tbuckley/cabot-search huggingface dataset:
Abstract P5-07-02: Mutant GATA3 causes precocious lobuloalveolar development in the mouse mammary gland and is associated with more aggressive human breast cancer
Authors: PA Kenny, N Chandiramani, EA Peterson
Journal: Cancer Research (2013)

Abstract GATA3 is an essential mediator of mammary gland development and is expressed at high levels in Estrogen Receptor positive tumors. This gene has recently emerged as one of the most frequently mutated genes in Estrogen Receptor positive breast cancer. GATA3 mutant tumors tend to retain and express the wild-type GATA3 allele which, together with the established role for GATA3 in maintaining luminal epithelial differentiation, has led to the suggestion that GATA3 is a haploinsufficient tumor suppressor gene in the mammary gland. We describe a striking contrast between the GATA3 mutation spectrum in breast cancer with that found in a true GATA3 haploinsufficiency syndrome and propose that this is indicative of a strong selective pressure to mutate and retain expression of a substantial portion of the GATA3 coding sequence. We demonstrate that the proteins encoded by GATA3 mutant alleles lack the capacity to bind to canonical GATA sequence motifs and acquire a new recognition specificity governed by the N-terminal zinc finger domain. Transgenic expression of the mutant protein results in a pronounced precocious lobuloalveolar development in 9 week old female mice, suggesting that the mutant gene is not a null allele and can regulate cell proliferation. In addition, we demonstrate that Estrogen Receptor positive GATA3 mutant human breast tumors arise at earlier ages than Estrogen Receptor GATA3 wild-type tumors, which further emphasizes the clinical relevance of these mutations. Based on the estimated mutation prevalence from the TCGA study, approximately 22,000 new cases of GATA3-mutant invasive breast cancer are diagnosed in the US each year. Collectively, our data indicate that GATA3 mutant tumors may comprise a breast cancer subset with distinct biological and clinical behavior and that a detailed understanding of the novel repertoire of target genes may yield useful clinical targets for this population. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-07-02.
Gallbladder and Small Intestinal Regulation of Biliary Lipid Secretion during Intraduodenal Infusion of Standard Stimuli
Authors: Gregory T. Everson, Michael J. Lawson, Carol McKinley, Radene Showalter, Fred Kern
Journal: Journal of Clinical Investigation (1983)

The gallbladder and small intestine are reservoirs for the bile acid pool during its enterohepatic circulation and, as such, may regulate biliary secretion of bile acid. During studies of biliary bile acid secretion, a stimulus to gallbladder contraction is continuously infused into the duodenum. Under these conditions, it is assumed that the gallbladder is tonically contracted and that the rate of bile acid secretion into the duodenum equals the hepatic bile acid secretion rate. However, secretion rates vary by as much as 100%, depending upon which of two standard stimuli is used. Therefore, we studied the role of gallbladder emptying and small intestinal transit in determining biliary lipid secretion rate and composition during infusion of these stimuli in five healthy subjects. Each subject was studied with a liquid formula containing 40% of calories as fat, and with an amino acid solution for 10 h. Bile acid, phospholipid, cholesterol, and markers were measured in duodenal bile and hourly secretion rates were calculated by marker dilution technique. Real-time gallbladder sonographs and serum pancreatic polypeptide levels were obtained every 30 min. Small bowel transit time was estimated levels were obtained every 30 min. Small bowel transit time was estimated by the breath hydrogen response after giving lactulose intraduodenally.
Intraosseous epidermoid cyst mimicking psoriasis.
Authors: K. Bhagwandas, N. Nicolaou, D.L. Roberts
Journal: British Journal of Dermatology (2001)

Journal Article Intraosseous epidermoid cyst mimicking psoriasis Get access K. Bhagwandas, K. Bhagwandas Department of Dermatology, Singleton Hospital, Sketty, Swansea SA2 8QA, U.K.E‐mail: krishnan_bhagwandas@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar N. Nicolaou, N. Nicolaou Department of Dermatology, Singleton Hospital, Sketty, Swansea SA2 8QA, U.K.E‐mail: krishnan_bhagwandas@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar D.L. Roberts D.L. Roberts Department of Dermatology, Singleton Hospital, Sketty, Swansea SA2 8QA, U.K.E‐mail: krishnan_bhagwandas@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 145, Issue 2, 1 August 2001, Pages 366–368, https://doi.org/10.1046/j.1365-2133.2001.04365.x Published: 01 August 2001
hCLCA2 Is a p53-Inducible Inhibitor of Breast Cancer Cell Proliferation
Authors: Vijay Walia, Ming Ding, Sumit Kumar, Daotai Nie, Louis S. Premkumar, Randolph C. Elble
Journal: Cancer Research (2009)

hCLCA2 is frequently down-regulated in breast cancer and is a candidate tumor suppressor gene. We show here that the hCLCA2 gene is strongly induced by p53 in response to DNA damage. Adenoviral expression of p53 induces hCLCA2 in a variety of breast cell lines. Further, we find that p53 binds to consensus elements in the hCLCA2 promoter and mutation of these sites abolishes p53-responsiveness and induction by DNA damage. Adenoviral transduction of hCLCA2 into immortalized cells induces p53, CDK inhibitors p21 and p27, and cell cycle arrest by 24 hours, and caspase induction and apoptosis by 40 hours postinfection. Transduction of the malignant tumor cell line BT549 on the other hand does not induce p53, p21, or p27 but instead induces apoptosis directly and more rapidly. Knockout and knockdown studies indicate that growth inhibition and apoptosis are signaled via multiple pathways. Conversely, suppression of hCLCA2 by RNA interference enhances proliferation of MCF10A and reduces sensitivity to doxorubicin. Gene expression profiles indicate that hCLCA2 levels are strongly predictive of tumor cell sensitivity to doxorubicin and other chemotherapeutics. Because certain Cl(-) channels are proposed to promote apoptosis by reducing intracellular pH, we tested whether, and established that, hCLCA2 enhances Cl(-) current in breast cancer cells and reduces pH to approximately 6.7. These results reveal hCLCA2 as a novel p53-inducible growth inhibitor, explain how its down-regulation confers a survival advantage to tumor cells, and suggest both prognostic and therapeutic applications.
Abnormal Phosphorylation of Pyridoxine in Patients with Refractory Sideroblastic Anemia.
Authors: John D. Hines
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971Abnormal Phosphorylation of Pyridoxine in Patients with Refractory Sideroblastic Anemia.John D. Hines, M.D. (Research Scholar)John D. Hines, M.D. (Research Scholar)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-826_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCertain indicators of vitamin B6metabolism were investigated in six patients with acquired refractory sideroblastic anemia who were only partially responsive to pyridoxine therapy. Two indexes of vitamin B6metabolism were assessed: [1] the in vivo conversion of pyridoxine (20 mg, intravenously) to pyridoxal phosphate was estimated by determination of serum pyridoxal phosphate levels from 0 to 300 min. [2] Erythrocyte and hepatic pyridoxal-phosphokinase activity were estimated from pyridoxal phosphate concentrations generated by incubation of erythrocyte hemolysates and liver tissue extracts incubated with equimolar adenosine triphosphate, pyridoxal and pyridoxine and Mg++at 37 C for 0, 30, and 60 min.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byVitamin B 6 Metabolism in Idiopathic Sideroblastic Anaemia and Related DisordersErythrocyte Pyridoxine Kinase Levels in Patients with Sideroblastic Anemia 1 May 1971Volume 74, Issue 5Page: 826-827KeywordsAdenosine triphosphateAnemiaAttentionLiverPhosphatesPyridoxine Issue Published: 1 May 1971 PDF downloadLoading ...
Clusterin Mediates TGF-β–Induced Epithelial–Mesenchymal Transition and Metastasis via Twist1 in Prostate Cancer Cells
Authors: Masaki Shiota, Anousheh Zardan, Ario Takeuchi, Masafumi Kumano, Eliana Beraldi, Seiji Naito, Amina Zoubeidi, Martin E. Gleave
Journal: Cancer Research (2012)

Abstract TGF-β promotes epithelial–mesenchymal transition (EMT) and induces clusterin (CLU) expression, linking these genes to cancer metastasis. CLU is a pleiotropic molecular chaperone that confers survival and proliferative advantage to cancer cells. However, the molecular mechanisms by which TGF-β regulates CLU expression and CLU affects metastasis remain unknown. In this study, we report that the transcription factor Twist1 mediates TGF-β–induced CLU expression. By binding to E-boxes in the distal promoter region of CLU gene, Twist1 regulated basal and TGF-β–induced CLU transcription. In addition, CLU reduction reduced TGF-β induction of the mesenchymal markers, N-cadherin and fibronectin, thereby inhibiting the migratory and invasive properties induced by TGF-β. Targeted inhibition of CLU also suppressed metastasis in an in vivo model. Taken together, our findings indicate that CLU is an important mediator of TGF-β–induced EMT, and suggest that CLU suppression may represent a promising therapeutic option for suppressing prostate cancer metastatic progression. Cancer Res; 72(20); 5261–72. ©2012 AACR.
Insulin and independence.
Authors: J D Eastwood
Journal: BMJ (1986)

nature had certainly influenced my thinking?and feeling?as a moral theologian. I could understand those people feeling im? prisoned within a deformed body and seeking revenge on the world?such as Gloucester. I flew back to England the next day as the trial continued. During the flight the young woman came to mind. Her mother had been in choking sobs during my testimony. I had articulated what her daughter could not. A certain sadness descended. It was one thing to write about an ear in the pages of this medical journal for a professional readership, or to speak to plastic surgeons, but to be examined in a court of law is altogether different. The woman's life would never be the same; and I formally announced the fact. Unexpected new doors
Subclinical Abnormalities in Sarcoplasmic Reticulum Ca2+ Release Promote Eccentric Myocardial Remodeling and Pump Failure Death in Response to Pressure Overload
Authors: Simon Sedej, Albrecht Schmidt, Marco Denegri, Stefanie Walther, Marinko Matovina, Georg Arnstein, Eva-Maria Gutschi, Isabella Windhager, Senka Ljubojević, Sara Negri, Frank R. Heinzel, Egbert Bisping, Marc A. Vos, Carlo Napolitano, Silvia G. Priori, Jens Kockskämper, Burkert Pieske
Journal: Journal of the American College of Cardiology (2013)
THE PROPHYLAXIS AND GENERAL MANAGEMENT OF ACUTE RHEUMATIC FEVER.
Authors: SOLOMON SOLIS-COHEN
Journal: JAMA (1907)

Prophylaxis depends on etiology and pathology; while general management must be co-ordinated with specific treatment, and modified to meet any complications that may arise. It is impossible, therefore, to discuss these two topics without some reference to the subjects that have been assigned to other speakers. Such reference will, however, be chiefly in the way of brief allusion, taking for granted the facts that have been, or will be, elaborated by my colleagues in the symposium. <h3>A. PROPHYLAXIS.</h3> The prophylaxis of acute articular rheumatism has four phases. These refer, respectively, to (1) the initial attack; (2) the complications, especially the cardiac affections; (3) relapses; (4) recurrences. At present this prophylaxis is, in all its phases, largely empirical, because pathology and etiology have not yet given us the necessary exact bases for an exact scientific preventive régime. We are all agreed that the condition called acute articular rheumatism is a special
Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies
Authors: Michele Pasotti, Catherine Klersy, Andrea Pilotto, Nicola Marziliano, Claudio Rapezzi, Alessandra Serio, Savina Mannarino, Fabiana Gambarin, Valentina Favalli, Maurizia Grasso, Manuela Agozzino, Carlo Campana, Antonello Gavazzi, Oreste Febo, Massimiliano Marini, Maurizio Landolina, Andrea Mortara, Giovanni Piccolo, Mario Viganò, Luigi Tavazzi, Eloisa Arbustini
Journal: Journal of the American College of Cardiology (2008)
Abstract 180: Quality of Chest Compressions Performed During 1 and 2 Minutes by Medical Students
Authors: Renan G Oliveira, Maria M Gonzalez, Ruana S Girardi, Naianne S Leão, Thalita R Barros, Caio B Vianna, Sergio Timerman
Journal: Circulation (2011)

Background: In order to perform an efficient CPR, it is very important to pay attention to the frequency of the thrusts and the depth of the movement being made into the chest. Studies have proven that the quality of the maneuver decreases over time as the minutes progress. Hypothesis: We hypothesized that chest compressions correctly performed during one minute are more effective than those continued during two minutes. Methods: We trained 48 first year medical students through the “Family and Friends CPR Anytime” course. Next, a minute of continuous compressions on the Resusci Anne training mannequin, with a PC reporting system, were performed. After one week, two minutes of continuous chest compressions were performed on the same mannequin. Results: The mean age was 20,94 ±3.51 years, the mean body mass index was 25.7 ±4.7 kg/m 2 and 25 students (55%) were of male gender. Comparing the compressions performed during one and two minutes, respectively: the average rate of compressions per minute were (116 vs. 123), the average of incomplete release (5% vs. 19%), the duty cycle (47% vs. 49%), percentage of compressions with no error (54% vs. 38%), with appropriate depth (57% vs. 48%) and the average depth (48mm vs. 45mm) show significant differences (p=0.01, p&lt;0.01, p=0.03, p=0.01, p=0.30, p=0.03, respectively). The only parameter evaluated that showed no significant difference was the percentage of compressions with correct hand position, 93% vs. 86%, respectively (p=0.35). Conclusion: The results of the study show significant differences in important parameters of chest compressions and reveal better quality when performed during one minute rather than two minutes. This corroborates that it would be better to change the rescuer even before the two minute mark has elapsed. Furthermore, the main parameter that needs improvement would be the depth of compressions, reinforcing the need of devices which measure the depth of chest compressions during CPR maneuvers.
Rapidly Reversible, Sedation-related Delirium versus Persistent Delirium in the Intensive Care Unit
Authors: Shruti B. Patel, Jason T. Poston, Anne Pohlman, Jesse B. Hall, John P. Kress
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Intensive care unit (ICU) delirium is associated with ventilator, ICU, and hospital days; discharge functional status; and mortality. Whether rapidly reversible, sedation-related delirium (delirium that abates shortly after sedative interruption) occurs with the same frequency and portends the same prognosis as persistent delirium (delirium that persists despite a short period of sedative interruption) is unknown.To compare rapidly reversible, sedation-related delirium and persistent delirium.This was a prospective cohort study of 102 adult, intubated medical ICU subjects in a tertiary care teaching hospital. Confusion Assessment Method for the ICU evaluation was performed before and after daily interruption of continuous sedation (DIS). Investigators were blinded to each other's assessments and as to whether evaluations were before or after DIS. The primary outcome was proportion of days with no delirium versus rapidly reversible, sedation-related delirium versus persistent delirium. Secondary outcomes were ventilator, ICU, and hospital days; discharge disposition; and 1-year mortality.The median proportion of ICU days with delirium was 0.57 before versus 0.50 after DIS (P < 0.001). The Confusion Assessment Method for the ICU indicated patients are 10.5 times more likely to have delirium before DIS versus after (P < 0.001). Rapidly reversible, sedation-related delirium showed fewer ventilator (P < 0.001), ICU (P = 0.001), and hospital days (P < 0.001) than persistent delirium. Subjects with no delirium and rapidly reversible, sedation-related delirium were more likely to be discharged home (P < 0.001). Patients with persistent delirium had increased 1-year mortality versus those with no delirium and rapidly reversible, sedation-related delirium (P < 0.001).Rapidly reversible, sedation-related delirium does not signify the same poor prognosis as persistent delirium. Degree of sedation should be considered in delirium assessments. Coordinating delirium assessments with daily sedative interruption will improve such assessments' ability to prognosticate ICU delirium outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 00919698).
Should computed tomography of the chest be recommended in the medical certification of professional divers?
Authors: I L Millar
Journal: British Journal of Sports Medicine (2004)

Chest CT should not be used in the assessment of fitness to dive

Toklu et al 1 have raised the question of whether routine high resolution computed tomographic (CT) scanning of the chest should form part of the initial diving medical examination for occupational divers. The authors make this proposition in discussing their series of three divers in which pulmonary abnormalities were discovered on high resolution CT scan after occupational diving incidents. One case involved a bulla, the second multiple air cysts, and the last a subpleural bleb. The authors assume that the initial mechanism of injury in each case was pulmonary barotrauma associated with the lesions revealed.

One could argue whether the second and third cases may have involved arterialisation of venous bubbles rather than pulmonary barotrauma, but any uncertainty does not invalidate consideration of the authors’ contentions. It is widely agreed that lung cysts, bullae, and blebs may all predispose to pulmonary barotrauma, and most authorities recommend disqualification from diving if such lesions are found.2–4 This report adds to others in which CT scans have revealed pulmonary abnormalities in diving accident victims where chest radiographs did not.5,6 I have also managed a similar case of apparently undeserved arterial gas embolism after years of uneventful diving in a healthy man with a normal chest radiograph. Subpleural blebs were discovered on incidental CT scan several years later.

Pulmonary barotrauma in divers often occurs in the provocative setting of uncontrolled ascent, with rapid gas expansion and the potential for high transthoracic pressures.6,7 It is estimated that a normal lung will rupture if a transtracheal pressure of 75–80 mm Hg is exceeded, and pulmonary structural predisposition is not needed to explain such incidents.8,9 Prevention of such cases should focus on psychological suitability for underwater …
Advantages of proton beam therapy in Ashya King's type of cancer are small, doctors say
Authors: N. Hawkes
Journal: BMJ (2014)

Ashya King, the five year old boy taken by his parents from Southampton General Hospital for proton beam therapy in Prague, is unlikely to benefit significantly and runs a risk of his treatment failing because it was delayed, doctors commenting on the treatment have implied.

At a Science Media Centre press conference in London, experts in proton beam therapy summarised the evidence for treating medulloblastoma, the type of cancer that Ashya has. They did not discuss the specifics of his case owing to patient confidentiality, but they made clear that the advantages of using a beam of protons rather than conventional x rays were small in this type of cancer, which has a good chance of cure if treated with normal radiotherapy in line with well defined protocols.

The United Kingdom does not yet have proton beam facilities, but they are being built at University College Hospital …
Computer service for obstetric records.
Authors: P Flamme
Journal: BMJ (1971)

administrative offices in the very best position, perhaps rightly so, but the medical records department will probably be located in the basement.It has not been redecorated recently, is miserable and ill equipped, but, never mind, nobody "important" goes there.Sir Herbert mentions training schemes.No doubt he knows only too well that 99% of new medical records staff are "trained" by sitting next to the girl who has been in the post a month or so longer.We call it "learning from Lucy."I think it an admirable suggestion that a rumpus be made to the Department for recognition, but would suggest that charity begins at home, with the medical staff at hospital level acknow- ledging the medical records officer as a pro- fessional in her own specialized field and supporting her in her attempts to improve and maintain a high standard of record keeping.
CAPON SPRINGS WATER
Authors: H. A. Hare
Journal: JAMA (1924)

<h3>To the Editor:</h3> —This part of the country is being "covered" through the mails and daily papers with literature on Capon Springs Water. This literature, so called, mentions a large number of physicians who have been dead for many years as recommending this water. They have seen fit to include my name in the list. I have never recommended it by word of mouth or in writing. I am under the impression that I am still professor of therapeutics in the Jefferson Medical College, but their literature refers to me as "formerly professor of therapeutics," etc. Apparently the thought of the compiler of this brochure was that dead men would not protest against the use of their names. A live one does. My object in writing toThe Journalis to let it be generally known by medical men that this use of my name is without any justification whatever.
Relation of High Blood Pressure to Headache, Epistaxis, and Selected Other Symptoms
Authors: Noel S. Weiss
Journal: New England Journal of Medicine (1972)

From the records of the Health Examination Survey of adults, 1960–62, the blood pressure of each of 6672 subjects was tabulated against his response to several questions on a self-administered medical history form. The responses to questions regarding headache, epistaxis, and tinnitus showed no relation to either systolic or diastolic blood pressure. The occurrence of dizziness was increased only in persons with very high diastolic pressure. The occurrence of fainting was inversely related to blood pressure. Headache, tinnitus, and dizziness were each reported slightly but significantly more often in subjects with than without retinopathy; this relation held true in both normotensive and hypertensive groups.