tbuckley/cabot-search huggingface dataset:
A Novel RARβ Isoform Directed by a Distinct Promoter P3 and Mediated by Retinoic Acid in Breast Cancer Cells
Authors: Xinjian Peng, Takeshi Maruo, Yanxia Cao, Vasu Punj, Rajeshwari Mehta, Tapas K. Das Gupta, Konstantin Christov
Journal: Cancer Research (2004)

Abstract Retinoids regulate gene transcription through activating retinoic acid receptors (RARs)/retinoic X receptors (RXRs). Of the three RAR receptors (α, β, and γ), RARβ has been considered a tumor suppressor gene. Here, we identified a novel RARβ isoform-RARβ5 in breast epithelial cells, which could play a negative role in RARβ signaling. Similar to RARβ2, the first exon (59 bp) of RARβ5 is RARβ5 isoform specific, whereas the other exons are common to all of the RARβ isoforms. The first exon of RARβ5 does not contain any translation start codon, and therefore its protein translation begins at an internal methionine codon of RARβ2, lacking the A, B, and part of C domain of RARβ2. RARβ5 protein was preferentially expressed in estrogen receptor-negative breast cancer cells and normal breast epithelial cells that are relatively resistant to retinoids, whereas estrogen receptor-positive cells that did not express detectable RARβ5 protein were sensitive to retinoid treatment, suggesting that this isoform may affect the cellular response to retinoids. RARβ5 isoform is unique among all of the RARs, because a corresponding isoform was not detectable for either RARα or RARγ. RARβ5 mRNA was variably expressed in normal and cancerous breast epithelial cells. Its transcription was under the control of a distinct promoter P3, which can be activated by all-trans-retinoic acid (atRA) and other RAR/RXR selective retinoids in MCF-7 and T47D breast cancer cells. We mapped the RARβ5 promoter and found a region -302/-99 to be the target region of atRA. In conclusion, we identified and initially characterized RARβ5 in normal, premalignant, and malignant breast epithelial cells. RARβ5 may serve as a potential target of retinoids in prevention and therapy studies.
Health impacts of pesticide exposure in a cohort of outdoor workers.
Authors: John Beard, Tim Sladden, Geoffrey Morgan, Geoffrey Berry, Lyndon Brooks, Anthony McMichael
Journal: Environmental Health Perspectives (2002)

We compared mortality of 1,999 outdoor staff working as part of an insecticide application program during 1935-1996 with that of 1,984 outdoor workers not occupationally exposed to insecticides, and with the Australian population. Surviving subjects also completed a morbidity questionnaire. Mortality was significantly higher in both exposed and control subjects compared with the Australian population. The major cause was mortality from smoking-related diseases. Mortality was also significantly increased in exposed subjects for a number of conditions that do not appear to be the result of smoking patterns. Compared with the general Australian population, mortality over the total study period was increased for asthma [standardized mortality ratio (SMR) = 3.45; 95% confidence interval (CI), 1.39-7.10] and for diabetes (SMR = 3.57; 95% CI, 1.16-8.32 for subjects working < 5 years). Mortality from pancreatic cancer was more frequent in subjects exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (SMR = 5.27; 95% CI, 1.09-15.40 for subjects working < 3 years). Compared with the control population, mortality from leukemia was increased in subjects working with more modern chemicals (standardized incidence ratio = 20.90; 95% CI, 1.54-284.41 for myeloid leukemia in the highest exposure group). There was also an increase in self-reported chronic illness and asthma, and lower neuropsychologic functioning scores among surviving exposed subjects when compared with controls. Diabetes was reported more commonly by subjects reporting occupational use of herbicides. These findings lend weight to other studies suggesting an association between adverse health effects and exposure to pesticides.
Echocardiographic Features of Atrial Septal Defect
Authors: MORTON A. DIAMOND, JAMES C. DILLON, CHARLES L. HAINE, SONIA CHANG, HARVEY FEIGENBAUM
Journal: Circulation (1971)

Echocardiographic studies were performed on 39 adult patients with atrial septal defects. Findings were compared with those from normal subjects, patients with other congenital left-to-right shunts (ventricular septal defect and patent ductus arteriosus), patients with uncomplicated right ventricular pressure overload (pulmonic stenosis and pulmonary hypertension), and patients with pulmonary hypertension complicated by tricuspid regurgitation. Two echocardiographic features were assessed: 1) a right ventricular dimension, or RVD Index, representing the distance between the right ventricular epicardial echoes and echoes from the right side of the interventricular septum divided by the patient's body surface area, and 2) motion of the interventricular septum. The increased RVD Index and abnormal septal motion observed in the patients with atrial septal defects provided an ultrasound complex that could clearly separate these patients from normal individuals, those with ventricular septal defect and patent ductus arteriosus, and those with uncomplicated right ventricular pressure overload. However, patients with tricuspid regurgitation could not be differentiated from the group with atrial septal defects, indicating that this echocardiographic complex reflected a volume overload of the right ventricle.
Totipotent stem cells could do everything ... or else nothing: the case of vascular reendothelialization
Authors: A. Cevese
Journal: Cardiovascular Research (2011)

This editorial refers to ‘Circulating endothelial progenitor cells do not contribute to regeneration of endothelium after murine arterial injury’ by M.K. Hagensen et al. , pp. 223–231, this issue. 

And the rib, which the Lord God had taken from man, made he a woman, and brought her unto the man. (Gen. 2:22) 

In 1868, Goujon1 was awarded a prize of 500 francs by l'Academie de France in Paris for his presentation of very well-performed experiments ‘Sur les Proprietes Physiologiques de la Moelle des Os’ (on the Physiological Properties of Bone Marrow) in which he demonstrated the formation of bone tissue from autologous grafts of red bone marrow within skeletal muscle tissue of rabbits, chickens, and pigeons. These seminal experiments probably initiated the search for stem cells, responding to a long-lasting longing for reconstruction of damaged tissues by undifferentiated cells. It was not, however, until 1968 that this possibility was firmly reassessed2 and the recent story of stem cell research and deployment was initiated, although the term ‘mesenchymal stem cells’ was first coined by Caplan3 in 1991.

This item is fully connected with the problem of repair of vascular injury, mainly caused by therapeutic interventions aimed at removing endoluminal (atherosclerotic) obstacles by angioplasty that by definition …
The distal end of the atrioventricular nodal artery serves as a landmark identifying the risk of complete heart block during radiofrequency catheter ablation of the slow pathway in atrioventricular nodal reentrant tachycardia
Authors: J.-L. Lin, L.-P. Lai, L.-J. Lin, Y.-Z. Tsong, W.-P. Lien, S.K.S. Huang
Journal: Journal of the American College of Cardiology (1998)
THE HOSPITAL POLICY OF THE LABOUR PARTY
Authors: Chas. Buttar
Journal: BMJ (1922)

COIr-REiE-FNDENCE.( TiMEDitTx -~~~~~~~~~~~~~~EDICAL JOUsLNAZ the Dublin Zoo.A good m-any lions are bred there, aud a very intelligent keeper discussed their healtlh and up- bringing.He said the chief trouble they had with them-l was rickets, but since they lhad increased the amount of fat in their diet no cases of rickets had occurred.This would tend to slhow that the food factor is of greater inmportance, as the lion hiouse is light and airy.-Iam, etc.,
Trends in Health-Insurance Operating Expenses
Authors: Robert J. Weiss, William H. Wiese, Joel C. Kleinman
Journal: New England Journal of Medicine (1972)

Abstract An examination of the operating expenses of 74 Blue Cross plans and 73 Blue Shield plans from 1965 through 1969 revealed that on a per enrollee basis, operating expenses nationally rose 66.2 per cent for Blue Cross and 60.6 per cent for Blue Shield plans. The rate of increase is sharper than for hospital daily charges from 1967 to 1969. The variation among Blue Cross plans in their 1969 operating expense per enrollee ranges from a low of $1.18 to a high of $8.74. The data raise serious questions about the desirability of expressing operating expenses of private health-insurance companies only as a percentage of subscription income. The inflation of operating expenses in private health insurance justifies a cautionary approach in the evaluation of those proposals for regulating private health-insurance companies, especially if they are to be used as fiscal intermediaries or carriers in public programs. More data are needed for an adequate assessment.
A "Relative Efficacy" System for New Drugs
Authors: PAUL D. STOLLEY
Journal: Annals of Internal Medicine (1970)

A new system for approving the placement of new drugs on the market, a "relative efficacy" system, is proposed. The system would insure that new drugs be not only as safe as drugs already marketed for similar indications but would also require that they be more efficacious. Such a requirement should encourage pharmaceutical manufacturers to direct their research towards the development of safe and more efficacious drugs.
How the Doctor Got Gagged-Reply
Authors: Madison Powers
Journal: JAMA (1992)

<h3>In Reply.</h3> —Drs Archer and Wood argue that our characterization of<i>Rust v Sullivan</i><sup>1</sup>as "a significant departure from established precedent" is incorrect. Each notes that aspects of the communication between physician and patient have long been regulated. And in this regard, they are correct. Both, however, fail to appreciate the point of our claim. The Supreme Court's decision in<i>Rust</i>is a significant departure from established precedent in three important respects. First, most legislative and judicial efforts to regulate physician-patient communication have been designed to expand the duty to provide full and complete information to patients so that they might make knowledgeable and informed health care decisions. In<i>Rust</i>, however, the regulation at issue departs from this rationale since it restricts, rather than expands, what health care workers tell their patients. Second, even when the stated rationale behind legislative attempts to control physician-patient communication has been to promote
Mobile "life's end" teams start work in Netherlands
Authors: T. Sheldon
Journal: BMJ (2012)

In the face of serious objections from the Dutch medical profession, the Dutch Right to Die Society this week launched its “Life’s End” euthanasia clinic, reporting initial interest from 70 people.

The society insists that it will work within Dutch law in responding to requests to die from up to 1000 people each year who satisfy the legal requirements for euthanasia but whose current doctor “cannot or will not” agree to their request.

But the Dutch Medical Association says that the clinic will create “a tunnel vision” where the only option is death and other solutions are excluded.

The clinic has begun …
Polymorphisms related to ORMDL3 are associated with asthma susceptibility, alterations in transcriptional regulation of ORMDL3, and changes in TH2 cytokine levels
Authors: Michaela Schedel, Sven Michel, Vincent D. Gaertner, Antoaneta A. Toncheva, Martin Depner, Aristea Binia, Maximilian Schieck, Marie T. Rieger, Norman Klopp, Andrea von Berg, Albrecht Bufe, Otto Laub, Ernst Rietschel, Andrea Heinzmann, Burkard Simma, Christian Vogelberg, Jon Genuneit, Thomas Illig, Michael Kabesch
Journal: Journal of Allergy and Clinical Immunology (2015)
Prevention and Treatment of Coronary Heart Disease
Authors: John C. LaRosa
Journal: Circulation (2001)

Coronary heart disease (CHD) remains a leading cause of morbidity and mortality in the United States, despite our better understanding of the pathobiology of atherosclerosis, our knowledge of risk factors, the widespread availability of inexpensive cholesterol screening, and the availability of effective and well-tolerated cholesterol-lowering agents. Advances in these areas have created controversies regarding who should be screened and treated for primary or secondary prevention of coronary events. The advent of the statin class of lipid-lowering agents represented a major advance, because they are much more effective and better tolerated than previous agents. There is general agreement that patients with hypercholesterolemia and established CHD require treatment for secondary prevention of recurrent coronary events. Primary prevention is controversial in all patient groups except those with diabetes, because their risk of developing CHD is dramatically increased. Postmenopausal women and the elderly are undertreated, whereas young adults may be underdiagnosed and undertreated. Several ongoing trials may resolve the controversies about which patient groups will benefit from different prevention and treatment strategies.
Parathyroid Gland Transplantation without Posttransplantation Immunosuppression
Authors: I.K. Chinn, B.H. Devlin, M.A. Alexieff, J. Li, E. McCarthy, M.A. Skinner, J.A. Olson, M.L. Markert
Journal: Journal of Allergy and Clinical Immunology (2006)
Strengthening Medical Product Regulation in Low- and Middle-Income Countries
Authors: Charles Preston, Mary Lou Valdez, Katherine Bond
Journal: PLoS Medicine (2012)

In summary, the case studies exploring global product supply chains and diethylene glycol poisoning in Panama, clinical trials regulation through AVAREF, premarket assurance through PEPFAR tentative approval, post-market surveillance in sub-Saharan Africa through research on drug and vaccine safety systems, and regulatory science through the creation of a low-cost meningitis vaccine for low- and middle-income countries, demonstrate the essential value of regulatory systems to low- and middle-income countries. When they work, people live; when they fail, people die. As the challenges of globalization mount, and efforts to provide medical products to low- and middle-income countries scale up, there is no better time to put regulatory system strengthening squarely on the global health and development agenda.
Hypoglycemia during Diarrhea in Childhood
Authors: Michael L. Bennish, Abul Kalam Azad, Omar Rahman, Rodney E. Phillips
Journal: New England Journal of Medicine (1990)

To determine the frequency and outcome of hypoglycemia during diarrhea in childhood, we screened 2003 consecutive patients less than 15 years of age who were admitted to a diarrhea treatment center in Dhaka, Bangladesh. Hypoglycemia, defined as a blood glucose concentration <2.2 mmol per liter, was found in 91 patients (4.5 percent), 39 (42.9 percent) of whom died. We also measured the plasma concentrations of glucoregulatory hormones and gluconeogenetic substrates in 46 of the patients with hypoglycemia who were 2 to 15 years old and in 25 normoglycemic patients matched with them for age and weight.
Reducing the toxicity of cancer therapy: recognizing needs, taking action
Authors: Charles S. Cleeland, Jeff D. Allen, Samantha A. Roberts, Joanna M. Brell, Sergio A. Giralt, Aarif Y. Khakoo, Rebecca A. Kirch, Virginia E. Kwitkowski, Zhongxing Liao, Jamey Skillings
Journal: Nature Reviews Clinical Oncology (2012)
Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already exists at onset
Authors: K Matsuda, S Matsuzaki, J Miki, E Hidaka, R Yanagisawa, Y Nakazawa, K Sakashita, T Kamijo, K Asami, K Sano, K Koike
Journal: Leukemia (2006)
Non-surgical removal of common bile duct stones.
Authors: M Classen, F W Ossenberg
Journal: Gut (1977)

Progress reportNon-surgical removal of common bile duct stones In Western countries most stones in the common bile duct originate from the gall bladder; only rarely do they arise de novo on the basis of biliary stasis and infection.Common bile duct stones that have been overlooked during a cholecystectomy have a particular clinical significance and often precipitate the need for a second operation6636'37.Despite routine intraoperative cholangiography, common bile duct stones are overlooked in 1 to 140% of cases23'39'41'60'74.Because of the high rate of complications-over 50 %84 that can be expected in cases of untreated cholelithiasis, the need to remove the stones from the bile duct is imperative.The majority of the procedures described aim either at destroying the stones in SitU2,3,7,10,"5,17,19,23,27,33,34,35, 38,43,47,49,56,58,[62][63][64][66][67][68][69][70] 73,[78][79][80] or removing them from the common bile duct by mechanical means5,8,13-'6,17,30,48,50-55,65 85; their application thus requires the presence of an indwelling T-tube.Only recently have procedures on July 13,
Loss of TGF-β signaling contributes to autoimmune pancreatitis
Authors: Ki-Baik Hahm, Young-Hyuck Im, Cecile Lee, W. Tony Parks, Yung-Jue Bang, Jeffrey E. Green, Seong-Jin Kim
Journal: Journal of Clinical Investigation (2000)

Recent observations suggest that immune response is involved in the development of pancreatitis. However, the exact pathogenesis underlying this immune-mediated response is still under debate. TGF-beta has been known to be an important regulating factor in maintaining immune homeostasis. To determine the role of TGF-beta in the initiation or progression of pancreatitis, TGF-beta signaling was inactivated in mouse pancreata by overexpressing a dominant-negative mutant form of TGF-beta type II receptor in the pancreas, under control of the pS2 mouse trefoil peptide promoter. Transgenic mice showed marked increases in MHC class II molecules and matrix metalloproteinase expression in pancreatic acinar cells. These mice also showed increased susceptibility to cerulein-induced pancreatitis. This pancreatitis was characterized by severe pancreatic edema, inflammatory cell infiltration, T- and B-cell hyperactivation, IgG-type autoantibodies against pancreatic acinar cells, and IgM-type autoantibodies against pancreatic ductal epithelial cells. Therefore, TGF-beta signaling seems to be essential either in maintaining the normal immune homeostasis and suppressing autoimmunity or in preserving the integrity of pancreatic acinar cells.
Doctors and commitment
Authors: C. Vaughan, R. Higgs
Journal: BMJ (1995)

Doctors' working lives are changing radically. Out of hours cover by general practitioners, the new deal on hours of work for junior hospital doctors, and the changing roles and responsibilities of hospital specialists all raise important questions about commitment. How should we, as people with careers to follow and home lives to lead, balance patients' expectations and the demands of reorganised health care with the need for a satisfying and creative job? The patient, the service, the profession, or some higher ideal—to whom or what should doctors be committed, and to what extent?

The doctor-patient relationship is still central to our work. The recent document from the General Medical Council in Britain underlines that doctors must make the care of their patients their first concern.1 This encapsulates a principle of practice that has remained unchanged for over 2000 years and underpins the idea of what a doctor is. However, the context in which this relationship exists is changing so fast that a gap seems to have opened between the ideals of medicine and the realities of doctors' work experience. The “good …
A Mechanistic Role for Type III IFN-λ<sub>1</sub> in Asthma Exacerbations Mediated by Human Rhinoviruses
Authors: E. Kathryn Miller, Johanna Zea Hernandez, Vera Wimmenauer, Bryan E. Shepherd, Diego Hijano, Romina Libster, M. Elina Serra, Niranjan Bhat, Juan P. Batalle, Yassir Mohamed, Andrea Reynaldi, Andrea Rodriguez, Monica Otello, Nestor Pisapia, Jimena Bugna, Miguel Bellabarba, David Kraft, Silvina Coviello, F. Martin Ferolla, Aaron Chen, Stephanie J. London, George K. Siberry, John V. Williams, Fernando P. Polack
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear.
Does the gut-brain axis control anticipatory food reward? Novel insights from bariatric surgery
Authors: Lukas Van Oudenhove
Journal: Gut (2013)

In an elegant, well-conducted and uniquely multidimensional study, Scholtz et al 1 used functional MRI (fMRI) to demonstrate that (morbidly) obese patients after Roux-en-Y gastric bypass (RYGB) show significantly lower responses to high-calorie food images in the reward system of the brain, compared with non-operated obese controls and obese patients after gastric banding. The RYGB group also rated the high-calorie food images as less appealing (anticipatory reward, ‘wanting’) and the subsequent ice cream lunch as less pleasant to eat (consummatory reward, ‘liking’). Further, the energy intake derived from fat as well as scores for restraint and external eating were lower in the RYGB group. Finally, these changes were accompanied by higher levels of the anorexigenic gut peptides glucagon-like peptide 1 and peptide YY, as well as bile acids, and lower levels of insulin during presentation of the images and/or meal intake.

This study adds significantly to an emerging body of literature on the key role of the brain's reward system in the control of food intake in health and obesity. The mesolimbic reward system has evolved in evolution to select and reinforce adaptive behaviour that serves to obtain ‘natural’ rewards crucial for survival, including food, in close interplay with homoeostatic circuits processing information on the metabolic state of the body. Although it may be a bridge too far to label all obese patients without any distinction as suffering from ‘food addiction’,2 on conceptual and empirical grounds, recent evidence does support …
Atypical pseudocholinesterase in leprosy.
Authors: S E Smith
Journal: BMJ (1972)

herbal and other aperients and enemata, and I suspect they often spend long periods straining in an effort to overcome supposed constipation.Could the suggestion that the squatting posture protects leg veins be tested by observing the prevalence of venous dis- orders in communities which have adopted low-residue diets but retained the traditional squatting position (such as some affluent Asian communities)?-Iam, etc.,