tbuckley/cabot-search huggingface dataset:
Evolution of the Insecticide Target Rdl in African Anopheles Is Driven by Interspecific and Interkaryotypic Introgression
Authors: Xavier Grau-Bové, Sean Tomlinson, Andrias O O’Reilly, Nicholas J Harding, Alistair Miles, Dominic Kwiatkowski, Martin J Donnelly, David Weetman
Journal: Molecular Biology and Evolution (2020)

Abstract The evolution of insecticide resistance mechanisms in natural populations of Anopheles malaria vectors is a major public health concern across Africa. Using genome sequence data, we study the evolution of resistance mutations in the resistance to dieldrin locus (Rdl), a GABA receptor targeted by several insecticides, but most notably by the long-discontinued cyclodiene, dieldrin. The two Rdl resistance mutations (296G and 296S) spread across West and Central African Anopheles via two independent hard selective sweeps that included likely compensatory nearby mutations, and were followed by a rare combination of introgression across species (from A. gambiae and A. arabiensis to A. coluzzii) and across nonconcordant karyotypes of the 2La chromosomal inversion. Rdl resistance evolved in the 1950s as the first known adaptation to a large-scale insecticide-based intervention, but the evolutionary lessons from this system highlight contemporary and future dangers for management strategies designed to combat development of resistance in malaria vectors.
Tree Pollen Allergy
Authors: S.‐O. Strandhede, J.‐Å. Wihl, N. E. Eriksson
Journal: Allergy (1984)

The distribution of trees and bushes in Sweden (viz. lignoses) of possible allergic importance is presented and comments made on analyses of pollen counts of lignose taxa from different parts of the country. Based on these data, 20 lignose taxa were selected for an allergen panel and used in a multi‐centre study covering Sweden with the aim of revealing the pattern of sensitization to these plants among sufferers of springtime hay fever.
Desquamative Interstitial Pneumonia
Authors: Edward A. Gaensler, Anne M. Goff, Clive M. Prowse
Journal: New England Journal of Medicine (1966)

DIFFUSE or miliary lung diseases are being recognized and labeled with increasing frequency, often with considerable importance in relation to therapy. However, a large group of these disorders still remains unclassified. They are the chronic interstitial pneumonias, which, in the absence of familial history, collagen diseases, inhalation of noxious agents or ingestion of certain drugs, are often referred to as chronic idiopathic interstitial fibrosis or Hamman-Rich disease. Unfortunately, the latter term tends to be applied loosely to chronic fibrosing lung diseases with greatly variable clinical and histologic features. Recently, Liebow, Steer and Billingsley1 called attention to a pathological picture that, . . .
Inhibition of Estrogen Sulfotransferase (SULT1E1/EST) Ameliorates Ischemic Acute Kidney Injury in Mice
Authors: Anne C. Silva Barbosa, Dong Zhou, Yang Xie, You-Jin Choi, Hung-Chun Tung, Xinyun Chen, Meishu Xu, Robert B. Gibbs, Samuel M. Poloyac, Silvia Liu, Yanping Yu, Jianhua Luo, Youhua Liu, Wen Xie
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Studies have suggested that estrogens may protect mice from AKI. Estrogen sulfotransferase ( SULT1E1 , or EST) plays an important role in estrogen homeostasis by sulfonating and deactivating estrogens, but studies of SULT1E1 ’s role in AKI are lacking. Using the ischemia-reperfusion model of AKI, the authors demonstrated that genetic ablation or pharmacologic inhibition of Sult1e1 can mitigate AKI in both male and female mice in a sex hormone-independent manner. A gene profiling analysis indicated that the renoprotective effect was associated with increased vitamin D receptor signaling. Liver-specific reconstitution of Sult1e1 resensitizes male Sult1e1 knockout mice to AKI, indicating that liver Sult1e1 is required for ischemic AKI in males. These findings suggest that pharmacologic inhibition of SULT1E1 might represent a novel approach for clinical management of AKI. Background Studies have suggested that estrogens may protect mice from AKI. Estrogen sulfotransferase ( SULT1E1 , or EST) plays an important role in estrogen homeostasis by sulfonating and deactivating estrogens, but studies on the role of SULT1E1 in AKI are lacking. Methods We used the renal ischemia-reperfusion model to investigate the role of SULT1E1 in AKI. We subjected wild-type mice, Sult1e1 knockout mice, and Sult1e1 knockout mice with liver-specific reconstitution of SULT1E1 expression to bilateral renal ischemia-reperfusion or sham surgery, either in the absence or presence of gonadectomy. We assessed relevant biochemical, histologic, and gene expression markers of kidney injury. We also used wild-type mice treated with the SULT1E1 inhibitor triclosan to determine the effect of pharmacologic inhibition of SULT1E1 on AKI. Results AKI induced the expression of Sult1e1 in a tissue-specific and sex-specific manner. It induced expression of Sult1e1 in the liver in both male and female mice, but Sult1e1 induction in the kidney occurred only in male mice. Genetic knockout or pharmacologic inhibition of Sult1e1 protected mice of both sexes from AKI, independent of the presence of sex hormones. Instead, a gene profiling analysis indicated that the renoprotective effect was associated with increased vitamin D receptor signaling. Liver-specific transgenic reconstitution of SULT1E1 in Sult1e1 knockout mice abolished the protection in male mice but not in female mice, indicating that Sult1e1 ’s effect on AKI was also tissue-specific and sex-specific. Conclusions SULT1E1 appears to have a novel function in the pathogenesis of AKI. Our findings suggest that inhibitors of SULT1E1 might have therapeutic utility in the clinical management of AKI.
BMS-554417, an inhibitor of the insulin-like growth factor I receptor and insulin receptor, inhibits proliferation and induces mitochondrial pathway-mediated apoptosis in cancer cell lines
Authors: Paul Haluska, Joan M. Carboni, David A. Loegering, Francis Y. Lee, Mark Saulnier, David Frennesson, Ricardo M. Attar, Kimberly R. Kalli, Cheryl A. Conover, Sumithra J. Mandrekar, Scott H. Kaufmann, Marco Gottardis, Charles Erlichman
Journal: Cancer Research (2005)

5043  The insulin-like growth factor receptor (IGF1R) and insulin receptor (IR) are overexpressed in many tumor types and contribute to tumorigenicity, proliferation, metastasis and resistance to standard therapies. Here we show that BMS-554417, a novel small molecule developed as an inhibitor of IGF1R, inhibits IGF1R and IR kinase activity, inhibits proliferation in vitro and reduces tumor xenograft growth in vivo. In a series of breast and ovarian cancer cell lines, the IC50 for proliferation ranged from 218 nM (MCF-7) to 8.5 μM (OV202). The sensitivities of tumor cells did not correlate with IGF1R or IR expression or the presence of stimulatory ligands. BMS-554417 treatment inhibited ERK phosphorylation, caused a G0/G1 arrest and prevented nuclear accumulation of cyclin D1 in response to the IGF-1 analog, IGF-1 LR3. At doses that inhibited proliferation, the compound also inhibited the PI3k/Akt pathway, as evidenced by decreased Akt phosphorylation at Ser473. Both MCF-7 and OV202 cells treated with BMS-554417 exhibited characteristics of apoptotic cell death, including nuclear fragmentation and cleavage of poly-ADP-ribose polymerase (PARP). To further elucidate whether apoptotic cell death occurred through the intrinsic (mitochondrial) or extrinsic (death receptor) pathways, sensitivity of a series of Jurkat T cell leukemia variants was investigated. In parental Jurkat cells, BMS-554417 induced apoptotic cell morphologic changes at 2.5 μM. However, in Jurkat cells overexpressing Bcl-2 or parental cells treated with a broad spectrum caspase inhibitor, there was no significant induction of apoptosis at the highest dose tested (10 μM). In contrast, loss of caspase 8, a blocking anti-Fas antibody, a synthetic decoy receptor for TRAIL or a caspase 8/10 inhibitor had no effect on the ability of BMS-554417 to induce apoptosis. These data suggest that this agent triggered apoptotic cell death via the mitochondrial pathway. BMS-554417 was orally bioavailable and inhibited the growth of salivary gland tumor xenografts engineered to express constitutively active IGF1R (IGF-1R Sal) in vivo. BMS-554417 is a member of a novel class of IGF1R/IR inhibitors that have potential clinical applications because of their antiproliferative activity in vitro and in vivo. Supported in part by CA15083, CA69008 and the Mayo Foundation.
Linking lodine with Autoimmune Thyroiditis
Authors: Noel R. Rose, Linda Rasooly, Ali M. Saboori, C. Lynne Burek
Journal: Environmental Health Perspectives (1999)

A great deal of circumstantial evidence has linked iodine with the rising incidence of autoimmune thyroiditis in the United States.In our investigations, we have shown directly that T cells from humans with chronic lymphocytic thyroiditis proliferate in the presence of iodinated but not in the presence of noniodinated human thyroglobulin.Moreover, the proliferative response is restored when the thyroglobulin is iodinated artificially in vitro.Using a panel of monoclonal antibodies, we found evidence that the presence of iodine induces a number of stereochemical changes in the conformation of the molecule, resulting in the loss of some antigenic determinants and the appearance of others.One prominent determinant was associated with the iodine-containing amino acid thyroxine.Both the number and position of the iodine substituents determine the precise specificity of this epitope.A new model for the study of the role of iodine in inducing thyroid autoimmunity has become available in the form of the nonobese diabetic (NOD)-H2h4 mouse.This animal develops autoimmune thyroiditis spontaneously but in relatively low prevalence.However, if iodine is added to the drinking water, the prevalence and severity of the thyroid lesions increase markedly.The immune response is specific for thyroglobulin, both in terms of the antibody response and T-cell proliferation.In fact, the appearance of lesions can be predicted by the presence of thyroglobulin-specific IgG2b antibody.The disease, moreover, can be transferred adoptively, using spleen cells from iodine-fed donors treated in vitro with iodinated thyroglobulin.The effects of iodine feeding are greater in conventional animals compared with those maintained under specific pathogen-free conditions.Based on T-cell proliferation, it appears that the NOD-H2h4 strain of mice has innately a greater response to murine thyroglobulin than do other mouse strains and that the proliferation is increased even more by feeding iodine.We suggest, therefore, that the presence of iodine increases the autoantigenic potency of thyroglobulin, a major pathogenic antigen in the induction of autoimmune thyroiditis.This animal model provides a unique opportunity for investigating in detail the mechanisms by which an environmental agent can trigger a pathogenic autoimmune response in a susceptible host.
Association between reperfusion therapy and outcomes in patients with acute pulmonary embolism and right heart thrombi
Authors: Behnood Bikdeli, David Jiménez, Alfonso Muriel, Deisy Barrios, Aitor Ballaz, Peter Verhamme, Manuel Monreal
Journal: European Respiratory Journal (2020)

<b>Right heart thrombi portend worse outcomes in pulmonary embolism (PE). In propensity-matched analyses of patients from a large registry, reperfusion therapy was not associated with significantly reduced odds of all-cause or PE-related mortality.</b>https://bit.ly/2WRLYnq
Ribavirin as Therapy for Chronic Hepatitis C
Authors: Adrian M. Di Bisceglie, Hari S. Conjeevaram, Michael W. Fried, Richard Sallie, Yoon Park, Cihan Yurdaydin, Mark Swain, David E. Kleiner, Kevin Mahaney, Jay H. Hoofnagle
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate ribavirin, an oral antiviral agent, as therapy for chronic hepatitis C. Design: Randomized, double-blind, placebo-controlled study. Setting: Clinical Center of the National I...
Teaching medical law
Authors: R. S. Fisher
Journal: JAMA (1968)

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
Abstract 3411: Underidentification of Need for Statin Therapy by ATP III NCEP Risk Assessment Compared to SHAPE Guidelines
Authors: Daniel S Berman, Romalisa S Miranda Peats, Heidi Gransar, Leslee J Shaw, Donna Polk, Johanna H Moon, Louise E Thomson, Sean W Hayes, John D Friedman, Alan Rozanski, Matt Budoff, Nathan D Wong
Journal: Circulation (2007)
Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis
Authors: Xiao-Yong Huang, Peng-Fei Zhang, Chuan-Yuan Wei, Rui Peng, Jia-Cheng Lu, Chao Gao, Jia-Bing Cai, Xuan Yang, Jia Fan, Ai-Wu Ke, Jian Zhou, Guo-Ming Shi
Journal: Molecular Cancer (2020)

Abstract Background Amplification of chromosome 7q21-7q31 is associated with tumor recurrence and multidrug resistance, and several genes in this region are powerful drivers of hepatocellular carcinoma (HCC). We aimed to investigate the key circular RNAs (circRNAs) in this region that regulate the initiation and development of HCC. Methods We used qRT-PCR to assess the expression of 43 putative circRNAs in this chromosomal region in human HCC and matched nontumor tissues. In addition, we used cultured HCC cells to modify circRNA expression and assessed the effects in several cell-based assays as well as gene expression analyses via RNA-seq. Modified cells were implanted into immunocompetent mice to assess the effects on tumor development. We performed additional experiments to determine the mechanism of action of these effects. Results circMET (hsa_circ_0082002) was overexpressed in HCC tumors, and circMET expression was associated with survival and recurrence in HCC patients. By modifying the expression of circMET in HCC cells in vitro, we found that circMET overexpression promoted HCC development by inducing an epithelial to mesenchymal transition and enhancing the immunosuppressive tumor microenvironment. Mechanistically, circMET induced this microenvironment through the miR-30-5p/Snail/ dipeptidyl peptidase 4(DPP4)/CXCL10 axis. In addition, the combination of the DPP4 inhibitor sitagliptin and anti-PD1 antibody improved antitumor immunity in immunocompetent mice. Clinically, HCC tissues from diabetic patients receiving sitagliptin showed higher CD8 + T cell infiltration than those from HCC patients with diabetes without sitagliptin treatment. Conclusions circMET is an onco-circRNA that induces HCC development and immune tolerance via the Snail/DPP4/CXCL10 axis. Furthermore, sitagliptin may enhance the efficacy of anti-PD1 therapy in a subgroup of patients with HCC.
Biomarker-driven management strategies for peripheral T cell lymphoma
Authors: Erin Mulvey, Jia Ruan
Journal: Journal of Hematology & Oncology (2020)

Abstract Peripheral T cell lymphomas are heterogeneous diseases which remain treatment challenges. Recent advances in molecular and genomic profiling have provided unprecedented insight into disease pathogenesis driven by distinct cells of origins and molecular pathways. The discovery and clinical application of molecular biomarkers in PTCL subtypes has the potential to transform personalized care for patients with PTCL in diagnosis, prognosis, and therapy. Targeting CD30+ PTCL with the antibody-drug conjugate brentuximab vedotin in the relapsed setting and in combination with chemotherapy in the frontline setting has improved patient survivals. Epigenetic modifying agents, including HDAC inhibitors and hypomethylating agents, have demonstrated broad clinical efficacy and durability and are in clinical development for combination strategies for both relapsed and frontline settings. Wide-ranging novel agents targeting critical intracellular pathways and tumor microenvironment are in active exploration to define clinical activities. This review summarizes PTCL-specific biomarkers which are increasingly incorporated in clinical practice to guide precision diagnosis and personalized treatment.
Antioxidant intake and adult-onset wheeze: a case-control study
Authors: C. Bodner, D. Godden, K. Brown, J Little, S Ross, A. Seaton
Journal: European Respiratory Journal (1999)

An increase in prevalence of wheezing illness in the UK has coincided with a reduction in the consumption of natural antioxidants, which may modulate the lung's response to oxidant stress, limiting the expression of airway inflammation and respiratory symptoms. The hypothesis that intakes and plasma levels of natural anti- oxidants would be determinants of adult-onset wheezing illness was tested. A nested case-control study was conducted in 94 cases with adult-onset wheeze and 203 controls aged 39-45 yrs identified in a 30-yr follow-up survey. Antioxidant intake was measured by a food frequency questionnaire, and plasma and red cell measure- ments of antioxidant status were obtained. Outcome measures were onset of wheeze since age 15 yrs (ever wheeze) and wheeze occurring in the past 12 months (current wheeze). After adjusting for the effects of smoking, socioeconomic status, atopy, family his- tory of atopic disease and total energy intake, intakes of vitamin E (odds ratio (OR)=4.02 for low compared to high tertile of intake) and plasma levels of ascorbate (OR=0.98 per unit) and a-tocopherol:triglyceride ratio (OR=0.34 per loge unit) were inversely related to adult-onset wheeze. In analyses stratified by social class and smoking, intakes of vitamin C and E and plasma levels of ascorbate and a-tocophe- rol:triglyceride ratio were inversely related to current wheeze in the manual social class and among current smokers. No independent associations of vitamin A, b-caro- tene or total plasma antioxidant capacity were found. The results support the hypothesis that deficiencies of vitamins C and E are associ- ated with wheezing symptoms. Smokers in the manual social class are particularly susceptible to these effects. Eur Respir J 1999; 13: 22-30.
Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study
Authors: Annieke W. Gotink, Steffi E. M. van de Ven, Fiebo J. C. ten Kate, Daan Nieboer, Lucia Suzuki, Bas L. A. M. Weusten, Lodewijk A. A. Brosens, Richard van Hillegersberg, Lorenza Alvarez Herrero, Cees A. Seldenrijk, Alaa Alkhalaf, Freek C. P. Moll, Erik J. Schoon, Ineke van Lijnschoten, Thjon J. Tang, Hans van der Valk, Wouter B. Nagengast, Gursah Kats-Ugurlu, John T. M. Plukker, Martin H. M. G. Houben, Jaap S. van der Laan, Roos E. Pouw, Jacques J. G. H. M. Bergman, Sybren L. Meijer, Mark I. van Berge Henegouwen, Bas P. L Wijnhoven, Pieter Jan F. de Jonge, Michael Doukas, Marco J. Bruno, Katharina Biermann, Arjun D. Koch
Journal: Endoscopy (2021)

Abstract Background Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC. Methods A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic. Results 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %–36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02–1.14, for every increase of 500 μm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95–4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10–1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75–0.86). Conclusions A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice.
The Medical Malpractice System
Authors: Lynn G. Lagerquist
Journal: Annals of Internal Medicine (1993)

Letters1 June 1993The Medical Malpractice SystemLynn G. Lagerquist, MDLynn G. Lagerquist, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-11-199306010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The 21% payment rate in cases where physician care was defensible contradicts the conclusion that unjustified payments are probably uncommon. I propose an alternative analysis of the data. Exorbitant awards are commonplace and can exceed a physician's coverage. The litigation itself is an agonizing process that drags on for years. Juries do not understand medical problems, especially those that are difficult or complex, and their decisions are arbitrary. These forces frequently lead to token settlements, which maintain privacy and are much less expensive and risky than jury trials. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1993Volume 118, Issue 11Page: 908-909 ePublished: 15 August 2000 Issue Published: 1 June 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Letter: HL-A antigens in thromboangiitis obliterans
Authors: T. Otawa
Journal: JAMA (1974)

<h3>To the Editor.—</h3> We have recently observed that the frequency of occurrence of a particular second sublocus group HL-A antigen (tentatively specified by us as J-1-1) was significantly higher (<i>P</i>&lt;.001) in Japanese patients with thromboangiitis obliterans (TAO) than it was in a population of normal Japanese. As shown in the Table, J-1-1 antigen was found in 46% of the TAO patients, relative to a normal population occurrence of 18%. Also, antigens HL-A9 and W10 showed an increased occurrence in TAO patients. However, antigen HL-A12 was not found in TAO patients, but it occurred with a frequency of 20% in the normal population. The Figure illustrates our classification of the J-1-1 antigen. In our study, 11 antisera from pregnant Japanese women showed a very high correlation with each other in their reactivities on the lymphocytotoxicity test (LCT), using normal Japanese panel lymphocytes. With the LCT test antisera, the antigen that