tbuckley/cabot-search huggingface dataset:
Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.
Authors: M H Drazner, K C Peppel, S Dyer, A O Grant, W J Koch, R J Lefkowitz
Journal: Journal of Clinical Investigation (1997)

Our laboratory has been testing the hypothesis that genetic modulation of the beta-adrenergic signaling cascade can enhance cardiac function. We have previously shown that transgenic mice with cardiac overexpression of either the human beta2-adrenergic receptor (beta2AR) or an inhibitor of the beta-adrenergic receptor kinase (betaARK), an enzyme that phosphorylates and uncouples agonist-bound receptors, have increased myocardial inotropy. We now have created recombinant adenoviruses encoding either the beta2AR (Adeno-beta2AR) or a peptide betaARK inhibitor (consisting of the carboxyl terminus of betaARK1, Adeno-betaARKct) and tested their ability to potentiate beta-adrenergic signaling in cultured adult rabbit ventricular myocytes. As assessed by radioligand binding, Adeno-beta2AR infection led to approximately 20-fold overexpression of beta-adrenergic receptors. Protein immunoblots demonstrated the presence of the Adeno-betaARKct transgene. Both transgenes significantly increased isoproterenol-stimulated cAMP as compared to myocytes infected with an adenovirus encoding beta-galactosidase (Adeno-betaGal) but did not affect the sarcolemmal adenylyl cyclase response to Forskolin or NaF. beta-Adrenergic agonist-induced desensitization was significantly inhibited in Adeno-betaARKct-infected myocytes (16+/-2%) as compared to Adeno-betaGal-infected myocytes (37+/-1%, P < 0.001). We conclude that recombinant adenoviral gene transfer of the beta2AR or an inhibitor of betaARK-mediated desensitization can potentiate beta-adrenergic signaling.
Biliorenous fistula related to self-expandable biliary metallic stent placement: a rare complication of endoscopic retrograde cholangiopancreatography
Authors: J. Vila, F. Jiménez, R. Irisarri, M. Vicuña, B. Martínez, F. Borda
Journal: Endoscopy (2007)

An 87-year-old woman was admitted to our hospital with cholangitis caused by a cholangiocarcinoma (Figure [1]). She refused surgery, so a self-expandable metallic stent (SEMS) (Memotherm; Bard Inc. Billerica, Massachusetts, USA) was placed endoscopically. One year later, she presented with cholangitis related to tumor progression. We placed a second and a third coaxial ”Y”-shaped SEMS (Luminexx, Bard Inc. Billerica, Massachusetts, USA) in the right and left bile ducts. Over the following 4 months she was admitted three times with sepsis of biliary origin, which resolved after cleansing of biliary sludge from the lumen of the stents. In the last episode, when contrast was injected at the proximal end of the right bile duct stent, a leak of contrast with rapid and turbulent flow was clearly seen, indicative of a biliovascular fistula (Figure [2]). We cleared out the bile duct once again and her symptoms resolved. She died 4 months later after general deterioration in her condition.
<i>IL15</i> gene variants are not associated with asthma and atopy
Authors: L. A. Pinto, M. Depner, L. Steudemann, N. Klopp, T. Illig, E. Von Mutius, M. Kabesch
Journal: Allergy (2008)

Interleukin 15 (IL15) promotes activation and proliferation of CD8+ T cells and enhances the differentiation into Th2 cells. A previous study described five polymorphisms in the IL15 gene to be associated with asthma in a haplotype analysis.We selected HapMap tagging single nucleotide polymorphisms (SNPs) from IL15 to systematically investigate these IL15 associations in a large population-based sample.Genotyping of seven IL15 SNPs was performed using MALDI-TOF MS in a cross-sectional study population of 3099 children from Dresden or Munich (age 9-11 years). All children were phenotyped by standardized and validated protocols for atopic phenotypes. Effects of single SNPs and haplotypes were studied using sas 9.1.3 and haploview. Equivalence tests were performed to prove the significance of negative results.Neither single IL15 polymorphisms nor haplotype analyses showed associations with asthma or atopy after correction for multiple testing.These results do not confirm previous case-control studies and suggest that IL15 gene variants do not play an important role in the development for asthma or other atopic disorders.
Testosterone Induces Dilation of Canine Coronary Conductance and Resistance Arteries In Vivo
Authors: Tony M. Chou, Krishnankutty Sudhir, Stuart J. Hutchison, Eitetsu Ko, Thomas M. Amidon, Peter Collins, Kanu Chatterjee
Journal: Circulation (1996)

Background Although estrogens have been shown to be vasoactive hormones, the vascular effects of testosterone are not well defined. Like estrogen, testosterone causes relaxation of isolated rabbit coronary arterial segments. We examined the vasodilator effects of testosterone in vivo in the coronary circulation and the potential mechanisms of its actions. Methods and Results Using simultaneous intravascular two-dimensional and Doppler ultrasound, we examined the effect of intracoronary testosterone in coronary conductance and resistance arteries in 10 anesthetized dogs (5 male, 5 female). We also assessed the contribution of NO, prostaglandins, ATP-sensitive K + channels, and classic estrogen receptors to testosterone-induced vasodilation. Testosterone induced a significant increase in cross-sectional area, average coronary peak flow velocity, and calculated volumetric coronary blood flow at the 0.1 and 1 μmol/L concentrations. This effect was independent of sex. Pretreatment with N ω -nitro- l -arginine methyl ester to block NO synthesis decreased testosterone-induced increase in cross-sectional area, average coronary peak flow velocity, and coronary blood flow. Pretreatment with glybenclamide to assess the role of ATP-sensitive K + channels did not influence testosterone-induced dilation in epicardial arteries but did attenuate its effect in the microcirculation. Pretreatment with indomethacin or the classic estrogen-receptor antagonist ICI 182,780 did not alter testosterone-induced changes. Conclusions Short-term administration of testosterone induces a sex-independent vasodilation in coronary conductance and resistance arteries in vivo. Acute testosterone-induced coronary vasodilation of epicardial and resistance vessels is mediated in part by endothelium-derived NO. ATP-sensitive K + channels appear to play a role in the vasodilatory effect of testosterone in resistance arteries.
Aplastic Anaemia with Recovery
Authors: T. H. Boon
Journal: BMJ (1938)

culosis is most often due to the bovine type of bacillus which is conveyed in milk.The researches of Blacklock and Griffith leave no doubt on this point, as they found the bovine type of bacillus in 80 to 82 per cent. of cases with primary foci in the abdomen.We are therefore entitled to assume that in our cases also the bovine type of bacillus predominated.This assumption is sustained by the fact that a majority of the children came from rural areas where children are more often fed on raw milk.It may be remarked that in Case III the parents declared that the child had been given only boiled milk.The possibilities in this case are, first, that the infection was of the huLman type, which is rare; and, secondly, that the milk had been insufficiently or not always boiled.To omit to boil milk properly on a single occasion is quite sufficient to allow the tubercle bacillus to enter the body and give rise to infection. ConclusionsPrimary abdominal tuberculosis is a commoner disease in children than is generally supposed, and the true inci- dence is much higher than post-mortem figures indicate.In primary abdominal infection, as in cases with a primary lung infection, the prognosis depends on the age of the child: the younger the child at the time of infection the worse the prognosis.We are unable to accept the current view that primary abdominal tuberculosis can be more lightly regarded in children than can a primary lung infection: the bad prog- nosis in young children refutes this view.Diagnosis in cases of primary abdominal tuberculosis in the living child is extremely difficult; consequently early treatment is rarely possible.Prevention of infection is therefore all-impor- tant.Many cases of tuberculous meningitis, miliary tuberculosis, and crippling deformities could be prevented.We should endeavour, as an ideal, to secure for children milk from tuberculin-tested herds only, but at present it is impossible to provide this for the whole population.Therefore the greatest measure of protection is afforded by milk which has been boiled or efficiently pasteurized.
The Natural History of Idiopathic Subfoveal Choroidal Neovascularization
Authors: Allen C. Ho, Lawrence A. Yannuzzi, Kristin Pisicano, Janet DeRosa
Journal: Ophthalmology (1995)

To study the long-term natural history of idiopathic subfoveal choroidal neovascularization (CNV) in young patients.A retrospective survey of 19 consecutive patients with idiopathic subfoveal CNV diagnosed in an urban eye hospital and a single practice.Twenty-three (26%) of 87 consecutive patients with idiopathic CNV demonstrated subfoveal CNV. Nineteen patients with subfoveal involvement were followed for a median of 87 months (range, 5-230 months). On initial examination, the median best-corrected Snellen visual acuity was 20/100 (range, 20/40-counting fingers); at final examination, the median visual acuity was 20/70 (range, 20/20-counting fingers). A total of 95% of patients had stable or significantly improved visual acuity, whereas only 5% had significant visual loss. Size of the CNV was the only variable associated with long-term final visual acuity. Lesions 1 disc area or smaller at the time of initial fluorescein angiography were more likely to be associated with a final visual acuity of 20/60 or better and less likely to be associated with a final visual acuity of 20/200 or worse (P = 0.038) as compared with larger lesions. These results were confirmed with multiple logistic regression analysis (P = 0.027). Fellow eyes remained unaffected during the follow-up period.The natural history of idiopathic subfoveal CNV is not necessarily associated with a profound loss of vision. Therapies for this type of subfoveal lesion must take into consideration the possibility of a favorable natural course.
Immunotherapy of Human Cancer
Authors: David S. Rosenthal
Journal: JAMA (1983)

Immunotherapy during the 1970s become a potential weapon against human cancers because of experimental beneficial results in animal models. An attempt has been made to put into clinical perspective the results of a large number of studies that have taken place over the past decade. This text consists of ten chapters broken down into disease categories such as the leukemias, lung cancer, melanoma, and breast cancer, with a final chapter dealing with new agents. Each chapter contains institutional or group clinical trials of various immunotherapy modalities. The various agents used include BCG vaccine, levamisole, interferon,<i>Corynebacterium parvum</i>, and irradiated malignant cells. This book is not intended as a review of clinical immunotherapy for the uninitiated, but rather presents results or representative studies in different cancers. The text is specifically designed as a reference for investigators involved with clinical cancer immunotherapy. Therefore, it has a very limited audience. The individual reports
IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS
Authors: Elvin A. Kabat, Harold Baer, Richard L. Day, Vesta Knaub
Journal: The Journal of Experimental Medicine (1950)

The reactions of hog, human, and horse blood group A substances with antibodies produced on injection of these substances into individuals of blood groups B and O have been studied by hemagglutination inhibition and by quantitative precipitin technics. Species differences in reactivity with antisera exist among these blood group A substances. Hog and human A substances are very closely related chemically as evidenced by their extensive cross-reaction while horse A substance crossreacts much less with antisera to both hog and human A substances. Analysis for hexosamine of specific precipitates of hog and human A substances and antibody to human A substance formed as a consequence of heterospecific pregnancy has shown that essentially all of the glucosamine of the blood group substance is precipitated.
Pediatric Respiratory Disease
Authors: Elizabeth R. Brown
Journal: JAMA (1982)

This fluent translation of a standard French text is a comprehensive overview of pediatric pulmonary disorders. It is geared toward the general pediatric practitioner rather than the pulmonary specialist. The book is disease oriented and includes general chapters on bronchial, bronchopulmonary, parenchymal, pleural, and mediastinal problems, with separate chapters for tuberculosis, asthma, and malformations of the lung. The opening chapters provide a clear discussion of basic lung anatomy and physiology. Of particular note is the excellent section by Dr Claude Gaultier in which he pairs the explanations of normal lung physiology to that of the methodology used to investigate and define abnormal physiology in the diseased state. Other strengths of the book are the chapters dealing with malformations and pulmonary infections. Dr Couvreur begins the malformation section with a concise description of the developmental anatomy of the lung, followed by an extensive chapter detailing the major lung malformations and how
Combined Inhibition of MAP Kinase and KIT Signaling Synergistically Destabilizes ETV1 and Suppresses GIST Tumor Growth
Authors: Leili Ran, Inna Sirota, Zhen Cao, Devan Murphy, Yuedan Chen, Shipra Shukla, Yuanyuan Xie, Michael C. Kaufmann, Dong Gao, Sinan Zhu, Ferdinando Rossi, John Wongvipat, Takahiro Taguchi, William D. Tap, Ingo K. Mellinghoff, Peter Besmer, Cristina R. Antonescu, Yu Chen, Ping Chi
Journal: Cancer Discovery (2015)

Abstract Gastrointestinal stromal tumor (GIST), originating from the interstitial cells of Cajal (ICC), is characterized by frequent activating mutations of the KIT receptor tyrosine kinase. Despite the clinical success of imatinib, which targets KIT, most patients with advanced GIST develop resistance and eventually die of the disease. The ETS family transcription factor ETV1 is a master regulator of the ICC lineage. Using mouse models of Kit activation and Etv1 ablation, we demonstrate that ETV1 is required for GIST initiation and proliferation in vivo, validating it as a therapeutic target. We further uncover a positive feedback circuit where MAP kinase activation downstream of KIT stabilizes the ETV1 protein, and ETV1 positively regulates KIT expression. Combined targeting of ETV1 stability by imatinib and MEK162 resulted in increased growth suppression in vitro and complete tumor regression in vivo. The combination strategy to target ETV1 may provide an effective therapeutic strategy in GIST clinical management. Significance: ETV1 is a lineage-specific oncogenic transcription factor required for the growth and survival of GIST. We describe a novel strategy of targeting ETV1 protein stability by the combination of MEK and KIT inhibitors that synergistically suppress tumor growth. This strategy has the potential to change first-line therapy in GIST clinical management. Cancer Discov; 5(3); 304–15. ©2015 AACR. See related commentary by Duensing, p. 231 This article is highlighted in the In This Issue feature, p. 213
Abstract 686: Warburg effect in mammary atypia from high-risk women
Authors: Victoria L. Seewaldt, Abigail Hoffman, Catherine Ibarra-Drendall
Journal: Cancer Research (2012)

Abstract Background: Aggressive cancers are known to consume glucose avidly and produce lactic acid (rather than fully metabolize glucose via the Tricarboxylic Acid (TCA) cycle). This shift toward lactate production, even in the presence of adequate oxygen, is termed the Warburg effect. The Warburg effect is thought to be a late event in breast cancer, however, our studies in high-risk women provide evidence that the Warburg effect occurs during cancer initiation. This is an important observation as glucose-signaling can be readily targeted for breast cancer prevention with minimal toxicity. Here we investigated the role of the Warburg effect in breast cancer initiation in young high-risk women. Methods and Results: Similar to fluorodeoxyglucose, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) is a fluorescent glucose analog that can be used to track glucose uptake and glycolysis. 2-NBDG spectroscopy provides a means to track glucose metabolism in live mammary epithelial cells from high-risk women. We used 2-NBDG spectroscopy to measure glucose uptake in ER- breast cancer and live atypical mammary epithelial cells from high-risk premenopausal women. We observe that both triple-negative breast cancer and a subset of atypia exhibits accumulation of 2-NBDG. There is growing recognition that phosphoprotein signaling networks (rather than single genes) play a key role in breast cancer initiation and progression. Our team used Reverse Phase Proteomic Microarray (RPPM) profiling to test for activation of phosphoprotein signaling networks in atypical RPFNA cytology from high-risk premenopausal women in our cohort. RPFNA were obtained from two independent sets of 39 and 38 high-risk premenopausal women; 45% of these women were African American. The signaling network most highly expressed in precancerous cells contained activated signaling proteins associated with the Warburg effect (AKT/mTOR/PI3K), insulin signaling (pACC, IRS1) and epithelial to mesenchymal transition (EMT) IL6/Stat3/vimentin. Conclusions: This is the first evidence that abnormal glucose uptake and the Warburg effect occurs during breast cancer initiation in high-risk premenopausal women. These studies demonstrate our ability to identify abnormal glucose and activated signaling networks associated with the Warbug effect in atypical mammary cells from high-risk women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 686. doi:1538-7445.AM2012-686
Mucinous Cystadenomas and Intraductal Papillary Mucinous Tumors of the Pancreas in Magnetic Resonance Cholangiopancreatography
Authors: J. Albert, D. Schilling, H. Breer, K.-P. Jungius, J. F. Riemann, H. E. Adamek
Journal: Endoscopy (2000)

In mucin-producing tumors of the pancreas, diagnosis using endoscopic retrograde cholangiopancreatography (ERCP) is limited to cystic formations that communicate with the main pancreatic duct. Magnetic resonance cholangiopancreatography (MRCP) is a new, sophisticated method which is currently under evaluation. The authors describe the usefulness of MRCP in diagnosis of mucin-producing tumors.Six patients with mucin-producing tumors were investigated using MRCP and ERCP. Imaging was compared with surgery and histopathological examinations.Three patients were found to have mucinous cystadenomas (MC), two patients had intraductal papillary mucinous tumors (IPMT) and one patient had a cystadenocarcinoma. MRCP demonstrated the cystic formations in all patients. Magnetic resonance imaging (MRI) showed contrast-mediated enhancement of the cystic wall in patients with MC, and visualized the pancreatic ducts completely in patients with IPMT. ERCP failed to visualize the cystic lesion in one patient with MC of the pancreatic tail. Furthermore, ERCP showed evidence of IPMT in dilated main ducts with multiple filling defects but did not visualize the ducts completely.MRCP provides visualization of pancreatic ducts, extraductal variations, and cystic formations more completely than ERCP does. It avoids complications seen in ERCP. MRCP may replace ERCP in the evaluation of mucin-producing tumors of the pancreas.
Abstract 1069: M1 macrophages suppress tumorigenesis via accumulated p53 and upregulated STAT1 in lung cancer
Authors: Yi-Jing Hsiao, Kang-Yi Su, Jian-Wei Chen, Sung-Liang Yu
Journal: Cancer Research (2014)

Abstract Purpose Macrophages involved in innate immunity and possess cytotoxicity via NO, ROS and pro-inflammatory cytokines, such as TNF-α and IFN-γ. But long-term effects of M1 macrophages on cancer cells, especially their tumoricidal activity, remain unclear. In our previous study, conditioned medium (CM) from M1 macrophages can induce A549 apoptosis and senescence, but detail mechanism is unexplored. Materials &amp; Methods Lung cancer cell lines, A549 and H460, are cells with wild-type p53, but H1299 is p53-null. Cytokine and cDNA microarray were used to evaluate the content of M1 macrophages and their effects on A549 cell. Flow cytometry was assessed cell apoptosis; real-time PCR and Western blot were assessed the expression of identified genes and proteins. Clinical statistical analysis for predicting survival of lung cancer patients was applied by a published clinical microarray dataset. Results According to our previous results of cDNA microarray, several significantly differential genes were the down-stream of p53, the important initiator for apoptosis. After M1 CM treatment, A549 and H460 cells went apoptosis and p53 was abundantly accumulated. But cell death was not observed in H1299 cells, unless exogenous wt-p53 was expressed and M1 CM treated. Another transcription factor STAT1 was also up-expressed at translational and transcriptional levels after M1 CM stimulation. STAT1 may interact and assist with p53 to cause cell death. IFN-γ which is a well known cytokine for STAT1 activation highly expresses in M1 macrophages, but antibody neutralization can not reverse cell apoptosis. M1 macrophages from human PBMCs also had tumoricidal activity for A549. Moreover, the M1/M2 gene signature from A549 cDNA microarray can predict the patients' survival. Conclusion Accumulated data show that p53 and STAT1 are the main tumoricidal regulators induced by M1 macrophages in long-term culture and that is IFNs independent signaling pathway. Those data imply that M1 macrophage plays an important role in the immune surveillance for cancer progression. That may be a potential immunol target therapy. Citation Format: Yi-Jing Hsiao, Kang-Yi Su, Jian-Wei Chen, Sung-Liang Yu. M1 macrophages suppress tumorigenesis via accumulated p53 and upregulated STAT1 in 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 1069. doi:10.1158/1538-7445.AM2014-1069