tbuckley/cabot-search huggingface dataset:
Harmful effects of ultraviolet radiation. Council on Scientific Affairs
Journal: JAMA (1989)

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
The Relationship between Cox-1 and Cox-2 Expression; Selective and Non Selective Cox Inhibitors and the Kinetics of the Intestinal Mucosa
Authors: MA McGarvey, R Ettarh
Journal: Endoscopy (2006)

Aims: Nimesulide a selective COX-2 inhibitor and indomethacin, a non selective inhibitor were compared with respect to their mechanistic relationships on mucosal kinetics and cyclooxygenase expression in the small intestine.
Abstract 3431: Pulse Pressure Is Inversely Related to Aortic Root Diameter: Implications for the Pathogenesis of Systolic Hypertension
Authors: S. Morteza Farasat, Christopher H Morrell, Angelo Scuteri, Chih-Tai Ting, Frank C Yin, Harold A Spurgeon, Chen-Huan Chen, Edward G Lakatta, Samer S Najjar
Journal: Circulation (2007)

Background: The age-associated increase in central arterial stiffness manifests as a rise in pulse pressure, which leads to a marked increase in the prevalence of systolic hypertension among older individuals. Aortic root diameter (AoD) also increases with advancing age. According to the prevailing views, hypertension contributes to a further increase in AoD. Conversely, it has been suggested that the age-associated increase in AoD may partially compensate for the increased arterial stiffness. We tested the hypothesis that AoD is inversely associated with pulse pressure. Methods: The study population comprised 1256 individuals, aged 30 –79 years (48% women, 48% hypertensive), none of whom were on antihypertensive medications. Brachial pulse pressure (bPP) was calculated as the difference between sphygmomanometric systolic and diastolic blood pressures. Central pulse pressure (cPP) was derived from calibrated carotid artery pressure waveforms. AoD was measured by echocardiography at the level of the Sinuses of Valsalva. The relationships of AoD with bPP and cPP were evaluated with multiple regression analyses. Results: bPP was 54 ± 18 mmHg in women and 50 ± 14 mmHg in men, and AoD was 28.9 ± 3.5 mm in women and 31.9 ± 3.5 mm in men. After adjusting for age, age 2 , height, weight, and mean arterial pressure, bPP was inversely associated with AoD in both sexes. This inverse association persisted even after adjusting for aortic pulse wave velocity, carotid intima-media thickness, reflected waves, and left ventricular end-diastolic diameter and wall thickness. In the fully adjusted models predicting bPP, the regression coefficients for AoD were −0.48 in men (p = 0.0003, model R 2 =0.51) and −0.40 in women (p = 0.01, model R 2 = 0.61). Similarly, cPP was inversely associated with AoD in both men (coefficient = −0.45, p = 0.0007, model R 2 =0.50) and women (coefficient = −0.40, p = 0.01 model R 2 = 0.61). Thus, each 1 mm increase in AoD was associated with a 0.4 – 0.5 mmHg decrease in bPP and cPP in both sexes. Conclusions: Contrary to the prevailing views, AoD is independently and inversely associated with both bPP and cPP. These findings suggest that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility.
Erratum: CORRIGENDUM: Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
Authors: C S Manno, V R Arruda, G F Pierce, B Glader, M Ragni, J Rasko, M C Ozelo, K Hoots, P Blatt, B Konkle, M Dake, R Kaye, M Razavi, A Zajko, J Zehnder, H Nakai, A Chew, D Leonard, J F Wright, R R Lessard, J M Sommer, M Tigges, D Sabatino, A Luk, H Jiang, F Mingozzi, L Couto, H C Ertl, K A High, M A Kay
Journal: Nature Medicine (2006)
Whole-Body 68Ga-DOTANOC PET/MRI Versus 68Ga-DOTANOC PET/CT in Patients With Neuroendocrine Tumors
Authors: Dominik Berzaczy, Chiara Giraudo, Alexander R. Haug, Markus Raderer, Daniela Senn, Georgios Karanikas, Michael Weber, Marius E. Mayerhoefer
Journal: Clinical Nuclear Medicine (2017)

The aim of this study was to assess the diagnostic performance of simultaneous whole-body Ga-DOTANOC PET/MRI compared with Ga-DOTANOC PET/CT for detection of distant metastatic disease in patients with well-differentiated neuroendocrine tumors (NETs).Patients with histologically proven, well-differentiated NET (G1 or G2) were included in this prospective, institutional review board-approved study. Patients underwent Ga-DOTANOC PET/CT and subsequent Ga-DOTANOC PET/MRI after a single tracer injection on the same day for staging or restaging purposes. Images were evaluated for the presence of NET lesions by 2 rater teams, each consisting of a nuclear medicine physician and a radiologist, in an observer-blinded fashion. Overall agreement, accuracy, sensitivity, and specificity, relative to a composite reference standard (consensus review including follow-up data), were calculated.Between July 2014 and June 2016, 28 patients were enrolled. Overall agreement and accuracy between the 2 rater teams were 91.7% (95% confidence interval [CI], 87.5%-95.9%) and 97% (95% CI, 94.4%-99.6%) for PET/MRI and 92.3% (95% CI, 88.3%-96.3%) and 94.6% (95% CI, 91.2%-98.1%) for PET/CT, respectively (P = 1.00).Overall, PET/MRI reached 89.8% sensitivity (95% CI, 77.8%-96.6%) and 100% specificity (95% CI, 97%-100%); PET/CT showed 81.6% sensitivity (95% CI, 68%-91.2%) and 100% specificity (95% CI, 97%-100%) for the detection of metastatic disease in NETs.Whole-body Ga-DOTANOC PET/MRI appears to be comparable to Ga-DOTANOC PET/CT for lesion detection in patients with well-differentiated NETs.
CNF2024 - The first clinical stage synthetic oral Hsp90 inhibitor
Authors: Karen Lundgren, Adeela Kamal, Rachel Lough, Noel Timple, John Sensintaffar, Cindy Yang, Hong Zhang, Gregg Timony, Kevin Hong, Srinivas Kasibhatla, Marcus Boehm, Francis Burrows
Journal: Cancer Research (2006)

4861  Hsp90 is a pleiotropic molecular chaperone that supports the maturation and stabilization of a wide range of signaling proteins. Mutated, overexpressed and constitutively or persistently active oncoproteins are particularly dependent on Hsp90 chaperone activity. In tumor cells, inhibition of HSP90 results in degradation of these proteins followed by cell death, making HSP90 a target of substantial interest for cancer therapy. Thus far, all clinical trials of Hsp90 inhibitors have employed 17-AAG, a derivative of the natural product geldanamycin, or close analogues thereof. 17-AAG has significant limitations as a drug, including poor solubility, low oral bioavailability and sensitivity to MDR efflux pumps. Here we describe the preclinical activity of CNF2024, the first-in-class fully synthetic Hsp90 inhibitor to enter the clinic. CNF2024 binds competitively with geldanamycin in the ATP binding pocket of Hsp90, and, as with the ansamycins, exhibits a striking selectivity for the activated, tumor-associated form of the chaperone. CNF2024 binding induces degradation of HER-2, Akt, Raf-1, PR, IGF-1R, HIF-1α and other client proteins at nanomolar concentrations, while also inducing the heat-shock proteins Hsp70 and Hsp27. Treatment with CNF2024 leads in vitro to the tumor cell growth inhibition and death. Furthermore, CNF2024 is not susceptible to tumor cell resistance mediated by MDR, MRP, NQO1 or other lesions that limit the potency of 17-AAG. When administered orally, CNF2024 causes the degradation of client proteins, induction of apoptosis and complete inhibition of tumor growth in a range of human tumor xenograft models at well-tolerated doses. CNF2024 is a promising new Hsp90 inhibitor that can be administered orally and is currently the subject of two Phase I clinical trials.
Abstract LB-178: The impact of the gut microbiome on the antitumor effects of radiotherapy
Authors: Andrea Facciabene, Stavros Rafail, Mireia Uribe-Herranz, Stefano Pierini, Kile Bittinger, Iannis Verginadis, Costas Koumenis, Amit Maity
Journal: Cancer Research (2017)

Abstract The sheer enormity of the microbial biomass in the human intestinal tract, the co-evolution between humans and the microbiota, and the established function of the gut microbes in regulating normal host physiologic functions, are all consistent with the idea that alterations in gut microbial ecology play a role in the pathophysiology of several conditions including cancer. Radiotherapy (RT) is an established curative and palliative cancer treatment regimen, with approximately half of cancer patients with solid tumors receiving RT some time during their disease. Mounting evidence also suggests that high-dose (hypofractionated) radiation exerts potent immune modulatory effects, prompting immunological active tumor cell death inducing tumor associated antigen (TAA) cross priming with elicitation of anti-tumor CD8+ T cells, and abscopal effects. Although there have been groundbreaking responses to immunotherapy in certain malignancies such as lung cancer and melanomas, so far, immunotherapy is effective only in a portion of patients19. This raises the issue of whether there are additional important regulators of T cell function that are relevant to tumor control and could be harnessed to enhance radiotherapy. In support of this hypothesis, we have generated preliminary results demonstrating that: a) Treatment with vancomycin, an antibiotic with action in the gut mostly against Gram+ bacteria, significantly increased the presence of overall tumor infiltrating T cells or cytotoxic CD8+ cells in tumors from mice treated with RT/vancomycin combination compared to RT alone; b) vancomycin caused a significant enhancement of the tumor inhibitory effect of targeted radiation. c) Vancomycin enhanced the ability of RT to increase the expression of IFN-g in CD8+ infiltrating T cells and antigen presentation in the tumor draining lymph nodes and d) the observed synergy between vancomycin and RT in eliciting an anti-tumor immune response and inhibiting tumor growth was abrogated in IFN-g KO animals or by CD8+ cell depletion. Citation Format: Andrea Facciabene, Stavros Rafail, Mireia Uribe-Herranz, Stefano Pierini, Kile Bittinger, Iannis Verginadis, Costas Koumenis, Amit Maity. The impact of the gut microbiome on the antitumor effects of radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-178. doi:10.1158/1538-7445.AM2017-LB-178
Prognostic significance of tumor subtypes in women with breast cancer according to stage: A population-based study.
Authors: Jose Pablo Leone, Julieta Leone, Ariel Osvaldo Zwenger, Carlos Teodoro Vallejo, Bernardo Amadeo Leone
Journal: Journal of Clinical Oncology (2017)

1070 Background: Tumor subtypes (TS) are an important prognostic tool in breast cancer patients (pts). However, with contemporary therapies the prognosis of different subtypes is unclear. Recently, the AJCC proposed to incorporate TS among other variables in the 8 th edition of the staging manual. The aim of this study was to analyze differences in overall survival (OS) by TS according to stage compared with other factors. Methods: We evaluated women with microscopically confirmed invasive breast cancer between 2010 and 2013 with known estrogen receptor (ER) and progesterone receptor (PR) (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status reported to the SEER program. Pts with other primary either before or after breast cancer were excluded. Pt characteristics were compared between TS. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Results: We included 166,054 pts. Median age was 60 years (range 18-108). Median follow-up was 21 months (range 1-48). TS distribution was: 72.5% HR+/HER2-, 10.8% HR+/HER2+, 4.8% HR-/HER2+ and 12% triple negative (TN). Pts with HR+/HER2- tumors were older, had lower grade and presented with earlier stage (all p &lt; 0.0001). OS at 3 years for each subtype according to stage is shown in the table (p for interaction &lt; 0.0001). These differences in OS by TS continued to be significant for each stage in multivariate analysis adjusted for age, race, grade, histology and marital status. Conclusions: In this cohort, we observed significant differences in pt characteristics according to TS. Although HR+/HER2- tumors had better clinicopathologic features, the HR+/HER2+ group had the best OS in most stages. OS was significantly different by TS in each of the 4 stages and these results remained significant in the multivariate model. Pts with TN stage 1 tumors had similar OS as pts with HR+/HER2+ stage 2 tumors. Our results support the incorporation of TS as part of the staging variables in breast cancer. [Table: see text]
The asbestos fibre burden in human lungs: new insights into the chrysotile debate
Authors: Inke Sabine Feder, Iris Tischoff, Anja Theile, Inge Schmitz, Rolf Merget, Andrea Tannapfel
Journal: European Respiratory Journal (2017)

The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation. The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years. Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4–21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%). This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.
Correlation of pd-l1 staining in tumor cells and tumor infiltrate between primary tumors and matched metastasis in advanced colorectal cancer patients
Authors: Marco Tampellini, Enrico Falco, Giovanni De Rosa, Francesca Montarolo, Riccardo Dacomo, Chiara Baratelli, Elisa Sperti, Massimo Di Maio, Vittorio Scagliotti Giorgio, Marco Volante
Journal: Annals of Oncology (2017)
Results from the Belgian mantle cell lymphoma registry
Authors: vibeke Vergote, Ann Janssens, M André, c Bonnet, Van hende, E Van Den Neste, K Van Eygen, M Maerevoet, D Pranger, W Schroyens, S Debussche, Maertens, K Beel, J Lemmens, C Caron, Delrieu, I Van Den Broeck, G Vanstraelen, C Jacquy, L Schauvlieghe, H De Samblanx, Madoe, S Meers, D Boulet, G Verhoef, A Van Hoof
Journal: Journal of Allergy and Clinical Immunology (2017)
Transcription Factor RUNX1 Regulates Platelet <i>PCTP</i> (Phosphatidylcholine Transfer Protein): Implications for Cardiovascular Events
Authors: Guangfen Mao, Natthapol Songdej, Deepak Voora, Lawrence E. Goldfinger, Fabiola E. Del Carpio-Cano, Rachel A. Myers, A. Koneti Rao
Journal: Circulation (2017)

PCTP (phosphatidylcholine transfer protein) regulates the intermembrane transfer of phosphatidylcholine. Higher platelet PCTP expression is associated with increased platelet responses on activation of protease-activated receptor 4 thrombin receptors noted in black subjects compared with white subjects. Little is known about the regulation of platelet PCTP. Haplodeficiency of RUNX1, a major hematopoietic transcription factor, is associated with thrombocytopenia and impaired platelet responses on activation. Platelet expression profiling of a patient with a RUNX1 loss-of-function mutation revealed a 10-fold downregulation of the PCTP gene compared with healthy controls.We pursued the hypothesis that PCTP is regulated by RUNX1 and that PCTP expression is correlated with cardiovascular events. We studied RUNX1 binding to the PCTP promoter using DNA-protein binding studies and human erythroleukemia cells and promoter activity using luciferase reporter studies. We assessed the relationship between RUNX1 and PCTP in peripheral blood RNA and PCTP and death or myocardial infarction in 2 separate patient cohorts (587 total patients) with cardiovascular disease.Platelet PCTP protein in the patient was reduced by ≈50%. DNA-protein binding studies showed RUNX1 binding to consensus sites in ≈1 kB of PCTP promoter. PCTP expression was increased with RUNX1 overexpression and reduced with RUNX1 knockdown in human erythroleukemia cells, indicating that PCTP is regulated by RUNX1. Studies in 2 cohorts of patients showed that RUNX1 expression in blood correlated with PCTP gene expression; PCTP expression was higher in black compared with white subjects and was associated with future death/myocardial infarction after adjustment for age, sex, and race (odds ratio, 2.05; 95% confidence interval 1.6-2.7; P<0.0001). RUNX1 expression is known to initiate at 2 alternative promoters, a distal P1 and a proximal P2 promoter. In patient cohorts, there were differential effects of RUNX1 isoforms on PCTP expression with a negative correlation in blood between RUNX1 expressed from the P1 promoter and PCTP expression.PCTP is a direct transcriptional target of RUNX1. PCTP expression is associated with death/myocardial infarction in patients with cardiovascular disease. RUNX1 regulation of PCTP may play a role in the pathogenesis of platelet-mediated cardiovascular events.
Abstract 096: Activation of Delta-Opioid Receptors Regulates Cardiac MicroRNA Expression Under Hypoxia
Authors: Feng Zhi, Yilin Yang, Xiao-Zhou He, Harleen K Sandhu, Xuezhi Kang, Dongman Chao, Rong Wang, Dong H Kim, Ying Xia
Journal: Circulation Research (2013)

Delta-opioid receptors (DOR) are involved in cardioprotection under hypoxia/ ischemia. However, the underlying mechanism is not well understood yet. We have recently shown that DOR activation significantly modify the expression of hypoxia-sensitive microRNAs (miRNAs) in the brain and kidney. In extension, we further investigated if DOR activation can regulate cardiac miRNAs in hypoxia. We compared global changes in miRNA gene expression in the rat heart following exposure to hypoxia for 10 days with those in normoxia using a low density miRNA microarray to delineate hypoxia-induced changes in the miRNA expression. The up-regulated miRNAs from the microarray analysis were selected for further investigating their response to hypoxia and DOR activation with a DOR agonist, UFP-512 after 1, 5, and 10 days. We found that 1) miR-376a increased after 1-day hypoxia and progressively increased with hypoxic duration; 2) miR-7b, miR-107, miR-134, miR-135a, miR-193a-3p, miR-196a and miR-324-3p progressively increased after 1-day hypoxia and reached a peak after 5-days; 3) miR-7a, miR-141, miR-196c, miR-200a, miR-200b, miR-203a and miR-324 increased only after 1-day hypoxia and significantly decreased after 5-10 days of hypoxia; 4) miR-128a did not significantly change after 1-10 days of hypoxia. After DOR activation with UFP-512, miR-128a, miR-135a, miR-193a-3p, miR-196a, miR-200a, miR-324-3p and miR-338 continued to increase after 1-day hypoxia, and then decreased after 5-10 days of hypoxia; 5) miR-7b and miR-134, in the condition of DOR activation, increased after 1-day hypoxia and further increased after 5-day hypoxia, while significantly decreased after 10-day exposure. In contrast, some miRNAs like miR-350 decreased in response to hypoxia, while DOR activation almost completely reversed such hypoxic reduction. These results suggest that cardiac miRNAs differentially respond to hypoxic stress with a variable degree directly related to the duration of hypoxic exposure, and DOR activation can regulate such hypoxic responses. Supported by HD034852 , AT004422 , NSFC31071046, CS20102010, ZD201007 , CY 20119004,CY20120003, STCSM10DZ1975800,NBRP09CB522901 &amp; 12CB518502.
Growing Discomfort With Comfort Care for Hypoplastic Left Heart Syndrome: Why We Should Still Defer to Parental Wishes
Authors: Erin A. Paul, Elizabeth M. Kohlberg, Kristina Orfali
Journal: The American Journal of Bioethics (2017)

"Growing Discomfort With Comfort Care for Hypoplastic Left Heart Syndrome: Why We Should Still Defer to Parental Wishes." The American Journal of Bioethics, 17(7), pp. 67–68
Persistent and inducible neogenesis repopulates progenitor renin lineage cells in the kidney
Authors: Linda Hickmann, Anne Steglich, Michael Gerlach, Moath Al-Mekhlafi, Jan Sradnick, Peter Lachmann, Maria Luisa S. Sequeira-Lopez, R. Ariel Gomez, Bernd Hohenstein, Christian Hugo, Vladimir T. Todorov
Journal: Kidney International (2017)