tbuckley/cabot-search huggingface dataset:
Abstract 4826: Enhancement of PTEN activity via peptidomimetics
Authors: Emily Palumbo, Peng Teng, Prerna Malaney, Jacob Wilson, Fiona Kearns, Michael T. Kemp, Zhi Tian, Vladimir Uversky, Diane Allen-Gipson, Yu Chen, H. Lee Woodcock, Jianfeng Cai, Vrushank Dave
Journal: Cancer Research (2019)

Abstract Compromised PTEN function is associated with multiple cancers. As per the continuum model, variable degree of PTEN inactivation drives distinct cancer phenotypes. Loss of PTEN activity, via genomic/non-genomic mechanisms, leads to enhanced oncogenic PI3K signaling. While kinase inhibitors have proved effective in the clinic, they are increasingly met with off-target effects and therapy-resistance due to compensatory feedback mechanisms. Although PTEN restoration therapy has proved promising in experimental models; implementation of these therapies in the clinic remains challenging. To fill this therapy gap, we have targeted endogenous PTEN for activation via peptidomimetics, mitigating PI3K signaling. Our selected peptidomimetics reduced cell proliferation, migration and cell cycle activity after treatment of non-small cell lung cancer cells expressing endogenous PTEN. Computational studies utilizing PTEN crystal structures revealed a binding site at the interface of the Phosphatase Domain (PD) and C2 Domain (C2D). Induced fit docking indicated that a unique functional group is responsible for peptidomimetic-mediated enhancement of PTEN activity. Molecular dynamics analysis revealed energetically favorable binding of our lead peptidomimetic at the PD/C2D interface, which allosterically modulated the conformation of the active site. Binding of our peptidomimetic altered the active site orientation of PIP3, increasing its binding affinity. In summary, we have developed the first-known direct PTEN activators and analyzed their effects in suppressing oncogenic activities in lung cancer. Refinement of our peptidomimetics, complemented with in vivo studies, will provide a novel clinical rationale to reduce doses of standard therapy and their associated toxicities, decreasing morbidity and mortality observed in the clinic. Citation Format: Emily Palumbo, Peng Teng, Prerna Malaney, Jacob Wilson, Fiona Kearns, Michael T. Kemp, Zhi Tian, Vladimir Uversky, Diane Allen-Gipson, Yu Chen, H. Lee Woodcock, Jianfeng Cai, Vrushank Dave. Enhancement of PTEN activity via peptidomimetics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4826.
Perinatal Exposure to Low Doses of Bisphenol A Affects Body Weight, Patterns of Estrous Cyclicity, and Plasma LH Levels
Authors: Beverly S. Rubin, Mary K. Murray, David A. Damassa, Joan C. King, Ana M. Soto
Journal: Environmental Health Perspectives (2001)

The nonsteroidal estrogenic compound bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics and resins. BPA may be ingested by humans as it reportedly leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. Because BPA is weakly estrogenic--approximately 10,000-fold less potent than 17beta-estradiol--current environmental exposure levels have been considered orders of magnitude below the dose required for adverse effects on health. Herein we demonstrate measurable effects on the offspring of Sprague-Dawley female rats that were exposed, via their drinking water, to approximately 0.1 mg BPA/kg body weight (bw)/day (low dose) or 1.2 mg BPA/kg bw/day (high dose) from day 6 of pregnancy through the period of lactation. Offspring exposed to BPA exhibited an increase in body weight that was apparent soon after birth and continued into adulthood. In addition, female offspring exposed perinatally to the high dose of BPA exhibited altered patterns of estrous cyclicity and decreased levels of plasma luteinizing hormone (LH) in adulthood. Administration of neither the doses of BPA that caused effects during perinatal exposure nor a 10-fold higher dose was able to evoke a uterotropic response in ovariectomized postpubertal females. These data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound.
Family practice. Here today, gone (again) tomorrow
Authors: D. N. Sundwall
Journal: JAMA (1977)

THE DEVELOPMENT of family practice as a new specialty is now a matter of history. It has been almost eight years since the American Academy of General Practice officially changed its name to the American Academy of Family Physicians, and the American Board of Medical Specialties recognized family practice as the 20th specialty. The forces that resulted in the elevation of the general medical practitioner to this lofty status are many and complex. In most cases, these changes were not brought about by forces within the hierarchy of the medical profession but were stimulated by the consumer of our health-care system, the politicians, and the practicing family physicians. Regardless of the motivating forces, much energy and money is being spent to educate a new breed of specialist, the family physician. I have been involved in family medicine almost since its inception as a recognized specialty, and much has happened in
People who decline psychiatric assessment are more likely to repeat self harm
Journal: BMJ (1998)

Multiple doses of anticholinergics are beneficial in severe, acute childhood asthmaThe addition of anticholinergics to 2 agonist inhalations remains controversial in the treatment of children and adolescents with asthma exacerbations.To examine the efficacy of three management strategies for adding anticholinergics to 2 agonists, Plotnick and Ducharme (p 971) systematically reviewed 10 randomised controlled trials, including single dose, multiple doses (predetermined protocol), and multiple doses (flexible protocol).Only the addition of multiple doses of anticholinergics to 2 agonists in a predetermined protocol reduced the risk of hospital admission (by 30%) and improved pulmonary function tests.Eleven children would need to be treated to avoid one admission.The use of anticholinergics in mild to moderate asthma is not supported by the available evidence.The number and size of pooled studies remain small, thus the conclusions are subject to change with future larger trials. Warm clothing and housing prevent excess winter mortalityCold weather increases death rates from heart disease, stroke, and all causes in western Europe.Donaldson et al studied mortality in Yakutsk in east Siberia, where temperatures average -26.6°C from October to March (p 978).Overall daily death rates did not rise even at temperatures of -48.2°C.An increase in deaths from respiratory disease below -20°C was balanced by a fall in deaths from injury at this temperature.The stable death rate is attributed to very warm outdoor clothing and housing as well as a reduction in outdoor trips at temperatures below -20°C.The authors suggest that most of the excess winter mortality in western Europe is preventable by personal cold protection.
Toxic wastes' health effects? No one has the answers
Authors: B. Bolsen
Journal: JAMA (1981)

Even a casual newspaper reader or television viewer could not have missed this classic scene at least once last year: A cleanup worker, wearing a respirator and coveralls, points with a gloved hand at a field of rusting metal drums or dips a stick in a pond of oily goo. In a headline or voice-over are the words "toxic wastes." It could be in New Jersey, where 34,000 barrels of explosive wastes blew up and burned, or in Kentucky's Valley of the Drums, where 17,000 barrels' worth of unidentified chemical wastes are slowly seeping into streams that feed the Ohio River, or at any of hundreds of abandoned hazardous waste sites that are regularly featured in news stories. And now, one of the decade's most vexing scientific problems: assessing the health effects of exposure to such toxic wastes. The Environmental Protection Agency (EPA) has identified almost 9,500 hazardous waste dumps,
Obituaries
Journal: JAMA (1975)

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
Introductory Remarks
Authors: Moore, Dan H.
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Introductory Remarks Get access Dan H. Moore Dan H. Moore Institute for Medical Research, Camden, New Jersey 08103 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 4, April 1972, Pages 1017–1019, https://doi.org/10.1093/jnci/48.4.1017 Published: 01 April 1972
Magnets
Authors: A. L Pahor
Journal: Journal of the Royal Society of Medicine (2005)

Erdheim-Chester diseaseDr Lee and his colleagues (April 2005 JRSM 1 ) describe a case of renal failure in which the radiographic appearance of bone pointed to Erdheim-Chester disease, a histiocytosis.Among the organs affected in this condition they mention pericardium.We think it important to emphasize the frequency with which heart, pericardium and great vessels are affected.Recording 6 new patients with cardiovascular involvement, Haroche et al. 2 have reviewed all 178 reported cases of Erdheim-Chester disease.56% had periaortic fibrosis, 44% pericardial infiltration and/or effusions and 31% myocardial infiltration.Interestingly, 6 patients had a right atrial myxoma.Of the 58 patients with follow-up data, 31% died from cardiovascular complications.
The benefits and risks of exercise training in patients with chronic coronary artery disease
Authors: P. D. Thompson
Journal: JAMA (1988)

WILLIAM Heberden, in his<i>Commentaries on the History and Cure of Diseases</i>published in 1802, had "little or nothing to advance..." for the treatment of angina pectoris but did know of one patient "who set himself a task of sawing wood for half an hour every day and was nearly cured."<sup>1</sup>Heberden's observation that physical training can nearly cure angina in some patients has been confirmed in recent studies,<sup>2-4</sup>and physical training remains one of the most effective methods for improving the functional capacity and psychological well-being of selected patients with coronary artery disease (CAD). This article summarizes the effect of CAD on exercise tolerance and the benefits and risks of exercise training in patients with CAD. <h3>ACUTE CARDIOVASCULAR RESPONSE TO EXERCISE</h3><h3>Healthy Subjects</h3> A brief review of the normal cardiovascular response to exercise is necessary to understand how CAD alters exercise performance. Functional capacity during dynamic exercise
Re: Peter Ström, Tobias Nordström, Henrik Grönberg, Martin Eklund. The Stockholm-3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker Contribution, and Reflex Test Potential. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2017.12.028
Authors: Ola Bratt, Anna Öfverholm
Journal: European Urology (2018)
CONDITIONED REFLEXES AND PHARMACOLOGY
Journal: JAMA (1930)

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
Management of heart failure. II. Counseling, education, and lifestyle modifications
Authors: K. Dracup
Journal: JAMA (1994)

<h3>Objective.</h3> —This article reviews the role of counseling, education, dietary modifications, and exercise for patients with heart failure due to left ventricular systolic dysfunction. <h3>Data Sources.</h3> —We reviewed studies published in English between 1966 and 1993 and referenced in MEDLINE or EMBASE. We used the search terms<i>heart failure, congestive; congestive heart failure; heart failure; cardiac failure</i>; and<i>dilated cardiomyopathy</i>in conjunction with terms for the specific areas of interest. Where data were lacking, we relied on opinions of panel members and peer reviewers. <h3>Study Selection and Data Synthesis.</h3> —Studies were reviewed to determine whether patients had heart failure due to systolic dysfunction (left ventricular ejection fraction, &lt;0.35 to 0.40) and whether clinical outcomes were reported. Studies that reported only intermediate outcomes (eg, hemodynamics) were not reviewed. <h3>Conclusion.</h3> —Counseling and education can improve patient outcomes and decrease unnecessary hospitalizations. Patients with mild to moderate heart failure should be restricted to 3 g/d of sodium initially. Those who are unresponsive to this dosage or who have more severe disease should be advised to consume 2 g/d or less. Patients should be strongly advised to drink no more than 30 mL/d of alcohol or, preferably, to abstain completely. Exercise training is safe and can improve exercise duration and symptoms. Adherence to the treatment plan should be stressed and monitored at each visit. Clinicians should inform patients of the seriousness of their disease and their prognosis, but they should emphasize that patients can continue to remain active and enjoy a reasonable quality of life. (<i>JAMA</i>. 1994;272:1442-1446)
PARIS
Journal: JAMA (1930)

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
Adult Weight Gain and Adiposity-Related Cancers: A Dose-Response Meta-Analysis of Prospective Observational Studies
Authors: NaNa Keum, Darren C Greenwood, Dong Hoon Lee, Rockli Kim, Dagfinn Aune, Woong Ju, Frank B Hu, Edward L Giovannucci
Journal: JNCI Journal of the National Cancer Institute (2015)

Background: Adiposity, measured by body mass index, is implicated in carcinogenesis.While adult weight gain has diverse advantages over body mass index in measuring adiposity, systematic reviews on adult weight gain in relation to adiposity-related cancers are lacking.Methods: PubMed and Embase were searched through September 2014 for prospective observational studies investigating the relationship between adult weight gain and the risk of 10 adiposity-related cancers.Dose-response meta-analyses were performed using a random-effects model to estimate summary relative risk (RR) and 95% confidence interval (CI) for each cancer type.All statistical tests were two-sided.Results: A total of 50 studies were included.For each 5 kg increase in adult weight gain, the summary relative risk was 1.11 (95% CI = 1.08 to 1.13) for postmenopausal breast cancer among no-or low-hormone replacement therapy (HRT) users, 1.39 (95% CI = 1.29 to 1.49) and 1.09 (95% CI = 1.02 to 1.16) for postmenopausal endometrial cancer among HRT nonusers and users, respectively, 1.13 (95% CI = 1.03 to 1.23) for postmenopausal ovarian cancer among no or low HRT users, 1.09 (95% CI = 1.04 to 1.13) for colon cancer in men.The relative risk of kidney cancer comparing highest and lowest level of adult weight gain was 1.42 (95% CI = 1.11 to 1.81).Adult weight gain was unrelated to cancers of the breast (premenopausal women, postmenopausal HRT users), prostate, colon (women), pancreas, and thyroid.An increase in risk associated with adult weight gain for breast cancer was statistically significantly greater among postmenopausal women (P heterogeneity = .001)and HRT nonusers (P heterogeneity = .001);that for endometrial cancer was alike among HRT nonusers (P heterogeneity = .04). Conclusions:Avoiding adult weight gain itself may confer protection against certain types of cancers, particularly among HRT nonusers.
Raccoon Roundworm Is on the Move
Journal: JAMA (2016)

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
Death Panels
Authors: Mark Vierra
Journal: Annals of Internal Medicine (2012)

On Being a Doctor6 March 2012Death PanelsMark Vierra, MDMark Vierra, MDFrom Monterey County Surgical Associates, Monterey, CA 93940.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-5-201203060-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail "He is 69 years old, on an experimental treatment for metastatic colon cancer, and he has free air," explained the emergency department physician. It was a Sunday afternoon, and I was the surgeon on call.The CT scan had been done without intravenous contrast, and the cava was flat, from which I inferred that his renal function was poor. He had liver metastases, but there was still plenty of normal liver, and the metastases alone would not explain this much ascites. There was scattered free air, but too much ascites to be from an acute perforation, and the pleural effusions ... Author, Article, and Disclosure InformationAffiliations: From Monterey County Surgical Associates, Monterey, CA 93940.Corresponding Author: Mark Vierra, MD, Monterey County Surgical Associates, 2 Upper Ragsdale, Suite 230, Building B, Monterey, CA 93940; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNonbeneficial CareImplementation of a Pilot Accountable Care Organization Payment Model and the Use of Discretionary and Nondiscretionary Cardiovascular Care 6 March 2012Volume 156, Issue 5Page: 394-395KeywordsCancer treatmentColorectal cancerComputed axial tomographyHealth careIntensive care unitsLegislationLiverMedicareMusclesVentilators ePublished: 6 March 2012 Issue Published: 6 March 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Dermatology
Authors: Roger W. Pearson
Journal: JAMA (1982)

Among the many newly emerging trends in dermatology, three areas of general medical interest are the therapeutic uses of retinoids, some new observations on Kaposi's sarcoma, and the increasing recognition of the malignant potential of some prelymphomatous "pseudolymphomatous" states. <h3>Retinoids</h3> The retinoids include vitamin A, its derivatives, and its analogues. Vitamin A (retinol) has long been known to have favorable effects on many disorders of keratinization, but these benefits have been limited by the toxic effects of vitamin A at therapeutic doses. Tretinoin (all transretinoic acid), the acid derivative of vitamin A, has been widely used topically; systemically, it is quite toxic, inducing the hypervitaminosis A syndrome at therapeutic doses. The search for therapeutically effective but less toxic agents has resulted in the emergence of a few promising compounds from more than 1,000 synthesized retinoids. A recent report on extensive basic and therapeutic studies of retinoids has documented the current
Cytomegalovirus Mononucleosis
Authors: Edwin E. Clizer
Journal: JAMA (1974)

CYTOMEGALOVIRUSES have been identified as causative agents of a variety of human infections, including conditions that more or less resemble viral hepatitis and infectious mononucleosis. Differential diagnosis is aided by demonstration of rising complement-fixation titers to cytomegalovirus. <h3>Report of a Case</h3> A 20-year-old white man was admitted to Broward General Medical Center, Fort Lauderdale, Fla, because of malaise, fatigue, and low-grade fever during the previous month. There was no history of significant past illness. At the time of admission, the patient had a temperature of 38.9 C (102 F). Physical examination showed mild tenderness in the right upper abdominal quadrant. The liver and spleen were not palpable, and the lymph nodes were not enlarged. The patient did not appear jaundiced. Laboratory values were as follows: hemoglobin, 14.9 gm/100 ml; and white blood cell count, 11,600/cu mm, with 72% lymphocytes, including a high percentage of atypical lymphocytes. Urinalysis was negative for