tbuckley/cabot-search huggingface dataset:
Relief of Angina Pectoris by Electrical Stimulation of the Carotid-Sinus Nerves
Authors: Eugene Braunwald, Stephen E. Epstein, Gerald Glick, Andrew S. Wechsler, Nina S. Braunwald
Journal: New England Journal of Medicine (1967)

BECAUSE angina pectoris is a consequence of inadequate myocardial oxygenation, ideal therapy for this incapacitating symptom would be directed toward both increasing coronary blood flow and decreasing myocardial oxygen requirements. In the setting of severe coronary-artery disease, however, the ability of the coronary vascular bed to dilate is limited so that methods designed to decrease myocardial oxygen requirements may provide a more fruitful approach. Recent experimental studies have demonstrated that these oxygen requirements are directly related to the heart rate, to the inotropic state of the myocardium and to the intraventricular pressure, which is a reflection of the intramyocardial wall . . .
Abstract 1764: Horizontal and vertical signal pathway inhibition in human tumor primary culture micro-spheroids
Authors: Robert Alan Nagourney, Paula J. Bernard, Federico R. Francisco, Steven S. Evans
Journal: Cancer Research (2010)

Abstract Introduction: Signal transduction pathways are targets for small molecule tyrosine and serine-threonine kinase inhibitors. Redundancy and cross talk between pathways can complicate the application of genomic signatures but proteomic and functional platforms may more closely approximate tumor phenotypes. We used EVA/PCD (ex vivo analysis of programmed cell death), a functional platform measuring both apoptotic &amp; non-apoptotic events to examine the PI3K and EGFr pathways in human 1° culture micro-spheroids. Methods: 337 tumor specimens provided from the OR were mechanically and enzymatically disaggregated and exposed to EGFr (Gefitinib), AKT (B-15), PI3K (LY294002) &amp; mTOR (Rapamycin) inhibitors with LC50 values interpolated from 5-point dose response curves. Synergy was assessed by median effect and correlation coefficients by Pearson Moment. Results: Parallel Pearson Moment analyses in 51 specimens by 2-tailed T, revealed LY vs. B15 (NS); LY vs. Rapa (P&amp;lt;0.02); B15 vs. Rapa (P&amp;lt;0.0025); Rapa vs. Gefitinib (P &amp;lt;0.001). Synergy analyses for Rapa &amp; Gefitinib revealed synergy in 29%, additivity in 41%, sub-additivity in 13% and antagonism in 17%. Exploratory synergy analyses that combined Gefitinib &amp; LY and Gefitinib &amp; B-15, favored the Gefitinib&amp; B-15 combination with 100% synergy in this small series. Conclusions: EVA/PCD analyses provide insights into cellular response to targeted therapies, alone and in combination. Correlative analyses identify points of commonality and/or disparity in downstream signaling that can be exploited in drug development and therapy. Synergy analyses reveal potentially important drug combinations. The EVA/PCD human tumor micro-spheroid platform provides a functional tool capable of streamlining drug development and cancer therapy. Supported by The Vanguard Cancer Foundation and the Nagourney Institute. 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 1764.
Delay in Progression of Malignant Lymphoma after BCG Vaccination
Authors: Joseph E. Sokal, C. William Aungst, Michael Snyderman, Paul J. Sokal
Journal: New England Journal of Medicine (1974)

To determine the effect of BCG vaccination on the course of malignant lymphoma in remission, 50 patients with Stage IA or IIA, were randomly assigned in 1965–67 to serve as controls or to receive BCG vaccination. These patients had been staged and treated by technics associated with a 74 per cent relapse rate. Among the controls, 77 per cent relapsed within a follow-up period of six to eight years, with a mean time to the first new lesion of 10.6 months. Among the vaccinated patients, 61 per cent relapsed, with a mean time to the first new lesion of 25.9 months. The differences in relapse patterns were statistically significant, and could not be accounted for by differences in host, tumor or treatment characteristics. Clinical and immunologic data were consistent with the hypothesis that these differences were due to effects of BCG, operating over a period averaging about 2 1/2 years. (N Engl J Med 291:1226–1230, 1974)
AN AGE AND SEX-SPECIFIC PERIPHERAL BLOOD GENE EXPRESSION SCORE IS ASSOCIATED WITH ATHEROSCLEROTIC PLAQUE VOLUME BY CARDIAC CT-ANGIOGRAPHY: INSIGHTS FROM PREDICT AND COMPASS STUDIES
Authors: Sina Rahmani, Negin Nezarat, Rine Nakanishi, Indre Ceponiene, Suguru Matsumoto, Mitsuru Kanisawa, Anas Alani, Michael Kim, Reshma Sabnani, Michael Zapien, Mark Monane, Steven Rosenberg, James Wingrove, Matthew Budoff
Journal: Journal of the American College of Cardiology (2016)
Heterotopic Ossification of a Midline Abdominal Incision
Authors: Mandeep Singh Ghuman, Kavita Saggar
Journal: New England Journal of Medicine (2014)

A 49-year-old man presented for routine follow-up after a left nephrectomy performed 2 years earlier for renal-cell carcinoma. CT of the abdomen revealed a vertically oriented, linear, calcified lesion in the incision scar on the anterior abdominal wall.
Electrolyte-Balance Studies in Normal Volunteers and Clinical Observations on the Effects of Cation-Exchange Resins in Patients with Cardiovascular Disease and in Subjects Receiving Pituitary Adrenocortico-Trophic Hormone (ACTH)
Authors: Charles D. Bonner
Journal: New England Journal of Medicine (1952)

IN 1946 Dock1 suggested that cation-exchange resins might prevent sodium retention. Some of the properties attributed to these resins are consistently found, and meet with common agreement. There are fundamentally two types of cation-exchange resins: carboxylic resins and sulfonic resins functioning in the H+ and NH4 + cycles respectively. Included among the resins that have been studied are Amberlite XE–642, Amberlite XE–662, Amberlite IR–100H, Ionac C–200, Ionac C–284, Permutit XAC3, Dowex 50, Liquonex CRW, Nalcite, Duolite, and Win 3000. During resin therapy, there is a decrease in urinary Na+, K+, Ca++, and Mg++ and . . .
Case 23-1975
Authors: John A. Hardin, Robert T. McCluskey
Journal: New England Journal of Medicine (1975)

Presentation of CaseA 59-year-old woman was admitted to the hospital because of dyspnea.In her youth she had had multiple attacks of pneumonia. For many years she had been treated intermittently with iron because of anemia. Twenty years before admission a pruritic maculopapular rash developed on the upper extremities; it lasted for 10 years and was unrelieved by multiple local measures. Ten years before entry she began to experience dryness of the eyes and mouth. Five years later she entered another hospital because of pleuritic pain. Heparin was given, but she was discharged with no definite diagnosis and without . . .
RESTING HEART RATE IS AN INDEPENDENT PREDICTOR OF ALL-CAUSE MORTALITY AND MYOCARDIAL INFARCTION IN THE MIDDLE-AGED GENERAL POPULATION
Authors: Florian Custodis, Ulla Roggenbuck, Nils Lehmann, Susanne Moebus, Ulrich Laufs, Amir A. Mahabadi, Gerd Heusch, Klaus Mann, Karl-Heinz Jöckel, Raimund Erbel, Michael Böhm, Stefan Möhlenkamp
Journal: Journal of the American College of Cardiology (2015)
Idiopathic Pulmonary Fibrosis
Authors: WILLIAM W. DOUGLAS, JAY H. RYU, DARRELL R. SCHROEDER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The clinical records of 487 patients seen at Mayo Clinic Rochester (MCR) during 1994 through 1996 who were diagnosed as having idiopathic pulmonary fibrosis of the usual interstitial pneumonia type (IPF/UIP) were reviewed. Computed tomography (CT) had been done in 94.7% of patients and surgical open lung biopsy (OLB) in 20.3%. Median survival was 3.2 yr. We compared survival as a function of treatment program, based on intent to treat at the time of the initial contact within the study window. Treatment advised included colchicine alone in 167, no therapy in 157, prednisone at maintenance dosages alone in 54, colchicine plus prednisone in 71, and other programs in 38. Oxygen therapy was advised in 133 patients. By univariate analysis, worse survival was associated with prednisone therapy compared with no therapy, and with oxygen therapy compared with no oxygen therapy. However, on multivariate analysis, worse survival was associated with older age, male gender, lower diffusing capacity for carbon monoxide (Dl CO), lower alveolar volume (Va), and a history of worsening pulmonary function. When adjustment was made for these factors, there was no significant difference in survival between those patients treated with colchicine or prednisone and those on no therapy, and no difference between those on oxygen therapy and those without oxygen.
Imaging of Cutaneous Recurrence of Gastric Cancer with F-18 FDG Positron Emission Tomography
Authors: Martha Hoffmann, Georg Oberhuber, Kurt Kletter, Alexander Becherer, Markus Raderer
Journal: Clinical Nuclear Medicine (2002)

HOFFMANN, MARTHA M.D.; OBERHUBER, GEORG M.D.; KLETTER, KURT M.D., Ph.D.; BECHERER, ALEXANDER M.D.; RADERER, MARKUS M.D. Author Information
Primary Myocardial Lymphoma Demonstrated by Tl-201, Tc-99m Sestamibi, and Ga-67 SPECT
Authors: S Kosuda, S Kusano, F Ohsuzu
Journal: Clinical Nuclear Medicine (1998)

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P633Ranolazine reduces arrhythmogeneicity in transgenic mouse models of hypertrophic cardiomyopathy
Authors: L Mazzoni, C Ferrantini, R Coppini, L Sartiani, JM Pioner, B Tosi, V Bargelli, C Poggesi, A Mugelli, E Cerbai
Journal: Cardiovascular Research (2014)

Introduction: Ca2+ handling abnormalities are a main determinant of electro-mechanical dysfunction in human hypertrophic cardiomyopathy (HCM), leading to a pro-arrhythmogenic cellular phenotype. The late-Na+ current blocker ranolazine reduced the rate of arrhythmogenic events in HCM human myocardium via shortening of action potentials and reduction of intracellular Na+ and Ca2+, with increased forward NCX function (Circulation. 2013 Feb 5;127(5):575-84).
Abstract 1973: Caveolin-1 promotes cell proliferation, EGFR activation and tumor growth in kidney cancer
Authors: Chao Ying (Sarah) Xu, Yi Wang, Olga Roche, Eduardo Moriyama, Michael Ohh
Journal: Cancer Research (2011)

Abstract Tumor hypoxia is associated with disease progression, drug resistance and poor prognosis. It has been shown previously that hypoxia prolongs the activation of epidermal growth factor receptor (EGFR) by delaying clathrin-dependent endocytosis-mediated deactivation of receptors. Recently, caveolin (CAV) mediated signaling and trafficking have been reported to be involved in the oncogenesis of many tumours, including clear cell renal cell carcinoma (CCRCC). However, the role of CAV-1 in the tumor progression is unclear. Here, we show that the loss of von Hippel-Lindau (VHL) protein – the principal negative regulator of hypoxia-inducible factor (HIF) – increases the auto-phosphorylation of epidermal growth factor receptor (EGFR), thus attributing to an enhanced ligand-independent cell signaling pathway, majorly Ras-Raf-MEK-ERK pathway, and leading to cell proliferation. The auto-phosphorylation of EGFR is due to the HIF-dependent overexpression of caveolin-1 (CAV-1) at the level of transcription, which enhances the association between EGFR and CAV-1 and the auto-dimerization of EGFR. Primary CCRCC tumors and numerous hypoxia treated tumor cell lines exhibit significantly higher expression of CAV-1 protein. Using a dorsal skin-fold window chamber on SCID mice, shCAV-1 knockdown 786-O tumor cell line exhibits lower growth than that of shscramble counterpart in xenografts. These findings support a model in which tumour hypoxia or oncogenic activation of HIF prolongs ligand-independent RTK signaling through the over-expression of CAV-1. Given the oncogenic role of CAV-1, it should be considered as a future therapeutic target in cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1973. doi:10.1158/1538-7445.AM2011-1973
Deletion in the Gene for the Low-Density-Lipoprotein Receptor in a Majority of French Canadians with Familial Hypercholesterolemia
Authors: Helen H. Hobbs, Michael S. Brown, David W. Russell, Jean Davignon, Joseph L. Goldstein
Journal: New England Journal of Medicine (1987)

We found a large deletion (more than 10 kilobases) in the gene for the low-density-lipoprotein receptor in 63 percent of French Canadians with heterozygous familial hypercholesterolemia. The deletion also occurred in homozygous form in four of seven French Canadian homozygotes. The deletion removes the promoter and first exon of the gene, and it abolishes the production of messenger RNA for the low-density-lipoprotein receptor. The high frequency of this mutation is presumably related to a founder effect among the 8000 ancestors of present-day French Canadians, who have had relatively little cross-breeding with groups of other national origins. This deletion has not been observed in any other ethnic group. It can be detected by analysis of genomic DNA from blood leukocytes, thus allowing direct diagnosis of familial hypercholesterolemia in a majority of affected French Canadians.
PTU-135 Incidence of HP infection in children and the assessment of histological staining practice
Authors: Z M Mead, B Vadgama, R Mead, D Fowler, S Holden
Journal: Gut (2012)

<h3>Introduction</h3> The exact incidence of Helicobacter pylori (HP) in childhood is unknown. There is a causal link between HP and development of peptic ulcers, gastric adenocarcinoma and lymphoma. However there is little evidence and guidance on the clinical management of HP in children. The North American Society for Paediatric Gastroenterology and Nutrition report there is no compelling evidence to treat children colonised with HP without histological evidence of gastritis. This reflects the current pathophysiological understanding of cancer development, where inflammation secondary to infection is believed to be the driver of dysplasia and cancer. In our tertiary referral centre current practice stains all paediatric gastric biopsies with Haematoxylin and Eosin stain (H+E) as well as Warthin Starry (WS) stain, specifically for HP-like organisms. The aim of this study was to investigate the incidence of HP infection in children undergoing endoscopy. We also examined the routine use of special staining on all gastric biopsies for HP and whether other histological features on H+E examination could act as reliable markers of infection allowing selective special staining. <h3>Methods</h3> We reviewed all gastric biopsies submitted between January 8 and September 11, in patients born after 1989. All reports were loaded onto a database and searched for key words with “helico”, “HLO” and “<i>H Pylori</i>”. Each report was then examined for evidence of HP, acute inflammation and lymphoid aggregates. <h3>Results</h3> 1102 cases were examined and 23/1102 were positive for HP, 2% of all cases. There was acute inflammation in 17/23 cases. In the six with no acute inflammation, two were suspected of having HP (one previously treated) and one had only a single biopsy from the body, not the antrum. 146/1102 (13%) cases had acute inflammation. Acute inflammation as a marker for HP has a sensitivity of 74%, specificity of 88%, PPV of 11% and NPV of 99%. Lymphoid aggregates and acute inflammation as markers of infection further increased HP detection. <h3>Conclusion</h3> This study shows our current practice involves special staining of all biopsies for low prevalence disease (2%). However H+E examination alone has low sensitivity for picking up HP in cases of low density infection. Acute inflammation as a marker for HP infection could aid selection of cases for special staining. The NPV of 99% suggests that very few cases would be missed. Selective staining of cases for HP would also save around £3000/year (excluding pathologist time). The disadvantage that a small number of children colonised with HP, without gastritis may be missed is of unclear significance. Further research is required in order to develop an integrated clinical and pathological approach into the investigation, diagnosis and treatment of HP in children. <h3>Competing interests</h3> None declared.
Abstract 3344: Two different stem cell populations exist in breast cancer to control tumor initiation
Authors: Denise Grant, Jun Ma, Stewart Sell, Gennadi Glinsky
Journal: Cancer Research (2010)

Abstract The cancer stem cell theory states that a determinate number of cells within a tumor have unique, stem cell-like features to regenerate the entire tumor mass. However, a cancer stem cell may need the right microenvironment to have its greatest tumor initiation potential. We have documented the presence of two stem cell populations within a tumor to yield consistent and most aggressive recapitulation of tumor initiation in vivo. To isolate cancer stem cells, we used the MMTV-PyMT transgenic model of breast cancer in mice to generate stable cell lines from spontaneous breast tumors. Stable in vitro cultures of FACS analyzed cancer stem cells and tumor-residing mesenchymal stem cells were established and tested for tumor initiating ability using two methods of implantation: subcutaneous (s.c.) injection and cleared mammary fat pad (CMFP) injection. To determine the limit of tumor initiation, a highly malignant cancer stem cell culture (419) was injected s.c. This cell culture produced tumors with 1×104, 1×103, and 1×102 cells with 100%, 93%, and 33% tumorigenicity, respectively. In comparison, 100% tumorigenicity was obtained with 1×102 419 cells implanted in the CMFP, a significant increase compared to s.c. injection (Chi-squared, p&amp;lt;0.001). S.c. injection of a less malignant cancer stem cell culture (145) produced tumors less efficiently, with 100% tumorigenicity with 1×104 cells but 13% tumorigenicity with 1×103 cells. To increase tumorigenicity at low cell numbers, cancer stem cell cultures were combined with tumor-residing mesenchymal stem cells just prior to injection. Cancer stem cell cultures were s.c. injected with 1×105 tumor-residing mesenchymal stem cells (383) at the tumor limiting dose, 1×101 for 419 and 1×103 for 145; tumorigenicity increased 160% in the highly malignant cells (419) and 133% in the less malignant cells (145). The tumor-residing mesenchymal stem cells increased tumorigenicity significantly compared to cancer stem cell injection alone (Chi-squared, p&amp;lt;0.002). Control experiments using non-tumorigenic mesenchymal cells did not produce any increase in tumorigenicity. Genome-wide expression profiling experiments were carried out to demonstrate the clinical relevance of the varying malignancy settings in the cancer stem cell and tumor-residing mesenchymal stem cell cultures. Our results suggest that the cellular composition of the local microenvironment within the breast tumors is the major determinant of efficiency of tumor initiation. The addition of tumor-residing mesenchymal stem cells markedly increases the tumor initiation potential of breast cancer stem cells. 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 3344.
ES1-3: Treatment of Metastatic Breast Cancer – Breast Cancer as a Chronic Disease: Triple Negative Breast Cancer.
Authors: V Stearns
Journal: Cancer Research (2011)

Abstract Carcinomas of the breast that do not express the estrogen or progesterone receptors (ER/PR) and are not associated with over-expression or amplification of HER2/neu have been designated triple negative breast cancer. These tumors represent approximately 15–20% of all breast cancers, but are more prevalent in younger women, in African Americans, and in BRCA1 mutation carriers. Molecular profiling data suggest that many of triple negative tumors, but not all, are basal-like. The basal-like tumors are more likely to be resistant to standard therapies resulting in disease recurrence and poor prognosis. It is likely that triple negative breast cancer will be further sub classified to several additional distinct subtypes. Regardless of additional sub classification of the entity, the only treatment currently available for women with triple negative breast cancer is chemotherapy-based. In this symposium, I will review current molecular classification, prognosis and predictive markers, treatment options, emerging approaches, and clinical trials. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES1-3.
Unusual Hepatic Visualization After Esophageal Scintigraphy
Authors: Venanzio Valenza, Francesca Reale, Venanzio Porziella, Michele Marchese, Pierluigi Granone, Giovanni D'Errico
Journal: Clinical Nuclear Medicine (2002)

VALENZA, VENANZIO M.D.†; REALE, FRANCESCA M.D.†; PORZIELLA, VENANZIO M.D.*; MARCHESE, MICHELE M.D.*; GRANONE, PIERLUIGI M.D.*; D’ERRICO, and GIOVANNI M.D.† Author Information