tbuckley/cabot-search huggingface dataset:
Abstract P2-13-16: Intraoperative ultrasound guided wire bracketing of nonpalpable breast lesions for excision
Authors: David T Rock, Aimee L Stewart, Samith Sandadi
Journal: Cancer Research (2015)

Abstract Background. Mammographic wire localization is the primary means of localizing nonpalpable breast lesions for excision. Unfortunately, that procedure is associated with patient discomfort and vasovagal responses, scheduling difficulties, and problems with inaccurate wire placement or wire displacement. In addition, the wires often enter far from the target and take an indirect course resulting in high positive margin rates. We reviewed our experience with intraoperative ultrasound guided bracketing of nonpalpable lesions to determine if the accuracy of the excision and patient factors could be improved. Methods. Patients that underwent intraoperative ultrasound guided wire bracketing were identified by electronic chart review. After the patient was anesthetized, high frequency linear array ultrasound was used to identify the target lesion. Under direct ultrasound visualization, the lesions were bracketed with 4 hook-wires placed perpendicular to the chest wall at the radial and antiradial margins of the lesion. Excision of the lesion was then performed with circumferential dissection around all 4 localization wires. Results. Intraoperative localization was planned on 80 patients. The lesion was identified by preoperative ultrasound in 76 of those patients (95%). The remaining patients required mammographic localization. In 67 patients (88%) the lesion was identified for bracketing, in the remaining 11 patients the biopsy clip was seen by ultrasound and bracketed. Only 2 patients had positive margins (no tumor touching ink) requiring re-excision (2.6%). Conclusions. The results of our experience show that intraoperative ultrasound guided wire bracketing is a reliable alternative to mammographic localization and is associated with a lower positive margin rate than reported for mammographic wire localization with a single wire. In addition, patient comfort is improved, cost is reduced, and there are no scheduling issues. The technique is especially useful for oncoplastic excisions where the incision is remote from the target lesion. Citation Format: David T Rock, Aimee L Stewart, Samith Sandadi. Intraoperative ultrasound guided wire bracketing of nonpalpable breast lesions for excision [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-16.
611. Group I Intron-Mediated Trans-Splicing Revision of Mutant p53 RNA Transcripts
Authors: Daniel J. Catron, Takashi Watanabe, Kyung-Sook Shin, Eric M. Toloza, Seong-Wook Lee, Bruce A. Sullenger
Journal: Molecular Therapy (2004)

Mutations in the gene encoding the p53 tumor suppressor are reported to be associated with more than half of reported cancer cases. Restoration of wild-type p53 function, as mediator of apoptosis and cell-cycle arrest, has been a popular cancer treatment strategy. Unregulated overexpression of wild-type p53 through conventional gene replacement therapy has been shown to induce deleterious phenotypic changes in normal tissue. We hypothesize that correction of native mutant RNA transcripts by a group I ribozyme can restore the wild-type function of p53 while maintaining endogenous physiologic expression levels. We have developed and characterized the activity of three group I ribozymes that specifically revise mutant p53 transcripts in vitro. Most p53 mutations affect its DNA binding domain, and certain mutations in p53 affect the transactivation of well-characterized p53-responsive genes, such as WAF1/p21, which is involved in cell-cycle inhibition, and the proapoptotic Bax. In the 2774 ovarian cancer cell line, the mutated p53 is unable to transactivate either gene. Ribozyme-mediated revision of the mutant p53 transcript in 2774 cells results in significant stimulation of expression for both p21 and Bax. At 72 hours post-transfection, apoptosis in ribozyme-transfected 2774 cells was increased 2.5 fold over that of mock trasfectants using a fluorescent TUNEL assay. This is achieved even though only about 10% of the mutant transcripts were repaired in the 2774 cells with transfection efficiency in the range of only 40–50% using our plasmid constructs. Certain mutations in p53 also affect the transcription of the multi-drug resistance gene (MDR1), whose gene product renders several structurally unrelated chemotherapeutic agents ineffective. Ribozyme-transfected tumor cells, which contained exogenous truncated p53 message, and cotransfected with the human MDR1 promoter upstream of the luciferase gene as a reporter plasmid were used to assay for functional p53 activity. Group I intron-mediated trans-splicing correction of truncated p53 to wild-type function results in the reduction of MDR1 expression by at least half in Saos-2 sarcoma cells. These results suggest that group I intron-mediated trans-splicing revision of cancer cells with mutant p53 RNA transcripts could be an effective method for reestablishing apoptosis and chemosensitivity in malignant tumors. We are currently using adenoviral ribozyme constructs to increase tumor cell transduction efficiency and mutant RNA transcript repair efficiency in preparation of a clinically applicable cancer treatment modality.
Individual Circadian Variation and Sudden Death
Authors: André d’Avila, Pedro Brugada
Journal: Circulation (1999)

To the Editor:The intriguing article by Jono et al 1 suggests that long-term supplementation with vitamin D for postmenopausal osteoporosis may increase vascular calcification.This is not a new concept 2 and raises important and practical issues.Alendronate, an inhibitor of osteoclast-mediated bone resorption, is widely promoted for the treatment and prevention of osteoporosis in postmenopausal women. 3 This group of women
Biased Agonism at G Protein-Coupled Receptors: The Promise and the Challenges-A Medicinal Chemistry Perspective
Authors: Jeremy Shonberg, Laura Lopez, Peter J. Scammells, Arthur Christopoulos, Ben Capuano, J. Robert Lane
Journal: Medicinal Research Reviews (2014)

Abstract Historically, determination of G protein‐coupled receptor (GPCR) ligand efficacy has often been restricted to identifying the ligand as an agonist or antagonist at a given signaling pathway. This classification was deemed sufficient to predict compound efficacy at all signaling endpoints, including the therapeutically relevant one(s). However, it is now apparent that ligands acting at the same GPCR can stabilize multiple, distinct, receptor conformations linked to different functional outcomes. This phenomenon, known as biased agonism, stimulus bias, or functional selectivity offers the opportunity to separate on‐target therapeutic effects from side effects through the design of drugs that show pathway selectivity. However, the medicinal chemist faces numerous challenges to develop biased ligands, including the detection and quantification of biased agonism. This review summarizes the current state of the field of research into biased agonism at GPCRs, with a particular focus on efforts to relate biased agonism to ligand structure.
Abstract #878: Reactive oxygen species in the ability of pro-apoptotic H-Ras to enhance apoptosis induced by histone deacetylase inhibitors
Authors: Shambhunath Choudhary, Kusum Rathore, Xiaoyu Song, Hwa-Chain Wang
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

This study is to understand the role of reactive oxygen species in the ability of pro-apoptotic H-Ras to enhance apoptosis induced by histone deacetylase inhibitors. Oncogenic induction of the ras genes is widely involved in human cancers. Expression of oncogenic H-Ras increases susceptibility of human and mouse cells to histone deacetylase inhibitors (HDACIs), such as FK228 and trichostatin A, for inducing caspase activation and selective apoptosis. HDACIs make up a new class of structurally diverse anticancer agents and have been shown to exhibit antimetastatic and antiangiogenic activities toward malignantly transformed cells. However, the mechanisms behind the proapoptotic ability of oncogenic H-Ras to enhance cell susceptibility to HDACIs still remain unclear. Our recent studies revealed that expression of oncogenic H-Ras potentiated intracellular reactive oxygen species (ROS) in human and mouse cells and enhanced HDACI-induced ROS to induce activation of caspase pathways for inducing selective apoptosis of oncogenic H-Ras-expressing cells versus parental cells. Expression of oncogenic H-Ras also increased cell susceptibility to hydrogen peroxide (H2O2) for inducing apoptosis and caspase activation. By studying IC50 values of FK228 and H2O2 for oncogenic H-Ras-expressing and parental cells and by quantifying cell death and caspase activation induced by FK228 and H2O2, we detected that intracellular ROS was cooperatively up-regulated by oncogenic H-Ras and FK228 treatment to induce apoptosis and caspase activation in a dose-dependent manner. Our results led us to a suggestion that increased ROS played a contributing role in the proapoptotic ability of oncogenic H-Ras to enhance FK228-induced activation of caspases for inducing selective apoptosis in a dose-dependent manner. The role of intracellular ROS in the novel proapoptotic activity of oncogenic H-Ras should be seriously considered as a potential target in developing therapeutic strategies to control oncogenic H-Ras-involved human cancers by HDACIs.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 878.
Comparative Effects of Losartan and Enalapril on Exercise Capacity and Clinical Status in Patients With Heart Failure fn1fn1This study was supported by a grant from Merck Research Laboratories, West Point, Pennsylvania.
Authors: Roberto M. Lang, Uri Elkayam, Laurence G. Yellen, Daniel Krauss, Robert S. McKelvie, Douglas E. Vaughan, Dawn E. Ney, Lukas Makris, Paul I. Chang
Journal: Journal of the American College of Cardiology (1997)
A New Modification of Milk for Use in the Dietary Treatment of Peptic Ulcer
Authors: Ray C. Blankinship, Wm. H. Oatway
Journal: Annals of Internal Medicine (1931)

Article1 April 1931A New Modification of Milk for Use in the Dietary Treatment of Peptic UlcerRAY C. BLANKINSHIP, M.D., WM. H. OATWAY Jr., M.D.RAY C. BLANKINSHIP, M.D.Search for more papers by this author, WM. H. OATWAY Jr., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-10-1257 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe ideal ulcer diet is one which furnishes the fundamental requisites (balanced, with adequate mineral and vitamin content) in a finely divided state and which brings about a minimum digestive effort. When properly modified, and slightly supplemented to overcome the distorted relationship between protein, fat and carbohydrate content, milk and cream can be made to form an excellent basis for such a diet. The pediatricians years ago recognized the importance in infant feeding of a fine soft curd, as well as a balanced diet and slightly acidified milk. Hess and Matzner,1in 1924, first recommended the addition of a small...Bibliography1 HESSMATZNER AFMJ: Jour. Amer. Med. Asso., May 17, 1924, v. 82, No. 20, page 1604. CrossrefGoogle Scholar2 COLEMAN W: Jour. Amer. Med. Asso., Sept. 20, 1924. Google Scholar3 COLE : Pract. Physiolog. Chem., p. 242. Google Scholar4 HARRIS S: Jour. Amer. Med. Asso., November 10, 1928. MedlineGoogle Scholar5 COWADIAS AP: The Practitioner, June, 1929, page 732. Google Scholar6 BULATACARLSON EAJ: Amer. J. of Phys., Vol. LXIX, page 107. Google Scholar7 STANDISHCOWGILLSHOHL WAGRAT: Am. J. of Phys., No. 81, June-Aug., 1927, p. 696. CrossrefGoogle Scholar8 BULATACARLSON EAJ: Amer. Jour. of Phys., Vol. LXIX, p. 107. Google Scholar9 GONCETEMPLETON JEHL: Am. J. Dis. of Child., Feb., 1930, Vol. 39, p. 265. Google Scholar10 BLANKINSHIP RC: Wis. Med. Jour., July, 1929. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Madison, Wisconsin*From the Department of Medicine, State of Wisconsin General Hospital, Madison, Wisconsin. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Effect of Fruit-syrup Supplements on the Assimilation of Food from the Alimentary CanalDuodenitis 1 April 1931Volume 4, Issue 10Page: 1257-1264KeywordsCarbohydratesDietFatsHospital medicineInfantsMilkPeptic ulcersProteinsUlcers ePublished: 1 December 2008 Issue Published: 1 April 1931 PDF downloadLoading ...
NIH Decides Against Continuing NGVLs in Their Current Form
Authors: David A Williams
Journal: Molecular Therapy (2007)

During the American Society of Gene Therapy (ASGT) Annual Meeting in 2006, there were many conversations concerning the potential discontinuation of the National Gene Vector Laboratories (NGVL) program by the National Institutes of Health (NIH). In light of concerns about what the NIH might be planning, Dr. Ted Friedmann, President of the ASGT, assembled an ad hoc committee to review the funding of gene therapy trials and to recommend a position on NGVLs for the society to communicate to the NIH. In editorials published in Molecular Therapy in November 2006 (“NIH Funding of Gene Therapy Trials”) and January 2007 (“ASGT Advises NIH in Funding of Gene Therapy Trials”), we expressed the strong view that NIH should revamp the way in which gene therapy trials are funded and that the NGVL program had been a valuable mechanism by which clinical-grade vectors were produced and certified. The ad hoc committee strongly urged that the NGVL program be continued, albeit with modifications in the review process that would be intended to make the entire process less cumbersome and more efficient. In a letter to Dr. Friedman dated 22 February 2007, Dr. Elias Zerhouni, Director of the NIH, thanked the ASGT for its input and informed him that the NIH would no longer fund vector production via NGVLs. However, there will be continued resources for repositories where master cell banks could be stored. Zerhouni explained that both the National Cancer Institute and the National Heart, Lung, and Blood Institute—which were major funding institutes for the NGVL—had decided to fund their own vector production centers. This is a disappointing course of action contrary to what the ASGT and end-users in the field recommended. It is ironic that Dr. Zerhouni should make this decision to further fragment vector funding, because his mantra has clearly been a call for trans-NIH programs that facilitate collaborative approaches to biology and therapy in a non-disease-specific fashion. I would argue that the NGVL was a successful example of this approach and, although not perfect, served an extremely useful purpose for the field. Apparently, considerations of the ASGT recommendations on the fundamental process by which gene therapy trials are funded by the NIH are still under consideration. In his letter to Dr. Friedman, Dr. Zerhouni said that he has “asked Amy Patterson of the Office of Biotechnology Activities to confer with relevant NIH Institutes and Centers regarding the problems that you (ASGT) identified and your recommendations.” One can only hope that the NIH is more amenable to follow-through on the thoughtful recommendations by the ASGT on new approaches for reviewing and funding gene therapy research. In the current climate, the field (as is NIH-supported research in general) is significantly underfunded, and, in addition, the process is nonharmonized and excessively burdensome.
DIFFERENTIAL DIAGNOSIS OF THE PAIN OF CORONARY HEART DISEASE
Authors: A C ERNSTENE
Journal: Annals of Internal Medicine (1957)

Article1 February 1957DIFFERENTIAL DIAGNOSIS OF THE PAIN OF CORONARY HEART DISEASEA. CARLTON ERNSTENE, M.D., F.A.C.P.A. CARLTON ERNSTENE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-46-2-247 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe three most common clinical manifestations of coronary heart disease are, in their order of frequency, angina pectoris, acute myocardial infarction and acute coronary failure. Each of these conditions is characterized by pain in the chest due to anoxia of one or more areas of the myocardium. The pain is similar in location in all three, and the syndromes are distinguished from one another chiefly by the length of time the distress persists and by whether the anoxia is of sufficient severity and duration to result in the death of myocardial tissue. Pain in the chest may also be caused...Bibliography1. LaDueNydickWroblewski JSIF: Serum glutamic oxalacetic transaminase as an index of acute heart muscle damage, Circulation 12: 735, 1955. Google Scholar2. ViarHarrison WNTR: Chest pain in association with pulmonary hypertension. Its similarity to the pain of coronary disease, Circulation 5: 1, 1952. CrossrefMedlineGoogle Scholar3. BlumgartSchlesingerDavis HLMJD: Studies on the relation of the clinical manifestations of angina pectoris, coronary thrombosis, and myocardial infarction to the pathologic findings with particular reference to the significance of the collateral circulation, Am. Heart J. 19: 1, 1940. CrossrefGoogle Scholar4. PrinzmetalMassumi MRA: The anterior chest wall syndrome—chest pain resembling pain of cardiac origin, J. A. M. A. 159: 177, 1955. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio*Presented at the Thirty-seventh Annual Session of The American College of Physicians, Los Angeles, California, April 19, 1956.From the Cleveland Clinic and the Frank E. Bunts Educational Institute, Cleveland, Ohio.Requests for reprints should be addressed to A. Carlton Ernstene, M.D., The Cleveland Clinic, 2020 East Ninety-third Street, Cleveland 6, Ohio. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDie Coronarerkrankungen. Coronarinsuffizienz, Angina pectoris und Herzinfarkt 1 February 1957Volume 46, Issue 2Page: 247-254KeywordsAnginaAortaCoronary heart diseaseElectrocardiographyEmphysemaHerniaMyocardiumOsteoarthritisThoraxWalking Issue Published: 1 February 1957 PDF downloadLoading ...
Studies on the absorption and metabolism of folic acid
Authors: C. M. Baugh, C. L. Krumdieck, H. J. Baker, C. E. Butterworth
Journal: Journal of Clinical Investigation (1971)

Folic acid absorption was studied in anesthetized dogs by determining the amount and chemical nature of folate in venous blood emerging from isolated intestinal segments containing free folic acid and/or pteroylpolyglutamates of a known chain length. Chromatographically pure test materials placed in the lumen were prepared by unambiguous solid phase synthetic methods. This synthetic procedure not only yields compounds of known structure, it also provides a means by which glutamic acid residues at any given position in the gamma glutamyl chain can be made radioactive. For example, teropterin (pteroyltriglutamate) was synthesized in such a way that (14)C was present only in the middle glutamic acid unit. Suitable placement of label permitted assessment of the extent of peptide cleavage. The action of plasma conjugase was inhibited by copper chloride. Plasma samples were analyzed by Lactobacillus casei and Streptococcus faecalis assay, by column chromatography, and by quantitative measurement of pteridine-bound radioactivity. It was observed that biologically active folate appeared in the mesenteric vein with either pteroylmono-, di-, tri-, penta-, or heptaglutamate in the lumen. Generally speaking the absorption rate appeared to be inversely related to the length of the gamma glutamyl side chain. Roughly twice as much folic acid appeared in the circulation from (3)H-labeled pteroylmonoglutamate as from (14)C-labeled pteroylpentaglutamate when equimolar amounts of each were placed simultaneously in a single intestinal segment. Pteroylmonoglutamate appeared to be the predominant form entering the blood from each of the precursors tested. However, evidence was obtained that pteroyldiglutamate may enter the mesenteric vein soon after placing pteroyldi-, or triglutamate in the lumen, but not with the higher polyglutamates. Comparison of radioactivity and biological activity patterns suggests little conversion, if any, to reduced or methylated forms during the first 30 min of passage through the intestinal mucosa. We conclude that both pteroylmonoglutamates and pteroyldiglutamates may across the intestinal mucosa of the dog, and that reduction and methylation are not essential to the absorption process.
Mycosis fungoides associated with splenic infarction and muscle involvement
Authors: M. Watanabe, H. Ujiie, K. Nishimura, T. Kamiyama, R. Abe, H. Shimizu
Journal: British Journal of Dermatology (2015)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Mycosis fungoides (MF), the most common cutaneous T‐cell lymphoma, usually progresses slowly but can involve multiple organs, such as the lung and spleen, at an advanced stage.1 Here we report an unusual case of MF associated with splenic infarction due to MF invasion that was histologically confirmed in life. A 72‐year‐old man had experienced multiple asymptomatic brownish‐red scaly macules, plaques and nodules on the extremities for 5 years without any extracutaneous lesions or internal involvement, as confirmed by computed tomography (CT) scan and bone marrow biopsy (Fig. 1a). Laboratory tests revealed a slight elevation in lactate dehydrogenase (LDH) (229 U L−1; normal range 119–229) and a marked elevation in soluble interleukin (IL)‐2 (1795 U mL−1; normal range 0–459). A skin biopsy specimen from the lower leg showed epidermotropism and upper‐dermal infiltration of atypical lymphocytes, which is consistent with MF (Fig. 1b, c).
Impact of pulmonary tuberculosis infection on chronic obstructive pulmonary disease
Authors: Hridaya Bibhu Ghimire, Jian Guo Li
Journal: European Respiratory Journal (2011)

Background:  Tuberculosis (TB) and chronic obstructive pulmonary disease (COPD) are common diseases in developing world, sharing some risk factors like smoking and low socioeconomic status.   Aim:  To find out whether TB is a risk factor of COPD and to investigate any changes in COPD patients having TB infection compared to non TB cases.   Method:  Retrospective study of 328 pulmonary function test (PFT) diagnosed COPD cases was done. Data of 81 patients with clinical and radiological signs of COPD, multiple bullae on radiography without lung function measurements were also taken. Control cases are 414 patients who had done chest radiography from different departments besides respiratory unit.   Result:  Of 328 PFT diagnosed COPD patients, 141 had radiological feature of TB but only 32 of 414 control cases had those features. Odds ratio (OR) was 9 with 95% confidence interval (CI) [5.9-13.7]. Of 134 COPD cases with multiple bullae, 94 had TB infection, with OR=2.8, 95% CI [1.8-4.3]. Likewise TB infected COPD patients had lower FEV 1 /FVC (p=0.046) compared to non TB group. But in case of COPD patients having TB disease in past, diseased group had lower FEV 1 , FEV 1 /FVC and inspiratory capacity (p 0.046, 0.041, 0.014 respectively) compared to COPD patients without TB disease. Also TB infected COPD patients had lower serum albumin and iron, and higher high sensitive C reactive protein (hsCRP) (p 0.027, 0.035, 0.016 respectively).   Conclusion:  Pulmonary tuberculosis infection increases the risk of COPD and its coincidence with COPD results in more severe lung damage and greater inflammation (determined by increase in bullae formation, lower FEV 1  value and higher hsCRP level) with decrease in nutritional status.