tbuckley/cabot-search huggingface dataset:
Medical Treatment of Peptic Ulcer Disease
Authors: Andrew H. Soll
Journal: JAMA (1996)

Objective.  —To integrate the realization that peptic ulcer most commonly reflects infection with Helicobacter pylori or use of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) into a disease management approach.  Participants.  —Guidelines were outlined by the author and presented for review to the American College of Gastroenterology (ACG) Practice Parameters Committee, selected by the president of the ACG, and a panel of experts in peptic ulcer, selected by the committee.  Evidence and Consensus Process.  —These guidelines were formulated following extensive review of the literature obtained by a MEDLINE search and presented for detailed review and revision to unpublicized committee meetings on three occasions and to experts by mail. These recommendations are an official statement of the ACG and have been approved by the American Gastroenterological Association and the American Society for Gastroenterological Endoscopy. Firm recommendations are discriminated from reasonable suppositions pending definitive data.  Conclusions.  —Since cure of H pylori infection decreases recurrence rates and facilitates healing, antibiotic therapy is indicated for all H pylori —infected ulcer patients. No optimal, simple antibiotic regimen has yet emerged. Simultaneous conventional ulcer therapy is recommended to facilitate symptom relief and healing. For refractory ulcers, only maximal acid inhibition offers advantage over continued conventional therapy; cure of H pylori infection is likely to facilitate healing of refractory ulcers. Only with complicated or refractory ulcers should conventional maintenance therapy be continued, at least until successful H pylori eradication is confirmed. A search for NSAID use is indicated for all ulcer patients. For NSAIDassociated ulcers these drugs should be discontinued if possible and H pylori , if present, should be cured.  ( JAMA . 1996;275:622-629)
Does COPD stand for “COmorbidity with Pulmonary Disease”?
Authors: Lowie E.G.W. Vanfleteren
Journal: European Respiratory Journal (2014)

Treating chronic obstructive pulmonary disease (COPD) as a pulmonologist may lead to existential questions. What's in the name "COPD" when it is only a disease label of a complex and heterogeneous group of patients who merely have persistent airflow limitation in common? What can I do as a "pulmonologist" when my patient with COPD suffers from multiple other diseases treated with numerous drugs that all together impact on his or her well-being? For those who deliver COPD care, it is time to zoom out and get an overview of the organism after a detailed focus on the organ. This without forgetting the human involved [1]. COPD is part of a multimorbid disease network in which chronic diseases develop in response to common risk factors <http://ow.ly/AYt2Y>
Haploinsufficiency of SAMD9L, an Endosome Fusion Facilitator, Causes Myeloid Malignancies in Mice Mimicking Human Diseases with Monosomy 7
Authors: Akiko Nagamachi, Hirotaka Matsui, Hiroya Asou, Yuko Ozaki, Daisuke Aki, Akinori Kanai, Keiyo Takubo, Toshio Suda, Takuro Nakamura, Linda Wolff, Hiroaki Honda, Toshiya Inaba
Journal: Cancer Cell (2013)
Biochemical Correlates of Cardiac Hypertrophy
Authors: John L. Skosey, Radovan Zak, Anne F. Martin, Vaclav Aschenbrenner, Murray Rabinowitz
Journal: Circulation Research (1972)

The incorporation of [2, 3- 3 H]proline into collagen hydroxyproline and into noncollagenous protein was measured during development of cardiac hypertrophy produced by surgical constriction of the ascending aorta in rats. Heart weight increased sharply during the first 4 days after aortic banding and then slowly rose to a plateau. Free intracellular proline concentration remained unaltered 2 days after banding and increased by 38% on the fifth postoperative day. Specific radioactivity of free proline 3 hours after injection of [ 3 H]proline was elevated by 40% on the second postoperative day but was unchanged on the fifth day. Incorporation of [ 3 H]proline into collagen hydroxyproline peaked sharply on the second day after aortic constriction (550% above control) in one experiment, and on the fourth day (330% above control) in another. The peak labeling of noncollagenous protein by [ 3 H]proline (100% over control) was less than that of collagen. To further evaluate the differences in synthetic response of muscle cells and interstitial cells to increased work load, incorporation of radioactive precursors into myosin, collagen, nuclear DNA, and noncollagenous protein were measured simultaneously, after aortic constriction. Collagen labeling was maximal either on day 2 or 4, depending on the degree of hypertrophy. Labeling of myosin and noncollagenous protein reached a plateau on day 4. Incorporation of [ 3 H]thymidine into nuclear DNA peaked on day 7. Thus both muscle cells and connective tissue cells respond independently during cardiac hypertrophy with an increased synthesis of specific proteins.
Altered Urinary Kallikrein Excretion in Rats with Hypertension
Authors: HARRY S. MARGOLIUS, RONALD GELLER, WYBREN de JONG, JOHN J. PISANO, ALBERT SJOERDSMA
Journal: Circulation Research (1972)

The urinary excretion of kallikrein, an enzyme which cleaves a vasodilator kinin from kininogen substrate, was examined in three types of hypertensive rats. Enzyme activity was measured by both esterase activity (isotopic assay) and bioassay with purified rat urinary kallikrein as a standard. Excretion of kallikrein was found to increase with age in spontaneously hypertensive rats, but levels were lower and stable in normotensive Wistar control animals. Rats with desoxycorticosterone-salt hypertension excreted markedly more, whereas rats with renal hypertension excreted significantly less kallikrein than did control animals. The alterations in kallikrein excretion were unrelated to changes in urine volume and protein excretion. The findings indicate that the kallikrein-kinin system may be involved in different forms of hypertension in the rat.
Omalizumab therapy is associated with reduced circulating basophil populations in asthmatic children
Authors: D. A. Hill, M. C. Siracusa, K. R. Ruymann, E. D. Tait Wojno, D. Artis, J. M. Spergel
Journal: Allergy (2014)

Abstract Basophils have been implicated in promoting the early development of T H 2 cell responses in some murine models of T H 2 cytokine‐associated inflammation. However, the specific role of basophils in allergic asthma remains an active area of research. Recent studies in animal models and human subjects suggest that IgE may regulate the homeostasis of human basophil populations. Here, we examine basophil populations in children with severe asthma before and during therapy with the IgE‐directed monoclonal antibody omalizumab. Omalizumab therapy was associated with a significant reduction in circulating basophil numbers, a finding that was concurrent with improved clinical outcomes. The observation that circulating basophils are reduced following omalizumab therapy supports a mechanistic link between IgE levels and circulating basophil populations, and may provide new insights into one mechanism by which omalizumab improves asthma symptoms.
HEMOPOIEITC SPLEEN COLONY STUDIES
Authors: J. L. Curry, J, J. Trentin, N. Wolf
Journal: The Journal of Experimental Medicine (1967)

The polycythemic repression of erythropoiesis and the restoration of erythropoiesis by specific stimulation were studied in the spleen colony system in irradiated mice. 1. A 5 day period of erythropoietin stimulation (exogenous erythropoietin) or repression (polycythemia) of the bone marrow donor only, does not significantly alter the number or type of colonies formed by the transplanted marrow cells. 2. Erythropoietin stimulation did not alter the number or type of endogenous colonies formed in mice receiving 580 R. Erythropoietin repression (polycythemia) markedly reduced the growth but not the number of erythroid colonies, while not affecting the other types of colonies formed endogenously. 3. Erythropoietin stimulation of the irradiated recipient during colony growth did not alter the number or type of spleen colonies formed by transplanted marrow. Erythropoietin repression by polycythemia during colony growth completely suppressed the appearance of morphologically erythroid colonies without significantly altering the incidence of the other colony types. This effect of polycythemia was completely prevented by exogenous erythropoietin. Irradiated mice are therefore presumed to be secreting sufficient erythropoietin for maximal erythroid colony development. 4. The erythroid colonies suppressed by polycythemia were recognizable as microscopic foci of undifferentiated cells. Exposure of these foci to erythropoietin stimulation at different periods in their development was manifested by different degrees of growth and differentiation, from which it is apparent that erythropoietin stimulates not only morphological differentiation but also rapid mitosis. Retransplantation of either erythroid or of neutrophilic primary spleen colonies gave rise to both erythroid and neutrophilic secondary spleen colonies. The percentage of erythroid secondary colonies was slightly but significantly higher among the progeny of transplanted erythroid primary colonies than among the progeny of transplanted neutrophilic primary colonies. On the basis of these and other results, a working hypothesis is proposed for factors controlling the growth and differentiation of spleen colonies from transplanted bone marrow. It is postulated that most but perhaps not all spleen colony-forming units are pluripotent hemopoietic stem cells. It is further postulated that hemopoietic-inductive microenvironments (HIM) of different kinds exist in both the spleen and the bone marrow, and that these determine the differentiation of pluripotent stem cells into each of the lines of hemopoietic differentiation. Erythropoietin therefore may "induce" erythroid differentiation of only those stem cells under the influence of an erythroid HIM. Alternatively erythropoietin may act only as a growth and function stimulant of those stem cells that have been "induced" by an erythroid HIM into a state of erythropoietin responsiveness. In the latter case morphological differentiation presumably results from the functional activity stimulated by ESF.
Expression of DNA mismatch repair proteins and <i>MSH2</i> polymorphisms in nonmelanoma skin cancers of organ transplant recipients
Authors: C.M. Perrett, C.A. Harwood, J.M. McGregor, J. Warwick, R. Cerio, P. Karran
Journal: British Journal of Dermatology (2009)

Background Organ transplant recipients (OTRs) have an increased risk of skin cancer. Treatment with azathioprine, commonly used in post-transplant immunosuppressive regimens, results in incorporation of 6-thioguanine (6-TG) into DNA. Mismatch repair (MMR)-defective cells are resistant to killing by 6-TG. Azathioprine exposure confers a survival advantage on MMR-defective cells, which are hypermutable and may therefore contribute to azathioprine-related nonmelanoma skin cancer, a phenomenon we have previously demonstrated in transplant-associated sebaceous carcinomas. The MSH2 protein is an important component of DNA MMR. The -6 exon 13 T>C MSH2 polymorphism is associated with impaired MMR, drug resistance and certain cancers. Objectives To investigate (i) whether loss of MMR protein expression and microsatellite instability are over-represented in squamous cell carcinomas (SCCs) from OTRs on azathioprine compared with SCCs from immunocompetent patients, and (ii) whether the MSH2 -6 exon 13 polymorphism is over-represented in OTRs with skin cancer on azathioprine. Methods (i) Immunohistochemical staining was used to assess expression of the MMR proteins MSH2 and MLH1 in cutaneous SCCs from OTRs on azathioprine and from immunocompetent patients. (ii) Blood samples from OTRs on azathioprine with and without skin cancer were genotyped for the -6 exon 13 MSH2 polymorphism. Results (i) MSH2 and MLH1 protein expression was not altered in SCCs from OTRs on azathioprine and there was no difference in expression between SCCs from OTRs and immunocompetent patients. (ii) There was no association between MSH2 polymorphism genotype frequency and OTR skin cancer status. Conclusions Despite previous findings in transplant-associated sebaceous carcinomas, defective MMR and the -6 exon 13 MSH2 polymorphism are unlikely to play a significant role in the development of SCC in OTRs on azathioprine.
The Tumor Suppressor Activity of MDA-7/IL-24 Is Mediated by Intracellular Protein Expression in NSCLC Cells
Authors: Kerry A Sieger, Abner M Mhashilkar, Alexis Stewart, R.Bryan Sutton, Randall W Strube, Si Yi Chen, Abujiang Pataer, Stephen G Swisher, Elizabeth A Grimm, Rajagopal Ramesh, Sunil Chada
Journal: Molecular Therapy (2004)

mda-7/IL-24 (HGMW-approved symbol IL24) is a tumor suppressor gene whose expression is lost during tumor progression. Gene transfer using adenoviral mda-7/IL-24 (Ad-mda7) exhibits minimal toxicity on normal cells while inducing potent apoptosis in a variety of cancer cell lines. Ad-mda7-transduced cells express high levels of MDA-7 protein intracellularly and also secrete a soluble form of MDA-7 protein. In this study, we sought to determine whether the intracellular or secreted MDA-7 protein was responsible for anti-tumor activity in H1299 lung tumor cells. Ad-mda7 transduction of lung tumor cells increased expression of stress-related proteins, including BiP, GADD34, PP2A, caspases 7 and 12, and XBP-1, consistent with activation of the UPR pathway, a key sensor of endoplasmic reticulum (ER)-mediated stress. Blocking secretion of MDA-7 did not inhibit apoptosis, demonstrating that intracellular MDA-7 was responsible for cytotoxicity. Consistent with this result, when applied directly to lung cancer cells, soluble MDA-7 protein exhibited minimal cytotoxic effect. We then generated mda-7 expression constructs using vectors that target the expressed protein to various subcellular compartments, including cytoplasm, nucleus, and ER. Only full-length and ER-targeted MDA-7 elicited cell death in tumor cells. Thus in lung cancer cells, Ad-mda7 activates the UPR stress pathway and induces apoptosis via intracellular MDA-7 expression in the secretory pathway.
Endoanaesthesia of left ventricular mechanoreceptors by steady state infusion of lignocaine and the influence of dopamine
Authors: A. VOGT, H. D. RI, G. SCHMIDT, H. KREUZER
Journal: Cardiovascular Research (1983)

We recorded the afferent activity of 11 left ventricular mechanoreceptors in filaments of the vagus nerve in 10 chloralose-anaesthetised cats. The fibres showed low irregular spontaneous activity of 2.9 (0.2 to 8.4) spikes · s−1. During temporary occlusion of the left anterior descending or left main coronary artery they were activated to 19.1 (4.8 to 47.0) spikes·s−1. Intravenous infusion of 0.175 and 0.35 mg·kg−1·min−1 lignocaine lowered heart rate and blood pressure. The spontaneous nerve fibre activity remained unchanged by the local anaesthetic, whereas the maximum activity evoked by coronary artery occlusion was reduced to 14.7 (2.6 to 34.1) and 10.9 (2.4 to 27.6) spikes·s−1. An additional infusion of 5 and 10 μg·kg−1·min−1 dopamine during continued application of 0.35 mg·kg−1·min−1 lignocaine raised heart rate and blood pressure to control values but had only minimal effects on the response of the fibres to coronary occlusion. It is concluded that lignocaine exerts a specific endoanaesthetic effect on the left ventricular mechanoreceptors, which is not mediated by its negative inotropic side effect.
Azelastine inhibits interleukin-6 (IL-6), IL-8 production by reducing intracellular calcium lon levels in human umbilical cord blood-derived cultured mast cells
Authors: D Kempuraj, M Huang, W Boucher, R Letourneau, A Athanasiou, TC Theoharides
Journal: Journal of Allergy and Clinical Immunology (2002)
Optimizing Aerosol Gene Delivery and Expression in the Ovine Lung
Authors: Gerry McLachlan, Alison Baker, Peter Tennant, Catherine Gordon, Christina Vrettou, Louise Renwick, Richard Blundell, Seng H Cheng, Ron K Scheule, Lee Davies, Hazel Painter, Rebecca L Coles, Anna E Lawton, Chris Marriott, Deborah R Gill, Stephen C Hyde, Uta Griesenbach, Eric W F W Alton, A Christopher Boyd, David J Porteous, D David S Collie
Journal: Molecular Therapy (2007)

We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.
Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer
Authors: K.I. Cao, N. Lebas, S. Gerber, C. Levy, R. Le Scodan, C. Bourgier, J.-Y. Pierga, A. Gobillion, A. Savignoni, Y.M. Kirova
Journal: Annals of Oncology (2014)
Right Heart Adaptation to Pulmonary Arterial Hypertension
Authors: Anton Vonk-Noordegraaf, François Haddad, Kelly M. Chin, Paul R. Forfia, Steven M. Kawut, Joost Lumens, Robert Naeije, John Newman, Ronald J. Oudiz, Steve Provencher, Adam Torbicki, Norbert F. Voelkel, Paul M. Hassoun
Journal: Journal of the American College of Cardiology (2013)
Delayed hematopoietic development in osteopetrotic (op/op) mice.
Authors: S K Begg, J M Radley, J W Pollard, O T Chisholm, E R Stanley, I Bertoncello
Journal: The Journal of Experimental Medicine (1993)

Changes in structure, cellularity, hematopoietic progenitor cell and macrophage content, and osteoclast activity were investigated in the hematopoietic organs of the colony-stimulating factor 1(CSF-1)-less osteopetrotic (op/op) mouse. The data indicated that op/op mice undergo an age-related hematopoietic recovery and resolution of osteopetrosis, suggesting that the hematopoietic system has the capacity to use alternative mechanisms to compensate for the absence of an important multifunctional growth factor, CSF-1. In young animals, op/op femurs were heavily infiltrated with bone, and marrow cellularity was significantly reduced. After 6 wk of age, there was an increase in the marrow space available for hematopoiesis. The femoral cavity of op/op mice progressively enlarged, and by 22 wk of age its appearance and marrow cellularity was comparable to that of controls. The percentage of op/op mononuclear phagocytes, defined by F4/80 antigen expression, progressively increased to normal levels by 35 wk of age. There was no difference in the incidence of both primitive and mononuclear phagocyte-committed, CSF-1-responsive progenitor cells in op/op marrow, but their femoral content was significantly reduced in young mice. During the period of reduced hematopoiesis in the marrow of young op/op mice, splenic hematopoietic activity was elevated. This mutant mouse represents a system for the study of the CSF-1-independent regulatory mechanisms involved in hematopoietic regulation.
Fast Molecular Evolution Associated with High Active Metabolic Rates in Poison Frogs
Authors: Juan C. Santos
Journal: Molecular Biology and Evolution (2012)

Molecular evolution is simultaneously paced by mutation rate, genetic drift, and natural selection. Life history traits also affect the speed of accumulation of nucleotide changes. For instance, small body size, rapid generation time, production of reactive oxygen species (ROS), and high resting metabolic rate (RMR) are suggested to be associated with faster rates of molecular evolution. However, phylogenetic correlation analyses failed to support a relationship between RMR and molecular evolution in ectotherms. In addition, RMR might underestimate the metabolic budget (e.g., digestion, reproduction, or escaping predation). An alternative is to test other metabolic rates, such as active metabolic rate (AMR), and their association with molecular evolution. Here, I present comparative analyses of the associations between life history traits (i.e., AMR, RMR, body mass, and fecundity) with rates of molecular evolution of and mitochondrial loci from a large ectotherm clade, the poison frogs (Dendrobatidae). My results support a strong positive association between mass-specific AMR and rates of molecular evolution for both mitochondrial and nuclear loci. In addition, I found weaker and genome-specific covariates such as body mass and fecundity for mitochondrial and nuclear loci, respectively. No direct association was found between mass-specific RMR and rates of molecular evolution. Thus, I provide a mechanistic hypothesis of the link between AMRs and the rate of molecular evolution based on an increase in ROS within germ line cells during periodic bouts of hypoxia/hyperoxia related to aerobic exercise. Finally, I propose a multifactorial model that includes AMR as a predictor of the rate of molecular evolution in ectothermic lineages.
THE INFECTION-ALLERGIC COMPLEX IN ARSPHENAMIN DERMATITIC REACTIONS, WITH SPECIAL REFERENCE TO DERMATOPHYTOSIS.
Authors: JOHN H. STOKES, GEORGE V. KULCHAR
Journal: British Journal of Dermatology (1934)

Journal Article THE INFECTION‐ALLERGIC COMPLEX IN ARSPHENAMIN DERMATITIC REACTIONS, WITH SPECIAL REFERENCE TO DERMATOPHYTOSIS. Get access JOHN H. STOKES, M.D., JOHN H. STOKES, M.D. (From the Department of Dermatology and Syphilology, School of Medicine, University of Pennsylvania: John H. Stokes, M.D., Director.) Search for other works by this author on: Oxford Academic Google Scholar GEORGE V. KULCHAR, M.D. GEORGE V. KULCHAR, M.D. (From the Department of Dermatology and Syphilology, School of Medicine, University of Pennsylvania: John H. Stokes, M.D., Director.) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 46, Issue 3, 1 March 1934, Pages 134–146, https://doi.org/10.1111/j.1365-2133.1934.tb11138.x Published: 01 March 1934
Type I interferon is selectively required by dendritic cells for immune rejection of tumors
Authors: Mark S. Diamond, Michelle Kinder, Hirokazu Matsushita, Mona Mashayekhi, Gavin P. Dunn, Jessica M. Archambault, Hsiaoju Lee, Cora D. Arthur, J. Michael White, Ulrich Kalinke, Kenneth M. Murphy, Robert D. Schreiber
Journal: The Journal of Experimental Medicine (2011)

Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN’s actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre+Ifnar1f/f mice) cannot reject highly immunogenic tumor cells and that CD8α+ DCs from these mice display defects in antigen cross-presentation to CD8+ T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α+ DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.