tbuckley/cabot-search huggingface dataset:
Abstract 4240: Targeting Galectin-3 to reverse tumor stemness and drug resistance
Authors: Shumei Kato, Laetitia Seguin, Aleksandra Franovic, Hisashi Kato, Maria Camargo, Jay Desgrosellier, Sudarshan Anand, Sara Weis, Sanford Shattil, David A. Cheresh
Journal: Cancer Research (2014)

Abstract We have recently linked integrin αvβ3 expression to metastatic potential, stemness, and therapy resistance due to its capacity to couple to KRAS. This leads to the induction of RalB/TBK-1 and the activation of NFκB to shift tumor cells to a stem-like phenotype. To understand how integrin αvβ3 couples to KRAS, we generated β3 domain swap mutants containing either the intracellular or extracellular domains of β1 integrin. Each chimera partially reduced KRAS association with αvβ3, suggesting interactions on each side of the plasma membrane may contribute. Since the short β3 cytoplasmic tail has no putative KRAS binding regions, we considered Galectin-3 as a putative scaffolding partner to facilitate the αvβ3/KRAS association due to its reported binding to both KRAS and integrins. Indeed, treating cells with GCS-100, a complex polysaccharide that has the ability to bind to and block the effects of Galectin-3, decreased Galectin-3 surface expression, αvβ3 clustering, and αvβ3/KRAS association. Exposing cells to this drug also decreased tumor stem properties. Our observations provide a molecular basis for the αvβ3/KRAS/Galectin-3 complex and highlight the potential for Galectin-3 blockade as a therapeutic approach to reverse the aggressive behavior of αvβ3-expressing tumors. Citation Format: Shumei Kato, Laetitia Seguin, Aleksandra Franovic, Hisashi Kato, Maria Camargo, Jay Desgrosellier, Sudarshan Anand, Sara Weis, Sanford Shattil, David A. Cheresh. Targeting Galectin-3 to reverse tumor stemness and drug resistance. [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 4240. doi:10.1158/1538-7445.AM2014-4240
Abstract 18541: Gastric Bypass Surgery is Associated with a Marked Reduction in Circulating High Sensitivity Cardiac Troponin I Concentrations: Comparison with Intensive Lifestyle Intervention
Authors: Magnus N Lyngbakken, Torbjørn Omland, Njord Nordstrand, Jon Norseth, Jøran Hjelmesæth, Dag Hofsø
Journal: Circulation (2014)

Introduction: Morbid obesity is associated with increased cardiac mass and cardiovascular risk. Circulating high sensitivity cardiac troponin I (hs-TnI) concentrations reflect cardiac mass and hemodynamic stress and are strongly predictive of subsequent risk of heart failure and premature death. The impact of weight loss induced by gastric bypass surgery (GBS) and intensive lifestyle intervention (ILI) on circulating hs-TnI is unknown. Hypothesis: Weight loss induced by GBS and ILI is associated with reduced circulating hs-TnI concentrations. Methods: The Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention study was a controlled clinical trial conducted from December 2005 to June 2009 at the Morbid Obesity Centre, Vestfold Hospital Trust, Tønsberg, Norway. A group of 139 morbidly obese subjects were treated either with GBS or ILI. Biochemical and clinical indices of cardiovascular and metabolic health were assessed at baseline and after 12 months of follow-up. Blood samples for hs-TnI analyses were available from 136 participants (94 female), out of whom 74 received GBS. Results: At baseline median hs-TnI levels were 2.35 (1.38-4.40) ng/L in the ILI group and 2.40 (1.28-3.95) ng/L in the GBS group (ns). After 12 months of follow-up, hs-TnI had decreased significantly more in the GBS group than in the ILI group (1.10 ng/L vs. 0.20 ng/L; p=0.002) (see Figure). Variables associated with the change in hs-TnI concentrations by univariate analyses included intervention group (p=0.002), changes in body mass index (p=0.002), body weight (p=0.003), waist circumference (p=0.04), serum total cholesterol (p=0.009), serum triglycerides (p=0.002) and HbA1c (p=0.017). Conclusions: In patients with morbid obesity, GBS was associated with a significantly greater reduction in hs-TnI than ILI, suggesting that bariatric surgery and/or large weight loss unloads the stressed heart and may lead to reduced cardiac mass and hemodynamic stress.
Acute cigarette smoke induces accelerated emphysema development in bENaC-overexpressed mice
Authors: Jie Jia, Lisa Merthan, Marcus A. Mall, Oliver Eickelberg, Ali Önder Yildirim
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodeling and emphysema. As a hallmark of COPD, mucus accumulation may result in airway hypersensitivity and small airway obstruction. Accelerated b-Epithelial Na +  channel (bENaC) in the lower airway epithelial membrane of mice leads to airway surface liquid depletion and mucocilia clearance dysfunction, which causes mucus accumulation and further, COPD like disease(Mall, M.A. A.M.J.Respir, 2008). However, it remains unclear how increased mucus production contributes to emphysema and COPD development.  10 day old bENaC mice and litter mate controls were exposed to filtered air or cigarette smoke, for 50min twice daily, 4 days at a particle concentration of 500mg/m 3 . On the 5th day lung function and cytospin from Bronco Alveolar Lavage (BAL) fluid was performed. HE0.01) and increased airspace enlargement compared to WT animals. Interestingly, emphysema development was associated with increased macrophage and neutrophil cell number in BAL fluids.  Our data demonstrate that the spontaneous development of emphysema ccompanied with the accumulation of mucus in the airways of bENaC transgenic mice results in airway hypersensitivity, and a severer inflammatory response following cigarette smoke exposure that may contribute to an accelerated COPD pathogenesis.
Pathophysiology and therapy of pruritus in allergic and atopic diseases
Authors: J. Buddenkotte, M. Steinhoff
Journal: Allergy (2010)

Pruritus (itch) is a major characteristic and one of the most debilitating symptoms in allergic and atopic diseases and the diagnostic hallmark of atopic dermatitis. Pruritus is regularly defined as an unpleasant sensation provoking the desire to scratch. Although we achieved rather good knowledge about certain inducers of itch such as neuropeptides, amines, mu-opioids, cytokines and proteases, for example, less is known about the pathophysiological specifities among the different diseases, and the therapeutic consequences which may derive thereoff. This review dissects the role of mediators, receptors and itch inhibitors on peripheral nerve endings, dorsal root ganglia, the spinal cord and the CNS leading to the amplification or - vice versa - suppression of pruritus. As the treatment of pruritus in allergic and atopic skin disease is still not satisfactory, knowing these pathways and mechanisms may lead to novel therapeutic approaches against this frequently encountered skin symptom.
EXCESSIVE SMOKING AS A POSSIBLE PRECIPITATING FACTOR IN DIABETIC GANGRENE; WITH A CASE REPORT
Authors: Harry Blotner
Journal: Annals of Internal Medicine (1936)

Case Reports1 January 1936EXCESSIVE SMOKING AS A POSSIBLE PRECIPITATING FACTOR IN DIABETIC GANGRENE; WITH A CASE REPORTHARRY BLOTNER, M.D.HARRY BLOTNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-7-987 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTobacco smoking became of interest to me as a result of the work by Wright and Moffat1who found that smoking produced in the great majority of normal individuals a marked drop in the surface temperature at the tips of the fingers and toes, and frequently a slowing and stoppage of the blood flow in the capillaries of the nail fold. Shortly after their paper was published I saw a young man with diabetic gangrene who gave a long history of smoking a great many cigarettes each day. The case of this man is recorded to suggest that excessive smoking...Reference1. WRIGHTMOFFAT ISD: The effects of tobacco on the peripheral vascular system, Jr. Am. Med. Assoc., 1934, ciii, 318. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication June 20, 1935.From the Medical Clinic of the Peter Bent Brigham Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1936Volume 9, Issue 7Page: 987-991KeywordsBlood flowCapillariesHospitalsTemperature ePublished: 1 December 2008 Issue Published: 1 January 1936 PDF downloadLoading ...
Abstract P182: Glycaemic Index and Glycaemic Load of East Asian foods: The INTERMAP Study
Authors: Li Yan, Queenie Chan, Ghadeer Aljuraiban, Linda M Oude Griep, Ioanna Tzoulaki, Jeremiah Stamler, Linda Van Horn, Martha L Daviglus, Martha L Daviglus, Katsuyuki Miura, Hirotsugu Ueshima, Liancheng Zhao, Gary Frost, Paul Elliott
Journal: Circulation (2014)

Background: According to recent national health surveys (2010-2013), diabetes mellitus (DM) is more prevalent in East Asian populations (11.6% in China, 11.3% in Japan) compared with Western populations (4.5% in UK and 8.3% in US), even though body weight and body mass index (BMI) are much lower in East Asian populations (mean ≈ 22-23 kg/m2 in China/Japan vs. ≈ 27-28 kg/m2 in UK/US, WHO 2008 report). Consumption of total available carbohydrate (CHO) (%kcal) in Eastern countries is higher than in Western countries. The patterns of CHO intake, dietary glycaemic Index (GI)/glycaemic Load (GL), may be important in accounting for these differences and their metabolic effects. Data on GI/GL of Asian foods are, however, limited. Objectives: To develop systematic methodology for assigning GI values to East Asian foods, and to identify East Asian foods contributing most to total GL, using data from the International Collaborative Study on Macro-/Micronutrients and Blood Pressure (INTERMAP). Methods: The INTERMAP Study is a cross-sectional epidemiologic investigation with standardized quality-controlled methods; it accrued four in-depth 24-hour dietary recalls, 2 timed 24-hour urine collections, 8 BP measurements and questionnaire data. National and International GI databases were used to develop a standardized algorithm for assigning GI values to the INTERMAP data on East Asian foods. “GL contribution of a food”, defined as the GI value of this food multiplied by total amount of available CHO contained in this food as consumed on average by all participants, was used to estimate total influence of each food on blood glucose, including absolute levels and relative percentages. Results: GI values of total of 2,928 East Asian individual food codes (2,030 Japanese food codes and 898 Chinese food codes) were assigned using this newly developed algorithm. Foods assigned with GI&gt;0 using this algorithm contributed 92% (Japan) and 98% (China) of total CHO intake per day. Among Japanese foods, high GI foods were sweet red bean paste (Monaka, GI=91), rice cookie (GI=91), and rice cracker (GI=91). Among Chinese foods, high GI foods were flour and flour products (e.g., Mantou, steamed bread, fried dough sticks, and noodles, GI=88) and glutinous rice (GI=87). Foods contributing most to GL in Japan were white rice (54%), white bread (5%), sugar, syrup and preserves (3%); for Chinese foods: flour and flour products (25%), white rice (21%), and baked products (10%). Conclusion: With the algorithm we developed, it was feasible to assign GI values to East Asian foods. The composition of top GL contributors is different between China and Japan.
Management of Heart Failure After Cardiac Resynchronization Therapy
Authors: Juan M. Aranda, Gregory W. Woo, Richard S. Schofield, Eileen M. Handberg, James A. Hill, Anne B. Curtis, Samuel F. Sears, J. Sean Goff, Daniel F. Pauly, Jamie B. Conti
Journal: Journal of the American College of Cardiology (2005)
Essential Medicines: 25 Years of Better Health
Authors: Gro Harlem Brundtland
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract P2-06-06: Mammospheres derived from circulating epithelial tumor cells are an indicator for presence of metastasis in patient with breast cancer
Authors: Monika Pizon, Dorothea Zimon, Ulrich Pachmann, Katharina Pachmann
Journal: Cancer Research (2015)

Abstract Background: A major obstacle in the successful treatment of cancer is the occurrence of metastasis. The presence of CETCs is closely related to tumor recurrence, but the mechanisms through which CETCs promote metastasis are still unclear. The aim of this study was to determine the proliferative capacity of CETCs by analyzing the frequency of mammosphere formation with subsequent phenotypic characterization of the spheres arising in breast cancer patients. Methods: CETCs were cultured under condition favoring growth of mammospheres from 38 patients with breast cancer, including a subpopulation of 13 patients with metastatic disease. Cell viability, stem cell marker expression and ALDH 1 activity was evaluated by fluorescence scanning microscope (Olympus Scan®R). Results: Sphere formation was observed in 74 % of patients with breast cancer. Patients with distant metastasis had higher numbers of mammospheres (median 13,0 vs 1,0; p≤0,001) compared to patients without metastasis. In multivariate analysis, a high number of mammospheres was associated with the presence of metastasis. The mammospheres area under the ROC curve was 0,99. Six or more spheres classified metastatic disease with a sensitivity and specificity of 96 % and 100 %, respectively. These results suggest that above cut-off six in the number of mammospheres is statistically highly indicator for disease progression. Analysis of surface marker expression profile of mammospheres showed that spheres cultured from CETCs had typical phenotype of cancer stem cells with a high enzymatic activity for ALDH 1 with the ALDEFLUOR assay. There was no sphere formation in a control group with 50 healthy donors. Conclusion This study demonstrates that a small fraction of CETCs has proliferative activity. Identifying the CETC subset with cancer stem cells properties may provide more clinically useful prognostic information and may be a new indicator for the presence of metastases. Citation Format: Monika Pizon, Dorothea Zimon, Ulrich Pachmann, Katharina Pachmann. Mammospheres derived from circulating epithelial tumor cells are an indicator for presence of metastasis in patient with breast cancer [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 P2-06-06.
Abstract 15546: Loss of Mitochondrial UCP3-Cytochrome c Oxidase Complexes Underlies Maladaptive Autophagy and Cardiac Failure in Anthracycline Cardiotoxicity
Authors: Rimpy Dhingra, Victoria Margulets, Davindar Jassal, Gerald Dorn, Lorrie A Kirshenbaum
Journal: Circulation (2014)

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure. Herein we demonstrate a novel signaling pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to doxorubicin cardiotoxicity. Perturbations to mitochondria including increased calcium, ROS, loss of αΨm and mPTP opening were observed in cardiac myocytes treated with doxorubicin. This coincided with a decline in maximal respiratory capacity, loss of respiratory chain complexes of uncoupling protein 3 (UCP3) and cytochrome c oxidase complex IV subunit 1, (COX) and cell viability. Impaired mitochondrial function was accompanied by an accumulated increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Interestingly, pharmacological or genetic inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-down suppressed necrotic cell death induced by doxorubicin. Conversely, loss of function of Bnip3 or mutations of Bnip3 defective for mitochondrial targeting restored UCP3-COX complexes, mitochondrial respiratory integrity and suppressed necrotic cell death induced by doxorubicin. Finally, mice germ-line deficient for Bnip3 were resistant to the cytotoxic effects of doxorubicin displaying mitochondrial morphology, cardiac function and survival rates comparable to vehicle treated control mice. To our knowledge the findings of the present study provide the first direct evidence that doxorubicin triggers maladaptive autophagy and necrotic cell death of ventricular myocytes by a mechanism mutually dependent and obligatorily linked to Bnip3. Hence, therapeutic interventions to selectively inhibit Bnip3 may prove beneficial in suppressing mitochondrial injury and heart failure in cancer patients undergoing doxorubicin treatment.
ACUTE HEMOLYTIC ANEMIA, HEMOGLOBINURIA AND UREMIA FOLLOWING SULFANILAMIDE
Authors: Gordon B. Myers, Jack Rom
Journal: Annals of Internal Medicine (1940)

Case Reports1 July 1940ACUTE HEMOLYTIC ANEMIA, HEMOGLOBINURIA AND UREMIA FOLLOWING SULFANILAMIDEGORDON B. MYERS, M.D., F.A.C.P., JACK ROM, M.D.GORDON B. MYERS, M.D., F.A.C.P.Search for more papers by this author, JACK ROM, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-1-164 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhile acute hemolytic anemia is a fairly common complication of sulfanilamide therapy and has been carefully studied by numerous workers,1, 2, 3massive hemoglobinuria is relatively rare and has received little attention. Among 21 cases of sulfanilamide hemolytic anemia reported by Wood,3free hemoglobin was found in the urine in only one instance. Bohlman,4in discussing the toxic manifestations of sulfanilamide, referred to a personal communication from Janeway, who had had one case with hemolytic anemia, hemoglobinuria and uremia. In five other cases of sulfanilamide hemolytic anemia, reported in three different papers,5, 6, 7hemoglobinuria was noted as an incidental...Bibliography1. HARVEYJANEWAY AMCA: Development of acute hemolytic anemia during administration of sulfanilamide, Jr. Am. Med. Assoc., 1937, cix, 12. CrossrefGoogle Scholar2. LONGBLISSFEINSTONE PHEAWH: Mode of action, clinical use and toxic action of sulfanilamide, Jr. Am. Med. Assoc., 1939, cxii, 115. CrossrefGoogle Scholar3. WOOD WB: Jr. Am. Med. Assoc., 1938, cxi, 1916. CrossrefGoogle Scholar4. BOHLMAN HR: Use of sulfanilamide, Dis. of Chest, 1937, iii, 24. CrossrefGoogle Scholar5. KOHN SE: Acute hemolytic anemia during treatment with sulfanilamide, Jr. Am. Med. Assoc., 1937, cix, 1005. CrossrefGoogle Scholar6. ANTOPOLAPPLEBAUMGOLDMAN WIL: Two cases of acute hemolytic anemia with auto-agglutination following sulfanilamide therapy, Jr. Am. Med. Assoc., 1939, cxiii, 488. CrossrefGoogle Scholar7. STRESSERSINGER AK: Über Prontosil-Haemoglobinurie und andere Sulfanilamid-Blutschädigungen, Med. Klin., 1938, xxxiv, 783. Google Scholar8. DEGOWINWARNERRANDALL ELEDWL: Renal insufficiency from blood transfusion, Arch. Int. Med., 1938, lxi, 609. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan*Received for publication December 7, 1939.From the Medical Department of Wayne University College of Medicine and City of Detroit Receiving Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrugs, Chemicals and HemolysisRenal Damage Following Intravascular Hemolysis 1 July 1940Volume 14, Issue 1Page: 164-168KeywordsHemoglobinHemolytic anemiaHospital medicineRisk managementUrine ePublished: 1 December 2008 Issue Published: 1 July 1940 PDF downloadLoading ...
US federally funded groups will be allowed to promote abortion
Authors: Rhona MacDonald
Journal: BMJ (2000)

Last week the Congressional Republicans in the United States agreed to remove the legal restrictions preventing private family planning groups that receive federal funds from using their own money to provide abortions or promote abortion rights (the so-called “gag rule”). Any group that had refused to adhere to this policy could only receive American aid if it obtained a waiver from the president.

The gag rule was first imposed …