tbuckley/cabot-search huggingface dataset:
Thromboxane mediates diapedesis after ischemia by activation of neutrophil adhesion receptors interacting with basally expressed intercellular adhesion molecule-1.
Authors: G Goldman, R Welbourn, J M Klausner, C R Valeri, D Shepro, H B Hechtman
Journal: Circulation Research (1991)

Ischemic injury is characterized by neutrophil (PMN)--endothelial cell adhesion and diapedesis associated with thromboxane (TX) generation. Neutrophil-endothelial cell interaction is regulated in part by the leukocyte adhesion receptor CD 18 glycoprotein complex and the endothelial intercellular adhesion molecule-1 (ICAM-1). This study tests the role of TX in ischemia-induced diapedesis and evaluates whether the diapedesis is regulated by neutrophil or endothelial adhesion receptors. Plasma derived from rabbit hind limbs made ischemic for 3 hours (n = 6) and reperfused for 10 minutes had increased levels of TXB2 3,450 pg/ml, which was higher than sham rabbit (n = 6) values of 653 pg/ml (p less than 0.05). When introduced into abraded skin chambers placed on the dorsum of other normal rabbits (n = 6), this ischemic plasma induced 1,000 pg/ml of new TX synthesis and diapedesis of 1,235 PMN/mm3. The total TX concentration and PMN accumulations in blister fluid were correlated (r = 0.88, p less than 0.05). In contrast, sham rabbit plasma induced no TX synthesis and diapedesis of only 77 PMN/mm3 (p less than 0.05). Administration of 50 ng/ml of authentic TXB2 into blisters induced an accumulation of 453 PMN/mm3, which was higher than that in saline controls (18 PMN/mm3) (p less than 0.05). Pretreatment of normal rabbits used for the diapedesis assay (n = 4) with the TX synthetase inhibitor OKY 046 (2 mg/kg/hr) limited ischemic plasma and authentic TXB2 induced diapedesis to 142 and 76 PMN/mm3, respectively (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Failure of Simple Clinical Measurements to Predict Perfusion Status after Intravenous Thrombolysis
Authors: ROBERT M. CALIFF
Journal: Annals of Internal Medicine (1988)

To determine whether coronary patency could be detected early during thrombolytic therapy, commonly used markers of perfusion were recorded in 386 patients with acute myocardial infarction treated with tissue plasminogen activator. Infarct artery angiography 90 minutes after initiation of therapy was used to determine perfusion status. Of patients with complete resolution of ST segment elevation before the angiogram, 96% (95% confidence interval, 79% to 100%) showed perfusion on the angiogram, and among those with partial improvement, 84% (95% confidence interval, 76% to 90%) showed perfusion, but these findings occurred in only 6% and 38% of patients respectively. When complete resolution of chest pain occurred before the angiogram, 84% of patients (95% confidence interval, 75% to 90%) showed perfusion, but this finding occurred in only 29% of patients. Although arrhythmias occurred frequently in the first 90 minutes of therapy, none were associated with a higher patency rate. No other factors predicted coronary patency. A logistic regression model showed 25% of patients with 90% or greater probability of patency, but 56% of patients with no ST segment or symptom resolution had patent arteries.
Accuracy and quantity are poor measures of recall and recognition
Authors: Andrew R. Mayes, Rob van Eijk, Patricia L. Gooding
Journal: Behavioral and Brain Sciences (1996)

Abstract The value of accuracy and quantity as memory measures is assessed. It is argued that (1) accuracy does not measure correspondence (monitoring) because it ignores omissions and correct rejections, (2) quantity is confounded with monitoring in recall, and (3) in recognition, if targets and foils are unequal, both measures, even together, still ignore correct rejections.
Phase 3 Randomized Trial on Larynx Preservation Comparing Sequential vs Alternating Chemotherapy and Radiotherapy
Authors: J. L. Lefebvre, F. Rolland, M. Tesselaar, E. Bardet, C. R. Leemans, L. Geoffrois, P. Hupperets, L. Barzan, D. de Raucourt, D. Chevalier, L. Licitra, F. Lunghi, R. Stupp, D. Lacombe, J. Bogaerts, J. C. Horiot, J. Bernier, J. B. Vermorken
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundBoth induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer.
Smoke exposure as a determinant of autoantibody titre in 1-antitrypsin deficiency and COPD
Authors: A.M. Wood, P. de Pablo, C.D. Buckley, A. Ahmad, R.A. Stockley
Journal: European Respiratory Journal (2010)

Liberation of elastin peptides from damaged lung may be a mechanism of autoimmune lung disease. Citrullination, and anti-citrullinated protein antibody formation occurs in smokers, but the role of smoking in autoantibody generation relevant to pulmonary disease is unclear. Anti-elastin, anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) antibodies were measured in 257 subjects with α 1 -antitrypsin deficiency (AATD), 113 subjects with usual chronic obstructive pulmonary disease (COPD) and 22 healthy nonsmokers. Levels were compared between groups, against phenotypic features and against smoke exposure. Anti-elastin antibodies were higher in controls relative to AATD (p = 0.008) and usual COPD (p&lt;0.00001), and in AATD relative to usual COPD (p&lt;0.00001). Anti-elastin levels showed a threshold at 10 pack-yrs, being higher in those who had smoked less (p = 0.004). No relationships between antibody levels and clinical phenotype were seen after adjustment for smoke exposure. Anti-CCP antibodies were higher in usual COPD than AATD (p = 0.002) but the relationship to smoke exposure was less clear. Smoke exposure is the main determinant of anti-elastin antibody levels, which fall after 10 pack-yrs. Local antibody complexes may be a better measure of elastin directed autoimmunity than circulating levels.
Neutral endopeptidase inhibitor thiorphan increases airway narrowing to inhaled sodium metabisulfite in normal subjects.
Authors: S Bellofiore, F Caltagirone, A Pennisi, N Ciancio, A Mistretta, G U Di Maria
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Possible mechanisms involved in inhaled sodium metabisulfite (MBS)-induced bronchoconstriction include cholinergic reflex and release of tachykinins from sensory nerve endings. Tachykinins are potent bronchoconstrictors cleaved and inactivated by neutral endopeptidase (NEP) in the airways. To investigate the role of tachykinins in airway response to MBS, we assessed the effect of NEP-inhibitor thiorphan on airway response to MBS in nine nonatopic, nonasthmatic subjects. Two inhalational challenges with doubling doses of MBS (0.03 to 16 mumol) were performed 3 d apart. Ten minutes before MBS challenge, subjects randomly inhaled either thiorphan (1.25 mg) or placebo according to a double-blind cross-over design. Airflow at 30% of vital capacity (V30p) from partial expiratory flow-volume curves was measured at baseline, 10 min after thiorphan or placebo, and 2 min after each MBS dose. The dose of MBS causing 40% fall in V30p (PD40V30p) was calculated. Neither thiorphan nor placebo affected baseline airway caliber. Thiorphan caused a leftward shift of the dose-response curve to MBS. After placebo a measurable PD40V30p was obtained in four of nine subjects. In these subjects PD40V30p fell significantly after thiorphan inhalation. Four of five subjects who did not exhibit PD40V30p after placebo showed measurable PD40V30p after thiorphan. Percent fall in V30p caused by highest dose of MBS was significantly greater after thiorphan compared with placebo (55.9 +/- 4.6% versus 30.8 +/- 5.6%; mean +/- SE; p < 0.001). Results of this study demonstrate that the NEP-inhibitor thiorphan increases MBS-induced bronchoconstriction in normal subjects, suggesting that tachykinins are involved in airway responses to inhaled MBS.
The Calcium-Dependent Protein Kinase CPK28 Buffers Plant Immunity and Regulates BIK1 Turnover
Authors: Jacqueline Monaghan, Susanne Matschi, Oluwaseyi Shorinola, Hanna Rovenich, Alexandra Matei, Cécile Segonzac, Frederikke Gro Malinovsky, John P Rathjen, Dan MacLean, Tina Romeis, Cyril Zipfel
Journal: Cell Host & Microbe (2014)
The electron microscopy of "fibrinoid necrosis" in pulmonary arteries.
Authors: D Heath, P Smith
Journal: Thorax (1978)

Fibrinoid necrosis was induced in the pulmonary arteries of five male Wistar albino rats by feeding them on a diet adulterated by the addition of 0.07% ground Crotalaria spectabilis seeds by weight. Electron microscopy of the arteries affected by the process showed fibrin in the thrombus occluding their lumens and in the arterial intima, held up from further penetration of the media by the inner elastic lamina. Naturally occurring gaps in this lamina were found, and it is postulated that they determine the characteristic histological configuration of fibrinous vasculosis. The smooth muscle cells of the media of the pulmonary veins showed clear evaginations, devoid of myofilaments and organells, indicative of sustained constriction compatible with viability of the cells. In contrast, the smooth muscle cells of the media of the pulmonary arteries showed loss of myofilaments leading to frank necrosis. Other cells seen in the media include fibrocytes and "vasoformative reserve cells." The authors consider that the latter have considerable and varied potential. Once liberated during the process of fibrinoid necrosis in the arterial media they may play an important part in pulmonary vascular pathology as, for example, in the formation of the plexiform lesion.
Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis
Authors: Alexander Mildner, Elik Chapnik, Ohad Manor, Simon Yona, Ki-Wook Kim, Tegest Aychek, Diana Varol, Gilad Beck, Zohar Barnett Itzhaki, Ester Feldmesser, Ido Amit, Eran Hornstein, Steffen Jung
Journal: Blood (2012)
A simple method for removal of fish hooks in the emergency department
Authors: H. P. Ma, A. C M Lin
Journal: British Journal of Sports Medicine (2005)

Fishing is a sport enjoyed by millions of people throughout the world. A common fishing injury is the embedment of the fish hook in the skin. All emergency department doctors have experimented with removing fish hooks. It is a challenging procedure because of the hook’s barb, although the external injury is usually minimal.

The parts of the hook are the eye, shank, bend, point, and barb. The function of the barb is to …
CCAAT/Enhancer-Binding Protein δ Contributes to Myofibroblast Transdifferentiation and Renal Disease Progression
Authors: Masanobu Takeji, Noritaka Kawada, Toshiki Moriyama, Katsuyuki Nagatoya, Susumu Oseto, Shizuo Akira, Masatsugu Hori, Enyu Imai, Takeshi Miwa
Journal: Journal of the American Society of Nephrology (2004)

Myofibroblasts are pivotal participants in pathologic processes in a wide variety of organs, such as lung, liver, and kidney, by producing several inflammatory cytokines and extracellular matrices. The mechanism by which transdifferentiation from original cell to myofibroblast occurs, however, is still unclear. The expression of smooth muscle α-actin (SMαA) is the most characteristic feature of myofibroblasts; therefore, it was speculated that any factors that promote SMαA expression might be the key to transdifferentiation to myofibroblasts and disease exacerbation. A transcription factor CCAAT/enhancer-binding protein δ (C/EBPδ) was identified and demonstrated to bind to sequences including the CArG motif from SMαA intron 1 and to increase transcriptional activity of this promoter. Expression of SMαA and C/EBPδ in the glomerular area was upregulated in rat anti-Thy1 glomerulonephritis and mouse Habu-venom glomerulonephritis, both of which are models of mesangioproliferative glomerulonephritis. In the latter model, C/EBPδ knockout mice demonstrated significantly less SMαA expression in the glomerular area on day 8 and less renal functional deterioration on day 14, compared with wild-type mice. These data suggest an important role for C/EBPδ in myofibroblast transdifferentiation and glomerulonephritis exacerbation.
PC3 prostate tumor-initiating cells with molecular profile FAM65Bhigh/MFI2low/LEF1low increase tumor angiogenesis
Authors: Kexiong Zhang, David J Waxman
Journal: Molecular Cancer (2010)

Cancer stem-like cells are proposed to sustain solid tumors by virtue of their capacity for self-renewal and differentiation to cells that comprise the bulk of the tumor, and have been identified for a variety of cancers based on characteristic clonal morphologies and patterns of marker gene expression. Single cell cloning and spheroid culture studies were used to identify a population of cancer stem-like cells in the androgen-independent human prostate cancer cell line PC3. We demonstrate that, under standard culture conditions, ~10% of PC3 cells form holoclones with cancer stem cell characteristics. These holoclones display high self-renewal capability in spheroid formation assays under low attachment and serum-free culture conditions, retain their holoclone morphology when passaged at high cell density, exhibit moderate drug resistance, and show high tumorigenicity in scid immunodeficient mice. PC3 holoclones readily form spheres, and PC3-derived spheres yield a high percentage of holoclones, further supporting their cancer stem cell-like nature. We identified one gene, FAM65B, whose expression is consistently up regulated in PC3 holoclones compared to paraclones, the major cell morphology in the parental PC3 cell population, and two genes, MFI2 and LEF1, that are consistently down regulated. This molecular profile, FAM65Bhigh/MFI2low/LEF1low, also characterizes spheres generated from parental PC3 cells. The PC3 holoclones did not show significant enriched expression of the putative prostate cancer stem cell markers CD44 and integrin α2β1. PC3 tumors seeded with holoclones showed dramatic down regulation of FAM65B and dramatic up regulation of MFI2 and LEF1, and unexpectedly, a marked increase in tumor vascularity compared to parental PC3 tumors, suggesting a role of cancer stem cells in tumor angiogenesis. These findings support the proposal that PC3 tumors are sustained by a small number of tumor-initiating cells with stem-like characteristics, including strong self-renewal and pro-angiogenic capability and marked by the expression pattern FAM65B high /MFI2 low /LEF1 low . These markers may serve as targets for therapies designed to eliminate cancer stem cell populations associated with aggressive, androgen-independent prostate tumors such as PC3.
Strain rate measurement by doppler echocardiography allows improvedassessment of myocardial viability inpatients with depressed left ventricular function
Authors: Rainer Hoffmann, Ertunc Altiok, Nicole Heussen, Peter Hanrath, Bernd Nowak, Hans-Jürgen Kaiser, Udalrich Büll, Harald Kühl
Journal: Journal of the American College of Cardiology (2002)
Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.
Authors: J Van Damme, G Opdenakker, R J Simpson, M R Rubira, S Cayphas, A Vink, A Billiau, J Van Snick
Journal: The Journal of Experimental Medicine (1987)

A factor that promotes the growth of certain B cell hybridomas and of plasmacytomas is shown to be produced by normal human fibroblasts and by a line of human osteosarcoma cells (MG-63) after treatment with IL-1 or TNF. The hybridoma-plasmacytoma growth factor (HPGF) is identified with a 26 kD protein whose mRNA was previously shown to be induced in the same cells by the same inducers. First, poly(A)-rich RNA extracted from IL-1-treated cells could be enriched in HPGF-mRNA content by hybridization to 26 kD cDNA. Second, MG-63-derived HPGF purified to electrophoretic homogeneity was subjected to amino acid sequence analysis, whereby the NH2-terminal sequence was found to match the nucleotide sequence of a 26 kD cDNA clone.
Ability of Serotonin and Norepinephrine to Mimic the Central Effects of Reserpine on Vasomotor Activity
Authors: J. W. McCUBBIN, Y. KANEKO, IRVINE H. PAGE
Journal: Circulation Research (1960)

Reserpine, serotonin, norepinephrine, 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine had qualitatively the same cardiovascular effects when they were injected into a lateral ventricle or into the cisterna magna. All lowered arterial pressure, usually caused bradycardia despite prior section of the vagus nerves, and caused marked inhibition of the pressor response to occlusion of the common carotid arteries. Essentially the same results were obtained in unanesthetized as in anesthetized dogs. On a weight basis, norepinephrine was the more active amine tested and 5-hydroxytryptophan was more active than serotonin and 3,4 dihydroxyphenylalanine. Reserpine injected centrally had an effect equivalent to that of 20 or more times larger dosage given intravenously. All drugs were more active against the response to carotid occlusion than against the reflex pressor response to stimulation of a cut central end of a sciatic or vagus nerve. Decreased afferent electric activity of the carotid sinus nerve accompanied lowering of arterial pressure following central injection of small dosage, or intravenous injection of large dosage, of 5-hydroxytryptophan, indicating that the cardiovascular effects are not due to a direct action of 5-hydroxytryptophan on carotid sinus baroceptors. Central injection of an amine oxidase inhibitor, beta-phenylisopropylhydrazine, markedly augmented and prolonged the cardiovascular effects of the amines and of reserpine as well. These results are all consistent with, though they do not validate, the premise that the acute cardiovascular effects of reserpine are mediated centrally by serotonin and/or norepinephrine, either released from a bound and inactive to a free and active form, or formed by decarboxylation of their respective amino acids.
Disorders of Glucose Metabolism in Acute Stroke Patients
Authors: Karl Matz, Katharina Keresztes, Claudia Tatschl, Monika Nowotny, Alexandra Dachenhausen, Michael Brainin, Jaakko Tuomilehto
Journal: Diabetes Care (2006)

To determine the prevalence of disturbances in glucose metabolism in patients with acute stroke.Consecutively admitted acute stroke patients (n = 286) were screened for glucose tolerance according to the standardized World Health Organization protocol in the 1st and 2nd week after the stroke event. In addition, we repeatedly measured fasting capillary blood glucose during the first 10 days.Measurements were not performed or cancelled if patients were not fully conscious or had severe dysphagia or early complications that made transfers to other hospitals necessary (n = 48). Of the remaining 238 patients, 20.2% had previously known diabetes; 16.4% were classified as having newly diagnosed diabetes, 23.1% as having impaired glucose tolerance (IGT), and 0.8% as having impaired fasting glucose; and only 19.7% showed normal glucose levels. Another 47 patients (19.7%) had hyperglycemic values only in the 1st week (transient hyperglycemia) or could not be fully classified due to missing data in the oral glucose tolerance test. Patients with diabetes compared with nondiabetic subjects had more severe strokes (National Institutes of Health Stroke Scale [NIHSS] on admission: 7.2 +/- 6.6 vs. 4.6 +/- 3.1, 4.2 +/- 4.4, and 3.7 +/- 3.6 for IGT, transient hyperglycemia, and normoglycemia, respectively; P < 0.001), a worse outcome (modified Rankin scale 0-1 at discharge: 40.2 vs. 54.4, 63.8, and 72.3% for IGT, transient hyperglycemia, and normoglycemia, respectively; P < 0.001), and a higher rate of infectious complications (35.6 vs. 12.3, 21.2, and 4.2% for IGT, transient hyperglycemia, and normoglycemia, respectively; P < 0.001). In the multivariate analysis, NIHSS on admission, female sex, and the occurrence of urinary tract infection were independently associated with newly diagnosed diabetes.The majority of acute stroke patients have disorders of glucose metabolism, and in most cases this fact has been unrecognized. Diabetes worsens the outcome of acute stroke. Therefore, in the post-acute phase, an oral glucose tolerance test should be recommended in all stroke patients with no prior history of diabetes.
Evidence for the Involvement of Type I Interferon in Pulmonary Arterial Hypertension
Authors: Peter M. George, Eduardo Oliver, Peter Dorfmuller, Olivier D. Dubois, Daniel M. Reed, Nicholas S. Kirkby, Nura A. Mohamed, Frederic Perros, Fabrice Antigny, Elie Fadel, Benjamin E. Schreiber, Alan M. Holmes, Mark Southwood, Guy Hagan, Stephen J. Wort, Nathan Bartlett, Nicholas W. Morrell, John G. Coghlan, Marc Humbert, Lan Zhao, Jane A. Mitchell
Journal: Circulation Research (2013)

Evidence is increasing of a link between interferon (IFN) and pulmonary arterial hypertension (PAH). Conditions with chronically elevated endogenous IFNs such as systemic sclerosis are strongly associated with PAH. Furthermore, therapeutic use of type I IFN is associated with PAH. This was recognized at the 2013 World Symposium on Pulmonary Hypertension where the urgent need for research into this was highlighted.To explore the role of type I IFN in PAH.Cells were cultured using standard approaches. Cytokines were measured by ELISA. Gene and protein expression were measured using reverse transcriptase polymerase chain reaction, Western blotting, and immunohistochemistry. The role of type I IFN in PAH in vivo was determined using type I IFN receptor knockout (IFNAR1(-/-)) mice. Human lung cells responded to types I and II but not III IFN correlating with relevant receptor expression. Type I, II, and III IFN levels were elevated in serum of patients with systemic sclerosis associated PAH. Serum interferon γ inducible protein 10 (IP10; CXCL10) and endothelin 1 were raised and strongly correlated together. IP10 correlated positively with pulmonary hemodynamics and serum brain natriuretic peptide and negatively with 6-minute walk test and cardiac index. Endothelial cells grown out of the blood of PAH patients were more sensitive to the effects of type I IFN than cells from healthy donors. PAH lung demonstrated increased IFNAR1 protein levels. IFNAR1(-/-) mice were protected from the effects of hypoxia on the right heart, vascular remodeling, and raised serum endothelin 1 levels.These data indicate that type I IFN, via an action of IFNAR1, mediates PAH.
Nasal CPAP reduces systemic blood pressure in patients with obstructive sleep apnoea and mild sleepiness
Authors: D S Hui, K W To, F W Ko, J P Fok, M C Chan, J C Ngai, A H Tung, C W Ho, M W Tong, C-C Szeto, C-M Yu
Journal: Thorax (2006)

A randomised controlled study was undertaken to examine the effect of nasal continuous positive airway pressure (CPAP) on 24 hour systemic blood pressure (BP) in patients with obstructive sleep apnoea (OSA).
Targeting of AML1-ETO in t(8;21) Leukemia by Oridonin Generates a Tumor Suppressor–Like Protein
Authors: Tao Zhen, Chuan-Feng Wu, Ping Liu, Hai-Yan Wu, Guang-Biao Zhou, Ying Lu, Jian-Xiang Liu, Yang Liang, Keqin Kathy Li, Yue-Ying Wang, Yin-Yin Xie, Miao-Miao He, Huang-Ming Cao, Wei-Na Zhang, Li-Min Chen, Kevin Petrie, Sai-Juan Chen, Zhu Chen
Journal: Science Translational Medicine (2012)

Oridonin treats AML by generating a truncated version of the AML1-ETO oncoprotein that functions as a tumor suppressor.