tbuckley/cabot-search huggingface dataset:
Paroxysmal nocturnal hemoglobinuria: deficiency in factor H-like functions of the abnormal erythrocytes.
Authors: M K Pangburn, R D Schreiber, J S Trombold, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1983)

Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) contained a subpopulation that lacked membrane-associated Factor H-like activity present on normal human erythrocytes. Initial deposition of C3b on the erythrocytes was effected using a fluid phase C3 convertase. The cells were then treated with fluorescein-labeled C3 and the cell-bound C3 convertase. Analysis utilizing the fluorescence-activated cell sorter revealed two distinct cell populations, one of which was highly fluorescent, indicating a large number of C3b molecules per cell. Only this population (43%) was susceptible to lysis (44%) when exposed to acidified serum before C3b deposition. The less fluorescent population resembled normal human erythrocytes and was not affected by prior treatment with acidified serum. Since C3b deposition occurred almost exclusively on the complement-sensitive cells in the PNH erythrocyte population, these cells could be examined for the Factor H-like regulatory activities without prior isolation. These functions include enhancement of inactivation of erythrocyte-bound C3b by Factor I and acceleration of the decay of erythrocyte-bound C3 convertase, C3b,Bb. It was found that C3b on PNH erythrocytes was 100-fold less susceptible to inactivation by Factor I than C3b on normal human erythrocytes. The half-life at 22 degrees C of C3b,Bb on PNH erythrocytes was threefold greater than on normal human erythrocytes and similar to that of the enzyme bound to particles that do not possess Factor H-like activity. These observations suggest that the abnormal susceptibility of PNH erythrocytes to lysis by complement is due to a functional deficiency in one or more of the Factor H-like proteins present on normal human erythrocytes.
Relevance of Cost-effectiveness Analysis to Clinicians and Policy Makers
Authors: Allan S Detsky, Andreas Laupacis
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
HOW DO MONOCLONAL ANTIBODIES INDUCE TOLERANCE? A Role for Infectious Tolerance?
Authors: Herman Waldmann, Stephen Cobbold
Journal: Annual Review of Immunology (1998)

▪ Abstract One of the major goals in therapeutic immunosuppression has been to achieve long-term benefit from short-term therapy. The discovery in the mid-1980s that CD4 antibodies can induce immunological tolerance without depleting CD4 + T cells has reawakened interest in the use of nondepleting monoclonal antibodies for reprogramming the immune system in autoimmunity and in transplantation. Since that time, antibodies to CD11a, CD4OL, CD25, CD3, and CTLA4-Ig have all been shown capable of facilitating tolerance. In order to apply the principle of reprogramming in the clinic, we have sought to understand the mechanisms that are involved in its induction and its maintenance. In a number of allogeneic transplant models (heart, skin, bone marrow) anti-CD4 (± CD8) antibodies can be shown to block the rejection process while selectively promoting the development of CD4 + regulatory T cells responsible for a dominant tolerance that is reflected in findings of linked suppression and infectious tolerance. In these models, T cells that have never been exposed to CD4 antibodies become tolerant to grafted antigens by experiencing antigen in the microenvironment of regulatory T cells. Dominant tolerance is not the only mechanism that can be facilitated by CD4 Mab therapy. If allogeneic marrow is given at high cell doses under the umbrella of CD4 and CD8 antibodies, then tolerance can be achieved through clonal deletion. The mechanism by which regulatory CD4 + T cells suppress is not yet defined but could be active or passive. We have proposed the “civil service model” to explain how tolerant T cells might interfere with the responses of competent T cells in such a way as to render them tolerant. The application of dominant infectious tolerance and linked suppression to clinical immunosuppression should not be underestimated because it suggests that tolerance acquired (through therapy) to a limited set of antigens can spread to embrace all others in the tissues under attack.
Modulation of histamine-induced bronchoconstriction with inhaled, oral, and intravenous clemastine in normal and asthmatic subjects.
Authors: V Hartmann, H Magnussen, J P Holle, E Schuler
Journal: Thorax (1981)

Although histamine plays an important role in the pathophysiology of asthma through stimulation of H1 receptors, H1 antagonists are of only limited use in this disease when given orally. In order to investigate the pharmacological response to a specific H1 antagonist administered by different routes, we measured the effect of inhaled clemastine on airway responsiveness to histamine aerosol and compared the results with those after oral and intravenous administration in normal and asthmatic subjects. Inhalation of 0.6 mg clemastine provided significant protection without side effects and was comparable to intravenous administration of 1.0 mg in both groups. In normal subjects 2.0 mg clemastine orally was significantly less effective than the two other routes of administration whereas in asthmatics an enhanced reaction to histamine was observed.
Specialists or Generalists? The Medical Outcomes Study
Authors: Roz Diane Lasker
Journal: JAMA (1992)

<h3>To the Editor.</h3> —In the Editorial by Rosenblatt<sup>1</sup>and in discussions at last month's National Primary Care Conference in Washington, DC, the two recent articles published inTHE Journalabout the Medical Outcomes Study (MOS)<sup>2,3</sup>were cited as supporting the premise that substantial savings in US health care costs could be achieved—without compromising quality of care—by increasing the relative proportion of generalists vs specialists. While there are good reasons to change the mix of practicing physicians, relying on studies such as these to predict substantial cost savings may be overly optimistic. In the MOS, endocrinologists and cardiologists were shown to use more resources than general internists and family physicians, even after applying certain adjustments for patient mix. But the adjustments used did not adequately account for differences in the mix of medical problems that physicians in each specialty managed. This is an important limitation because different medical problems
PASSIVE TRANSFER OF ADJUVANT ARTHRITIS BY LYMPH NODE OR SPLEEN CELLS
Authors: Carl M. Pearson, Fae D. Wood
Journal: The Journal of Experimental Medicine (1964)

All adjuvant-induced arthritis has been passively transferred in a highly inbred strain of rats by transfer of viable lymph node or spleen cells, but not thymus cells, to normal recipients. After an interval averaging 4.3 days recipients developed arthritis, whereas animals actively sensitized with adjuvant never developed disease before the 9th day (average 11.3 days). The transferred disease had all of the gross and pathological characteristics of primary disease, except for a lesser severity. Control studies using non-viable cells either of lymphoidal or other tissue origin were always negative. It is concluded that adjuvant arthritis is the result of an immunologic reaction which is perhaps similar to delayed hypersensitivity. The antigen in this reaction so far remains obscure.
PREVALENCE OF ANTIBODY TO HUMAN T-LYMPHOTROPIC VIRUS TYPE III IN AIDS AND AIDS-RISK PATIENTS IN BRITAIN
Authors: R Cheingsong-Popov, R.A Weiss, A Dalgleish, R.S Tedder, D.J Jeffries, D.C Shanson, R.B Ferns, E.M Briggs, I.V.D Weller, S Mitton, M.W Adler, C Farthing, A.G Lawrence, B.G Gazzard, J Weber, J.R.W Harris, A.J Pinching, J Craske, J.A.J Barbara
Journal: The Lancet (1984)
Subthalamic Nucleus Stimulation in Severe Obsessive–Compulsive Disorder
Authors: Luc Mallet, Mircea Polosan, Nematollah Jaafari, Nicolas Baup, Marie-Laure Welter, Denys Fontaine, Sophie Tezenas du Montcel, Jérôme Yelnik, Isabelle Chéreau, Christophe Arbus, Sylvie Raoul, Bruno Aouizerate, Philippe Damier, Stephan Chabardès, Virginie Czernecki, Claire Ardouin, Marie-Odile Krebs, Eric Bardinet, Patrick Chaynes, Pierre Burbaud, Philippe Cornu, Philippe Derost, Thierry Bougerol, Benoit Bataille, Vianney Mattei, Didier Dormont, Bertrand Devaux, Marc Vérin, Jean-Luc Houeto, Pierre Pollak, Alim-Louis Benabid, Yves Agid, Paul Krack, Bruno Millet, Antoine Pelissolo
Journal: New England Journal of Medicine (2008)

Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option.In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests.After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events.These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)
Screening Sensitivity and Sojourn Time From Breast Cancer Early Detection Clinical Trials: Mammograms and Physical Examinations
Authors: Yu Shen, Marvin Zelen
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To estimate sensitivities of breast cancer screening modalities and preclinical duration of the disease from eight breast cancer screening clinical trials. PATIENTS AND METHODS: Screening programs invariably lead to diagnosis of disease before signs or symptoms are present. Two key quantities of screening programs are the sensitivity of the disease detection modality and the mean sojourn time (MST). The observed screening histories in a periodically screened cohort make it possible to estimate these quantities of interest. We applied recently developed statistical methods to data from eight randomized breast cancer screening trials to estimate the sensitivities of early detection modalities and MST. Moreover, when a screening trial involved two screening modalities, our methods enabled the estimation of the individual sensitivity of each screening modality. RESULTS: We analyzed breast cancer data from several screening trials and have relatively complete data from the Health Insurance Plan (HIP), Edinburgh, and two Canadian studies. The screening sensitivity for mammography, physical examination, and MST were, respectively, HIP: 0.39, 0.47, and 2.5 years; Edinburgh: 0.63, 0.40, and 4.3 years; Canadian (age 40 to 49 at entry): 0.61, 0.59, and 1.9 years; Canadian (age 50 to 59 at entry): 0.66, 0.39, and 3.1 years. CONCLUSION: The public debate on early breast cancer detection is mainly centered on mammograms. However, the current study indicates that a physical examination is of comparable importance. Cautious interpretation of trial differences is required as a result of various experimental designs and the age dependency of screening sensitivity and MST.
Platelet-associated CD154 in immune thrombocytopenic purpura
Authors: Anne Solanilla, Jean-Max Pasquet, Jean-François Viallard, Cécile Contin, Christophe Grosset, Julie Déchanet-Merville, Maryse Dupouy, Marc Landry, Francis Belloc, Paquita Nurden, Patrick Blanco, Jean-François Moreau, Jean-Luc Pellegrin, Alan T. Nurden, Jean Ripoche
Journal: Blood (2004)
LXRα Regulates Macrophage Arginase 1 Through PU.1 and Interferon Regulatory Factor 8
Authors: Benoit Pourcet, Jonathan E. Feig, Yuliya Vengrenyuk, Adrian J. Hobbs, Diane Kepka-Lenhart, Michael J. Garabedian, Sidney M. Morris, Edward A. Fisher, Inés Pineda-Torra
Journal: Circulation Research (2011)

Rationale: Activation of liver X receptors (LXRs) inhibits the progression of atherosclerosis and promotes regression of existing lesions. In addition, LXRα levels are high in regressive plaques. Macrophage arginase 1 (Arg1) expression is inversely correlated with atherosclerosis progression and is markedly decreased in foam cells within the lesion. Objective: To investigate LXRα regulation of Arg1 expression in cultured macrophages and atherosclerotic regressive lesions. Methods and Results: We found that Arg1 expression is enhanced in CD68+ cells from regressive versus progressive lesions in a murine aortic arch transplant model. In cultured macrophages, ligand-activated LXRα markedly enhances basal and interleukin-4–induced Arg1 mRNA and protein expression as well as promoter activity. This LXRα-enhanced Arg1 expression correlates with a reduction in nitric oxide levels. Moreover, Arg1 expression within regressive atherosclerotic plaques is LXRα-dependent, as enhanced expression of Arg1 in regressive lesions is impaired in LXRα-deficient CD68+ cells. LXRα does not bind to the Arg1 promoter but instead promotes the interaction between PU.1 and interferon regulatory factor (IRF)8 transcription factors and induces their binding of a novel composite element. Accordingly, knockdown of either IRF8 or PU.1 strongly impairs LXRα regulation of Arg1 expression in macrophage cells. Finally, we demonstrate that LXRα binds the IRF8 locus and its activation increases IRF8 mRNA and protein levels in these cells. Conclusions: This work implicates Arg1 in atherosclerosis regression and identifies LXRα as a novel regulator of Arg1 and IRF8 in macrophages. Furthermore, it provides a unique molecular mechanism by which LXRα regulates macrophage target gene expression through PU.1 and IRF8.
ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin
Authors: R. M. Wösten-van Asperen, R. Lutter, J. J. Haitsma, M. P. Merkus, J. B. van Woensel, C. M. van der Loos, S. Florquin, B. Lachmann, A. P. Bos
Journal: European Respiratory Journal (2007)

Ventilator-induced lung injury is characterised by inflammation and apoptosis, but the underlying mechanisms are poorly understood. The present study proposed a role for angiotensin-converting enzyme (ACE) via angiotensin II (Ang II) and/or bradykinin in acute lung injury. The authors assessed whether ACE and, if so, Ang II and/or bradykinin are implicated in inflammation and apoptosis by mechanical ventilation. Rats were ventilated for 4 h with low- or high-pressure amplitudes in the absence or presence of the ACE inhibitor captopril. Nonventilated animals served as controls. ACE activity, Ang II and bradykinin levels, as well as inflammatory parameters (total protein, macrophage inflammatory protein-2 and interleukin-6) were determined. Apoptosis was assessed by the number of activated caspase-3 and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labelling)-positive cells. Bronchoalveolar lavage fluid ACE activity, levels of total protein, inflammatory parameters and the number of apoptotic cells were increased in the high-pressure amplitude group as compared with the control group. Blocking ACE activity by captopril attenuated inflammation and apoptosis in the latter group. Similar results were obtained by blocking Ang II receptors, but blocking bradykinin receptors did not attenuate the anti-inflammatory and anti-apoptotic effects of captopril. The current authors conclude that inflammation and apoptosis in ventilator-induced lung injury is, at least in part, due to angiotensin-converting enzyme-mediated angiotensin II production.
CXCL13 and CXCL12 in Central Nervous System Lymphoma Patients
Authors: Lars Fischer, Agnieszka Korfel, Sebastian Pfeiffer, Philipp Kiewe, Hans-Dieter Volk, Hüsniye Cakiroglu, Thomas Widmann, Eckhard Thiel
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Homing of malignant lymphocytes to the central nervous system (CNS) may play a role in the pathogenesis of CNS lymphoma. In this study, we evaluated the chemokines CXCL12 and CXCL13 in the cerebrospinal fluid (CSF) and serum of patients with CNS lymphoma. Experimental Design: Samples from 30 patients with CNS lymphoma (23 with primary and 7 with secondary CNS lymphoma; all B-cell lymphoma) and 40 controls (10 patients with other CNS malignancies and 30 without a malignant CNS disease) were examined. CXCL12 and CXCL13 concentrations were measured using enzyme-linked immunosorbent assays. The grade of blood-brain barrier disruption was estimated by the CSF/serum albumin ratio. Results: CNS lymphoma patients and controls did not differ in CXCL12 serum and CSF levels. Serum levels of CXCL13 were generally low. CXCL13 CSF levels, however, were significantly higher in CNS lymphoma patients as compared with controls (P &amp;lt; 0.0001). Chemokine levels in CSF and serum did not correlate. In CNS lymphoma, CXCL13 concentration in CSF correlated with the degree of blood-brain barrier disruption (R = 0.66; P = 0.003). Elevated CSF levels of CXCL12 and CXCL13 measured in seven CNS lymphoma patients during therapy decreased in five patients who responded to chemotherapy and increased in two with lymphoma progression. Conclusions: Our results suggest a production of CXCL13 within the CNS of CNS lymphoma patients, which decreases with response to therapy. Thus, CXCL13 may represent a marker for further diagnostic and prognostic studies. (Clin Cancer Res 2009;15(19):5968–73)
Beware of Pity
Authors: Jerry O’Sullivan
Journal: BMJ (2008)

Stefan Zweig’s novel Ungeduld des Herzens (literally “The Heart’s Impatience”) is well known as a study of two types of pity, but it is also noteworthy for its portrayal of one of the most iconic doctors in fiction. The action is set in 1914 in a garrison town near Vienna. Edith von Kekesfalva is a rich, pretty, 17 year old girl, who has been left crippled by polio. Initially, her father consulted numerous distinguished physicians, but now she is attended by Dr Condor, a family physician from Vienna. Lieutenant Hofmiller, a cavalry officer, feels sorry for Edith and falls into the habit of visiting her almost …
Behavior of eosinophil leukocytes in acute inflammation. I. Lack of dependence on adrenal function.
Authors: D A Bass
Journal: Journal of Clinical Investigation (1975)

Acute infection is accompanied by a characteristic reduction in circulating eosinophils. This study examined the generally held assumption that the eosinopenia of infection is a manifestation of adrenal stimulation. Trichinosis, Escherichia coli pyelonephritis, and early subcutaneous pneumococcal abscess were used as experimental infections of limited severity. Trichinosis is associated with eosinophilia, but pyelonephritis and pneumococcal infection produce eosinopenia. An assay for serum corticosterone was developed that is sufficiently sensitive to be performed with the small volumes of blood obtained sequentially from individual mice. The corticosterone response to trichinosis fits the sterotyped reaction previously reported for several other bacterial, viral, and rickettsial infections. The peak concentrations of corticosterone in serum from mice with trichinosis was approximately twice normal and occurred at the onset of clinical illness. Serum corticosterone levels gradually declined to the normal range over the next several days. E. coli pyelonephritis produced a similar adrenal response, although the peak serum corticosterone caused by pyelonephritis was less than the serum corticosterone occurring during the first peak of eosinophilia during trichinosis. Infection of a subcutaneous air pouch with penumococci produced eosinopenia within 6 h after inoculation, but there was no rise in serum corticosterone during the first 12 h of the pneumococcal infection. In addition, the eosinopenic response produced by a 12-hpneumococcal abscess occurred mice adrenalectomized 1-4 days before infection with pneumococci. The eosinopenia of acute infection cannot be ascribed to adrenal stimulation.
Hemocyanin, Troponin C and Fatty Acid-binding Protein (FABP) May be Cross-reactive Allergens Between Crustaceans, Cockroach and Dust Mites
Authors: R. Ayuso, G. Grishina, M. Pascal, S. Sanchez-Garcia, D. Towle, C. Smith, M. Ibáñez, H.A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2011)
The Interplay of Coronary Vascular Resistance and Myocardial Compression in Regulating Coronary Flow
Authors: CARL J. WIGGERS
Journal: Circulation Research (1954)

By integrating phasic coronary sinus flow curves in such a way that volume flow during systole plus isometric contraction and that during the remainder of diastole can be compared, the relative contribution of ventricular compression and coronary resistance to mean coronary flow can be assessed. It was found that anoxia, adenylic acid, compression of the aorta or pulmonary artery reduces coronary vascular resistance while epinephrine increases it. The augmentation in coronary mean flow following epinephrine is due solely to the greater force of ventricular contractions. On the basis of such evidence a revival of the "massaging theory" in modified form is suggested. Evidence was incidentally obtained which supports a former conclusion that the coronary sinus drains territories supplied by the right as well as the left coronary artery.