tbuckley/cabot-search huggingface dataset:
<i>ARID1A</i>Mutations in Endometriosis-Associated Ovarian Carcinomas
Authors: Kimberly C. Wiegand, Sohrab P. Shah, Osama M. Al-Agha, Yongjun Zhao, Kane Tse, Thomas Zeng, Janine Senz, Melissa K. McConechy, Michael S. Anglesio, Steve E. Kalloger, Winnie Yang, Alireza Heravi-Moussavi, Ryan Giuliany, Christine Chow, John Fee, Abdalnasser Zayed, Leah Prentice, Nataliya Melnyk, Gulisa Turashvili, Allen D. Delaney, Jason Madore, Stephen Yip, Andrew W. McPherson, Gavin Ha, Lynda Bell, Sian Fereday, Angela Tam, Laura Galletta, Patricia N. Tonin, Diane Provencher, Dianne Miller, Steven J.M. Jones, Richard A. Moore, Gregg B. Morin, Arusha Oloumi, Niki Boyd, Samuel A. Aparicio, Ie-Ming Shih, Anne-Marie Mes-Masson, David D. Bowtell, Martin Hirst, Blake Gilks, Marco A. Marra, David G. Huntsman
Journal: New England Journal of Medicine (2010)

Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described.We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas.ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions.These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).
Re: Mecedes Marín-Aguilera, Lourdes Mengual, María José Ribal et al. Utility of Fluorescence In Situ Hybridization as a Non-invasive Technique in the Diagnosis of Upper Urinary Tract Urothelial Carcinoma. Eur Urol 2007;51:409–15 and Alan M. Nieder, Mark S. Soloway and Harry W. Herr. Should We Abandon the FISH Test? Eur Urol 2007;51:1469–71
Authors: Tine Hajdinjak, Nadja Kokalj-Vokač
Journal: European Urology (2007)
Health Care Delivery in Rural Areas
Authors: Bond L. Bible
Journal: JAMA (1971)

"Physicians are not needed in every hamlet, village, or township." This conviction was emphasized as the 24th National Conference on Rural Health met in Atlanta, March 25-26, 1971, to discuss the many aspects of change for rural health in the coming decades. The program, sponsored by the AMA Council on Rural Health, focused on delivery systems, health manpower and the health team concept, community health planning, and effective utilization of health services. In the keynote address, "Rural Health Care Systems," by Vernon E. Wilson, MD, which appears in this issue ofThe Journal(p 1623), particularly interesting approaches are suggested to meet the health care needs of the rural population. The health problems of rural America are well known and the causes well documented. Rural areas have limited health facilities and often serious shortages of health manpower. In addition, these areas are often characterized by below-average incomes and considerable poverty.
Copy-and-Paste-and-Paste
Authors: Thomas R. Yackel, Peter J. Embi
Journal: JAMA (2006)

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
Cause of Aortic Rupture
Authors: Boris Gueft
Journal: JAMA (1964)

<h3>To the Editor:—</h3> After reading the report, "Aortic Rupture After a Minor Fall in a Patient With Extreme Cardiomegaly," by Dr. Willard Aronson (<i>JAMA</i><b>186</b>:729 [Nov 16] 1963), I should like to suggest that this is a case of what is popularly called "Marfan's syndrome." The cardiomegaly appears, in my opinion, to be due to an extreme stretching of the aortic valve ring. The tear is quite characteristic of dissecting aneurysms, and the deformed aortic valve is commonly seen in this disease. I doubt that an endocarditis was the cause of the valve deformity. The relation of trauma to death is possibly as the author states, but the basic disease of weak blood vessels, rather than the immediate exertion, determined the course of the illness. It is possible that precocious or poorly understood heart disease may be common in this family and that the relatives should be examined and
The Treatment of Dacryostenosis-Reply
Authors: John W. Cowden
Journal: JAMA (1988)

In Reply.—  We thank Dr Frankel for emphasizing the primary treatment for congenital dacryostenosis. He refers to several studies that indicate that persistent lacrimal sac massage usually will result in resolution of the stenosis within seven to 13 months of age, alleviating the need for probing and possible intubation. While we prefer earlier probing than does Dr Frankel, it does not need to be done under general anesthesia as originally stated. In fact, lacrimal duct probing in infants younger than 1 year of age usually is done in the office without anesthesia on two or three occasions before resorting to a general anesthetic with possible intubation. Probing, whether early or late, usually is curative.  In our opinion, probing of the nasolacrimal duct should be performed if three months of diligent nasolacrimal duct massage is ineffective to prevent recurrent bouts of conjunctivitis and potential corneal ulceration.
Differential regulation of renal phospholipase C isoforms by catecholamines.
Authors: P Y Yu, L D Asico, G M Eisner, P A Jose
Journal: Journal of Clinical Investigation (1995)

Dopamine and D1 agonists and NE all increase phosphatidyl inositol-specific phospholipase C (PLC) activity, but whereas dopamine produces a natriuresis, NE has an antinatriuretic effect. To determine if catecholamines differentially regulate the expression of PLC isoforms, we infused fenoldopam, a D1 agonist, or pramipexole, a D1/D2 agonist, intravenously or infused fenoldopam or NE into the renal artery of anesthetized rats. After 3-4 h of infusion, when the expected natriuresis (fenoldopam or pramipexole) or antinatriuresis (NE) occurred, the kidneys were removed for analysis of PLC isoform protein expression activity. Western blot analysis revealed that in renal cortical membranes, fenoldopam and pramipexole increased expression of PLC beta 1 and decreased expression of PLC gamma 1; PLC delta was unchanged. In the cytosol, pramipexole and fenoldopam increased expression of both PLC beta 1 and PLC gamma 1. No effects were noted in the medulla. A preferential D1 antagonist, SKF 83742, which by itself had no effect, blocked the effects of pramipexole, thus confirming the involvement of the D1 receptor. In contrast, NE also increased PLC beta 1 but did not affect PLC gamma 1 protein expression in membranes. The changes in PLC isoform expression were accompanied by similar changes in PLC isoform activity. These studies demonstrate for the first time differential regulation of PLC isoforms by catecholamines.
Diversification of T Cell Responses to Carboxy-terminal Determinants within the 65-kD Heat-shock Protein Is Involved in Regulation of Autoimmune Arthritis
Authors: Kamal D. Moudgil, Tammy T. Chang, Herbert Eradat, Audrey M. Chen, Radhey S. Gupta, Ernest Brahn, Eli E. Sercarz
Journal: The Journal of Experimental Medicine (1997)

The T cell response to the 65-kD mycobacterial heat-shock protein (Bhsp65) has been implicated in the pathogenesis of autoimmune arthritis. Adjuvant arthritis (AA) induced in the Lewis rat (RT-1l) by injection of Mycobacterium tuberculosis serves as an experimental model for human rheumatoid arthritis (RA). However, the immunological basis of regulation of acute AA, or of susceptibility/resistance to AA is not known. We have defined the specificity of the proliferative T cell responses to Bhsp65 during the course of AA in the Lewis rat. During the early phase of the disease (6–9 d after onset of AA), Lewis rats raised T cell responses to many determinants within Bhsp65, spread throughout the molecule. Importantly, in the late phase of the disease (8–10 wk after onset of AA), there was evidence for diversification of the T cell responses toward Bhsp65 carboxy-terminal determinants (BCTD) (namely, 417–431, 441–455, 465–479, 513–527, and 521–535). Moreover, arthritic rats in the late phase of AA also raised vigorous T cell responses to those carboxy-terminal determinants within self(rat) hsp65 (Rhsp65) that correspond in position to the above BCTD. These results suggest that the observed diversification is possibly triggered in vivo by induction of self(Rhsp65)-reactive T cells. Interestingly, another strain of rat, the Wistar Kyoto (WKY/NHsd) rat (RT-1l), with the same major histocompatibility complex class II molecules as the Lewis rat, was found to be resistant to AA. In WKY rats, vigorous responses to the BCTD, to which the Lewis rat responded only in the late phase of AA, were observed very early, 10 d after injection of M. tuberculosis. Strikingly, pretreatment with the peptides comprising the set of BCTD, but not its amino-terminal determinants, provided significant protection to naive Lewis rats from subsequent induction of AA. Thus, T cell responses to the BCTD are involved in regulating inflammatory arthritis in the Lewis rat and in conferring resistance to AA in the WKY rat. These results have important implications in understanding the pathogenesis of RA and in devising new immunotherapeutic strategies for this disease.
I. The New Frontier in Public Health
Authors: Leslie W. Knott
Journal: JAMA (1962)

OURGREATEST RESPONSIBILITY in public health today is to apply the knowledge that research has given us, to narrow the gap between what we know and what we do for increasing millions of chronically ill and aged in our population.  Our greatest danger is what I call the Great Day Syndrome, the futile waiting with idle hands and bleeding hearts for that great day when science will have given us immunity to cancer, heart disease, and the other chronic killers and cripplers.  In our efforts to avoid this danger and to deal with the chronic diseases, the   of public health are not enough. And by traditional methods I mean the impersonal approach to public health, the reliance on environmental sanitation and public education which has served so effectively in the battle against infectious disease.  This battle goes on and the   must not be neglected. But on
Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: The Framingham Heart Study
Authors: Caroline S. Fox, Martin G. Larson, Michelle J. Keyes, Daniel Levy, Melvin E. Clouse, Bruce Culleton, Christopher J. O'Donnell
Journal: Kidney International (2004)

Among patients with end-stage renal disease (ESRD), the risk of cardiovascular disease is 10 to 20 times higher than the general population. Adults with ESRD have increased coronary-artery calcification (CAC) detected by electron-beam computed tomography (EBCT). Because the risk of coronary heart disease is increased even at moderate declines in kidney function, we sought to test whether high CAC scores are seen among those with mild reductions in kidney function.Men and women free of symptomatic cardiovascular disease underwent EBCT. Coronary calcium was quantified using the method described by Agatston. Renal function was estimated by glomerular filtration rate (GFR). Spearman correlation coefficients were used to test the association between GFR and CAC.Three hundred nineteen subjects (162 men/157 women), mean age 60, were included. Mean GFR was 86 +/- 23 mL/min/1.73 m2 (range 31-169; 10% with GFR <60 mL/min/1.73 m2). The median CAC scores by quartile of GFR were 85.9, 48.1, 7.9, and 2.7. Overall, the unadjusted correlation of GFR and CAC was -0.28 (P < 0.0001). This remained significant after adjustment for age and sex (-0.11, P < 0.05), and additionally after adjustment for body mass index (-0.11, P < 0.05), hypertension (-0.11, P < 0.05), or total cholesterol (-0.12, P= 0.04). A similar correlation was noted after multivariable adjustment (-0.10, P < 0.08).Mild declines in kidney function are associated with subclinical coronary artery calcification in a sample of subjects free of clinically apparent cardiovascular disease. This might help explain the increased risk of cardiovascular disease among individuals with renal dysfunction. Larger ongoing studies are needed to better quantify this finding.
Project HOPE Helps China Build a New Foundation for Pediatric Medicine
Authors: Andrew A. Skolnick
Journal: JAMA (1996)

Shanghai, China—Workers in Shanghai are now pouring the foundation for China's first major pediatric teaching and referral hospital. Expected to open in late 1997, The Shanghai Children's Medical Center will serve as a national training center for China's health professionals and provide state-of-the-art clinical care for children with serious health problems. Thanks in part to the crippling of its educational system during the Cultural Revolution (1966-1976), China lags behind the West in advanced training in many areas of medicine. With approximately one fifth of the world's children, China has an enormous need for modern pediatric teaching facilities. So, beginning in the early 1990s, the global health care foundation Project HOPE (see accompanying article) began a partnership with the Chinese government, the City of Shanghai, and Shanghai Second Medical University to build a world-class pediatric teaching hospital. The Shanghai Children's Medical Center will provide advanced medical care for approximately 250 000
ERAP1 Regulates Natural Killer Cell Function by Controlling the Engagement of Inhibitory Receptors
Authors: Loredana Cifaldi, Paolo Romania, Michela Falco, Silvia Lorenzi, Raffaella Meazza, Stefania Petrini, Marco Andreani, Daniela Pende, Franco Locatelli, Doriana Fruci
Journal: Cancer Research (2015)

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by MHC class I (MHC-I) molecules. Herein, we demonstrate that genetic or pharmacological inhibition of ERAP1 on human tumor cell lines perturbs their ability to engage several classes of inhibitory receptors by their specific ligands, including killer cell Ig-like receptors (KIR) by classical MHC-I-peptide (pMHC-I) complexes and the lectin-like receptor CD94-NKG2A by nonclassical pMHC-I complexes, in each case leading to natural killer (NK) cell killing. The protective effect of pMHC-I complexes could be restored in ERAP1-deficient settings by the addition of known high-affinity peptides, suggesting that ERAP1 was needed to positively modify the affinity of natural ligands. Notably, ERAP1 inhibition enhanced the ability of NK cells to kill freshly established human lymphoblastoid cell lines from autologous or allogeneic sources, thereby promoting NK cytotoxic activity against target cells that would not be expected because of KIR-KIR ligand matching. Overall, our results identify ERAP1 as a modifier to leverage immune functions that may improve the efficacy of NK cell-based approaches for cancer immunotherapy.
Predicting Plasma Concentrations of Bisphenol A in Children Younger Than 2 Years of Age after Typical Feeding Schedules, using a Physiologically Based Toxicokinetic Model
Authors: Andrea N. Edginton, Len Ritter
Journal: Environmental Health Perspectives (2008)

Concerns have recently been raised regarding the safety of potential human exposure to bisphenol A (BPA), an industrial chemical found in some polycarbonate plastics and epoxy resins. Of particular interest is the exposure of young children to BPA via food stored in BPA-containing packaging.In this study we assessed the age dependence of the toxicokinetics of BPA and its glucuronidated metabolite, BPA-Glu, using a coupled BPA-BPA-Glu physiologically based toxicokinetic (PBTK) model.Using information gathered from toxicokinetic studies in adults, we built a PBTK model. We then scaled the model to children < 2 years of age based on the age dependence of physiologic parameters relevant for absorption, distribution, metabolism, and excretion.We estimated the average steady-state BPA plasma concentration in newborns to be 11 times greater than that in adults when given the same weight-normalized dose. Because of the rapid development of the glucuronidation process, this ratio dropped to 2 by 3 months of age. Simulation of typical feeding exposures, as estimated by regulatory authorities, showed a 5-fold greater steady-state BPA plasma concentration in 3- and 6-month-olds compared with adults, reflecting both a reduced capacity for BPA metabolism and a greater weight-normalized BPA exposure. Because of uncertainty in defining the hepatic BPA intrinsic clearance in adults, these values represent preliminary estimates.Simulations of the differential BPA dosimetry between adults and young children point to the need for more sensitive analytical methods for BPA to define, with greater certainty, the adult hepatic BPA intrinsic clearance, as well as a need for external exposure data in young children.
Policy: Chrysotile on Ice
Authors: Rebecca Renner
Journal: Environmental Health Perspectives (2007)

Rallying Around the Environmental FlagSocial scientists have long studied competition for natural resources as a source of conflict around the world, but they have paid little attention to the environment in postconflict societies.Must the environment invariably suffer in the wake of conflict?Can former combatants rally around the environment to help sustain peace?These were the types of questions asked at a November
Against the unification of the behavioral sciences
Authors: Steve Clarke
Journal: Behavioral and Brain Sciences (2007)

The contemporary behavioral sciences are disunified and could not easily become unified, as they operate with incompatible explanatory models. According to Gintis, tolerance of this situation is “scandalous” (sect. 12). I defend the ordinary behavioral scientist's lack of commitment to a unifying explanatory model and identify several reasons why the behavioral sciences should remain disunified for the foreseeable future.
Answer: What is the Diagnosis?
Authors: J O'Brien, J Taunton, J Larsen, B B Forster
Journal: British Journal of Sports Medicine (2011)

Femoral neck stress fracture (FNSF), with subsequent progression to a complete fracture of the right femoral neck.

The plain radiograph of the right hip (figure 3) demonstrates sclerosis on the medial aspect of the femoral neck (arrow).



Figure 3 
Radiograph of the right hip demonstrating a horizontal area of sclerosis on the medial aspect of the right femoral neck extending to the medial cortex. There is no visible fracture line.



A selective coronal image from the fat suppressed T2-weighted MRI sequence (figure 4) demonstrates an area of high T2 signal representing bone marrow oedema (arrow) on the medial aspect of the femoral neck. There is a horizontal linear area of low T2 signal within the region of bone marrow oedema, representing the stress fracture.



Figure 4 
(A) Coronal magnetic resonance image from a fast spin echo T2 sequence demonstrating high T2 signal bone marrow oedema on the medial aspect of the right femoral neck with a linear area of low T2 signal within it, representing the stress fracture at this site. (B) Coronal T1-weighted magnetic resonance image, which demonstrates a horizontal linear area of low signal on the medial aspect of the right femoral neck representing a stress fracture of the medial cortex.



Stress fractures are classified based on the condition of the underlying bone; insufficiency fractures, when a fracture occurs as result of normal stress on abnormal bone; and stress fractures, which occur when there is excessive stress on a normal bone. Remodelling is the normal response of stress on a bone, and a stress fracture occurs as result of increased remodelling and microfracture in a bone. It has been reported that stress fractures may occur in up to 15% of athletes and …
Office-Based Testing for Fecal Occult Blood
Authors: Edward P. Hoffer
Journal: Annals of Internal Medicine (2005)

Letters2 August 2005Office-Based Testing for Fecal Occult BloodEdward P. Hoffer, MDEdward P. Hoffer, MDFrom Framingham, MA 01702.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-3-200508020-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The recent paper (1) denigrating the use of single-specimen FOBT done at an office visit compared with a mail-in multiple-specimen test failed to take into account an important factor: adherence. It would appear to be only common sense that a test with relatively low sensitivity (and also specificity!) would have a higher yield when done on multiple specimens, as was the main point of the paper.I switched to in-office testing when I realized that most of my patients who were given take-home kits failed to return the kits. The sensitivity of a test never done is ...Reference1. Sox HC. Office-based testing for fecal occult blood: do only in case of emergency [Editorial]. Ann Intern Med. 2005;142:146-8. [PMID: 15657163] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Edward P. Hoffer, MDAffiliations: From Framingham, MA 01702.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOffice-Based Testing for Fecal Occult Blood: Do Only in Case of Emergency Harold C. Sox Office-Based Testing for Fecal Occult Blood Christian Jackson and Robert Craig Office-Based Testing for Fecal Occult Blood Harold C. Sox Office-Based Testing for Fecal Occult Blood Michael L. Wolff Metrics 2 August 2005Volume 143, Issue 3Page: 235KeywordsColonoscopyConflicts of interestHematologic testsSpecificity ePublished: 2 August 2005 Issue Published: 2 August 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...