tbuckley/cabot-search huggingface dataset:
Use of mouth pressure twitches induced by cervical magnetic stimulation to assess voluntary activation of the diaphragm
Authors: P F de Bruin, R A Watson, N Khalil, N B Pride
Journal: European Respiratory Journal (1998)

There is a need for a simple method to assess the adequacy of diaphragm activation during voluntary inspiratory efforts in patients with suspected respiratory muscle weakness. We have compared mouth (Pmo,t), oesophageal (Poes,t) and transdiaphragmatic (Pdi,t) twitch pressure elicited by cervical magnetic stimulation (CMS) in five normal men (mean (SD) age 32.2 (1.8) yrs) on two separate study days. Single magnetic stimuli were delivered at functional residual capacity during relaxation and during graded voluntary inspiratory efforts against a closed airway. As voluntary-effort transdiaphragmatic and oesophageal pressure increased, Pdi,t and Poes,t decreased linearly (r range, respectively, 0.82-0.98 and 0.87-0.95). During relaxation, Pmo,t was unreliable due to the poor transmission of intrathoracic pressure, but during inspiratory efforts, the relation between voluntary mouth pressure and Pmo,t was also linear (r range 0.84-0.95). On average, our subjects voluntarily generated 99, 100 and 102% of the maximum transdiaphragmatic, oesophageal and mouth pressures predicted by the respective linear regression equations. Pmo,t was correlated to both Poes,t and Pdi,t during inspiratory efforts, but not during relaxation. These studies confirm that twitch pressures induced by CMS during inspiratory efforts can be assessed at the mouth in normal subjects, providing a simple and non-invasive technique for assessing diaphragm activation during voluntary inspiratory efforts. Potentially, this technique could be made more sensitive and accurate and applied to detect submaximal efforts in patients.
GROUP A STREPTOCOCCAL BACTERIOCIN
Authors: John R. Tagg, Adnan S. Dajani, Lewis W. Wannamaker, Ernest D. Gray
Journal: The Journal of Experimental Medicine (1973)

A bacteriocin, streptocin A, was isolated from the supernatant fluid of tryptic soy broth cultures of Group A streptococcus strain FF-22. Evidence was obtained which supports the view that the failure to recover active streptocin A after growth of the producer strain in certain fluid media is due to the inactivation of the bacteriocin by concomitantly synthesized streptococcal proteinase. The bacteriocin was purified 139-fold and the active product appeared to be of uniform size, having a molecular weight of approximately 8,000. Streptocin A was bactericidal, but not lytic, for a susceptible Group A streptococcus and the lethal effect was markedly temperature dependent. The bacteriocin inhibited the synthesis of DNA, RNA, and protein, and also prevented the uptake and incorporation of glucose by the sensitive cells. Degradation of RNA occurred, but appeared to be less than that produced by a staphylococcal bacteriocin. This effect may be due to differences in the killing potency of the two bacteriocins in preparations having similar inhibitory activity when measured by lawn culture assays.
Apparent but not real increase in asthma prevalence during the 1990s
Authors: R. Barraclough, G. Devereux, D.J. Hendrick, S.C. Stenton
Journal: European Respiratory Journal (2002)

The authors investigated changes in asthma prevalence and perception of bronchoconstriction over 6 yrs in adults of Newcastle-upon-Tyne. Postal questionnaires were sent to 6,000 subjects aged 20–44 yrs in 1992–1993 and 1998–1999. Random samples of 600 responders had assessments of atopy, airway responsiveness, and their ability to perceive methacholine-induced bronchoconstriction. The prevalences of asthmatic symptoms, physician-diagnosis, and medication use increased by an average of 4.4%, particularly in subjects aged &lt;30 yrs (8.7 versus 2.7). Atopy prevalence increased from 25% to 31% but atopics and nonatopics had similar mean changes in questionnaire data (5.2 versus 3.4). The probability of a positive methacholine test decreased as did the mean methacholine dose/response slope (0.00527 to 0.00379), indicating lower levels of airway responsiveness. This can be largely explained by an increase in use of inhaled corticosteroids (5.0–9.3%). The proportion of subjects perceiving bronchoconstriction during methacholine tests increased from 63 to 77%. The authors conclude that current changes in asthma epidemiology in adults may result from increased awareness of symptoms (and/or an increased willingness to report them), and from an increased willingness of physicians to make the diagnosis and prescribe treatment, not from increased disease prevalence.
Quantitative Reverse Transcriptase Polymerase Chain Reaction and the Onco<i>type</i> DX Test for Assessment of Human Epidermal Growth Factor Receptor 2 Status: Time to Reflect Again?
Authors: John M.S. Bartlett, Jane Starczynski
Journal: Journal of Clinical Oncology (2011)

It seems that controversy is ever present regarding the optimal approach to testing for human epidermal growth factor receptor 2 (HER2) status in breast cancer. There are at least two aspects to the controversy. First, is there an optimal test or approach for all patients? Second, is it reasonable to expect perfection with any single approach? These issues are highlighted by several recent reports that focus on the use of reverse transcriptase polymerase chain reaction (RT-PCR) for HER2. In a study of more than 800 patients from three hospitals, Dabbs et al suggests that RT-PCR, specifically when performed in the context of the Oncotype DX test, showed a striking level of discordance with immunohistochemistry (IHC)/fluorescent in situ hybridization (FISH) results. In their report, Dabbs et al focus on the high false-negative rate for a HER2 quantitative RT-PCR (qRT-PCR) approach in cases that are clearly HER2 positive according to FISH analyses. These data seem to contradict data from an earlier study by Baehner et al, which suggested that concordance between the qRT-PCR component of the Oncotype DX assay and FISH was greater than the 95% threshold required by the American Society of Clinical Oncology (ASCO) –College of American Pathologists (CAP) guidelines on HER2 testing for the validation of a novel approach for HER2 testing. Clinicians and patients alike need a clear understanding of the differences, if any, between the reports by Baehner et al and Dabbs et al. In addition, we needguidelines(providedbyASCO-CAPandotherexperts, forexample) regarding the appropriate use of additional tests beyond conventional IHC and FISH. Finally, the present findings should be considered carefully by those using or supplying qRT-PCR tests.
Identification of HBV DNA sequences that are predictive of response to lamivudine therapy
Authors: Alessia Ciancio, Antonina Smedile, Mario Rizzetto, Marco Lagget, John Gerin, Brent Korba
Journal: Hepatology (2004)

Numerous studies have shown that resistance to long-term lamivudine therapy occurs in as many as (2/3) of hepatitis B virus (HBV) chronic carriers. Additional studies have shown that reversion of HBV mutations in the precore/core promoter region conferring an HBeAg-negative phenotype/genotype can occur in up to 30% of lamivudine-treated patients. In this study, sequences of the HBV polymerase and precore/core coding regions in 26 HBV-infected patients (24 with HBeAg-negative virus infection, 25 genotype D, 1 genotype A) treated for 27 to 53 months with lamivudine were analyzed to determine the relationship between pretreatment HBV DNA sequence patterns and long-term treatment response, and the effect of therapy on the status of HBV precore mutations. Reversions of precore mutations A1762T/G1764A and G1896A were observed in 29% and 25% of patients, respectively, but none became HBeAg-positive. These data are consistent with previously published reversion frequencies for 2 other groups of lamivudine-treated patients. Two naturally-occurring DNA polymorphisms at aa91 and aa256 of the HBV polymerase were observed in the pretreatment serum samples, which correlated with extended treatment failure. In conclusion, reversion of mutations conferring an HBeAg-negative phenotype occur relatively frequently under lamivudine therapy. Furthermore, at least in HBeAg-negative patients infected predominantly with HBV genotype D, specific viral DNA sequences which are present before therapy appear to be useful as predictors of long-term response to lamivudine treatment.
Macrolide Resistance in<i>Treponema pallidum</i>in the United States and Ireland
Authors: Sheila A. Lukehart, Charmie Godornes, Barbara J. Molini, Patricia Sonnett, Susan Hopkins, Fiona Mulcahy, Joseph Engelman, Samuel J. Mitchell, Anne M. Rompalo, Christina M. Marra, Jeffrey D. Klausner
Journal: New England Journal of Medicine (2004)

An HIV-infected patient in San Francisco with primary syphilis was treated with azithromycin, but the lesion did not resolve. The authors of this case report confirmed resistance to azithromycin and identified a mutation in the 23S rRNA genes of T. pallidum. The mutation was also found in samples collected in Baltimore, Seattle, and Dublin.
LIPIDS AND IMMUNOLOGICAL REACTIONS
Authors: Frank L. Horsfall, Kenneth Goodner
Journal: The Journal of Experimental Medicine (1936)

1. Complete lipid patterns of specific precipitates from horse and rabbit Type I antipneumococcus sera, as well as of the sera themselves, have been determined by gasometric micro methods. 2. The lipid patterns of horse and rabbit antisera are very similar, and as regards the phosphatide fractions are relatively identical. 3. The lipid patterns of specific precipitates from horse and rabbit antisera show one outstanding qualitative difference. The specific precipitate from horse antiserum contains an amino phosphatide, which is probably cephalin, while that from rabbit antiserum contains a non-amino phosphatide, which is thought to be lecithin.
Effects of Nitric Oxide Synthase Inhibition on Basal Function and the Force-Frequency Relationship in the Normal and Failing Human Heart In Vivo
Authors: James M. Cotton, Mark T. Kearney, Philip A. MacCarthy, Richard M. Grocott-Mason, Dougal R. McClean, Christophe Heymes, Peter J. Richardson, Ajay M. Shah
Journal: Circulation (2001)

Background Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. Methods and Results We compared the effects of intracoronary NO synthase inhibition with N G -monomethyl- l -arginine (L-NMMA; 25 μmol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt max (from 1826 to 1578 mm Hg/s; P &lt;0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt max were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt max (from 1313 to 1337 mm Hg/s; P =NS). The blunted pacing-induced rise in LV dP/dt max in these patients was unaltered by L-NMMA. Conclusion Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.
Functional respiratory imaging to decide between a conservative or surgical approach in patients with unilateral diaphragmatic paralysis
Authors: Glenn Leemans, Cedric Van Holsbeke, Wim Vos, Samir Vinchurkar, Jan De Backer, Paul Van Schil, Wilfried De Backer
Journal: European Respiratory Journal (2013)

Introduction 

Patients with unilateral diaphragmatic paralysis (UDP) who still experience symptoms despite optimal therapy, diaphragm plication is indicated. Despite the promising clinical results, selection of suitable patients is important.

Case presentation 

Two patients with a UDP presented with recent increase in dyspnea. Pulmonary function test (PFT) showed a reduced lung function. CT revealed atelectasis in the inferior parts of the lung at the side of the paralysis. To investigate regional ventilation to the lower lobes, Functional Respiratory Imaging (FRI) was performed. The lobar expansion from functional residual capacity (FRC) to total lung capacity (TLC) was considered as a measure for lobar ventilation as this represents the internal airflow lobar distribution (IALD). FRI analysis showed a poor IALD of the inferior parts of subject one and a diaphragm plication was performed. Subject two had still IALD to the lower lobe even though the presence of atelectasis and a conservative approach with regular follow-up was therefore chosen. After 6 months, both approaches were effective in the treatment of dyspnea.

![Figure][1] 



Conclusions 

Despite having the same clinical and radiological findings, FRI showed a clear difference in regional ventilation.This demonstrate the possible potential of FRI to assist the clinical decision making process between conservative versus surgical approach.

 [1]: pending:yes
MicroRNAs and atrial fibrillation: new fundamentals
Authors: Z. Wang, Y. Lu, B. Yang
Journal: Cardiovascular Research (2010)

Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia associated with pronounced morbidity, mortality, and socio-economic burden. This pathological entity is associated with an altered expression profile of genes that are important for atrial function. MicroRNAs (miRNAs), a new class of non-coding mRNAs of around 22 nucleotides in length, have rapidly emerged as one of the key players in the gene expression regulatory network. The potential roles of miRNAs in controlling AF have recently been investigated. The studies have provided some promising results for our better understanding of the molecular mechanisms of AF. In this review article, we provide a synopsis of the studies linking miRNAs to cardiac excitability and other processes pertinent to AF. To introduce the main topic, we discuss basic knowledge about miRNA biology and our current understanding of mechanisms for AF. The most up-to-date research data on the possible roles of miRNAs in AF initiation and maintenance are presented, and the available experimental results on miRNA and AF are discussed. Some speculations pertinent to the subject are made. Finally, perspectives on future directions of research on miRNAs in AF are provided.
1001 RAPID, MARKED WASH OUT AT CONTRAST ENHANCED ULTRASOUND IN NODULES IN CIRRHOSIS SHOULD RAISE THE SUSPICION OF CHOLANGIOCARCINOMA
Authors: M. Galassi, F. Piscaglia, V. Lucidi, M. Renzulli, M. Cescon, L. Venerandi, J. Corbelli, F. Vasuri, R. Golfieri, L. Bolondi
Journal: Journal of Hepatology (2011)
Vagal Reflexes Following an Exercise Stress Test
Authors: Lia Crotti, Carla Spazzolini, Alessandra P. Porretta, Federica Dagradi, Erika Taravelli, Barbara Petracci, Alessandro Vicentini, Matteo Pedrazzini, Maria Teresa La Rovere, Emilio Vanoli, Althea Goosen, Marshall Heradien, Alfred L. George, Paul A. Brink, Peter J. Schwartz
Journal: Journal of the American College of Cardiology (2012)
A rare complication of a metal stent
Authors: Z Liao, Z-S Li
Journal: Gut (2008)

A 58-year old man was admitted to our hospital because of diarrhoea of 5 months duration and 1 month of painless jaundice. MRI and endoscopic retrograde cholangiopancreatography showed a mass in the head of the pancreas and pancreaticobiliary duct dilation. Endoscopic ultrasonography …
* Substantial chemopreventative effect of piroxicam in min mice independent of peroxisome proliferator activated receptor alpha
Authors: K. M. Mccartney, A. Bennett, C. Hawkey
Journal: Gut (2011)

Introduction Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have chemopreventative properties against the development of colon polyps and cancer. We have previously shown that peroxisome proliferator activated receptor (PPAR) – alpha also acts to constrain polyp development in APCMin+/− mice. As both eicosanoids and NSAIDs are ligands for PPARα we investigated the hypothesis that the effects of NSAIDs may be mediated through activation of PPARα by comparing the effect of the Cox1/2 inhibitor piroxicam in APCMin+/− PPARα+/+ mice and APCMin+/− PPARα−/− mice. Aims & Hypothesis The effect of genotype and piroxicam treatment on longevity, colon and small bowel polyp number and area were investigated. We hypothesise that piroxicam may be prolonging longevity in Min mice due to inhibition of Cox enzyme activity and a resultant activation of PPARα due to altered eicosanoid metabolism; a reduction in the number of polyps in the small and large bowel will result, inhibiting development of classic Min phenotype (anaemia, white paw and weight loss). Methods Min mice of PPARα+/+ or PPARα−/− genotype were fed standard chow (+ piroxicam 100 ppm or control). Mice were culled if they showed signs of white paw, weight loss >15% or tumour-induced prolapse, or at 1 year old if they remained healthy. Large and small bowel tissue was removed, flushed and analysed for polyp number and area. Results Mean age of death in PPAR−/− control mice (n=22) was 22.31±1.20 (SEM) weeks and 47.67±1.69 (SEM) weeks in piroxicam treated mice (n=23, p<0.0001), PPAR+/+ control mice (n=22) was 24.21± 0.67 (SEM) weeks and 52.23±0.37 (SEM) weeks in piroxicam treated mice (n=23, p<0.0001) The number of polyps in the mouse colon reduced significantly in piroxicam treated mice (age corrected). PPAR−/− control (n=18) versus PPAR−/− piroxicam (n=18, p=0.028), PPAR+/+ control (n=18) versus PPAR+/+ piroxicam (n=18, p=0.0048) There was no significant difference in total polyp area (age corrected). The number of polyps in the small bowel reduced significantly in piroxicam treated mice (age corrected). PPAR−/− control (n=13) versus PPAR−/− piroxicam (n=10, p=0.0001), PPAR+/+ control (n=11) versus PPAR+/+ piroxicam (n=11, p=0.0004) Total polyp area was significantly reduced in piroxicam treated mice (age corrected). PPAR−/− control versus PPAR−/− piroxicam p<0.0001, PPAR+/+ control versus PPAR+/+ piroxicam p<0.0001. Total polyp area (age corrected) was lower in PPAR+/+ control mice than in PPAR−/− control mice (p=0.0489). Conclusion Piroxicam at 100 ppm results in substantial prolongation of life, to an age greater than previously reported for Min mice. PPARα status may influence small bowel polyp area but has minimal impact on the effect of piroxicam overall.
Giving early solids to infants. Beware of misclassifying eczema.
Authors: H C Williams
Journal: BMJ (1993)

<h3>Abstract</h3> Recently, a novel purple-pericarp super-sweetcorn line, ‘Tim1’ (<i>A1A1</i>.<i>sh2sh2</i>) is derived from the purple-pericarp maize ‘Costa Rica’ (<i>A1Sh2</i>.<i>A1Sh2</i>) and white <i>shrunken2</i> (<i>sh2</i>) super-sweetcorn ‘Tims-white’ (<i>a1sh2</i>.<i>a1sh2</i>), however information regarding purple colour controlling anthocyanin biosynthesis genes and sweetcorn gene is lacking. Specific sequence differences in the CDS (coding DNA sequence) and promoter regions of the anthocyanin biosynthesis structural genes, <i>anthocyanin1</i> (<i>A1</i>), <i>purple aleurone1</i> (<i>Pr1</i>) and regulatory genes, <i>purple plant1</i> (<i>Pl1</i>), <i>plant colour1</i> (<i>B1</i>), <i>coloured1</i> (<i>R1</i>), and the sweetcorn structural gene, <i>shrunken2</i> (<i>sh2</i>) were investigated using the publicly available annotated yellow starchy maize, B73 (NAM5.0) as a reference genome. In the CDS region, the <i>A1, Pl1</i> and <i>R1</i> gene sequence differences of ‘Tim1’ and ‘Costa Rica’ were similar, as they control purple-pericarp pigmentation, however the <i>B1</i> gene showed similarity between the ‘Tim1’ and ‘Tims-white’ lines, which may indicate that it does not have a role in controlling pericarp colour, unlike a previous study. In case of <i>Pr1</i> gene, unlike ‘Costa Rica’, 6- and 8-bp dinucleotide (TA) repeats were observed in the promoter region of the ‘Tims-white’ and ‘Tim1’ lines, respectively, indicating the defective functionality (redder colour in ‘Tim1’ than purple in ‘Costa Rica’) of the recessive <i>pr1</i> allele. In the sweetcorn structural gene (<i>sh2</i>), sequence similarity was observed between purple-sweet ‘Tim1’ and its white-sweet parent ‘Tims-white’, as both display a shrunken phenotype in their mature kernels. These findings revealed that the developed purple-sweet line is different than the reference yellow-nonsweet line regarding both the anthocyanin biosynthesis and sweetcorn genes.
Acquired Initiating Mutations in Early Hematopoietic Cells of CLL Patients
Authors: Frederik Damm, Elena Mylonas, Adrien Cosson, Kenichi Yoshida, Véronique Della Valle, Enguerran Mouly, M'boyba Diop, Laurianne Scourzic, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Yoshikane Kikushige, Frederick Davi, Jérôme Lambert, Daniel Gautheret, Hélène Merle-Béral, Laurent Sutton, Philippe Dessen, Eric Solary, Koichi Akashi, William Vainchenker, Thomas Mercher, Nathalie Droin, Seishi Ogawa, Florence Nguyen-Khac, Olivier A. Bernard
Journal: Cancer Discovery (2014)

Appropriate cancer care requires a thorough understanding of the natural history of the disease, including the cell of origin, the pattern of clonal evolution, and the functional consequences of the mutations. Using deep sequencing of flow-sorted cell populations from patients with chronic lymphocytic leukemia (CLL), we established the presence of acquired mutations in multipotent hematopoietic progenitors. Mutations affected known lymphoid oncogenes, including BRAF, NOTCH1, and SF3B1. NFKBIE and EGR2 mutations were observed at unexpectedly high frequencies, 10.7% and 8.3% of 168 advanced-stage patients, respectively. EGR2 mutations were associated with a shorter time to treatment and poor overall survival. Analyses of BRAF and EGR2 mutations suggest that they result in deregulation of B-cell receptor (BCR) intracellular signaling. Our data propose disruption of hematopoietic and early B-cell differentiation through the deregulation of pre-BCR signaling as a phenotypic outcome of CLL mutations and show that CLL develops from a pre-leukemic phase.The origin and pathogenic mechanisms of CLL are not fully understood. The current work indicates that CLL develops from pre-leukemic multipotent hematopoietic progenitors carrying somatic mutations. It advocates for abnormalities in early B-cell differentiation as a phenotypic convergence of the diverse acquired mutations observed in CLL.
Multiplex immune serum biomarker profiling in sarcoidosis and systemic sclerosis
Authors: P. Beirne, P. Pantelidis, P. Charles, A. U. Wells, D. J. Abraham, C. P. Denton, K. I. Welsh, P. L. Shah, R. M. du Bois, P. Kelleher
Journal: European Respiratory Journal (2009)

<h3>Abstract</h3> The TAR DNA Binding Protein (TARDBP) gene has gained attention in biomedicine after the discovery of several pathogenic mutations. The lack of knowledge about its evolutionary history contrasts with a large number of studies in the biomedical area. This study aimed to investigate the retrotransposition evolutionary dynamics associated with this gene in primates. We identified retropseudogenes that originated in the ancestors of anthropoids, catarrhines, and lemuriformes, i.e. the strepsirrhine clade that inhabit Madagascar. We also found species-specific retropseudogenes in the philippine tarsier, Bolivian squirrel monkey, capuchin monkey and vervet. Although retropseudogenes are not able to produce a functional protein, we can not rule out that they may represent genetic material upon which evolution acts on, especially with regulatory functions.