tbuckley/cabot-search huggingface dataset:
A QUEST FOR ERYTHROPOIETIN OVER NINE DECADES
Authors: James W. Fisher
Journal: The Annual Review of Pharmacology and Toxicology (1998)

[Figure: see text] ▪ Abstract The major research accomplishments of the author are described from the time of his PhD thesis work on the mechanism of cobalt polycythemia to the present day. His early work on the quest for the cell that produces erythropoietin (Epo) to his current work on oxygen sensing and signal transduction pathways involved in erythropoietin gene expression are reported. He describes his main research interest in the mechanism of cobalt polycythemia between 1954 and 1962 and his research on how hormones such as the glucocorticoids function in the regulation of erythropoiesis (1956–1962). His major findings during this period were the discovery that hydrocortisone and corticosterone stimulated erythropoiesis (1958) and that cobalt increased erythropoietin production in the isolated perfused dog kidney (1961). He describes how he was led astray in some of his early studies on the cells in the kidney that produce erythropoietin, because of the less-developed technology available to him at that time; and how in situ hybridization and other molecular biology techniques enabled him to confirm some of the earlier work in mice by other investigators that interstitial cells in the kidney were the site of production of erythropoietin in the primate. His work in the controversial area of the mechanism of the anemia of end-stage renal disease is described in detail, as it pertains to Epo deficiency and suppressed erythroid progenitor cell response to Epo. He also discusses his recent work on signal transduction pathways (hypoxia, nitric oxide, adenosine, and C kinase) in oxygen sensing and Epo gene expression.
The infant lung function model: a mechanical analogue to test infant lung function equipment
Authors: U. Frey, B. Reinmann, J. Stocks
Journal: European Respiratory Journal (2001)

To facilitate international multicentre studies and quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society (ERS-ATS) working group for infant lung function testing aims to develop specifications for standardized infant lung function equipment and software. However, a standardized test device is also needed to test whether existing infant lung function equipment is able to meet these requirements. The authors have built a "mechanical model baby" consisting of a linear pump which can reproduce prerecorded tidal flow waveforms with a precision of 0.5% (full stroke), enabling the simulation of tidal and forced flow patterns. This linear pump can be connected to a series of copper lung volumes (range 50-300 mL) with known time constants, so that lung volumes can be reproduced with a precision of +/-1% at frequencies 10-120bpm. Five airflow resistors were built using sinter material. When assessed using flows 0-300 mL.s(-1) all resistors showed a quasilinear pressure/ flow relationship, with slopes 1.0-5.6 kPa.L(-1).s. These resistances could be reproduced with a precision of +/-2.5%. The infant lung model can also be used to assess frequency responses of infant lung function equipment, since the pump is capable of delivering low amplitude volumes up to 20 Hz in a pseudorandom noise manner. In summary, based on error estimations, this infant lung model is able to test whether or not infant lung function equipment meets the requirements suggested by the European Respiratory Society-American Thoracic Society standardization group, that is: flow measurements within +/-2.5%, volume and resistance measurements within +/-5%, frequency response: magnitude attenuation <+/-10% and phase shift <+/-3 degrees at 10 Hz.
THE STRUCTURE OF SEBORRHOEIC KERATOSES
Authors: K. V. Sanderson
Journal: British Journal of Dermatology (1968)

SUMMARY. A series of different types of seborrhoeic keratosis has been dissected after maceration in acetic acid and dermo‐epidermal separation. In all lesions the dermal papillae are enlarged and in many they are branched. The underside of the keratosis has slits and channels from which the papillae have been extracted. The earliest epidermal changes are deepening and hyperpigmentation of the interpapillary ridges. Further development may produce thin membrances of epidermis covering greatly elongated papillae or a more exuberant and often darkly pigmented fleshy mass. Pearly structures develop in the epidermal parenchyma of the keratosis. They may be isolated or grouped within a common membrane. Some pearls are attached to the horny layer and others may be found in the keratin debris on the surface. The outer surface, after the loose keratin is removed, has a papillary outline in most cases. The papillae may project freely or be embedded in the walls of a honeycomb filled with loose keratin. Smooth surfaced keratoses have keratinfilled adnexal ducts punctuating the surface. The findings are in keeping with the concept that seborrhoeic keratoses develop because of a local arrest of maturation of keratinocytes.
Isoform Divergence of the Filamin Family of Proteins
Authors: B. A. Kesner, S. L. Milgram, B. R.S. Temple, N. V. Dokholyan
Journal: Molecular Biology and Evolution (2009)

The vertebrate filamin family (A, B, and C) is part of the spectrin family of actin cross-linking proteins. Family members share high sequence similarity (>64%) and have both common and isoform-distinct functionalities. To identify the basis for isoform-specific functionality, we perform an evolutionary trace of chordate filamin at the granularity of single residues. Our trace methodology is constrained to focus on neofunctionality by requiring that one isoform remain the ancestral type, whereas at least one isoform has an accepted mutation. We call divergence meeting these characteristics "class-distinctive." To obtain a temporal and spatial context for class-distinctive residues, we derive an all-atom model of full-length filamin A by homology modeling and joining individual domains. We map onto our model both conserved and class-distinctive residues along with the period (Teleostei, Amphibian, and Mammalian) in which they diverged. Our phylogenetic analysis suggests that filamins diverged from a common ancestral gene between urochordate and vertebrate lineages. Filamins also diverged the most just after gene duplication, in the Teleostei period, with filamin C remaining closest to ancestral filamin. At the residue level, domains with well-characterized interfaces, IgFLN 17 and IgFLN 21 (immunoglobulin, Ig), have diverged in potentially critical residues in their adhesion protein–binding interfaces, signifying that isoforms may bind or regulate ligand binding differentially. Similarly, isoform divergence in a region associated with F actin–binding regulation suggests that isoforms differentially regulate F-actin binding. In addition, we observe some class-distinctive residues in the vicinity of missense mutations that cause filamin A and B–associated skeletal disorders. Our analysis, utilizing both spatial and temporal granularity, has identified potentially important residues responsible for vertebrate filamin isoform–specific divergence—significantly in regions where few binding partners have been discovered to date— and suggests yet to be discovered filamin-binding partners and isoform-specific differential regulation with these binding partners.
Mild Cognitive Impairment and Dementia
Authors: Marilyn S. Albert, Deborah Blacker
Journal: Annual Review of Clinical Psychology (2006)

Mild cognitive impairment (MCI) is a clinical syndrome thought to represent the transition between normal function and dementia. This review describes data that support the existence of such a transitional phase, outlines the heterogeneity of MCI and how that has influenced the evolving concept of MCI, and discusses the impact of heterogeneity on recent MCI clinical trials.
Users' Guides to the Medical Literature
Authors: W. Scott Richardson, Allan S. Detsky, Gordon Guyatt, Deborah Cook, Hertzel Gerstein, Robert Hayward, Anne Holbrook, Roman Jaeschke, Elizabeth Juniper, Mitchell Levine, David Naylor, Andrew Oxman, David Sackett, Sean Tunis, Stephen Walter, John Williams, Mark Wilson
Journal: JAMA (1995)

YOU RECALL from the first of our two articles concerning clinical decision analysis<sup>1</sup>that your patient is a middle-aged man with heart failure from an idiopathic dilated cardiomyopathy. You are trying to decide whether to recommend anticoagulation with warfarin to prevent systemic or pulmonary thromboembolism. Your literature search showed that no randomized clinical trials of warfarin for this use have been published. The search did discover a clinical decision analysis,<sup>2</sup>and in the first article, we showed you how to evaluate its validity. In this article, we will show you how to interpret the results and generalizability of a clinical decision analysis (Table). As shown in the Figure, decision trees are displayed graphically, oriented from left to right, with the decision to be analyzed on the left, the compared strategies in the center, and the clinical outcomes on the right. The square box, termed a "decision node," represents
Arterial Supply to the Nodal Tissue in the Dog Heart
Authors: MYRON H. HALPERN
Journal: Circulation (1954)

A study of the hearts of 107 dogs revealed that the blood supply to the sinoatrial node was from three sources: right coronary artery, left coronary artery, and right internal mammary artery. A dominant pattern of supply was found in 90 hearts. Three variations are described. The importance of arterial anastomoses to the sinus node and their role in the formation of an extracardiac coronary arterial system are discussed.
TH17 cells mediate pulmonary collateral priming
Authors: Melanie Albrecht, Hui-Chen Chen, Paula Preston-Hurlburt, Patricia Ranney, Heinz-Gerd Hoymann, Joachim Maxeiner, Valérie Staudt, Christian Taube, H. Kim Bottomly, Anna-Maria Dittrich
Journal: Journal of Allergy and Clinical Immunology (2011)
Acute hepatic necrosis and fulminant hepatic failure.
Authors: B Rueff, J P Benhamou
Journal: Gut (1973)

Progress report Acute hepatic necrosis and fulminant hepatic failureFulminant hepatic failure' is defined as severe, acute impairment of hepatic function culminating in hepatic encephalopathy, the encephalopathy being the result of hepatocellular failure and supervening within three weeks of the onset of symptoms*.This definition excludes the hepatic encephalopathy of hepatic cirrhosis and of chronic hepatitis, which produces a slightly different clinical picture, but fulminant hepatic failure as defined here may of course occur as a superimposed phenomenon in patients with these conditions.Likewise excluded is encephalopathy caused by sedatives in patients with viral hepatitis or by a direct cerebral action of certain halogenated hydrocarbons in subjects whose livers are already damaged by these compounds.The clinical features of a typical attack of fulminant hepatic failure are progressive jaundice of acute onset, shrinkage of the liver, foetor hepaticus, and hepatic coma"2.Characteristic biochemical changes are increased prothrombin time, elevated serum transaminase activity, and raised blood ammonia concentration3.*In order to be included in the fulminant hepatic failure surveillance study", the syndrome must occur within eight weeks of the onset of illness; we, however, regard this interval as too long.
CALCITONIN GENE-RELATED PEPTIDE: POTENT VASODILATOR AND MAJOR PRODUCT OF CALCITONIN GENE
Authors: SamiaI. Girgis, JohnC. Stevenson, Catherine Lynch, ColinH. Self, DavidW.R. Macdonald, PeterJ.R. Bevis, SunilJ. Wimalawansa, HowardR. Morris, Iain Macintyre
Journal: The Lancet (1985)
Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum
Authors: M. Guilarte, J. Santos, I. de Torres, C. Alonso, M. Vicario, L. Ramos, C. Martinez, F. Casellas, E. Saperas, J. R. Malagelada
Journal: Gut (2006)

<b>Background:</b> Increased numbers of mast cells and mast cell activation in distal gut segments are associated with symptom onset and severity in irritable bowel syndrome (IBS). Although upper gut symptoms are common, mast cells have not been thoroughly evaluated in proximal gut in IBS patients. <b>Methods:</b> Jejunal biopsies obtained by Watson’s capsule, aspiration of intestinal fluid and one blood sample were obtained in 20 diarrhoea-predominant patients with IBS (D-IBS) and 14 healthy volunteers (H). Psychological stress (Holmes-Rahe Scale) and depression (Beck’s Depression Inventory) were evaluated at baseline and food and respiratory allergy excluded. Biopsies were processed for H&amp;E staining and microscopic inflammation assessed by counting intraepithelial lymphocytes. Mast cells in lamina propria were counted by immunohistochemistry with CD117 (<i>c-kit</i>). Tryptase concentration was measured in intestinal fluid and serum. <b>Results:</b> D-IBS patients showed higher psychological stress than healthy volunteers (D-IBS: 203 (SD 114) <i>v</i> H: 112 (SD 99); p = 0.019). Immunohistochemical staining of jejunal mucosa revealed mild increase in intraepithelial CD3+ cells in D-IBS patients (D-IBS: 15.3 (SD 5.5; 95% CI 12.7 to 17.9) <i>v</i> H: 10.3 (SD 3.9; 95% CI 8.0 to 12.5); p = 0.006). Moreover, D-IBS patients showed marked increase in mast cells numbers (D-IBS: 34 (SD 9.3); H: 15.3 (SD 4.4) mast cells/hpf; p&lt;0.001) and higher tryptase concentration in jejunal fluid (D-IBS: 0.45 (SD 0.38); H: 0.09 (SD 0.10) µg/l; p = 0.005). Upper gut symptoms were not associated with gender, mast cell counts, jejunal tryptase or basal stress. <b>Conclusion:</b> This jejunal mucosal inflammatory profile may help identify diarrhoea-predominant IBS, a stress-related disorder.
Hierarchical and Redundant Lymphocyte Subset Control Precludes Cytomegalovirus Replication during Latent Infection
Authors: Bojan Polić, Hartmut Hengel, Astrid Krmpotić, Joanne Trgovcich, Ivica Pavić, Pero Lučin, Stipan Jonjić, Ulrich H. Koszinowski
Journal: The Journal of Experimental Medicine (1998)

Reactivation from latent cytomegalovirus (CMV) infection is often associated with conditions of immunosuppression and can result in fatal disease. Whether the maintenance of systemic CMV latency is mainly governed by factors of the infected cell or by immune control functions is unknown. Likewise, the putative immune control mechanisms which could prevent the induction and spread of recurrent CMV infection are not clearly identified. We took advantage of latently infected B cell-deficient mice and a sensitive method for virus detection to study CMV reactivation after ablation of lymphocyte subsets. A crucial role of both T lymphocytes and natural killer (NK) cells was demonstrated. Within 5 d after depletion of lymphocytes, productive infection occurred in 50% of mice, and 14 d later 100% of mice exhibited recurrent infection. A hierarchy of immune control functions of CD8(+), NK, and CD4(+) cells was established. Reactivation was rare if only one of the lymphocyte subsets was depleted, but was evident after removal of a further subset, indicating a functional redundancy of control mechanisms. The salivary glands were identified as the site of most rapid virus shedding, followed by the detection of recurrent virus in the lungs, and eventually in the spleen. Our findings document a previously unknown propensity of latent CMV genomes to enter productive infection immediately and with a high frequency after immune cell depletion. The data indicate that only the sustained cellular immune control prevents CMV replication and restricts the viral genome to a systemic state of latency.
Administration, distribution, metabolism and elimination of polymer therapeutics
Authors: Ela Markovsky, Hemda Baabur-Cohen, Anat Eldar-Boock, Liora Omer, Galia Tiram, Shiran Ferber, Paula Ofek, Dina Polyak, Anna Scomparin, Ronit Satchi-Fainaro
Journal: Journal of Controlled Release (2011)
Exercises in Self-Observation: A Workshop for Instructors in Psychiatry
Authors: HYMAN L. MUSLIN, HUGH T. CARMICHAEL
Journal: American Journal of Psychiatry (1967)

The authors describe a method of observing the teaching of clinical psychiatry based on the filming of teacher-student dyads; showing of the film is followed by "group supervision" of the instructor by a workshop group. The method is aimed at the formation of a group alliance to derive insights into the complicated transactions of student and teacher.
Regulation of cytokine production in the human thymus: epidermal growth factor and transforming growth factor alpha regulate mRNA levels of interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6 in human thymic epithelial cells at a post-transcriptional level.
Authors: P T Le, S Lazorick, L P Whichard, B F Haynes, K H Singer
Journal: The Journal of Experimental Medicine (1991)

Human thymic epithelial (TE) cells produce interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6, cytokines that are important for thymocyte proliferation. The mRNAs for these cytokines are short-lived and are inducible by multiple stimuli. Thus, the steady-state levels for IL-1 and IL-6 mRNAs are critical in establishing the final cytokine protein levels. In this study we have evaluated the effect of epidermal growth factor (EGF), a growth factor for TE cells, and its homologue transforming growth factor alpha (TGF-alpha), on primary cultures of normal human TE cells for the levels of IL-1 alpha, IL-1 beta, IL-6, and TGF-alpha mRNA. We showed that TE cells expressed EGF receptors (EGF-R) in vitro and in vivo, and that treatment of TE cells with EGF or TGF-alpha increased IL-1 and IL-6 biological activity and mRNA levels for IL-1 alpha, IL-1 beta, and IL-6. Neither EGF nor TGF-alpha increased transcription rates of IL-1 alpha, IL-1 beta, and IL-6 genes, but rather both EGF and TGF-alpha increased cytokine mRNA stability. By indirect immunofluorescence assay, TGF-alpha was localized in medullary TE cells and thymic Hassall's bodies while EGF-R was localized to TE cells throughout the thymus. Thus, TGF-alpha and EGF are critical regulatory molecules for production of TE cell-derived cytokines within the thymus and may function as key modulators of human T cell development in vivo.
Magnetic Resonance Image-Guided Transcatheter Closure of Atrial Septal Defects
Authors: Carsten Rickers, Michael Jerosch-Herold, Xudong Hu, Naveen Murthy, Xiaoen Wang, Huafu Kong, Ravi Teja Seethamraju, Jochen Weil, Norbert M. Wilke
Journal: Circulation (2003)

Background— Recent developments in cardiac MRI have extended the potential spectrum of diagnostic and interventional applications. The purpose of this study was to test the ability of MRI to perform transcatheter closures of secundum type atrial septal defects (ASD) and to assess ASD size and changes in right cardiac chamber volumes in the same investigation. Methods and Results— In 7 domestic swine (body weight, 38±13 kg), an ASD (Q p :Q s =1.7±0.2) was created percutaneously by balloon dilation of the fossa ovalis. The ASD was imaged and sized by both conventional radiography and MRI. High-resolution MRI of the ASD diameters correlated well with postmortem examination ( r =0.97). Under real-time MR fluoroscopy, the introducer sheath was tracked toward the left atrium with the use of novel miniature MR guide wires. The defect was then closed with an Amplatzer Septal Occluder. In all animals, it was possible to track and interactively control the position of the guide wire within the vessels and the heart, including the successful deployment of the Amplatzer Septal Occluder. Right atrial and ventricular volumes were calculated before and after the intervention by using cine-MRI. Both volumes were found to be significantly reduced after ASD closure ( P &lt;0.005). Conclusions— These in vivo studies demonstrate that catheter tracking and ASD device closure can be performed under real-time MRI guidance with the use of intravascular antenna guide wires. High-resolution imaging allows accurate determination of ASD size before the intervention, and immediate treatment effects such as changes in right cardiac volumes can also be measured.
Iron, Inflammation, and Early Death in Adults With Sickle Cell Disease
Authors: Eduard J. van Beers, Yanqin Yang, Nalini Raghavachari, Xin Tian, Darlene T. Allen, James S. Nichols, Laurel Mendelsohn, Sergei Nekhai, Victor R. Gordeuk, James G. Taylor, Gregory J. Kato
Journal: Circulation Research (2014)

Patients with sickle cell disease (SCD) have markers of chronic inflammation, but the mechanism of inflammation and its relevance to patient survival are unknown.
Localization of major histocompatibility complex class I and II mRNA in human first-trimester chorionic villi by in situ hybridization.
Authors: J A Lata, R S Tuan, K J Shepley, M M Mulligan, L G Jackson, J B Smith
Journal: The Journal of Experimental Medicine (1992)

Maternal immune recognition of pregnancy occurs despite the nonexpression of classical major histocompatibility complex (MHC) antigenic determinants by chorionic villous trophoblast, which comprise the major surface area where maternal blood contacts fetal-derived cells. cDNA-mRNA in situ hybridization was used to probe expression of transcripts corresponding to nonpolymorphic MHC determinants in first-trimester chorionic villus samples. The HLA-B7 probe hybridization signals were localized to syncytiotrophoblast and to cells of the mesenchyme but not to villous cytotrophoblast. HLA-G mRNA was found only in syncytiotrophoblast. A DR beta clone hybridized to both villous cytotrophoblast and syncytiotrophoblast. The results suggest that expression of trophoblast class I and class II determinants early in gestation (10 wk) may be regulated by posttranscriptional events. This also suggests the potential for maternal antifetal alloimmune responses.
How and Why US Health Care Differs From That in Other OECD Countries
Authors: Victor R. Fuchs
Journal: JAMA (2013)

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Autologous transplantation of granulocyte colony-stimulating factor–primed bone marrow is effective in supporting myeloablative chemotherapy in patients with hematologic malignancies and poor peripheral blood stem cell mobilization
Authors: Roberto M. Lemoli, Antonio de Vivo, Daniela Damiani, Alessandro Isidori, Monica Tani, Alessandro Bonini, Claudia Cellini, Antonio Curti, Luigi Gugliotta, Giuseppe Visani, Renato Fanin, Michele Baccarani
Journal: Blood (2003)