tbuckley/cabot-search huggingface dataset:
Abstract 5256: Mechanism of field cancerization
Authors: Bogdan A. Czerniak, Sangkyou Lee, Jolanta Bondaruk, Sooyong Lee, Tadeusz Majewski, Shizhen Zhang, Li Shen, Yuexin Liu, Charles Guo, Colin Dinney, H. Barton Grossman, Wei Zhang, Menashe Bar-Eli, Keith Baggerly, Richard Behringer, David McConkey, David McConkey, Margaret Knowles, Woonbok Chung, Jean-Pierre Issa
Journal: Cancer Research (2014)

Abstract We developed a strategy that combines histologic and genetic mapping that permits interrogation of the chronology of genetic changes associated with cancer development on a whole-organ scale. By using this approach, we analyzed the sequence of genetic alterations contiguous to the tumor suppressor RB1 and identified a set of alternative target genes that we term “forerunner” (FR) genes whose silencing was associated with development of clonal plaque-like mucosal field effects initiating bladder carcinogenesis. Expression and methylation studies identified five candidate FR genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11). In vitro mechanistic studies demonstrated that three of these genes (ITM2B, LPAR6 and ARL11) control cell survival and proliferation consistent with their loss of function being contributory to tumorigenesis, and in vivo genetic ablation of Lpar6 in a mouse model resulted in activation of basal/stem cell transcriptional programs involving STAT3 and NFκB causing proliferative expansion of the basal layer of the urothelium. Whole genome analyses of the field effects in a representative whole-organ map revealed a sequential accumulation of alterations in RHO/RAC/Cdc42 pathways that control invasion and cell motility. These studies identify FR genetic alterations in tissue fields as one of the earliest events in carcinogenesis and provide comprehensive description of field cancerization in a primary human tumor. The results have important implications for the development of novel detection markers and chemoprevention therapeutic strategies. Citation Format: Bogdan A. Czerniak, Sangkyou Lee, Jolanta Bondaruk, Sooyong Lee, Tadeusz Majewski, Shizhen Zhang, Li Shen, Yuexin Liu, Charles Guo, Colin Dinney, H. Barton Grossman, Wei Zhang, Menashe Bar-Eli, Keith Baggerly, Richard Behringer, David McConkey, David McConkey, Margaret Knowles, Woonbok Chung, Jean-Pierre Issa. Mechanism of field cancerization. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5256. doi:10.1158/1538-7445.AM2014-5256
Update in General Internal Medicine
Authors: Betty A. Mincey
Journal: Annals of Internal Medicine (2001)

Letters21 August 2001Update in General Internal MedicineBetty A. Mincey, MDBetty A. Mincey, MDMayo Clinic, Jacksonville, FL 32224 (Mincey)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-4-200108210-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their otherwise excellent review of recently published studies on osteoporosis treatment and prevention, Roach and colleagues (1) state that “Raloxifene and tamoxifen reduce the risk for breast cancer.” This statement is misleading because it implies that the two drugs are equally effective for this purpose. Although the Multiple Outcomes of Raloxifene Evaluation noted a significant reduction in breast cancer risk (2), this trial was not designed with breast cancer incidence as a primary end point. Tamoxifen is approved by the U.S. Food and Drug Administration for reduction of incidence of breast cancer in high-risk women, but ...References1. Roach K, Stern S, Altkorn D, Cifu A, Levinson W. Update in general internal medicine. Ann Intern Med. 2000;133:209-17. [PMID: 10906836] LinkGoogle Scholar2. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al . The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999;281:2189-97. [PMID: 10376571] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Mayo Clinic, Jacksonville, FL 32224 (Mincey) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Tragic Events of April 1996 Jack Coulehan Update in General Internal Medicine Keith Roach , Scott Stern , Diane Altkorn , Adam Cifu , and Wendy Levinson Metrics 21 August 2001Volume 135, Issue 4Page: 300-301KeywordsBreast cancerCancer preventionCancer treatmentDrugsFood and Drug AdministrationOsteoporosis ePublished: 21 August 2001 Issue Published: 21 August 2001 CopyrightCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
[651] USE OF HEMATOPOIETIC GROWTH FACTORS AS ADJUVANT THERAPY OF CHRONIC HEPATITIS C: A FRENCH NATIONAL SURVEY
Authors: T. Thevenot, J.F. Cadranel, V. Di Martino, A. Pariente, X. Causse, C. Renou, H. Hagege, I. Denis, F. Lunel-Fabiani
Journal: Journal of Hepatology (2007)
Language heterogeneity and self-organizing consciousness
Authors: William S.-Y. Wang, Jinyun Ke
Journal: Behavioral and Brain Sciences (2002)

While the current generative paradigm in linguistics leans heavily toward computation, investigations on conscious representations are much welcome. The SOC model examines the acquisition of complex representations in individuals. We note that heterogeneity of representation in populations is a central issue that must be addressed as well. In addition to the self-organizing processes proposed for the individual, interactions among individuals must be incorporated in any comprehensive account of language.
Autoimmune Hemolytic Anemia With Both Cold and Warm Autoantibodies
Authors: Neil Jay Nusbaum, Sundeep Khosla
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Shulman and colleagues<sup>1</sup>describe a syndrome of autoimmune hemolytic anemia with both warm and cold autoantibodies. We, too, have followed up a patient with this syndrome who was initially seen at 47 years of age with hemolytic anemia, thrombocytopenia, and neutropenia. <h3>Report of a Case.—</h3> The patient demonstrated a direct antiplatelet antibody and a direct antineutrophil antibody. He had a positive direct Coombs' test for IgG and his indirect Coombs' test confirmed the presence of a warm-reacting antibody, but he also had a cold agglutinin titer of 1:16. His antinuclear antibody test results were negative, and he had no evidence of connective tissue disease at the time of the physical examination. The patient's condition improved dramatically on a regimen of high-dose steroids, the dose of which was then tapered. Over two months he maintained a mild compensated hemolysis. As his steroid regimen was reduced below 30 mg/day,
The effect of glutamine administration on urinary ammonium excretion in normal subjects and patients with renal disease
Authors: Tomas Welbourne, Michael Weber, Norman Bank
Journal: Journal of Clinical Investigation (1972)

The effect of acute changes in the delivery rate of glutamine to the kidney on urinary ammonium excretion was studied in man. Healthy subjects and patients with intrinsic renal disease were studied under three different acid-base conditions: unaltered acid-base balance; NH4Cl-induced acidosis; and NaHCO3-induced alkalosis. Anhydrous L-glutamine was administered orally in a single dose of 260 mmoles during each of these three acid-base states. We found that endogenous venous plasma glutamine concentration fell during acidosis and rose during alkalosis in both healthy subjects and patients with renal disease. In healthy subjects, orally administered glutamine raised plasma glutamine concentration markedly over a 2-3 hr period. This was accompanied by an increase in urinary ammonium excretion and a rise in urine pH under normal acid-base conditions and during metabolic acidosis. No increase in ammonium excretion occurred when glutamine was administered during metabolic alkalosis in spite of an equivalent rise in plasma glutamine concentration. In patients with renal disease, endogenous venous plasma glutamine concentration was lower than in healthy subjects, perhaps as a result of mild metabolic acidosis. Acute oral glutamine loading failed to increase urinary ammonium excretion significantly during either unaltered acid-base conditions or after NH4Cl-induced acidosis, even though plasma glutamine rose as high as in healthy subjects. We conclude from these observations that glutamine delivery to the kidney is a rate-limiting factor for ammonium excretion in healthy subjects, both before and after cellular enzyme adaptation induced by metabolic acidosis. In contrast, in patients with renal disease, glutamine delivery is not rate-limiting for ammonium excretion. Presumably other factors, such as surviving renal mass and the activity of intracellular enzymes necessary for ammonia synthesis limit ammonium excretion in these patients.
Treatment of Congenital and Acquired Heart Block with an Implantable Pacemaker
Authors: RODMAN E. TABER, LUDOVICO R. ESTOYE, EDWARD R. GREEN, THOMAS GAHAGAN
Journal: Circulation (1964)

The Chardack-Greatbatch implantable pacemaker has proved a worthwhile device for the management of both congenital and acquired heart block. The procedure used for implantation in 38 patients is described. The most frequent indication for use of the pacemaker is syncope due to heart block. Progressive cardiac enlargement was also an indication for pacemaker implantation in two of four children with congenital heart block. The pacemaker has also been useful in the management of surgically induced heart block and coexisting heart block that accompanies intracardiac lesions, such as aortic stenosis, which require open-heart surgery. Pacemaker failure due to electrode breakage occurred in two patients. In both instances, a replacement unit was successfully used. Three of the 38 patients have subsequently died from causes unrelated to pacemaking while one death resulted from pacemaker failure 12 months after implantation. The remaining 34 patients have remained free from cardiac symptoms during observation periods of 2 to 24 months.
Treating Diabetic Foot Osteomyelitis Primarily With Surgery or Antibiotics: Have We Answered the Question?
Authors: Benjamin A. Lipsky
Journal: Diabetes Care (2014)

Foot infections are among the most frequent diabetes-related causes for hospitalization and the usual immediate predecessor to lower-extremity amputation in these patients (1). Infection usually starts in ulcerated soft tissues, but can spread contiguously to underlying bone (2). Overall, about 20% of patients with a diabetic foot infection (and over 60% of those with severe infections [3]) have underlying osteomyelitis, which dramatically increases the risk of lower-extremity amputation (4). Indeed, optimally managing diabetic foot osteomyelitis is widely considered the most difficult and controversial aspect of dealing with diabetic foot infections (5–7).

In the preantibiotic era, the only option for treating osteomyelitis was surgical resection of all necrotic and infected bone. Because surgeons feared further spread of infection up the limb in what was then called “diabetic gangrene,” most procedures were major (often above the knee) amputations (8). The advent of antibiotic therapy led to a marked reduction in both mortality (9–11) and need for major amputations (10,11) in patients with diabetic foot infections. Antibiotic therapy was largely considered adjunctive to surgery, but in the past two decades reports appeared of patients with diabetic foot osteomyelitis apparently cured by antibiotic therapy with little or no surgical resection (12), leading some to reexamine the belief that surgery was almost always needed for this form of chronic osteomyelitis (13).

There are potential advantages, as well as disadvantages, to both medical and surgical treatment of diabetic foot osteomyelitis (Table 1). In some clinical situations, it is clear that one or the other approach is most appropriate (Table 2), but in most cases the …
Hair Loss with 5-Aminosalicylic Acid Enemas
Authors: WALTER H.C. BURGDORF
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 March 1983Hair Loss with 5-Aminosalicylic Acid EnemasWALTER H.C. BURGDORF, M.D., DENNIS A. WEIGAND, M.D.WALTER H.C. BURGDORF, M.D.Search for more papers by this author, DENNIS A. WEIGAND, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-3-419_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Kutty and associates (1) report hair loss after the use of 5-aminosalicylic acid enemas. Hair loss is too inexact a term to allow satisfactory understanding. Patients with severe inflammatory bowel disease are likely to develop telogen effluvium, which is a widespread loss of hair after major metabolic events. This disorder can be easily diagnosed because the bulk of the hairs that are lost have the characteristic bulbs of telogen hairs, and are of equal diameter and color.In contrast, an anagen hair loss with immediate damage to the hair root from 5-aminosalicylic acid enemas would be most...Reference1. OCHOA M. Clinical Interpretation and Practice of Cancer Chemotherapy [Book review]. Ann Intern Med. 1982;97:943. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The University of Oklahoma Oklahoma City, OK 73190 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1983Volume 98, Issue 3Page: 419-419KeywordsInflammatory bowel disease Issue Published: 1 March 1983 PDF DownloadLoading ...
Dramatic Response to Crizotinib in an ALK-Positive Adenocarcinoma Patient with Disseminated Intravascular Coagulation
Authors: Gouji Toyokawa, Mitsuhiro Takenoyama, Sawori Watanabe, Ryo Toyozawa, Eiko Inamasu, Miyako Kojo, Yoshimasa Shiraishi, Yosuke Morodomi, Tomoyoshi Takenaka, Fumihiko Hirai, Masafumi Yamaguchi, Kenichi Taguchi, Takashi Seto, Yukito Ichinose
Journal: Journal of Thoracic Oncology (2013)
IODINE IN TUBERCULOSIS
Authors: Scott R. Edwards
Journal: JAMA (1926)

To the Editor:  — In regard to the communication of Dr. E. A. Peterson (The Journal, June 26, p. 1995), in which he states that he doubts that any authentic experiments have ever been done to show that iodine breaks down a lung in a tuberculous animal or in man, the following facts may have some bearing:  Several years ago Jobling and Peterson, while working on ferments, showed that iodine had the power of saturating the unsaturated radicals of fatty acids, and that when these fatty acids were acting as antitryptic ferments, saturation of these unsaturated bonds tended to reverse the reaction and liberate trypsin. When it is considered that a tubercle has a high percentage of fatty acids in its composition and that the probabilities are that these fatty acids are acting as antitryptic ferments, the importance of iodine in releasing the trypsin by saturating these unsaturated fatty acids
THE DIARY OF CROSSE OF NORWICH
Authors: V. G. Plarr
Journal: BMJ (1921)

TIlE DIAUW OF CROSSE OF NORWICH.well illustrated by photographs.In addition to Algiers itself and Hammam-R'Irha, there are short notes on many more distant places to which agreeable excursions can be made.The book appears to be issued for private circulation,
P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers.
Authors: T Lasky, E Silbergeld
Journal: Environmental Health Perspectives (1996)

In this paper we describe a statistical analysis of the European Molecular Library p53 mutation database comparing p53 mutations occurring in breast, colorectal, liver, lung, and ovarian cancers. The analyses show that mutation hot spots vary by cancer and that base pair changes and predicted amino acid changes in the gene product vary by cancer and by codon. The analyses use relative frequencies and epidemiologic measures of effect (prevalence ratios) not applied previously to these data. The five cancers in the database with the largest sample sizes were breast (418), colorectal (398), liver (341), non-small cell lung (313), and ovarian cancers (251), for a total of 1,721 reports of p53 mutations. The five cancers varied considerably in the distribution of mutations over sites, with different hot spots in each cancer. At the six most frequently reported codon sites, we compared base pair and amino acid changes by type of cancer. The comparison of base pair changes indicated a predominance of particular base pair changes at a codon (for example, C-->T and G-->A changes at Codon 248) and their association with specific cancers (C-->T changes with colorectal cancer and G-->A changes with both colorectal and breast cancers at codon 248). Comparing predicted amino acid changes by codon and cancer was also intriguing, as in codons 175 and 273, where arginine to cysteine and arginine to histidine changes were frequent in breast, colorectal, and ovarian cancers. Variations in p53 mutational distributions by cancer may be explained by different exposures to carcinogens or by organ-specific clonal selection. Further research may be stimulated by this analysis.
Salt, volume and the prevention of hypertension.
Authors: E D Freis
Journal: Circulation (1976)

The evidence supporting the thesis that hypertension can be prevented by eliminating salt from the diet is based on four principal sources: (1) epidemiological studies in unacculturated peoples showing that the prevalence of hypertension is inversely correlated with the degree of salt intake; (2) hemodynamic studies suggesting that the development of chronic experimental hypertension is a homeostatic response to a maintained increase in extracellular fluid volume (ECF); (3) evidence that the ECF of "salt eaters" is expanded in comparison to that of "no-salt eaters"; and (4) investigations in hypertensive patients receiving either diets greatly restricted in salt or continuous diuretic therapy which correlate the fall in blood pressure with a reduction in ECF. Although this mechanism of essential hypertension is still obscure the evidence is very good if not conclusive that reduction of salt in the diet to below 2 g/day would result in the prevention of essential hypertension and its disappearance as a major public health problem.
Story of a Parade
Authors: Hugh H. Hussey
Journal: JAMA (1976)

This editorial is not about a military march; more nearly, a parade of incensed demonstrators comes to mind. The story begins with the March 28, 1976, issue of<i>Parade</i>—a magazine supplement inserted in many Sunday editions of newspapers. That issue published an article by Donald Robinson that struck a spark with its banner line—"Does Your Doctor Know How to Treat Cancer?"—and then huffed and puffed to light a flame. Just as unchecked cancer spreads like fire throughout the body, cancerphobia spreads through the mind and so damages personal fulfillment of the individual as sometimes to be a threat of substantial magnitude. And Robinson's message was calculated to have that effect. To whet the reader's appetite for scandal, the author described the cases of cancer in two women whose initial attending physicians were portrayed as inept and whose lives were saved because they somehow (Robinson doesn't say how) received "curative"
Prazosin and Clonidine for Moderately Severe Hypertension
Authors: Walter M. Kirkendall, Jeremy J. Hammond, James C. Thomas, Merrill L. Overturf, Andrea Zama
Journal: JAMA (1978)

In a single-blind comparative study of the cases of 30 moderately hypertensive patients, clonidine hydrochloride and prazosin hydrochloride had similar effectiveness in lowering blood pressure. Neither agent had significant effects on the renin-aldosterone axis. Addition of polythiazide to prazosin and chlorthalidone to clonidine notably increased the antihypertensive effect of both drugs. Serum cholesterol levels were observed to decrease when prazosin and clonidine were given and to rise when the diuretics were added to the regimen. The patients treated with clonidine were troubled by side effects, particularly drowsiness and dry mouth. Prazosin was better tolerated, with side effects tending to diminish with time. The "first-dose" effect was seen in two patients given prazosin, but it did not limit treatment. Both diuretics induced notable hypokalemia. (<i>JAMA</i>240:2553-2556, 1978)
Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells.
Authors: C S Long, C P Ordahl, P C Simpson
Journal: Journal of Clinical Investigation (1989)

During pressure-load hypertrophy of the adult heart in vivo, there is up-regulation of the mRNA encoding skeletal alpha-actin, the sarcomeric actin iso-mRNA characteristic of mature skeletal muscle and the fetal/neonatal heart. We have shown previously that during alpha 1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes, the induction of skeletal alpha-actin mRNA is greater than that of the mRNA encoding cardiac alpha-actin, the sarcomeric actin iso-mRNA characteristic of the adult heart. To determine if this actin iso-mRNA switch during cardiac hypertrophy reflects changes in the transcriptional status of the myocyte nucleus, we quantified the rate of transcription of actin mRNAs and total RNA, using an in vitro run-on transcription assay with nuclei isolated from the cultured myocytes after stimulation with norepinephrine (NE). Transcription of skeletal alpha-actin was increased at 3 h after NE, reached a maximum 6.1-fold increase at 12 h, and returned to the control level at 24 h. The EC50 for NE was 200 nM, and pharmacologic studies indicated alpha 1-receptor specificity. Transcription of cardiac alpha-actin was also increased rapidly by NE (maximum 4.6-fold vs. control at 3 h). However, cardiac alpha-actin transcription had returned to the control level at 6 h, when NE-stimulated skeletal alpha-actin transcription was still increasing. Transcription of the cytoskeletal (beta) actin gene was not changed significantly by NE treatment. Total RNA transcription was not increased until 6 h after NE (1.5-fold vs. control) and remained elevated through 24 h. Inhibition of protein synthesis did not attenuate NE-stimulated actin gene transcription. Thus the alpha 1-adrenoceptor mediates a rapid, transient, and selective increase in transcription of the sarcomeric actin isogenes during cardiac myocyte hypertrophy. Skeletal alpha-actin, the fetal/neonatal isogene, is induced preferentially to cardiac alpha-actin, the adult isogene. The different kinetics of actin isogene and total RNA transcription and the independence of transcription from protein synthesis suggest that transcriptional induction via the alpha 1 receptor is complex and may involve preexisting regulatory factors. These results are the first to demonstrate that the alpha 1-adrenergic receptor is a molecular mediator of transcriptional changes underlying an isogene switch that is known to be associated with cardiac myocyte hypertrophy.
Metastatic endometrial cancer; a rare intestinal localization
Authors: W. Thijs, A. Karrenbeld, L. van der Zouwen, L. de Haan
Journal: Endoscopy (2007)

Endometrial cancer can give rise to hematogenous metastases, most often in lungs, brain, and bones. We describe a patient with metastases of endometrial cancer in the small bowel.
Audit of reports of randomised clinical trials published in one journal over 45 years
Authors: C. L van der Wijden, J. A Overbeke
Journal: BMJ (1995)

other drugs (6).In 1992, of 118 patients followed up at one month, 40 (34%) were prescribed 13 blockers, of whom 36 had been discharged taking the drug.This compared with 53/116 (46%) in 1993 and 51.