tbuckley/cabot-search huggingface dataset:
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors
Authors: Jörg Hamann, Gabriela Aust, Demet Araç, Felix B Engel, Caroline Formstone, Robert Fredriksson, Randy A Hall, Breanne L Harty, Christiane Kirchhoff, Barbara Knapp, Arunkumar Krishnan, Ines Liebscher, Hsi-Hsien Lin, David C Martinelli, Kelly R Monk, Miriam C Peeters, Xianhua Piao, Simone Prömel, Torsten Schöneberg, Thue W Schwartz, Kathleen Singer, Martin Stacey, Yuri A Ushkaryov, Mario Vallon, Uwe Wolfrum, Mathew W Wright, Lei Xu, Tobias Langenhan, Helgi B Schiöth
Journal: Pharmacological Reviews (2015)

The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein–coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1), ADGRB2 (BAI2), ADGRB3 (BAI3), ADGRC1 (CELSR1), ADGRC2 (CELSR2), ADGRC3 (CELSR3), ADGRD1 (GPR133), ADGRD2 (GPR144), ADGRE1 (EMR1, F4/80), ADGRE2 (EMR2), ADGRE3 (EMR3), ADGRE4 (EMR4), ADGRE5 (CD97), ADGRF1 (GPR110), ADGRF2 (GPR111), ADGRF3 (GPR113), ADGRF4 (GPR115), ADGRF5 (GPR116, Ig-Hepta), ADGRG1 (GPR56), ADGRG2 (GPR64, HE6), ADGRG3 (GPR97), ADGRG4 (GPR112), ADGRG5 (GPR114), ADGRG6 (GPR126), ADGRG7 (GPR128), ADGRL1 (latrophilin-1, CIRL-1, CL1), ADGRL2 (latrophilin-2, CIRL-2, CL2), ADGRL3 (latrophilin-3, CIRL-3, CL3), ADGRL4 (ELTD1, ETL), and ADGRV1 (VLGR1, GPR98). This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential.
BMI is superior to symptoms in predicting response to proton pump inhibitor: randomised trial in patients with upper gastrointestinal symptoms and normal endoscopy
Authors: J. Fletcher, M. H. Derakhshan, G.-R. Jones, A. A. Wirz, K. E. L. McColl
Journal: Gut (2010)

<h3>Objectives</h3> In most patients undergoing endoscopy for upper gastrointestinal (GI) symptoms in the Western world, no macroscopic abnormality or evidence of <i>Helicobacter pylori</i> infection is identified. Following this negative investigation, proton pump inhibitor (PPI) therapy is usually prescribed. The aim of this study was to assess the value of such treatment compared with placebo and to identify predictors of response. <h3>Design</h3> Prospective parallel randomised study. <h3>Setting</h3> Dyspepsia Research Clinic. <h3>Participant</h3> 105 patients (49 men, median age 44 years, IQR 22) with normal endoscopy and <i>H pylori</i> negative with ongoing upper GI symptoms following 2-week run-in period. <h3>Intervention</h3> Full demographic symptom severity and characteristics were assessed and 24 h oesophageal pH metry and oesophageal manometry were performed prior to randomisation to 2 weeks of treatment with lansoprazole 30 mg/day or placebo (2:1), with reassessment of symptom severity during the second week of treatment. <h3>Primary outcome</h3> 50% reduction in Glasgow Dyspepsia Severity Score (GDSS). <h3>Results</h3> According to intention to treat analysis, the response was 35.7% for the active group and 5.7% for the placebo group (p&lt;0001). The only non-invasive independent predictor of response to PPI in multivariable analysis was the patient9s body mass index (BMI) (p=0.003). The association of BMI with response to PPI was apparent across the full range of quartiles (p values for trend=0.01). BMI had a similar predictive value to either 24 h oesophageal pH metry or manometry. Predominant symptom and symptom subgroups were unhelpful in predicting the response to PPI. Including all pretreatment assessments, only BMI (p&lt;0.05) and lower oesophageal sphincter pressure (p&lt;0.05) were independent predictors of response. <h3>Conclusion</h3> The response to PPI therapy is likely to be related to underlying acid reflux. The strong predictive value of BMI is probably due to its association with underlying reflux disease and the fact that it is a more objective and reproducible measure than symptom characteristics. It is recommended that BMI should be measured in patients with upper GI symptoms. <h3>Trial Registration Number</h3> ISRCTN 32863375.
Diagnosing primary ciliary dyskinesia
Authors: C. O'Callaghan, M. Chilvers, C. Hogg, A. Bush, J. Lucas
Journal: Thorax (2007)

A nationally funded diagnostic service should lead to improved outcome

The National Specialist Commissioning Advisory Group (NSCAG) has funded three centres to establish and provide a national diagnostic service for England for children and adults suspected of suffering from primary ciliary dyskinesia (PCD). This is welcomed, as state of the art diagnostic testing will be available nationally which will increase the numbers of patients diagnosed with a condition in which early diagnosis has a very significant effect on both short-term and long-term morbidity. Inheritance is autosomal recessive with an incidence of around 1:15 000 in the Caucasian population and, as expected, we have found a much higher incidence in ethnic groups where consanguineous marriages are common. Accurate diagnosis will allow appropriate genetic counselling of families.

PCD is caused by one of a number of different ciliary defects that result in ineffective mucociliary clearance. Although most patients with PCD have symptoms from birth or early infancy,1 the diagnosis is frequently delayed2 and it is likely that a significant number of patients are never diagnosed.3 Failure to diagnose PCD leads to progressive and permanent lung destruction owing to obstruction of the airways with secretions and subsequent infection, leading to bronchiectasis. …
Lord Byron's first voyage in Greece (1810) and the neglected case of malaria
Authors: Costas Tsiamis, G Kalantzis, N Tompros, E Poulakou-Rebelakou
Journal: Journal of the Royal Society of Medicine (2011)

The aim of our report is to present the case of the illness which probably affected Lord Byron's health for the rest of his life. We present three letters of the famous British poet and fighter of the Greek Revolution in 1821, which were sent between 25 September and 3 October 1810. These letters are associated with Byron's illness during his excursion in the ancient monuments of Peloponnese. Lord Byron describes his clinical features with an irregular fever close to malaria but the identification of Plasmodium spp is difficult. According to the environmental conditions and the endemicity of the area, the hypothesis of a mixed species malaria cannot be excluded.
The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors
Authors: Francesco Di Virgilio
Journal: Pharmacological Reviews (2013)

Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by pathogens, cells, and tissues. It was initially thought that the inflammasomes participated only in pathogen recognition and in the pathogenesis of a few, rare, hereditary inflammatory disorders. On the contrary, it is now clear that they have a central role in the pathogenesis of basically all types of chronic inflammation, in metabolic diseases and cancer. So far, six or possibly eight inflammasome subtypes have been identified. Their main, but by no means exclusive, function is to catalyze conversion of pro-IL-1<i>β</i> and pro-IL-18 into their respective mature forms. However, the different inflammasome subtypes may also participate in additional responses, e.g., proliferation, regulation of glycolytic metabolism, or cell activation, albeit it is not clear whether these effects are still mediated through IL-1<i>β</i> release or via modulation of other caspase-1-dependent or -independent pathways. Central to inflammasome organization and activity are proteins belonging to the nucleotide binding domain, leucine-rich repeat, or NOD-like receptor family. One relevant exception is the AIM2 inflammasome. NOD-like receptors belong to the superfamily of pattern recognition receptors, a group of highly conserved molecules specialized in the recognition of invariant molecular patterns diffused across species. Given their potent proinflammatory activity, it is anticipated that inflammasome activation is tightly controlled. In this review, I will summarize essential features of the known NOD-like receptors, the basic molecular structure of inflammasomes, their participation in pathophysiological responses, and their possible exploitation for therapy.
Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system
Authors: Mikiko Ohno, Yoshinori Hiraoka, Tatsuhiko Matsuoka, Hidekazu Tomimoto, Keizo Takao, Tsuyoshi Miyakawa, Naoko Oshima, Hiroshi Kiyonari, Takeshi Kimura, Toru Kita, Eiichiro Nishi
Journal: Nature Neuroscience (2009)
The −670G&gt;A polymorphism in the <i>FAS</i> gene promoter region influences the susceptibility to systemic sclerosis
Authors: V Liakouli, M Manetti, A Pacini, B Tolusso, C Fatini, A Toscano, P Cipriani, S Guiducci, L Bazzichi, V Codullo, L Ruocco, L Dell’Orso, F Carubbi, A Marrelli, R Abbate, S Bombardieri, G Ferraccioli, C Montecucco, G Valentini, M Matucci-Cerinic, L Ibba-Manneschi, R Giacomelli
Journal: Annals of the Rheumatic Diseases (2008)

To evaluate the role of the single-nucleotide polymorphism (SNP) at position -670 in the FAS gene promoter (FAS-670G>A) in influencing the susceptibility, clinical features and severity of systemic sclerosis (SSc).350 white Italian SSc patients (259 with limited cutaneous SSc (lcSSc) and 91 with diffuse cutaneous SSc (dcSSc)) and 232 healthy individuals were studied. Patients were assessed for the presence of autoantibodies (anticentromere, anti-topoisomerase I (anti-Scl-70) antibodies), interstitial lung disease (ILD), pulmonary arterial hypertension and scleroderma renal crisis. FAS-670G>A SNP was genotyped by PCR restriction fragment length polymorphism assay. Serum levels of soluble FAS (sFAS) were analysed by ELISA.A significant difference in FAS-670 genotype distribution was observed between SSc patients and healthy individuals (p = 0.001). The frequency of the FAS-670A allele was significantly greater in SSc than in controls (p = 0.001). No significant difference in genotype distribution and allele frequencies was observed between lcSSc and dcSSc, although a greater frequency of the FAS-670A allele was found in dcSSc. The FAS-670AA genotype significantly influenced the predisposition to SSc (OR 1.97, 95% CI 1.35 to 2.88, p = 0.001) and to both lcSSc (OR 1.84, 95% CI 1.23 to 2.75, p = 0.003) and dcSSc (OR 2.37, 95% CI 1.41 to 3.99, p = 0.001). FAS-670A allele frequency was greater, although not significantly, in anti-Scl-70 antibody-positive dcSSc and ILD dcSSc. sFAS was significantly higher in patients and controls carrying the FAS-670AA genotype compared with those carrying the FAS-670GG genotype (p = 0.003 in SSc, p = 0.004 in controls).The FAS-670A allele is significantly associated with susceptibility to SSc, suggesting a role for a genetic control of apoptosis in the pathogenesis of the disease.
Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice
Authors: Antonio Nocito, Panco Georgiev, Felix Dahm, Wolfram Jochum, Michael Bader, Rolf Graf, Pierre-Alain Clavien
Journal: Hepatology (2007)

Hepatic ischemia and reperfusion (I/R) leads to the formation of leukocyte-platelet aggregates. Upon activation, platelets generate reactive oxygen species and release proapoptotic and proinflammatory mediators as well as growth factors. In cold hepatic ischemia, adhesion of platelets to endothelial cells mediates sinusoidal endothelial cell apoptosis. Furthermore, platelet-derived serotonin mediates liver regeneration. We hypothesized that platelets may contribute to reperfusion injury and repair after normothermic hepatic ischemia. The aim of this study was to assess the impact of platelets in normothermic hepatic I/R injury using models of impaired platelet function and immune thrombocytopenia. Inhibition of platelet function in mice was achieved via clopidogrel feeding. Immune thrombocytopenia was induced via intraperitoneal injection of anti-CD41 antibody. Platelet-derived serotonin was investigated using mice lacking tryptophan hydroxylase 1. Mice were subjected to 60 minutes of partial hepatic ischemia and various time points of reperfusion. Hepatic injury was determined via AST and histological analysis of the necrotic area as well as leukocyte infiltration. Liver regeneration was determined via proliferating cell nuclear antigen and Ki67 immunohistochemistry. Neither inhibition of platelet function nor platelet depletion led to a reduction of I/R injury. Liver regeneration and repair were significantly impaired in platelet-depleted animals. Mice lacking peripheral serotonin were deficient in hepatocyte proliferation, but otherwise displayed normal tissue remodeling.Platelets have no direct impact on the pathogenesis of normothermic I/R injury. However, they mediate tissue repair and liver regeneration. Furthermore, platelet-derived serotonin is a mediator of hepatocyte proliferation in the postischemic liver, but has no impact on tissue remodeling.
Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing
Authors: Roman K Thomas, Elizabeth Nickerson, Jan F Simons, Pasi A Jänne, Torstein Tengs, Yuki Yuza, Levi A Garraway, Thomas LaFramboise, Jeffrey C Lee, Kinjal Shah, Keith O'Neill, Hidefumi Sasaki, Neal Lindeman, Kwok-Kin Wong, Ana M Borras, Edward J Gutmann, Konstantin H Dragnev, Ralph DeBiasi, Tzu-Hsiu Chen, Karen A Glatt, Heidi Greulich, Brian Desany, Christine K Lubeski, William Brockman, Pablo Alvarez, Stephen K Hutchison, J H Leamon, Michael T Ronan, Gregory S Turenchalk, Michael Egholm, William R Sellers, Jonathan M Rothberg, Matthew Meyerson
Journal: Nature Medicine (2006)
Nitrogen Dioxide—Induced Respiratory Illness in Ice Hockey Players
Authors: Nathaniel Rothman
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Hedberg et al<sup>1</sup>recently reported on an epidemiologic investigation of an outbreak of nitrogen dioxide— induced illness in a group of high school ice hockey players. The results of both early (within 10 days of last exposure) and late (2 months after last exposure) follow-up spirometric testing were presented for exposed and unexposed athletes. Hedberg et al concluded that there were no differences in the five lung function indexes, either between exposure groups or between early and late follow-up. We tested this conclusion for the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV<sub>1</sub>/FVC), since acute exposure to nitrogen dioxide has been reported to cause an obstructive lung-function pattern.<sup>2</sup> We combined the singly and multiply exposed hockey players (Table 3 of the article) into one exposed group, because even a single exposure to nitrogen dioxide levels in the arena
Effect of Chemotherapy on IRC 741 Leukemia in Fischer Rats I. Development of Attenuated and Resistant Sublines
Authors: Veronica Armaghan
Journal: Cancer Research (1962)

This is a report showing that attenuation of malignancy induced in IRC 741 leukemia of Fischer rats, following early treatment with dimethylbenzimidazole (DMBZ), persisted for more than 40 transfer generations without treatment. The survival of rats bearing the attenuated tumor, IRC 741/A546, ranged from 24 to 43 days compared with 11 to 18 days' survival of rats bearing implants of IRC 741 tumor tissue. Resistance to DMBZ was developed in IRC 741 by initiating treatment 10 days after transplantation and in the attenuated subline, IRC 741/A546R, by initiating treatment of the host 20 days after tumor transplantation. Rats bearing implants of IRC 741R (DMBZ) lived 13–14 days after tumor transplantation, and A546R lived 21–39 days. Daily treatment of the sensitive subline proved to be twice as effective as treatment on alternate days. Daily treatment of the resistant subline was no more effective than treatment on alternate days. It was possible to cure some of the isologous hosts of IRC 741/A546 leukemia by initiating treatment 10–22 days after transplantation; but none of the rats given inoculations of IRC 741 were cured when treatment was initiated later than 4 days after transplantation. Rats cured of established tumors were resistant or immune to reinoculation with the altered and/or the parent tumor.
Clinical Presentation of Inhalational Anthrax Following Bioterrorism Exposure
Authors: T A Mayer, S Bersoff-Matcha, C Murphy, J Earls, S Harper, D Pauze, M Nguyen, J Rosenthal, D Cerva, G Druckenbrod, D Hanfling, N Fatteh, A Napoli, A Nayyar, E L Berman
Journal: JAMA (2001)

The use of anthrax as a weapon of biological terrorism has moved from theory to reality in recent weeks. Following processing of a letter containing anthrax spores that had been mailed to a US senator, 5 cases of inhalational anthrax have occurred among postal workers employed at a major postal facility in Washington, DC. This report details the clinical presentation, diagnostic workup, and initial therapy of 2 of these patients. The clinical course is in some ways different from what has been described as the classic pattern for inhalational anthrax. One patient developed low-grade fever, chills, cough, and malaise 3 days prior to admission, and then progressive dyspnea and cough productive of blood-tinged sputum on the day of admission. The other patient developed progressively worsening headache of 3 days' duration, along with nausea, chills, and night sweats, but no respiratory symptoms, on the day of admission. Both patients had abnormal findings on chest radiographs. Non–contrast-enhanced computed tomography of the chest showing mediastinal adenopathy led to a presumptive diagnosis of inhalational anthrax in both cases. The diagnoses were confirmed by blood cultures and polymerase chain reaction testing. Treatment with antibiotics, including intravenous ciprofloxacin, rifampin, and clindamycin, and supportive therapy appears to have slowed the progression of inhalational anthrax and has resulted to date in survival.
Release of the antimicrobial peptide LL-37 from DNA/F-actin bundles in cystic fibrosis sputum
Authors: R. Bucki, F. J. Byfield, P. A. Janmey
Journal: European Respiratory Journal (2007)

Cationic antibacterial peptides (ABPs) are secreted in the airways and function in the first line of defence against infectious agents. They attack multiple molecular targets to cooperatively penetrate and disrupt microbial surfaces and membrane barriers. Antibacterial properties of ABPs, including cathelicidin LL-37, are reduced in cystic fibrosis (CF) airways as a result of direct interaction with DNA and filamentous (F)-actin. Microscopic evaluation of a mixed solution of DNA and F-actin, after the addition of rhodamine-B-labelled LL-37 peptide, revealed the presence of a bundle structure similar to that present in CF sputum. Analysis of CF sputum after centrifugation showed that LL-37 was mostly bound to components of the pellet fraction containing DNA, F-actin and cell remnants. Factors that dissolve DNA/actin bundles and fluidise CF sputum, such as Dornase alfa (recombinant human DNase I), gelsolin, polyaspartate or their combinations, increased the amount of LL-37 peptide detected in the supernatant of CF sputum. The presence of the bacterial endotoxin lipopolysaccharide (LPS) in CF sputum and the ability of LPS to inhibit the antibacterial activity of LL-37 suggests that inactivation of LL-37 function in CF sputum partially results from its interaction with LPS. LL-37–LPS interaction was prevented by an LPS-binding protein (LBP)-derived peptide known for its ability to neutralise LPS, whereas LBPW91A, a mutant peptide that lacks ability to bind LPS, had no effect. A combination of factors that dissolve DNA/filamentous-actin aggregates together with lipopolysaccharide-binding agents may represent a potential treatment for the chronic infections that occur in cystic fibrosis airways.
Nitroglycerin-induced coronary vasodilation in cardiac transplant recipients. Evaluation with in vivo intracoronary ultrasound.
Authors: F J Pinto, F G St Goar, T A Fischell, M L Stadius, H A Valantine, E L Alderman, R L Popp
Journal: Circulation (1992)

BACKGROUND Coronary artery vasomotion is altered after cardiac transplantation. The impact of accelerated transplant coronary atherosclerosis and myocardial rejection on vasomotion is not well understood. Intravascular ultrasound is a new imaging method with the ability to study real-time changes in coronary artery dimensions. METHODS AND RESULTS Epicardial coronary artery response to nitroglycerin was studied in 32 cardiac transplant recipients (age, 47 +/- 11 years) 3 weeks to 10 years after transplantation with intracoronary ultrasound. Cross-sectional luminal area and diameter were measured at a fixed position in the left anterior descending artery immediately before and every 30 seconds for 5 minutes after 0.4 mg of sublingual nitroglycerin. Cross-sectional area increased from a baseline of 13.1 +/- 3.9 mm2 to 15.8 +/- 3.9 mm2 at maximal vasodilation; luminal diameter increased from 4.0 +/- 0.6 mm to 4.5 +/- 0.6 mm. This increase reached statistical significance (p less than 0.001) at 1.5 minutes after administration of nitroglycerin; mean maximum increase occurred at 4.5 minutes (24% for cross-sectional area and 11% for luminal diameter). Patients with biopsy-proven mild or moderate concurrent rejection had a significantly blunted vasodilatory response versus the nonrejection group (9% versus 27% for cross-sectional area, p less than 0.04), although a vasodilatory effect was still present. Nitroglycerin response was well preserved in patients up to 10 years after transplantation; however, there was a trend toward a decreased response in patients studied immediately after transplantation (21% versus 29%, p = 0.37). Coronary intimal thickness, as measured by ultrasound, had no impact on the vasodilatory response (R = 0.23, p = 0.34). CONCLUSIONS Vasodilatory response to nitroglycerin in cardiac transplant recipients is attenuated during episodes of cardiac rejection. This response is preserved in long-term survivors and is independent of the degree of intimal thickening. Intravascular ultrasound provides a new method to document real-time epicardial coronary vasomotion.