tbuckley/cabot-search huggingface dataset:
Posttranscriptional Regulation of the Breast Cancer Susceptibility Gene <i>BRCA1</i> by the RNA Binding Protein HuR
Authors: Jodi M. Saunus, Juliet D. French, Stacey L. Edwards, Dianne J. Beveridge, Esme C. Hatchell, Sarah A. Wagner, Sandra R. Stein, Andrew Davidson, Kaylene J. Simpson, Glenn D. Francis, Peter J. Leedman, Melissa A. Brown
Journal: Cancer Research (2008)

Abstract BRCA1 is a breast cancer susceptibility gene that is down-regulated in a significant proportion of sporadic breast cancers. BRCA1 is posttranscriptionally regulated by RNA-binding proteins, the identities of which are unknown. HuR is an RNA binding protein implicated in posttranscriptional regulation of many genes and is overexpressed in sporadic breast cancer. To investigate the possibility that these two molecules are functionally linked in breast cancer, we performed bioinformatic analysis of the BRCA1 3′ untranslated region (UTR), RNA-protein assays with the HuR protein and the BRCA1 3′UTR, and immunohistochemical analysis of a cohort of breast tumors using antibodies against BRCA1 and HuR. Here, we describe the identification of two predicted HuR-binding sites in the BRCA1 3′UTR, one of which binds specifically to HuR. We also show that this interaction is disrupted by single nucleotide substitutions in the BRCA1 3′UTR and that endogenous HuR protein associates with BRCA1 transcripts in T47D and MCF7 breast cancer cells. Expression of ectopic HuR results in a significant decrease in BRCA1 protein expression and also BRCA1 3′UTR activity. Immunohistochemical analysis revealed that although BRCA1 and HuR expression were associated with some clinicopathologic features of the tumors, there was no statistically significant correlation between BRCA1 and HuR protein expression. These results identify the first posttranscriptional protein regulator of BRCA1 and have implications for understanding BRCA1 regulation in human breast cancer. [Cancer Res 2008;68(22):9469–78]
Medical Education Revisited
Authors: John A.D. Cooper
Journal: New England Journal of Medicine (1980)

This issue of the Journal includes a remarkable case study that is not likely to be repeated. It is the report of observations and reflections on medical education by a physician who attended a medical school and received a second M.D. degree after retirement from a long and distinguished career as a physiologist, a clinical investigator, a cardiologist, a medical educator, and above all a physician. Ludwig Eichna first graduated from medical school at the University of Pennsylvania in 1931. He served on the medical faculty at New York University and then became chairman of the Department of Medicine at . . .
WAR EDEMA (KRIEGSOEDEM)
Authors: F. S. PARK
Journal: JAMA (1918)

organized philanthropy if wisely directed.Yet all these means will fail to attain what we could wish unless we add one additional measure, the segregation of the infant from sources of contagion.The French have seen the light more distinctly than other nations.In France the formula is : Either remove the young child from the presence of the consumptive or the consumptive from his family, if there are young chil- dren.The child must by all means be prevented from From the Medical and Laboratory Services, Base Hospital, Camp
Monocyte-chemotactic activity of defensins from human neutrophils.
Authors: M C Territo, T Ganz, M E Selsted, R Lehrer
Journal: Journal of Clinical Investigation (1989)

We investigated the monocyte-chemotactic activity of fractionated extracts of human neutrophil granules. Monocyte-chemotactic activity was found predominantly in the defensin-containing fraction of the neutrophil granules. Purified preparations of each of the three human defensins (HNP-1, HNP-2, HNP-3) were then tested. HNP-1 demonstrated significant chemotactic activity for monocytes: Peak activity was seen at HNP-1 concentrations of 5 X 10(-9) M and was 49 +/- 20% (mean +/- SE, n = 9) of that elicited by 10(-8) M FMLP. HNP-2 (peak activity at 5 X 10(-9) M) was somewhat less active, yielding 19 +/- 10% (n = 11). HNP-3 failed to demonstrate chemotactic activity. Checkerboard analysis of monocyte response to HNP-1 and HNP-2 confirmed that their activity was chemotactic rather than chemokinetic. Neutrophils demonstrated a low level of response to defensins but this reaction was primarily chemokinetic. Defensins may play a role in the recruitment of monocytes by neutrophils into inflammatory sites.
Three in five NHS trusts in England fail on basic care
Authors: Michael Day
Journal: BMJ (2006)

Three in five NHS trusts in England are failing basic standards of care and safety set by the government, it emerged this week.

The failings were admitted by the trusts themselves in the first ever national self assessment exercise, which replaces the star rating system.

The most common breaches included failure to decontaminate reusable equipment, poor management of patients' records, lack of compliance with guidelines on diagnosis and treatment, and faults in staff training procedures.

Just over a third of trusts claimed to be meeting all the Healthcare Commission's 44 core standards of basic competence. A quarter admitted failing at least four standards, and 10 trusts said they were deficient on at least 14. Any trust that failed 14 or more standards was judged to have failed overall.

Anna Walker, the chief executive of the Healthcare Commission, said: “We are encouraged by the …
India agrees to help Nigeria tackle the import of fake drugs
Authors: A. Raufu
Journal: BMJ (2003)

India, one of the largest exporters of fake and substandard drugs to Nigeria, has agreed to take measures to tackle the problem. It is concerned about Nigeria's threat to ban the import of all drugs from countries that export fake drugs to its shores.

The Indian minister of state for commerce and industry, Mr Shri Rajiv Pratap Rudy, visited Nigeria last week and said that his government had introduced …
A New Era of Cardiovascular Disease Epidemiology
Authors: Bruce M. Psaty, Donna Arnett, Gregory Burke
Journal: JAMA (2007)

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
Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis
Authors: Ronald L. Gibson, Jane L. Burns, Bonnie W. Ramsey
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

This comprehensive State of the Art review summarizes the current published knowledge base regarding the pathophysiology and microbiology of pulmonary disease in cystic fibrosis (CF). The molecular basis of CF lung disease including the impact of defective cystic fibrosis transmembrane regulator (CFTR) protein function on airway physiology, mucociliary clearance, and establishment of Pseudomonas aeruginosa infection is described. An extensive review of the microbiology of CF lung disease with particular reference to infection with P. aeruginosa is provided. Other pathogens commonly associated with CF lung disease including Staphylococcal aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans and atypical mycobacteria are also described. Clinical presentation and assessment of CF lung disease including diagnostic microbiology and other measures of pulmonary health are reviewed. Current recommendations for management of CF lung disease are provided. An extensive review of antipseudomonal therapies in the settings of treatment for early P. aeruginosa infection, maintenance for patients with chronic P. aeruginosa infection, and treatment of exacerbation in pulmonary symptoms, as well as antibiotic therapies for other CF respiratory pathogens, are included. In addition, the article discusses infection control policies, therapies to optimize airway clearance and reduce inflammation, and potential future therapies.
Paracrine and Endocrine Effects of Adipose Tissue on Cancer Development and Progression
Authors: Jiyoung Park, David M. Euhus, Philipp E. Scherer
Journal: Endocrine Reviews (2011)

The past few years have provided substantial evidence for the vital role of the local tumor microenvironment for various aspects of tumor progression. With obesity and its pathophysiological sequelae still on the rise, the adipocyte is increasingly moving center stage in the context of tumor stroma-related studies. To date, we have limited insight into how the systemic metabolic changes associated with obesity and the concomitant modification of the paracrine and endocrine panel of stromal adipocyte-derived secretory products (“adipokines”) influence the incidence and progression of obesity-related cancers. Here, we discuss the role of adipocyte dysfunction associated with obesity and its potential impact on cancer biology.
Respiratory Syncytial Virus Bronchiolitis
Authors: Ann R. Punnoose, Robert M. Golub
Journal: JAMA (2012)

Respiratory Syncytial Virus BronchiolitisR espiratory syncytial virus (RSV) usually causes cold-like symptoms but can also cause more severe diseases, such as pneumonia and bronchiolitis.Bronchiolitis, an inflammation of the small airways in the lung with increased mucus production and bronchospasms (contraction and relaxation of the small airways), most often occurs in children younger than 2 years.In children, RSV infections may start out with fever, mild cough, and congestion.This can lead to worsening cough and labored and rapid breathing that interfere with the ability to eat and drink.In the United States, RSV infections usually occur between November and May but may occur earlier in the year in some areas.The infection spreads by contact with an infected person's saliva and mucus containing the virus.
EU commissioner promises a European centre for disease control by 2005
Authors: Ben Duncan
Journal: BMJ (2002)

The European health commissioner, David Byrne, has promised to create a European centre for disease control by 2005, when his role as health commissioner comes to an end.

Speaking at a press conference at the annual European health forum in Gastein, Austria, Byrne outlined plans for a centre bringing together expertise on epidemic control from around the European Union and coordinating European strategies against bioterrorism. The centre might also act as a contact point between health policy makers and the pharmaceutical industry.

The European Commission will present enabling legislation in the spring. Byrne will then press EU law makers in the European parliament and the Council of Ministers to pass the legislation within 18 months or less, so that …
First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases
Authors: M. Louise Markert, José G. Marques, Bénédicte Neven, Blythe H. Devlin, Elizabeth A. McCarthy, Ivan K. Chinn, Adriana S. Albuquerque, Susana L. Silva, Claudio Pignata, Geneviève de Saint Basile, Rui M. Victorino, Capucine Picard, Marianne Debre, Nizar Mahlaoui, Alain Fischer, Ana E. Sousa
Journal: Blood (2010)
Atrial natriuretic peptide enhances microvascular albumin permeability by the caveolae-mediated transcellular pathway
Authors: Wen Chen, Birgit Gaßner, Sebastian Börner, Viacheslav O. Nikolaev, Nicolas Schlegel, Jens Waschke, Nadine Steinbronn, Ruth Strasser, Michaela Kuhn
Journal: Cardiovascular Research (2011)

Cardiac atrial natriuretic peptide (ANP) participates in the maintenance of arterial blood pressure and intravascular volume homeostasis. The hypovolaemic effects of ANP result from coordinated actions in the kidney and systemic microcirculation. Hence, ANP, via its guanylyl cyclase-A (GC-A) receptor and intracellular cyclic GMP as second messenger, stimulates endothelial albumin permeability. Ultimately, this leads to a shift of plasma fluid into interstitial pools. Here we studied the role of caveolae-mediated transendothelial albumin transport in the hyperpermeability effects of ANP. Intravital microscopy studies of the mouse cremaster microcirculation showed that ANP stimulates the extravasation of fluorescent albumin from post-capillary venules and causes arteriolar vasodilatation. The hyperpermeability effect was prevented in mice with conditional, endothelial deletion of GC-A (EC GC-A KO) or with deleted caveolin-1 (cav-1), the caveolae scaffold protein. In contrast, the vasodilating effect was preserved. Concomitantly, the acute hypovolaemic action of ANP was abolished in EC GC-A KO and Cav-1−/− mice. In cultured microvascular rat fat pad and mouse lung endothelial cells, ANP stimulated uptake and transendothelial transport of fluorescent albumin without altering endothelial electrical resistance. The stimulatory effect on albumin uptake was prevented in GC-A- or cav-1-deficient pulmonary endothelia. Finally, preparation of caveolin-enriched lipid rafts from mouse lung and western blotting showed that GC-A and cGMP-dependent protein kinase I partly co-localize with Cav-1 in caveolae microdomains. ANP enhances transendothelial caveolae-mediated albumin transport via its GC-A receptor. This ANP-mediated cross-talk between the heart and the microcirculation is critically involved in the regulation of intravascular volume.
Performance indicators in general practice.
Authors: R F Jankowski
Journal: BMJ (1993)

We question what improvement in the data is afforded by treating thQse who do not sit a voluntary examination as equivalent to those who enter and fail it.In the emerging atmosphere of higher education, in which quality and value for money are watchwords, funding bodies are increasingly using performance indicators.Such indicators include numbers of staff and students; school leaving qualifications; drop out rates; quality of educational provision; pass rates; measures of graduates' subsequent success; and excellence and productivity of research.Data on many of these have been published or made available to universities, and they provide material for reflection-for example, one of us has reported substantial differences in the clinical experience provided by groups of medical schools (London, Oxford and Cambridge, England and Wales, Scotland and Northern Ireland).'Medical education is a continuum from under- graduate training through to continuing medical education.One object of undergraduate training is to prepare students for postgraduate training, which is typically assessed at some point by the examinations of the royal colleges.Measures of success in medicine are thus likely to include the results of these examinations, and we do not think that this is inappropriate.To this end it is desirable that all royal colleges publish data on the performance in their examinations of British graduates by medical school.
National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys
Authors: Maya N. Mascarenhas, Seth R. Flaxman, Ties Boerma, Sheryl Vanderpoel, Gretchen A. Stevens
Journal: PLoS Medicine (2012)

Gretchen Stevens and colleagues use information from demographic reproductive health surveys to estimate the global, regional, and country levels, patterns, and trends in infertility between 1990 and 2010.
Anterior septal coronary artery infarction in the canine: a model of ventricular tachycardia with a subendocardial origin. Ablation and activation sequence mapping.
Authors: J S Tweddell, C K Rokkas, A Harada, J S Pirolo, B H Branham, R B Schuessler, J P Boineau, J L Cox
Journal: Circulation (1994)

BACKGROUND In humans, chronic ventricular tachycardia (VT) is usually associated with myocardial infarcts that involve the interventricular septum. In an effort to more closely mimic the anatomic substrate that gives rise to chronic VT in humans, we developed a canine model of VT in which the anterior septal coronary artery was ligated. The site of earliest activation, the subsequent activation sequence, and the mechanism of VT associated with the resultant ventricular septal infarct was then evaluated to determine if this model accurately reflected the characteristics of human VT. METHODS AND RESULTS Seventeen dogs underwent occlusion-reperfusion ventricular septal infarcts. Four to 7 days later, electrophysiological studies were performed. VT was initiated by programmed electrical stimulation and terminated by pacing at a cycle length of 50% to 75% of the VT cycle length. Electrophysiological studies were performed using a 256-channel mapping system. A total of 15 VT morphologies were mapped in 9 animals. Fourteen of 15 morphologies had septal subendocardial sites of earliest activation and 1 had a septal midwall site of earliest activation. VT ablation was performed using a nitrous oxide cryoprobe and confirmed the site of earliest activation by subsequently rendering VT noninducible. Electrophysiological studies demonstrated four distinct VT activation sequences: (1) circular reentrant (n = 7), (2) concentric spread (n = 5), (3) figure-of-eight (n = 2), and (4) septal midwall (n = 1). CONCLUSIONS This canine model of ventricular septal infarction produces VTs with sites of earliest activation and activation sequences similar to those in humans. A reentrant mechanism as the basis of these arrhythmias is supported by the following observations: (1) all VT was initiated and terminated with programmed electrical stimulation; (2) VT activation sequences were consistent with reentry; and (3) precise interruption of the sequence terminated the VT and rendered it noninducible.
Australian government tries to solve doctors indemnity crisis
Authors: C. Zinn
Journal: BMJ (2003)

The Australian government has introduced a package of measures designed to tackle the country's medical indemnity crisis, which has been characterised by soaring premiums and the collapse of Australia's biggest medical insurance company. The package includes a subsidy of premiums for obstetricians, neurosurgeons, and GPs who perform certain procedures.

The Australian Medical Association has said that it does not go far enough and has predicted that 20% of rural GPs who provide obstetric services will quit rather than face much higher premiums.

The association said that despite …
Phase I Pharmacokinetic and Pharmacodynamic Study of Carboplatin and Topotecan Administered Intravenously Every 28 Days to Patients with Malignant Solid Tumors
Authors: David S. Boss, Wandena S. Siegel-Lakhai, Nadja E. van Egmond-Schoemaker, Dick Pluim, Hilde Rosing, Wim W. ten Bokkel Huinink, Jos H. Beijnen, Jan H.M. Schellens
Journal: Clinical Cancer Research (2009)

Preclinical studies have shown that the combination of topotecan and carboplatin is synergistic. To evaluate the schedule dependency of this interaction, the following phase I trial was designed to determine the safety and maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carboplatin and topotecan in patients with malignant solid tumors.In part 1, patients received carboplatin on day 1 and topotecan on days 1, 2, and 3 (C-->T schedule). In part 2, topotecan was administered on days 1, 2, and 3, followed by carboplatin on day 3 (T-->C schedule). Pharmacokinetics were determined in plasma and DNA topoisomerase I catalytic activity and Pt-DNA adducts in WBC and tumor tissue.Forty-one patients were included. Dose-limiting toxicities during the C-->T schedule were grade 4 thrombocytopenia and febrile neutropenia (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 4 min mg/mL; topotecan, 0.5 mg/m(2)/d). Dose-limiting toxicities during the T-->C schedule included grade 4 neutropenia, thrombocytopenia, neutropenic fever, and grade 4 nausea and vomiting (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 6 min mg/mL; topotecan, 0.9 mg/m(2)/d). One complete response and five partial responses were observed. The clearance of and exposure to carboplatin and topotecan did not depend on the sequence of drug administration. No schedule-dependent effects were seen in Pt-DNA levels and DNA topoisomerase I catalytic activity in WBC and tumor tissue. However, myelotoxicity was clearly more evident in the C-->T schedule.The T-->C schedule was better tolerated because both hematologic and nonhematologic toxicities were milder. Other pharmacodynamic factors than the ones investigated must explain the schedule-dependent differences in toxicities.
Potent and Long-Lasting Vasodilatory Effects of Adrenomedullin in Humans
Authors: Motoyuki Nakamura, Hiroaki Yoshida, Shinji Makita, Naoshi Arakawa, Hiroyuki Niinuma, Katsuhiko Hiramori
Journal: Circulation (1997)

Background Adrenomedullin (ADM) is a recently discovered hypotensive peptide that has been isolated from human pheochromocytoma cells. Observations that ADM is produced from cardiovascular tissue and is found in plasma suggest that it may be important in the regulation of regional vascular resistance. Methods and Results Limb vascular responses to ADM were examined in 10 healthy subjects and compared with those in 18 patients with chronic heart failure (CHF). The peptide increased forearm blood flow (FBF) from 2.7±0.3 to 11.8±0.9 mL·min −1 ·100 mL −1 in the control group and from 2.4±0.3 to 6.5±0.7 mL·min −1 ·100 mL −1 in the CHF group. The ADM-induced FBF increase was significantly impaired in the CHF group ( P &lt;.01). After cessation of the infusion, an increased FBF level was sustained for &gt;60 minutes in the control group, whereas in the CHF group the response returned to the baseline in &lt;30 minutes. The ADM infusion increased forearm skin blood flow in both groups ( P &lt;.05), whereas the skin blood flow response was impaired in the CHF group ( P &lt;.01). The role of nitric oxide in ADM-induced vasorelaxation was also studied in 11 healthy subjects and 6 patients with CHF. FBF and skin blood flow responses during ADM administration were significantly attenuated by N G -monomethyl- l -arginine administration in healthy control subjects ( P &lt;.05), whereas both flow responses remained the same in the CHF group. Conclusions These observations demonstrate that ADM exerts a potent and long-lasting vasodilatory effect on skeletal muscle arteries with involvement of nitric oxide–dependent mechanisms in normal human peripheral vasculature and that these vascular effects are significantly attenuated in patients with CHF, in part because of impaired production of nitric oxide in the forearm resistance vessels.
Effect of vasopressin on esophageal varices blood flow in patients with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow
Authors: Tadashi Iwao, Atsushi Toyonaga, Kazuhiko Oho, Hiroyuki Shigemori, Teruhiro Sakai, Chizuru Tayama, Hideo Masumoto, Masahiro Sato, Kyuichi Tanikawa
Journal: Journal of Hepatology (1996)