tbuckley/cabot-search huggingface dataset:
Interleukin 1 activates soluble guanylate cyclase in human vascular smooth muscle cells through a novel nitric oxide-independent pathway.
Authors: D Beasley, M McGuiggin
Journal: The Journal of Experimental Medicine (1994)

Recent demonstration of cytokine-inducible production of nitric oxide (NO) in vascular smooth muscle cells (VSMC) from rat aorta has implicated VSMC-derived NO as a key mediator of hypotension in septic shock. Our studies to determine whether an inducible NO pathway exists in human VSMC have revealed a novel cytokine-inducible, NO-independent pathway of guanylate cyclase activation in VSMC from human saphenous vein (HSVSMC). Interleukin 1 (IL-1), tumor necrosis factor (TNF), interferon gamma (IFN-gamma) and Escherichia coli lipopolysaccharide (LPS) increased cGMP at 24 h, whereas IL-2 and IL-6 were ineffective. The effect of IL-1 on cyclic guanosine 3',5'-monophosphate (cGMP) was delayed, occurring after 6 h of exposure, and was maximal after 10 h. Methylene blue and LY83583 reversed the IL-1-induced increase in cGMP, suggesting that it was mediated by activation of soluble guanylate cyclase. However, IL-1-induced cGMP in HSVSMC was not inhibited by extracellular hemoglobin. Also, the effect of IL-1 on cGMP was not reversed by nitro- or methyl-substituted L-arginine analogs, aminoguanidine, or diphenyleneiodonium, all of which inhibit IL-1-induced NO synthase in rat aortic VSMC (RAVSMC). IL-1-induced cGMP in HSVSMC was also independent of tetrahydrobiopterin and extracellular L-arginine, as it was not affected by 2,4-diamino-6-hydroxyprytimidine, an inhibitor of tetrahydrobiopterin biosynthesis, and was similar in L-arginine-free and L-arginine-containing media. Analysis of NO synthase mRNA with the use of polymerase chain reaction indicates that levels of mRNA for inducible NO synthase are several orders of magnitude lower in IL-1-treated human HSVSMC than in IL-1-treated RAVSMC. IL-1-induced cGMP was also NO independent in human umbilical artery VSMC, and NO dependent in rat vena cava VSMC. Together these results indicate that IL-1 activates a novel NO-independent pathway of soluble guanylate cyclase activation in human VSMC.
Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma*1
Authors: S KAR
Journal: Hepatology (1995)

A large percentage of patients with advanced-stage hepatocellular carcinoma (HCC) have a recurrence of tumor in the liver or lung after primary resection and even after orthotopic liver transplantation. One reason for this may be the presence of small numbers of tumor cells circulating in the blood before surgery or the liberation of tumor cells into circulation during surgical manipulation. We tested this hypothesis by measuring messenger RNA (mRNA) for human albumin gene as a liver cell marker with the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) technique. Albumin mRNA was not found in peripheral blood from normal humans (0 of 6), from patients with liver cirrhosis (0 of 10), from other tumors metastatic to liver (0 of 10), or during liver transplant surgery for cirrhosis (0 of 10). In patients with advanced-stage HCC (TNM stages III and IV), albumin mRNA was detected (16 of 17) in peripheral blood. After liver transplantation in the HCC patients, the level of mRNA decreased below the detectable limit (0 of 9). Three of these patients again had detectable mRNA levels when they had recurrence of HCC after liver transplantation. Patients with stage I HCC did not have detectable expression. These results suggest that circulating tumor cells are present in patients with advanced-stage HCC, which may be one of the reasons why these patients have a high incidence of tumor recurrence after apparently definitive surgical resection and even after liver transplantation.
Diagnosis of Mongolism in Infancy
Authors: H. R. E. Wallis
Journal: BMJ (1955)

MEDICAL MEMORANDAMmIC"oHUaNs and divided, only the mesentery remaining to be dealt with.A drainage tube to the gall-bladder bed was brought out through the upper part of the wound, which was then closed in layers.The patient's general condition remained satis- factory during and after the operation.Her general con- dition improved considerably during the next twenty-four hours; she continued to make good progress until her dis- charge from hospital on the fourteenth post-operative day.COMMENT One very interesting clinical sign in this case was the distinct zone of acute tenderness over a small area.This had previously been noted by Case (1951).The gall-bladder was relatively free and mobile, but when torsion occurred it became relatively fixed and firmly abutted against the anterior parietal peritoneum.The small zone of maximal tenderness therefore corresponds fairly accurately to the area in contact with the gangrenous gall-bladder.The patient's convalescence was without incident, which is not only gratifying but interesting; Arthur (1937) esti- mated the mortality to be 16%.
Vitamin B_12 Binding Capacity Correlates with Intrinsic Factor Activity in Normal Human Gastric Juice.
Authors: Julius J. Chosy
Journal: Annals of Internal Medicine (1965)

s1 November 1965Vitamin B12 Binding Capacity Correlates with Intrinsic Factor Activity in Normal Human Gastric Juice.Julius J. Chosy, M.D., Mary Muckerheide, B.S., Robert F. Schilling, M.D.Julius J. Chosy, M.D.Search for more papers by this author, Mary Muckerheide, B.S.Search for more papers by this author, Robert F. Schilling, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-913_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is known that human gastric juice contains vitamin B12 binders that possess intrinsic factor activity and other B12 binders lacking such activity. Data from our studies on normal human gastric juice secreted after histamine stimulation indicate that B12 binding capacity in vitro is an excellent indicator of intrinsic factor activity measured in vivo. Volume and nitrogen content of gastric juice do not correlate well with intrinsic factor activity. There is a good correlation between total B12 binding capacity and the amount of binding capacity that can be blocked by spontaneously appearing antibody to intrinsic factor.For purposes of study... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Julius J. Chosy, M.D.; Mary Muckerheide, B.S.; Robert F. Schilling, M.D.Affiliations: Madison, Wisconsin PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 913-913KeywordsHistamine ePublished: 1 December 2008 Issue Published: 1 November 1965 PDF downloadLoading ...
Radiological cervical arthritis in populations.
Authors: J S Lawrence
Journal: Annals of the Rheumatic Diseases (1976)

The prevalence of cervical rheumatoid arthritis and its relationship to rheumatoid serum factors and erosive arthritis in peripheral joints has been studied in radiographs of the cervical spine and of the hands and feet drawn from 12 population samples. The changes were graded in accordance with the Atlas of Standard Radiographs of Arthritis. Rheumatoid arthritis of the cervical spine (grades 2-4) was observed in 4.1% of males and 4.7% of females aged 15 and over. Prevalence was greatest in those born before 1900, 15% of whom were affected. There was a significant association with the sheep cell agglutination test but not with the bentonite flocculation test, though the latter correlated well with erosive arthritis in the joints of the hands and feet. Arthritis of the cervical spine showed a significant correlation with both seropositive and seronegative erosive arthritis in the peripheral joints. A significantly higher prevalence of cervical arthritis than expected was noted in two population samples, one in Germany and the other in West Africa, though in neither was there a high prevalence of peripheral arthritis. The German population had relatively high antistreptolysin titres. A low prevalence of cervical arthritis was noted in populations in Czechoslovakia and in Arizona. 'Congenital' block vertebra had a prevalence of 0.9% in persons born before 1935, but none was observed in those born since. The figures suggest that environmental influences predisposing to cervical arthritis and block vertebra have changed in the last 40 years.
Measuring Coverage in MNCH: Challenges and Opportunities in the Selection of Coverage Indicators for Global Monitoring
Authors: Jennifer Harris Requejo, Holly Newby, Jennifer Bryce
Journal: PLoS Medicine (2013)

In a PLOS Medicine Review, Jennifer Requejo, Holly Newby and Jennifer Bryce discuss the five-step process that underlies the generation of data for global monitoring of intervention coverage for maternal and child health and describe the problems associated with selecting appropriate coverage indicators for global monitoring.
604. Long-Term, Erythroid-Specific Expression of Human Factor IX in Hemophilic Mice Engrafted with Lentiviral Vector-Transduced Hematopoietic Stem Cells
Authors: Alex H. Chang, Matthias Stephan, Michel Sadelain
Journal: Molecular Therapy (2005)

Current attempts to treat hemophilia with stem cell-based gene therapy make use of oncoretroviral or lentiviral vectors with ubiquitous promoters to express human FVIII or FIX. However, studies in mouse models of hemophilia have resulted in low transgene expression (Evans & Morgan, 1998; Kootstra & Verma, 2003; Tiede & Scherr, 2003), only achieving therapeutic expression levels following high copy gene transfer (>5 copies/cell, Bigger and Thermis, 2004). A recent study by Moayeri et al. (Mol. Ther., 2004) demonstrated long-term therapeutic levels of factor VIII expression in immunocompromised hemophilic mice engrafted with pre-selected, oncoretroviral vector transduced hematopoietic stem cells (HSCs). However, non-specific promoters may pose a greater risk of inducing insertional oncogenesis than vectors whose expression is restricted to terminally differentiated progeny, such as maturing erythroblasts.
Abstract 521: 4, 4′-Dichlorodiphenyltrichloroethane (DDT) and Triclosan (TCS) decrease tumor-cell-binding capacity and cell-surface protein expression of human natural killer cells
Authors: Tasia D. Hurd-Brown, Felicia Udoji, Tamara Martin, Margaret Whalen
Journal: Cancer Research (2012)

Abstract 4, 4′-Dichlorodiphenyltrichloroethane (DDT) and Triclosan (TCS) are organochlorine compounds that contaminate the environment, are found in human blood, and have been shown to decrease the tumor-cell killing (lytic) function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. This study examined concentrations of DDT and PCP that decrease lytic function for alteration of NK binding to tumor targets. Levels of either compound that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. CD16 is an Fc receptor and CD56 is a cognate of neural cell adhesion molecules, both of which are present on NK cells and involved in recognition and lysis of NK target. NK cells exposed to 2.5 µM DDT for 24 h (which caused a greater than 55% loss of lytic function) showed a decrease in NK binding function of about 23%, and a decrease in CD16 of 20%. NK cells exposed to 5 µM TCS for 24 h showed a decrease in ability to bind tumor cells of 44% and a decrease in expression of CD56 of about 34%. This same treatment caused a decrease in lytic function of greater than 87%These results indicated that only a portion of the loss of NK lytic function seen with exposures to these compounds could be accounted for by loss of binding function and also accompanied by loss of cell-surface protein expression. Supported by NIH grant 1U54CA163066-01 and S06 GM008092-35 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 521. doi:1538-7445.AM2012-521
Can computerised decision support systems deliver improved quality in primary care?
Authors: B. C Delaney, D. A Fitzmaurice, A. Riaz, F D R. Hobbs
Journal: BMJ (1999)

Computerised decision support systems or “expert systems” are computer software systems that are designed to aid clinical decision making Computerised decision support has been defined as provision of assessments or prompts specific to the patient and selected from a knowledge base on the basis of individual patient data.1 At its simplest this definition will include programs that suggest alternatives for treatment or diagnosis on the basis of a simple algorithm. More complex systems model the likelihood of future events and the effectiveness of proposed interventions based on individual patient data and “knowledge” of risks and the effectiveness of interventions.2 

Primary care more than any other specialty is characterised by uncertainty This is not only because it is the first point of contact and the recipient of undifferentiated problems, but also because primary care has the role of monitoring and providing optimal continuing care for many common chronic conditions. Improvement of quality by a reduction of the variation in primary care practice is a key component of UK national health policy.3 Computerised decision support systems have potential to drive reminders, provide alerts for prescribing interactions or test results, interpret complex investigations (or electrocardiograms), predict mortality on the basis of epidemiological data, aid diagnosis, and calculate drug doses. The question examined by this review is how may computerised decision support systems contribute to improving quality in primarycare?

#### Summary points

Computerised reminder and recall systems increase the frequency of monitoring and preventive tasks in the management of chronic disease

Computerised dosing systems for warfarin improve the control of anticoagulation

Computerised diagnostic decision support has not yet been developed to the stage where it can significantly aid diagnostic accuracy

There is a lack of research with patient oriented outcomes in this topic

Shared decision making between doctors and patients is an issue where …
The Pathway of Ventricular Depolarization in the Dog
Authors: ALLEN M. SCHER, ALLAN C. YOUNG, Robert V. Erickson, Rolfe A. Becker, Juhan Liikane, Otis F. Brorun
Journal: Circulation Research (1956)

Studies of ventricular depolarization with multichannel recording technics permit detailed three dimensional analysis of the process. Activity commences on the mid left septal surface, followed by activity on the right septum. Rapid endocardial excitation follows and leads to endoepicardial activation of the walls. The latest areas activated are in the basal septum. These findings are related to the genesis of the normal QRS. Theories of simultaneous activation and electrocardiographic silent areas are discussed.
Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency
Authors: Dorothee Schott, Carl-Erik Dempfle, Peter Beck, Andreas Liermann, Anita Mohr-Pennert, Michael Goldner, Peter Mehlem, Hiroyuki Azuma, Volker Schuster, Anne-Marie Mingers, Hans Peter Schwarz, Michael Dieter Kramer, Hans Liesenhoff, Karl Heinz Niessen
Journal: New England Journal of Medicine (1998)

Ligneous conjunctivitis is a rare disease characterized by acute or chronic recurrent conjunctivitis in which the conjunctival membranes acquire a wood-like consistency, due primarily to deposits of fibrin.1,2 Corneal involvement and chronic obstruction of the eye may lead to blindness. The disease is frequently associated with nasopharyngitis, tracheobronchial obstruction, otitis media, vulvovaginitis, and defective wound healing.2–9 Pseudomembranous conjunctivitis was first described in 1847 by Bouisson,10 and the term “conjunctivitis lignosa” was introduced by Borel in 1933.11 More than 100 cases have been reported in the literature, but no satisfactory treatment has yet been found. The results of therapy . . .
Effects of Intracellular Angiotensin II in Vascular Smooth Muscle Cells
Authors: Hermann Haller, Carsten Lindschau, Bettina Erdmann, Petra Quass, Friedrich C. Luft
Journal: Circulation Research (1996)

Angiotensin (Ang) II is present inside vascular smooth muscle cells (VSMCs); however, its intracellular functions, if any, are unknown. We tested the hypothesis that intracellular Ang II exerts effects on cytosolic Ca 2+ ([Ca 2+ ] i ) in VSMCs. Ang II was administered via microinjection. Intracellular Ang II localization was demonstrated by fluorescein-labeled Ang II and electron microscopy. [Ca 2+ ] i was monitored by confocal microscopy with fluo 3. Ang II was identified in endosomes and in the nucleus by both localizing techniques. Microinjection of Ang II (10 −10 mol/L) led to a rapid increase in [Ca 2+ ] i in the cytosol and in the nucleus. The [Ca 2+ ] i increase was due to the influx of extracellular Ca 2+ ions. The intracellular Ang II effect was totally inhibited by the concomitant injection of the Ang II antagonist CV-11947. Desensitization of extracellular Ang II receptors, on the other hand, did not influence the intracellular effects, nor did extracellular CV-11947. The increase in [Ca 2+ ] i was observed not only in the microinjected cell but also in directly adjacent VSMCs. In contrast to the microinjected cells, the [Ca 2+ ] i increase in the adjacent cells was mostly due to release from intracellular stores. Pretreatment with thapsigargin abolished the Ang II response in adjacent cells. Microinjection of inositol tris-phosphate induced a [Ca 2+ ] i response in adjacent cells that was similar to the Ang II–induced effects. Preincubation of VSMCs with the uncoupling substances dimethyl sulfoxide and heptanol did not decrease the Ang II response but instead prevented a [Ca 2+ ] i surge in adjacent cells. We conclude that intracellular Ang II binds to intracellular Ang II receptors and elicits an increased [Ca 2+ ] i in the injected cell and, thereafter, cells in the immediate neighborhood. Cell-cell contact is necessary for the Ang II–mediated effects. The data suggest that intracellular Ang II may stimulate a cluster of VSMCs from a single cell via the release of second messengers.
Cough and breathlessness not responding to inhalers
Authors: R. Alluri, M. Chetty, G. P Currie
Journal: BMJ (2009)

A 29 year old unemployed woman who had never smoked was referred to the outpatient clinic with a 10 month history of non-productive cough, breathlessness, and chest tightness. Her exercise tolerance had reduced dramatically from breathlessness on exertion to symptoms at rest over six months. She had been treated for asthma in the community for six months before attendance, although inhalers had conferred little improvement in symptoms. She lived alone and had kept budgies for several years. She did not have cyanosis or clubbing. Her pulse rate was 80 beats/min regular, blood pressure was 124/88 mm Hg, and her heart sounds were normal. On auscultation she had vesicular breath sounds with fine inspiratory bilateral basal crackles. Routine haematological and biochemical parameters were normal. Her urinalysis was negative. Chest radiography showed diffuse bilateral air space consolidation, and electrocardiography was normal. Her forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were 1.8 l (predicted 3.3 l) and 2.1 l (3.9 l), respectively. ### Short answers
The problem of multiple inference in identifying point-source environmental hazards.
Authors: D C Thomas
Journal: Environmental Health Perspectives (1985)

Point-source environmental hazards are often identified by examination of unusual clusters of disease cases. The very large number of potential clusters give rise to the statistical problem of "multiple inference," i.e., the more clusters examined, the greater the risk of "false-positive" associations emerging by chance alone. This paper first distinguishes the situation of clusters identified by anecdotal observation from those that emerge from systematic searches. The latter may or may not include a systematic enumeration of potential causal factors associated with each potential disease cluster. If exposure information is not systematically available, empirical Bayes procedures are suggested as a basis for ranking the observed clusters in order of priority for further investigation. If exposure information is systematically available, empirical Bayes procedures can be used to select associations to report or to rank them in order of priority for confirmation. In addition, procedures are described for testing the global null hypothesis of no exposure-disease associations and for estimating the number of true-positive associations. These approaches are advocated in preference to classical frequentist approaches of multiplying p values by the number of tests performed.
Inflammatory Bowel Disease: What is New?
Authors: P. Marteau, F. Daniel, P. Seksik, R. Jian
Journal: Endoscopy (2004)

This article reviews a selection of 50 papers on inflammatory bowel disease published between April 2002 and August 2003. The new information and progress summarized here includes: the role of bacteria, their interaction with CARD15/NOD2 gene products and the modulating effects of probiotics; new imaging techniques, such as wireless capsule endoscopy and chromoendoscopy for detecting dysplasia, and fecal markers. It has not been possible to review every aspect of treatment, and the focus here is on factors capable of predicting the efficacy and tolerance of infliximab and new treatments, including natalizumab, thalidomide, cyclophosphamide and 6-thioguanine.
Pharmacokinetics and short-term safety and tolerability of intranasally administered triamcinolone acetonide aqueous spray in 2-5 year old patients with Perennial Allergic Rhinitis (PAR) and adult patients with PAR
Authors: P.D. Cooper, J.D. Conner, P.J. Mustillo, V. Sekar, J. Garcia, G. Georges, S.J. Kovacs
Journal: Journal of Allergy and Clinical Immunology (2005)
Perspectives in NHS management. Doctors have management responsibilities too.
Authors: D S Grimes
Journal: BMJ (1984)

Management is entering into the work of clinicians and is threatening to take up an increasing amount of their time.The cause is obvious.In an era of government cash limits over- spending of district funds is illegal.Doctors control most clinical activity, which consumes virtually all the cash allocation of a district, so the pressure is on them to work "economically" and "responsibly."But what does this mean?The doctor's first responsibility is to his patients.He or she is trained to do the best for each individual patient, an ethos that applies whether he is in a clinical specialty with direct patient contact or in a service specialty such as histopathology.Excellence is the ground rule for the medical profession, and the royal colleges oversee this aim by insisting on exacting standards so that consultants are of high calibre at the time of appointment.
Abstract 17548: Computed Tomography Stress Myocardial Perfusion for Diagnosing Myocardial Ischemia - A Comparison with Quantitative Coronary Angiography and Fractional Flow Reserve
Authors: Brian S Ko, James D Cameron, Michael Leung, Sam Lehman, Sarah Hope, Marcus Crossett, John Troupis, Paul Antonis, Ian T Meredith, Tony DeFrance, Sujith Seneviratne
Journal: Circulation (2010)

Purpose: To determine the accuracy of 320 slice adenosine stress computed tomography myocardial perfusion imaging (CTP) for detection of significant myocardial ischemia using combined QCA on invasi...