tbuckley/cabot-search huggingface dataset:
Epidemiology of Heart Failure
Authors: Véronique L. Roger
Journal: Circulation Research (2013)

Heart failure (HF) has been singled out as an epidemic and is a staggering clinical and public health problem, associated with significant mortality, morbidity, and healthcare expenditures, particularly among those aged ≥65 years. The case mix of HF is changing over time with a growing proportion of cases presenting with preserved ejection fraction for which there is no specific treatment. Despite progress in reducing HF-related mortality, hospitalizations for HF remain frequent and rates of readmissions continue to rise. To prevent hospitalizations, a comprehensive characterization of predictors of readmission in patients with HF is imperative and must integrate the impact of multimorbidity related to coexisting conditions. New models of patient-centered care that draw on community-based resources to support HF patients with complex coexisting conditions are needed to decrease hospitalizations.
Mucosal subepithelial binding sites for the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP)
Authors: P Anton, J O’Connell, D O’Connell, L Whitaker, G C O’Sullivan, J K Collins, F Shanahan
Journal: Gut (1998)

Background —The bacterial chemotactic peptide N- formyl-methionine-leucine-phenylalanine (FMLP) is produced by enteric flora and is one of the factors implicated in contributing to inflammatory bowel disease. Expression of receptors for FMLP on human phagocytes (polymorphs and monocytes) is well established, but there is conflicting evidence regarding the potential expression of FMLP receptors on other cells within the mucosa, particularly the epithelial cells. Aims —To map FMLP receptors within intestinal mucosa using several different experimental approaches. Methods and results— Radioligand binding assays with 3 H-FMLP revealed no specific binding to primary cultured colonic enterocytes or to the cell line HT29, whereas neutrophils, as expected, exhibited specific binding with a Kd of 19 nM and approximately 2 × 10 4 receptors per cell. FITC labelled FMLP exhibited specific, displaceable binding on flow cytometry to neutrophils and monocytes but not to 10 gastrointestinal epithelial cell lines. Isolated lamina propria lymphocytes and peripheral blood lymphocytes exhibited no binding. To confirm the absence of receptors on epithelia, reverse transcription polymerase chain reaction for mRNA for the classic FMLP receptor was performed. While the presence of message was detected in activated peripheral blood phagocytes, it was not detected in epithelial cell lines. To exclude the possibility of FMLP binding to other receptors such as tachykinin receptors on epithelia, FITC labelled FMLP binding in tissue sections confirmed that the binding is subepithelial—that is, in the lamina propria. Conclusion —Receptors for FMLP are subepithelial and map to the lamina propria of the gastrointestinal mucosa.
Effect of the oxLDL Binding Protein Fc-CD68 on Plaque Extension and Vulnerability in Atherosclerosis
Authors: Stephan Zeibig, Zhongmin Li, Silvia Wagner, Hans-Peter Holthoff, Martin Ungerer, Andreas Bültmann, Kerstin Uhland, Jasmin Vogelmann, Thomas Simmet, Meinrad Gawaz, Götz Münch
Journal: Circulation Research (2011)

Rationale: There is strong evidence that oxidative modification of low-density lipoprotein (oxLDL) plays a critical role in atherogenesis and that oxLDL may profoundly influence the mechanical stability of atherosclerotic plaques. Objective: To block oxLDL, we designed, expressed, and tested Fc-CD68, a soluble oxLDL binding protein consisting of human Fc and the extracellular domain of the human oxLDL-binding receptor CD68. Methods and Results: Fc-CD68 bound with high specific affinity to oxLDL and strongly bound and colocalized with oxLDL in plaques. To study the effects of repeated administrations of Fc-CD68 on the progression of atherosclerosis and plaque vulnerability, 12- and 16-week old cholesterol-fed ApoE −/− mice received either Fc-CD68 (n=6) or Fc control protein (n=6 to 8) thrice weekly for 4 weeks. Macroscopic and histological analysis of Sudan red lipid staining showed strong and significant reduction of plaque extension in the aorta and in the aortic root, respectively. Histological analysis of pentachrome- and Sirius-stained sections of the brachiocephalic arteries of 20 week-old ApoE −/− mice revealed that Fc-CD68 significantly reduced the occurrence of spontaneous ruptures of established plaques by ≈20%, compared with Fc and drastically increased the collagen content of plaques. Furthermore, in immunostained sections of the brachiocephalic artery and the aortic root, Fc-CD68 reduced the infiltration of plaques with T lymphocytes, and macrophages by ≈50% and 30%, respectively. Conclusions: The oxLDL binding protein Fc-CD68 attenuates atherosclerosis and strengthens the stability of atherosclerotic plaques.
Factor VIII inhibitor in insulin‐dependent diabetes mellitus
Authors: Takeshi Wajima, Gregory Hall
Journal: American Journal of Hematology (1989)

Abstract Acquired factor VIII inhibitor was found in a 69‐year‐old white male with insulin‐dependent diabetes mellitus. He presented with left lower abdominal pain and hematoma after a fall. Preoperative hemostasis studies were normal except for prolonged aPTT. Prolonged aPTT was not corrected by 1:1 mixture with normal fresh plasma and incubation showed further prolongation with time. Factor VIII:c was 3.5%. The inhibitor titer was 7.5 Bethesda units. The possible mechanism causing antibody to factor VIII was postulated to be an autoimmune process and/or increased immunogenicity owing to glycosy‐lation of factor VIII coagulant protein.
Lack of Expression of the EP2 but not EP3 Receptor for Prostaglandin E2 Results in Suppression of Skin Tumor Development
Authors: You Me Sung, Guobin He, Susan M. Fischer
Journal: Cancer Research (2005)

Abstract The EP2 receptor for prostaglandin E2 (PGE2) is a membrane receptor that mediates at least part of the action of PGE2. It has been shown that EP2 plays a critical role in tumorigenesis in mouse mammary gland and colon. However, the possibility that the EP2 receptor is involved in the development of skin tumors was unknown. The purpose of this study was to investigate the role of the EP2 receptor in mouse skin carcinogenesis. Unlike EP3 knockout mice, the EP2 knockout mice produced significantly fewer tumors and reduced tumor incidence compared with wild type (WT) mice in a 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) two-stage carcinogenesis protocol. EP2 knockout mice had significantly reduced cellular proliferation of mouse skin keratinocytes in vivo and in vitro compared with that in WT mice. In addition, the epidermis of EP2 knockout mice 48 hours after topical TPA treatment was significantly thinner compared with that of WT mice. The inflammatory response to TPA was reduced in EP2 knockout mice, based on a reduced number of macrophages in the dermis and a reduced level of interleukin-1α mRNA expression, compared with WT mice. EP2 knockout mice also had significantly reduced epidermal cyclic AMP levels after PGE2 treatment compared with WT mice. Tumors from WT mice produced more blood vessels and fewer apoptotic cells than those of EP2 knockout mice as determined by immunohistochemical staining. Our data suggest that the EP2 receptor plays a significant role in the protumorigenic action of PGE2 in skin tumor development.
Hereditary Hemochromatosis — A New Look at an Old Disease
Authors: Antonello Pietrangelo
Journal: New England Journal of Medicine (2004)

For many years, hereditary hemochromatosis was regarded as a clinically and genetically unique entity marked by a classic presentation consisting of diabetes, bronze skin pigmentation, and cirrhosis. In 1996, identification of "the hemochromatosis gene," HFE, was reported; since then, several other iron-metabolism genes have also been identified. This article reviews the current understanding and management of hereditary iron-overload disorders.
Analytic morphology in clinical and experimental dermatology
Authors: Josef Smolle, Wilhelm Stolz, Friedrich A. Bahmer, Stefan el-Gammal, Georg Heinisch, Torsten Mattfeldt, Martin Nilles, Friedrich Otto, Ralf U. Peter, Hans P. Soyer, Norbert Sepp, Thomas Vogt
Journal: Journal of the American Academy of Dermatology (1993)
Changes in lung lymphocyte populations reflect those seen in peripheral blood in HIV-1 positive individuals
Authors: M Bofill, M Lipman, JE McLaughlin, MA Johnson, LW Poulter
Journal: European Respiratory Journal (1998)

We have investigated the level of lymphocytosis present in the lung of human immunodeficiency virus (HIV)-1+ infected patients with and without pulmonary disease and how changes in natural killer (NK), B and T-cells seen in peripheral blood (PB) compare with those seen in bronchoalveolar lavage fluid (BALF). Lymphocyte subpopulations and their expression of activation, cytotoxic markers and memory status were characterized by triple immunofluorescence. Macrophages accounted for over 80% of the BAL cells. Only three out of 72 patients had a lymphocyte percentage >30%. No statistically significant differences in the relative proportions of NK, CD4 and CD8 populations were seen in BALF when compared to PB, except for a twofold increase in the percentage of activated CD8 cells in BALF. The only differences in BALF populations between the HIV-1+ groups were a lower percentage of CD4+ cells, and a higher percentage of activated CD8+ cells in the patients with pneumonitis. In the present cohort of patients there was little evidence for an overall lymphocytosis in bronchoalveolar lavage fluid of HIV-1+ subjects. Changes observed in lymphocyte subsets of bronchoalveolar lavage fluid populations reflected those in peripheral blood, and were similar for patients with and without pneumonitis. Evidence of increased CD8 subset activity in bronchoalveolar lavage fluid did, however, emerge.
Restoration of Interferon Potentiation of a Recombinant Ricin A Chain Immunotoxin Following Cytoreduction of Xenografts of Advanced Ovarian Tumors
Authors: J. W. Pearson, W. E. Fogler, K. Volker, C. W. Riggs, E. Gruys, E. S. Groves, R. H. Wiltrout, D. L. Longo
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Restoration of Interferon α Potentiation of a Recombinant Ricin A Chain Immunotoxin Following Cytoreduction of Xenografts of Advanced Ovarian Tumors Get access John W. Pearson, John W. Pearson Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute (NCI), NCI-Frederick Cancer Research and Development Center (FCRDC)Frederick, Md. Correspondence to: John W. Pearson, Ph.D., NCI-FCRDC Bldg. 560, Rm. 31–93, Frederick, MD 21702-1201. Search for other works by this author on: Oxford Academic PubMed Google Scholar William E. Fogler, William E. Fogler Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute (NCI), NCI-Frederick Cancer Research and Development Center (FCRDC)Frederick, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kirk Volker, Kirk Volker Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorpFrederick Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles W. Riggs, Charles W. Riggs Data Management Services, Inc., NCI-FCRDCFrederick Search for other works by this author on: Oxford Academic PubMed Google Scholar Eileen Gruys, Eileen Gruys Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute (NCI), NCI-Frederick Cancer Research and Development Center (FCRDC)Frederick, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Eric S. Groves, Eric S. Groves Cetus CorporationEmeryville, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert H. Wiltrout, Robert H. Wiltrout Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute (NCI), NCI-Frederick Cancer Research and Development Center (FCRDC)Frederick, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan L. Longo Dan L. Longo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 11, 2 June 1993, Pages 907–912, https://doi.org/10.1093/jnci/85.11.907 Published: 02 June 1993 Article history Received: 10 October 1992 Accepted: 11 March 1993 Published: 02 June 1993
Identification and unusual tissue distribution of the canine and human homologues of Thy-1 (theta).
Authors: R Dalchau, J W Fabre
Journal: The Journal of Experimental Medicine (1979)

The tissue distribution of the canine and human homologues of Thy-1 were studied using quantitative absorption analyses of liver absorbed anti-brain xenosera assayed on thymus cells. Cross-reactivity studies with pure rat Thy-1 established that the assays were detecting the homologues of rat Thy-1. The results showed that the tissue distribution of Thy-1 varies remarkably between species. Canine Thy-1 was found in large amounts only on adult brain. It was present in much smaller amounts on thymus (8% compared with brain), and was also found on lymph node, spleen and bone marrow (3, 1 and 0.5%, respectively, compared with brain). Surprisingly, it was found on kidney in amounts equal to that on thymus. Studies with the fluorescence-activated cell sorter established that canine Thy-1 was present on all thymocytes and peripheral T lymphocytes. Neonatal thymus and kidney had adult levels of Thy-1, but only small amounts of Thy-1 were present on neonatal brain. In man, brain was again the only tissue to contain large amounts of Thy-1. Surprisingly, it was absent from human thymus, and present on human kidney in amounts roughly equivalent to that seen in the dog. It was absent from spleen, lymph node, bone marrow, liver, heart, erythrocytes, platelets, and serum. Cross-reactivity studies showed that dog and human Thy-1 showed extensive serological cross-reaction, and that the dog-rat and human-rat cross-reactive components were identical.
Significant Contribution of Germline <b> <i>BRCA2</i> </b> Rearrangements in Male Breast Cancer Families
Authors: Isabelle Tournier, Brigitte Bressac-de Paillerets, Hagay Sobol, Dominique Stoppa-Lyonnet, Rosette Lidereau, Michel Barrois, Sylvie Mazoyer, Florence Coulet, Agnès Hardouin, Agnès Chompret, Alain Lortholary, Pierre Chappuis, Violaine Bourdon, Valérie Bonadona, Christine Maugard, Brigitte Gilbert, Catherine Nogues, Thierry Frébourg, Mario Tosi
Journal: Cancer Research (2004)

Although screening for large deletions or duplications of the BRCA1 gene is becoming a routine component of the molecular diagnosis of familial breast cancer, little is known about the occurrence of such rearrangements in the BRCA2 gene. Because of the high frequency of BRCA2 mutations in breast cancer families with at least one case of male breast cancer, we selected a cohort of 39 such families, tested negative for mutations in the coding regions of BRCA1 and BRCA2, and developed an assay for BRCA2 rearrangements, based on quantitative multiplex PCR of short fluorescent fragments (QMPSF). We found three rearrangements: (1) a deletion of exons 12 and 13; (2) a duplication of exons 1 and 2; and (3) a complete deletion of BRCA2. We determined the boundaries of the deletion of exons 12 and 13, showing that it resulted from an unequal recombination between Alu sequences. We mapped the complete BRCA2 deletion, which extends over at least 298 kb and showed that it does not affect APRIN/AS3, previously characterized as a tumor suppressor gene, but it comprises several loci corresponding to proven or putative transcripts of unknown functional significance. These data suggest that screening for BRCA2 rearrangements should be done, especially in male breast cancer families tested negative for BRCA1 and BRCA2 mutations.
Measurement and Interpretation of Synovial Fluid Viscosities
Authors: C. H. Barnett
Journal: Annals of the Rheumatic Diseases (1958)

The highly viscous nature of synovial fluid is one of its most striking physical properties.Since the viscosity is altered in many joint diseases (Ropes and Bauer, 1953) and pathological fluid is usually obtainable without difficulty, one would expect that the determination of viscosities would be a common procedure.In fact, this is rarely undertaken, either because many of the measuring techniques advocated in the literature seem very elaborate or because the figures obtained are difficult to interpret.By using simple apparatus and recording the findings graphically, however, results may be achieved that are of value in assessing objectively the progress of articular disease or the response to therapy.Material Synovial fluid was aspirated from the apparently normal knee joints of six post-mortem subjects, within 3 hours of death.All were under 40 years of age, showed no oedema, and died of non-articular conditions.Although such fluid could not strictly be regarded as "normal", it was considered that aspiration of healthy joints during life was unjustifiable.Fluid was also obtained, under general anaesthesia, from the joints of two sacred baboons, the only large primate species available.In addition, fluid was aspirated from the diseased knee joints of patients who were receiving intra- articular medication.Methods All fluids were brought to a temperature of 20°C.and the viscosities estimated the same day.A modification of the apparatus and technique described by Davies (1944) was used (Fig. 1).,--L
Glioma virus therapies between bench and bedside
Authors: J. K. Kaufmann, E. A. Chiocca
Journal: Neuro-Oncology (2014)

Despite extensive research, current glioma therapies are still unsatisfactory, and novel approaches are pressingly needed. In recent years, both nonreplicative viral vectors and replicating oncolytic viruses have been developed for brain cancer treatment, and the mechanistic background of their cytotoxicity has been unveiled. A growing number of clinical trials have convincingly established viral therapies to be safe in glioma patients, and maximum tolerated doses have generally not been reached. However, evidence for therapeutic benefit has been limited: new generations of therapeutic vectors need to be developed in order to target not only tumor cells but also the complex surrounding microenvironment. Such therapies could also direct long-lasting immune responses toward the tumor while reducing early antiviral reactions. Furthermore, viral delivery methods are to be improved and viral spread within the tumor will have to be enhanced. Here, we will review the outcome of completed glioma virus therapy trials as well as highlight the ongoing clinical activities. On this basis, we will give an overview of the numerous strategies to enhance therapeutic efficacy of new-generation viruses and novel treatment regimens. Finally, we will conclude with approaches that may be crucial to the development of successful glioma therapies in the future.
Accuracy of ECG interpretation in competitive athletes: the impact of using standardised ECG criteria
Authors: Jonathan A Drezner, Irfan M Asif, David S Owens, Jordan M Prutkin, Jack C Salerno, Robyn Fean, Ashwin L Rao, Karen Stout, Kimberly G Harmon
Journal: British Journal of Sports Medicine (2012)

Interpretation of ECGs in athletes is complicated by physiological changes related to training. The purpose of this study was to determine the accuracy of ECG interpretation in athletes among different physician specialties, with and without use of a standised ECG criteria tool.Physicians were asked to interpret 40 ECGs (28 normal ECGs from college athletes randomised with 12 abnormal ECGs from individuals with known ciovascular pathology) and classify each ECG as (1) 'normal or variant--no further evaluation and testing needed' or (2) 'abnormal--further evaluation and testing needed.' After reading the ECGs, participants received a two-page ECG criteria tool to guide interpretation of the ECGs again.A total of 60 physicians participated: 22 primary care (PC) residents, 16 PC attending physicians, 12 sports medicine (SM) physicians and 10 ciologists. At baseline, the total number of ECGs correctly interpreted was PC residents 73%, PC attendings 73%, SM physicians 78% and ciologists 85%. With use of the ECG criteria tool, all physician groups significantly improved their accuracy (p<0.0001): PC residents 92%, PC attendings 90%, SM physicians 91% and ciologists 96%. With use of the ECG criteria tool, specificity improved from 70% to 91%, sensitivity improved from 89% to 94% and there was no difference comparing ciologists versus all other physicians (p=0.053).Providing standised criteria to assist ECG interpretation in athletes significantly improves the ability to accurately distinguish normal from abnormal findings across physician specialties, even in physicians with little or no experience.
Abnormalities of the enteric nervous system in heterozygous endothelin B receptor deficient (spotting lethal) rats resembling intestinal neuronal dysplasia
Authors: G B T von Boyen
Journal: Gut (2002)

<b>Background:</b> A homozygous mutation of the endothelin B receptor (<i>EDNRB</i>) gene in spotting lethal (sl/sl) rats leads to Hirschsprung9s disease (HSCR) with long segmented aganglionosis. However, the effects on the development of the enteric nervous system (ENS) promoted by a heterozygous mutation of the <i>EDNRB</i> gene are not known. The present study aimed to describe and morphometrically assess the phenotypic abnormalities of the ENS in heterozygous (+/sl) <i>EDNRB</i> deficient rats in comparison with homozygous (sl/sl) <i>EDNRB</i> deficient and wild-type (+/+) rats. <b>Methods:</b> The distal small intestine, caecum, and colon were obtained from sl/sl, +/sl, and +/+ rats. To demonstrate the three dimensional organisation of the ENS, the intestinal wall was microdissected into wholemounts and incubated against the pan-neuronal marker protein gene product 9.5. Assessment of the ENS included morphometric quantification of ganglionic size and density, the number of nerve cells per ganglia, and the diameter of nerve fibre strands within both the myenteric and submucous plexus. <b>Results:</b> Sl/sl rats were characterised by complete aganglionosis resembling the same histopathological features observed in patients with HSCR. +/sl rats revealed more subtle abnormalities of the ENS: the submucous plexus was characterised by a significantly increased ganglionic size and density, and the presence of hypertrophied nerve fibre strands. Morphometric evaluation of the myenteric plexus did not show statistically significant differences between +/sl and +/+ rats. <b>Conclusions:</b> In contrast with sl/sl rats, +/sl rats display non-aganglionated malformations of the ENS. Interestingly, these innervational abnormalities resemble the histopathological criteria for intestinal neuronal dysplasia (IND). Although IND has been described in several intestinal motility disorders, the concept of a clearly defined clinical-histopathological entity is still controversially discussed. The present findings support the concept of IND based on clearly defined morphological criteria suggesting a genetic link, and thus may provide a model for human IND. Furthermore, the data underline the critical role of the “gene dose” for the phenotypic effects promoted by the <i>EDNRB</i>/<i>EDN3</i> system and confirm that the development of the ENS is not an “all or none” phenomenon.