tbuckley/cabot-search huggingface dataset:
Antagonism of prostaglandin EP4 receptor enhances Natural Killer cell activity and inhibits metastasis
Authors: Namita Kundu, Xinrong Ma, Tonya Walser, Dawn Holt, Amy M. Fulton
Journal: Cancer Research (2006)

632   Breast and other malignancies often have high COX-2 levels, which contribute to malignant behavior. The COX-2 product PGE 2  contributes to the high metastatic capacity of some tumors. Our published data indicates that inhibition of PGE 2  synthesis by the dual COX-1/COX-2 inhibitor, indomethacin, or a selective COX-2 inhibitor prevents metastasis in a preclinical model of metastatic breast cancer. We postulated that tumor-PGE 2  promotes metastasis in an autocrine manner via prostaglandin E (EP) receptor signaling. Murine and human breast cancer cells express all four isoforms of the EP receptors that bind PGE 2  (EP1-4). We now show that pharmacologic antagonism of the EP4 receptor with AH23848 inhibits tumor metastasis to the same degree as indomethacin. The antimetastatic activity of both indomethacin and AH23848 was compromised in mice depleted of functioning Natural Killer cells. Furthermore, AH23848 enhanced NK-mediated tumor cell lysis in vitro. NK cells are activated by recognition of decreased expression of MHC class I on tumor target cells. Preliminary data shows that AH23848 decreased class I expression on murine mammary tumor cells, consistent with the increased sensitivity to NK lysis. These studies support the further investigation of EP receptor antagonists to inhibit metastatic disease and suggest that NK activation may be critical to this therapy.
A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene
Authors: Maria Bitner-Glindzicz, Keith J. Lindley, Paul Rutland, Diana Blaydon, Virpi V. Smith, Peter J. Milla, Khalid Hussain, Judith Furth-Lavi, Karen E. Cosgrove, Ruth M. Shepherd, Philippa D. Barnes, Rachel E. O'Brien, Peter A. Farndon, Jane Sowden, Xue-Zhong Liu, Matthew J. Scanlan, Sue Malcolm, Mark J. Dunne, Albert Aynsley-Green, Benjamin Glaser
Journal: Nature Genetics (2000)
Abstract 1637: Discovery of ATR kinase inhibitors from natural products
Authors: Hui-Chun Wang, Alan Yueh-Luen Lee, Chin-Chung Wu, Yang-Chang Wu
Journal: Cancer Research (2014)

Abstract Inhibition of the DNA damage checkpoint and repair functions is a promising approach to improve chemosensitivity. Ataxia telangiectasia and Rad3-related protein (ATR) is an important checkpoint kianse responsible for organizing both normal and stressful DNA replication. In previous, we discovered a natural compound protoapigenone (WYC02) and its synthetic derivate WYC0209 are able to inhibit ATR-mediated Chk1 phosphorylation, impair the G2/M checkpoint, and improve cancer sensitivity to cisplatin both in vitro and in vivo. Although all evidences convince ATR signaling is disrupted by WYC compounds, the effect of compounds on ATR kinase activity is still unknown. In this study, we further provide evidences to prove that WYC02 and WYC0209 are undoubted ATR inhibitors by using of in vitro kinase assay. The data showed WYC0209 inhibits ATR kinase activity at least 4 times greater than WYC02, and enhances MDA-MB-231cells sensitivity to DNA replication-affecting agents such as doxorubicin, mitomycin C, and etoposide, but has little or no effect to mitosis-affecting microtubule inhibitor palcitaxol. The result of this study proposes a strategy to improve most of current chemotherapeutics in which aim to selective disrupting DNA replication in fast growing cancers. Citation Format: Hui-Chun Wang, Alan Yueh-Luen Lee, Chin-Chung Wu, Yang-Chang Wu. Discovery of ATR kinase inhibitors from natural products. [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 1637. doi:10.1158/1538-7445.AM2014-1637
Relationship of Beta-Blocker Dose With Outcomes in Ambulatory Heart Failure Patients With Systolic Dysfunction
Authors: Mona Fiuzat, Daniel Wojdyla, Dalane Kitzman, Jerome Fleg, Steven J. Keteyian, William E. Kraus, Ileana L. Piña, David Whellan, Christopher M. O'Connor
Journal: Journal of the American College of Cardiology (2012)
A randomised controlled trial of CPAP vs non-invasive ventilation for initial treatment of obesity hypoventilation syndrome
Authors: Mark Howard, Amanda Piper, Bronwyn Stevens, Anne Holland, Brendon Yee, Eli Dabscheck, Duncan Mortimer, Angela Burge, Daniel Flunt, Catherine Buchan, Linda Rautela, Nicole Sheers, David Hillman, David Berlowitz
Journal: European Respiratory Journal (2014)

Background  Although obesity hypoventilation syndrome (OHS) has become the most common indication for domiciliary Non-Invasive Ventilation (NIV) optimal treatment remains unclear.   Methods  We undertook a 3 month randomised controlled trial of NIV (spontaneous-timed mode bi-level positive airway pressure – Bi-level PAP) vs CPAP for initial treatment of OHS and evaluated the impact on treatment failure (hospital admission, persistent ventilatory failure or non-compliance), quality of life and control of ventilatory failure.   Results  60 participants were randomised (29 Bi-level PAP and 31 CPAP, age 53 y (SD 10), BMI 55 kg/m 2  (SD 12), PaCO2 60 mmHg (SD 14)). There was no difference between groups in treatment failure at 3 months (Bi-level PAP, 17.2% vs CPAP, 12.9%, p=0.65). Sleepiness (Epworth Sleepiness Scale (ESS)), quality of life (SF36 and Severe Respiratory Insufficiency questionnaire (SRI)), obesity and ventilatory failure improved in both groups (pl0.01 for all), however there was no difference between groups.   Conclusions  CPAP and Bi-level PAP provided similar improvements in symptoms, quality of life and ventilatory failure for OHS after 3 months with no difference in treatment failure.   Supported By:  The ResMed Foundation.
A memorable patient: Check, check, and check again
Authors: G. Scott
Journal: BMJ (2000)

A well known author came in at the end of our tuberculosis clinic with an x ray which suggested tuberculosis. He was well but his contact was a man with AIDS and tuberculosis on the ward. He had no symptoms and the physical examination was normal so, as is customary, I asked him to provide some sputum, which he managed with great perseverance, and blood and arranged to see him a few days later.

He had a partner and child, and I called them to the contact clinic for Heaf tests and chest x ray examinations, which turned out to be negative. His blood tests were normal and the sputum was negative on direct examination, but I was so sure that his chest x ray …
Metabolic syndrome in patients with COPD admitted for exacerbation: Preliminary data
Authors: Evgeni Mekov, Yanina Slavova, Svetlana Hadjieva, Adelina Tsakova, Marianka Genova
Journal: European Respiratory Journal (2014)

Introduction: The Metabolic syndrome (MS) affects 21-53% of patients with COPD with a higher prevalence in the early stages of COPD, which is highly variable in different studies and subgroup examined.  Aim: To examine the prevalence of MS and its correlation with comorbidities and disease characteristics of patients with COPD admitted for exacerbation.  Methods: 92 patients were investigated for the presence of MS. All of them were also examined for diabetes mellitus (DM). Data were gathered for smoking status and exacerbations in the last year. The patients completed CAT and mMRC questionnaires and underwent spirometry.  Results: 23,9% (n=22) of patients have MS. 76% (n=70) of patients are on therapy for arterial hypertension. 20% of the male and 31,3% of the female patients have MS (p>0,05). The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p=0.049 and p=0.015 respectively). Average BMI is 28,33. None of the patients had MS and BMI   Conclusions: This study finds relatively low prevalence of MS compared to previously published data (21-53%). Having in mind that MS is more common in the early stages and decreases with COPD progression, these patients may be considered as having advanced COPD.
Ophthalmoplegia and Graves' Disease
Authors: John L. Garvey
Journal: Annals of Internal Medicine (1930)

Article1 March 1930Ophthalmoplegia and Graves' DiseaseJOHN L. GARVEY, M.D., F.A.C.P.JOHN L. GARVEY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-9-917 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIf one may judge from the literature ophthalmoplegia as a sign of Graves' disease is extremely rare. Yet other eye signs as exophthalmos, lack of coordination between the movements of the upper lid and the elevation or depression of the visual axis and many others are well recognized and constitute some of the cardinal signs of exophthalmic goiter. Heuer (1) in 1916 reviewed the literature of the disturbance in function of the cranial nerves associated with exophthalmic goiter and reported a case of external ophthalmoplegia with Graves' disease. He pointed out how infrequently it occurred but that the ocular muscles...Bibliography1 HEUER CJ: Cerebral Nerve Disturbances in Exophthalmic Goiter, Am. J. Med. Sci., 1916, 151, 339. CrossrefGoogle Scholar2 HOLLOWAYFRYWENTWORTH : Ocular signs in One Hundred Unselected Cases of Goiter, J. Am. Med. Ass'n., 1929, 92, 35. CrossrefGoogle Scholar3 DUDGEONURQUHART : Lymphorrhages in the Muscles in Exophthalmic Goiter, Brain, 1926, 49:2, 182. CrossrefGoogle Scholar4 POTTER EB: Persistent Thymus in Exophthalmic Goiter, Contributions to Medical Science Dedicated to Aldred Scott Warthin, 1927, 205. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JOHN L. GARVEY, M.D., F.A.C.P.Affiliations: Milwaukee, Wisconsin*From the Department of Neurology, University of Michigan Medical School, Ann Arbor, Mich. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMYASTHENIA GRAVIS AND HYPERTHYROIDISM: REPORT OF TWO CASES AND REVIEW OF THE LITERATURE*GEORGE D. WEICKHARDT, M.D., F.A.C.P., ARTHUR J. REDMOND, M.D.Die einzelnen endokrinen Drüsen und bestimmte Hormone in Physiologie und Pathologie des Sehorganes 1 March 1930Volume 3, Issue 9 Page: 917-919 Keywords Ataxia Cranial nerves Muscles Neurology ePublished: 1 December 2008 Issue Published: 1 March 1930 PDF downloadLoading ...
Researchers Uncover Novel Spatially Defined Stem Cells
Authors: Tracy Hampton
Journal: JAMA (2015)

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
Fibrosis in transplanted heart.
Authors: D C Sprigings
Journal: Circulation (1990)

Pickering and Boughner1 state that the degree of fibrosis in endomyocardial biopsy specimens taken 5-10 days after cardiac transplantation is dependent on the total ischemic time of the transplanted heart.However, the plot of myocardial collagen content versus ischemic time (Figure 51) shows substantial scatter about the regression line (r=0.60),suggesting that other factors might be important.We speculate that myocardial fibrosis is due in part to myocyte necrosis before graft harvesting.The authors do not include information regarding the cause of death in the donors.Subarachnoid hemorrhage and acute head injury are common causes of death in organ donors, and focal myocardial necrotic lesions have been reported in association with both,23 probably reflecting intense efferent cardiac sympathetic activity.Such myocardial lesions may underlie the ventricular wall motion abnormalities observed on echocardiographic study of patients with subarachnoid hemorrhage.4If this speculation is correct, it would argue for the increased use of /8-adrenoceptor antagonists to prevent or limit such lesions3'5 in patients with these disorders, particularly if brain stem death occurs and organ donation is considered.
Abstract 232: Prevalence and Resolution of Post--Cardiac Arrest Myocardial Dysfunction
Authors: Katie Carlson, Jacob Jentzer, Gavin Hickey, Asher Shafton, Hussein Abu Daya, Jon Rittenberger
Journal: Circulation (2014)

Background: In animal models, post-cardiac arrest myocardial dysfunction (PAMD), defined as a decrease in left ventricular ejection fraction (LVEF) from baseline following cardiac arrest and demonstrating resolution shortly thereafter, is common. PAMD may dispose to hemodynamic instability and increased mortality. Data on the prevalence and recovery of PAMD is limited. Hypothesis: We hypothesized PAMD is common in subjects resuscitated from cardiac arrest and results in inotropic, vasopressor and fluid support. Methods: Review of subjects >18 years of age treated between 1/1/2009 and 12/31/2010 with Pre (<1 year prior to arrest), Immediate Post, (<24 hours of arrest) and Delayed Post (<1 year post cardiac arrest) transthoracic echocardiogram measurements. Demographics, catheterization, inotropic support, vasopressor dose (defined using the cumulative vasopressor index- CVI) and fluid balance during the first 24 and 36 hours were recorded. Change in LVEF and the difference in CVI, inotropes and intake/outp...
Biotechnology Products and University-Based Science
Authors: Philip Lempert
Journal: JAMA (2005)

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
Why Are Children Who Exhibit Psychopathology at High Risk for Psychopathology and Dysfunction in Adulthood?
Authors: Benjamin B. Lahey
Journal: JAMA Psychiatry (2015)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
Abstract P4-05-10: PRKCQ, a novel protein kinase C preferentially expressed in triple negative breast cancer, drives oncogenic growth, survival and migration
Authors: Hanna Y Irie, Gwyneth Halstead-Nussloch, Koichi Ito
Journal: Cancer Research (2015)

Abstract Background/Rationale: PRKCQ, a member of the novel protein kinase C family, was identified in a functional genomic screen for regulators of anoikis resistance/anchorage-independent survival (Irie et al., 2010). Interestingly, it is preferentially expressed in the triple negative/basal subtype of breast tumors compared to Luminal or Her2+ tumors. We sought to determine the functional role of PRKCQ in triple negative breast cancer and evaluate PRKCQ as a candidate therapeutic target for this subtype. Materials and Methods. Consistent with its expression in triple negative patient breast tumors, PRKCQ is also highly expressed in several triple negative breast cancer cell lines. We utilized both gain- and loss-of-function approaches in these cell lines to determine the requirement for PRKCQ in oncogenic growth and survival using in vitro and in vivo models. Results. Isoform-specific downregulation of PRKCQ using shRNA vectors severely impaired growth of triple negative breast cancer cells in 2D monolayer and 3D Matrigel cultures. In 3D cultures, PRKCQ downregulation not only inhibited growth, but impaired the formation of invasive branching. PRKCQ downregulation also inhibited the growth of MDA231 primary tumor xenografts. All of these data support a requirement for PRKCQ expression in triple negative breast cancer cell growth. To determine if PRKCQ is sufficient to drive oncogenic phenotypes, we overexpressed PRKCQ in a non-transformed immortalized breast epithelial cell line, MCF-10A. PRKCQ expression conferred EGF-independent growth, migration and anoikis resistance. In PRKCQ-expressing MCF-10A cells, EGFR phosphorylation and activation were preserved in the absence of exogenous EGF ligand addition. We are currently elucidating the mechanisms responsible for PRKCQ-mediated, sustained activation of EGFR. Conclusions. PRKCQ is critically required for growth of triple negative breast cancer cells. Increased expression of PRKCQ is sufficient to drive oncogenic, growth factor-independent growth, survival and migration. Interestingly, PRKCQ could play a dual role in the development of triple negative breast cancer, as it may also function in the immune microenvironment to support the growth of these tumors. Therefore, PRKCQ is an attractive candidate therapeutic target for patients with triple negative breast cancer. Citation Format: Hanna Y Irie, Gwyneth Halstead-Nussloch, Koichi Ito. PRKCQ, a novel protein kinase C preferentially expressed in triple negative breast cancer, drives oncogenic growth, survival and migration [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-10.
Aberrant C nerve fibre function of the healthy scalp
Authors: G.A. Bin Saif, A. Alajroush, A. McMichael, S.G. Kwatra, Y.-H. Chan, F. McGlone, G. Yosipovitch
Journal: British Journal of Dermatology (2012)

The scalp is commonly associated with itch and burning sensations. Previous studies have shown the scalp is highly innervated compared with other body areas. However, limited data are available on sensory testing associated with C nerve fibres of the healthy scalp.To examine the function of C nerve fibre-mediated sensations such as warmth, heat pain, itch and neurogenic inflammation in two areas of the scalp (crown and occiput) in comparison to forearm skin.Twenty-two healthy subjects (11 women, 11 men) underwent quantitative computerized thermosensory testing to assess warmth and heat pain thresholds. Itch was induced using histamine iontophoresis and application of cowhage spicules, and the intensity of each itch was assessed. Skin blood flow was measured at baseline and after each itch induction to assess degree of neurogenic inflammation.A majority (64%) of the crown warmth threshold measurements exceeded 50°C while all 22 forearm warmth thresholds measurements were significantly lower than 50°C. Both scalp sites had significantly higher warmth and heat pain thresholds compared with the forearm (P<0·001). Itch ratings of histamine and cowhage on both scalp sites were significantly lower than on the forearm (P≤0·001). Histamine and cowhage induced an increase in skin blood flow from baseline on the forearm compared with the scalp (P< 0·001).This study demonstrates a significant insensitivity of C nerve fibres of the scalp to warmth, heat pain, itch and neurogenic inflammation. These results suggest that the scalp has an aberrant response of C nerve fibres.
Abstract 10882: The Associations of Plasma Phospholipid Omega-6 and Omega-3 Fatty Acid Levels and Cardiac Magnetic Resonance Imaging Measures of Left Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis
Authors: Jennifer S Anderson, Jennifer A Nettleton, Gregory Hundley, Michael Y Tsai, Lyn Steffen, Rozenn N Lemaitre, David Siscovick, Joao Lima, Martin A Prince, David M Herrington
Journal: Circulation (2010)
Discovery Boosts Hope for Heart Repair
Authors: Bridget M Kuehn
Journal: JAMA (2005)

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 Journals 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
School-Based Interventions for Children Exposed to ViolenceSchool-Based Interventions for Children Exposed to Violence
Authors: Nancy Rappaport
Journal: JAMA (2003)

To the Editor: Dr Stein and colleagues1 found that a 10-session, school-based cognitive-behavioral treatment (CBT) program was effective for reducing the levels of posttraumatic stress disorder (PTSD) and depression among children exposed to violence.