tbuckley/cabot-search huggingface dataset:
Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness
Authors: Hiromasa Inoue, Reiko Kato, Satoru Fukuyama, Atsushi Nonami, Kouji Taniguchi, Koichiro Matsumoto, Takako Nakano, Miyuki Tsuda, Mikiko Matsumura, Masato Kubo, Fumihiko Ishikawa, Byoung-gon Moon, Kiyoshi Takatsu, Yoichi Nakanishi, Akihiko Yoshimura
Journal: The Journal of Experimental Medicine (2005)

T helper 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, play a critical role in allergic asthma. These cytokines transmit signals through the Janus kinase/signal transducer and activator of transcription (STAT) and the Ras–extracellular signal-regulated kinase (ERK) signaling pathways. Although the suppressor of cytokine signaling (SOCS) family proteins have been shown to regulate the STAT pathway, the mechanism regulating the ERK pathway has not been clarified. The Sprouty-related Ena/VASP homology 1–domain-containing protein (Spred)-1 has recently been identified as a negative regulator of growth factor–mediated, Ras-dependent ERK activation. Here, using Spred-1–deficient mice, we demonstrated that Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness, without affecting helper T cell differentiation. Biochemical assays indicate that Spred-1 suppresses IL-5–dependent cell proliferation and ERK activation. These data indicate that Spred-1 negatively controls eosinophil numbers and functions by modulating IL-5 signaling in allergic asthma.
Perfluorocarbon compounds: Effects on the rheological properties of sickle erythrocytes in vitro
Authors: C. A. Reindorf, J. Kurantsin‐Mills, J. B. Allotey, O. Castro
Journal: American Journal of Hematology (1985)

The effects of oxygenated perfluorotributylamine (Fluosol-43) on the rheological properties of sickle (HbSS) erythrocytes have been determined by means of microviscometry and positive pressure cell filtration. Incubation of deoxygenated sickled erythrocytes (pO2 congruent to 30 mmHg) with oxygenated Fluosol-43 reduced the percentage of sickled erythrocytes from about 63 to 33%. Deoxygenation of 40% suspension of sickle erythrocytes in autologous plasma increased the viscosity by about 160% at shear rate of 1.15 sec-1. Incubation of the deoxygenated sickled erythrocytes with oxygenated Fluosol-43 significantly reduced the viscosity at the low shear rates. Filtration of 0.2% suspension of deoxygenated sickle erythrocytes through capillary-sized Nuclepore filters showed high resistance at low flow rates. Oxygenated Fluosol-43 increased the deformability of HbSS erythrocytes and thereby reduced the resistance at flow rates less than 1 ml/min. These data suggest that perfluorocarbons may be useful in reducing the propensity of hemoglobin S polymerization and sickling and thereby prevent tissue infarction in vaso-occlusive crisis. Therefore, the concept of examining the potential application of perfluorochemicals for alleviating severe vaso-occlusive events may be useful.
Proteomic discovery of Max as a novel interacting partner of C/EBPα: a Myc/Max/Mad link
Authors: A A Zada, J A Pulikkan, D Bararia, M Geletu, A K Trivedi, M Y Balkhi, W D Hiddemann, D G Tenen, H M Behre, G Behre
Journal: Leukemia (2006)
Mitogen-Activated Protein/Extracellular Signal–Regulated Kinase Inhibition Attenuates Angiotensin II–Mediated Signaling and Contraction in Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells
Authors: R. M. Touyz, M. El Mabrouk, G. He, X-H. Wu, E. L. Schiffrin
Journal: Circulation Research (1999)

Abstract —This study investigates the role of extracellular signal–regulated kinases (ERKs) in angiotensin II (Ang II)–generated intracellular second messengers (cytosolic free Ca 2+ concentration, ie, [Ca 2+ ] i , and pH i ) and in contraction in isolated vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats (WKY) using the selective mitogen-activated protein (MAP)/ERK inhibitor, PD98059. VSMCs from mesenteric arteries were cultured on Matrigel basement membrane matrix. These cells, which exhibit a contractile phenotype, were used to measure [Ca 2+ ] i , pH i , and contractile responses to Ang II (10 –12 to 10 –6 mol/L) in the absence and presence of PD98059 (10 –5 mol/L). [Ca 2+ ] i and pH i were measured by fura-2 and BCECF methodology, respectively, and contraction was determined by photomicroscopy. Ang II–stimulated ERK activity was measured by Western blot analysis using a phospho-specific ERK-1/ERK-2 antibody and by an MAPK enzyme assay. Ang II increased [Ca 2+ ] i and pH i and contracted cells in a dose-dependent manner. Maximum Ang II–elicited contraction was greater ( P &lt;0.05) in SHR (41.9±5.1% reduction in cell length relative to basal length) than in WKY (28.1±3.0% reduction in cell length relative to basal length). Basal [Ca 2+ ] i , but not basal pH i , was higher in SHR compared with WKY. [Ca 2+ ] i and pH i effects of Ang II were enhanced ( P &lt;0.05) in SHR compared with WKY (maximum Ang II–induced response [E max ] of [Ca 2+ ] i , 576±24 versus 413±43 nmol/L; E max of pH i , 7.33±0.01 versus 7.27±0.03, SHR versus WKY). PD98059 decreased the magnitude of contraction and attenuated the augmented Ang II–elicited contractile responses in SHR (E max ,19.3±3% reduction in cell length relative to basal length). Ang II–stimulated [Ca 2+ ] i (E max , 294±55 nmol/L) and pH i (E max , 7.27±0.04) effects were significantly reduced by PD98059 in SHR. Ang II–induced ERK activity was significantly greater ( P &lt;0.05) in SHR than in WKY. In conclusion, Ang II–stimulated signal transduction and associated VSMC contraction are enhanced in SHR. MAP/ERK inhibition abrogated sustained contraction and normalized Ang II effects in SHR. These data suggest that ERK-dependent signaling pathways influence contraction and that they play a role in vascular hyperresponsiveness in SHR.
SOME PATHOLOGICAL FINDINGS IN SCHIZOPHRENICS
Authors: DONALD L. HOWIE
Journal: American Journal of Psychiatry (1960)

Pathological and clinical findings were reviewed in 50 schizophrenic patients. Only 2, both alcoholics, had no notable pathological brain abnormalities. Vascular diseases and malformations of the brain were particularly frequent. The diversity of findings was a prominent feature, and tended to support the thesis that schizophrenia is a syndromic diagnosis. The series suggests that some of the findings may be causally related to the schizophrenic symptoms.
Effect of Phenobarbital on the Development of Liver Tumors in Juvenile and Adult Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;4&lt;/xref&gt;
Authors: M A Pereira, J E Klaunig, S L Herren-Freund, R J Ruch
Journal: JNCI Journal of the National Cancer Institute (1986)

The effect of long-term exposure to phenobarbital (CAS: 50-06-6) subsequent to tumor initiation on the development of liver tumors in BALB/c and (C57BL/6 X C3H/Anf)F1 (B6C3F1) mice was determined. In male B6C3F1 mice that received either 15 or 45 ppm diethylnitrosamine [(DENA) CAS: 55-18-5] between 6 and 10 weeks of age, subsequent treatment with 500 ppm sodium phenobarbital in the drinking water resulted in the promotion of liver tumors. However, in male B6C3F1 mice initiated on day 15 of age with 25 mg DENA/kg, beginning long-term treatment of 500 ppm sodium phenobarbital at 4 weeks of age inhibited the development of liver tumors, whereas in male BALB/c mice initiated with 25 mg DENA/kg on day 15 of age, beginning the long-term treatment with 500 ppm sodium phenobarbital at 4 weeks of age promoted the development of liver tumors. Hence phenobarbital can either enhance or inhibit the formation of liver tumors, depending both on the mouse strain used and the animal's age at the start of exposure.
Severity scales in community-acquired pneumonia: what matters apart from death?
Authors: K. Challen
Journal: Thorax (2010)

Chalmers et al 1 and Loke et al 2 present excellent meta-analyses of the value of various tools in predicting mortality from community-acquired pneumonia (CAP). There is a continuing fallacious belief, however, that only patients at high risk of death are at high risk of complications. Of the …
Mhc-DRB genes of the pigtail macaque (Macaca nemestrina): implications for the evolution of human DRB genes.
Authors: Z F Zhu, V Vincek, F Figueroa, C Schönbach, J Klein
Journal: Molecular Biology and Evolution (1991)

The DRB family of human class II major histocompatibility complex (Mhc) loci is unusual in that individuals differ in the number and combination of genes (haplotypes) they carry. Indications are that both the allelic and haplotype polymorphisms of the DRB loci predate speciation. Searching for the evolutionary origins of these polymorphisms, we have sequenced five DRB clones isolated from a cDNA library of a pigtail macaque (Macaca nemestrina) B lymphocyte line. The clones represent five different genes which we designate Mane-DRB*01-Mane-DRB*05. The genes appears to be approximately equidistant from each other, so that allelic relationships between them cannot be established on the basis of the sequence data alone. If positions coding for the peptide-binding region of the class II beta chains are eliminated from sequence comparisons, the Mane-DRB genes appear to be most closely related to the human (HLA) DRB1 genes of the DRw52 group. We interpret this finding to indicate that the ancestral gene of the DRw52 group of human DRB1 alleles separated from the rest of the HLA-DRB1 alleles before the separation of the Old World monkeys (Cercopithecoidea) from the apes (Hominoidea) in the early Oligocene. After this separation, the ancestral DRB1 gene of the DRw52 group duplicated in the Old World monkey lineage to give rise to genes at three loci at least, while in the ape lineage this gene may have remained single and diverged into a number of alleles instead. These findings suggest that some of the polymorphism currently present at the DRB1 locus is greater than 35 Myr old.
From registry to quality management: the German Cystic Fibrosis Quality Assessment project 1995 2006
Authors: M. Stern, B. Wiedemann, P. Wenzlaff
Journal: European Respiratory Journal (2007)

Since 1995, the German Cystic Fibrosis Quality Assessment project has collected demographic data and outcome parameters. It aims to develop tools for quality management. The basic data of 6,835 patients has been collected annually by 93 centres. Weight for height and body mass index (BMI) indicated nutritional status, and forced expiratory volume in one second (FEV 1 ) served as the central respiratory parameter. Data on mortality and survival were calculated. The mean age of all patients has increased from 13.9 yrs in 1995 to 17.7 yrs in 2005, and the percentage of adult patients has increased from 28.4 to 43.4%. Benchmarking diagrams and centre reports indicated considerable differences between the centres. The achievement of basic aims at the age of 6, 12 and 18 yrs indicated a positive development in 1995 to 2005. In 2005, median age at death was 23.7 yrs and the median cumulative survival was 37.4 yrs. Mortality correlated with a BMI &lt;19 kg·m −2 and an FEV 1 &lt;80%. No sex gap in mortality was detected. “Learning from the best” is now possible. Further improvements in the system of cystic fibrosis care are required, such as: defining alarm signals for early treatment; involvement of patients and their families in quality management; auditing; benchmarking; and in-house training.
An Effective Strategy for Diagnosing Occupational Asthma
Authors: Frédéric Girard, Simone Chaboillez, André Cartier, Johanne Côté, Frederick E. Hargreave, Manon Labrecque, Jean-Luc Malo, Susan M. Tarlo, Catherine Lemière
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Monitoring airway inflammation by means of induced sputum cell counts seems to improve the management of asthma. We sought to assess whether such monitoring at the end of periods at and away from work combined with the monitoring of PEF could improve the diagnosis of occupational asthma. We enrolled subjects suspected of having occupational asthma. Serial monitoring of PEF was performed during 2 weeks at and away from work. At the end of each period, induced sputum was collected. Specific inhalation challenge was subsequently performed. PEF graphs were interpreted visually by five independent observers. Forty-nine subjects, including 23 with positive specific inhalation challenge, completed the study. The addition of sputum cell counts to the monitoring of PEF increased the specificity of this test, respectively, by 18 (range [r] 13.7-25.5) or 26.8% (r 24.8-30.4) depending if an increase of sputum eosinophils greater than 1 or 2% when at work was considered as significant. The sensitivity increased by 8.2% (r 4.1-13.4) or decreased by 12.3% (r 3.1-24.1) depending on the cutoff value in sputum eosinophils chosen (greater than 1 or 2%, respectively). The addition of sputum cell counts to PEF monitoring is useful to improve the diagnosis of occupational asthma.
Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice.
Authors: T Akaike, M Ando, T Oda, T Doi, S Ijiri, S Araki, H Maeda
Journal: Journal of Clinical Investigation (1990)

We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15 +/- 0.05 (control; no infection) to 1.06 +/- 0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.
From the Museum: the Art of Thinking. Part Four: Debate
Authors: Tom Kotsimbos
Journal: European Respiratory Journal (2014)

The Raft of the Medusa is an iconic, history-style painting of a then contemporary shipwreck (French frigate Méduse , June 17, 1816) that paradoxically helped realise the truth of the actual event despite widespread news coverage. Here, the Neoclassicism of the Enlightenment gives way to the passion filled realism of Romanticism. Classical pyramidal composition is no longer accompanied by an ideal beauty but by dark turbulence and the cruel reality of the ever-present scramble for life over piled-up corpses. Géricault's violent visual portrayal was a triumph of feeling that infused the debate regarding the shipwreck with a visceral aesthetic that dramatically widened the lens of truth through which society saw itself. Historically, post-Napoleonic France was "adrift" at the time and "the whole of society was aboard the Medusa" : from the incompetent captain to the corrupt system that had appointed him; from the lifeboats reserved for the wealthy to the poor souls left behind to fend for themselves; from the disaster of the shipwreck to the nightmare of animal brutality and cannibalism on the raft (with few survivors left to tell the tale). The painting stands as a synthetic view of human life abandoned to its fate and as such fascinated and upset the public, divided critics and generated much debate.
Determinants of exhaled NO in a population of subjects with different respiratory symptoms - Results from the Swedish GA2LEN survey
Authors: Andrei Malinovschi, Kjell Alving, Linda Ekerljung, Bo Lundbäck, Roelinde Middelveld, Sven-Erik Dahlén, Lars Modig, Bertil Forsberg, Christer Janson
Journal: European Respiratory Journal (2012)

Fraction of NO in exhaled air (FeNO) is a common method to assess airways inflammation. Determinants of FeNO have nevertheless mostly been studied in the healthy general population. Therefore, we studied determinants of FeNO in a large population of subjects with respiratory symptoms that may reflect the type of patients seen in clinical practice.  FeNO was measured in 1018 subjects with asthma, sinusitis, asthma and sinusitis, or symptoms suggestive of asthma but without fulfilling the asthma diagnosis criteria, aged 17-76 years (median 45 yrs).  Female gender, current smoking and having both parents smoking during childhood were related to lower FeNO while increased height, age, atopy and asthma diagnosis were related to higher FeNO, both before and after adjustments for variables given in Table.  In conclusion, constitutional factors, such as male gender, increased height and age, are related to increased FeNO in subjects with respiratory symptoms. They should be accounted for in clinical practice as their effect size is comparable to the effect of diagnosed asthma. Parental smoking during childhood was related to decreased FeNO and this warrants further studies.
Differential Properties of Mucous Glycoproteins in Rat Nasal Epithelium
Authors: TAKESHI SHIMIZU, HITOMI HIRANO, SHINO SHIMIZU, CHIKAKO KISHIOKA, YASUO SAKAKURA, YUICHI MAJIMA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To examine the differential properties of mucous glycoproteins, we produced hypertrophic and metaplastic changes in goblet cells of rat nasal epithelium by intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats, and by intranasal lipopolysaccharide (LPS) instillation. The epithelial mucosubstance was quantitatively examined by alcian blue-periodic acid-Schiff (AB-PAS) and lectin histochemistry. The newly produced mucin after OVA challenge or LPS instillation contained a high amount of sulfomucin and a low amount of neutral glycoprotein: LPS-induced mucin contained more sulfomucin (70.1% of total) and less neutral glycoprotein (8.6%) than OVA-induced mucin (sulfomucin, 33.6%; neutral glycoprotein, 41.8%; p < 0.01). Four of the lectins stained some of the mucosubstance, indicating the presence of galactose-N-acetylgalactosamine, alpha2,3- and alpha2,6-linked sialic acid-galactose, and fucose residues. After LPS instillation, the reactivity was higher for galactose-N-acetylgalactosamine (64.8% of total) and alpha2,3-linked sialic acid-galactose (75.8%) than after saline instillation (3.5 and 19.1%, respectively) or OVA challenge (5.8 and 32.3%; p < 0.05). OVA challenge did not induce the alteration of terminal sugar residues. A 2-fold increase in mucin mRNA (rat Muc5ac) expression was induced after LPS instillation or OVA challenge, compared with animals treated with saline instillation (p < 0.05). These results indicate that mucin mRNA expression (for peptide backbone) increases similarly after LPS instillation or OVA challenge; however, carbohydrate compositions of newly produced mucin are different between the two groups.
The acute swollen knee: diagnosis and management
Authors: Chinmay Gupte, Jean-Pierre St Mart
Journal: Journal of the Royal Society of Medicine (2013)

The acutely swollen knee is a common presentation of knee pathology in both primary care and the emergency department. The key to diagnosis and management is a thorough history and examination to determine the primary pathology, which includes inflammation, infection or a structural abnormality in the knee. The location of pain and tenderness can aid to localization of structural pathology even before radiological tests are requested, and indeed inform the investigations that should be carried out. Aspiration of an acutely swollen knee can aid diagnosis and help relieve pain. The management of the swollen knee depends on underlying pathology and can range from anti-inflammatory medication for inflammation to operative intervention for a structural abnormality.
Acetylcholine causes coronary vasodilation in dogs and baboons.
Authors: D M Van Winkle, E O Feigl
Journal: Circulation Research (1989)

Intracoronary administration of acetylcholine or efferent vagal stimulation causes coronary vasodilation in dogs. However, in baboons it has been reported that intracoronary acetylcholine results in a fall in coronary blood flow and that stimulation of the vagi is without effect. The dose response of intracoronary acetylcholine and the effect of efferent vagal stimulation on the coronary circulation were reinvestigated in closed-chest, anesthetized dogs and baboons. The left main coronary artery was cannulated and perfused at constant pressure. alpha-Adrenergic and beta-adrenergic receptors were pharmacologically blocked with phenoxybenzamine and propranolol. Heart rate was held constant by right ventricular pacing. In dogs, intracoronary infusion of acetylcholine (1-300 micrograms/min) elicited a dose-dependent increase in steady-state coronary blood flow and coronary sinus oxygen tension, without a change in myocardial oxygen consumption. Vagal stimulation caused a coronary vasodilation that was attenuated by a metabolically mediated decrease in flow. In baboons, acetylcholine increased steady-state coronary blood flow in the dose range of 1-10 micrograms/min, caused little change at 30 micrograms/min, and decreased flow at 100-300 micrograms/min. Coronary sinus oxygen tension increased in a dose-dependent manner up to 10 micrograms/min. Myocardial oxygen consumption was unchanged in the dose range of 1-10 micrograms/min and declined between 30 and 300 micrograms/min. Efferent stimulation of the vagi resulted in coronary dilation obscured by a metabolic reduction of flow. It is concluded that 1) low doses of acetylcholine elicit a primary coronary vasodilation in both species, but in baboons high doses of acetylcholine cause a reduction of both myocardial oxygen consumption and coronary blood flow below control values and 2) vagal stimulation causes a competition between coronary vasodilation and metabolic reduction of flow in dogs and baboons.
Chemical Composition of the Rabbit Aorta during Development
Authors: D. IAN MCCLOSKEY, EDWARD G. CLEARY
Journal: Circulation Research (1974)

Changes in both the relative and the absolute amounts of collagen and elastin in segments of the aortic wall of New Zealand white rabbits (1-130 weeks old) were determined by chemical analysis. As in other mammals, elastin was the major component of the wall of the thoracic aorta although the proportion of collagen increased along the abdominal aorta and into the more distant arteries. Data on the absolute amounts of collagen and elastin per aorta showed that collagen and elastin deposition was most rapid during the early postnatal weeks. Although this deposition slowed in later weeks, it continued in both segments of the aorta throughout the period of this study. The proportion of the wall mass attributable to collagen and to elastin increased very rapidly during the first postnatal weeks and then, after 20 weeks, declined. The results of the present study indicate that there is a significant increase in some unidentified nonscleroprotein component within the aortic wall of older rabbits.
SRPX2 is a Novel Chondroitin Sulfate Proteoglycan that is Overexpressed in Gastrointestinal Cancer
Authors: K. Tanaka, T. Arao, D. Tamura, K. Aomatsu, K. Furuta, K. Matsumoto, H. Kaneda, K. Kudo, Y. Fujita, H. Kimura, K. Yanagihara, Y. Yamada, I. Okamoto, K. Nakagawa, K. Nishio
Journal: Annals of Oncology (2012)