tbuckley/cabot-search huggingface dataset:
Calcineurin Splicing Variant Calcineurin Aβ1 Improves Cardiac Function After Myocardial Infarction Without Inducing Hypertrophy
Authors: Leanne E. Felkin, Takuya Narita, Renée Germack, Yasunori Shintani, Kunihiko Takahashi, Padmini Sarathchandra, Marina M. López-Olañeta, Jesús M. Gómez-Salinero, Ken Suzuki, Paul J.R. Barton, Nadia Rosenthal, Enrique Lara-Pezzi
Journal: Circulation (2011)

Calcineurin is a calcium-regulated phosphatase that plays a major role in cardiac hypertrophy. We previously described that alternative splicing of the calcineurin Aβ (CnAβ) gene generates the CnAβ1 isoform, with a unique C-terminal region that is different from the autoinhibitory domain present in all other CnA isoforms. In skeletal muscle, CnAβ1 is necessary for myoblast proliferation and stimulates regeneration, reducing fibrosis and accelerating the resolution of inflammation. Its role in the heart is currently unknown.We generated transgenic mice overexpressing CnAβ1 in postnatal cardiomyocytes under the control of the α-myosin heavy chain promoter. In contrast to previous studies using an artificially truncated calcineurin, CnAβ1 overexpression did not induce cardiac hypertrophy. Moreover, transgenic mice showed improved cardiac function and reduced scar formation after myocardial infarction, with reduced neutrophil and macrophage infiltration and decreased expression of proinflammatory cytokines. Immunoprecipitation and Western blot analysis showed interaction of CnAβ1 with the mTOR complex 2 and activation of the Akt/SGK cardioprotective pathway in a PI3K-independent manner. In addition, gene expression profiling revealed that CnAβ1 activated the transcription factor ATF4 downstream of the Akt/mTOR pathway to promote the amino acid biosynthesis program, to reduce protein catabolism, and to induce the antifibrotic and antiinflammatory factor growth differentiation factor 15, which protects the heart through Akt activation.Calcineurin Aβ1 shows a unique mode of action that improves cardiac function after myocardial infarction, activating different cardioprotective pathways without inducing maladaptive hypertrophy. These features make CnAβ1 an attractive candidate for the development of future therapeutic approaches.
Abstract 2025: Prevention of mammary tumor progression via intraductal injection of nanoparticle-formulated siRNA.
Authors: Silva Krause, Amy Brock, Michael Goldberg, Donald E. Ingber
Journal: Cancer Research (2013)

Abstract The contribution of specific genes to the development and progression of mammary tumors has been hampered by the inability to silence these genes locally in the mammary gland. Localized intraductal chemotherapy treatments have been explored and offer significant advantages in terms of reduced toxicity and side effects. Therefore, we wanted to explore the possibility of gene knockdown using siRNA delivery via intraductal injection. FVB C3(1)-SV40Tag transgenic female mice spontaneously develop hyperplastic mammary lesions that progress to invasive mammary tumors. Hyperplastic ducts form as early as 12 weeks of age and progress into DCIS-resembling tumors by 16 weeks of age. These further develop into invasive tumors that invade locally into adipose tissue and muscle and occasionally form metastases to lung by 18 to 20 weeks of age. We intraductally injected nanoparticle-formulated siRNA targeted to the SV40 T-antigen transgene beginning at 8 weeks of age through 23 weeks of age into the mammary gland twice a month. As controls, transgenic females were either left untreated or intraductally injected with a non-targeting siRNA. Tumor formation was monitored using ultrasound technology that allows for tumor detection as early as 0.4mm in diameter. At 23 weeks of age, when 100% of the control mice developed tumors, only 1 of 8 mice that received siRNA to the transgene had developed a small tumor. Histological analysis of the mammary glands confirmed development of early lesions but tumor progression was successfully prevented. Mammary lesions were analyzed for proliferation, apoptosis and expression of various markers of differentiation, including hormone receptor status. We showed that siRNA was not detectable in any other organs of the mouse, including the liver. Furthermore, we confirmed that frequent intraductal siRNA injection did not interfere with subsequent pregnancy or lactation, a period in which the mammary gland undergoes extensive remodeling to allow for milk production. Our long-term goal is to leverage the information we uncovered through this effort to target key genes we identified through gene network analysis aiming to prevent the progression of DCIS to invasive tumors. Moreover, this new technology can be utilized to explore the role of genes during specific times during development and tumor formation. Citation Format: Silva Krause, Amy Brock, Michael Goldberg, Donald E. Ingber. Prevention of mammary tumor progression via intraductal injection of nanoparticle-formulated siRNA. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2025. doi:10.1158/1538-7445.AM2013-2025
Medicine 100 Years Ago
Authors: Lester S. King
Journal: JAMA (1987)

IN THE 1880s the aristocrat of medical journals was undoubtedly<i>The American Journal of Medical Sciences</i>(founded in 1827). A quarterly, with about 300 octavo pages per issue, it was easily the most scholarly medical periodical in the United States. The contributors included leading British as well as American physicians and surgeons. Publication was prompt, and there was "liberal compensation for articles used." Each issue had about ten "original communications." Some dealt in depth with clinical conditions, others with various aspects of the preclinical sciences. Much experimental work was included. In a single issue the papers would range from an experimental study of ulcerative endocarditis to pancreatic surgery to a clinical study of cerebral localization. Much of the journal was devoted to long, critical, and analytic book reviews that were usually superbly informative. At least 90 pages per issue were given to a systematic survey of current literature, arranged in
Series Introduction: JAK-STAT signaling in human disease
Authors: Christian W. Schindler
Journal: Journal of Clinical Investigation (2002)

JAK-STAT signaling in human diseaseCytokines, a large family of extracellular ligands, stimulate biological responses in virtually all cell types.One important subfamily of cytokines, the hematopoietins, evolved largely to regulate host responses to exogenous stresses, especially infection with pathogens.They stimulate these responses by binding to and activating a family of structurally and functionally conserved receptors.As is the case for many types of receptor families, downstream signaling entails tyrosine phosphorylation.However, the activation of the Janus kinases (Jaks) and their downstream signal transducer and activator of transcription (Stat) proteins is both characteristic of and unique to this hematopoietin family.This signaling paradigm first appeared in invertebrates and has continued to grow in complexity through vertebrate and mammalian evolution.There are about 50 members of the hematopoietin family in mammals, and they transduce their signals through four Jaks and seven Stats.Consistent with their identity as ILs, many of these ligands play a critical role in regulating leukocyte maturation and activity.Others regulate more central aspects of cellular homeostasis, reflecting the role Stats play in invertebrates.This Perspective series will provide an overview of the Jak-Stat pathway (reviewed in more detail in refs.1-4) and will explore the important role this pathway plays in regulating immune responses and cellular homeostasis in human health and disease.The series will explore human ailments affected by this pathway, including immunodeficiency, asthma, and cancer.It will also examine the role Stats play in regulating innate immunity and the unique role Stat3 plays in regulating cellular homeostasis.
Anti–CTLA-4 therapy broadens the melanoma-reactive CD8 <sup>+</sup> T cell response
Authors: Pia Kvistborg, Daisy Philips, Sander Kelderman, Lois Hageman, Christian Ottensmeier, Deborah Joseph-Pietras, Marij J. P. Welters, Sjoerd van der Burg, Ellen Kapiteijn, Olivier Michielin, Emanuela Romano, Carsten Linnemann, Daniel Speiser, Christian Blank, John B. Haanen, Ton N. Schumacher
Journal: Science Translational Medicine (2014)

Anti–CTLA-4 treatment increases the diversity of the melanoma-specific CD8 T cell response.
Health Care Reform in France — The Birth of State-Led Managed Care
Authors: Victor G. Rodwin, Claude Le Pen
Journal: New England Journal of Medicine (2004)

The World Health Organization recently ranked the French health care system the best in the world.1 Although the methods and data on which this assessment was based have been criticized, there are good grounds for being impressed by the French system. Yet in August 2004, with the national health insurance (NHI) system facing a severe financial crisis, France enacted Minister of Health Philippe Douste-Blazy's reform plan. Like previous efforts at health care reform, this one seeks to preserve a system of comprehensive benefits, which is supported by the major stakeholders.(Figure)French policymakers typically view their NHI system as . . .
The Scent of a Diagnosis
Authors: James L. Glazer
Journal: JAMA (2003)

Thick tires made a crunching sound on the gravel of the drive. An engine sputtered to a stop and settled into a rapid ticking as it cooled. A car door slammed and footsteps hurried to the door of the clinic. Then came the sound of a fist knocking solidly against the oak planks.
Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92
Authors: Dörthe O. Harms, Ulrich Göbel, Hans J. Spaar, Ulrike B. Graubner, Norbert Jorch, Peter Gutjahr, Gritta E. Janka-Schaub
Journal: Blood (2003)
Assessing the public health benefits of reduced ozone concentrations.
Authors: J I Levy, T J Carrothers, J T Tuomisto, J K Hammitt, J S Evans
Journal: Environmental Health Perspectives (2001)

In this paper we examine scientific evidence and related uncertainties in two steps of benefit-cost analyses of ozone reduction: estimating the health improvements attributable to reductions in ozone and determining the appropriate monetary values of these improvements. Although substantial evidence exists on molecular and physiologic impacts, the evidence needed to establish concentration-response functions is somewhat limited. Furthermore, because exposure to ozone depends on factors such as air conditioning use, past epidemiologic studies may not be directly applicable in unstudied settings. To evaluate the evidence likely to contribute significantly to benefits, we focus on four health outcomes: premature mortality, chronic asthma, respiratory hospital admissions, and minor restricted activity days. We determine concentration-response functions for these health outcomes for a hypothetical case study in Houston, Texas, using probabilistic weighting reflecting our judgment of the strength of the evidence and the possibility of confounding. We make a similar presentation for valuation, where uncertainty is due primarily to the lack of willingness-to-pay data for the population affected by ozone. We estimate that the annual monetary value of health benefits from reducing ozone concentrations in Houston is approximately $10 per person per microgram per cubic meter (24-hr average) reduced (95% confidence interval, $0.70-$40). The central estimate exceeds past estimates by approximately a factor of five, driven by the inclusion of mortality. We discuss the implications of our findings for future analyses and determine areas of research that might help reduce the uncertainties in benefit estimation.
Remedial Actions for the Physical Inactivity of Hospitalized Patients With Type 2 Diabetes
Authors: Sandrine Pezzino, Stéphane Florenty, Cédric Fagour, Henri Gin, Vincent Rigalleau
Journal: Diabetes Care (2010)

OBJECTIVE Physical inactivity is often suspected in hospitalized patients with type 2 diabetes but has yet to be quantified. RESEARCH DESIGN AND METHODS We measured the level of physical activity of 36 hospitalized (H) and 36 free-living nonhospitalized (NH) type 2 diabetic subjects with actimeters (SenseWear Arm-Band). RESULTS The number of steps (H: 4,381 ± 3,742 steps/24 h, NH: 7,220 ± 4,763 steps/24 h; P &amp;lt; 0.01), duration of physical activity (H: 45 ± 57 min/24 h, NH: 148 ± 116 min/24 h; P &amp;lt; 0.005), and physical activity expenditure (H: 287 ± 390 kcal/24 h, NH: 1,035 ± 1,006 kcal/24 h; P &amp;lt; 0.005) were two- to threefold lower in the hospitalized patients. Simple advice enabled us to increase their recorded levels of physical activity by ∼50% (P &amp;lt; 0.005), and a further 50% (P &amp;lt; 0.05) was obtained by the use of a pedometer. CONCLUSIONS The physical inactivity of hospitalized patients with type 2 diabetes is significant and remediable, although the advice given must take into account the existence of sensory neuropathy and silent myocardial ischemia.
Vernal keratoconjunctivitisResult of a novel therapy with 0.1% topical ophthalmic FK-506 ointment
Authors: Pakit Vichyanond, Chiraphan Tantimongkolsuk, Puttachart Dumrongkigchaiporn, Orathai Jirapongsananuruk, Nualanong Visitsunthorn, Panida Kosrirukvongs
Journal: Journal of Allergy and Clinical Immunology (2004)
New Device Measures Atmospheric Isocyanic Acid
Authors: Carol Potera
Journal: Environmental Health Perspectives (2011)

the U.S. EPA finalized the Cross-State Air Pollution Rule to reduce SO 2 and NO X emissions from power plants using available emissions control technologies. 1SO 2 and NO X contribute to ground-level ozone and fine particle pollution and often cross state lines, ending up far from their provenance.The rule is projected to achieve up to $280 billion in annual health benefits by preventing avoidable illnesses, sick days at work, and premature deaths.Within three years the rule is expected to help reduce SO 2 emissions by 73% and NO X emissions by 54% over 2005 levels.
Critical Condition: Human Health and the Environment
Authors: M Braddick
Journal: BMJ (1994)

Ed Eric Chivian, Michael McCally, Howard Hu, Andrew Haines MIT Press, £14.25, pp 240 ISBN 0-262-53118-6

There is a real danger that concern for the environment will turn to apathy. Critical Condition, a report by Physicians for Social Responsibility, is therefore to be welcomed because it takes a fresh approach - examining the impact of environmental change on human health. Physicians for Social Responsibility shared the 1985 Nobel peace prize with International Physicians for Prevention of Nuclear War, for educating the public about the medical consequences of nuclear war. It is appropriate that …
Total Fluid and Water Consumption and the Joint Effect of Exposure to Disinfection By-Products on Risk of Bladder Cancer
Authors: Dominique S. Michaud, Manolis Kogevinas, Kenneth P. Cantor, Cristina M. Villanueva, Monteserrat Garcia-Closas, Nathaniel Rothman, Nuria Malats, Francisco X. Real, Consol Serra, Reina Garcia-Closas, Adonina Tardon, Alfredo Carrato, Mustafa Dosemeci, Debra T. Silverman
Journal: Environmental Health Perspectives (2007)

Findings on water and total fluid intake and bladder cancer are inconsistent; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case-control studies observed a positive association between tap water and bladder cancer but none for nontap fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk.We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case-control study in Spain.A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders.Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0.62; 95% confidence interval (CI), 0.40-0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47; 95% CI, 0.33-0.66; p for trend < 0.0001), but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure; we found no statistical interaction (p for interaction = 0.13).Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level.
Tubercular Meningitis in an Adult Idiot: No Tubercle Found in Lungs
Authors: O. T. Woods
Journal: BMJ (1874)

The chief points of interest in this case appear to me to be- I.The Ruzeril/y.-Ihave not been able to get at the statistics of such cases ; but, consideringthat the external iliac has only been tied about a hundred and fifty times during the last twenty years, very few of those operattions must have been for a double aneurism, but generally for aneurism of the femoral artery.
Hospital Readmission in Patients Treated With Tiered-Therapy Implantable Defibrillators
Authors: Gerard J. Fahy, Elena B. Sgarbossa, Patrick J. Tchou, Sergio L. Pinski
Journal: Circulation (1996)

We wished to determine the incidence, reasons, costs, and predictors of cardiac-related hospital readmission in patients with tiered-therapy implantable defibrillators. Hospital readmission in patients with defibrillators reduces their quality of life and increases the cost associated with such therapy.We retrospectively studied 65 consecutive local patients (median age, 67 years; median ejection fraction, 0.34) who underwent tiered-therapy defibrillator implantation at this institution. Patients were followed for a median of 19 months (interquartile range, 10 to 27 months). The cause, duration, costs, and predictors of cardiac-related rehospitalizations were analyzed. There were 76 cardiac admissions for 34 patients. The rate of cardiac-related hospital readmission was 0.72 per patient-year of follow-up. Arrhythmia-related admissions accounted for 43 of such admissions in 24 patients. Actuarial freedom from cardiac-related admissions was 0.57 and 0.40 at 1 and 2 years, respectively. The median length of stay for hospital readmissions was 5 days (interquartile range, 3 to 8 days). The median cost per admission was $5842 (interquartile range, $3549 to $12 170). The time to first readmission and the total rehospitalization time per year of follow-up were associated with a poor preimplant New York Heart Association functional class. Readmission for cardiac arrhythmias was not predicted by clinical parameters.Rehospitalization for cardiac reasons is common in patients receiving implantable defibrillators and is responsible for substantial resource consumption. The need for readmission for arrhythmia-related reasons cannot be predicted by clinical parameters at the time of device implantation.
A Practical Treatise on Medical Diagnosis for Students and Physicians.
Authors: John Herr Musser
Journal: JAMA (1901)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Relief of Nocturnal Intractable Low Back and Sciatic Pain by "Chair Sleep"
Authors: Michael Scott
Journal: JAMA (1966)

LOW BACK PAIN and sciatic pain, worse at night, unrelieved by bed rest and by large doses of the usual anodynes, and occasionally associated with minimal abnormal neurological signs, is a common symptom found in cauda equina tumor, usually a benign neurofibroma or meningioma. The writer reports an additional phenomenon which he has noted in the histories of some of these patients, namely an attempt by the patient to obtain relief of pain and its resulting insomnia, by sleeping in a chair at night. Although the use of a rocking chair for the diurnal relief of back pain of varied etiology is well known, the writer believes that this nocturnal chair sitting discovered by the patient as a therapeutic measure has not been emphasized in the medical literature as an important warning to the physician of the possibility of an intraspinal tumor as a cause for the patient's complaints, and
FDA finally approves Plan B—but with restrictions
Authors: Janice Hopkins Tanne
Journal: BMJ (2006)

The US Food and Drug Administration has finally approved the emergency contraceptive Plan B for sale over the counter to women aged 18 or over.

Plan B is a two pill, high dose regimen of the oral contraceptive levonorgestrel. It is about 90% effective in preventing pregnancy when taken within 72 hours of unprotected sex.

Plan B will be available towards …
Extrapancreatic, Extraintestinal Gastrinoma
Authors: M. Michael Wolfe, Ronald W. Alexander, James E. McGuigan
Journal: New England Journal of Medicine (1982)

OPTIMAL therapy for patients with the Zollinger–Ellison syndrome due to gastrinoma is currently in a state of evolution and reevaluation. Although treatment must be directed toward correction of gastric acid hypersecretion, selection of therapy must also take into consideration the malignant potential of these gastrin-releasing tumors (gastrinomas).1 2 3 Until recently, total gastrectomy was uniformly accepted as appropriate treatment for these patients.4 However, with the development of the histamine H2-receptor antagonist cimetidine, a medical therapeutic alternative to surgery became available.5 , 6 Treatment with cimetidine has been shown to be effective in reducing gastric acid hypersecretion, improving symptoms, and inducing ulcer . . .
LONG-TERM SUCCESS LIABILITY AND IMPACT OF BALLOON SIZE STRATEGY ON ANTRAL CRYO ISOLATION OF PULMONARY VEINS
Authors: Juergen Vogt, Johannes Heintze, Klaus J. Gutleben, Bogdan G. Muntean, Marios Vlachojannis, David Vogler, Dieter Horstkotte, Georg Noelker
Journal: Journal of the American College of Cardiology (2011)
The Case for More U.S. Medical Students
Authors: F Mullan
Journal: New England Journal of Medicine (2000)

Allopathic medical schools in the United States enroll and graduate a total of about 16,000 students a year — a number that has been remarkably consistent for two decades.1 Interest in medical education has remained high throughout this period, with the result that more applications to medical schools have been rejected every year than have been accepted, despite the excellent qualifications of many of the candidates whose applications are rejected. At the same time, the number of entry-level residency positions in U.S. teaching hospitals has greatly exceeded the number of graduates of U.S. medical schools. As a result, teaching hospitals . . .