tbuckley/cabot-search huggingface dataset:
Abstract LB-138: Autophagy regulator BECN1 acts as a context-dependent tumor suppressor opposing parity-associated and WNT1-driven mammary tumorigenesis
Authors: Michelle Cicchini, Rumela Chakrabarti, Sameera Kongara, Sandy Price, Ritu Nahar, Fred Lozy, Hua Zhong, Alexei Vazquez, Yibin Kang, Vassiliki Karantza
Journal: Cancer Research (2014)

Abstract Earlier studies reported allelic deletion of the essential autophagy regulator BECN1 in breast cancers implicating BECN1 loss and defective autophagy in tumorigenesis. Recent studies questioned the tumor suppressive role of autophagy, as Atg defects, including Becn1 deletion, suppress tumorigenesis in mouse tumor models. For the first time, we report that monoallelic Becn1 loss has a context-specific tumor-promoting function in parity-associated and WNT-driven mammary tumorigenesis. Our studies demonstrate that Becn1 heterozygocity promotes immature mammary epithelial cell expansion, Receptor Activator of NFκB (RANK) signaling and mammary tumorigenesis in cooperation with the progenitor cell-transforming WNT pathway. Similar to our mouse model, low BECN1 expression and WNT pathway activation in human breast tumors correlate with triple negative breast cancers (TNBCs), RANK axis activation and poor prognosis. Our results provide novel insight in the seemingly paradoxical role of BECN1 in tumorigenesis and the basis for further studies on pathophysiology and treatment of clinically aggressive TNBCs. Citation Format: Michelle Cicchini, Rumela Chakrabarti, Sameera Kongara, Sandy Price, Ritu Nahar, Fred Lozy, Hua Zhong, Alexei Vazquez, Yibin Kang, Vassiliki Karantza. Autophagy regulator BECN1 acts as a context-dependent tumor suppressor opposing parity-associated and WNT1-driven mammary tumorigenesis. [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 LB-138. doi:10.1158/1538-7445.AM2014-LB-138
CD1a-positive familial cutaneous mastocytosis without germ-line or somatic mutations in c-kit
Authors: N. Arase, M. Wataya-Kaneda, N. Oiso, H. Arase, I. Katayama
Journal: British Journal of Dermatology (2013)

Journal Article CD1a‐positive familial cutaneous mastocytosis without germ‐line or somatic mutations in c‐kit Get access N. Arase, N. Arase Department of Dermatology Graduate School of Medicine Osaka University 2‐2, Yamadaoka Suita Osaka 565‐0871 Japan Search for other works by this author on: Oxford Academic Google Scholar M. Wataya‐Kaneda, M. Wataya‐Kaneda Department of Dermatology Graduate School of Medicine Osaka University 2‐2, Yamadaoka Suita Osaka 565‐0871 Japan Search for other works by this author on: Oxford Academic Google Scholar N. Oiso, N. Oiso Department of Dermatology Faculty of Medicine Kinki University Osakasasayama Japan Search for other works by this author on: Oxford Academic Google Scholar H. Arase, H. Arase Laboratory of Immunochemistry WPI Immunology Frontier Research Center Department of Immunochemistry Research Institute for Microbial Diseases Osaka University Suita JapanCore Research for Evolutional Science and Technology Japan Science and Technology Agency Kawaguchi Japan Search for other works by this author on: Oxford Academic Google Scholar I. Katayama I. Katayama Department of Dermatology Graduate School of Medicine Osaka University 2‐2, Yamadaoka Suita Osaka 565‐0871 Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue 1, 1 July 2013, Pages 201–204, https://doi.org/10.1111/bjd.12265 Published: 01 July 2013
Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.
Authors: C Pothoulakis, R J Gilbert, C Cladaras, I Castagliuolo, G Semenza, Y Hitti, J S Montcrief, J Linevsky, C P Kelly, S Nikulasson, H P Desai, T D Wilkins, J T LaMont
Journal: Journal of Clinical Investigation (1996)

The intestinal effects of Clostridium difficile toxin A are inidated by toxin binding to luminal enterocyte receptors. We reported previously that the rabbit ileal brush border (BB) receptor is a glycoprotein with an alpha-d-galactose containing trisaccharide in the toxin-binding domain (1991. J. Clin. Invest. 88:119-125). In this study we characterized the rabbit ileal BB receptor for this toxin. Purified toxin receptor peptides of 19 and 24 amino acids showed 100% homology with rabbit sucrase-isomaltase (SI). Guinea pig receptor antiserum reacted in Western blots with rabbit SI and with the purified toxin receptor. Antireceptor IgG blocked in vitro binding of toxin A to rabbit ileal villus cell BB. Furthermore, anti-SI IgG inhibited toxin A-induced secretion (by 78.1%, P < 0.01), intestinal permeability (by 80.8%, P < 0.01), and histologic injury (P < 0.01) in rabbit ileal loops in vivo. Chinese hamster ovary cells transfected with SI cDNA showed increased intracellular calcium increase in response to native toxin (holotoxin) or to a recombinant 873-amino acid peptide representing the receptor binding domain of toxin A. These data suggest that toxin A binds specifically to carbohydrate domains on rabbit ileal SI, and that such binding is relevant to signal transduction mechanisms that mediate in vitro and in vivo toxicity.
Repeat intracoronary gamma radiation for patients with in-stent restenosis who failed radiation therapy
Authors: Ron Waksman, Andrew E. Ajani, Lowell F. Satler, Kenneth M. Kent, Michael Parrazzo, Neil J. Weissman, Robert Lew, Rebecca Torguson, Edourd F. Cheneau, Ellen Pinnow, Daniel A. Canos, Augusto D. Pichard
Journal: Journal of the American College of Cardiology (2003)
Oncologists’ Attitudes Toward and Practices in Giving Bad News: An Exploratory Study
Authors: Walter F. Baile, Renato Lenzi, Patricia A. Parker, Robert Buckman, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2002)

To examine the attitudes and practices of oncologists in disclosure of unfavorable medical information to cancer patients.A questionnaire was administered to a group of physicians who attended the 1999 Annual Meeting of the American Society of Clinical Oncology. The questionnaire assessed demographic and practice-related information and the frequency of patient encounters in which unfavorable cancer-related information was disclosed. Participants were also asked about difficulties they had when approaching stressful discussions and communication strategies used in giving unfavorable information.The questionnaire was completed by 167 oncologists. Sixty-four percent were medical oncologists. Thirty-eight percent practiced in North America, 26% practiced in Europe, 13% practiced in South America, and 13% practiced in Asia. Participants gave bad news to patients an average of 35 times per month. Discussing no further curative treatment and hospice was reported as most difficult. In disclosing the cancer diagnosis and prognosis, physicians from Western countries were less likely to withhold unfavorable information from the patient at the family's request, avoid the discussion entirely, use euphemisms, and give treatments known not to be effective so as not to destroy hope than physicians from other countries. There was significant variability in opinions regarding the best time to discuss resuscitation, with 18% of respondents believing that it should be done close to the end of life.There was significant variability in how physicians approach information disclosure to cancer patients. Factors such as geographical region and cultural and family variables may be important influences in this process.
New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes
Authors: Helen Sheldon, Emily Heikamp, Helen Turley, Rebecca Dragovic, Peter Thomas, Chern Ein Oon, Russell Leek, Mariola Edelmann, Benedikt Kessler, Richard C. A. Sainson, Ian Sargent, Ji-Liang Li, Adrian L. Harris
Journal: Blood (2010)
The Development of the Science of Nutrition in Relation to Disease
Authors: J. B. Orr
Journal: BMJ (1931)

ME BRAL 883indication to the patient that his current activities are harmful and must be stopped at once, or death will ensue.But there remain a few patients whose sufferings are so severe that relief at any cost seems desirable.Numerous operations on the cervical nerves and ganglia have been performed with the object of severing the sensory communications between the heart and the brain; but so far as our knowledge goes these operations are based upon erroneous theories.The sensory tracts run into the upper dorsal segments of the spinal cord, and not along the neck.It is known that left-sided pain is referred from the heart to the upper five or six segments, the chief pathway being along the inferior cardiac nerves, the stellate ganglion, the vertebral sympathetic ganglia, and the white rami communicantes to the spinal cord.Subsidiary pathways may exist along the middle cardiac nerves and the lower cervical sympathetic trunk to the stellate ganglion ; and directly from the heart to the upper dorsal vertebral ganglia' (Fig. 2).C r > ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. 2 4 ' ~~~~~~~~6 3 I~~~~~~~.DH= ,
Letter: Propanidid in dysrrhythmias.
Authors: S Homsek
Journal: BMJ (1976)

extremely well, obviating the need for intrathecal administration.Also we are not aware of any evidence to suggest that penicillin allergy increases the risk of adverse reactions to chloramphenicol.Consequently it would appear that when the organism is sensitive to chloramphenicol this drug is the treatment of choice for bacterial meningitis in the penicillinallergic patient.
Survey shows serious shortage of medical academics in the UK
Authors: R. MacDonald
Journal: BMJ (2002)

Polymorphism of MHC and MHC-linked genes is tightly associated with susceptibility to type 1 diabetes (T1D) in human and animal models. Despite the extensive studies, however, the role of MHC and MHC-linked genes expressed by T cells on T1D susceptibility remains unclear. Because T cells develop from TCR<sup>−</sup> thymic precursor (pre-T) cells that undergo MHC restriction mediated by thymic stroma cells, we reconstituted the T cell compartment of NOD.scid-RIP-B7.1 mice using pre-T cells isolated from NOD, NOR, AKR, and C57BL/6 (B6) mice. T1D developed rapidly in the mice reconstituted with pre-T cells derived from NOD or NOR donors. In contrast, most of the NOD.scid-RIP-B7.1 mice reconstituted with pre-T cells from AKR or B6 donors were free of T1D. Further analysis revealed that genes within MHC locus of AKR or B6 origin reduced incidence of T1D in the reconstituted NOD.scid-RIP-B7.1 mice. The expression of MHC class I genes of <i>k</i>, but not <i>b</i> haplotype, in T cells conferred T1D resistance. Replacement of an interval near the distal end of the D region in T cells of B6 origin with an identical allele of 129.S6 origin resulted in T1D development in the reconstituted mice. These results provide evidence that the expression of MHC class I and MHC-linked genes in T cells of NOD mice indeed contributes to T1D susceptibility, while expression of specific resistance alleles of MHC or MHC-linked genes in T cells alone would effectively reduce or even prevent T1D.
Escherichia coli and Tropical Sprue
Authors: Michael D. Dickman, R. W. Schaedler, A. R. Chappelka
Journal: Annals of Internal Medicine (1974)

Comments1 July 1974Escherichia coli and Tropical SprueMICHAEL D. DICKMAN, PH.D., R. W. SCHAEDLER, M.D., A. R. CHAPPELKAMICHAEL D. DICKMAN, PH.D., R. W. SCHAEDLER, M.D., A. R. CHAPPELKAAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-1-128_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The report of Klipstein and colleagues (Ann Intern Med 79:632-641) that stresses the isolation of toxin-producing Enterobacteriaciae from the midjejenum of patients with tropical sprue is consistent with our findings in a patient studied for more than 1 year.Patient B came to the Philadelphia Naval Hospital after the completion of his second tour of duty in Vietnam. Initial complaints were of acute watery episodes of diarrhea with the passage of 10 to 15 fluid stools daily, tenesmus, and weight loss.The diagnosis of tropical sprue was based on an abnormal Schilling test (3%), D-xylose excretion (10%),...References1. ARANKISYEDKENNEY ASE: Isolation of anaerobic bacteria from human gingiva and mouse cecum by means of a simplified glove box procedure. Appl Microbiol 17:568-576, 1969 CrossrefMedlineGoogle Scholar2. SCHAEDLERDUBOSCOSTELLO RRR: The development of the bacterial flora in the gastrointestinal tract of mice. J Exp Med 122:59-66, 1965 CrossrefMedlineGoogle Scholar3. FINEGOLDSUTTERBOYLE SVJ: The normal flora of ileostomy and transverse colostomy effluents. J Infect Dis 122:376-381, 1970 CrossrefMedlineGoogle Scholar4. KLIPSTEINBEAUCHAMPCORCINO FIJ: Nutritional status and intestinal function among rural populations in the West Indies. Gastroenterology 63:758-767, 1972 CrossrefMedlineGoogle Scholar5. SPRINZSRIBHIBHADHGANGAROSA HRE: Biopsy of small bowel of Thai people. Am J Clin Pathol 38:43-51, 1962 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: MC USN Department of Internal Medicine Gastroenterology Branch U.S. Naval Hospital Philadelphia, Pennsylvania 19145 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAcute Bacterial GastroenteritisContamination of the Small Intestine by Enterotoxigenic Coliform Bacteria among the Rural Population of Haiti 1 July 1974Volume 81, Issue 1Page: 128-128KeywordsDiarrheaEscherichia coliExcretionWeight lossXylose ePublished: 1 December 2008 Issue Published: 1 July 1974 PDF downloadLoading ...
Couple wins right to select embryo
Authors: C. Dyer
Journal: BMJ (2003)

A couple hoping to conceive a baby whose umbilical cord blood could save the life of their 4 year old son was given the go-ahead for the treatment by the Court of Appeal this week.

The couple, Raj and Shahana Hashmi, from Leeds, had their hopes dashed last December, when a High Court judge, Mr Justice Maurice Kay, ruled that the Human Fertilisation and Embryology Authority (HFEA) had no power to license the treatment—tissue typing with embryo selection.

The HFEA took the case to the Court of Appeal. On Tuesday, Lord Phillips, master of the rolls, Lord Justice Schiemann, and Lord Justice Mance, overturned the High Court …
C-Reactive Protein Promotes Monocyte Chemoattractant Protein-1—Mediated Chemotaxis Through Upregulating CC Chemokine Receptor 2 Expression in Human Monocytes
Authors: Ki Hoon Han, Kyung-Hee Hong, Jae-Hyeong Park, Jesang Ko, Duk-Hyun Kang, Kee-Joon Choi, Myeong-Ki Hong, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2004)

Inflammation plays a crucial role in atherosclerosis. An elevated serum C-reactive protein (CRP) level is a strong marker for future atherosclerotic cardiovascular diseases. In addition, recent data suggest that CRP may directly promote atherogenesis. In this study, we investigated whether CRP can directly activate human circulating monocytes.Incubation of THP-1 monocytes with CRP (10 microg/mL) increased CC chemokine receptor 2 (CCR2) expression at both the protein and transcript levels, which in turn enhanced chemotaxis mediated by monocyte chemoattractant protein-1 (MCP-1) up to 2-fold. The CRP-induced upregulation of CCR2 expression involved binding of CRP to the FcgammaR, most notably FcgammaRI, and phospholipase D1 activation. Serum high-sensitivity CRP levels in 52 normocholesterolemic human subjects were positively correlated with CCR2 surface expression on circulating monocytes (r=0.62, P<0.001) and MCP-1-mediated monocyte chemotaxis (r=0.53, P<0.001).Elevated blood CRP levels may promote accumulation of monocytes in the atherogenic arterial wall by increasing chemotactic activities of monocytes in response to MCP-1.
John Gordon Edgar
Authors: J S Metcalfe
Journal: BMJ (2001)

Former general practitioner Pudsey in Yorkshire and Southsea (b 1927; q Leeds 1951; DCH, MRCGP), died from heart failure on 7 September 2001.

As a student he developed asthma and rhinitis, which was to affect his whole life but not prevent its fulfilment. He served in the Royal Naval Volunteer Reserve after and before posts in Yorkshire hospitals. He became an assistant in general practice in 1956. In 1958 he joined a group practice in Pudsey. In 1981, on medical advice, he left Yorkshire for the kinder weather of a Southsea practice. He left this in 1985 to become a paediatric chief medical officer until 1993, when he had a myocardial infarction. Despite several further illnesses, he was active before and after retirement, playing golf, walking, gardening, birdwatching, and travelling widely. He leaves a wife, Pam; three sons; and five grandchildren.
THE METABOLIC FACTOR IN CHRONIC RHEUMATISM WITH SPECIAL REFERENCE TO FIBROSITIS
Authors: R. G. Gordon
Journal: BMJ (1936)

OBJECTIVE:To quantify longitudinal changes in gait in Friedreich’s Ataxia (FA) patients compared to controls during a 24-month period using the GAITRite Walkway System. BACKGROUND:FA is a devastating neurodegenerative disease. Measures to accurately quantify small changes in neurological function in FA patients are needed to facilitate therapeutic clinical trials. DESIGN/METHODS:This was a prospective, longitudinal study that assessed ambulatory FA patients compared to age- and gender-matched controls. FA patients were examined at baseline and at 6, 12, and 24 months, using the GAITRite Walkway system, a portable instrument used to assess gait parameters, and the Friedreich’s Ataxia Rating Scale (FARS). Controls were evaluated at baseline and 12 months. Changes in various gait parameters over time were estimated and compared using descriptive statistics and multilevel modeling. RESULTS:Eight FA patients (aged 29.4 ± 9.0) and 8 controls (aged 29.6 ± 9.1) were included in this analysis. In FA patients, the mean FARS score increased 21.0[percnt] over two years (baseline: 40.6; 12 months: 45.4; 24 months: 49.1). Using longitudinal multilevel modeling, the FARS score was estimated to increase 0.13 points per month in FA patients, reflecting an increase in neurological dysfunction. Comfortable gait velocity declined 15[percnt] after 12 months and 30.5[percnt] after 24 months in the FA group, and showed high validity for measuring neurological dysfunction. Comfortable gait velocity correlated strongly with the FARS total score (r=-0.536;p &lt;0.002), FARS lower extremity coordination (r=-0.424;p = 0.015) and FARS upright stability score (r=-0.191;p =0.002), and had high reproducibility (r=0.90). CONCLUSIONS:Comfortable gait velocity as measured by the GAITRite system showed better sensitivity to changing gait that did the FARS, and had excellent reproducibility in controls whose gait was not expected to change. Comfortable gait velocity is easily performed, and may be an important and clinically relevant endpoint for future clinical trials. Study Supported by:Friedreich9s Ataxia Research Alliance (FARA) <b>Disclosure:</b> Dr. Zesiewicz has received personal compensation for activities with Teva Neuroscience, General Electric, ProCe, and UCB Pharma as a speaker. Dr. Zesiewicz has received research support from Friedreich9s Ataxia Research Alliance. Dr. Gooch has received personal compensation for activities with NeuralStem, Baxter Pharmaceuticals, Multifocal Motor Neuropathy, and CSL Behring. Dr. Gooch has received research support from Baxter Pharmaceuticals. Dr. Kim has nothing to disclose. Dr. Farmer has nothing to disclose. Dr. Jahan has nothing to disclose. Dr. Huang has nothing to disclose. Dr. Salemi has nothing to disclose. Dr. Sullivan has nothing to disclose. Dr. Stephenson has nothing to disclose.
Brachytherapy Using Injectable Seeds That Are Self-Assembled from Genetically Encoded Polypeptides <i>In Situ</i>
Authors: Wenge Liu, Jonathan McDaniel, Xinghai Li, Daisuke Asai, Felipe Garcia Quiroz, Jeffery Schaal, Ji Sun Park, Michael Zalutsky, Ashutosh Chilkoti
Journal: Cancer Research (2012)

Brachytherapy is a common clinical technique involving implantation of sealed radioactive "seeds" within a tumor to selectively irradiate the tumor mass while minimizing systemic toxicity. To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, we have developed an alternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with (131)I that self-assembles into radionuclide seeds upon intratumoral injection. The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy.
Constitutive Notch2 signaling induces hepatic tumors in mice
Authors: Michael T. Dill, Luigi Tornillo, Thorsten Fritzius, Luigi Terracciano, David Semela, Bernhard Bettler, Markus H. Heim, Jan S. Tchorz
Journal: Hepatology (2012)

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCC) are the most common liver tumors and a leading cause for cancer-related death in men. Notch2 regulates cellular differentiation in the developing and adult liver. Although aberrant Notch signaling is implicated in various cancers, it is still unclear whether Notch2 regulates proliferation and differentiation in liver carcinogenesis and thereby contributes to HCC and CCC formation. Here, we investigated the oncogenic potential of constitutive Notch2 signaling in the liver. We show that liver-specific expression of the intracellular domain of Notch2 (N2ICD) in mice is sufficient to induce HCC formation and biliary hyperplasia. Specifically, constitutive N2ICD signaling in the liver leads to up-regulation of pro-proliferative genes and proliferation of hepatocytes and biliary epithelial cells (BECs). Using the diethylnitrosamine (DEN) HCC carcinogenesis model, we further show that constitutive Notch2 signaling accelerates DEN-induced HCC formation. DEN-induced HCCs with constitutive Notch2 signaling (DEN(N2ICD) HCCs) exhibit a marked increase in size, proliferation, and expression of pro-proliferative genes when compared with HCCs from DEN-induced control mice (DEN(ctrl) HCCs). Moreover, DEN(N2ICD) HCCs exhibit increased Sox9 messenger RNA (mRNA) levels and reduced Albumin and Alpha-fetoprotein mRNA levels, indicating that they are less differentiated than DEN(ctrl) HCCs. Additionally, DEN(N2ICD) mice develop large hepatic cysts, dysplasia of the biliary epithelium, and eventually CCC. CCC formation in patients and DEN(N2ICD) mice is accompanied by re-expression of hepatocyte nuclear factor 4α(HNF4α), possibly indicating dedifferentiation of BECs.Our data establish an oncogenic role for constitutive Notch2 signaling in liver cancer development.