tbuckley/cabot-search huggingface dataset:
DO ANIMALS TALK?
Authors: A. L. Benedict
Journal: JAMA (1923)

To the Editor:  —The quotation inThe Journal(March 17, p. 764), mentioning the white mountain goat as intelligent reminds me that the caretaker of a small herd at an amusement park called his dog to drive them from another dog that they were annoying. The herd ran as soon as they heard the name of the dog of which they were afraid, apparently indicating that they understood language.  Dogs to a high degree and, to a less degree, cats, horses, cattle, sheep, elephants and probably other animals associated with man understand a good many words. One of the best evidences of understanding on the part of animals is the failure to understand under different circumstances. For instance, sheep habituated to the call Co'nan do not respond to Co'day, and vice versa. In Strasbourg, my wife called a dogchienwithout getting a response, but he responded immediately toHund
Thymic lymphoproliferative disease after successful correction of CD40 ligand deficiency by gene transfer in mice
Authors: Michael P. Brown, David J. Topham, Mark Y. Sangster, Jingfeng Zhao, Kirsten J. Flynn, Sherri L. Surman, David L. Woodland, Peter C. Doherty, Andrew G. Farr, Paul K. Pattengale, Malcolm K. Brenner
Journal: Nature Medicine (1998)
Prognostic Significance of Rheological and Biochemical Findings in Patients with Intermittent Claudication
Authors: J. A. Dormandy, E. Hoare, A. H. Khattab, D. E. Arrowsmith, T. L. Dormandy
Journal: BMJ (1973)

To assess the prognostic significance of clinical and laboratory findings in intermittent claudication a group of 62 untreated patients was followed up in detail for periods of from one to three years. There was a significant correlation between progressive deterioration of the peripheral circulatory disturbance and the initial blood viscosity, the plasma fibrinogen level, and the susceptibility of red cell lipids to autoxidation.
Intractable Ventricular Tachycardia
Authors: GURDARSHAN S. THIND
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 April 1970Intractable Ventricular TachycardiaGURDARSHAN S. THIND, M.B.B.S., M.S.GURDARSHAN S. THIND, M.B.B.S., M.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-4-603 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Ritter claims to have described the first reported patient with ventricular tachycardia refractory to modern pharmaceutical and electrical conversion methods (Ann Intern Med71:1155, 1969). Such patients have been previously reported in the literature (1-3). Salokannel, Waris, and Kreus (1) described the occurrence of innumerable episodes of ventricular tachycardia refractory to drug therapy in a 56-year-old man over a 2-year period, necessitating electrical defibrillation 47 times. Pickers, Goldberg, and Watson (2) reported the use of paired pacing of the heart as lifesaving in the management of recurrent ventricular tachycardia refractory to other modes of medical management in...References1. SALOKANNELWARISKREUS JEK: Recurrent ventricular tachycardia. Brit Heart J 31:517-519, 1969 CrossrefMedlineGoogle Scholar2. PICKERSGOLDBERGWATSON BMC: Termination of a tachyarrhythmia by paired pacing. Brit Med J 2:161-162, 1969 CrossrefMedlineGoogle Scholar3. HUNTSLOMANWESTLAKE DGG: Ventricular aneurysmectomy for recurrent tachycardia. Brit Heart J 31:264-266, 1969 CrossrefMedlineGoogle Scholar4. THINDBLAKEMOREZINSSER GWH: Continued longterm survival after ventricular aneurysmectomy for recurrent ventricular tachycardia. In preparation Google Scholar5. ESCHER D: The treatment of tachyarrhythmias by artificial cardiac pacing. Amer Heart J 78:829-832, 1969 CrossrefMedlineGoogle Scholar6. DUBNOWBURCHELLTITUS MHJ: Post-infarction ventricular aneurysm. A clinicomorphologic and electrocardiographic study of 80 cases. Amer Heart J 70:753-760, 1965 CrossrefMedlineGoogle Scholar7. FAVALOROEFFLERGROVES RDL: Ventricular aneurysm—clinical experience. Amer Thorac Surg 6:277-243, 1968 CrossrefMedlineGoogle Scholar8. LIKOFFBAILEY WC: Problem of myocardial aneurysm: recognition and treatment. Circulation 14:968, 1956 Google Scholar9. COUCH O: Cardiac aneurysm with ventricular tachycardia and subsequent excision of aneurysm. Circulation 20:251-253, 1959 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine The Graduate Hospital of the University of Pennsylvania Philadelphia, Pa. 19146 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRecurrent Ventricular Tachycardia Successfully Treated by Excision of Ventricular Aneurysm 1 April 1970Volume 72, Issue 4Page: 603-604KeywordsDrug therapyHeartVentricular tachycardia Issue Published: 1 April 1970 PDF DownloadLoading ...
Purpose and guidelines for toxicokinetic studies within the National Toxicology Program.
Authors: J R Buchanan, L T Burka, R L Melnick
Journal: Environmental Health Perspectives (1997)

Toxicokinetic studies undertaken within the National Toxicology Program are intended to aid the design of toxicology and carcinogenicity studies, help interpret the results of toxicology and carcinogenicity studies with respect to the relationship between toxic effects and external exposure, and define the parameters of dose, distribution, metabolism, and elimination that can be used in human risk assessment. Descriptions of two study designs presented here represent the possible extremes in approaches to toxicokinetic studies. The comprehensive approach is geared toward the development of physiology based pharmacokinetic models that relate external exposure to target organ dosimetry and addresses the questions: Is the chemical absorbed? How is the chemical metabolized? Where are the chemical and/or metabolites distributed in the body? What are the elimination rate and route of the chemical? What is the effect of dose on absorption, distribution, metabolism, and elimination? The minimal study design is more limited in scope than the comprehensive design and addresses primarily the issues of absorption, distribution, and elimination of the parent chemical. Study protocols for most chemicals lie somewhere between these two extreme approaches. An increased understanding of the relationships between external exposure, target organ dosimetry, and adverse effects should provide greater confidence in making low-dose extrapolations of human risk. This paper focuses on the collection of data from animal toxicokinetic studies. The construction of comparable models to characterize target organ dosimetry in exposed humans would certainly require the use of human parameter values obtained from human tissue samples and volunteers.
The Medical Society of New Jersey Since 1766
Authors: Fred B. Rogers
Journal: JAMA (1966)

Chronologically oldest state medical society in the United States, The Medical Society of New Jersey was founded on July 23, 1766, at a meeting held in New Brunswick. The 17 physicians who adopted the "instruments of association" on that day met in response to a notice, published in the<i>New York Mercury</i>, June 27, which read: A considerable number of the practitioners of physic and surgery in New Jersey, having agreed to form a society for the advancement of their profession and promotion of the public good, request and invite every gentleman of the profession in the province to attend a meeting at Mr. Duff's, in the city of New Brunswick, on Wednesday, the 23d of July, at which time and place, the Constitution and Regulations of the Society are to be settled and subscribed. The group elected as its first president the Reverend Robert McKean, pastor and physician who
NICE to confer on taking greater account of patients' views
Authors: C. White
Journal: BMJ (2008)

The National Institute for Health and Clinical Excellence (NICE) is to invite patients and health economists to comment on the factors it uses to decide which drugs to recommend for use in the NHS. But it has denied suggestions in press reports that it will be radically overhauling its processes. 

The move comes in the wake of research that proposes an alternative way of apportioning monetary value to drugs that is based on what patients would be prepared to pay in return for living longer ( Health Economics , doi:10.1002/hec.1416).

In common with other public sector healthcare bodies NICE uses the quality adjusted …
Endogenous Basic Fibroblast Growth Factor Displaced by Heparin From the Lumenal Surface of Human Blood Vessels Is Preferentially Sequestered by Injured Regions of the Vessel Wall
Authors: Benjamin Medalion, Gideon Merin, Helena Aingorn, Hua-Quan Miao, Arnon Nagler, Amir Elami, Rivka Ishai-Michaeli, Israel Vlodavsky
Journal: Circulation (1997)

Background Proliferation of smooth muscle cells (SMCs) of the arterial wall in response to local injury is an important factor in vascular proliferative disorders. Among the growth factors that promote SMC proliferation is basic fibroblast growth factor (bFGF), which is characterized by a high affinity for heparin and is associated with heparan sulfate on cell surfaces and extracellular matrices. We investigated whether heparin can displace endogenous active bFGF from the lumenal surface of blood vessels, whether bFGF is preferentially bound to injured blood vessels, and whether a synthetic, polyanionic, heparin-mimicking compound (RG-13577) can prevent sequestration of bFGF by the vessel wall. Methods and Results Injured and noninjured saphenous vein segments were perfused with or without heparin, in the absence or presence of 125 I-bFGF and/or RG-13577 (a polymer of 4-hydroxyphenoxy acetic acid). Heparin displaced bFGF from the lumenal surface of the vein, and the released bFGF stimulated proliferation of SMCs. Likewise, systemic administration of heparin during open heart surgery resulted in a marked increase in plasma bFGF levels. Injured veins sequestered 125 I-bFGF to a much higher extent than noninjured vein segments, both in the absence and presence of heparin. This sequestration was inhibited by compound RG-13577. Conclusions Despite its beneficial effects, heparin may displace active bFGF, which subsequently may be preferentially deposited on injured vessel walls, thus contributing to the pathogenesis of restenosis. This effect may be prevented by a synthetic heparin-mimicking compound.
T lymphocyte-mediated suppression of myeloma function in vitro. III. Regulation of antibody production in hybrid myeloma cells by T lymphocytes.
Authors: A K Abbas, S J Burakoff, M L Gefter, M I Greene
Journal: The Journal of Experimental Medicine (1980)

To investigate the mechanisms by which T lymphocytes regulate myeloma function in vitro, the effects of regulatory T cells on antibody secretion by a hybrid myeloma cell line were examined. Suppressor T cells (Ts) specific for idiotypic determinants on M315 (IgA, lambda 2 anti-2,4-dinitrophenol and anti-2,4,6-trinitrophenol [TNP]) and MPC 11 (IgG2b, kappa) myeloma proteins inhibit antibody secretion by the appropriate parental myeloma cells. When cocultured with a hybrid cell line derived by fusion of MOPC 315 and MPC 11 myelomas, the idiotype-reactive Ts inhibit secretion of only the immunoglobulin (Ig) bearing the relevant idiotype. In contrast, syngeneic TNP-reactive cytolytic T lymphocytes (CTL) inhibit antibody secretion by TNP-binding MOPC 315 cells but not by MPC 11 cells in the presence of soluble TNP-keyhole limpet hemocyanin (KLH), and this inhibition probably represents a prelytic effect of the CTL. Such TNP-reactive CTL, in the presence of TNP-KLH, inhibit both IgA and IgG secretion by the MOPC 315-MPC 11 hybrid, which is consistent with a prelytic effect. Thus, myeloma hybrids are a useful tool for investigating the effector function of regulatory T cells. These results are discussed with reference to the mechanisms of action of regulatory T cells and their relevance to modulation of physiologic humoral immune responses.
Scintigraphic Imaging of Matrix Metalloproteinase Activity in the Arterial Wall In Vivo
Authors: Michael Schäfers, Burkhard Riemann, Klaus Kopka, Hans-Jörg Breyholz, Stefan Wagner, Klaus P. Schäfers, Marilyn P. Law, Otmar Schober, Bodo Levkau
Journal: Circulation (2004)

Matrix metalloproteinases (MMPs) are enzymes involved in the proteolytic degradation of extracellular matrix. They play an important role in several disease processes, such as inflammation, cancer, and atherosclerosis.In this study, we have used the broad-spectrum MMP inhibitor CGS 27023A to develop the radioligand [123I]I-HO-CGS 27023A for in vivo imaging of MMP activity. Using this radioligand, we were able to specifically image MMP activity by scintigraphy in vivo in the MMP-rich vascular lesions that develop after carotid artery ligation and cholesterol-rich diet in apolipoprotein E-deficient mice. These results were confirmed by gamma counting of lesional tissue (counts per minute per milligram).Imaging of MMP activity in vivo is feasible using radiolabeled MMP inhibitors. Additional studies are needed to test the potential of this approach as a novel noninvasive clinical diagnostic tool for the management of human MMP-related diseases.
Abstract 1501: Pan-cancer PathSeq analysis on TCGA data for pathogen discovery.
Authors: Joonil Jung, Chandra Sekhar Pedamallu, Aleksander D. Kostic, Samuel Freeman, Akinyemi I. Ojesina, Alice Berger, Ami Bhatt, Fujiko Duke, Gad Getz, Matthew Meyerson
Journal: Cancer Research (2013)

Abstract An estimated 15-20% of all human malignancies is caused by infectious agents, such as human papillomavirus (HPV), Epstein-Barr virus (EBV) or Helicobacter pylori (H. pylori). The recent development of massively parallel next generation sequencing technology led to the discovery of Merkel cell polyomavirus, and more recently a significant enrichment of Fusobacterium nucleatum (F. nucleatum) and related Fusobacterium species in colorectal carcinomas compared to non-neoplastic colon tissue from the same patients. However, these studies involved relatively small number of samples and there are likely many additional cancer-associated microbes that are yet to be discovered. TCGA sequencing data from over 20 human cancer types provide an unprecedented opportunity for cancer-associated pathogen discovery. Using PathSeq, software for pathogen discovery by computational subtraction, we have begun analyzing TCGA sequencing data for the presence of viral, fungal or bacterial sequences. We will present our preliminary data from the analysis of mRNA-seq data including evidence for (1) a greater role of viral integration into tumor suppressor gene loci in HPV-driven tumors and (2) complex interplay between viruses, bacteria and host cancer cells in various cancer types. We will also discuss our discovery efforts for previously unannotated pathogens in the TCGA dataset. Citation Format: Joonil Jung, Chandra Sekhar Pedamallu, Aleksander D. Kostic, Samuel Freeman, Akinyemi I. Ojesina, Alice Berger, Ami Bhatt, Fujiko Duke, Gad Getz, Matthew Meyerson. Pan-cancer PathSeq analysis on TCGA data for pathogen discovery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1501. doi:10.1158/1538-7445.AM2013-1501
Jack Winkler replies to Joachim von Braun
Authors: J. T. Winkler
Journal: BMJ (2011)

Von Braun is right: we are into our second food price crisis in four years.1 Worse, such crises will recur throughout the 21st century as climate change desiccates swathes of the earth, spreading food insecurity. He proposes a long term programme to cope: improve agriculture, reform trade, increase reserves, control speculation, end export bans, create safety nets, provide preventive healthcare. It would work—on some more blessed planet. But in the venal contemporary world we actually inhabit, full of gross income inequalities, nationalist agricultural subsidies, and inadequately regulated global markets, it is just a laundry list of desiderata. We are moving in the opposite direction. Consider what has happened in the past two months alone.
Electrocardiographic Alterations Produced by a Decrease in Plasma pH, Bicarbonate and Sodium as Compared with those Produced by an Increase in Potassium
Authors: KATHLEEN E. ROBERTS, MELVILLE G. MAGIDA
Journal: Circulation Research (1953)

The effects of a decrease in plasma pH, bicarbonate and sodium on the electrocardiographic pattern are compared with those produced by elevation of serum potassium and lithium in the dog. The electrocardiographic alterations were found to be similar in form and progression. The alterations can be correlated with those found in isolated nerve and muscle preparations.
Abstract 884: Basonuclin1 (BNC1): A novel therapeutic target in ovarian cancer identified through integrative TCGA-based functional genomic analysis
Authors: Sherry Y. Wu, Anna K. Unruh, Geoffrey Bartholomeusz, Cristina Ivan, Chad V. Pecot, Rajesha Rupaimoole, Hee-Dong Han, Justin Bottsford-Miller, Susan L. Tucker, Robert L. Coleman, Gabriel Lopez-Berestein, Keith A. Baggerly, Anil K. Sood
Journal: Cancer Research (2012)

Abstract High-grade serous ovarian cancer (HGS-OvCa) is the most common and lethal type of ovarian carcinoma. While TCGA provides comprehensive genomic profiling of clinically annotated HGS-OvCa tumors, identification of novel therapeutic targets using this dataset is still needed. We coupled TCGA mRNA expression and clinical response data to systematically identify genes which could alter progression of HGS-OvCa and investigated associated alterations in DNA promoter methylation and microRNA expression. For selected targets, we also used siRNA functional studies to clarify gene-specific effects. We identified 102 genes as up-regulated in tumors from patients whose cancer had progressed within 7 months of diagnosis (chemo-resistant group: 53 cases) compared to tumors from patients who had no disease progression for more than 3 years (chemo-sensitive group: 57 cases). These genes had two-sample t-test p-values &amp;lt; 0.05 according to level 3 TCGA data from both Agilent and Affymetrix platforms. Basonuclin1 (BNC1), a transcription factor which regulates ribosomal biogenesis, cell proliferation, and epithelial differentiation, was one of the key targets identified. Its expression was found to be increased by more than two-fold (Agilent platform; p=0.001) in chemo-resistant tumors. While no significant associated changes in microRNA expression were evident in TCGA for the BNC1 gene, we found that the expression of BNC1 negatively correlated with the degree of methylation at the promoter region of transmembrane 4 superfamily member 1, TM4SF1 (-0.42, Agilent platform), a known up-regulated pro-angiogenic gene in ovarian cancer. Importantly, the siRNA functional study had revealed a 35% reduction in cell viability in cisplatin-resistant A2780-CP20 cells following BNC1 siRNA treatment, and a further 15% reduction was noted when the cells were treated with cisplatin at the IC30 concentration determined using the chemo-sensitive parental cell line. Overall, our results demonstrate (a) the feasibility of using TCGA data, coupled with functional siRNA studies, to identify novel targets for the treatment of ovarian cancer and (b) the potential of targeting BNC1 as a treatment strategy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 884. doi:1538-7445.AM2012-884
Abstract PD4-6: Combined analysis of gene expression, DNA copy number and mutation profiling data to display biological process anomalies in individual cancers
Authors: W Shi, B Balazs, Y Qi, B Györffy, B Wang, C-G Liu, CY Shiang, V Valero, S Moulder-Thompson, R Avritscher, G Powis, GN Hortobagyi, R Natowicz, V Wali, J Weinstein, WF Symmans, L Pusztai
Journal: Cancer Research (2013)

Abstract Background: The goal of this analysis was to develop a computational tool that integrates gene expression, DNA copy number and sequence abnormalities in individual cancers in the framework of biological processes. Methods and Findings: We used the hierarchical structure of the Gene Ontology (GO) database to create a reference network and projected mRNA expression, DNA copy number and mutation anomalies detected in single samples into this space. We applied our method to 59 breast cancers where all three types of molecular data were available. Each cancer had a large number of disturbed biological processes. Locomotion, multicellular organismal process and signal transduction pathways were the most commonly affected GO terms but the individual molecular events were different from case-to-case. Estrogen receptor-positive and -negative cancers had different repertoire of anomalies. We tested the functional impact of 27 mRNAs that had overexpression in cancer with variable frequency (&amp;lt;2-42%) using an siRNA screen. Each of these genes inhibited cell growth in at least some of 18 breast cancer cell lines. Conclusions We developed a free, on-line software tool (http://netgoplot.org) to display the complex genomic abnormalities in individual cancers in the biological framework of the GO biological processes. We show that each cancer harbors a large number and unique combination of pathway anomalies, the individual molecular events that underlie the pathway level disturbances vary from case-to-case. Our in vitro experiments indicate that even rare case-specific molecular abnormalities can play a functional role and driver events may vary from case to case depending on the constellation of other molecular anomalies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD4-6.
IL-1 mediates TNF-induced osteoclastogenesis
Authors: Shi Wei, Hideki Kitaura, Ping Zhou, F. Patrick Ross, Steven L. Teitelbaum
Journal: Journal of Clinical Investigation (2005)

TNF-induced receptor activator NF-kappaB ligand (RANKL) synthesis by bone marrow stromal cells is a fundamental component of inflammatory osteolysis. We found that this process was abolished by IL-1 receptor antagonist (IL-1Ra) or in stromal cells derived from type I IL-1 receptor-deficient (IL-1RI-deficient) mice. Reflecting sequential signaling of the cytokines TNF and IL-1, TNF induces stromal cell expression of IL-1 and IL-1RI. These data suggest that TNF regulates RANKL expression via IL-1, and, therefore, IL-1 plays a role in TNF-induced periarticular osteolysis. Consistent with this posture, TNF-stimulated osteoclastogenesis in cultures consisting of WT marrow macrophages and stromal cells exposed to IL-1Ra or in cocultures established with IL-1RI-deficient stromal cells was reduced approximately 50%. The same magnitude of osteoclast inhibition occurred in IL-1RI-deficient mice following TNF administration in vivo. Like TNF, IL-1 directly targeted osteoclast precursors and promoted the osteoclast phenotype in a TNF-independent manner in the presence of permissive levels of RANKL. IL-1 is able to induce RANKL expression by stromal cells and directly stimulate osteoclast precursor differentiation under the aegis of p38 MAPK. Thus, IL-1 mediates the osteoclastogenic effect of TNF by enhancing stromal cell expression of RANKL and directly stimulating differentiation of osteoclast precursors.