tbuckley/cabot-search huggingface dataset:
Resistance to CDK2 Inhibitors Is Associated with Selection of Polyploid Cells in<i>CCNE1</i>-Amplified Ovarian Cancer
Authors: Dariush Etemadmoghadam, George Au-Yeung, Meaghan Wall, Chris Mitchell, Maya Kansara, Elizabeth Loehrer, Crisoula Batzios, Joshy George, Sarah Ftouni, Barbara A. Weir, Scott Carter, Irma Gresshoff, Linda Mileshkin, Danny Rischin, William C. Hahn, Paul M. Waring, Gad Getz, Carleen Cullinane, Lynda J. Campbell, David D. Bowtell
Journal: Clinical Cancer Research (2013)

Amplification of cyclin E1 (CCNE1) is associated with poor outcome in breast, lung, and other solid cancers, and is the most prominent structural variant associated with primary treatment failure in high-grade serous ovarian cancer (HGSC). We have previously shown that CCNE1-amplified tumors show amplicon-dependent sensitivity to CCNE1 suppression. Here, we explore targeting CDK2 as a novel therapeutic strategy in CCNE1-amplified cancers and mechanisms of resistance.We examined the effect of CDK2 suppression using RNA interference and small-molecule inhibitors in SK-OV-3, OVCAR-4, and OVCAR-3 ovarian cancer cell lines. To identify mechanisms of resistance, we derived multiple, independent resistant sublines of OVCAR-3 to CDK2 inhibitors. Resistant cells were extensively characterized by gene expression and copy number analysis, fluorescence-activated cell sorting profiling and conventional karyotyping. In addition, we explored the relationship between CCNE1 amplification and polyploidy using data from primary tumors.We validate CDK2 as a therapeutic target in CCNE1-amplified cells by showing selective sensitivity to suppression, either by gene knockdown or using small-molecule inhibitors. In addition, we identified two resistance mechanisms, one involving upregulation of CDK2 and another novel mechanism involving selection of polyploid cells from the pretreatment tumor population. Our analysis of genomic data shows that polyploidy is a feature of cancer genomes with CCNE1 amplification.These findings suggest that cyclinE1/CDK2 is an important therapeutic target in HGSC, but that resistance to CDK2 inhibitors may emerge due to upregulation of CDK2 target protein and through preexisting cellular polyploidy.
Autoimmune thrombocytopenic purpura. Comparison of three different methods for the detection of platelet antibodies
Authors: Gilberto J. Vizcaíno, María Diez‐Ewald
Journal: American Journal of Hematology (1983)

Abstract An evaluation of three techniques for detection of antiplatelet antibodies in ATP is made. The platelet factor 3 availability after immunoinjury and the immunohystochemical technique using immunoperoxidase were more sensitive than 14 C‐5HT release from platelets for this purpose. The percentage of positive cases was similar in acute and chronic ATP patients while it significantly fell in cases in remission. A high proportion of patients in clinical remission had normal platelet aggregation, despite the persistence of antiplatelet antibodies.
Tumor-Associated Galectin-3 Modulates the Function of Tumor-Reactive T Cells
Authors: Weiyi Peng, Helen Y. Wang, Yoshihiro Miyahara, Guangyong Peng, Rong-Fu Wang
Journal: Cancer Research (2008)

Abstract T cells play an important role in cancer immunosurveillance and tumor destruction. However, tumor cells alter immune responses by modulating immune cells through antigen stimulation and immunoregulatory cytokines. A better understanding of the interplay between tumor cells and T cells might provide new strategies to enhance antitumor immunity. Through an antigen-screening approach using colorectal tumor–reactive T cells, we identified an HLA-DR11–restricted T-cell epitope encoded by KIAA0040 as well as MHC-unrestricted human galectin-3 (Gal-3) expressed by tumor cells. Although the biological function of KIAA0040 remains to be determined, we found that Gal-3 functioned as an immune regulator for direct T-cell activation and function. T-cell activation induced by Gal-3 resulted in T-cell apoptosis. We showed that a high level of expression of Gal-3 promoted tumor growth in vitro and in vivo. Using a mouse tumor model, we showed that delivery of high doses of Gal-3 inhibited tumor-reactive T cells and promoted tumor growth in mice receiving tumor-reactive CD8+ T cells. These findings suggest that Gal-3 may function as an immune regulator to inhibit T-cell immune responses and promote tumor growth, thus providing a new mechanism for tumor immune tolerance. [Cancer Res 2008;68(17):7228–36]
Gynaecography in Premature Ovarian Failure and Ovarian Dysgenesis
Authors: L. Kreel, J. Ginsburg, M. F. Green
Journal: BMJ (1969)

Gynaecography-the radiological visualization of the internal female genitalia after pneumoperitoneum-is a safe and simple procedure. When taken in conjunction with the clinical and laboratory findings the results of gynaecography are often a sufficient basis for diagnosis and a plan of management in women presenting with menstrual irregularity or infertility.
Circulating human CD4 and CD8 T cells do not have large intracellular pools of CCR5
Authors: Heather A. Pilch-Cooper, Scott F. Sieg, Thomas J. Hope, Ann Koons, Jean-Michel Escola, Robin Offord, Ronald S. Veazey, Donald E. Mosier, Brian Clagett, Kathy Medvik, Julie K. Jadlowsky, Mark R. Chance, Janna G. Kiselar, James A. Hoxie, Ronald G. Collman, Nadeene E. Riddick, Valentina Mercanti, Oliver Hartley, Michael M. Lederman
Journal: Blood (2010)
Gastric Acid Production in Infections
Authors: LOUIS F. MARTIN
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 October 1980Gastric Acid Production in InfectionsLOUIS F. MARTIN, M.D.LOUIS F. MARTIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-4-644_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the June issue, Kisloff (1) presents the case of a patient whose gastric acid output was not influenced by cimetidine administration. This topic has interested us for some time since we first noted 11 critically ill patients who failed to maintain a gastric pH above 4 while receiving cimetidine (2). In February 1980, at the Annual Meeting of the Society of University Surgeons, we presented data accumulated from 77 critically ill patients suggesting that persistent failure of antacids or cimetidine or both together to maintain gastric pH above 4 is an indicator of infection (3)The...References1. KISLOFF B. Cimetidine-resistant gastric acid secretion in humans. Ann Intern Med. 1980;92:791-3. LinkGoogle Scholar2. MARTINSTALOCHSIMONOWITZDELLINGERMAX LDPEM. Failure of cimetidine prophylaxis in the critically ill. Arch Surg. 1979;114:492-6. CrossrefMedlineGoogle Scholar3. MARTINMAXPOLK LMH. Failure of gastric pH control by antacids or cimetidine in the critically ill: a valid sign of sepsis. Surgery. 1980;88:59-68. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LOUIS F. MARTIN, M.D.Affiliations: University of Louisville School of Medicine Louisville, KY 40292 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byF 1 October 1980Volume 93, Issue 4Page: 644-645KeywordsSurgeons ePublished: 1 December 2008 Issue Published: 1 October 1980 PDF downloadLoading ...
Targeted Ablation, Silencing, and Activation Establish Glycinergic Dorsal Horn Neurons as Key Components of a Spinal Gate for Pain and Itch
Authors: Edmund Foster, Hendrik Wildner, Laetitia Tudeau, Sabine Haueter, William T. Ralvenius, Monika Jegen, Helge Johannssen, Ladina Hösli, Karen Haenraets, Alexander Ghanem, Karl-Klaus Conzelmann, Michael Bösl, Hanns Ulrich Zeilhofer
Journal: Neuron (2015)

The gate control theory of pain proposes that inhibitory neurons of the spinal dorsal horn exert critical control over the relay of nociceptive signals to higher brain areas. Here we investigated how the glycinergic subpopulation of these neurons contributes to modality-specific pain and itch processing. We generated a GlyT2::Cre transgenic mouse line suitable for virus-mediated retrograde tracing studies and for spatially precise ablation, silencing, and activation of glycinergic neurons. We found that these neurons receive sensory input mainly from myelinated primary sensory neurons and that their local toxin-mediated ablation or silencing induces localized mechanical, heat, and cold hyperalgesia; spontaneous flinching behavior; and excessive licking and biting directed toward the corresponding skin territory. Conversely, local pharmacogenetic activation of the same neurons alleviated neuropathic hyperalgesia and chloroquine- and histamine-induced itch. These results establish glycinergic neurons of the spinal dorsal horn as key elements of an inhibitory pain and itch control circuit.
Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins versus oxygen-derived free radicals.
Authors: E E Ustinova, H D Schultz
Journal: Circulation Research (1994)

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are known to be produced during prolonged ischemia and reperfusion, contribute to this afferent excitation. We recorded activity from 47 chemosensitive vagal afferent fibers in 31 rats; the endings of these fibers were located in the left ventricle. Chemosensitive endings were identified with topical applications of capsaicin (10 micrograms) to the surface of the heart. Reactivity of the endings to oxygen-derived free radicals was assessed by topical application of H2O2 (3 to 9 mumol). Activity of the vagal fibers was recorded during 30 minutes of occlusion of the left anterior descending coronary artery (LAD) and 10 minutes of subsequent reperfusion. The activity of chemosensitive endings within the ischemic zone increased in the first 2 minutes of LAD occlusion from 2.2 +/- 0.4 to 4.3 +/- 0.9 impulses per second (107 +/- 30% increase, P &lt; .05). This increased activity waned after 3 to 5 minutes of occlusion. Endings outside the ischemic zone did not increase, their activity at the beginning of ischemia. Reperfusion caused a rapid elevation of activity only in chemosensitive fibers whose endings were found to respond to topical H2O2. The reperfusion-sensitive endings were located both within and outside the ischemic zone of the left ventricle. Indomethacin (5 mg/kg i.v., 20 minutes before occlusion) effectively prevented activation of chemosensitive afferent endings at the beginning of LAD occlusion regardless of their sensitivity to H2O2 but had no effect on the activation at reperfusion.
A Family with Hypogonadotropic Hypogonadism and Mutations in the Gonadotropin-Releasing Hormone Receptor
Authors: N de Roux, J Young, M Misrahi, R Genet, P Chanson, G Schaison, E Milgrom
Journal: New England Journal of Medicine (1997)

Hypogonadotropic hypogonadism is often associated with anosmia in a condition known as Kallmann's syndrome. The gene for the X-linked form of Kallmann's syndrome has been mapped to chromosome Xp22.3,1 and several mutations have been described.2–4 In idiopathic hypogonadotropic hypogonadism there is no anosmia, and the involved genes have not been characterized. One possible candidate is the gene for gonadotropin-releasing hormone (GnRH), especially since hypogonadal mice with the deletion of this gene have been identified.5 However, no abnormality of the gene for GnRH has been found in several patients with idiopathic hypogonadotropic hypogonadism.6–9 The gene for the GnRH receptor . . .
Flight plans, patient safety and American hospitals – is it time to check the baggage of private sector oversight?
Authors: Anthony PH Walsh, Jonathan D Baum, David J Walsh
Journal: Journal of the Royal Society of Medicine (2010)

A recent JRSM paper1 compared efforts to improve healthcare quality with various aspects of the aviation industry. Although there are similarities between the airline industry and surgery, key differences also exist in exchange of safety data, particularly in the United States.

At institutional levels, the National Transportation Safety Board publishes detailed reports on air crashes investigated in USA. But reports and recommendations concerning inspected American hospitals are the property of private certifying groups like the Joint Commission. That crucial information is kept secret; it is left to the hospital to decide what, if anything, is disclosed to the general public.

At the individual level, the most junior team member in the cockpit can advise and correct a senior pilot.1 When aviation safety problems go beyond the cockpit, a US government programme legally shields the whistleblower from any retaliation.2 Yet, a hospital staff member who reports a breach of hospital policy in good faith can find their own safety complaint simply handed over to the hospital and used against them in a civil trial.3 Since hospital accreditation remains the exclusive province of the private sector, the ‘best hospitals in America’ can turn out to be most any hospital that can pay for a Joint Commission site survey.4 There is no parallel to this in the aviation industry.

Vigilant and unbiased monitoring of institutional quality systems by public forums and meaningful certification has become a hallmark of aviation safety. The Institute of Medicine (USA) estimates that over 90,000 patient fatalities occur every year from preventable medical error – the equivalent of a catastrophic jumbo jet crash each day.5 As quality management structures are compared across hospital surgery and aviation, increased transparency in US hospital inspection and accreditation processes would be a welcome step to address this problem.
An Address on a Useful Technique in Removing Tubercular Disease from the Hip-Joint
Authors: A. E. Barker
Journal: BMJ (1889)

the 31st they were not noticeable, and he remained well afterwards.He took the drug for twelve days altogether, and it was then discontinued because of an erythematous eruption that appeared.He was in the hospital three weeks.A third case, a girl of 8, under the care of Dr. Cooper, of Rotherhithe-a very bad case indeed, associated with much wasting, imbecility, paralysis, and pericarditis-was given also five grains three times a day.She took it for eight days, and was by that time so much improved that it was discontinued for iron and digitalis.The improvement began within forty-eight houirs
Molecular cloning, expression, and characterization of a major 38-kd cochineal allergen
Authors: Yoko Ohgiya, Fumihiro Arakawa, Hiroshi Akiyama, Yasuo Yoshioka, Yoshiki Hayashi, Shinobu Sakai, Sumio Ito, Yuko Yamakawa, Satoru Ohgiya, Zenro Ikezawa, Reiko Teshima
Journal: Journal of Allergy and Clinical Immunology (2009)
Detection and quantitation of serum HCV-RNA by branched DNA amplification in anti-HCV positive blood donors
Authors: Michèle Martinot-Peignoux, Patrick Marcellin, Jérôme Gournay, Franck Gabriel, Françoise Courtois, Michel Branger, Anne Marie Wild, Serge Erlinger, Jean Pierre Benhamou
Journal: Journal of Hepatology (1994)
Abstract 5135: A chromatin modifier from the 8p11 amplicon in luminal breast cancer
Authors: Brittany Turner Ivey, Steve Guest, Stephen P. Ethier
Journal: Cancer Research (2014)

Abstract The chromosome 8p11-p12 amplicon is present in 12-15% of breast cancers, resulting in an increase in both copy number and expression of several chromatin modifiers in these tumors, including KAT6A, WHSC1L1, and ASH2L. Previous analyses in SUM52 breast cancer cells showed amplification and over-expression of KAT6A, and subsequent RNAi screening identified KAT6A as a potential driving oncogene. Also known as MYST3, KAT6A is a histone acetyltransferase (HAT) with intrinsic HAT activity towards itself and lysine residues on histone 2B, histone 3, and histone 4. Previously identified as a fusion partner with CREB binding protein (CREBBP) in acute myeloid leukemia, KAT6A is amplified in 8.7% of invasive breast cancers according to the Cancer Genome Atlas (TCGA). Knockdown of KAT6A with several shRNAs in SUM52 cells, a luminal breast cancer cell line harboring the 8p11 amplicon, resulted in reduced growth rate compared to non-silencing controls and profound loss of clonogenic capacity both in mono-layer and in soft agar. The normal cell line MCF10A, however, did not exhibit slower growth with knockdown of KAT6A, nor did other breast cancer cell lines without KAT6A amplfied. Interestingly, SUM52 cells with KAT6A knockdown formed fewer mammospheres in culture compared to non-silencing controls, suggesting a possible role for KAT6A in breast cancer stem cell activity and self-renewal. Further analysis of cell surface markers CD24 and CD44 in KAT6A knockdown cells revealed an increase in cells double positive for CD24 and CD44 expression, a characteristic of increased cell differentiation. Previous work from our laboratory identified FGFR2 as a driving oncogene in SUM52 cells. While FGFR inhibition can completely arrest the growth of these cells, it is completely reversible. Thus, exposure of SUM52 cells to FGFR inhibitors does not significantly affect the colony forming ability of the cells. By contrast, the colony forming efficiency of SUM52 KAT6A knockdown cells in the presence of the FGFR inhibitor PD170374 was significantly reduced compared to cells with KAT6A knockdown only. These data suggest that KAT6A may be a potential novel oncogene in breast cancers bearing the 8p11 amplicon and that it interacts with FGFR2 to regulate expression of transformed phenotypes. While there are other putative oncogenes in the amplicon, the identification of KAT6A as a driving oncogene suggests that chromatin-modifying enzymes are a key class of oncogenes in these cancers, and play an important role in the selection of this amplicon in luminal B breast cancers. Citation Format: Brittany Turner Ivey, Steve Guest, Stephen P. Ethier. A chromatin modifier from the 8p11 amplicon in luminal breast cancer. [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 5135. doi:10.1158/1538-7445.AM2014-5135
Outcome of breech delivery at term.
Authors: S. Paterson-Brown, N. M. Fisk
Journal: BMJ (1992)

psychological and physical consequences of abdominal delivery other than those directly affect- ing subsequent pregnancies are often overlooked.From a review of the literature Bingham and Lilford concluded that planned abdominal delivery of fetuses presenting by the breech at term might be a safer option for the mother even if only 17% of trials of vaginal breech delivery were unsuccessful.'However, the authors used estimates of maternal mortality and morbidity, and postpartum hysterectomy was the only measure of serious postpartum morbidity.Long term morbidity after discharge from hospital was not addressed.Feldman and Freiman, using a mathematical analysis of American data (Commission on Profes- sional and Hospital Activities 1974 and 1978), calculated that routine elective caesarean section might be safer when the incidence of failed trial of labour was greater than 26%./.They also concluded that the excess maternal mortality resulting from a complete shift of all women in labour to prophy- lactic caesarean section would be 1 in 18000.No measure of morbidity was included in this analysis, and the authors concluded that extrapolating retro- spectively accumulated data to projections in hypothetical new approaches could lead to un- reliable conclusions.Unfortunately, Thorpe-Beeston and colleagues have not told us why the nine "normal" term infants died; possibly, breech presentation was undiagnosed, the mothers presented in advanced labour, or there was cord prolapse.Such accidents would occur even if a policy of wholesale caesarean section was introduced.Certainly, delivery in breech presentations at term should be made safer, but before a shift away from vaginal breech delivery is advocated the impact this would almost certainly have on both morbidity and mortality for the delivering mother must be addressed.
PREDICTORS OF ADVERSE CARDIAC EVENTS IN NONCOMPACTION CARDIOMYOPATHY: DATA FROM THE GERMAN NONCOMPACTION REGISTRY (ALKK)
Authors: Rolf Engberding, Claudia Stoellberger, Wolfgang Fehske, Matthias Gietzelt, Reinhold Haux, Birgit J. Gerecke
Journal: Journal of the American College of Cardiology (2014)
Thallium-201 for myocardial imaging. Relation of thallium-201 to regional myocardial perfusion.
Authors: H W Strauss, K Harrison, J K Langan, E Lebowitz, B Pitt
Journal: Circulation (1975)

Following intravenous administration, the myocardial concentration of tracer thallium-201, potassium-43, and rubidium-81 were determined in mice; thallium was present in the greatest concentration in the myocardium (2.08% compared 1.25% for potassium and 1.15% for rubidium at 10 minutes). The regional myocardial distribution of thallium-201 was determined in dogs under conditions of normal flow, and total occlusion, and compared with potassium-43 (r=0.97). The regional distribution of thallium-201 was compared to microspheres under conditions of partial occlusion and reactive hyperemia (r=0.97). Thallium-201 was evaluated in a series of phantom scans, which demonstrated that the low energy X-ray of thallium was suitable for imaging. These results suggest that thallium-201 can be used for the evaluation of the distribution of regional myocardial perfusion.
Thermography in Breast Cancer
Authors: Harold J. Isard
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Having used thermography in conjunction with mammography for over two decades in the evaluation of breast diseases, I find that Paul Cotton's<sup>1</sup>discussion of thermography presents an unbalanced review of the usefulness of thermography in breast cancer. While quoting an unfavorable report that "thermography detected only 39% of 130 proven malignancies,"<sup>2</sup>had he delved further he could have found the report entitled "Breast Thermography After Four Years and 10 000 Studies,"<sup>3</sup>and noted that among 5662 symptomatic patients there were 270 with proven cancer, and thermography had a true-positive result rate of 72%. In this group, the results of physical examination were positive in 82% and mammography results were positive in 85%. Accuracy was improved to 92% when all three modalities were considered. Among the 4393 asymptomatic patients, there were 36 clinically occult cancers, 30 (83%) detected by mammography and 22 (61%) suspected using