tbuckley/cabot-search huggingface dataset:
Molecular evolution of a duplication: the sex-peptide (Acp70A) gene region of Drosophila subobscura and Drosophila madeirensis
Authors: S. Cirera, M. Aguade
Journal: Molecular Biology and Evolution (1998)

In Drosophila melanogaster, the Acp70A gene, which is involved in the postmating reactions of the female, is a single-copy gene. However, in Drosophila subobscura, the gene is duplicated and both copies are transcribed. To study the molecular evolution of the duplication, a 2.1-kb fragment encompassing both copies of the duplication was sequenced for 10 lines of D. subobscura and one line of Drosophila madeirensis. Estimates of the divergence between the two copies of the duplicated region and between the two species studied, D. subobscura and D. madeirensis, revealed that both copies of the Acp70a gene had evolved independently since their duplication. The ratio of nonsynonymous to silent divergence between copies was generally higher than one. The McDonald and Kreitman test revealed an excess of nonsynonymous changes fixed since the duplication and before the split of the D. subobscura and D. madeirensis lineages. These results point to natural selection driving protein evolution after the duplication. Specifically, adaptive evolution appears to have caused the initial differentiation between copies of the N-terminal parts of the proteins, while purifying selection could be responsible for the high conservation of the C-terminal parts.
Evolution and therapeutical features in post-intubation tracheal stenosis in COPD patients
Authors: Emilia Crisan, Alina Croitoru, Ruxandra Ulmeanu, Mihai Alexe, Ion Cordos, Nicolae Galie, Cristian Paleru, Codin Saon, Genoveva Cadar, Iolanda Ion
Journal: European Respiratory Journal (2011)

Post-intubation tracheal stenosis represents a severe complication in patients with hypercapnic respiratory failure due to COPD. We present a series of iatrogenic tracheal stenoses in COPD patients addressed to the Bronchology Department during 5 years. There were 13 patients (10 males, 46% over 60 years-old), COPD stage III-IV GOLD, who suffered a severe exacerbation that required oro-tracheal intubation; 8 needed tracheotomy.Tracheal stenoses developed after a mean period of 24 days (7-42) and were clinically significant. Bronchoscopy revealed tracheal stenosis with diameter less than 5 mm. 8 were located in proximal trachea and 5 in medial trachea, with length more than 2 cm in 7 cases and less than 2 cm in other 6. Initially, all were treated with interventional bronchoscopy (dilatation, granuloma resection) but the results were instable in time, requiring other methods: prosthetics (8 cases) or surgery (5 cases). In the patients treated by prosthesis, the stent was removed in 3 cases after 1,5-2 years, the rest remained chronic carriers of prostheses. The patients treated by surgery had significant complications: 1 death by mediastinis, 3 stenosis relapse on the anastomosis line (finally resolved with interventional bronchoscopy). Only one case was successfully solved after surgery. In conclusion, interventional bronchoscopy had a higher success rate (37%) than surgical therapy (20%), also solving the cases complicated post-surgery with reoccurrence of stenosis. While for different etiologies of tracheal stenosis, surgical resection is the first choice of treatment, in patients suffering from COPD, interventional bronchoscopy remains the only way to solve it.
Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer
Authors: Shibu Thomas, Jonathan B. Overdevest, Matthew D. Nitz, Paul D. Williams, Charles R. Owens, Marta Sanchez-Carbayo, Henry F. Frierson, Martin A. Schwartz, Dan Theodorescu
Journal: Cancer Research (2010)

Abstract In bladder cancer, increased caveolin-1 (Cav-1) expression and decreased Src expression and kinase activity correlate with tumor aggressiveness. Here, we investigate the clinical and functional significance, if any, of this reciprocal expression in bladder cancer metastasis. We evaluated the ability of tumor Cav-1 and Src RNA and protein expression to predict outcome following cystectomy in 257 patients enrolled in two independent clinical studies. In both, high Cav-1 and low Src levels were associated with metastasis development. We overexpressed or depleted Cav-1 and Src protein levels in UMUC-3 and RT4 human bladder cancer cells and evaluated the effect of this on actin stress fibers, migration using Transwells, and lung metastasis following tail vein inoculation. Cav-1 depletion or expression of active Src in metastatic UMUC-3 cells decreases actin stress fibers, cell migration, and metastasis, while Cav-1 overexpression or Src depletion increased the migration of nonmetastatic RT4 cells. Biochemical studies indicated that Cav-1 mediates these effects via its phosphorylated form (pY14), whereas Src effects are mediated through phosphorylation of p190RhoGAP and these pathways converge to reduce activity of RhoA, RhoC, and Rho effector ROCK1. Treatment with a ROCK inhibitor reduced UMUC-3 lung metastasis in vivo, phenocopying the effect of Cav-1 depletion or expression of active Src. Src suppresses whereas Cav-1 promotes metastasis of bladder cancer through a pharmacologically tractable common downstream signaling pathway. Clinical evaluation of personalized therapy to suppress metastasis development based on Cav-1 and Src profiles seems warranted. Cancer Res; 71(3); 832–41. ©2010 AACR.
The role of Epstein-Barr virus in pleural effusions of unknown aetiology: an interesting clinical perspective
Authors: E. Martró, V. Ausina
Journal: European Respiratory Journal (2005)

Pleural effusion is a relatively common clinical condition that requires a differential diagnosis as it may represent the primary manifestation of certain diseases; however, it is commonly observed as a secondary manifestation or complication of other diseases. Primary causes include cardiac failure, infectious aetiology (75% bacterial and 25% viral), and malignancy (mostly lung and breast cancer), while the other diseases comprise pulmonary embolism, liver cirrhosis, subphrenic abscess or pancreatitis 1. In addition, symptoms associated with pleural effusions, such as cough, dyspnoea and chest pain, are nonspecific. Therefore, the history of the patient, physical findings and laboratory tests are necessary for the clinician to narrow down the differential diagnosis 2.

The cause of pleural effusion may be determined in most cases, depending on clinical presentation, imaging techniques and pleural fluid analysis. Pleural fluid analysis is the most useful test and, together with clinical information, usually allows the diagnosis of pleural effusion in ∼75% of patients 3. A definite diagnosis can generally be obtained in ∼25% of cases, after finding malignant cells or microorganisms. In ∼50% of cases, only a presumptive diagnosis can be obtained based on clinical impression. After excluding an infection as the cause of the pleural effusion, clinical orientation upon pleural fluid analysis is possible in a greater percentage of patients. In cases where a diagnosis cannot be obtained, observation of the patient, repeated pleural fluid analysis or more invasive procedures may be indicated. Even after invasive procedures, such as thoracoscopy, are used, the cause of the pleural effusion cannot be established in up to 15% of patients 4.

Thoracocentesis is indicated in all clinically significant pleural effusions of unknown origin and in effusions that do not respond to treatment. Pleural fluid biochemical analysis allows the classification into transudates (caused by imbalances between the hydrostatic …
Pressure Pulse in Small Arteries
Authors: Takero Sugiura, Edward D. Freis
Journal: Circulation Research (1962)

Pressure pulse contours have been obtained in the small mesenteric and intestinal arteries of the dog. The principal change in the pressure pulse during transmission from large to small arteries appeared to be the gradual and progressive development of damping. The pressure drop from the aorta to arteries of 200 µ internal diameter averaged 17 per cent systolic and 12 per cent diastolic. Elevation of blood pressure with norepinephrine or angiotensin decreased the large-to-small artery pressure gradient, as well as the apparent degree of damping. Reduction of arterial pressure following hexamethonium or hemorrhage had the opposite effect. The evidence suggested that arteries of 200 µ diameter and larger function primarily as transport vessels and play no important role in altering the peripheral vascular resistance.
Reduction of the Membrane Fluidity of Human Breast Cancer Cells by Tamoxifen and 17beta-Estradiol
Authors: R. Clarke, H. W. van den Berg, R. F. Murphy
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Reduction of the Membrane Fluidity of Human Breast Cancer Cells by Tamoxifen and 17β-Estradiol Get access Robert Clarke, Robert Clarke * Vincent T. Lombardi Cancer Research Center, Georgetown University Medical SchoolWashington, DC. * Correspondence to: Robert Clarke, M.Sc., Ph.D., Vincent T. Lombardi Cancer Research Center. Georgetown University Medical School, 3800 Reservoir Rd., N.W., Rm. S128, Washington, DC 20007. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hendrik W. van den Berg, Hendrik W. van den Berg Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Medical Biology CenterBelfast, Northern Ireland, United Kingdom. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard F. Murphy Richard F. Murphy Department of Biochemistry, The Queen's University of Belfast, Medical Biology CenterBelfast, Northern Ireland, United Kingdom 4 Present address: R. F. Murphy, Department of Biomedical Sklciences, Creighton University,l Omaha, Neb. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 21, 7 November 1990, Pages 1702–1705, https://doi.org/10.1093/jnci/82.21.1702 Published: 07 November 1990 Article history Received: 17 April 1990 Revision received: 07 August 1990 Accepted: 10 August 1990 Published: 07 November 1990
Pim-1 Kinase Protects Mitochondrial Integrity in Cardiomyocytes
Authors: Gwynngelle A. Borillo, Matt Mason, Pearl Quijada, Mirko Völkers, Christopher Cottage, Michael McGregor, Shabana Din, Kimberlee Fischer, Natalie Gude, Daniele Avitabile, Steven Barlow, Roberto Alvarez, Silvia Truffa, Ross Whittaker, Matthew S. Glassy, Asa B. Gustafsson, Shigeki Miyamoto, Christopher C. Glembotski, Roberta A. Gottlieb, Joan Heller Brown, Mark A. Sussman
Journal: Circulation Research (2010)

Cardioprotective signaling mediates antiapoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector of AKT-mediated cardioprotection but the mechanistic basis for maintenance of mitochondrial integrity by Pim-1 remains unexplored. This study details antiapoptotic actions responsible for enhanced cell survival in cardiomyocytes with elevated Pim-1 activity.
Do-Not-Resuscitate Orders in Intensive Care Units
Authors: R L Jayes, J E Zimmerman, D P Wagner, E A Draper, W A Knaus
Journal: JAMA (1993)

To describe the characteristics of patients with do-not-resuscitate (DNR) orders and the frequency and timing of these orders in a representative sample of intensive care units (ICUs) and to compare practices from 1980 to 1990.Prospective inception cohort.A total of 42 ICUs in 40 US hospitals with 200 or more beds; 26 randomly selected hospitals and 14 large, tertiary care hospitals that volunteered to be studied.A consecutive sample of 17,440 ICU admissions from 1988 to 1990.Patient demographic characteristics, comorbid conditions, disease, and physiological abnormalities.Frequency and timing of DNR orders; ICU resource use before and after DNR orders; and patients' hospital and ICU discharge status.Physicians wrote DNR orders for 1577 ICU admissions (9%) (hospital range, 1.5% to 22%). Patients with ICU DNR orders were older, more functionally impaired, had more comorbid illness, a higher severity of illness, and required the use of more ICU resources compared with patients without DNR orders. Compared with data from a similar survey from 1979 to 1982, ICU DNR orders were more frequent in 1988 to 1990 (9% vs 5.4%; P < .001) and preceded 60% of all in-unit deaths compared with only 39% in 1979 to 1982 (P < .001). Do-not-resuscitate orders were written sooner (for 3.6% vs 2.0% of patients on day 1 in the ICU) and patients with DNR orders remained in the ICU longer in 1988 to 1990 (2.8 vs 1.4 days) than in 1979 to 1982, and had lower ICU and hospital mortality rates (64% vs 74%, P < .001; and 85% vs 94%, P < .001).Over the last decade physicians and patients' families set limits earlier and more frequently in cases likely to have poor outcomes. We attribute this change to a greater dialogue about setting limits to care and a greater knowledge of treatment outcomes among physicians and families. These changes in practice preceded implementation of the Patient Self-determination Act, designed to ensure patient autonomy for decisions about life-sustaining therapy.
Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers
Authors: Azad Rahimpour, Hui Fern Koay, Anselm Enders, Rhiannon Clanchy, Sidonia B.G. Eckle, Bronwyn Meehan, Zhenjun Chen, Belinda Whittle, Ligong Liu, David P. Fairlie, Chris C. Goodnow, James McCluskey, Jamie Rossjohn, Adam P. Uldrich, Daniel G. Pellicci, Dale I. Godfrey
Journal: The Journal of Experimental Medicine (2015)

Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4−CD8−, CD4−CD8+, and CD4+CD8− subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44hiCD62Llo memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-γ, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid–related orphan receptor γt (RORγt), whereas RORγtlo MAIT cells predominantly express T-bet and produce IFN-γ. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Vα19 TCR transgenic mice are PLZF− and express a naive CD44lo phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease.
Lowered serum cholesterol and low mood
Authors: S L. Brown
Journal: BMJ (1996)

Reducing serum cholesterol has long been seen as a desirable goal, particularly for those with high concentrations of serum cholesterol and a history of atherosclerotic disease. Recently, the value of lowering (or low) serum cholesterol concentrations has been called into question. A meta-analysis of six primary prevention trials suggested that coronary heart disease mortality tended to be lower in men who were treated with cholesterol lowering regimens, but that the overall mortality did not decline because of a significant increase in deaths from external causes (accidents, suicide, or homicide).1 This increased risk for violent death was apparent whether cholesterol lowering was by drug or dietary intervention. Subsequent studies on this phenomenon have not resolved the issue but have caused further debate on the design and meaning of each study as well as the central issue of whether low serum cholesterol is a desirable goal.

Because death from external causes has a behavioural component, the search for an explanation of the association between low cholesterol concentrations and these deaths has focused on the possibility that lowering or low cholesterol concentrations influence mood …
A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes.
Authors: J W Barnwell, A S Asch, R L Nachman, M Yamaya, M Aikawa, P Ingravallo
Journal: Journal of Clinical Investigation (1989)

Plasmodium falciparum-infected erythrocytes (IE) specifically adhere to vascular endothelium in vivo and to human endothelial cells, some human melanoma cell lines, and human monocytes in vitro. The tissue cell receptor for a ligand on the surface of the infected erythrocytes is an Mr 88,000 glycoprotein (GP88) recognized by the MAb OKM5, which also blocks cytoadherence of IE. Isolated, affinity-purified GP88 (CD36) competitively blocks cytoadherence and when absorbed to plastic surfaces, specifically binds P. falciparum IE. Additionally, monoclonal and polyclonal antibodies to GP88 block cytoadherence to both target cells and immobilized GP88. Binding to GP88 by IE is unaffected by the absence of calcium or the absence of thrombospondin, a putative mediator for cytoadherence of P. falciparum IE. Thus, GP88 (CD36), which has been demonstrated to be the same as platelet glycoprotein IV, interacts directly with P. falciparum IE, presumably via a parasite-induced ligand exposed on the surface of the infected erythrocytes. CD36 is shown to be present on brain endothelium in both individuals without malaria and individuals with cerebral malaria. This would suggest that factors other than just cerebral sequestration of IE play an initiating role in the genesis of cerebral malaria.
Dual effect of thrombin on voltage-dependent Ca2+ channels of portal vein smooth muscle cells.
Authors: A Baron, G Loirand, P Pacaud, C Mironneau, J Mironneau
Journal: Circulation Research (1993)

Thrombin induces a number of physiological responses in several types of cells. To determine the action of thrombin in the vein, the electrophysiological and mechanical effects of thrombin were studied in rat portal vein smooth muscle cells. Ca2+ channel currents were recorded using the whole-cell patch-clamp technique. Thrombin had both inhibitory and stimulatory effects on the Ca2+ channel current. The inhibitory effect was reversed on washout of thrombin, whereas the stimulatory effect was maintained after thrombin was removed. Thrombin (1 unit/ml) produced a reversible decrease of 27.3 +/- 3.3% (n = 12) in the current amplitude and a sustained increase of 71.2 +/- 12.9% (n = 20). The thrombin-induced inhibition of Ca2+ channel current was blocked by the thrombin inhibitor hirudin and by the protease inhibitor leupeptin. The stimulatory effect of thrombin was inhibited by hirudin, by intracellular application of guanosine 5'-O-(beta-thio)diphosphate, and by antiphophatidylinositide antibodies but not by pertussis toxin. The thrombin-induced enhancement of the Ca2+ channel current amplitude was not observed when the current was previously stimulated by phorbol 12,13-dibutyrate. This suggests that the inhibitory effect of thrombin was related to its proteolytic activity and that the stimulatory effect involved activation of a pertussis toxin-insensitive GTP-binding protein, phosphatidylinositide hydrolysis, and protein kinase C activation. Both thrombin effects occurred in the same concentration range (0.001-10 units/ml). The thrombin-induced contraction of portal vein strips was completely inhibited by isradipine, and thrombin did not produce an increase in cytosolic [Ca2+], measured by indo-1 fluorescence in cells clamped at -50 mV, sufficient to activate Ca(2+)-dependent chloride current.(ABSTRACT TRUNCATED AT 250 WORDS)
Painful red nodules of the legs: A manifestation of chronic infection with gram-negative organisms
Authors: D S Nieves, W D James
Journal: Journal of the American Academy of Dermatology (1999)

Skin infection secondary to gram-negative organisms is uncommon and is typically limited to persons who are immunocompromised. When these do occur, they are acute, progressive, and severe. Here we report 2 cases of painful red nodules that presented with a waxing and waning course over a long period. One case is that of a 45-year-old healthy white man who developed Serratia marcescens infection in 1 leg. The other case is that of a 78-year-old man with chronic lymphocytic leukemia treated with prednisone who developed infection of the leg secondary to Pseudomonas aeruginosa. In the first case, symptoms were present for 2 years before definitive diagnosis and treatment. In the second case, 4 months elapsed. Ultimately, both patients responded to antibiotic therapy and recovered. These cases illustrate an unusual presentation of chronic red painful nodules of the leg secondary to infection with gram-negative organisms and underscore the importance of culture even when infection seems unlikely.
Different effects of long- and short-acting loop diuretics on survival rate in Dahl high-salt heart failure model rats
Authors: J YOSHIDA, K YAMAMOTO, T MANO, Y SAKATA, M NISHIO, T OHTANI, M HORI, T MIWA, T MASUYAMA
Journal: Cardiovascular Research (2005)

Objectives: We compared therapeutic effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in hypertensive heart failure rats to test the hypothesis that long-acting diuretics are superior to short-acting types in heart failure.
Adjuvant prophylactic regional radiotherapy versus observation in stage I Merkel cell carcinoma: a multicentric prospective randomized study
Authors: T. Jouary, C. Leyral, B. Dreno, A. Doussau, B. Sassolas, M. Beylot-Barry, C. Renaud-Vilmer, B. Guillot, P. Bernard, C. Lok, C. Bedane, F. Cambazard, L. Misery, E. Estève, S. Dalac, L. Machet, F. Grange, P. Young, F. Granel-Brocard, F. Truchetet, B. Vergier, M.M. Delaunay, J.J. Grob
Journal: Annals of Oncology (2011)
ADVANCED BIFURCATION SYSTEMSTM NOVEL MODULAR PLATFORM IN TREATMENT OF CORONARY BIFURCATION DISEASE. INITIAL RESULTS OF THE PROSPECTIVE, MULTICENTER, FIRST-IN-HUMAN FEASIBILITY TRIAL
Authors: Mehran J. Khorsandi, Alex Abizaid, Sameer Dani, Sepehr Fariabi, Henry Bourang, Ricardo Costa, Saibal Kar, Raj Makkar
Journal: Journal of the American College of Cardiology (2011)
Angiotensin and Endothelin
Authors: David E. Dostal, Kenneth M. Baker
Journal: Circulation Research (1998)

hanges in intracellular pH (pH i ) can produce marked effects on cardiac function, and, therefore, it is important that the cell possess mechanisms by which pH i is regulated, especially after intracellular acidosis associated with myocardial ischemia.The Na ϩ /H ϩ exchanger (NHE) and the Na ϩ /HCO 3 Ϫ symport represent the 2 major pathways by which alkalinization occurs in cardiac cells.The NHE not only regulates pH i but also cell volume and intracellular signaling in response to a variety of stimuli.