tbuckley/cabot-search huggingface dataset:
Abstract 2947: PARP-1 regulates death receptor 5-mediated apoptosis in pancreatic cancer.
Authors: Kaiyu Yuan, Yong Sun, Tong Zhou, Jay McDonald, Yabing Chen
Journal: Cancer Research (2013)

Abstract Pancreatic cancer is a highly malignant tumor with limited therapy and poor prognosis. Activation of death receptors (DR)-induced apoptotic pathways using antibodies or agonists for the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapy. However, most pancreatic tumors are resistant to TRAIL therapy. The present studies aimed to identify combination therapies that enhance the efficacy of TRAIL therapy by sensitizing resistant pancreatic cancer cells to TRAIL-induced apoptosis, and to investigate the underlying mechanisms. Using TRA-8, a monoclonal agonistic antibody specific for DR5, we demonstrated that TRA-8 induced apoptosis of 60% and 83% of BxPc-3 and MiaPaCa-2 pancreatic cancer cells in 24 hours. By contrast, only 20% and 24% of PANC-1 and Suit-2 cells underwent apoptosis in response to TRA-8 (n=3), despite the fact that they express high levels of the DR5 receptor. The expression of poly(ADP-ribose) polymerase-1 (PARP-1) was higher in the PANC-1 and Suit-2 cells than that BxPc-3 and MiaPaCa-2 cells, which may contribute to their resistance to TRA-8-induced apoptosis. Inhibition of PARP-1 with a pharmacologic inhibitor (PJ-34) sensitized PANC-1 to TRA-8 induced apoptosis in a dose-dependent manner. Furthermore, small interfering RNAs specifically knocking down PARP-1 in PANC-1 cells enhanced TRA-8-induced apoptosis in vitro by 2.5 fold, as well as the efficacy of TRA-8 therapy on tumorigenesis of PANC-1 cells in a mouse xenograft model by 3.8 fold (n=8, p&amp;lt;0.01). PARP-1 knockdown increased TRA-8-induced activation of caspase-8 in the death-induced signaling complex (DISC). Immuoprecipitation with DR5 antibody identified the recruitment of PARP-1 and PARP1-mediated protein poly-ADP-ribosylation(pADPr) modification in the DR5-associated DISC, which was associated with caspase 8 activation in the DISC. Our studies determined a novel function of PARP-1, independent of its known function in DNA repair, in regulating caspase 8 activation in the DISC. These results not only provide novel molecular insights into the function of PARP-1 in regulating the extrinsic apoptosis machinery, but also support the intervention of combining PARP inhibitors with death receptor agonists to enhance the efficacy of pancreatic cancer therapy. Citation Format: Kaiyu Yuan, Yong Sun, Tong Zhou, Jay McDonald, Yabing Chen. PARP-1 regulates death receptor 5-mediated apoptosis in pancreatic cancer. [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 2947. doi:10.1158/1538-7445.AM2013-2947
A CLINICAL TRIAL OF ALPHA-METHYLDOPA IN ELATED STATES
Authors: LOREN R. MOSHER, GERALD L. KLERMAN, JOSEPH F. GREANEY
Journal: American Journal of Psychiatry (1966)

A clinical trial of alpha-methyldopa (Aldomet) in elated states is reported. Four drug trials were conducted in three "manic" patients at dosage levels up to 6 gms. per day. No therapeutic effect was noted, although a pharmacologic effect as evidenced by a fall in blood pressure in three of four trials was noted. However, further studies with this compound in psychiatric patients are indicated before final conclusions can be drawn.
Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells
Authors: Amanda B Hummon, Jason J Pitt, Jordi Camps, Georg Emons, Susan B Skube, Konrad Huppi, Tamara L Jones, Tim Beissbarth, Frank Kramer, Marian Grade, Michael J Difilippantonio, Thomas Ried, Natasha J Caplen
Journal: Molecular Cancer (2012)

Abstract Background Colorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. Results A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2 / FLASH . To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2 / FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2 / FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2 / FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH), a protein recently linked to regulation of the AKT1/ß-catenin pathway. Conclusions We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH .
PATCH TEST REACTIONS TO MERTHIOLATE IN HEALTHY YOUNG SUBJECTS
Authors: HOLGER HANSSON, HALVOR MOLLER
Journal: British Journal of Dermatology (1970)

A high incidence of positive patch tests to merthiolate (thimerosal) has been observed in young adult males without previous or present skin disease. In battery-tested clinical material several positive merthiolate tests occurred, mainly in the younger age groups, while a high-age group did not react even to a strong merthiolate patch test. Although the clinical and histological features of the reaction are mainly of an allergic type, evidence is presented that the merthiolate reaction should be considered a false positive test, peculiar to that substance and to young skin.
Muscle Sympathetic Nerve Activity Averaged Over 1 Minute Parallels Renal and Cardiac Sympathetic Nerve Activity in Response to a Forced Baroreceptor Pressure Change
Authors: Atsunori Kamiya, Toru Kawada, Kenta Yamamoto, Daisaku Michikami, Hideto Ariumi, Tadayoshi Miyamoto, Kazunori Uemura, Masaru Sugimachi, Kenji Sunagawa
Journal: Circulation (2005)

Despite the accumulated knowledge of human muscle sympathetic nerve activity (SNA) as measured by microneurography, whether muscle SNA parallels renal and cardiac SNAs remains unknown.In experiment 1, muscle (microneurography, tibial nerve), renal, and cardiac SNAs were recorded in anesthetized rabbits (n=6) while arterial pressure was changed by intravenous bolus injections of nitroprusside (3 microg/kg) followed by phenylephrine (3 microg/kg). In experiment 2, the carotid sinus region was vascularly isolated in anesthetized, vagotomized, and aorta-denervated rabbits (n=10). The 3 SNAs were recorded while intracarotid sinus pressure was increased stepwise from 40 to 160 mm Hg in 20-mm Hg increments maintained for 60 seconds each. Muscle SNA averaged over 1 minute was well correlated with renal (r=0.96+/-0.01, mean+/-SE) and cardiac (r=0.96+/-0.01) SNAs in experiment 1 (baroreflex closed-loop condition) and also with renal (r=0.97+/-0.01) and cardiac (r=0.97+/-0.01) SNAs in experiment 2 (baroreflex open-loop condition).Muscle SNA averaged over 1 minute parallels renal and cardiac SNAs in response to a forced baroreceptor pressure change.
George Birch ("Tom") Smith
Authors: A. M Smith
Journal: BMJ (2002)

General practitioner Leeton, New South Wales, Australia, 1958-90 (b 1922; q St Thomas's Hospital, London, 1944), died on 24 December 2001 from brain cancer.

After qualifying, he travelled to Australia for a couple of years before returning to the United Kingdom for further surgical experience. He then returned to Australia and joined a practice in the small rural town of Leeton (population 7000), where he performed many operations and delivered more than 2000 babies. In his latter years he developed a passion for bird watching. He leaves a wife; four children; and 11 grandchildren.
509. Endogenous Estradiol Augments RGD Modified AAV2-Mediated Gene Transfer in Human Ovarian Epithelial Cancer
Authors: Wenfang Shi, Jeffery Bartlett
Journal: Molecular Therapy (2005)

Ovarian cancer remains a leading cause for women's death due to gynecologic malignancy. A women's average lifetime risk for developing ovarian cancer is about 1 in 70. Despite the frequency of temporary remission achieved with current therapies, long-term survival has improved little in the past 30 years. Unfortunately, the majority of ovarian cancers are not diagnosed until the disease has reached an advanced stage and the five-year survival rates are only 28%. Worldwide nearly 150,000 die from this disease each year. Most effective systemic therapies are clearly needed. In the present study, the expression of heparin sulfate proteoglycan (HSPG) and the integrins |[alpha]||[nu]||[beta]|3 and |[alpha]||[nu]||[beta]|5 were analyzed with flow cytometry on seven human ovarian cancer cell lines ( PA-1, OV-3, OV-4, OVCAR-3, OVCAR-3N, SKOV-3, SKOV-3ip and Hey) and three control cell lines ( HBK-293, HeLa and HepG2). The gene transduction efficiencies were evaluated by rAAV-GFP/LacZ or RGD-rAAV-GFP/LacZ transduction followed by flow cytometry and histochemistry. The effect of 17|[beta]|-estradiol on cell growth, HSPG and integrins expression, rAAV gene transduction efficiency were determined. The levels of HSPG, integrins |[alpha]||[nu]||[beta]|3 and |[alpha]||[nu]||[beta]|5 showed great variation between cell lines. Whereas the expression of HSPG appeared to be essential for and positively correlated with rAAV transduction efficiency, the integrins |[alpha]||[nu]||[beta]|3 and |[alpha]||[nu]||[beta]|5 were not absolutely necessary for rAAV transduction even though their presence may facilitate transduction. 17beta estradiol influences on some ovarian carcinoma cell line's proliferation and significantly increase integrin beta 5 expression on all the three tested ovarian carcinoma cell lines. Integrin-retargeted RGD-modified rAAV showed much higher gene transfer on ovarian carcinoma cell lines than rAAV with/without estradiol, which implies RGD-AAV2 may be an prospective alternative gene delivery vector for ovarian cancer therapy in vivo.
DIET IN DISEASE.
Authors: CHARLES H. SHEPARD
Journal: JAMA (1898)

There is no function of the human body so essential to its existence as the process of digestion, and it may be stated as a fundamental proposition that those foods having a natural proportion of the elements of nutrition are the most desirable for maintaining a correct balance of the system and retaining its vigor. No infringement of this law is tolerated. When we attempt to nourish the body on any one element of food, such as starch, sugar or fat, it is sure eventually to prove a failure, and bring on gastric disturbance and functional incapacity. Whenever an excess of even the simplest and most appropriate kind of food is taken, the digestive organs become overtaxed. If this excess is persisted in, nature refuses its assistance and allows that which it can not utilize to remain unappropriated, from lack of digestive fluid to complete the process, and from being
Neurotoxic and pharmacokinetic responses to trichloroethylene as a function of exposure scenario.
Authors: W K Boyes, P J Bushnell, K M Crofton, M Evans, J E Simmons
Journal: Environmental Health Perspectives (2000)

Strategies are needed for assessing the risks of exposures to airborne toxicants that vary over concentrations and durations. The goal of this project was to describe the relationship between the concentration and duration of exposure to inhaled trichloroethylene (TCE), a representative volatile organic chemical, tissue dose as predicted by a physiologically based pharmacokinetic model, and neurotoxicity. Three measures of neurotoxicity were studied: hearing loss, signal detection behavior, and visual function. The null hypothesis was that exposure scenarios having an equivalent product of concentration and duration would produce equal toxic effects, according to the classic linear form of Haber's Rule ((italic)C(/italic) times t = k), where C represents the concentration, t, the time (duration) of exposure, and k, a constant toxic effect. All experiments used adult male, Long-Evans rats. Acute and repeated exposure to TCE increased hearing thresholds, and acute exposure to TCE impaired signal detection behavior and visual function. Examination of all three measures of neurotoxicity showed that if Haber's Rule were used to predict outcomes across exposure durations, the risk would be overestimated when extrapolating from shorter to longer duration exposures, and underestimated when extrapolating from longer to shorter duration exposures. For the acute effects of TCE on behavior and visual function, the estimated concentration of TCE in blood at the time of testing correlated well with outcomes, whereas cumulative exposure, measured as the area under the blood TCE concentration curve, did not. We conclude that models incorporating dosimetry can account for differing exposure scenarios and will therefore improve risk assessments over models considering only parameters of external exposure.
Persistently Activated Stat3 Maintains Constitutive NF-κB Activity in Tumors
Authors: Heehyoung Lee, Andreas Herrmann, Jie-Hui Deng, Maciej Kujawski, Guilian Niu, Zhiwei Li, Steve Forman, Richard Jove, Drew M. Pardoll, Hua Yu
Journal: Cancer Cell (2009)
Esophageal Pseudoworm: "Pasta, not Parasite"
Authors: SARKIS J. CHOBANIAN
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 July 1986Esophageal Pseudoworm: "Pasta, not Parasite"SARKIS J. CHOBANIAN, M.D., CHARLES WINTERS, M.D., WILLIAM MARTLAND, M.D., DAVID A. JOHNSON, M.D., JAMES L. BUCK, M.D., EDWARD L. CATTAU JR., M.D.SARKIS J. CHOBANIAN, M.D.Search for more papers by this author, CHARLES WINTERS, M.D.Search for more papers by this author, WILLIAM MARTLAND, M.D.Search for more papers by this author, DAVID A. JOHNSON, M.D.Search for more papers by this author, JAMES L. BUCK, M.D.Search for more papers by this author, EDWARD L. CATTAU JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-1-138_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Working at an international referral hospital, we have seen many exotic diseases among our well-traveled patients. It was with little excitement, therefore, that we agreed to see a patient with multiple serpiginous filling defects seen during an upper gastrointestinal tract series. Fully expecting the radiographic picture of ascaris infection, we were taught a valuable lesson by the ultimate endoscopic and histologic diagnosis: when one hears hoofbeats, do not assume you hear a member of the animal kingdom.A 56-year-old Japanese woman was referred with solid-food dysphagia of 10 days' duration. She denied pyrosis, hematemesis, or ingestion of...References1. DENZLERGUNNING TJ. Ascaris lumbricoides: a reminder. Arch Intern Med. 1976;136:1044-5. CrossrefMedlineGoogle Scholar2. PAUL M. The movements of the adult Ascaris lumbricoides. Br J Surg. 1972;59:437-42. CrossrefMedlineGoogle Scholar3. WINTERSCHOBANIANBENJAMINFERGUSONCATTAU CSSRE. Endoscopic documentation of ascaris-induced acute pancreatitis. Gastrointest Endosc. 1984;30:83-4. CrossrefMedlineGoogle Scholar4. EISENBERG R. Gastrointestinal Radiology. Philadelphia: J. B. Lippincott; 1983. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SARKIS J. CHOBANIAN, M.D.; CHARLES WINTERS, M.D.; WILLIAM MARTLAND, M.D.; DAVID A. JOHNSON, M.D.; JAMES L. BUCK, M.D.; EDWARD L. CATTAUJR., M.D.Affiliations: Naval Hospital, and the Uniformed Services University of the Health Sciences Bethesda, MD 20814-5011 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1986Volume 105, Issue 1Page: 138-138KeywordsDysphagiaGastrointestinal tractIngestion ePublished: 1 December 2008 Issue Published: 1 July 1986 PDF downloadLoading ...
Involved-Field Radiotherapy Before High-Dose Therapy and Autologous Stem-Cell Rescue in Diffuse Large-Cell Lymphoma: Long-Term Disease Control and Toxicity
Authors: Bradford S. Hoppe, Craig H. Moskowitz, Daniel A. Filippa, Chaya S. Moskowitz, Tarun Kewalramani, Andrew D. Zelenetz, Joachim Yahalom
Journal: Journal of Clinical Oncology (2008)

Purpose To analyze outcome, prognostic factors, and toxicities in patients with diffuse large-cell lymphoma (DLCL) who received involved-field radiotherapy (IFRT) before high-dose chemotherapy with autologous stem-cell rescue (ASCR). Patients and Methods Between January 1990 and August 2006, 164 patients with relapsed or refractory DLCL received IFRT at Memorial Sloan-Kettering Cancer Center (New York, NY) before high-dose chemotherapy and ASCR. IFRT was delivered to involved sites measuring more than 5 cm or to sites with residual disease more than 2 cm. Radiotherapy was administered in 1.5-Gy fractions twice daily to a total dose of 30 Gy. Progression-free survival and overall survival were calculated, and short- and long-term toxicity was assessed according to National Cancer Institute Common Toxicity Criteria (version 2.0). Median follow-up was 60 months (range, 2 to 187 months). Results Two- and 5-year progression-free survival was 62% and 53%; 2- and 5-year overall survival was 67% and 58%, respectively. Sixty-seven patients relapsed; only 10 patients relapsed completely within the radiotherapy field. There were seven early treatment-related mortalities and 11 secondary cancers (including four myelodysplastic syndromes), one of which occurred within the IFRT site and five after total-body irradiation. Conclusion Minimal treatment-related mortality and morbidity resulted from short, intensive, involved-field radiotherapy before high-dose chemotherapy and ASCR, which was incorporated into a salvage regimen for patients with relapsed/refractory DLCL. This chemoradiotherapy salvage regimen resulted in a low local relapse rate that could potentially translate into an improved total outcome.
Tumor Cell Invasion Is Promoted by Interstitial Flow-Induced Matrix Priming by Stromal Fibroblasts
Authors: Adrian C. Shieh, Hallie A. Rozansky, Boris Hinz, Melody A. Swartz
Journal: Cancer Research (2011)

Abstract Interstitial flow emanates from tumors into the microenvironment where it promotes tumor cell invasion. Fibroblasts are key constituents of the tumor stroma that modulate the mechanical environment by matrix remodeling and contraction. Here, we explore how interstitial fluid flow affects fibroblast–tumor cell interactions. Using a 3-dimensional invasion assay and MDA-MB-435S cells cocultured with dermal fibroblasts in a collagen matrix, we showed a synergistic enhancement of tumor cell invasion by fibroblasts in the presence of interstitial flow. Interstitial flow also drove transforming growth factor (TGF)-β1 and collagenase-dependent fibroblast migration, consistent with previously described mechanisms in which flow promotes invasion through autologous chemotaxis and increased motility. Concurrently, migrating fibroblasts enhanced tumor cell invasion by matrix priming via Rho-mediated contraction. We propose a model in which interstitial flow promotes fibroblast migration through increased TGF-β1 activation and collagen degradation, positioning fibroblasts to locally reorganize collagen fibers via Rho-dependent contractility, in turn enhancing tumor cell invasion via mechanotactic cues. This represents a novel mechanism in which interstitial flow causes fibroblast-mediated stromal remodeling that facilitates tumor invasion. Cancer Res; 71(3); 790–800. ©2011 AACR.
Allopurinol metabolism in a patient with xanthine oxidase deficiency.
Authors: H Yamanaka, K Nishioka, T Suzuki, K Kohno
Journal: Annals of the Rheumatic Diseases (1983)

A patient with complete deficiency of xanthine oxidase would not be expected to oxidase allopurinol to oxipurinol if allopurinol did not have any alternative metabolic pathway. 400 mg of allopurinol was administered to a patient with xanthine oxidase deficiency, and plasma allopurinol, oxipurinol, hypoxanthine, and xanthine levels were determined serially by the use of high-performance liquid chromatography (HPLC). Plasma oxipurinol as well as allopurinol was increased after the administration of allopurinol, and oxipurinol reached a maximum level of 13.1 micrograms/ml at 6 hours after the administration. This was the same pattern as that of normal controls. This result demonstrated the existence of some other oxidising enzyme of allopurinol than xanthine oxidase.
Gastrointestinal Hemorrhage due to Carcinoid Tumors of the Small Intestine
Authors: David J. Kreis, Jorge J. Guerra, Marcia Saltz, Roberto Santiesteban, Patricia Byers
Journal: JAMA (1986)

MALIGNANT tumors of the small intestine account for about 2% of all gastrointestinal malignancies.<sup>1</sup>The majority of these lesions are adenocarcinomas, followed by carcinoid tumors, lymphomas, and sarcomas. The most common site for carcinoid tumors is the appendix, followed by the jejunoileum. The most common clinical manifestation of jejunoileal carcinoids is small-bowel obstruction.<sup>1,2</sup>Gastrointestinal bleeding from jejunoileal carcinoids is rare but is surgically correctable. It is often difficult to locate the source of small intestinal hemorrhage prior to exploratory laparotomy. We recently treated a patient with multiple jejunoileal carcinoids associated with massive gastrointestinal hemorrhage. This case is presented along with a complete review of the pertinent literature to update the workup and treatment of bleeding small-bowel tumors. <h3>Report of a Case</h3> A 53-year-old man was admitted to the University of Miami/Jackson Memorial Medical Center on June 12, 1984, with near syncope. His medical history included chronic iron deficiency anemia
Problems Associated With Rabies Preexposure Prophylaxis
Authors: Walton R. Garner
Journal: JAMA (1976)

With the rabies vaccine presently available for preexposure prophylaxis, 20% of all individuals do not have seroconversion following routine immunizations, and 5% are allergic to this vaccine. Two experimental rabies vaccines of cell culture origin offering greater purity and potency were evaluated by means of a double-blind experiment. Thirty-one volunteers who did not have seroconversion or who were allergic to duck embryo rabies vaccine received rabies vaccine produced in either human diploid cell culture (WI38), or hamster kidney-cell culture. All volunteers had seroconversion within 14 days of receiving a single injection of either experimental vaccine. Clinical side effects were only minor. (<i>JAMA</i>235:1131-1132, 1976)
Tuberous Sclerosis and Cardiac Arrhythmia in Three Zulu Patients
Authors: J. E. Cosnett, B. H. Gibb
Journal: BMJ (1969)

Cardiac arrhythmias, in the form of multiple atrial or ventricular extrasystoles together with various types of conduction defect, occurred in three Zulu patients with tuberous sclerosis. Probably this association occurs more often than has been suspected.