tbuckley/cabot-search huggingface dataset:
Abstract 2741: NF-κB activation by IL-1α and p62 feedforward loops is required for Kras-induced pancreatic ductal adenocarcinoma.
Authors: Jianhua Ling, Ya'an Kang, Paul Chiao
Journal: Cancer Research (2013)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a less than six month mean survival period and less than five percent of an overall five-year survival rate. Despite developments in the management of pancreatic cancer, the survival rate has remained unchanged in the past 50 years. Thus, a better understanding of the mechanism of pancreatic cancer inception and development is the key to identifying prevention strategies and therapeutic targets for increasing patient survival rates, which is one of the greatest challenges in pancreatic cancer research. The mutational activation of Kras is an early event in PDAC development and has been detected in 90% of PDAC and 50% of pancreatic intraepithelial neoplasia (PanIN). The genetic mutation of oncogenic Kras in the pancreas induces chronic pancreatitis and pancreatic cancer. However, the key signaling pathway of the downstream Kras remains unidentified. Here, we report that pancreas-specific targeted IKK2/β inactivation inhibited NF-κB activation and PDAC development in KrasG12D and KrasG12D; Ink4a/ArfF/F mice, demonstrating a mechanistic link between IKK2/β/NF-kB signaling pathway and KrasG12D signaling pathways in PDAC inception. Our findings reveal that KrasG12D-activated AP-1 induces IL-1α, which, in turn, activates NF-κB and its target genes IL-1α and p62, to initiate IL-1α/p62 feedforward loops for inducing and sustaining NF-κB activity. Furthermore, IL-1α overexpression correlates with Kras mutation, NF-κB activity, and poor survival in PDAC patients. Knock-down of IL-1α in mouse PDAC cell lines and lung adenocarcinoma cell lines significantly reduces tumorigenesis in orthotopic xenograft mouse and subcutaneous xenograft mouse models. Therefore, our findings demonstrate the new mechanism by which IKK2/β/NF-κB is activated by KrasG12D through dual feedforward loops of IL-1α/p62 to promote development of PDAC. This suggests that the interruption of the dual feedforward loops of IL-1α/p62 could be the therapeutic targets for inhibiting oncogenic Kras signaling in PDAC. Citation Format: Jianhua Ling, Ya'an Kang, Paul Chiao. NF-κB activation by IL-1α and p62 feedforward loops is required for Kras-induced pancreatic ductal adenocarcinoma. [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 2741. doi:10.1158/1538-7445.AM2013-2741
Early recovery of impaired coronary flow reserve by carvedilol therapy in patients with idiopathic dilated cardiomyopathy: A serial transthoracic Doppler echocardiographic study
Authors: Kenichi Sugioka, Takeshi Hozumi, Yasuhiko Takemoto, Keiji Ujino, Yoshiki Matsumura, Hiroyuki Watanabe, Kohei Fujimoto, Minoru Yoshiyama, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2005)
Increasing Bacterial Resistance to the Antibiotics
Authors: DAVID C. LEVINSON, GEORGE C. GRIFFITH, HAROLD E. PEARSON
Journal: Circulation (1950)

Observations on bacterial resistance to antibiotics in 64 patients with bacterial endocarditis are reported. Streptococcus endocarditis is contrasted with staphylococcus endocarditis as regards course, bacterial resistance to antibiotics, and mortality. The management of bacterial resistant patients is stressed and particular emphasis is placed upon the role of the newer antibiotics such as aureomycin.
A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke
Authors: Mark Parsons, Neil Spratt, Andrew Bivard, Bruce Campbell, Kong Chung, Ferdinand Miteff, Bill O'Brien, Christopher Bladin, Patrick McElduff, Chris Allen, Grant Bateman, Geoffrey Donnan, Stephen Davis, Christopher Levi
Journal: New England Journal of Medicine (2012)

Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent.
COMPARISON OF INTERMEDIATE TERM LATE LUMEN LOSS AFTER CORONARY IMPLANTATION OF BARE OR PACLITAXEL ELUTING ABSORBABLE METAL SCAFFOLDS: RESULTS FROM PROGRESS-AMS AND BIOSOLVE-1 TRIALS
Authors: Michael Haude, Raimund Erbel, Stefan Verheye, Ron Waksman, Neil Weissman, Hubertus Degen, Dirk Boese, Paul Erne, Jacques Koolen
Journal: Journal of the American College of Cardiology (2012)
Arterioportal Fistula Complicating Endoscopic Retrograde Cholangiography
Authors: G. C. Sotiropoulos, J. Treckmann, A. Radtke, G. Antoch, E. I. Brokalaki, J. Schlaak, C. E. Broelsch
Journal: Endoscopy (2005)

Arterioportal fistula following diagnostic or therapeutic interventions is rarely reported in the literature. It most commonly complicates percutaneous liver biopsy or it is seen after liver injury [1]. Arterioportal fistula accompanying hepatic hemangioma or following hepatobiliary surgery occurs rarely [2]. It presents clinically with unexpected esophageal variceal bleeding [3]. To our knowledge, arterioportal fistula following endoscopic retrograde cholangiography (ERC) has not been described in the literature.
1965-1995: Medicare at a Crossroads
Authors: Bill Thomas
Journal: JAMA (1995)

<h3>How Medicare Grew</h3> In 1965, after years of debate, Republicans and Democrats joined to pass legislation establishing the Medicare program. Designed originally to provide health insurance coverage for America's low-income elderly, the program has since been expanded beyond its initial scope. Medicare now covers nearly all Americans over the age of 65 and includes benefits not envisioned by the original intent of the program, which have increased costs to the taxpayer and skewed the original sharing formula between the government and beneficiary. We are to the point now where on the 30th anniversary of the establishment of Medicare we are faced with a fundamental challenge: how to make the Medicare Hospital Trust Fund solvent and improve the program through additional choices for our Medicare beneficiaries. Medicare Part A was designed originally in 1965 to pay for the in-hospital expenses of America's seniors. It was set up to be a self-supporting
Suppression of Tumor Growth<i>In vivo</i>by the Mitocan α-tocopheryl Succinate Requires Respiratory Complex II
Authors: Lan-Feng Dong, Ruth Freeman, Ji Liu, Renata Zobalova, Alvaro Marin-Hernandez, Marina Stantic, Jakub Rohlena, Karel Valis, Sara Rodriguez-Enriquez, Bevan Butcher, Jacob Goodwin, Ulf T. Brunk, Paul K. Witting, Rafael Moreno-Sanchez, Immo E. Scheffler, Stephen J. Ralph, Jiri Neuzil
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Vitamin E analogues are potent novel anticancer drugs. The purpose of this study was to elucidate the cellular target by which these agents, represented by α-tocopoheryl succinate (α-TOS), suppress tumors in vivo, with the focus on the mitochondrial complex II (CII). Experimental Design: Chinese hamster lung fibroblasts with functional, dysfunctional, and reconstituted CII were transformed using H-Ras. The cells were then used to form xenografts in immunocompromized mice, and response of the cells and the tumors to α-TOS was studied. Results: The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to α-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to α-TOS. Thus, growth of CII-functional and CII-reconstituted tumors was strongly suppressed by the agent, and this was accompanied by high level of apoptosis induction in the tumor cells. On the other hand, α-TOS did not inhibit the CII-dysfuntional tumors. Conclusions: We document in this report a novel paradigm, according to which the mitochondrial CII, which rarely mutates in human neoplasias, is a plausible target for anticancer drugs from the group of vitamin E analogues, providing support for their testing in clinical trials.
Identification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy.
Authors: K Ikeda, M Mangin, B E Dreyer, A C Webb, J T Posillico, A F Stewart, N H Bander, E C Weir, K L Insogna, A E Broadus
Journal: Journal of Clinical Investigation (1988)

The syndrome of humoral hypercalcemia of malignancy (HHM) appears to be mediated in many instances by a parathyroid hormone-like peptide, which has recently been purified, sequenced, and cloned. Using a probe representing the coding region of the human PTH-like peptide, we examined by Northern analysis poly (A)+ RNA from a variety of human and animal tumors associated with HHM. Hybridizing transcripts were identified in mRNA from each of 12 human and each of four animal HHM-associated tumors, with a complex hybridization pattern observed in the human mRNAs and a relatively simple pattern observed in the animal mRNAs. Poly (A)+ RNA prepared from tumors of similar histological types unassociated with HHM failed to hybridize with the probe. Messenger RNA-dependent biological activity from the animal tumors was entirely eliminated in a hybridization-arrest experiment using a complementary oligonucleotide spanning the region of homology between human PTH and the PTH-like peptide. These findings indicate that the PTH-like peptide is associated with the syndrome of HHM in a wide spectrum of tumor types from a variety of mammalian species and that the PTH-like sequence in the proximal amino terminus of the peptide is highly conserved.
Effects of dietary fibre.
Authors: L J Bruce-Chwatt
Journal: BMJ (1972)

If te = migration in presence of antigen tc = migration without antigen: then te > tc, and te-tc/tc x 100 represents the slowing induced by antigen and is a measure of lymphocyte sensitization.' Differences > 2-1 are significant at P = 0-01.stimulatory capacity of the cultured cells limited to fetal lung but occurred also with fetal brain and thymus.
Plaque psoriasis vs. atopic dermatitis and lichen planus: a comparison for lesional T-cell subsets, epidermal proliferation and differentiation
Authors: H.J. Bovenschen, M.M.B. Seyger, P.C.M. Van De Kerkhof
Journal: British Journal of Dermatology (2005)

Journal Article Plaque psoriasis vs. atopic dermatitis and lichen planus: a comparison for lesional T‐cell subsets, epidermal proliferation and differentiation Get access H.J. Bovenschen, H.J. Bovenschen Department of Dermatology, University Medical Center St Radboud, Nijmegen, René Descartes dreef 1, PO Box 9101, 6500 HB, Nijmegen, The Netherlands H.J. Bovenschen. E‐mail: J.Bovenschen@derma.umcn.nl Search for other works by this author on: Oxford Academic Google Scholar M.M.B. Seyger, M.M.B. Seyger Department of Dermatology, University Medical Center St Radboud, Nijmegen, René Descartes dreef 1, PO Box 9101, 6500 HB, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.C.M. Van De Kerkhof P.C.M. Van De Kerkhof Department of Dermatology, University Medical Center St Radboud, Nijmegen, René Descartes dreef 1, PO Box 9101, 6500 HB, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 1, 1 July 2005, Pages 72–78, https://doi.org/10.1111/j.1365-2133.2005.06538.x Published: 01 July 2005 Article history Accepted: 24 October 2004 Published: 01 July 2005
Site and Size of Bleeding Peptic Ulcer. Is there any Relation to the Efficacy of Hemostatic Sclerotherapy?
Authors: E. Brullet, R. Campo, G. Bedos, S. Barcons, J. M. Gubern, J. M. Bordas
Journal: Endoscopy (1991)

In 78 patients with high-risk bleeding peptic ulcers (either with active bleeding or non-bleeding visible vessel) endoscopic hemostasis by injection of adrenaline and polidocanol was attempted. Sclerotherapy was performed in 70 (90%) patients. Initial hemostasis was achieved in 35 (94.5%) patients with active bleeding, and permanent hemostasis in 61 (87%). Efficacy of injection therapy was significantly lower in ulcers larger than 2 cm (p = 0.001), and in those located on the posteroinferior duodenal wall (p = 0.03). It was not possible to perform endoscopic injection in 8 (10%) patients due to difficulty of access, lesions located mainly high on the lesser gastric curvature and on the posteroinferior duodenal wall. From these results we conclude that endoscopic injection is a very useful technique for the initial treatment of high-risk bleeding peptic ulcer, although the size and anatomical location of the lesions may be a limitation of its use.
A phase I/II trial of 13-cis retinoic acid, alpha interferon, docetaxel, and estramustine (R.I.T.E.) for the treatment of hormone refractory prostate cancer (HRPC)
Authors: Y. A. Elsayed, A. Altscher, B. Hillard, S. Doyle-Lindrud, E. Teller, S. Goodin, W. J. Shih, E. H. Rubin, R. S. Dipaola
Journal: Journal of Clinical Oncology (2004)

4707 Background: Chemotherapy is limited for the treatment of HRPC secondary to the development of multiple mechanisms of resistance, such as the overexpression of Bcl-2. To test the hypothesis that 13-cis retinoic acid (R) and interferon alpha (I), which have been shown to decrease the expression of Bcl-2, are capable of improving the results of standard chemotherapy with docetaxel (T) and estramustine (E), we began a phase I/II study in patients with HRPC. Methods: Patients received retinoic acid, 1 mg/kg and interferon, six million units/m2 on days 1–4, estramustine, 280mg, orally tid on days 1–5, with escalating doses of docetaxel (0, 40, 50, 60mg/m2) on day 2. The treatment was repeated every 21 days. Each patient had peripheral blood mononuclear cells (PBMCs) obtained prior to therapy and on days 1–4 of the first cycle to assess the effect of therapy on Bcl-2 by immunoblot. Results: Ten patients have been enrolled in this ongoing phase I part of the study with 9-HRPC and1-Colon cancer. Nine of 10 patients had progressed on prior therapy. Therapy was well tolerated in this study. Grade 3 fatigue occurred in the first cycle of 2 patients in cohorts 3 and 4, defining a DLT, and in 3 additional patients beyond the first cycle. Fatigue resolved with interferon dose reduction, as planned per study. Grade 3 hypophosphotemia transiently occurred after the first cycle of therapy in 2 patients in cohort 2 and 1 patient in cohort 3. Grade 3 nausea/vomiting occurred in 2 patients beyond the first cycle in cohorts 1 and 3. Grade 4 neutropenia without fever occurred in 2 patients. Grade 3 hyperbilirubinemia transiently seen in 1 patient in cohort 3. PSA decreased in 9/9 patients with HRPC in the ongoing phase I study (mean decrease of 35%). A PSA decrease of ≥ 50% was seen in 2/9 patients. Assessment of Bcl-2 expression in PMCs is ongoing. Conclusions: RITE therapy is well tolerated and active in this ongoing phase I/II study. Following determination of the MTD, a phase II study in patients with HRPC will be completed. Assessment of RITE effect on PBMC Bcl-2 expression is ongoing and will be presented. This study is supported by DOD and Aventis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis; Neopharm; Esai; Supergene; Bristol-Myers Squibb; Wyeth
Time-Oriented Patient Records and a Computer Databank
Authors: James F. Fries
Journal: JAMA (1972)

Changes in clinical variables with time are critically important for evaluation of patient course, prognosis, and response to therapy. Traditional medical recording relates the individual observation to a "normal" value rather than to previous and subsequent observations. In a "time-oriented patient record," the record displays changes in clinical data with time, utilizing a "flow sheet" format. This record facilitates chart review and encourages use of data rather than memory in management decisions. The record is computer-compatible and permits development of a computer databank which may be flexibly utilized to answer a large variety of clinical questions. Patient status may be summarized, variables cross-correlated, clinical conditions reviewed, prognostic indicators measured, and response to various therapies compared. This type of computer record facilitates direct analysis of primary data and is a possible adjunct to traditional review of the literature. Output may be used for formal scientific study, for informal discussion, or for assistance in management of the individual patient.
A Mysterious Cluster of Deaths and Cardiopulmonary Arrests in a Pediatric Intensive Care Unit
Authors: Gregory R. Istre, Tracy L. Gustafson, Roy C. Baron, Deborah L. Martin, James P. Orlowski
Journal: New England Journal of Medicine (1985)

In the period April 1981 through June 1982, there was an unusual increase in the number of deaths and cardiopulmonary arrests in the pediatric intensive care unit at a large medical center hospital in San Antonio, Texas. During this period, 34 of 42 deaths (81 per cent) occurred in the evening work shift, as compared with 36 of 106 (34 per cent) during the previous four years (P less than 0.0001). Reviews of records of patients revealed no association between death in this 15-month epidemic period and a variety of demographic, historical, medical, and admission characteristics; medical or surgical procedures; or the severity of illness. The findings of a blinded clinical consultant support the conclusion that the increase in deaths and cardiopulmonary arrests could not be explained on the basis of the clinical status of the patients, and the consultant concluded that during the epidemic period, there were more deaths and cardiopulmonary arrests that were either unexpected in timing or inconsistent with the previous clinical course. The presence of one nurse was associated with the increased numbers of deaths (relative risk, 10.7; 95 per cent confidence limits, 6.4 to 17.9), cardiopulmonary arrests (relative risk = 25.5, confidence limits = 16.8 to 38.6), and unexpected clinical events, (relative risk, infinite; confidence limits, 33.7 to infinity). Although the cause of the epidemic remains unclear, the findings illustrate that surveillance of deaths and cardiopulmonary resuscitation may allow early recognition of similar problems in other hospitals.
And 'tis a kind of Good Deed to Say Well: and yet Words are no Deeds
Authors: Jerome A. Motto
Journal: JAMA (1965)

To the Editor:—  No amount of semantic maneuvering, hard logic, or heartfelt persuasion will take away the meaning or power of a word. Lives are sacrificed, battles won, causes surge to fulfillment, nations and peoples express their aspirations by rallying to a word. Whether attached to God, Freedom, Traitor, or ----, such concentrated emotional investment deserves the most serious consideration, since it may operate effectively to help or hinder attainment of goals.  The intensity of current enthusiasm and effort associated with the community psychiatric facilities and programs is being sabotaged by a stultifying word, Mental.  This word is rivalled only by Psycho as a handicap to overcoming an obstacle to preventive psychiatry: the obstacle of obtaining acceptance of psychiatric help by persons who need it. While Psycho is avoided by sensible persons, the word is voiced freely by workers concerned with bringing psychiatric skills to those who need them.  The reason
Cyclosporine's acceptance heralds new era in immunopharmacology
Authors: C. Macek
Journal: JAMA (1983)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Tissue engineered ceramic artificial joint—ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis
Authors: Hajime Ohgushi, Noriko Kotobuki, Hiroyuki Funaoka, Hiroko Machida, Motohiro Hirose, Yasuhito Tanaka, Yoshinori Takakura
Journal: Biomaterials (2005)
Sequelae and support after termination of pregnancy for fetal malformation.
Authors: J Lloyd, K M Laurence
Journal: BMJ (1985)

A retrospective study examined the reactions to the termination of pregnancy for fetal malformation and the follow up services that were available. Women resident in Mid Glamorgan who had had a termination between 1977 and 1981 because of positive findings after midtrimester prenatal diagnostic tests for neural tube defect or chromosome abnormalities were interviewed at home using a semistructured interview schedule. Three retrospective internal comparison groups were formed from those women who had also had a spontaneous abortion, previous stillbirth, or neonatal death or previous termination for medicosocial reasons early in pregnancy. Of the 48 women interviewed, 37 (77%) experienced an acute grief reaction after the index pregnancy was ended. This reaction was akin to that documented after stillbirth or neonatal death. Twenty two women (46%) remained symptomatic six months after the pregnancy had been ended, some requiring psychiatric support, compared with no such reaction after spontaneous abortion or termination for medicosocial reasons. All the women who had previously had a stillbirth or neonatal death were visited at home either by the general practitioner or by the midwife after that event but such follow up was limited to only eight of the study group after termination for fetal malformation. The findings suggest that support is inadequate for these patients and that improved follow up and counselling services may lessen the adverse sequelae of termination for fetal malformation.
Drug resistant tuberculosis
Authors: P D O Davies
Journal: BMJ (1995)

0Io io io 40 O 10 20 30 40 5o Week Weekly measles notifications in 1987-8 (when last measles epidemic occurred) and 1994, England and Wales their stage of development, to break chains of transmission.When the campaign was planned different methods of delivering services were costed.The cost of preventing an epidemic was estimated at around C20m for the vaccine,