tbuckley/cabot-search huggingface dataset:
Age-Dependent Impairment of Endothelial Progenitor Cells Is Corrected by Growth Hormone Mediated Increase of Insulin-Like Growth Factor-1
Authors: Thomas Thum, Sarah Hoeber, Sabrina Froese, Ivonne Klink, Dirk O. Stichtenoth, Paolo Galuppo, Marten Jakob, Dimitrios Tsikas, Stefan D. Anker, Philip A. Poole-Wilson, Jürgen Borlak, Georg Ertl, Johann Bauersachs
Journal: Circulation Research (2007)

Aging is associated with an increased risk for atherosclerosis. A possible cause is low numbers and dysfunction of endothelial progenitor cells (EPC) which insufficiently repair damaged vascular walls. We hypothesized that decreased levels of insulin-like growth factor-1 (IGF-1) during age contribute to dysfunctional EPC. We measured the effect of growth hormone (GH), which increases endogenous IGF-1 levels, on EPC in mice and human subjects. We compared EPC number and function in healthy middle-aged male volunteers (57.4+/-1.4 years) before and after a 10 day treatment with recombinant GH (0.4 mg/d) with that of younger and elderly male subjects (27.5+/-0.9 and 74.1+/-0.9 years). Middle-aged and elderly subjects had lower circulating CD133(+)/VEGFR-2(+) EPC with impaired function and increased senescence. GH treatment in middle-aged subjects elevated IGF-1 levels (126.0+/-7.2 ng/mL versus 241.1+/-13.8 ng/mL; P<0.0001), increased circulating EPC with improved colony forming and migratory capacity, enhanced incorporation into tube-like structures, and augmented endothelial nitric oxide synthase expression in EPC comparable to that of the younger group. EPC senescence was attenuated, whereas telomerase activity was increased after GH treatment. Treatment of aged mice with GH (7 days) or IGF-1 increased IGF-1 and EPC levels and improved EPC function, whereas a two day GH treatment did not alter IGF-1 or EPC levels. Ex vivo treatment of EPC from elderly individuals with IGF-1 improved function and attenuated cellular senescence. IGF-1 stimulated EPC differentiation, migratory capacity and the ability to incorporate into forming vascular networks in vitro via the IGF-1 receptor. IGF-1 increased telomerase activity, endothelial nitric oxide synthase expression, phosphorylation and activity in EPC in a phosphoinositide-3-kinase/Akt dependent manner. Small interference RNA-mediated knockdown of endothelial nitric oxide synthase in EPC abolished the IGF-1 effects. Growth hormone-mediated increase in IGF-1 reverses age-related EPC dysfunction and may be a novel therapeutic strategy against vascular disorders with impairment of EPC.
Money Causes Cancer: Ban It
Authors: George E. Moore
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The decision-makers in the Food and Drug Administration have done it again: protected the rat, reduced the credibility of cancer scientists, and kept their string of inane pronouncements on cancer dangers intact. Their forthright attacks on cranberries, food dyes, cyclamate, estrogen, plastic bottles, and now saccharin are indeed a remarkable display of bureaucratic footwork when tobacco is exported by the federal government as a foodstuff under several "food programs." In response to this nonsense, we inserted sterilized dimes into the peritoneal cavity of 35 rats on March 28, 1976. As expected, the first sarcoma was noted ten months later. In only 14 months, nine rats have sarcomas and nine have distinct abdominal masses. The malignancy of the first and second tumors has been confirmed by successful transplantation. We estimate that malignant neoplasms will develop in more than 50% of the rats. The FDA and Consumer Product Safety
The Anatomy of the Atrioventricular Conduction System in Ventricular Septal Defect and Tetralogy of Fallot: Correlations with the Electrocardiogram and Vectorcardiogram
Authors: ROBERT H. FELDT, JAMES W. DUSHANE, JACK L. TITUS
Journal: Circulation (1966)

The atrioventricular conduction system was studied by a technique of selected serial histological sections in examples of tetralogy of Fallot and ventricular septal defect to correlate the anatomic findings observed with the electrophysiological findings as manifested by the vectorcardiographic pattern. Eight hearts were studied; two examples of each anomaly had electrocardiographic and VCG patterns in the frontal plane similar to A-V canal defects and two examples of each had ECG and VCG patterns usually associated with these lesions. Of the four examples of tetralogy, the two examples with VCG patterns similar to the A-V canal pattern differed from the other examples in that the distance between the A-V node and the origin of left bundle branching was shorter and the fibers destined to become the right bundle branch took an elongated course. The VSD examples offered less striking differences. A short distance from the A-V node to the onset of left bundle branching was seen in both examples with VCG patterns similar to the A-V canal pattern, but one example of VSD with a representative VCG pattern had a similar anatomic configuration. When measurement ratios were compared, the right bundle took its origin at a relatively greater distance from the A-V node in the examples with VCG patterns similar to the A-V canal pattern. The anatomic configuration of those examples of tetralogy and VSD with VCG patterns similar to the A-V canal pattern was such that relatively early conduction to the left bundle branch system could occur.
936 COMBINATION OF THE NS3/4A PROTEASE INHIBITOR ITMN-191 WITH THE ALLOSTERIC NS5B POLYMERASE INHIBITOR ITMN-8020 ENHANCES REPLICON CLEARANCE AND REDUCES THE EMERGENCE OF DRUG RESISTANT VARIANTS
Authors: H. Tan, G. Wang, C. Moy, K. Kossen, R. Rajagopalan, S. Misialek, D. Ruhrmund, L. Hooi, N. Snarskaya, A. Stoycheva, B. Buckman, S. Seiwert, L. Beigelman
Journal: Journal of Hepatology (2009)
Developing Clinical Facilities in Forensic Psychiatry
Authors: MELVIN S. HELLER, ROBERT L. SADOFF, SAMUEL POLSKY
Journal: American Journal of Psychiatry (1968)

Comprehensive clinical facilities in forensic psychiatry have been developed at Temple University through its unit in law and psychiatry over the past ten years. They range from evaluation and therapeutic services in a state penitentiary and county prison to a psychiatric clinic of the Quarter Sessions Court and a civil-legal clinic evaluating clients for the Legal Aid Society and the Community Legal Services, Inc. These facilities provide a strong clinical base for continued research and comprehensive training in forensic psychiatry.
Abstract 629: Hepatocyte growth factor induces resistance to an irreversible epidermal growth factor receptor inhibitor in <i>EGFR</i>-T790M mutant lung cancer
Authors: Tadaaki Yamada, Kunio Matsumoto, Ivan Shterev Donev, Yoshitaka Sekido, Yasuhiko Nishioka, Saburo Sone, Seiji Yano
Journal: Cancer Research (2010)

Abstract Purpose: Epidermal growth factor receptor (EGFR)-activating mutations, such as deletion in exon 19 and L858R point mutation in exon 21,were found in non-small cell lung cancer and associated with favorable response to the reversible EGFR tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib. However, almost all NSCLC patients with EGFR mutations who show response to reversible EGFR-TKI ultimately develop resistance to these agents. Recently, several mechanisms were reported to induce acquired resistance to reversible EGFR-TKI for non-small cell lung cancer with EGFR-activating mutations. Of these, the secondary T790M mutation in EGFR is the most frequent cause of acquired resistance to the reversible EGFR-TKI. Irreversible EGFR-TKIs are expected to overcome the reversible EGFR-TKI resistance of lung cancer harboring T790M mutation in EGFR. However, it is clear that resistance may also develop to this class of inhibitors. We showed previously that hepatocyte growth factor (HGF) induced gefitinib resistance of lung cancer harboring EGFR-activating mutations. Here, we investigated whether HGF induced resistance to the irreversible EGFR-TKI, CL-387,785, in lung cancer cells (H1975) harboring both L858R activating mutation and T790M secondary mutation in EGFR. Experimental Design: CL-387,785 sensitivity and signal transduction in H1975 cells were examined in the presence or absence of HGF or HGF-producing fibroblasts with or without HGF-MET inhibitors. Results: HGF induces resistance to CL-387,785 in H1975 cells. Western blotting and small interfering RNA analyses indicated that HGF-induced resistance was mediated by the MET/phosphoinositide 3-kinase/Akt signaling pathway independent of EGFR, ErbB2, ErbB3, and ErbB4. Resistance of H1975 cells to CL-387,785 was also induced by coculture with high-level HGF-producing lung fibroblasts. The resistance was abrogated by treatment with anti-HGF neutralizing antibody, HGF antagonist NK4, or MET-TKI. Conclusions: We showed HGF-mediated resistance as a novel mechanism of resistance to irreversible EGFR-TKIs. Our findings provide a novel insight into the involvement of HGF-MET mediated signaling in de novo and acquired resistance to irreversible EGFR-TKIs in lung cancer harboring T790M mutation in EGFR. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 629.
Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route
Authors: Claire E. Dearden, Amit Khot, Monica Else, Mike Hamblin, Effie Grand, Ashok Roy, Saman Hewamana, Estella Matutes, Daniel Catovsky
Journal: Blood (2011)
Block of T cell development in P53-deficient mice accelerates development of lymphomas with characteristic RAG-dependent cytogenetic alterations
Authors: Brian B. Haines, Chun Jeih Ryu, Sandy Chang, Alexei Protopopov, Andreas Luch, Yun Hee Kang, Dobrin D. Draganov, Maria F. Fragoso, Sang Gi Paik, Hyo Jeong Hong, Ronald A. DePinho, Jianzhu Chen
Journal: Cancer Cell (2006)
Scottish national survey of tuberculosis notifications 1993 with special reference to the prevalence of HIV seropositivity.
Authors: A. G. Leitch, M. Rubilar, J. Curnow, G. Boyd, G. I. Forbes, S. Burns, B. Watt
Journal: Thorax (1996)

This study investigated the circumstances and problems that departments of forensic medicine encounter with bereaved families regarding samples obtained from medico-legal autopsies. A questionnaire was posted to all 76 departments of forensic medicine performing medico-legal autopsies in Japan, and responses were received from 48 (63.2%). Of the respondents, 12.8% had approached and communicated with bereaved families about collecting samples from the deceased person during an autopsy and the storage of the samples. In addition, 23.4% of these had informed families that samples might be used in research. Eighteen departments had received enquiries and requests from families about the samples, with most requests concerning their return. The response to such requests varied according to the department. Few departments interacted with the bereaved families regarding the procedure for obtaining autopsy samples, and their methods for handling family concerns differed depending on the person within the department authorised to contact the family. Moreover, the procedures for engaging in such communication have long been unclear, and no legal or ethical consensus or agreement with the general public has been established. It is important for researchers to further discuss the correct way for forensic medicine departments to communicate with bereaved families.
Abstract 2913: Identification of GSK2636771, a potent and selective, orally bioavailable inhibitor of phosphatidylinositol 3-kinase-beta (PI3Kα) for the treatment of PTEN deficient tumors
Authors: Ralph A. Rivero, Mary Ann Hardwicke
Journal: Cancer Research (2012)

Abstract Dysregulation of the PI3K pathway is one of the most common causes of tumorigenesis. Aberrant pathway activation occurs frequently through loss of the tumor suppressor protein, PTEN. Loss of PTEN protein has been observed in approximately 40% of glioblastoma, 50% of prostate, 57% of endometrial cancers, as well as in a number of other tumor types, including melanoma and breast cancers. Preclinical studies have shown that selective depletion of the PI3Kα isoform inhibits tumorigenesis and reduces downstream PI3K signaling in PTEN deficient tumors. This data presents an opportunity for a clear patient selection strategy based on the presence or absence of PTEN. During an extensive knowledge-based lead identification and optimization effort starting from the reported PI3K beta-selective compound TGX-221, we identified several unique series of potent and selective inhibitors with less than desirable pharmacokinetic properties. Through a combination of structure-based and knowledge-based design, we ultimately identified substituted benzimidazole GSK2636771 as a potent, orally bioavailable, PI3K beta-selective inhibitor. The evolution of our selective inhibitors, leading to the discovery, design, and optimization of GSK2636771 and related analogs, will be described. 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 2913. doi:1538-7445.AM2012-2913
Progressive Multifocal
Authors: Michael B. Mosher
Journal: JAMA (1971)

A 47-year-old woman with Hodgkin's disease developed progressive multifocal leukoencephalopathy (PML). Sodium pertechnetate Tc 99m brain scans were initially abnormal, but in time reverted to normal. At autopsy, gross demyelinating lesions diagnostic of PML were present in areas corresponding to the defects seen on the original scan.
Effects on human thyroid function of sulphonamide and trimethoprim combination drugs.
Authors: H N Cohen, G H Beastall, W A Ratcliffe, C Gray, I D Watson, J A Thomson
Journal: BMJ (1980)

Changes in pain score and respiratory function after intrathecal injection of 4 mg morphine.Naloxone was given after the 12-hour observations.Hours after injection 0 4 12 16 24 44 Pain score* 8 0 0 0 0 8 Pao, (kPa) 6-8 10-2 7-7 10-3 F1o0 0-21 0-28 0-21 0-21 Paco2 (kPa) 7-25 6-62 6-25 4-63 Respiratory rate (breaths/min) 16 12 8 20 12 14 Heart rate (beats/min) 90 80 120 110 75 100 *0 = No pain; 10 = worst pain imaginable.Pao2 = Arterial oxygen pressure.F1o2 = Fractional inspired oxygen.Paco2 = Arterial carbon dioxide pressure.Conversion: SI to traditional units-Pao2 and Paco2: 1 kPa 7-5 mm Hg. CommentThis patient is unusual because she presented with severe osteomalacia, the hypercalcaemia being an unexpected observation.
International variation in the interpretation of renal transplant biopsies: Report of the CERTPAP Project11A complete listing of the participants who all contributed equally to the work of the CERTPAP Project includes Peter N. Furness (Leicester, UK); Nicholas Taub (Leicester, United Kingdom); Karel J.M. Assmann (Nijmegen, The Netherlands); Giovanni Banfi (Milan, Italy); John N. Botelis (Athens, Greece); Marta Carrera (Barcelona, Spain); Jean-Pierre Cosyns (Brussels, Belgium); Anthony M. Dorman…
Authors: Peter N. Furness, Nicholas Taub
Journal: Kidney International (2001)
Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy
Authors: Cécile Delettre, Guy Lenaers, Jean-Michel Griffoin, Nadine Gigarel, Corinne Lorenzo, Pascale Belenguer, Laetitia Pelloquin, Josiane Grosgeorge, Claude Turc-Carel, Eric Perret, Catherine Astarie-Dequeker, Laetitia Lasquellec, Bernard Arnaud, Bernard Ducommun, Josseline Kaplan, Christian P. Hamel
Journal: Nature Genetics (2000)
ANTIGENS IN IMMUNITY
Authors: G. J. V. Nossal, G. L. Ada, Caroline M. Austin
Journal: The Journal of Experimental Medicine (1965)

Flagellar antigens from S. adelaide bacteria were labelled with carrier-free (125)I so as to achieve a substitution rate of 0.1 to 2.1 radioactive iodine atoms per flagellin molecule. Lymph nodes from rats injected with small amounts of these antigens were teased into a single cell suspension. Single antibody-forming cells were identified and submitted individually to autoradiography so as to measure their content of iodine (125)I. The study was confined to the 7S phase of the primary response. Grain counts over 216 single antibody-forming cells were no higher than counts over equivalent background areas in the emulsion. This finding suggested that the cells contained little or no macromolecular antigen, and it was considered very unlikely that there were sufficient macromolecules of antigen in a plasma cell to act as a direct template on polysomes for the formation of antibody. The question of the possible presence, in such cells, of fragments of antigen was considered. This possibility, while not supported by the present results, cannot be excluded at present.
Influence of Diabetes Mellitus on the Results of Coronary Bypass Surgery
Authors: Gerald M. Lawrie, George C. Morris, Donald H. Glaeser
Journal: JAMA (1986)

To determine the long-term influence of the severity of preoperative diabetes mellitus on the results of coronary bypass, a review was made of 212 diabetics operated on between 1968 and 1973, of whom 87 patients (41%) were receiving no drugs, 108 patients (50.9%) were receiving oral hypoglycemic agents, and 17 patients (8%) were receiving insulin. They were compared with 1,222 nondiabetic patients operated on over the same period. Perioperative mortality was similar in the diabetics and nondiabetics: 7.1% vs 4.5%. Improvement in anginal symptoms was similar in all patient groups: 85.9% to 92.7%. Overall 15-year survival probability was .53 for the nondiabetic group, .43 for the diabetics not receiving drugs, .33 for those receiving oral agents, and .19 for the insulin-treated patients. Late graft patency ranged from 78% to 90% and was comparable in all groups. The preoperative blood glucose level was an important predictor of late mortality in all diabetic patients. Thus, coronary bypass surgery was effective in all groups of diabetic patients in long-term relief of anginal symptoms. Intermediate-term survival rates were good in all groups, but the initial severity of the diabetes was an important determinant of long-term survival rates.
Metal-Binding in Medicine: Proceedings of a Symposium Sponsored by Hahnemann Medical College and Hospital, Philadelphia
Authors: Edward Bigg
Journal: JAMA (1960)

The introduction of metal-binding or chelating agents has resulted in unique and fascinating observations on trace metals and their role in normal and abnormal physiology. In the past few years, data have been accumulating at a rapid rate, and, in order to present as complete a summation of our present knowledge of this subject as possible, a conference of outstanding workers and contributors in this field was held. This book represents a crystallization of the material presented, with a comprehensive survey of activities, both those accomplished and those in progress. The papers are organized to cover six facets of the problem, ranging from fundamental concepts in trace metal research through clinical application of metal-binding agents, with discussion of practical as well as hypothetical applications of the metalbinding principle in clinical therapy. At the close of each group of papers, an informal panel discussion is recorded with questions posed and answered
Glomerular procoagulant activity in human proliferative glomerulonephritis.
Authors: P G Tipping, J P Dowling, S R Holdsworth
Journal: Journal of Clinical Investigation (1988)

Mechanisms for initiation of glomerular fibrin deposition were studied using renal tissue obtained from two patients with rapidly progressive, crescentic glomerulonephritis. Histological examination showed extensive glomerular monocyte infiltration and fibrin deposition in both patients. Sonicated cell suspensions of isolated glomeruli from these patients contained markedly augmented levels of procoagulant activity (PCA) compared with the levels found in normal glomeruli. This PCA was characterized as tissue factor by its functional dependence on Factors VII and V, independence of Factors VIII and XII, inhibition by concanavalin A and phospholipase C, and association with cell membranes. Its coagulant activity was also inhibited by a specific monoclonal anti-human tissue factor antibody. Tissue factor could be identified in glomeruli from these two patients by indirect immunofluorescence using this antibody. These studies implicate extrinsic pathway activation via tissue factor in intraglomerular deposition of fibrin in these patients. Activated monocytes, known to be a potent source of procoagulant activity and seen in large numbers within glomeruli from these patients, are a likely source of this tissue factor.
Basic Concepts and Methods for Joint Models of Longitudinal and Survival Data
Authors: Joseph G. Ibrahim, Haitao Chu, Liddy M. Chen
Journal: Journal of Clinical Oncology (2010)

Joint models for longitudinal and survival data are particularly relevant to many cancer clinical trials and observational studies in which longitudinal biomarkers (eg, circulating tumor cells, immune response to a vaccine, and quality-of-life measurements) may be highly associated with time to event, such as relapse-free survival or overall survival. In this article, we give an introductory overview on joint modeling and present a general discussion of a broad range of issues that arise in the design and analysis of clinical trials using joint models. To demonstrate our points throughout, we present an analysis from the Eastern Cooperative Oncology Group trial E1193, as well as examine some operating characteristics of joint models through simulation studies.
A Reluctant Doctor Shopper
Authors: Michael A. LaCombe
Journal: Annals of Internal Medicine (1998)

Letters1 May 1998A Reluctant Doctor ShopperMichael A. LaCombe, MDMichael A. LaCombe, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-9-199805010-00040 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Drs. Sklaver, MacDonald, Cassiere, and Matz raise several valid points pertaining to the piece by Ms. Bingham. First, to Dr. MacDonald's central question: Is the story true? To our satisfaction, the answer is “yes.” In the patient's initial telephone encounter with her internist, she is told to call a neurologist. That could hardly have been fabricated. As a response from her physician, it is unacceptable, as Dr. Cassiere rightly points out.Second, Dr. Sklaver asks whether any of Ms. Bingham's demands are unrealistic. Perhaps. She certainly has a right to a quick and accurate diagnosis when giving such ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1998Volume 128, Issue 9Page: 786KeywordsMotivation Issue Published: 1 May 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Signaling via IL-2 and IL-4 in JAK3-Deficient Severe Combined Immunodeficiency Lymphocytes: JAK3-Dependent and Independent Pathways
Authors: Scott A. Oakes, Fabio Candotti, James A. Johnston, Yi-Qing Chen, John J. Ryan, Naomi Taylor, Xiuwen Liu, Lothar Hennighausen, Luigi D. Notarangelo, William E. Paul, R.Michael Blaese, John J. O'Shea
Journal: Immunity (1996)