Schonlein Purpura
Authors: Guy Rostoker
Journal: Annals of Internal Medicine (1994)

Objective: To determine if polyvalent IgG is promising therapy for severe IgA nephropathy. Design: Open prospective cohort study. Setting: Referral nephrology unit. Patients: 11 adult patients with severe IgA nephropathy (9 who had idiopathic disease and 2 who had Henoch-Schonlein purpura) and indicators of poor prognosis. Intervention: Patients were given high-dose immunoglobulins (2 g/kg each month) for 3 successive months, followed by intramuscular immunoglobulins (preparation content, 16.5%; 0.35 mL/kg every 15 days) for another 6 months. Measurements: Histologic changes were analyzed by comparing pre- and post-therapy renal biopsy specimens blindly, using an activity index (14-point scale), a sclerosis index (10-point scale), and a semiquantitative immunofluorescence test of immune deposits. Proteinuria, hematuria, leukocyturia, enzymuria, and global renal function (creatinine and polyfructosan clearances) were evaluated before and after intervention. Results: Proteinuria (median level before intervention, 5.20 g/d; median level after intervention, 2.25 g/d), hematuria, and leukocyturia decreased substantially. The decrease in glomerular filtration rate was greatly slowed or stopped (median rate of decline in glomerular filtration before, −3.78 mL/min per month; after, 0 mL/min per month). The histologic index of activity (median index before, 5; after, 2) and the staining intensity of glomerular IgA and C3 deposits also decreased. Immunoglobulin therapy was well tolerated. Conclusions: Immunoglobulin therapy may be effective in treating severe IgA nephropathy and protecting renal function. However, prospective controlled trials must confirm these preliminary results.
'How Do You Do, Miss Manners.... I'm Dave, Your Doctor'
Authors: G. David Dixon
Journal: JAMA (1985)

<h3>To the Editor.—</h3> The editorial in the July 12th issue by Dr King<sup>1</sup>left me a bit perplexed. His opening statement, "How should a physician address his patients?" was answered in his final paragraph by "if you are a mature patient and your doctor calls you by your first name, then in return address him by his first name." The question posed seems addressed to his physician audience; however, the reply seems addressed to the physician's patients. In considering the question of how to address patients, a recent column by "Miss Manners" is notable (<i>Minne</i><i>apolis Star and Tribune</i>, April 24, 1985, p 15DX). In it, columnist Judith Martin attacks the "unauthorized use of first names in impersonal situations as, for example, by doctors and nurses who have the mistaken notion that this makes patients feel better." The following day, the<i>Minneapolis Star and Tribune</i>commented on this position
The Toll–Interleukin-1 Receptor Member SIGIRR Regulates Colonic Epithelial Homeostasis, Inflammation, and Tumorigenesis
Authors: Hui Xiao, Muhammet Fatih Gulen, Jinzhong Qin, Jianhong Yao, Katarzyna Bulek, Danielle Kish, Cengiz Zubeyir Altuntas, David Wald, Caixia Ma, Hang Zhou, Vincent K. Tuohy, Robert L. Fairchild, Carol de la Motte, Daniel Cua, Bruce A. Vallance, Xiaoxia Li
Journal: Immunity (2007)
International Union of Pharmacology XLIV. Nomenclature for the Oxoeicosanoid Receptor
Authors: Charles Brink, Sven-Erik Dahlén, Jeffrey Drazen, Jilly F. Evans, Douglas W. P. Hay, G. Enrico Rovati, Charles N. Serhan, Takao Shimizu, Takehiko Yokomizo
Journal: Pharmacological Reviews (2004)

Oxoeicosanoids are a family of biologically active arachidonic acid derivatives that have been intimately linked with cellular migration. These metabolites are not only potent chemotaxins but also elicit oxygen radical production as well as induce secretory events in different cells. The most potent native ligand reported is 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), and the cell membrane receptor activated has now been cloned. This receptor is distinct from those receptors activated by either the prostaglandins or the leukotrienes. The purpose of this review is to briefly summarize the molecular evidence and highlight the significance of this receptor. In addition, an official nomenclature for this oxoeicosanoid receptor is proposed.
Windows on Renal Biopsy Interpretation
Authors: Liliane J. Striker, Gary E. Striker
Journal: Journal of the American Society of Nephrology (2003)

Renal biopsies, introduced in the 1960s, have become a commonly used clinical diagnostic tool. While they have provided considerable descriptive information and have allowed the classification of histologic changes in both native and allograft kidneys, the prediction of progression or regression has
The Issue of CPR
Authors: Carin M. Olson
Journal: JAMA (1992)

The 1992 Guidelines on Cardiopulmonary Resuscitation and Emergency Cardiac Care are published in this issue ofThe JOURNALas reports of low rates of meaningful survival from attempted cardiopulmonary resuscitation (CPR) continue to raise questions about the efficacy and appropriateness of CPR in certain instances and among certain populations. Survival to hospital discharge has been reported as 2% among 3221 victims of nontraumatic out-of-hospital cardiac arrest in Chicago—and only 3% among those whose initial rhythm was ventricular fibrillation<sup>1</sup>; 0 among 185 people who arrested outside the hospital and failed attempts at prehospital resuscitation<sup>2</sup>; and 0 among 45 residents of long-term care facilities who were at least 60 years old.<sup>3</sup> Earlier reports of survival to hospital discharge have been similarly dismal for those failing prehospital resuscitation<sup>4</sup>; for nursing home residents<sup>5</sup>; for patients at least 70 years old arresting either<sup>6</sup>in or out of the hospital
PTU-023 The use of Prokinetics in Small-Bowel Capsule Endoscopy: a Systematic Review and Meta-Analysis
Authors: A Koulaouzidis, A Giannakou, D E Yung, J N Plevris
Journal: Gut (2013)

<h3>Introduction</h3> Small-bowel capsule endoscopy (SBCE) is often limited by incomplete small-bowel transit. Although there are available meta-analysis data on the use of purgatives in SBCE, there is no similar data or consensus regarding the regular use of prokinetics for capsule ingestion. Our aim was to systematically review existing literature on the use of prokinetics in SBCE. <h3>Methods</h3> Thorough and extensive, recursive search of PubMed/MEDLINE, Embase and Scopus databases for studies, published to the end of Nov 2012, was performed. No language, time or age limits were used. Abroad search strategy was employed, using the MeSH term <b>"capsule endoscopy</b>" connected with the following keywords by "AND": "<b>prokinetic</b>", "<b>promotility</b>", "<b>metoclopramide</b>", "<b>domperidone</b>", "<b>erythromycin</b>", "<b>antiemetic</b>", "<b>ondensetron</b>", "<b>completion</b>", "<b>gastric emptying</b>", "<b>transit</b>", "<b>ingestion</b>", "<b>preparation</b>", "<b>oral/liquid</b>", "<b>intramuscular</b>" &amp; "<b>retention</b>". Additionally, the reference list of all the selected articles was manually checked for potentially suitable references that were not identified by the initial search. Studies were selected based on title and/or abstract. Eligible studies were included if the met <b>all</b> of the following criteria: (1)published as full articles of randomised control trials, (2)contained information on the type of the SBCE system used, (3)used prokinetics in (at least) one of the reported study arms/groups, (4)specified the type and dose of prokinetics used &amp; (5)contained data on the rate of SBCE completion to caecum (CR). Data were extracted by the first author using a predifined Excel sheet. Primary end-point: the effect of prokinetics to SBCE CR. <h3>Results</h3> A total of 13 studies (all prospective, randomised-controlled, single-centre; total of 1439 subjects) was selected for final review and analysis. In 11 of them, PillCam® (Given®Imaging Ltd) was used; 2 studies were performed with OMOM® (Chongqingjinshan Science &amp; Tech Co, Ltd). 6 studies were designed to look at the value of metoclopramide vs control. In the remainder, other type of prokinetic factors (Erythromycin, Mosapride, Lubiprostone, Deikenchuto or chewing gum) was administered. Using random effects model analysis, the use of prokinetics seem to improve CR in SBCE (OR = 1.888, 95% C.I. = 1.178, 3.02; <i>I</i><sup><i>2</i></sup> = 52.5%, <i>P</i> = 0.014). Moreover, in the sub-analysis for metoclopramide studies using fixed effect model, the results were similar (OR = 1.711 95% C.I. = 1.138, 2.573; <i>I</i><sup><i>2</i></sup> = 42.3%, <i>P</i> = 0.123). <h3>Conclusion</h3> Pooled data show that in comparison to no prokinetic, any type of administered prokinetic factor, before SBCE, improves the SBCE completion rate. Furthermore, most data to present are behind the use of Metoclopramide. <h3>Disclosure of Interest</h3> None Declared
Using Consensus Networks to Visualize Contradictory Evidence for Species Phylogeny
Authors: B. R. Holland
Journal: Molecular Biology and Evolution (2004)

Building species phylogenies from genome data requires the evaluation of phylogenetic evidence from independent gene loci. We propose an approach to do this using consensus networks. We compare gene trees for eight yeast genomes and show that consensus networks have potential for helping to visualize contradictory evidence for species phylogenies.
The Hypothalamic-Pituitary-Adrenal Axis in Pregnancy: Challenges in Disease Detection and Treatment
Authors: John R. Lindsay, Lynnette K. Nieman
Journal: Endocrine Reviews (2005)

Pregnancy dramatically affects the hypothalamic-pituitary-adrenal axis leading to increased circulating cortisol and ACTH levels during gestation, reaching values in the range seen in Cushing's syndrome (CS). The cause(s) of increased ACTH may include placental synthesis and release of biologically active CRH and ACTH, pituitary desensitization to cortisol feedback, or enhanced pituitary responses to corticotropin-releasing factors. In this context, challenges in diagnosis and management of disorders of the hypothalamic-pituitary-adrenal axis in pregnancy are discussed. CS in pregnancy is uncommon and is associated with fetal morbidity and mortality. The diagnosis may be missed because of overlapping clinical and biochemical features in pregnancy. The proportion of patients with primary adrenal causes of CS is increased in pregnancy. CRH stimulation testing and inferior petrosal sinus sampling can identify patients with Cushing's disease. Surgery is a safe option for treatment in the second trimester; otherwise medical therapy may be used. Women with known adrenal insufficiency that is appropriately treated can expect to have uneventful pregnancies. Whereas a fetal/placental source of cortisol may mitigate crisis during gestation, unrecognized adrenal insufficiency may lead to maternal or fetal demise either during gestation or in the puerperium. Appropriate treatment and management of labor are reviewed.
The roles of FOXM1 in pancreatic stem cells and carcinogenesis
Authors: Ming Quan, Peipei Wang, Jiujie Cui, Yong Gao, Keping Xie
Journal: Molecular Cancer (2013)

Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses among all cancers. Over the past several decades, investigators have made great advances in the research of PDAC pathogenesis. Importantly, identification of pancreatic cancer stem cells (PCSCs) in pancreatic cancer cases has increased our understanding of PDAC biology and therapy. PCSCs are responsible for pancreatic tumorigenesis and tumor progression via a number of mechanisms, including extensive proliferation, self-renewal, high tumorigenic ability, high propensity for invasiveness and metastasis, and resistance to conventional treatment. Furthermore, emerging evidence suggests that PCSCs are involved in the malignant transformation of pancreatic intraepithelial neoplasia. The molecular mechanisms that control PCSCs are related to alterations of various signaling pathways, for instance, Hedgehog, Notch, Wnt, B-cell-specific Moloney murine leukemia virus insertion site 1, phosphoinositide 3-kinase/AKT, and Nodal/Activin. Also, authors have reported that the proliferation-specific transcriptional factor Forkhead box protein M1 is involved in PCSC self-renewal and proliferation. In this review, we describe the current knowledge about the signaling pathways related to PCSCs and the early stages of PDAC development, highlighting the pivotal roles of Forkhead box protein M1 in PCSCs and their impacts on the development and progression of pancreatic intraepithelial neoplasia.
Erythrocyte Velocity and a Velocity Pulse in Minute Blood Vessels on the Surface of the Mouse Brain
Authors: WILLIAM I. ROSENBLUM
Journal: Circulation Research (1969)

High-speed microcinematography of vessels in the subarachnoid space of the anesthetized mouse was used to measure the velocity of erythrocytes in arterioles and venules less than 30µ in diameter. Within arterioles the velocity averaged 3.5 mm/sec, while in venules an average value of 1.9 mm/sec was obtained. A rhythmic alteration in velocity was often observed in the arterioles and was seen occasionally in venules. This cyclical change in velocity was termed the "velocity pulse." The frequency of the velocity pulse was virtually identical to that of the peripheral pulse and is believed to result from a propagation of that pulse into the microcirculation. The velocity pulse was not recognizable in vessels 5µ to 10µ wide. In vessels 10µ, to 30µ, in diameter, the velocity pulse was not accompanied by changes in the width of the vessels.