tbuckley/cabot-search huggingface dataset:
Abstract P5-05-08: Obesity suppresses estrogen receptor beta expression in breast cancer cells via a HER2-mediated pathway
Authors: MA Wiese, LW Bowers, RR Tekmal, AJ Brenner, SD Hursting, LA deGraffenried
Journal: Cancer Research (2013)

Abstract Purpose: Increased levels of estrogen receptor beta (ERb) are correlated with an improved breast cancer prognosis. Our preliminary data suggests that obesity may decrease ERβ expression in certain breast cancer subtypes and may contribute to the more aggressive disease associated with obesity. This study aims to elucidate a potential mechanism(s) mediating this suppression. Experimental Design: We utilized an in vitro model of obesity in which breast cancer cells were exposed to sera collected from postmenopausal breast cancer patients at the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio (UTHSCSA) and pooled by BMI category (obese (OB): ≥30 kg/m2; normal weight (NW): 18.5-24.9 kg/m2). Four human mammary tumor cell lines were used: SKBR3 (HER2 over-expressing, ERα negative), MCF-7 and ZR75 (ERα positive, HER2 negative) and MDA-MB-231 (triple negative), in addition to the mouse mammary tumor cell line, MMTV/neu (HER2 over-expressing). The effects of the sera on ERβ expression were assessed by qPCR. Protein expression levels were determined using Western blot analyses. Herceptin, a HER2 antagonist, was used to evaluate the role of HER2 in OB sera-induced ERβ modulation. Results: OB sera exposure led to lower ERβ expression in SKBR3 and MMTV/neu cells in comparison to NW. Treatment of the SKBR3 cells with Herceptin at the time of OB sera exposure resulted in a three-fold increase in ERβ expression. In contrast, there was only a small increase in SKBR3 cell ERβ expression when Herceptin was added to NW sera, suggesting that the effects of the OB sera may be mediated by HER2 activity. In support of this hypothesis, exposure to OB versus NW sera did not modulate ERβ expression in MDA-MB-231, MCF-7 and ZR75 cells, which have very low levels of HER2. Lapatinib, another HER2 antagonist, will be used to inhibit HER2 signaling in MMTV/neu cells. On-going studies utilizing siRNA to the HER2 receptor aim to elucidate the HER2-regulated pathways contributing to the ERβ suppressing effects of OB sera in SKBR3 cells. Conclusion: Based on our preliminary data, we hypothesize that obesity suppresses ERβ expression in breast cancer cells via a HER2-mediated pathway. Elucidation of the mechanism(s) mediating this effect could provide important insight into both the regulation of ERβ expression as well as how obesity promotes a more aggressive disease. Increased knowledge regarding the regulation of this effect may result in the identification of a new treatment target for the obese breast cancer patient population. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-08.
Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in mice
Authors: Ping Gong, Jelita Roseman, Celia G Fernandez, Kulandaivelu S Vetrivel, Vytautas P Bindokas, Lois A Zitzow, Satyabrata Kar, Angèle T Parent, Gopal Thinakaran
Journal: Molecular Neurodegeneration (2011)

Abstract Background p23 belongs to the highly conserved p24 family of type I transmembrane proteins, which participate in the bidirectional protein transport between the endoplasmic reticulum and Golgi apparatus. Mammalian p23 has been shown to interact with γ-secretase complex, and modulate secretory trafficking as well as intramembranous processing of amyloid precursor protein in cultured cells. Negative modulation of β-amyloid production by p23 in cultured cell lines suggested that elevation of p23 expression in neurons might mitigate cerebral amyloid burden. Results We generated several lines of transgenic mice expressing human p23 in neurons under the control of Thy-1.2 promoter. We found that even a 50% increase in p23 levels in the central nervous system of mice causes post-natal growth retardation, severe neurological problems characterized by tremors, seizure, ataxia, and uncoordinated movements, and premature death. The severity of the phenotype closely correlated with the level of p23 overexpression in multiple transgenic lines. While the number and general morphology of neurons in Hup23 mice appeared to be normal throughout the brain, abnormal non-Golgi p23 localization was observed in a subset of neurons with high transgene expression in brainstem. Moreover, detailed immunofluorescence analysis revealed marked proliferation of astrocytes, activation of microglia, and thinning of myelinated bundles in brainstem of Hup23 mice. Conclusions These results demonstrate that proper level of p23 expression is critical for neuronal function, and perturbing p23 function by overexpression initiates a cascade of cellular reactions in brainstem that leads to severe motor deficits and other neurological problems, which culminate in premature death. The neurological phenotype observed in Hup23 mice highlights significant adverse effects associated with manipulating neuronal expression of p23, a previously described negative modulator of γ-secretase activity and β-amyloid production. Moreover, our report has broader relevance to molecular mechanisms in several neurodegenerative diseases as it highlights the inherent vulnerability of the early secretory pathway mechanisms that ensure proteostasis in neurons.
Myocardial Fibrosis in DOCA-Salt Hypertensive Rats
Authors: Fatima Ammarguellat, Isabelle Larouche, Ernesto L. Schiffrin
Journal: Circulation (2001)

Background —To test the hypothesis that endothelin-1 contributes to cardiac fibrosis, cardiac collagen deposition was studied in deoxycorticosterone acetate–salt (DOCA-salt) hypertensive rats, in which the endothelin system is activated. The effects of the ET A -selective endothelin receptor antagonist A-127722 were evaluated. Methods and Results —A-127722 (30 mg/kg per day) was administered for 4 weeks. Myocardial fibrosis was evaluated after Sirius red F3BA staining. Systolic blood pressure was 103±1.6 mm Hg in unilaterally nephrectomized rats (Uni-Nx), 202±3.2 mm Hg in DOCA-salt rats ( P &lt;0.01 versus Uni-Nx), and 182±3.1 mm Hg in ET A antagonist–treated DOCA-salt rats ( P &lt;0.01 versus DOCA-salt or Uni-Nx). In DOCA-salt rats, interstitial and perivascular collagen density was increased in the subendocardial and midmyocardial regions of the left ventricle (3- to 4-fold, P &lt;0.05), whereas in subepicardial myocardium, the increase was predominantly perivascular. The ET A antagonist prevented cardiac fibrosis in DOCA-salt rats. Procollagen I and III mRNA, which were increased in hearts of DOCA-salt rats, were normalized by ET A antagonist treatment. TGF-β 1 mRNA and TGF-β 1 protein increased at 1 week in DOCA-salt rats and were lowered in ET A antagonist–treated rats. Conclusions —ET A receptor–mediated collagen deposition in hearts of DOCA-salt rats results from increased procollagen synthesis associated with an initial increment in expression of TGF-β 1 . These results support the hypothesis of a role for endothelin-1 in cardiac collagen deposition in mineralocorticoid hypertension, which may have pathophysiological and pharmacological implications in hypertensive heart disease.
Experimental chemotherapy-induced skin necrosis in swine. Mechanistic studies of anthracycline antibiotic toxicity and protection with a radical dimer compound.
Authors: S D Averbuch, M Boldt, G Gaudiano, J B Stern, T H Koch, N R Bachur
Journal: Journal of Clinical Investigation (1988)

The reactivity of antitumor anthracycline and mitomycin C antibiotics with the oxomorpholinyl radical dimers, bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM3) and bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3), was studied in vitro. The oxomorpholinyl radical reduced daunorubicin to a quinone methide intermediate that reacted with solvent to form 7-deoxydaunorubicinone. The solvolysis reaction followed first order kinetics, and the reactivity rate constants (k2) measured for seven anthracycline analogues ranged from 2 X 10(-2) s-1 to 8.0 X 10(-4) s-1. The chemical reactivity of each anthracycline quinone methide correlated with the total skin toxicity caused by the respective parent anthracycline following injection into swine skin. Microscopic examination of experimental lesions in swine skin resemble those observed in humans after inadvertant chemotherapy extravasation. Hydrocortisone sodium succinate was not effective for the treatment of doxorubicin-induced skin necrosis, whereas DHM3 was effective for the treatment of skin necrosis caused by all seven anthracyclines and by the quinone containing antibiotic, mitomycin C.
Use of the Thymus Gland: An Original Theory, with Explanatory Remarks
Authors: H. G. Wright
Journal: BMJ (1852)

far the largest proportion of cases of fever there treated are cases of typhus.Thus, of the 4,819 cases treated during 1848, 4,694 were cases of typhus; 101 cases of febricula; 3 of dothinentenrtis, or typhoid; and 21 of intermittent fever; while of the 313 cases of fever treated in the Royal Free Hospital, during the three years here reported upon, 44 were cases of intermittent fever, a very large proportion were cases of typhoid, remittent or relapsing, or ephemeral fever, and but very few cases of true typhus occurred.At present, however, I am not able to give the proportions of these several forms of disease; though, should leisure permit, I shal hope to do so hereafter.
QT-Interval Prolongation, Paroxysmal Ventricular Arrhythmias, and Convulsive Syncope
Authors: ROBERT A. RATSHIN
Journal: Annals of Internal Medicine (1971)

A patient with prolonged QTc interval, paroxysmal ventricular tachycardia, and syncope was studied. Her syncopal episodes were often precipitated by stress or unexpected stimuli. Neurological evaluation showed no abnormalities. Right and left stellate ganglion blockade and intravenous atropine, calcium gluconate, and digoxin did not shorten QTc-interval duration. Ventricular pacing and intravenous phenobarbital suppressed ventricular tachyarrhythmias. Sodium diphenylhydantoin (Dilantin Sodium®) produced QTc shortening and controlled ectopic rhythms. Neural influence on synchrony of ventricular repolarization may predispose to the paroxysmal arrhythmias associated with this syndrome. Central nervous and asymmetrical cardiac sympathetic nervous stimulation may produce an increase in temporal dispersion of repolarization and a prolonged refractory period, thus facilitating reentrant rhythms and tachyarrhythmias. Sodium diphenylhydantoin shortens repolarization and effective refractory period and increases the conduction velocity of ectopic ventricular impulses, reducing temporal dispersion and suppressing reentrant rhythms. QT-prolongation syndromes are potentially lethal and may account for a number of cases of "atypical epilepsy."
99mTcO4 Visualization of Septic Pulmonary Emboli During Thyroid Scintigraphy
Authors: Zeynep Erdoğan, Güler Silov, Ümmühan Abdülrezzak, Ali İhsan Günal, Zerrin Bozbey
Journal: Clinical Nuclear Medicine (2013)

A case of 99mTcO4 accumulation within the thorax is reported, consistent with septic emboli and thyroiditis during routine thyroid scintigraphy for subclinical hyperthyroidism. After antibiotic treatment, repeated 99mTcO4 imaging revealed complete resolution of foci of septic emboli.
In vivo disassembly of IV administered siRNA matrix nanoparticles at the renal filtration barrier
Authors: Broes Naeye, Hendrik Deschout, Vicky Caveliers, Benedicte Descamps, Kevin Braeckmans, Christian Vanhove, Jo Demeester, Tony Lahoutte, Stefaan C. De Smedt, Koen Raemdonck
Journal: Biomaterials (2012)
Ki11502, a novel multitargeted receptor tyrosine kinase inhibitor, induces growth arrest and apoptosis of human leukemia cells in vitro and in vivo
Authors: Chie Nishioka, Takayuki Ikezoe, Jing Yang, Atsushi Miwa, Taizo Tasaka, Yoshio Kuwayama, Kazuto Togitani, H. Phillip Koeffler, Akihito Yokoyama
Journal: Blood (2008)
Hospital Librarian and Continuing Education
Authors: JO-ANN M. BABISH
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 August 1980Hospital Librarian and Continuing EducationJO-ANN M. BABISH, MSLSJO-ANN M. BABISH, MSLSSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-2-381_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I was pleased to read your recent editorial (1) that Dr. Huth concluded with a reference to well-equipped hospital libraries as one possible aid in meeting educational needs of physicians. I should point out, however, that a resource more valuable than a room full of books and journals is an educated librarian able to meet these needs.Hospital librarians are doing an excellent job not only of maintaining useful library collections but also of delivering good information services to hospital staffs. Your editorial comments that continuing education must include a means for getting information to clinicians quickly...References1. HUTH E. Continuing medical education: needs, costs, and consequences. Ann Intern Med. 1980;92:698-9. Editorial. LinkGoogle Scholar2. ARCARI R and LAMB G. The librarian in clinical care. Hosp Med Staff. 1977;6:18-23. MedlineGoogle Scholar3. SOWELL S. LATCH at the Washington Hospital Center, 1967-1975. Bull Med Libr Assoc. 1978;66:218-22. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JO-ANN M. BABISH, MSLSAffiliations: Moses Taylor Hospital Library Scranton, PA 18510 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1980Volume 93, Issue 2Page: 381-382KeywordsLibraries ePublished: 1 December 2008 Issue Published: 1 August 1980 PDF downloadLoading ...
Analysis of a T-cell receptor V beta segment implicated in susceptibility to rheumatoid arthritis: V beta 2 germline polymorphism does not encode susceptibility.
Authors: K Pile, P Wordsworth, F Liote, T Bardin, J Bell, F Cornelis
Journal: Annals of the Rheumatic Diseases (1993)

The assessment of allelic polymorphism of the T cell receptor gene segment, TCRBV2S1, in rheumatoid arthritis.A total of 136 patients with rheumatoid arthritis (RA) (ACR criteria) and 150 controls were TCRBV2S1 genotyped using a nested PCR amplification strategy followed by single-strand conformation polymorphism (SSCP) analysis.The SSCP typing method detected two previously unknown alleles of the TCRBV2S1 gene segment. The TCRBV2S1 allele, genotype and inferred phenotype frequencies were similar in the RA patients and controls. No differences were apparent after the RA patients had been partitioned according to their HLA-DR genotypes.SSCP analysis is a rapid and efficient method of typing T cell receptor germline polymorphisms. Allelic polymorphism of the T cell receptor variable segment, TCRBV2S1, does not influence susceptibility to RA.
Acute myocardial infarction with normal coronary arteries: a possible manifestation of the billowing mitral leaflet syndrome.
Authors: E Chesler, R E Matisonn, J B Lakier, W A Pocock, I W Obel, J B Barlow
Journal: Circulation (1976)

The findings in four young patients with the billowing mitral leaflet syndrome who presented with evidence of acute myocardial infarction are reported. Because technically adequate coronary arteriograms demonstrated patent vessels and the electrocardiograms initially showed pronounced elevation of the ST segments as occurs in Prinzmetal's angina, it is postulated that spasm of normal coronary arteries was the operative factor. Scrutiny of those cases of clinically apparent ischemic heart disease with normal coronary angiograms is suggested to establish whether there is in fact a causal relationship with the billowing mitral leaflet syndrome.
Critical Care Medicine
Authors: Harry B. Greenberg
Journal: JAMA (1975)

Reading about critical care medicine is easy and often entertaining. The recovery rooms and the newly expanded intensive care, coronary care, and respiratory care units of our hospitals provide elaborate life support systems. Patients get new drugs, treatment moves quickly, minutes count.  The man surviving a ruptured berry aneurysm needs surgery as soon as his condition permits. Unwarranted delay risks further hemorrhage, more brain damage, and death. On the other hand, surgery is best avoided when the patient has intracranial hemorrhage. Giving him cerebral dehydrating agents at the right time can help him escape uncal herniation and brain stem compression. Aggressively managing a patient with stroke in evolution may involve immediate anticoagulation with heparin as well as giving him vasopressor drugs, and urea, mannitol, glycerol, or dexamethasone, or all of these.  When trauma sends large quantities of liquid fat into a patient's bloodstream, he may suffer focal neurologic defects, confusion,
A walk on the wild side—emerging wildlife diseases
Authors: Andrew A Cunningham
Journal: BMJ (2005)

Likewise, liaison between organisations at government and national levels is a prerequisite for deciding policies and disseminating information clearly and quickly.Local collaboration also has an important role in discussing local and national issues.Meetings are currently mostly confined to regular and ad hoc meetings between professionals from organisations such as the state veterinary service, health protection agencies, and local and water authorities. 10Little routine local collaboration occurs between the medical and veterinary professions in general practice.But sharing local knowledge and expertise would have real benefits for the immediate human and animal populations.Sporadic or community and animal outbreaks of salmonellosis may, for example, have a common source of which only one profession is aware.Other potential benefits include reduced incidence of antibiotic resistance through sharing and comparing use, highlighting common environmental hazards such as farm discharges, and identifying research priorities.The time has surely come for medical and veterinary general practitioners to get together to share knowledge and voice concerns.Local concerns, which may become national problems, can be identified only through an open and integrated professional approach.Willingness by both the veterinary and medical professions at both local and national levels to collaborate and share information is therefore essential for the protection and promotion of public health.
Withdrawal of a novel-design duodenoscope ends outbreak of a VIM-2-producing Pseudomonas aeruginosa
Authors: Charlotte Verfaillie, Marco Bruno, Anne F. Voor in ’t holt, Jolanda Buijs, Jan-Werner Poley, Arjo Loeve, Juliette Severin, Leo Abel, Bert Smit, Inge de Goeij, Margreet Vos
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Infections are a recognized risk of endoscopic retrograde cholangiopancreatography (ERCP). This paper reports on a large outbreak of VIM-2-producing <i>Pseudomonas aeruginosa</i> that was linked to the use of a recently introduced duodenoscope with a specific modified design (Olympus TJF-Q180V). <b>Methods:</b> Epidemiological investigations and molecular typing were executed in order to identify the source of the outbreak. Audits on implementation of infection control measures were performed. Additional infection control strategies were implemented to prevent further transmission. The design and the ability to clean and disinfect the duodenoscope were evaluated, and the distal tip was dismantled. <b>Results:</b> From January to April 2012, 30 patients with a VIM-2-positive <i>P. aeruginosa</i> were identified, of whom 22 had undergone an ERCP using a specific duodenoscope, the TJF-Q180V. This was a significant increase compared with the hospital-wide baseline level of 2 – 3 cases per month. Clonal relatedness of the VIM-2 <i>P. aeruginosa</i> was confirmed for all 22 cases and for the VIM-2 strain isolated from the recess under the forceps elevator of the duodenoscope. An investigational study of the new modified design, including the dismantling of the duodenoscope tip, revealed that the fixed distal cap hampered cleaning and disinfection, and that the O-ring might not seal the forceps elevator axis sufficiently. The high monthly number of cases decreased below the pre-existing baseline level following withdrawal of the TJF-Q180V device from clinical use. <b>Conclusions:</b> Duodenoscope design modifications may compromise microbiological safety as illustrated by this outbreak. Extensive pre-marketing validation of the reprocessability of any new endoscope design and stringent post-marketing surveillance are therefore mandatory.
Response to Comment on: Torres-Mejía et al. Moderate-Intensity Physical Activity Ameliorates the Breast Cancer Risk in Diabetic Women. Diabetes Care 2012;35:2500–2502
Authors: Gabriela Torres-Mejía, Carolina Ortega-Olvera, Louis Martínez-Matsushita, Eduardo Lazcano-Ponce, Elad Ziv, Angélica Angeles-Llerenas
Journal: Diabetes Care (2013)

We appreciate the comments of Zhang et al. (1). We agree with them that the reduction in breast cancer (BC) risk was very strong, particularly in postmenopausal women (2). Our results are consistent with their recent meta-analysis (3). In our study, after analyzing moderate-intensity physical activity as a continuous variable, we found that for each h/week increment in moderate-intensity physical activity, the odds of having BC decreased by 2% (odds ratio [OR] = 0.98, 95% CI 0.97–0.99, P = 0.003) in premenopausal women and by 3% (OR = 0.97, 95% CI 0.95–0.98, P < 0.001) in postmenopausal women. Our results also agree with those that have shown that there is a stronger effect …
Diagnosing Vertebral Wedge Deformities
Authors: Paul Drinka
Journal: JAMA (1985)

<h3>To the Editor.—</h3> There is little information on the prevalence of osteopenic vertebral deformities in elderly males.<sup>1</sup>Review of the literature reveals prevalence data ranging from less than 6% to 47%.<sup>2-4</sup>We investigated the prevalence of vertebral wedge deformities in 67 unselected male veterans aged 85 years and older who had recently been hospitalized at the Madison (Wis) VA Hospital and had technically suitable lateral chest roentgenograms. Patients unable to support themselves in an upright position were excluded. Lateral chest roentgenograms are a readily available but neglected source of information on vertebral contour. We examined only the thoracic spine down to approximately T-11. Vertebral wedging was diagnosed if posterior vertebral height was 25% greater than anterior vertebral height. Posterior height included the prominence related to the rib facet. Only vertebrae in which all four corners of the vertebral body could be defined were judged to be wedged. Wedging
Is There Tension in Hypertension?
Authors: Samuel J. Mann
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The notion that tension or anxiety is a predictor of hypertension has been assumed intuitively and has been studied by many over decades. Yet convincing evidence of such a relationship has not appeared. The recent article by Dr Markovitz and colleagues<sup>1</sup>purportedly demonstrates that anxiety levels predict development of hypertension in middle-aged men. However, the findings are open to question on several grounds. First, there was no evidence of a relationship between tension and development of hypertension in women or in older men. Thus, in three of four groups tested, no relationship was seen. Further, the odds of a type I error are substantial. Given the number of subgroups, the number of predictors tested, and the stated<i>P</i>value of.04, there is a 39% likelihood of a chance association between some predictor and hypertension. For the .02 value reported with multivariate analysis, there is a 20% likelihood