tbuckley/cabot-search huggingface dataset:
The Pathogenesis of Chronic Airway Obstruction.
Authors: Roger S. Mitchell
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970The Pathogenesis of Chronic Airway Obstruction.Roger S. Mitchell, M.D., F.A.C.P., Thomas L. Petty, M.D., (Associate), Giles F. Filley, M.D., F.A.C.P., Gladys A. Dart, B.A., G. Wayne Silvers, M.S., John C. Maisel, M.D.Roger S. Mitchell, M.D., F.A.C.P.Search for more papers by this author, Thomas L. Petty, M.D., (Associate)Search for more papers by this author, Giles F. Filley, M.D., F.A.C.P.Search for more papers by this author, Gladys A. Dart, B.A.Search for more papers by this author, G. Wayne Silvers, M.S.Search for more papers by this author, John C. Maisel, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-810_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBetween 1959 and 1968 special studies were made of the lungs from 500 autopsied subjects—mostly men and all over 40 year old—with and without chronic airway obstruction. Attention was focused on [1] the severity of destructive emphysema and on inflammatory and atrophic changes within the airways and [2] the speed of airway collapse on the application of 10 cm water positive pressure to lungs inflated in an artificial thorax after the airways had been coated with finely powdered barium and monitored by cinefluoroscopy. The clinical state of chronic airway obstruction correlated well with objective evidence of airway collapse when it... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Roger S. Mitchell, M.D., F.A.C.P.; Thomas L. Petty, M.D., (Associate); Giles F. Filley, M.D., F.A.C.P.; Gladys A. Dart, B.A.; G. Wayne Silvers, M.S.; John C. Maisel, M.D.Affiliations: Denver, Colo. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 810-810KeywordsEmphysemaLungsPathogenesisThorax ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...
Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity
Authors: Kenji Kabashima, Takahiko Murata, Hiroyuki Tanaka, Toshiyuki Matsuoka, Daiji Sakata, Nobuaki Yoshida, Koko Katagiri, Tatsuo Kinashi, Toshiyuki Tanaka, Masayuki Miyasaka, Hiroichi Nagai, Fumitaka Ushikubi, Shuh Narumiya
Journal: Nature Immunology (2003)
Book: Field Guide to the Difficult Patient Interview
Authors: C. Martyn
Journal: BMJ (1999)

Frederic W Platt, G H Gordon Lippincott Williams and Wilkins, £17.95, pp 250 ISBN 0 7817 2044 3 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> There has been much research into communication between doctors and patients, and, for the most part, doctors come out of it badly. We're not very good at transmitting information, and we're no better at picking up the signals that patients try to send. Observers of doctor-patient transactions make the telling point … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Hello and goodbye
Authors: C. Douglas
Journal: BMJ (1999)

As another batch of junior house officers ticks off the last few days to full registration and yet another brood of recently retired medical students assembles nervously to fill their places, I worry all over again about what the former have endured and what the latter are about to face.

I worry both as a current user of quite large numbers of house officers and as the survivor or the very different regime of 30 years ago. I claim no expertise, only …
NOTE on the SPECIFIC ACTION of NORMAL HUMAN SERUM upon the BACILLUS COLI COMMUNIS
Authors: S. R. Christophers
Journal: BMJ (1898)

THE BRITI8H ; (Zeiss obj. A. oc.2).Every colony resembling in its appearance the B. typhosus was picked out with a platinum needle and examined in haDging drop with a Zeiss obj.,'and oc. 6.v. Those which were found to be short motile bacilli were at once sub- cultured into milk.vI.Those milk tubes which became coagulated after incubation were rejected.vii.The milk tubes which did not become coagulated were subcultured into bouillon for indol and also into glucose gelatine for gas formation or into Theobald Smith's tubes and on to potatoes.viii.Pure cultures on agar were then obtained, and the organism ex- amined by Van Ermengen's or Loefflers method as to the disposition of their flagella, and also as to its reaction with typhoid serum of known strength.
Mutations in the cardiac myosin binding protein–C gene on chromosome 11 cause familial hypertrophic cardiomyopathy
Authors: Hugh Watkins, David Conner, Ludwig Thierfelder, John A. Jarcho, Calum MacRae, William J. McKenna, Barry J. Maron, J.G. Seidman, Christine E. Seidman
Journal: Nature Genetics (1995)
TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements
Authors: Hong-Yan Du, Elena Pumbo, Jennifer Ivanovich, Ping An, Richard T. Maziarz, Ulrike M. Reiss, Deborah Chirnomas, Akiko Shimamura, Adrianna Vlachos, Jeffrey M. Lipton, Rakesh K. Goyal, Frederick Goldman, David B. Wilson, Philip J. Mason, Monica Bessler
Journal: Blood (2008)
Neutrophil adherence to human endothelium in vitro occurs by CDw18 (Mo1, MAC-1/LFA-1/GP 150,95) glycoprotein-dependent and -independent mechanisms.
Authors: G A Zimmerman, T M McIntyre
Journal: Journal of Clinical Investigation (1988)

Components of the CDw18 leukocyte surface glycoprotein complex (Mo1/LFA-1/GP 150,95 or MAC-1, LFA-1 family) are required for some adhesion-related functions of human neutrophils (PMNs). We evaluated the ability of monoclonal antibodies (MoAb) directed against specific determinants on the CDw18 glycoproteins to inhibit neutrophil adherence to cultured human endothelial cells (EC) stimulated by a variety of agonists, including thrombin and leukotriene C4, which induce the EC-dependent adhesion of PMNs. MoAb 60.3, an antibody that binds to an epitope common to the 3 heterodimer subunits of the neutrophil CDw18 complex, potently inhibited (90-100%) the rapid (5-30 minute) adherence response stimulated by N-formyl-methyionyl-leucyl-phenylalanine, leukotriene B4, platelet-activating factor, phorbol myristate acetate, Ionophore A23187, and tumor necrosis factor. MoAbs directed against epitopes on the alpha polypeptide of the CD11b (Mol, MAC-1) heterodimer also inhibited PMN adherence to EC and to cell-free surfaces induced by these agonists. In contrast, the anti-CDw18 MoAbs had a trivial effect on maximal EC-dependent neutrophil adherence stimulated by thrombin and leukotriene C4, and incompletely inhibited PMN adherence induced by these agonists under submaximal conditions. These findings indicate that there is an alternative mechanism for neutrophil adherence, presumably resulting from molecular alterations of the EC surface, that does not require the PMN CDw18 glycoproteins. They also suggest that the inability to adhere to endothelium may not completely account for the defect in chemotaxis that is observed in vivo in neutrophils that are deficient in the CDw18 complex.
The Prognosis and Treatment of Actinomycosis
Authors: W. B. Ransom
Journal: BMJ (1894)

In conclusion, I beg to suggrest that the phase of disease pre- sented in this case, from its mode of evolution and subsequent behaviour-especially under treatment, and from its, general symptoms-indicates:1.An inflammatory process or dermatitis simulating psoriasis.2. That it owes its origin to the seborrhleic conditions of the ekin, especially the head.3. That it is DrobablV parasitic.
Induction of Labor
Authors: Nathan Kase
Journal: JAMA (1965)

For high-risk pregnancies, modern obstetrical practice demands prompt recognition and judicious but active management. The ability of the obstetrician to control when, where, and how a particular labor and delivery may occur has reduced the fetal and maternal risks of the major complications of late pregnancy. The benefits of the proper application of oxytocin induction are amply demonstrated in this monograph. The authors analyze almost 7,000 labors which were either electively induced or required induction or stimulation of labor. Their results support the clinical conviction that, when spontaneous labor is considered indicated and safe, induced labor is also indicated and safe. In all cases, the technique was intravenous administration of dilute oxytocin followed by amniotomy. With standard indications, nonelective labor was induced and delivery accomplished without maternal deaths. There were six intrapartum (0.9%) and nine neonatal (1.4%) deaths. While the results are admirable, nevertheless the authors correctly comment that many
Introduction and recommendations: working group on indoor air and other complex mixtures.
Authors: J M Samet, F E Speizer
Journal: Environmental Health Perspectives (1993)

Air in indoor and outdoor environments typically contains many gaseous and particulate pollutants that may affect adversely any individual at sufficiently high concentrations and more sensitive individuals at lower concentrations. The public health relevance of addressing the effects of mixtures is becoming increasingly evident as we improve the concept of total personal exposure to pollution and obtain more data from personal monitoring. The papers within this volume represent the deliberations of a working group assembled with the goal of improving the epidemiologic approach to investigating the health effects of indoor air pollution and other complex mixtures. The group, composed of epidemiologists, human and animal toxicologists, and experts on biomarkers, comprehensively reviewed the methodologic issues involved in investigating complex mixtures. Members noted the deficiencies of current epidemiologic methodology for studying complex mixtures and called for broad-based advances in study design, exposure assessment, outcome assessment, and data analysis and interpretation. Understanding the health effects of complex mixtures will require multidisciplinary research using not only epidemiologic studies incorporating the new methods of exposure assessment but animal and clinical toxicology.
Patient participation: more pipedream than practice
Authors: J P Graffy
Journal: BMJ (1981)

LY 127935 or moxalactam is an oxa-r-lactam under clinical study, and CGP 7174/E or cefsulodin is an antipseudomonal cephalo- sporin.When we measured the area under the curve of protein-free drug concentration against time from 0 to 6 h (AUC 0-6 h) as an indicator of "tissue" penetration we found that there was an almost linear relationship between penetration and percentage binding.100 9 e Flucloxacillin '80 \ 70 \ Cefoxitin ~50-5 0 ~~~~~~~LY127935 *C 40 Bay k4999 n 6 CGP 7174/Cefuroxime °' 20\ * 10 Amoxycilli 0 5 10 15 20 25 30 35 40 45 50 AUC 0-6 h free antibiotic in blister fluid (mg/I x h)The relationship between percentage protein bind- ing in blister fluid and penetration of seven lactams into blister fluid.Although Drs Lindup and Orme are correct in suggesting that protein binding is of greater significance when it exceeds 70% it is import- ant to note that there is an effect on drug distribution at all levels of binding.
I-A alpha polymorphic residues that determine alloreactive T cell recognition.
Authors: M Pierres, S Marchetto, P Naquet, D Landais, J Peccoud, C Benoist, D Mathis
Journal: The Journal of Experimental Medicine (1989)

An individual's T lymphocytes are highly reactive to allogeneic MHC molecules. As a step in deciphering the mechanism of allorecognition by T lymphocytes, we have attempted to identify the TCR's target on MHC class II molecules, in particular the polymorphic residues that determine the specificity of recognition. We have generated a panel of Ak-reactive, Ab-nonreactive T cell hybridomas, and sets of L cell transfectants displaying A alpha A beta molecules with wild-type, chimeric or single site-mutated A alpha chains, with reciprocal interchanges between Ak and Ab. We then measured the stimulation of the T hybridomas in response to the transfectants. The results indicate that the hybridomas recognize diverse and complex determinants, with contributions from both A alpha and A beta chains, and from several regions or amino acids of the A alpha chain. The data are most consistent with a model in which alloreactivity results from the presentation of peptides to the T cell by an allogeneic MHC molecule, peptides that cannot be presented by the responder's own MHC complexes. The specificity of allorecognition seems to be imparted mainly by peptide/MHC molecule rather than TCR/MHC molecule contacts.
Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins
Authors: Houria Bachtarzi, Mark Stevenson, Vladimir Šubr, Karel Ulbrich, Leonard W. Seymour, Kerry D. Fisher
Journal: Journal of Controlled Release (2010)

Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. Tumour-associated endothelium offers an additional mechanism for enhanced viral uptake into tumours which is accessible for systemic gene delivery. Building on expertise in using polymer 'stealthed' viruses for targeting in vivo, adenovirus expressing luciferase (Adluc) was coated with an amino-reactive polymer based on poly [N-(2-hydroxypropyl) methacrylamide] to ablate normal infection pathways. Direct linkage of a monoclonal antibody against E-selectin (MHES) demonstrated E-selectin-specific transduction of tumour necrosis factor-α (TNF-α)-activated endothelial cells. A two-component targeting system using protein G was developed, to provide optimal antibody orientation. We report an enhancement in transduction of TNF-α-activated endothelium in vitro and ex vivo in a human umbilical vein cord model using the MHES antibody. Similarly a virus retargeted using a chimeric P-selectin Glycoprotein Ligand-1-Fc fusion (PSGL-1) protein showed better circulation kinetics and significant uptake into HepG2 xenografts following systemic administration in mice, with 36-fold higher genome copies, compared with non-modified virus. Immunohistochemistry staining of tumour sections from mice treated with PSGL-1-retargeted virus showed a co-localisation of firefly luciferase with CD31 suggesting selective endothelial targeting. Employment of optimal viral modification using protein G will enable exploration and comparison of alternative targeting ligands targeting tumour-associated endothelium.
Abstract 3830: Inhibition of IL-4 function decreases fibrosis and lymphatic dysfunction in a mouse model of lymphedema
Authors: Tomer Avraham, Sanjay V. Daluvoy, Essie Kueberuwa, Jamie C. Zampell, Alan Yan, Babak J. Mehrara
Journal: Cancer Research (2010)

Abstract Background: Lymphedema, commonly encountered in cancer survivors, is characterized by chronic swelling and fibrosis. Previous studies have shown that fibrotic disorders involving other organ systems are dependent on T-helper 2 (Th-2) chronic inflammatory changes. The purpose of these experiments was therefore to evaluate the role of Th-2 cells in the pathological changes associated with lymphedema. Methods: We developed a surgical mouse model that results in tail lymphedema for prolonged periods (&amp;gt;9 weeks) and is histologically is similar to clinical lymphedema. Using this model in wild-type and athymic nude mice we evaluated the role of T-cells in general on the development of lymphedema and fibrosis. Furthermore, using a specific monoclonal neutralizing antibody against IL-4, a molecule necessary for Th-2 differentiation, we evaluated the role of Th2 cells in the initiation and maintenance of chronic lymphedema. Results: Lymphedema in wild-type mice resulted in a chronic inflammation consisting predominantly of CD-4+cells with a mixed Th1-Th2+ differentiation. Interestingly, application of this model to athymic nude mice resulted in markedly decreased tail edema and fibrosis, demonstrating that these outcomes are T-cell dependent. While inhibition of Th2 differentiation immediately after surgery did not prevent initiation of lymphedema, it did result in early resolution, with a marked reduction in fibrosis and improved lymphatic function 6 weeks post-operatively. Consistent with this, inhibition of Th2 cell function in mice with established lymphedema resulted in resolution of lymphedema and fibrosis with just 3 weekly treatments. In contrast, lymphedema was sustained in animals treated with isotype control. Conclusions: We have shown that Th2 differentiation is necessary for maintenance of the pathologic changes associated with lymphedema. Inhibition of Th2 differentiation completely reversed the fibrosis and lymphatic dysfunction in animals with established lymphedema, with resultant resolution of swelling. These results indicate that similar approaches may be clinically useful in patients with chronic lymphedema. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3830.
Mitotic Disturbances and Micronucleus Induction in Syrian Hamster Embryo Fibroblast Cells Caused by Asbestos Fibers
Authors: Elke Dopp, Jutta Saedler, Helga Stopper, Dieter G. Weiss, Dietmar Schiffmann
Journal: Environmental Health Perspectives (1995)

Asbestos and other mineral fibers have long been known to induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We investigated the occurrence of mitotic disturbances induced by asbestos (amosite, crocidolite, chrysotile) in an in vitro approach using Syrian hamster embryo (SHE) fibroblast cells. The following endpoints were investigated: micronucleus formation as a result of mitotic disturbances and characterization of the induced micronucleus population by kinetochore staining and visualization of the spindle apparatus. Supravital UV-microscopy was used to analyze changes in interphase chromatin structure, impaired chromatid separation, and blocked cytokinesis. All three asbestos fiber types induced a high frequency of micronucleus formation in SHE cells (> 200/2000 cells) in a dose-dependent manner (0.1-5.0 micrograms/cm2), with a maximum between 48 hr and 66 hr exposure time. At higher concentrations (more than 5.0 micrograms/cm2) the micronucleus formation decreased again as a result of increased toxicity. Kinetochore staining of micronuclei revealed that 48 +/- 2% of asbestos-induced micronuclei reacted positively with CREST (antikinetochore) serum. Furthermore, spindle apparatus deformations occurred in cells with disturbed metaphases and anaphases, while the spindle fiber morphology appeared unchanged. Our results show that asbestos fibers may cause both loss and breakage of chromosomes in the absence of direct interaction with spindle fibers.
SERIAL MEASUREMENT OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7 PREDICTS CHRONIC HEART FAILURE OUTCOMES AND VENTRICULAR REMODELING: RESULTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE THERAPY (PROTECT) STUDY
Authors: Shweta Motiwala, Anju Bhardwaj, Jackie Szymonifka, Arianna Belcher, Rory Weiner, Aaron Baggish, Hanna Gaggin, James Januzzi
Journal: Journal of the American College of Cardiology (2013)
Chronic alcohol consumption increases the sensitivity of rat liver mitochondrial respiration to inhibition by nitric oxide
Authors: Aparna Venkatraman, Sruti Shiva, Ashley J. Davis, Shannon M. Bailey, Paul S. Brookes, Victor M. Darley-Usmar
Journal: Hepatology (2003)

Chronic alcohol consumption is a well-known risk factor for hepatic injury, and mitochondrial damage plays a significant role in this process. Nitric oxide (NO) is an important modulator of mitochondrial function and is known to inhibit mitochondrial respiration. However, the impact of chronic alcohol consumption on NO-dependent control of liver mitochondrial function is unknown. This study examines the effect of alcohol exposure on liver mitochondria in a rat model and explores the interaction of NO and mitochondrial respiration in this context. Mitochondria were isolated from the liver of both control and ethanol-fed rats after 5 to 6 weeks of alcohol consumption. Mitochondria isolated from ethanol-treated rats showed a significant decrease in state 3 respiration and respiratory control ratio that was accompanied by an increased sensitivity to NO-dependent inhibition of respiration. In conclusion, we show that chronic alcohol consumption leads to increased sensitivity to the inhibition of respiration by NO. We propose that this results in a greater vulnerability to hypoxia and the development of alcohol-induced hepatotoxicity.
Toward RNAi Therapy for the Polyglutamine Disease Machado–Joseph Disease
Authors: Maria do Carmo Costa, Katiuska Luna-Cancalon, Svetlana Fischer, Naila S Ashraf, Michelle Ouyang, Rahil M Dharia, Lucas Martin-Fishman, Yemen Yang, Vikram G Shakkottai, Beverly L Davidson, Edgardo Rodríguez-Lebrón, Henry L Paulson
Journal: Molecular Therapy (2013)

Machado–Joseph disease (MJD) is a dominantly inherited ataxia caused by a polyglutamine-coding expansion in the ATXN3 gene. Suppressing expression of the toxic gene product represents a promising approach to therapy for MJD and other polyglutamine diseases. We performed an extended therapeutic trial of RNA interference (RNAi) targeting ATXN3 in a mouse model expressing the full human disease gene and recapitulating key disease features. Adeno-associated virus (AAV) encoding a microRNA (miRNA)-like molecule, miRATXN3, was delivered bilaterally into the cerebellum of 6- to 8-week-old MJD mice, which were then followed up to end-stage disease to assess the safety and efficacy of anti-ATXN3 RNAi. Despite effective, lifelong suppression of ATXN3 in the cerebellum and the apparent safety of miRATXN3, motor impairment was not ameliorated in treated MJD mice and survival was not prolonged. These results with an otherwise effective RNAi agent suggest that targeting a large extent of the cerebellum alone may not be sufficient for effective human therapy. Artificial miRNAs or other nucleotide-based suppression strategies targeting ATXN3 more widely in the brain should be considered in future preclinical tests. Machado–Joseph disease (MJD) is a dominantly inherited ataxia caused by a polyglutamine-coding expansion in the ATXN3 gene. Suppressing expression of the toxic gene product represents a promising approach to therapy for MJD and other polyglutamine diseases. We performed an extended therapeutic trial of RNA interference (RNAi) targeting ATXN3 in a mouse model expressing the full human disease gene and recapitulating key disease features. Adeno-associated virus (AAV) encoding a microRNA (miRNA)-like molecule, miRATXN3, was delivered bilaterally into the cerebellum of 6- to 8-week-old MJD mice, which were then followed up to end-stage disease to assess the safety and efficacy of anti-ATXN3 RNAi. Despite effective, lifelong suppression of ATXN3 in the cerebellum and the apparent safety of miRATXN3, motor impairment was not ameliorated in treated MJD mice and survival was not prolonged. These results with an otherwise effective RNAi agent suggest that targeting a large extent of the cerebellum alone may not be sufficient for effective human therapy. Artificial miRNAs or other nucleotide-based suppression strategies targeting ATXN3 more widely in the brain should be considered in future preclinical tests.
Elderly people who get stuck in the bath
Authors: M A Cadier, P J Shakespeare
Journal: BMJ (1994)

EDITOR, - Considering the alarmingly high incidence of elderly patients becoming stuck in the bath (1 in 7 patients interviewed) it would appear very fortunate that only one of C Gooptu and G P Mulley's patients required skin grafting.1 Since 1984 14 patients over the age of 70 have …