tbuckley/cabot-search huggingface dataset:
The Thymic "Myoidzellen" and Myasthenia Gravis
Authors: Robert L. Van de Velde
Journal: JAMA (1966)

It has been known for a long time that there is an association of some sort between thymic lesions, thymomas in particular, and myasthenia gravis.<sup>1</sup>More recently, cross-reactions have been demonstrated between antimuscle antibodies in the sera of individuals suffering from myasthenia gravis and certain cells of the thymus.<sup>2,3</sup>There is little doubt that the reactive elements in the thymus are not entodermal reticular elements, but actual muscle cells, the "myoidzellen" of the old anatomists.<sup>4</sup> Elongated, occasionally stellate, eosinophilic cells containing cross-striated fibrils have been reported among thymocytes and reticular cells of the thymus in a variety of vertebrates. First described by Mayer<sup>5</sup>in the frog's thymus, they were observed by him as long, spindle-shaped elements showing distinct striations and closely resembling rudimentary skeletal muscle fibers. Pensa<sup>6</sup>found these strange cells to be particularly numerous and well developed in the thymus of chickens and called
Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations
Authors: T. Suzuki, B. Maranda, T. Sakagami, P. Catellier, C-Y. Couture, B.C. Carey, C. Chalk, B.C. Trapnell
Journal: European Respiratory Journal (2010)

To the Editors:

Pulmonary alveolar proteinosis (PAP) is a syndrome characterised by accumulation of surfactant in alveoli resulting in respiratory insufficiency 1. Surfactant homeostasis is critical for lung function and is tightly regulated, in part, by pulmonary granulocyte-macrophage colony-stimulating factor (GM-CSF), which is required for surfactant clearance by alveolar macrophages 2 and alveolar macrophage maturation 1. The effects of GM-CSF are mediated by cell-surface receptors composed of GM-CSF-binding α-chains and affinity-enhancing β-chains (encoded by CSF2RA and CSF2RB , respectively) 3. Ligand binding activates signalling via multiple pathways including the signal transducer and activator of phosphorylation (STAT)5 4. Disruption of GM-CSF signalling causes PAP by impairing surfactant catabolism in alveolar macrophages 1. In 90% of patients, PAP is caused by neutralising GM-CSF auto-antibodies 5, 6. Through the Rare Lung Diseases Network global PAP detection programme, we identified PAP caused by recessive CSF2RA mutations and developed novel diagnostic methods to identify patients with PAP caused by GM-CSF receptor dysfunction 4, 7. Herein, we report a case of hereditary PAP caused by disruption of GM-CSF receptor β-chain function.

A previously healthy 9-yr-old female presented with bilateral pneumonia, followed 3 months later by progressive dyspnoea of insidious onset. The diagnosis of PAP was suggested by chest radiograph findings, high-resolution computed tomography and bronchoalveolar cytology, and was confirmed by surgical lung biopsy. Pulmonary histopathology was typical of primary PAP (fig. 1) and she was successfully treated by serial whole lung lavage therapy. Details of the case history are included in the online supplement. A GM-CSF auto-antibody test was negative and the serum GM-CSF level was increased (25.9 pg·mL−1) suggesting GM-CSF receptor dysfunction as the molecular basis of PAP 4, 7. A molecular evaluation was undertaken and included GM-CSF receptor detection, STAT-5 phosphorylation, CSF2RA …
Cd1b-Mediated T Cell Recognition of a Glycolipid Antigen Generated from Mycobacterial Lipid and Host Carbohydrate during Infection
Authors: D. Branch Moody, Mark R. Guy, Ethan Grant, Tan-Yun Cheng, Michael B. Brenner, Gurdyal S. Besra, Steven A. Porcelli
Journal: The Journal of Experimental Medicine (2000)

T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) α and β chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria.
FEV1/FVC agreement study between two different seasons
Authors: Pedro Carreiro-Martins, Iolanda Caires, João Marques, José Araújo-Martins, Joana Valente, Myriam Lopes, Carlos Borrego, Nuno Neuparth
Journal: European Respiratory Journal (2013)

Introduction: There is still a controversy about which spirometric criteria should be used to diagnose chronic obstructive pulmonary disease (COPD). Longitudinal studies comparing the agreement of those criteria along the time are lacking in the literature.  Aim: To evaluate the agreement of the fixed ratio (FEV1/FVC  Methods: In the scope of INSPIRAR prospective study we assessed on 196 participants from one of the largest Portuguese chemical industrial complexes (Estarreja) the frequency of COPD established by two different spirometric criteria during two different seasons: June 2011 (Visit 1) and February 2012 (Visit 2). The considered criteria were the existence of a FEV1/FVC   Results: The mean age of the participants was 43.9 ± 10.6 years and 75% of them were males. The frequency of FEV1/FVC   Conclusion: The moderate agreement found suggests the existence of an intra-individual variability between the two seasons. Despite this the agreement was higher for the fixed ratio criteria.  Fundacao para a Ciencia e Tecnologia – INSPIRAR Project PTDC/AAC-AMB/103895/2008.
AC and DC Countershock for Arrhythmias
Authors: Paul M. Zoll, Arthur J. Linenthal
Journal: JAMA (1964)

<h3>To the Editor:—</h3> In the Jan 4, 1964, issue ofThe Journal(<b>187</b>:60) Kong and Proudfit reported the external application of 140 direct-current countershocks for recurrent ventricular fibrillation in a patient whose heart showed no resulting damage. External alternating-current countershock, which has been in clinical use since 1955,<sup>1</sup>was also shown early to be safe in this regard. We applied from 21 to over 300 alternating-current countershocks for the termination of ventricular fibrillation or tachycardia in four patients whose hearts subsequently showed no resulting damage.<sup>2</sup> DC countershock is said to be more effective in terminating arrhythmias and to have smaller risks of producing ventricular fibrillation. Our conclusions are not in accord with these views. On the basis of our clinical experience over a period of nine years with many hundreds of countershock terminations of ventricular fibrillation and of over 200 terminations of other arrhythmias, we can say
Intestinal Mucosal Inflammation Leads to Systemic Genotoxicity in Mice
Authors: Aya M. Westbrook, Bo Wei, Jonathan Braun, Robert H. Schiestl
Journal: Cancer Research (2009)

Abstract Inflammatory bowel disease, including ulcerative colitis and Crohn's disease, substantially increases the risk of colorectal cancer. However, mechanisms linking mucosal inflammation to the sequence of dysplasia are incompletely understood. Whereas studies have shown oxidative damage to the colon, this study tests whether genotoxicity is elicited systemically by acute and chronic intestinal inflammation. In this study, genotoxic endpoints were assessed in peripheral leukocytes (DNA single- and double-stranded breaks and oxidative DNA damage) and normochromatic erythrocytes (micronuclei) during chemical or immune-mediated colitis. During three consecutive cycles of intestinal inflammation induced by dextran sulfate sodium administration, genotoxicity to peripheral leukocytes and erythroblasts was detected in both acute and chronic phases of dextran sulfate sodium–induced inflammation. Reactive oxygen species–mediated oxidative stress and DNA damage was confirmed with positive 8-oxoguanine and nitrotyrosine staining in peripheral leukocytes. Levels of DNA damage generally decreased during remission and increased during treatment, correlating with clinical symptoms and systemic inflammatory cytokine levels. In Gαi2−/− and interleukin-10−/− transgenic mice susceptible to immune-mediated colitis and inflammation-associated adenocarcinoma, similar levels of peripheral leukocyte and erythroblast genotoxicity were also observed. Moreover, this systemic genotoxicity was observed in mice with subclinical inflammation, which was further elevated in those with severe mucosal inflammation. We propose that mucosal inflammation, by eliciting substantial and ongoing systemic DNA damage, contributes early on to genetic instability necessary for progression to inflammatory bowel disease–associated dysplasia and the development of cancer. [Cancer Res 2009;69(11):4827–34]
Comparison of Breast Cancer Recurrence and Outcome Patterns Between Patients Treated From 1986 to 1992 and From 2004 to 2008
Authors: Rachel J.D. Cossetti, Scott K. Tyldesley, Caroline H. Speers, Yvonne Zheng, Karen A. Gelmon
Journal: Journal of Clinical Oncology (2014)

Purpose To determine whether the patterns of relapse according to estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status changed in the contemporary era. Patients and Methods Female patients referred to the British Columbia Cancer Agency with biopsy-proven stage I to III breast cancer (BC), diagnosed between 1986 and 1992 (cohort 1 [C1]) and between mid-2004 and 2008 (cohort 2 [C2]), and with known ER and HER2 status were eligible. Data were prospectively collected. C2 patients were matched to C1 patients for stage, grade, and ER and HER2 status. The primary end point was hazard rate of relapse (HRR) for BC by study cohort according to biomarker status. Secondary outcomes included HRR according to stage, grade, and age and hazard rate of death (HRD). Results After matching, 7,178 patients were included (3,589 patients in each cohort). BC subtype distribution was as following ER positive/HER2 negative, 70.8%; ER positive/HER2 positive, 6.9%; ER negative/HER2 positive, 6.6%; and ER negative/HER2 negative, 15.8%. For the overall population, the HRR approximately halved in all yearly intervals to year 9 in C2 compared with C1. Differences in HRR between cohorts were greater in the initial five intervals for HER2-positive and ER-negative/HER2-negative BC. The HRR decreased in C2 compared with C1 for all disease stages and grades. The HRD in C2 also decreased compared with C1, although to a lesser extent. Conclusion Although the pattern of relapse remains similar, there has been a significant improvement in BC relapse-free survival. Outcomes have improved for all BC subtypes, especially HER2-positive and ER-negative/HER2-negative BC, with the early spike in disease recurrence markedly decreased. These contemporary hazard rates are important for treatment decisions, patient discussions, and planning clinical trials of early BC.
Bronchiolar epithelial catalase is diminished in smokers with mild COPD
Authors: Tomoko Betsuyaku, Satoshi Fuke, Takashi Inomata, Kichizo Kaga, Toshiaki Morikawa, Nao Odajima, Tracy Adair-Kirk, Masaharu Nishimura
Journal: European Respiratory Journal (2012)

This study aimed to investigate bronchiolar catalase expression and its relationship with smoking and/or chronic obstructive pulmonary disease (COPD) in humans and to determine the dynamic change of bronchiolar catalase expression in response to cigarette smoke in mice. Lung tissue was obtained from 36 subjects undergoing surgery for peripheral tumours, consisting of life-long nonsmokers and smokers with or without COPD. Male C57BL/6 mice were subjected to cigarette smoke exposure for up to 3 months followed by a 28-day cessation period. We quantified bronchiolar catalase mRNA using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction. C22 club cells (Clara cells) in culture were exposed to cigarette smoke extract and monitored for viability when catalase expression was decreased by siRNA. Catalase was decreased at mRNA and protein levels in bronchiolar epithelium in smokers with COPD. In mice, bronchiolar catalase is temporarily upregulated at 1 day after cigarette smoke exposure but is downregulated by repeated cigarette smoke exposure, and is not restored long after withdrawal once emphysema is developed. Decreasing catalase expression in C22 cells resulted in greater cigarette smoke extract-induced cell death. Bronchiolar catalase reduction is associated with COPD. Regulation of catalase depends on the duration of cigarette smoke exposure, and plays a critical role for protection against cigarette smoke-induced cell damage.
Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients
Authors: K Bodger
Journal: Gut (2006)

<b>Background and aims:</b> Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose β1, 3 <i>N</i>-acetylgalactosamine α-), among the same IBD twins. <b>Materials and methods:</b> Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn's disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor κB (NFκB) activation with investigators blinded to the diagnosis. <b>Results:</b> Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p&lt;0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NFκB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p = 0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFκB. <b>Conclusions:</b> Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "preinflammatory" NFκB activation.
Effect of lung volume on the oesophageal diaphragm EMG assessed by magnetic phrenic nerve stimulation
Authors: Y.M. Luo, R.A. Lyall, M.L. Harris, P. Hawkins, N. Hart, M.I. Polkey, J. Moxham
Journal: European Respiratory Journal (2000)

Previous studies have shown conflicting results on the effect of lung volume on the diaphragm compound muscle action potential (CMAP). Consequently, the ability to quantify the oesophageal diaphragm electromyography (EMG) has been questioned. If lung volume changes have little effect on the diaphragm CMAP the accurate measurement of voluntary EMG, as an index of respiratory drive, may be possible. Furthermore, the measurement of CMAP could provide useful clinical information when evaluating patients with neuromuscular disease. To reassess the effect of lung volume on the oesophageal diaphragm CMAP, six normal subjects were studied using an oesophageal catheter incorporating seven electrodes (number one being proximal and seven distal) that were 1 cm in length and 1 cm apart. Electrode number three was positioned at the centre of the electrically active region of the diaphragm (EARdi) at functional residual capacity (FRC). The diaphragm CMAP elicited by bilateral magnetic stimulation of the phrenic nerves was simultaneously recorded from four electrode pairs. Pair one was created from electrodes one and three, pair two from electrodes two and four, pair three from electrodes three and five, and pair four from electrodes five and seven. Phrenic nerve stimulation was at residual volume (RV), FRC, FRC+1.0 L, FRC+2.0 L, and total lung capacity (TLC). The CMAP recorded from pair one was least influenced by changes in lung volume and the amplitude was 2.41+/-0.39 (mean+/-SD), 2.60+/-0.27, 2.64+/-0.29, and 2.71+/-0.45 mV at RV, FRC, FRC+1.0 L and FRC+2.0 L, respectively. At TLC the CMAP was more variable. The CMAP amplitude recorded from pair two increased with increasing lung volume and at FRC+2.0 L was 3.7 times larger than that at FRC. Pair four usually recorded substantially smaller CMAPs at all lung volumes. This study shows that the diaphragm compound muscle action potential recorded from an oesophageal electrode just above the diaphragm is relatively stable over the lung volume range residual volume to functional residual capacity+2.0 L.
Abi3bp Regulates Cardiac Progenitor Cell Proliferation and Differentiation
Authors: Conrad P. Hodgkinson, Jose A. Gomez, Alan J. Payne, Lunan Zhang, Xiaowen Wang, Sophie Dal-Pra, Richard E. Pratt, Victor J. Dzau
Journal: Circulation Research (2014)

Cardiac progenitor cells (CPCs) are thought to differentiate into the major cell types of the heart: cardiomyocytes, smooth muscle cells, and endothelial cells. We have recently identified ABI family, member 3 (NESH) binding protein (Abi3bp) as a protein important for mesenchymal stem cell biology. Because CPCs share several characteristics with mesenchymal stem cells, we hypothesized that Abi3bp would similarly affect CPC differentiation and proliferation.
The utility of ultrasound-guided thoracentesis and pleural biopsy in undiagnosed pleural exudates: Figure 1
Authors: Coenraad Frederik N Koegelenberg, Elvis Malcom Irusen, Florian von Groote-Bidlingmaier, Johannes Willem Bruwer, Enas Mansour A Batubara, Andreas Henri Diacon
Journal: Thorax (2015)

We assessed the utility of ultrasound to guide the selection of closed pleural biopsy technique and site and to assess the respective contributions of repeat thoracentesis and closed pleural biopsy in 100 consecutive patients with undiagnosed pleural exudates. Thoracentesis was more likely to be diagnostic in TB than malignancy (77.8% vs 31.0%, p&lt;0.001). The addition of ultrasound-guided biopsy increased the combined yield for all diagnoses from 48.0% to 90.0% (p&lt;0.001), for malignancy from 31.0% to 89.7% (p&lt;0.001) and for TB from 77.8% to 88.9% (p=0.688). Our findings suggest that this minimally invasive approach has a high diagnostic yield.
The effects of ryanodine on calcium-overloaded sheep cardiac Purkinje fibers.
Authors: M Valdeolmillos, D A Eisner
Journal: Circulation Research (1985)

Prolonged exposure to high concentrations of strophanthidin produces an initial increase followed by a subsequent decrease of twitch tension. The slow decrease is termed calcium overload. The aim of the present work was to investigate the effects of ryanodine (an inhibitor of calcium release from the sarcoplasmic reticulum) on calcium-overloaded sheep cardiac Purkinje fibers. The fibers were voltage-clamped, and tension was measured while monitoring the intracellular calcium concentration with the photoprotein aequorin. When strophanthidin (10 microM) was applied to produce calcium overload, a depolarizing pulse produced twitch, and tonic components of tension and repolarization produced an aftercontraction. These components of tension were accompanied by corresponding increases of aequorin light. Ryanodine (1 microM) gave a transient increase of twitch tension. The twitch then decreased to very low levels. The aftercontraction and its corresponding aequorin light signal decreased monotonically on application of ryanodine. It has been suggested that the fall of force in calcium overload may be due to random diastolic release of calcium from the sarcoplasmic reticulum interfering with subsequent systolic calcium release. We suggest that the positive inotropic effect of ryanodine can be explained if ryanodine decreases the diastolic release of calcium. The transient positive inotropic effect of ryanodine reported here is therefore consistent with the hypothesis that the fall of force in calcium overload is due to diastolic calcium oscillations.
Spontaneous pneumothorax following regression of pulmonary metastases
Authors: N Kryger-Baggesen
Journal: European Respiratory Journal (1990)

Spontaneous pneumothorax (SP) caused by necrosis in combination with regression of lung metastases is a rare complication to cancer chemotherapy. Few case reports have previously been presented, and mostly in patients with sarcomas. A patient is presented with spontaneous pneumothorax probably caused by chemotherapy-induced cell necrosis in bilateral lung metastases secondary to an endometrioid cancer. The literature is surveyed. Because of the increasing use of effective chemotherapeutic drugs, it is expected that this rare complication will occur more often.
Nicotine replacement therapy in pregnancy
Authors: Thomas D Stringfellow, John D Blakey
Journal: Thorax (2012)

CLUB Nicotine replacement therapy in pregnancyCigarette smoking is a major modifiable cause of adverse pregnancy outcomes.Nicotine-replacement therapy (NRT) is recommended in guidelines, but its efficacy and safety during pregnancy is uncertain.This multicentre double-blind trial recruited 1050 pregnant participants who were in their 12-24 weeks' gestation periods.All of them smoked ≥5 cigarettes per day (median 20).Participants were randomly assigned NRT (15 mg/16 h) or placebo patches for 8 weeks.All individuals received behavioural support given the sound evidence base in pregnancy.The primary outcome was abstinence from individually set quit dates through to delivery.Self-reported smoking status was validated using salivary cotinine and exhaled carbon monoxide concentration.NRT significantly increased quit rates at 1 month, but by term there was no difference between abstinence rates in the NRT (9.4%) and placebo (7.6%) arms (OR=1.26(95% CI 0.82 to 1.96)).Rates of adverse pregnancy and birth outcomes (such as stillbirth, miscarriage and low birth weight) were no different in the two groups.A key finding was low adherence to therapy: 7.2% in the intervention group and 2.8% in the placebo group used patches for >1 month.Poor adherence due to perceived lack of efficacy has been seen repeatedly in other trials of NRT, and this study may have been particularly affected due to the increases in nicotine and cotinine clearance during pregnancy.Moreover, the low adherence rate limits the inference that can be made from the data on adverse outcomes.This study, taken together with previous investigations, suggests NRT should not be routinely recommended in pregnancy.
Percutaneous left ventricular catheterisation with an ultraminiature catheter-tip pressure transducer
Authors: W. W. NICHOLS, C. J. PEPINE, H. D. MILLAR, L. G. CHRISTIE, C. R. CONTI
Journal: Cardiovascular Research (1978)

Percutaneous left ventricular catheterisation with a 4F (O.D. 1.33 mm) catheter-tip pressure transducer is described. The transducer is small enough so that it can be introduced through a short 4F arterial insertion sheath or a Brockenbrough Trans-septal catheter. Experience in 35 patients suggests that this ultraminiatufe catheter mounted pressure transducer is a valuable addition to the cardiac catheterisation laboratory.