tbuckley/cabot-search huggingface dataset:
Bronchoalveolar lavage fluid urea as a measure of pulmonary permeability in healthy smokers
Authors: C. Ward, F. Thien, J Secombe, S Gollant, E.H Walters
Journal: European Respiratory Journal (2000)

The effects of cigarette smoking on blood to airway pulmonary permeability to the low-molecular-weight solute urea were investigated, in an attempt to evaluate its use as a dilution marker for bronchoalveolar lavage (BAL) studies. Five healthy normal smokers who smoked a cigarette 10 min prior to undergoing a 3 x 60 mL bronchoalveolar lavage (BAL), and five nonsmokers who also underwent BAL but without cigarette smoke exposure were studied. Five minutes before bronchoscopy, 4 MBq 3H-water and 1 MBq 14C-urea were injected intravenously and biochemical urea assays and an indirect radiotracer method were used to evaluate permeability. It was shown that the smoking group had less urea in their BAL supernatants compared to nonsmokers the results using the radiotracer method being significant (p<0.005). Using both methods, it was shown that levels of urea increased in sequentially aspirated aliquots in both groups. The median directly assayed levels of urea in the smokers rose as follows: aliquot 1 0.05 micromol x mL(-1), (range 0.03-0.14), aliquot 2 0.10 micromol x mL(-1) (0.07-0.17), aliquot 3 0.12 micromol x mL(-1) (0.06-0.23) (p<0.05). This led to significantly increased calculated levels of epithelial lining fluid in the sequential aliquots (p<0.05). In addition, there were large but variable amounts of labelled water detected in both subject groups indicating a complex interaction between the BAL procedure and the circulation. Changing urea measurements during the bronchoalveolar lavage procedure confound the use of the urea (epithelial lining fluid) method for normalizing dilution factors. The use of epithelial lining fluid determinations in smokers ignores the additional and probably complex permeability changes. The present data suggest that acute exposure to cigarette smoke in smokers may decrease blood to airway permeability.
French's Index of Differential Diagnosis
Authors: John H. Talbott
Journal: JAMA (1961)

A 50-year survival of a textbook is rather remarkable in contemporary medicine. The record probably belongs to Hippocrates, whose works were useful in clinical medicine for more than two millennia. The first edition of French's<i>Differential Diagnosis</i>was published in 1912. It was designed to cover the "whole ground of medicine, surgery, gynecology, ophthalmology, dermatology, and neurology." Arthur H. Douthwaite is the senior editor of the eighth edition, which follows the traditional format. I owned and used one of the interim editions for a number of years. It was a valuable reference work. I question whether I reached a specific conclusion on the basis of reference to this volume on any diagnosis of a difficult nature. I am sure that it contributed, however, in a number of instances. Since current diagnosis requires a tremendous amount of data supplementary to signs and symptoms, such a volume probably contributes less to the
Anisocoria From Scopolamine Patches
Authors: William Davenport
Journal: JAMA (1985)

To the Editor.—  In the March 15 issue ofThe Journal, Dr Price1reported on a 25-year-old woman who had a unilateral anisocoria with the pupil on the left fixed to light and convergence. This was undoubtedly due to topical scopolamine having been transferred manually from a scopolamine patch placed behind her left ear.  What is not clear is the sequence of events that followed the discovery of the patch. Dr Price states that he removed the patch and observed her pupil return to normal over the next four hours. Since the effect on her pupil is not systemic (if it had been she would have had bilaterally dilated pupils), why was there any effect from removing her patch and why so soon? As those of us who use scopolamine on a regular basis in the eye know, the effect of this drug is quite long, frequently lasting as
Furosemide and bumetanide, but not nedocromil sodium, modulate nonadrenergic relaxation in guinea pig trachea in vitro.
Authors: G M Verleden, J L Pype, M G Demedts
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Furosemide has recently been shown to be effective in inhibiting various indirect challenges in asthmatic patients, but its mode of action is not yet clear. There is some evidence that furosemide has an inhibitory effect on sensory and cholinergic nerves in the airways. We have investigated the effects of furosemide, bumetanide, and nedocromil sodium on inhibitory nonadrenergic, noncholinergic (iNANC) responses in guinea pig trachea in vitro using electrical field stimulation (50 V, 0.5 ms, 2 to 32 Hz for 30 s) and exogenously applied vasoactive intestinal peptide (VIP) or nitroprusside. In the presence of atropine (1 microM), indomethacin (10 microM), and propranolol (1 microM), both furosemide and bumetanide but not nedocromil sodium produced a concentration-dependent inhibition of the iNANC response (maximum inhibition, 31.2 +/- 5.6% with 100 microM furosemide at 16 Hz and 44.2 +/- 4.1% with 10 microM bumetanide at 4 Hz). Furthermore, after pretreatment of the tissues with L-NG-monomethyl arginine (90 microM), alpha-chymotrypsin (2 U/ml), or both, furosemide and bumetanide produced a further inhibition of the iNANC relaxation. Neither loop diuretic had any effect on the concentration-response curves to exogenous VIP (10(-9) to 10(-7) M) or nitroprusside (10(-8) to 10(-6) M). These results indicate that loop diuretics may inhibit nonadrenergic relaxation in guinea pig trachea in vitro by a prejunctional mechanism, probably through inhibition of nerve activation, the exact mechanism of which is still undefined.
Carbon Monoxide and Electrocardiograms
Authors: W. CHANNING NICHOLAS
Journal: Annals of Internal Medicine (1976)

Comments and Corrections1 April 1976Carbon Monoxide and ElectrocardiogramsW. CHANNING NICHOLAS, M.D., JAMES L. HODGSON, PH.D., STEVEN E. LINBERG, M.S.W. CHANNING NICHOLAS, M.D.Search for more papers by this author, JAMES L. HODGSON, PH.D.Search for more papers by this author, STEVEN E. LINBERG, M.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-4-495 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We were intrigued with Aronow and Cassidy's timely paper, "Effect of Carbon Monoxide on Maximal Treadmill Exercise. A Study in Normal Persons" (Ann Intern Med 83:496-499, 1975). Their stated purpose was to confirm a decrease in exercise performance and to study the effects, on the exercise electrocardiogram, on normal middle-aged-persons who were exposed to low levels of carbon monoxide such that their carboxyhemoglobin levels were about 4.0% ± 0.5%.We were disappointed to discover that the electrocardiograms presented were not taken during exercise but at rest, and (alas) supine.The two traces shown (left and center traces)...Reference1. ARONOW W: Postexercise evaluation of ischemic heart disease by electrocardiography, phonocardiography, apexcardiography, and systolic time intervals, in Noninvasive Methods in Cardiology, edited by ZONERAICH S. Springfield, Illinois, Charles C Thomas, Publisher, 1975, p. 246 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 199 Noll Laboratory The Pennsylvania State University University Park, Pennsylvania 16802 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByA Critical Review of the Literature on Carbon Disulfide Toxicity 1 April 1976Volume 84, Issue 4Page: 495-496KeywordsCarbon monoxideCarboxyhemoglobinElectrocardiographyExercise Issue Published: 1 April 1976 PDF DownloadLoading ...
Cutaneous Lesion in Muscle Disease
Authors: D. L. MCNEIL
Journal: Annals of Internal Medicine (1980)

Letters1 March 1980Cutaneous Lesion in Muscle DiseaseD. L. MCNEIL, M.D.D. L. MCNEIL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-92-3-439_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the October issue Stahl and associates (1) describe a "distinctive cutaneous lesion" seen in patients with connective tissue diseases which "appear to be associated with an inflammatory myopathy." The occurrence of this sign is suggested to be indicative of myositis.Carl Pearson (2) describes a similar phenomenon in dermatomyositis and other types of polymyositis: "hyperemia at the base of the fingernails, along the sides of the nails and on the fingerpads. The pads may become shiny, red and atrophic and are constantly flaking or peeling."It appears that this is not an uncommon or recently...References1. STAHLKLIPPELDECKER NJJ. A cutaneous lesion associated with myositis. Ann Intern Med. 1979;91:577-9. LinkGoogle Scholar2. PEARSON C. Polymyositis and dermatomyositis. In: SAMTER M, ed. Immunological Diseases. 3rd ed. Boston: Little, Brown and Co.; 1978:1094. Google Scholar1. PEARSON C. Polymyositis and dermatomyositis. In: SAMTER M, ed. Immunological Diseases. 3rd ed. Boston: Little, Brown and Co.; 1978:1094. Google Scholar2. STAHLKLIPPELDECKER NJJ. A cutaneous lesion associated with myositis. Ann Intern Med. 1979;91:577-9. LinkGoogle Scholar3. PEARSON C. Diagnosis and treatment of polymyositis. Geriatrics. 1964;19:484-95. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1980Volume 92, Issue 3Page: 439-439KeywordsConnective tissue diseasesDermatomyositisLesionsMyositisPolymyositis Issue Published: 1 March 1980 PDF DownloadLoading ...
SWI/SNF Factors Required for Cellular Resistance to DNA Damage Include ARID1A and ARID1B and Show Interdependent Protein Stability
Authors: Reiko Watanabe, Ayako Ui, Shin-ichiro Kanno, Hideaki Ogiwara, Takahiro Nagase, Takashi Kohno, Akira Yasui
Journal: Cancer Research (2014)

Abstract The SWI/SNF chromatin-remodeling family contains various protein complexes, which regulate gene expression during cellular development and influence DNA damage response in an ATP- and complex-dependent manner, of which details remain elusive. Recent human genome sequencing of various cancer cells revealed frequent mutations in SWI/SNF factors, especially ARID1A, a variant subunit in the BRG1-associated factor (BAF) complex of the SWI/SNF family. We combined live-cell analysis and gene-suppression experiments to show that suppression of either ARID1A or its paralog ARID1B led to reduced nonhomologous end joining activity of DNA double-strand breaks (DSB), decreased accumulation of KU70/KU80 proteins at DSB, and sensitivity to ionizing radiation, as well as to cisplatin and UV. Thus, in contrast to transcriptional regulation, both ARID1 proteins are required for cellular resistance to various types of DNA damage, including DSB. The suppression of other SWI/SNF factors, namely SNF5, BAF60a, BAF60c, BAF155, or BAF170, exhibits a similar phenotype. Of these factors, ARID1A, ARID1B, SNF5, and BAF60c are necessary for the immediate recruitment of the ATPase subunit of the SWI/SNF complex to DSB, arguing that both ARID1 proteins facilitate the damage response of the complex. Finally, we found interdependent protein stability among the SWI/SNF factors, suggesting their direct interaction within the complex and the reason why multiple factors are frequently lost in parallel in cancer cells. Taken together, we show that cancer cells lacking in the expression of certain SWI/SNF factors, including ARID1A, are deficient in DNA repair and potentially vulnerable to DNA damage. Cancer Res; 74(9); 2465–75. ©2014 AACR.
X-Rated Words
Authors: Edward Trapido
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In response to the editorial entitled "X-Rated Words" (235: 64, 1976), I would like to share a note from a lecture I attended. The speaker, an eminent physician who was obviously concerned about the possibility of sexism in the lecture, stated that "the vaccine should not be used when he or she [the patient] is allergic to eggs, or when he or she is pregnant." Perhaps we are carrying things a bit too far!
Towards early detection of pulmonary hypertension: a call to arms
Authors: K. Whyte
Journal: European Respiratory Journal (2013)

The imperative over the coming decade is to improve our ability to diagnose pulmonary hypertension early http://ow.ly/pUM2YThe more powerful the obstacle, the more glory we have in overcoming it -Mascarille, Molie `re, L'E ´tourdi ou Les Contretemps, Act V, Scene XI Emerging evidence demonstrates that early detection alters outcomes in systemic sclerosis-related pulmonary arterial hypertension (PAH) [1].The endeavours of the pulmonary hypertension community over the last 20 years have improved survival with modern treatment strategies but prognosis remains poor [2].On average, even in the current era, patients have been symptomatic for .2years by the time the diagnosis of pulmonary hypertension is made [3,4].If our understanding of the pathobiology of PAH is correct, then by the time of diagnosis, there will have been extensive remodelling and/or obliteration of a very significant proportion of the small muscular pulmonary arteries in our patients.The imperative over the coming decade for those of us treating pulmonary hypertension is to improve our ability to diagnose it early, when permanent damage to the pulmonary circulation is limited, leading to improved outcomes and, potentially, a normal quality of life with modern therapy.In response to these facts, patient-led support groups in Europe, North America and Australia have instigated campaigns not only to raise awareness of the existence of PAH but also to encourage individuals with unexplained breathlessness or fatigue to pursue a diagnosis with their doctors.This will inevitably lead to increasing referrals to pulmonary vascular clinics of patients with unexplained dyspnoea, syncope or fatigue.In some of these individuals, investigation will confirm a diagnosis of established PAH and, in others, alternative causes of their symptoms will be diagnosed.However, clinicians will be faced with symptomatic patients who have a moderate-to-high pre-test probability of pulmonary vascular disease based on clinical history or examination in whom echocardiography and other assessments at rest are unremarkable, and resting mean pulmonary artery pressure (mPAP) is normal or ''borderline'' at right heart catheterisation.How can we improve detection of early pulmonary vascular disease when such patients present to our clinics?Currently, we have no proven investigative strategy to identify which of these patients have early pulmonary vascular disease and who would potentially benefit from early treatment.As not all subjects with indeterminate initial investigations can be sent to large national or supraregional centres, such an investigative strategy must be applicable locally, or at least regionally, to be effective in leading to an earlier diagnosis of PAH.What tools should we use to investigate further such individuals?Exercise ''stress'' testing during right heart catheterisation was the next investigative tool in a limited number of specialised centres until it was
What about the NICE guidelines?
Authors: T. D. Pinkney, S. Pandey, S. Radley, T. Ismail
Journal: BMJ (2010)

The Ym1/2 lectin is expressed abundantly in the allergic mouse lung in an IL-13-dependent manner. However, the role of Ym1/2 in the development of allergic airways disease is largely unknown. In this investigation, we show that treatment of mice with anti-Ym1/2 Ab during induction of allergic airways disease attenuated mediastinal lymph node production of IL-5 and IL-13. Ym1/2 was found to be expressed by dendritic cells (DCs) in an IL-13-dependent manner and supplementation of DC/CD4<sup>+</sup> T cell cocultures with Ym1/2 enhanced the ability of IL-13<sup>−/−</sup> DCs to stimulate the secretion of IL-5 and IL-13. Affinity chromatography identified 12/15(<i>S</i>)-lipoxygenase (12/15-LOX) as a Ym1/2-interacting protein and functional studies suggested that Ym1/2 promoted the ability of DCs to stimulate cytokine production by inhibiting 12/15-LOX-mediated catalysis of 12-hydroxyeicosatetraenoic acid (12(<i>S</i>)-HETE). Treatment of DC/CD4<sup>+</sup> T cell cultures with the 12/15-LOX inhibitor baicalein enhanced, whereas 12(<i>S</i>)-HETE inhibited the production of Th2 cytokines. Notably, delivery of 12(<i>S</i>)-HETE to the airways of mice significantly attenuated the development of allergic airways inflammation and the production of IL-5 and IL-13. In summary, our results suggest that production of Ym1/2 in response to IL-13 promotes Th2 cytokine production and allergic airways inflammation by inhibiting the production of 12(<i>S</i>)-HETE by 12/15-LOX.
Abstract 4925: Targeted metabolic profiling of gliomas and glioma stem cells identifies methionine as a differentially regulated metabolite: Proof of principle supporting methionine-pet imaging
Authors: Kamalakannan Palanichamy, Thirumoorthy Krishnan, Nikhil Sebastian, Rajbir Singh, Suman Kanji, Arnab Chakravarti
Journal: Cancer Research (2014)

Abstract Purpose: At present, 18F-Fluorodeoxyglucose(FDG)-positron emission tomography (PET) is the most commonly used diagnostic imaging modality in clinical practice for predicting prognosis in malignant brain tumors. The diffusive nature of glioblastoma (GBM) often makes FDG-PET detection inaccurate and there is no diagnostic gold-standard for GBM. Thus, it is necessary to find new criteria independent of conventional FDG-PET diagnosis to delineate tumor versus normal tissues. Molecular imaging using 11C-Methionine-PET (Met-PET) is one of the most promising approaches to this challenge. Methods: We employed a targeted metabolomic approach to study the extracellular and intracellular levels of methionine in established (ATCC) and patient derived primary glioblastoma (GBM) cell lines, glioma stem cells (GSC) and normal human astrocytes (NHA) to gain a better understanding of methionine uptake. Methylthioadenosine phosphorylase (MTAP) is an enzyme that plays a vital role in polyamine metabolism and methionine salvage. Therefore, we determined the expression profile of MTAP in these cells using RT-qPCR. We then extracted the intracellular and extracellular metabolites of GBM, GSC and NHA to estimate their methionine levels using LC-MS Quadropole Time of Flight (Q-TOF) and LC-MS Triple Quad (QQQ) instruments. Thus, by using metabolic fingerprints of methionine, we quantified methionine accumulation / uptake in GBM, GSC and NHA. Results and Conclusion: PET provides real-time information of metabolism through the behavior of single molecules. Despite clinical trials advocating Met-PET imaging as a superior imaging modality compared to FDG-PET for brain tumors, to date Met-PET has not been widely used in clinical diagnostics. Through this metabolic profiling of gliomas, we have shown for the first time that GBM and GSC accumulate methionine when compared to NHA. Uptake studies through exogenous addition of methionine in GBM, GSC and NHA show a significant uptake of methionine by GBM and GSC when compared to NHA. The results of our study establish the scientific basis for Met-PET imaging in GBM and provide a rationale for incorporating Met-PET imaging in future brain tumor clinical trials to evaluate its prognostic value. Citation Format: Kamalakannan Palanichamy, Thirumoorthy Krishnan, Nikhil Sebastian, Rajbir Singh, Suman Kanji, Arnab Chakravarti. Targeted metabolic profiling of gliomas and glioma stem cells identifies methionine as a differentially regulated metabolite: Proof of principle supporting methionine-pet imaging. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4925. doi:10.1158/1538-7445.AM2014-4925
Blanket ban on tobacco funded research risks missing out on good quality studies
Authors: A. Jacobs
Journal: BMJ (2013)

It is easy to understand the BMJ ’s policy on refusing research funded by the tobacco industry, given the harm that the industry does.1

However, a blanket policy of rejecting all research from the tobacco industry makes me uncomfortable. This policy is based on nothing other than an ad hominem fallacy.2 Much research funded by the tobacco industry is …
Comparison of the ability of adeno-associated viral vectors pseudotyped with serotype 2, 5, and 8 capsid proteins to mediate efficient transduction of the liver in murine and nonhuman primate models
Authors: Andrew M. Davidoff, John T. Gray, Catherine Y.C. Ng, Youbin Zhang, Junfang Zhou, Yunyu Spence, Yusura Bakar, Amit C. Nathwani
Journal: Molecular Therapy (2005)

A detailed comparison of recombinant adeno-associated viral (rAAV) vectors of serotypes 2, 5, and 8 was performed in mice and nonhuman primates. Differences within the capsid proteins and viral terminal repeats of rAAV-2 and -5 did not significantly influence their ability to transduce murine liver. However, vectors pseudotyped with AAV-8 capsid (rAAV-2/8) mediated transgene expression more rapidly and from lower doses than possible with rAAV-2 and -5, although expression declined from peak values in a distinct dose-dependent manner prior to reaching steady-state levels. Nevertheless, at all time points and vector doses, rAAV-2/8 transgene levels were 17- to 84-fold higher than with rAAV-2 or -5 due to a more rapid conversion of the single-stranded genome to transcriptionally active stable duplex DNA. In nonhuman primates, liver-targeted administration of rAAV-5 and rAAV-2/8 vectors established therapeutic levels of transgene expression. The importance of preexisting serotype immunity was highlighted by the inability to achieve successful transduction in the presence of serotype-specific antibodies, although this impediment was successfully avoided through the use of alternative serotypes. In summary, serotype-specific differences in transduction biology and the appreciation of preexisting immunity will likely influence the selection of the rAAV serotype for future clinical trials.