tbuckley/cabot-search huggingface dataset:
Abstract 4826: Mobilization of tumor cells into the circulation during radiation therapy for lung cancer
Authors: Michael MacManus, Robin Anderson, Prudence Russell, Ashley Cox, Agnieszka Swierczak, Judy P. Doherty, Daphne Jacobs, Jai Smith, Shankar Siva, Patricia E. Daly, David L. Ball, Roger F. Martin, Olga A. Martin
Journal: Cancer Research (2014)

Abstract Thousands of patients die annually with distant metastasis after curative-intent or “radical” radiation therapy (RT). Because non-small cell lung cancer (NSCLC), the most common cause of cancer-related mortality, exhibits an especially high rate of distant metastasis after radical RT or chemo-RT for locoregionally-advanced disease, it represents a suitable model to investigate the relationship between RT and metastasis. We hypothesized that disruption of tumour architecture during RT could result in the release of viable tumor cells into the peripheral circulation. We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated sorting (FACS) or by immunofluorescence microscopy. Twenty seven RT-treated NSCLC patients had blood samples analyzed by one or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. CTCs were also identified, singly and in clumps in large numbers during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied), and first experiments revealed that these cells survive in bloodstream of NOD/SCID mice for several months. CTCs formed γ-H2AX foci in response to ex vivo irradiation providing further evidence of their viability. Although of concern, these findings could represent an opportunity to monitor and target CTCs during RT. They provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by co-administering systemic therapies. Citation Format: Michael MacManus, Robin Anderson, Prudence Russell, Ashley Cox, Agnieszka Swierczak, Judy P. Doherty, Daphne Jacobs, Jai Smith, Shankar Siva, Patricia E. Daly, David L. Ball, Roger F. Martin, Olga A. Martin. Mobilization of tumor cells into the circulation during radiation therapy for lung cancer. [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 4826. doi:10.1158/1538-7445.AM2014-4826
852 B-LYMPHOCYTE STIMULATOR (BLys) AND HCV GENOTYPE OR IL28B SNPs FOR PREDICTION OF RAPID VIROLOGIC RESPONSE IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: J. Liu, Z.-B. Wu, Z.-S. Mo, Q.-X. Cai, X. Zhu, Z.-L. Gao
Journal: Journal of Hepatology (2013)
Chronic diabetes mellitus prolongs action potential duration of rat ventricular muscles: circumstantial evidence for impaired Ca2+ channel
Authors: S. Nobe, M. Aomine, M. Arita, S. Ito, R. Takaki
Journal: Cardiovascular Research (1990)

Study objective – The aim of the study was to investigate the effects of chronic diabetes mellitus on electromechanical properties of ventricular papillary muscles. Design – Conventional glass microelectrodes and tension recording techniques were used in isolated hearts of rats made diabetic for 30-40 weeks by single intravenous injections of streptozotocin. Subjects – Experimental animals were male Wistar rats of 200-250 g. Diabetic rats (n = 14) were given streptozotocin 65 mg·kg−1; controls (n = 15) were given vehicle only. Measurements and main results – (1) The maximum upstroke velocity of the action potential duration of diabetic muscles was decreased compared to control, with no difference in the resting potential. (2) At all stimulation frequencies (0.2, 1 and 5 Hz), and particularly the lower ones, the action potential duration of diabetic muscles was longer than control. (3) In diabetic muscles, frequency dependent shortening of the late phase of action potential duration (APD75, APD90) was more pronounced, and frequency dependent lengthening of the early phase (APD25, APD50) was less pronounced. (4) A blocker of transient outward current, 4-aminopyridine, lengthened the early phase of action potential durations by the same amount in diabetic and control muscles. (5) A Ca2+ channel blocker, CoCl2, dramatically shortened all levels of action potential duration, with much greater effect on diabetic muscles. (6) Ryanodine lengthened the early phase of action potential duration and shortened the late phase in both diabetic and control muscles. It enhanced the difference between the groups in the early phase. (7) Developed tension in the presence of ryanodine (ryanodine resistant tension component) was greater in diabetic muscles than in control. Conclusions – The findings suggest that altered Ca2+ current, but not altered Na+-Ca2+ exchange current or altered transient outward current, significantly prolongs action potential duration in diabetic rat ventricular muscles.
Atopic diseases by filaggrin mutations and birth year
Authors: J. P. Thyssen, A. Linneberg, J. D. Johansen, B. C. Carlsen, C. Zachariae, M. Meldgaard, P. B. Szecsi, S. Stender, T. Menné
Journal: Allergy (2012)

The prevalence of atopic disorders has increased in recent years. The pathogenesis is complex with genetic and environmental risk factors. Filaggrin loss-of-function mutations are common and associated with atopic disorders. We investigated whether the prevalence of filaggrin mutations increased in different birth cohorts in adults from the general population in Denmark.Cross-sectional questionnaire and filaggrin gene mutation (R501X and 2282del4) data from 3335 18- to 69-year-old adults were available for analyses.The effect of filaggrin mutations on the prevalence of atopic diseases, albeit not statistically significant, depended mostly on birth year for atopic dermatitis (AD). A nonsignificant increase in the prevalence of filaggrin mutations was noted across birth year groups reporting AD, with 12.9% in adults born in 1936-1949 and 19.0% born in 1976-1988.If confirmed in other populations, the observed increase suggests that mutation carriers have been more susceptible to environmental changes accentuating the rise in AD prevalence.
Current Interpretation of the Sodium Iodohippurate I131 Renocystogram
Authors: Earl K. Dore
Journal: JAMA (1963)

New terminology for the renogram's three segments is recommended, namely, tracer appearance, blood flow, and drainage, to replace the original terms, vascular, tubular, and excretion. The first, or tracer appearance segment, is no longer considered a useful index of renal vascular capacity because activity of blood within the kidney contributes in only a minor way to the height of the first segment. The slope of the second segment is an index of renal blood flow because tracer is retained in the kidney during this time and the extraction efficiency of the kidney for tracer quantities of sodium iodohippurate is approximately 92%. The third segment indicates the state of mechanical drainage from the kidney. The term "renal transit time" is added as another parameter of the renocystogram and provides an index of individual urine flow and has special significance in hypertension due to renal artery occlusive disease.
A Behavioral Framework for the Study of Human Disease
Authors: HORACIO FABREGA
Journal: Annals of Internal Medicine (1976)

A frame of reference for studying human disease is presented. An individual's social behavior serves as the orienting theme. Special forms of social behavior are in effect what tie an individual to his physical and social space, and alterations here can lead to disease. Causes of disease can thus be linked to behaviors of the individual. Although associated with basic changes in the psysiologies and chemistries of the individual, disease invariably comes to affect the individual's behavior and adaptation. Different ways in which such behavioral changes can be conceptualized are discussed. The individual relies on these behavioral changes as the data for evaluating his disease and deciding about medical treatment. A model of how an individual processes information about illness and makes decisions designed to alleviate his condition is presented. Finally, the rationale and value of keeping behavior and adaptation in mind when studying disease are discussed.
Antinuclear antibodies in the relatives of patients with systemic sclerosis
Authors: K. TAKEHARA, Y. MOROI, Y. ISHIBASHI
Journal: British Journal of Dermatology (1985)

Antinuclear antibodies were studied by indirect immunofluorescence and double immunodiffusion in 21 patients with systemic sclerosis and 35 of their relatives. When HEp-2 cells were used as the substrate, the frequency of antinuclear antibodies in the patients' sera was 100% and that in the relatives was 26%. When rat liver sections were used, the values were 86% and 17%, respectively. Anticentromere antibody was detected in the serum from the mother of one patient whose serum had anti-Scl-70 antibody. Antibody to n-RNP was positive in the sera from the brother and daughter of another patient whose serum was positive for anti-n-RNP and anti-Scl-70 antibodies. The high frequency of antinuclear antibodies in the sera from the relatives of systemic sclerosis patients suggests that immunological abnormalities play a part in the pathogenesis of this condition.
LECTURES ON INTRACRANIAL SURGERY.III—REMOVAL OF THE GASSERIAN GANGLION.
Authors: EMORY LANPHEAR
Journal: JAMA (1895)

Tic douloureux (prosopalgia, epileptiform neuralgia or Fothergill's neuralgia) usually is due to some disease of the trigeminal nerve in front of the ganglion of Gasser—frequently a low grade of neuritis, sometimes an atrophic process dependent upon an obliterative endarteritis of the vessels supplying thenerves. Occasionally the disease may be traced to trouble in the alveolus, when it can be easily remedied; but commonly no local cause can be discovered, internal medication proves useless and life becomes a burden to the sufferer. Under such circumstances, removal of the ganglion is justifiable. Three methods of reaching the ganglion have been proposed: Opening the middle fossa through the temporal region; Ablation of the superior maxilla and trephining the base of the skull; Entering the cranium through the pterygoid region. Before discussing these methods it is well to recall the anatomic relations of the ganglion. The fifth or trifacial nerve arises
Enteroscopic Cyanoacrylate Sclerotherapy of Jejunal and Gallbladder Varices in a Patient with Portal Hypertension
Authors: S. Getzlaff, C.A. Benz, D. Schilling, J.F. Riemann
Journal: Endoscopy (2001)

Bleeding from varices outside the gastroesophageal region is a rare, but regularly reported complication of portal hypertension. The treatment differs from the management of esophageal and gastric varices. We present here a report on the diagnosis and treatment of bleeding jejunal and gallbladder varices in a man with portal hypertension caused by chronic calcifying pancreatitis. The patient was suffering from recurrent, frequent, and massive gastrointestinal bleeding from varices at the anastomotic area of a cholecystojejunostomy. For diagnostic purposes, we carried out percutaneous Duplex ultrasonography and push enteroscopy with the Doppler technique.
Abstract 526: Combined inhibition of mTOR and AKT activity induces potent apoptosis in epithelial ovarian cancer cells .
Authors: Azhar R. Hussain, Shahab Uddin, Maqbool Ahmed, Khawla S. Al-Kuraya
Journal: Cancer Research (2013)

Abstract Mammalian target of rapamycin (mTOR) and Phosphatidylinositol 3-kinase (PI3K) are two key components of the PI3K/Akt/mTOR signaling pathway. These two signal transduction cascades regulate a number of physiological cell functions including differentiation, proliferation, apoptosis and autophagy. Dysregulation of these pathways have been found in many cancers including DLBCL, thyroid cancer, breast cancer, prostate cancer and lung cancer. mTOR has been shown to activate the PI3-kinase/AKT survival pathway and understanding the interplay among signaling molecules in the PI3K/Akt/mTOR pathway is of utmost importance. Two distinct mTOR complexes; mTORC1 and mTORC2, have been identified. mTORC1 is downstream of Akt, sensitive to rapamycin inhibition, and controls cap-dependent protein translation. In contrast, mTORC2 is directly upstream of Akt and is resistant to rapamycin. In this study, we investigated the effect of mTOR inhibition on cell viability and induction of apoptosis in epithelial ovarian cancer (EOC) cells, either alone or in combination with PI3-kinase/AKT inhibitor. We found that Torin2, an mTOR inhibitor, decreased cell viability and induced apoptosis in EOC cell lines in a dose dependent manner. Torin2 also inactivated mTOR1 and mTOR2 as well as downstream targets of mTOR; 4E-BP1 and p70S6. Torin2 treatment of EOC cell lines also induced mitochondrial dependent apoptosis via activation and cleavage of caspases. Finally, combination treatment of EOC cells with Torin2 and LY294002, a PI3-kinase/AKT inhibitor induced a synergistic apoptotic response via inactivation of AKT, mTOR1 and mTOR2 and activation of caspases. These studies will give us an insight on the molecular relationship between these survival pathways and suggest that simultaneous inhibition of mTOR and PI3-kinase/AKT pathways may be beneficial for the management of EOC. Citation Format: Azhar R. Hussain, Shahab Uddin, Maqbool Ahmed, Khawla S. Al-Kuraya. Combined inhibition of mTOR and AKT activity induces potent apoptosis in epithelial ovarian cancer cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 526. doi:10.1158/1538-7445.AM2013-526
Warfarin or Not Warfarin?
Authors: Margaret C. Fang, Daniel E. Singer
Journal: Annals of Internal Medicine (2005)

Letters19 April 2005Warfarin or Not Warfarin?Margaret C. Fang, MD, MPH and Daniel E. Singer, MDMargaret C. Fang, MD, MPHFrom University of California, San Francisco, San Francisco, CA 94143, and Massachusetts General Hospital, Boston, MA 02114.Search for more papers by this author and Daniel E. Singer, MDFrom University of California, San Francisco, San Francisco, CA 94143, and Massachusetts General Hospital, Boston, MA 02114.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-142-8-200504190-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:High-quality randomized trials demonstrate that warfarin therapy dramatically reduces the risk for ischemic stroke associated with atrial fibrillation (1). These trials and observational studies also indicate that the benefit of anticoagulation is markedly reduced at INRs lower than 2.0 (2). Our study showed that the risk for intracranial hemorrhage increases with age and with INRs above 3.5. However, patients receiving anticoagulation did not have a reduced risk for intracranial hemorrhage at INRs less than 2.0. Thus, it appears that maintaining the INR in the 2.0 to 3.0 range maximizes the benefits of warfarin while minimizing the risks.Unfortunately, ...References1. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized, controlled trials. Arch Intern Med. 1994;154:1449-57. [PMID: 8018000] CrossrefMedlineGoogle Scholar2. Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med. 1996;335:540-6. [PMID: 8678931] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Margaret C. Fang, MD, MPH; Daniel E. Singer, MDAffiliations: From University of California, San Francisco, San Francisco, CA 94143, and Massachusetts General Hospital, Boston, MA 02114. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAdvanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for Atrial Fibrillation Margaret C. Fang , Yuchiao Chang , Elaine M. Hylek , Jonathan Rosand , Steven M. Greenberg , Alan S. Go , and Daniel E. Singer Warfarin or Not Warfarin? Francisco J. Ruiz-Ruiz Metrics 19 April 2005Volume 142, Issue 8Page: 676KeywordsAtrial fibrillationElderlyFrailtyHemorrhageHemorrhagic strokeInternational normalized ratioIschemic strokeObservational studiesRandomized trialsRisk assessments ePublished: 19 April 2005 Issue Published: 19 April 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The influence of linker length on the properties of cathepsin S cleavable 177Lu-labeled HPMA copolymers for pancreatic cancer imaging
Authors: Wen Shi, Sunny M. Ogbomo, Nilesh K. Wagh, Zhengyuan Zhou, Yinnong Jia, Susan K. Brusnahan, Jered C. Garrison
Journal: Biomaterials (2014)
HRT does not prevent heart disease
Authors: J. H. Tanne
Journal: BMJ (2003)

Hormone replacement therapy (HRT) should not be used to prevent coronary heart disease, experts advise, after a study showed that it does not prevent the disease and almost doubles a woman's risk during the first year of use.

Furthermore, HRT does not slow progression of established coronary artery disease.

These findings come from two studies published in the New England Journal of Medicine .

Dr JoAnn Manson and colleagues reported final results of the arm of the Women's Health Initiative trial that compared combined oestrogen and progestogen treatment with placebo (2003;349: 523-34). The trial, sponsored by the US National Institutes of Health, was stopped in 2002 because the risks of …
Wisconsin Medical Society Proceedings.
Authors: Arthur J. Patek
Journal: JAMA (1904)

Milwaukee, Wis., July 11, 1904. <h3>To the Editor:</h3> —I beg leave to call your attention to an error in the report of the recent meeting of the Wisconsin State Medical Society inThe Journal, July 2, page 65. The paragraph referred to reads that "A contract was made with the<i>Milwaukee Medical Journal</i>for the publication of the proceedings of the society for the ensuing year on the same terms as preceding contract." This contract has been made with the<i>Wisconsin Medical Journal</i>.
Clinical features and causes of coaxial polyurethane ICD lead failure
Authors: Norman Ratliff, Robert G. Hauser, G. Frank, O. Tyers, David L. Hayes, Andrew E. Epstein, Stephen C. Vlay, John Hayes, Seymour Furman, Jay Gross, Victor Parsonnet, David Cannom
Journal: Journal of the American College of Cardiology (2002)
Control of hepatitis B and C worldwide
Authors: R. Aggarwal, A. Goel
Journal: BMJ (2009)

<h3>Abstract</h3> Mitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist. We undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC), and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay), and 1338 UKBS females (17-69 years) were included in a meta-analysis. Sensitivity analyses restricted to females with white cell-extracted DNA, and adjusted for estimated or assayed cell proportions. Associations were also explored in ALSPAC children, and UKBS males. A neutrophil-associated locus approached genome-wide significance (rs709591 [<i>MED24</i>], β[SE] −0.084 [0.016], <i>p</i>=1.54e-07) in the main meta-analysis of adult females. This association was concordant in magnitude and direction in UKBS males and ALSPAC neonates. SNPs in and around <i>ABHD8</i> were associated with mtDNA CN in ALSPAC neonates (rs10424198, β[SE] 0.262 [0.034], <i>p</i>=1.40e-14), but not other study groups. In a meta-analysis of unrelated individuals (N=11253), we replicated a published association in <i>TFAM</i> β[SE] 0.046 [0.017], <i>p</i>=0.006), with an effect size much smaller than that observed in the replication analysis of a previous <i>in silico</i> GWAS. In a hypothesis-generating GWAS, we confirm an association between <i>TFAM</i> and mtDNA CN, and present putative loci requiring replication in much larger samples. We discuss the limitations of our work, in terms of measurement error and cellular heterogeneity, and highlight the need for larger studies to better understand nuclear genomic control of mtDNA copy number.
The use of IIb/IIa inhibitors in patients with in-stent restenosis treated with intracoronary gamma radiation: Results from the clinical trial INTEGRILIN WRIST
Authors: Ron Waksman, Edouard F. Chenneau, Robert Lew, Augusto Pichard, Lowell F. Satler, William O. Suddath, Laurent Leborgne, Regina Dieble, Rebecca Torguson, Maria Medina, Afework GebreEyesus, Joseph Lindsay
Journal: Journal of the American College of Cardiology (2003)
Perception of bronchial obstruction in asthmatic patients. Relationship with bronchial eosinophilic inflammation and epithelial damage and effect of corticosteroid treatment.
Authors: G L Roisman, C Peiffer, J G Lacronique, A Le Cae, D J Dusser
Journal: Journal of Clinical Investigation (1995)

We studied the perception of bronchoconstriction in asthmatic subjects who were randomly treated with inhaled beta 2 agonist given either alone (n = 9) or associated with inhaled corticosteroids (n = 9). Methacholine and bradykinin challenges, bronchoalveolar lavage, and bronchial biopsies were performed in all subjects. After each dose of agonist, breathlessness was assessed using a visual analog scale (VAS) and the forced expiratory volume in 1 s (FEV1) was measured. The relationship between VAS scores and FEV1 and the slope of the regression line of VAS scores on the corresponding FEV1 (VAS/FEV1 slope) were analyzed for each agonist. Subjects without corticosteroids had good perception of methacholine but poor perception of bradykinin-induced bronchoconstriction. In subjects with corticosteroids, bronchoconstriction was well perceived whatever the agonist. VAS/FEV1 slopes for bradykinin but not for methacholine correlated negatively with the magnitude of eosinophilic inflammation in airway mucosa. VAS/FEV1 slopes for each agonist correlated positively with the percentage of basement membrane covered by airway epithelium. We conclude that in asthmatic patients perception of bronchoconstriction is related to eosinophilic inflammation and to epithelial damage in airways and that corticosteroid treatment is associated with improved perception of bronchoconstriction induced by bradykinin, a mediator endogenously produced in asthma.