tbuckley/cabot-search huggingface dataset:
Alveolar epithelial fluid transport in acute lung injury: new insights
Authors: C. Sartori, M.A. Matthay
Journal: European Respiratory Journal (2002)

Pulmonary oedema is a life-threatening condition that frequently leads to acute respiratory failure. From a physiological perspective, pulmonary oedema develops either because of an increase in lung vascular hydrostatic pressure or an increase in lung vascular permeability. Resolution of alveolar oedema depends on the active removal of salt and water from the distal air spaces of the lung across the distal lung epithelial barrier. Much has been learned about the molecular and cellular basis for oedema fluid reabsorption, including the role of apical ion transporters for sodium (epithelial sodium channel) and chloride (cystic fibrosis transmembrane conductance regulator), as well as the central importance of the sodium pump. The rate of fluid clearance can be upregulated by both catecholamine-dependent and -independent mechanisms. Injury to the alveolar epithelium can disrupt the integrity of the alveolar barrier or downregulate ion transport pathways, thus, reducing net alveolar fluid reabsorption and enhancing the extent of alveolar oedema. Endogenous catecholamines upregulate alveolar fluid clearance in several experimental models of acute lung injury, but this upregulation may be short term and insufficient to counterbalance alveolar flooding. There is new evidence, however, that pharmacological treatment with β 2 -adrenergic agonists and/or epithelial growth factors may influence a more sustained stimulation of alveolar fluid reabsorption and in turn facilitate recovery from experimental pulmonary oedema. Similar results have been achieved experimentally by gene transfer to enhance the abundance of sodium transporters in the alveolar epithelium. Clinical studies show that impaired alveolar fluid transport mechanisms contribute to the development, severity and outcome of pulmonary oedema in humans. Very recent data suggest that mechanisms that augment transepithelial sodium transport and enhance the clearance of alveolar oedema may lead to more effective prevention or treatment for some types of pulmonary oedema.
A First-in-Man Phase I and Pharmacokinetic Study on CHR-2797 (Tosedostat), an Inhibitor of M1 Aminopeptidases, in Patients with Advanced Solid Tumors
Authors: Alison H.M. Reid, Andrew Protheroe, Gerhardt Attard, Nikki Hayward, Laura Vidal, James Spicer, Heather M. Shaw, Elizabeth A. Bone, Joanne Carter, Leon Hooftman, Adrian Harris, Johann S. De Bono
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To determine the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary therapeutic activity profile of CHR-2797 (tosedostat), a novel, orally bioavailable inhibitor of the M1 family of aminopeptidases with antiproliferative and antiangiogenic activity in vitro. Experimental Design: A phase I study of accelerated titration design that escalated through nine doses (10-320 mg) in patients (Eastern Cooperative Oncology Group performance status, ≤2) with advanced solid tumors. CHR-2797 was administered once daily. Results: Forty patients (median age, 60 years; range, 24-80 years; male, 27; female, 13) were treated in 12 cohorts with once daily doses (10-320 mg). Dose-limiting toxicities were thrombocytopenia, dizziness, and visual abnormalities in one patient, and anemia, blurred vision, and vomiting in a second patient at 320 mg, resulting in an inability to complete 28 days of study drug. The most commonly observed toxicities were fatigue, diarrhea, peripheral edema, nausea, dizziness, and constipation. One patient had a partial response (renal cell carcinoma) and four patients had stable disease for &amp;gt;6 months. CHR-2797 and its active metabolite, CHR-79888, show dose-proportional increases in plasma AUC and Cmax. The terminal half-life for CHR-2797 is ∼1 to 3.5 hours and between 6 and 11 hours for CHR-79888. Intracellular (packed blood cells) exposure to CHR-79888 is consistent with intracellular levels that proved to be efficacious in xenograft models. Conclusion: CHR-2797 is well tolerated and can be safely administered at doses that result in intracellular levels of CHR-79888 that are associated with activity in preclinical models. The recommended dose for single agent therapy in solid tumors is 240 mg/d.
Expression of glucocorticoid receptors and in steroid sensitive and steroid insensitive interstitial lung diseases
Authors: L Pujols
Journal: Thorax (2004)

Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors alpha (GRalpha) and beta (GRbeta). A study was undertaken to assess GRalpha and GRbeta expression in steroid insensitive interstitial lung disease (idiopathic pulmonary fibrosis (IPF)) and steroid sensitive interstitial lung diseases (sarcoidosis and cryptogenic organising pneumonia (COP)).Lung tissue was obtained from control subjects and from patients with IPF, sarcoidosis, and COP. Pulmonary function tests were carried out at the time of lung biopsy and every 3 months. GRalpha and GRbeta expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25-75th percentile.GRalpha mRNA expression (10(5) cDNA copies/ micro g total RNA) was higher in patients with steroid sensitive interstitial lung diseases (10.0; 7.8-14.9; n = 11) than in patients with IPF (4.4; 3.2-6.6; n = 19; p<0.001). GRbeta expression was at least 1000 times lower than that of GRalpha and did not differ between the three groups. A negative correlation was found between GRalpha mRNA levels and the fibrotic pathology score of the tissue (r = -0.484, p<0.01) and a positive correlation was found between GRalpha mRNA levels and improvement in forced vital capacity (r = 0.633; p<0.01) after treatment of patients with glucocorticoids. Immunoreactivity for GR protein was also higher in patients with sarcoidosis and COP than in those with IPF.The variable response of some interstitial lung diseases to steroid treatment may be the result of differences in the expression of GRalpha.
Lower Neck Neurilemmoma Can Masquerade as Lymph Node Metastasis on FDG PET/CT in Patient With Nasopharyngeal Carcinoma
Authors: Te-Chun Hsieh, Yu-Chin Wu, Cheng-Nan Hsu, Chun-Fan Yang, Kuo-Yang Yen, Chia-Hung Kao, Shung-Shung Sun
Journal: Clinical Nuclear Medicine (2011)

A 50-year-old man with nasopharyngeal carcinoma was suspected to have progressive malignant disease because of an unexpected FDG-avid finding that was suspected to be neck lymph node metastasis on the follow-up FDG PET/CT after the definite anticancer therapy. However, after carefully correlating with the relevant MRI findings because of the atypical depth of the neck lesion and possible connection with the spinal nerve, the FDG-avid finding was reconsidered to be a tumor that originated from the nerve. The subsequent histologic examination confirmed the diagnosis of neurilemmoma.
Intravenous Labetalol in Acute Aortic Dissection-Reply
Authors: Blair P. Grubb
Journal: JAMA (1987)

In Reply.—  Dr Eisele's point is well taken; however, the package insert for labetalol states that 300 mg is the usual intravenous dosage required prior to starting oral therapy, rather than an absolute maximum. In addition, it states that the infusion may be adjusted as needed to maintain an adequate blood pressure response.  Our patient was maintained atnon peros status due to his nausea with vomiting and because surgery was considered an option had medical therapy proved unsuccessful. Thus, rather than risk a rebound of blood pressure in a patient with aortic dissection, we chose to continue intravenous labetalol therapy at a low, effective, well-tolerated dose until oral therapy could be initiated.
Increased calmodulin levels in fibroblasts from progressive systemic sclerosis
Authors: M. SEISHIMA, S. NAGAO, M. KUWAHARA, S. MORI, Y. NOZAWA
Journal: British Journal of Dermatology (1992)

Calmodulin levels in cultured skin fibroblasts from patients with progressive systemic sclerosis (PSS) and healthy controls were measured by their ability to activate cyclic AMP-phosphodiesterase. Calmodulin levels were significantly increased in PSS fibroblasts compared with normal control fibroblasts. The changes in calmodulin content of PSS fibroblasts were also assessed by a radioimmunoassay. These findings suggest that an elevated level of calmodulin may play a role in the pathogenesis of PSS.
Systolic Blood Pressure Levels Among Adults With Hypertension and Incident Cardiovascular Events
Authors: Carlos J. Rodriguez, Katrina Swett, Sunil K. Agarwal, Aaron R. Folsom, Ervin R. Fox, Laura R. Loehr, Hanyu Ni, Wayne D. Rosamond, Patricia P. Chang
Journal: JAMA Internal Medicine (2014)

Studies document a progressive increase in heart disease risk as systolic blood pressure (SBP) rises above 115 mm Hg, but it is unknown whether an SBP lower than 120 mm Hg among adults with hypertension (HTN) lowers heart failure, stroke, and myocardial infarction risk.To examine the risk of incident cardiovascular (CV) events among adults with HTN according to 3 SBP levels: 140 mm Hg or higher; 120 to 139 mm Hg; and a reference level of lower than 120 mm Hg.A total of 4480 participants with HTN but without prevalent CV disease at baseline (years 1987-1989) from the Atherosclerosis Risk in Communities Study were included. Measurements of SBP were taken at baseline and at 3 triennial visits; SBP was treated as a time-dependent variable and categorized as elevated (≥140 mm Hg), standard (120-139 mm Hg), and low (<120 mm Hg). Multivariable Cox regression models included baseline age, sex, diabetes status, BMI, high cholesterol level, smoking status, and alcohol intake.Incident composite CV events (heart failure, ischemic stroke, myocardial infarction, or death related to coronary heart disease).After a median follow-up of 21.8 years, a total of 1622 incident CV events had occurred. Participants with elevated SBP developed incident CV events at a significantly higher rate than those in the low BP group (adjusted hazard ratio [HR], 1.46; 95% CI, 1.26-1.69). However, there was no difference in incident CV event-free survival among those in the standard vs low SBP group (adjusted HR, 1.00; 95% CI, 0.85-1.17). Further adjustment for BP medication use or diastolic BP did not significantly affect the results.Among patients with HTN, having an elevated SBP carries the highest risk for cardiovascular events, but in this categorical analysis, once SBP was below 140 mm Hg, an SBP lower than 120 mm Hg did not appear to lessen the risk of incident CV events.
Neuroendocrine Prostate Cancer After Hormonal Therapy: Knowing Is Half the Battle
Authors: Scott T. Tagawa
Journal: Journal of Clinical Oncology (2014)

Article Tools ONCOLOGY GRAND ROUNDS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2014.57.5100 Journal of Clinical Oncology - published online before print September 15, 2014 PMID: 25225431 Neuroendocrine Prostate Cancer After Hormonal Therapy: Knowing Is Half the Battle Scott T. TagawaxScott T. TagawaSearch for articles by this author Show More Weill Cornell Medical College, New York, NY https://doi.org/10.1200/JCO.2014.57.5100 First Page Full Text PDF Figures and Tables © 2014 by American Society of Clinical Oncology
Cilium Evolution: Identification of a Novel Protein, Nematocilin, in the Mechanosensory Cilium of Hydra Nematocytes
Authors: J. S. Hwang, Y. Takaku, J. Chapman, K. Ikeo, C. N. David, T. Gojobori
Journal: Molecular Biology and Evolution (2008)

The cnidocil at the apical end of Hydra nematocytes is a mechanosensory cilium, which acts as a “trigger” for discharge of the nematocyst capsule. The cnidocil protrudes from the center of the cnidocil apparatus and is composed of singlet and doublet microtubules surrounding an electron-dense central filament. In this paper, we identify a novel protein, nematocilin, which is localized in the central filament. Immunofluorescence staining and immunogold electron microscopy show that nematocilin forms filaments in the central core of the cnidocil. Nematocilin represents a new member of the intermediate filament superfamily. Two paralogous sequences of nematocilin are present in the Hydra genome and appear to be the result of recent gene duplication. Comparison of the exon–intron structure suggests that the nematocilin genes evolved from the nuclear lamin gene by conserving exons encoding the coiled-coil domains and replacing the C-terminal lamin domains. Molecular phylogenetic analyses also support the hypothesis of a common ancestor between lamin and nematocilin. Comparison of cnidocil structures in different cnidarians indicates that a central filament is present in the cnidocils of several hydrozoan and a cubozoan species but is absent in the cnidocils of anthozoans. A nematocilin homolog is absent in the recently completed genome of the anthozoan Nematostella. Thus, the evolution of a novel ciliary structure, which provides mechanical rigidity to the sensory cilium during the process of mechanoreception, is associated with the evolution of a novel protein.
Modulation of Cardiac Calcium Sensitivity: a New Approach to Increasing the Strength of the Heart.
Authors: R A Chapman
Journal: Cardiovascular Research (1994)

Journal Article Modulation of Cardiac Calcium Sensitivity: a New Approach to Increasing the Strength of the Heart. Get access R A Chapman R A Chapman Bristol, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 5, May 1994, Pages 723–724, https://doi.org/10.1093/cvr/28.5.723 Published: 01 May 1994
Genomic Profiling of Hepatocellular Adenomas Reveals Recurrent FRK-Activating Mutations and the Mechanisms of Malignant Transformation
Authors: Camilla Pilati, Eric Letouzé, Jean-Charles Nault, Sandrine Imbeaud, Anaïs Boulai, Julien Calderaro, Karine Poussin, Andrea Franconi, Gabrielle Couchy, Guillaume Morcrette, Maxime Mallet, Saïd Taouji, Charles Balabaud, Benoit Terris, Frédéric Canal, Valérie Paradis, Jean-Yves Scoazec, Anne de Muret, Catherine Guettier, Paulette Bioulac-Sage, Eric Chevet, Fabien Calvo, Jessica Zucman-Rossi
Journal: Cancer Cell (2014)
CHARACTERS OF HUNTINGTON'S CHOREA
Authors: C. Allbutt
Journal: BMJ (1918)

<h3>SUMMARY:</h3> Reversible cerebral vasoconstriction syndrome is a clinical and radiologic syndrome that represents a common presentation of a diverse group of disorders. The syndrome is characterized by thunderclap headache and reversible vasoconstriction of cerebral arteries, which can either be spontaneous or related to an exogenous trigger. The pathophysiology of reversible cerebral vasoconstriction syndrome is unknown, though alterations in cerebral vascular tone are thought to be a key underlying mechanism. The syndrome typically follows a benign course; however, reversible cerebral vasoconstriction syndrome may result in permanent disability or death in a small minority of patients secondary to complications such as ischemic stroke or intracranial hemorrhage.
Serum Cathepsin S Is Associated With Decreased Insulin Sensitivity and the Development of Type 2 Diabetes in a Community-Based Cohort of Elderly Men
Authors: Elisabeth Jobs, Ulf Risérus, Erik Ingelsson, Johan Sundström, Magnus Jobs, Elisabet Nerpin, David Iggman, Samar Basu, Anders Larsson, Lars Lind, Johan Ärnlöv
Journal: Diabetes Care (2012)

OBJECTIVE To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes. RESEARCH DESIGN AND METHODS Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up. RESULTS After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase −0.09 [95% CI −0.14 to −0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08–2.01], P = 0.01). CONCLUSIONS Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.
Effects of cisapride on parameters of oesophageal motility and on the prolonged intraoesophageal pH test in infants with gastro-oesophageal reflux disease.
Authors: S Cucchiara, A Staiano, A Boccieri, M De Stefano, C Capozzi, G Manzi, F Camerlingo, F M Paone
Journal: Gut (1990)

The effect of cisapride, a new gastrointestinal prokinetic drug, on oesophageal motility and acid reflux was studied in 14 children with gastro-oesophageal reflux disease, receiving either placebo or cisapride 0.15 mg/kg intravenously. Cisapride significantly (p less than 0.01) increased the lower oesophageal sphincter pressure (+124%), the amplitude (+84%) and duration (+24%) of oesophageal peristaltic waves, whereas the placebo treatment did not produce any changes. Subsequently, all 14 children underwent 24 hour oesophageal pH-monitoring before and after four weeks of treatment with oral cisapride 0.2 mg/kg tid given in addition to postural therapy and thickened feedings. The 24 hour intraoesophageal pH recordings and symptomatic scores were compared with those of 10 control patients treated only by postural therapy and thickened feedings. When compared with baseline pH data, cisapride significantly reduced the oesophageal acid exposure time, the mean duration of each reflux episode, the duration of the longest reflux episode and the number of long lasting reflux episodes; the number of reflux episodes was not influenced. The effect of cisapride was marked and consistent during fasting and sleep periods. Oesophageal acid exposure was reduced more significantly in patients given cisapride (-61%) than in controls (-24%; p less than 0.001). Symptom improvement was greater after four weeks of cisapride treatment (score reduction: 61%) than after postural and dietary therapy alone (score reduction: 42%; p less than 0.01). No adverse effects occurred. These findings suggest that cisapride is a valuable drug in the management of gastro-oesophageal reflux disease in children.
Long term serological surveillance after treatment of Helicobacter pylori infection.
Authors: R A Veenendaal, A S Pena, J L Meijer, H P Endtz, M M van der Est, W van Duijn, F Eulderink, J Kreuning, C B Lamers
Journal: Gut (1991)

Fifteen patients with type B gastritis caused by Helicobacter pylori infection were treated with 'triple' therapy consisting of colloidal bismuth subcitrate, amoxycillin, and metronidazole. All were followed up as outpatients every three months for at least one year. After 'triple' therapy a significant (p less than 0.01) and persistent reduction in IgA and IgG antibody levels against H pylori was detected. In three patients recurrent active infection with H pylori at nine and 12 months was detected by a rise in IgA (three patients) and IgG (two patients) antibody levels against H pylori and worsening of symptoms, and was confirmed by culture and histology. In 11 patients, the absence of infection at 12 months was confirmed by culture and histology. In a control group of 13 patients with type B gastritis who received no antibacterial treatment, specific IgA and IgG antibody levels against H pylori remained unchanged during 12 months of follow up. Although specific IgG against H pylori is the most widely used serological test for screening, our data indicate that specific IgA is also valuable in monitoring treatment. These serological tests are easy to perform, relatively inexpensive, devoid of radioactivity and are very acceptable to patients. It is concluded that serological testing is the preferred method for follow up after treatment for H pylori infection and will probably replace endoscopy or the urea breath test.
CAROTID ARTERY INTIMA-MEDIA THICKNESS (CIMT) ACCRETION RATE AND RISK OF ATHEROGENESIS IN A PRIMARY PREVENTION POPULATION
Authors: Uchechukwu K.A. Sampson, Fazio Sergio, John W. Patton, Anne-Sophie Sillesen, Amanda K. Wake, Andre L. Churchwell, Alfred S. Callahan
Journal: Journal of the American College of Cardiology (2010)
Variant Variant Angina Pectoris
Authors: MICHAEL A. NEVINS
Journal: Annals of Internal Medicine (1974)

Comments1 May 1974Variant Variant Angina PectorisMICHAEL A. NEVINS, M.D., F.A.C.P.MICHAEL A. NEVINS, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-5-673_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent case report by Gorfinkel and colleagues (Ann Intern Med79:795-799, 1973) illustrates another variant of variant angina pectoris. One aspect of this case that bears reemphasis is that classical ST elevations may be manifest in electrocardiographic leads reflecting the frontal plane. A recent study by Bete and associates (1) indicated that ST elevations in Prinzmetal's angina occur with equal frequency in anterior and inferior leads. The electrode placement system commonly employed in coronary care units, as well as for ambulatory monitoring, provides information that is essentially limited to the horizontal plane. Thus, when using conventional...Reference1. BETESHUBROOKSBLOCK JSP: Prinzmetal's angina pectoris (PAP), clinical and anatomical spectrum and results of coronary artery bypass surgery (abstract). Circulation 48(suppl 4):145, 1973 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MICHAEL A. NEVINS, M.D., F.A.C.P.Affiliations: Bergen Pines County Hospital Paramus, New Jersey 07652 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySyndrome of symptomatic coronary arterial spasm with nearly normal coronary arteriogramsAcute myocardial infarction and angiographically normal coronary arteries. An unproven combination. 1 May 1974Volume 80, Issue 5Page: 673-673KeywordsAnginaCardiac care unitElectrocardiographyInformation technology ePublished: 1 December 2008 Issue Published: 1 May 1974 PDF downloadLoading ...
THE COMPOSITION OF SOME SO-CALLED SYNTHETICS AND "ETHICAL" NOSTRUMS.
Authors: WILLIAM J. ROBINSON
Journal: JAMA (1904)

One fine morning, some weeks ago, a young lady, an actress by profession, came to consult me about an obstinate headache.  have used everything you can think of, she said.  have used antikamnia, Kohler's headache powders,—'s migraine tablets, orangeine, Hegeman's headache wafers and a lot of other things. At first they used to relieve me, but now they don't do me any good. The self-drugging young woman enumerated five different articles which she had used; different articles in name, but identically the same so far as composition is concerned. Everyone of those articles consists of acetanilid, sodium bicarbonate and a little caffein. Finding a malarial history, I prescribid quinin and ergotin, and her headaches promptly vanished.  About two weeks later a young practitioner approached me at the close of a medical meeting with the following words : Doctor, I wish you would recommend me something good for dysmenorrhea.
Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the α-thalassemia myelodysplasia syndrome (ATMDS)
Authors: Richard J Gibbons, Andrea Pellagatti, David Garrick, William G Wood, Nicola Malik, Helena Ayyub, Cordelia Langford, Jacqueline Boultwood, James S Wainscoat, Douglas R Higgs
Journal: Nature Genetics (2003)