tbuckley/cabot-search huggingface dataset:
Tracing the Roots of Cancer Evolution
Authors: Yanwen Jiang, Olivier Elemento
Journal: Cancer Discovery (2014)

Abstract Summary: By comparing the genomes of progenitor cells and mature cells of lymphoid and myeloid lineages in patients with chronic lymphocytic leukemia (CLL), Damm and colleagues confirmed that CLL originates from preleukemic CD34+ progenitor cells and identified early CLL mutations that are associated with these progenitor cells. Moreover, they discovered that deregulation of B-cell receptor signaling may be one of the hallmarks of CLL, particularly in tumors with EGR2 mutations. Cancer Discov; 4(9); 995–7. ©2014 AACR. See related article by Damm et al., p. 1088
Corin Gene Minor Allele Defined by 2 Missense Mutations Is Common in Blacks and Associated With High Blood Pressure and Hypertension
Authors: Daniel L. Dries, Ronald G. Victor, J. Eduardo Rame, Richard S. Cooper, Xiaodong Wu, Xiaofeng Zhu, David Leonard, Su-Inn Ho, Qingyu Wu, Wendy Post, Mark H. Drazner
Journal: Circulation (2005)

Background— The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes. Method and Results— This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in &amp;12% of blacks but was extremely rare in whites (&lt;0.5% were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension (odds ratio, 1.63; 95% CI, 1.11 to 2.38; P =0.013). The corin I555 (P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7±20.7 versus 129.4±17.4 mm Hg; P =0.029) and adjusted (132.5±1.6 versus 128.9±0.6 mm Hg; P =0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis (odds ratio, 1.50; 95% CI, 1.09 to 2.06; P =0.014). In addition, the association of the minor corin I555 (P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8±1.9 versus 121.4±0.7 mm Hg; P =0.03). Conclusions— The corin I555 (P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension.
Abstract 1145: Cytoplasmic p27 promotes epithelial-mesenchymal transition and tumor progression via Twist1 upregulation
Authors: Dekuang Zhao, Alexandra H. Besser, Wen Zhou, Seth A. Wander, Jun Sun, Michael Durante, Feng Hong, Bin Wang, Tan Ince, Karoline Briegel, Joyce M. Slingerland
Journal: Cancer Research (2014)

Abstract p27 is a cell cycle regulator that acts largely to restrain normal cell growth. It is rarely mutated or deleted in human cancers, but is often degraded or mislocalized to the cytoplasm in aggressive tumors. Phosphorylation at T157 or T198 by different PI3K effector kinases leads to p27 cytoplasmic accumulation and enhanced cell motility and invasion in part via effects on the actin cytoskeleton, which are independent of its cell cycle role. However, the functional contributions of C-terminally phosphorylated, cytoplasmic p27 to cancer progression remain poorly understood. Targeted inhibition of PI3K/mTOR impaired tumor cell motility and metastasis via modulation of p27 in a bone metastatic model (Wander, S. et al. BCRT 2013). We observed that p27 knockdown in highly metastatic cancer lines with high levels of cytoplasmic p27pT157pT198 reverted EMT and impaired tumor cell invasion in vitro and metastasis in vivo. This led us to investigate whether PI3K-activated, phosphorylated p27 may function as a novel EMT regulator. A cell cycle defective (CK-) and double phosphomimetic p27 mutant (T157D/T198D or DD) was introduced into immortal human mammary epithelial cells with low PI3K activity. This revealed a novel, oncogenic function of p27 in regulating tumor progression, in that p27CK-DD induced epithelial-mesenchymal transition (EMT) and soft agar colony formation. p27CK-DD also increased motility, invasion and formation of metastasis in bladder and breast cancer models. A RT-PCR screen for potential p27-induced EMT mediators revealed a 20-fold increase in expression of the Twist1 transcription factor in p27CK-DD-transduced cells. Knockdown of Twist reversed the p27CK-DD-mediated increase in EMT marker expression. p27 knockdown rapidly attenuated Twist1-promoter activity and reduced Twist1 mRNA levels and also increased E-cadherin expression in metastatic cells, suggesting that Twist1 may play a critical role in p27CK-DD-induced EMT. These data extend our understanding of p27 function in human cancer and suggest that PI3K deregulated p27 may promote EMT and tumor metastasis through transcriptional activation of TWIST1. Citation Format: Dekuang Zhao, Alexandra H. Besser, Wen Zhou, Seth A. Wander, Jun Sun, Michael Durante, Feng Hong, Bin Wang, Tan Ince, Karoline Briegel, Joyce M. Slingerland. Cytoplasmic p27 promotes epithelial-mesenchymal transition and tumor progression via Twist1 upregulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1145. doi:10.1158/1538-7445.AM2014-1145
Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Detected by Clonotypic Polymerase Chain Reaction Despite Continuous Pathologic Remission Induced by Involved-Field Radiotherapy
Authors: Ariela Noy, Joachim Yahalom, Leah Zaretsky, Ian Brett, Andrew D. Zelenetz
Journal: Journal of Clinical Oncology (2005)

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is indolent and often associated with Helicobacter pylori bacterial infection. H pylori-independent MALT develops either in the absence of the bacteria or persists after bacterial eradication. We have previously demonstrated long-term pathologic remission after involved-field radiotherapy therapy (IFRT). We determined molecular remission status by clonotypic polymerase chain reaction (PCR).Twenty-four consecutive patients with stage I to IIE gastric MALT lymphoma who obtained a pathologic remission after IFRT alone were evaluated. All had at least two follow-up endoscopic gastroduodenal biopsies at Memorial Sloan-Kettering Cancer Center. IFRT median dose was 30 Gy (range, 28.5 to 43.5 Gy). Post-treatment biopsies were subjected to semi-nested clonotypic PCR.All patients obtained a complete response based on routine immunohistochemical pathologic analysis of random post-treatment gastric biopsies. Median follow-up from completion of IFRT was 63 months (range, 19 to 117 months). Event-free survival was 96%; 23 of 34 patients remained in clinical and pathologic complete remission. Baseline DNA extraction yielded 17 clone-specific primer pairs. At the first follow-up test, 14 of 17 pairs were PCR positive. Eight remained persistently positive; and one was persistently negative. Others were intermittently positive.Despite sustained biopsy-proven remissions for as long as 117 months after radiation, the vast majority of patients remain positive by clonotypic PCR. This suggests that the malignant clone is present but missing either an internal or external signal essential to the cancer phenotype. One possibility is that radiation eradicates the polyclonal H pylori-specific T cells eliminating critical local factors necessary for proliferation of the monoclonal B cells.
The fate of pentagastrin
Authors: Brian H. Stagg, John M. Temperley, John H. Wyllie
Journal: Gut (1971)

Pentagastrin is rapidly removed from the circulation of the dog.It is excreted by the liver into the bile, largely in an inactivated form.Preliminary results indicate that it meets the same fate in man. BIOASSAYThe anaesthetized rat preparation of Smith, Lawrence, Colin-Jones, and Schild (1970) was used to measure pentagastrin in plasma and bile.Standard and test doses of pentagastrin were injected intra- 825 on August 20,
Engagement of Glycoprotein IIb/IIIa (α <sub>IIb</sub> β <sub>3</sub> ) on Platelets Upregulates CD40L and Triggers CD40L-Dependent Matrix Degradation by Endothelial Cells
Authors: Andreas E. May, Thorsten Kälsch, Steffen Massberg, Yared Herouy, Roland Schmidt, Meinrad Gawaz
Journal: Circulation (2002)

Background— CD40L-CD40 interactions induce inflammatory signals in cells of the vascular wall. We evaluated the effects of glycoprotein (GP) IIb/IIIa (α IIb β 3 ) engagement that occurs during platelet-endothelium interactions on CD40L surface exposure on platelets and initiation of proteolytic activity in human umbilical vein endothelial cells (HUVECs). Methods and Results— Transient (60-minute) adhesion of thrombin-prestimulated platelets enhanced HUVEC expression of urokinase-type plasminogen activator receptor and membrane type-1 matrix metalloproteinase (MT1-MMP) (reverse transcriptase–polymerase chain reaction, flow cytometry) and secretion of urokinase-type plasminogen activator, tissue-type plasminogen activator, and MMP-1 (ELISA) and induced proteolytic activity via MMP-2 and MMP-9 (gelatin zymography). These effects were abrogated by hindrance of physical platelet-endothelial contacts using transwell systems or inhibited by GRGDSP, mAbs anti–GP IIb/IIIa (7E3), anti-α v β 3 (LM609), or anti-CD40L (TRAP1). In addition, MMP-2 and MMP-9 were inhibited by specific GP IIb/IIIa antagonists tirofiban, lamifiban, or integrelin. On endothelial cells, induction of proteolytic activity by activated platelets was mimicked by CD40 engagement using soluble CD40L but not affected by antibody clustering of α v β 3 . On platelets, CD40L and CD62P exposure was enhanced on adhesion to HUVECs or immobilized fibrinogen and was abrogated by GRGDSP or LM609. In suspension, cross-linking of GP IIb/IIIa by fibrinogen plus secondary mAb upregulated CD40L surface exposure. Consistently, bivalent mAb 7E3 upregulated CD40L, whereas ligation of GP IIb/IIIa by soluble fibrinogen alone or monovalent Fab-fragment c7E3 had no effect. Conclusions— Platelet adhesion via GP IIb/IIIa upregulates CD40L and CD62P surface exposure. Proteolytic activity of HUVEC is induced by the concerted action of β 3 -integrin–mediated platelet adhesion and subsequent CD40L-induced signals in HUVECs. Effective anti–GP IIb/IIIa or anti-CD40L strategies might, therefore, contribute to plaque stabilization.
Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination of the Peripheral and Central Nervous System
Authors: Bastian G. Brinkmann, Amit Agarwal, Michael W. Sereda, Alistair N. Garratt, Thomas Müller, Hagen Wende, Ruth M. Stassart, Schanila Nawaz, Christian Humml, Viktorija Velanac, Konstantin Radyushkin, Sandra Goebbels, Tobias M. Fischer, Robin J. Franklin, Cary Lai, Hannelore Ehrenreich, Carmen Birchmeier, Markus H. Schwab, Klaus Armin Nave
Journal: Neuron (2008)
How do respiratory state and measurement method affect bra size calculations?
Authors: D E McGhee, J R Steele
Journal: British Journal of Sports Medicine (2006)

Objectives: To investigate the effects of respiratory state and measurement method on bra size calculation. Methods: The bra sizes of 16 large-breasted women were measured during two respiratory states, end voluntary inspiration and relaxed voluntary expiration, and using two sizing methods, which were compared against subject-reported bra sizes. Results: Both respiratory state and measurement method significantly affected bra size estimations, whereby measuring chest circumference during inspiration increased both band and decreased cup size. However, whereas bra size calculated using the standard method differed significantly from subject-reported bra size, cup size calculated using the breast hemi-circumference method did not differ significantly from subject-reported cup size. Conclusions: As respiratory state significantly affects bra sizes, it should be standardised during bra size measurements. A more valid and reliable bra sizing method should be developed, possibly using the breast hemi-circumference method for cup size estimations and raw under-bust chest circumference values for band size.
Coronary Stent Fracture Complicated Multiple Aneurysms Confirmed by 3-Dimensional Reconstruction of Intravascular-Optical Coherence Tomography in a Patient Treated With Open-Cell Designed Drug-Eluting Stent
Authors: Sunwon Kim, Chang-Soo Kim, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Seung-Woon Rha, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh, Hongki Yoo, Jin Won Kim
Journal: Circulation (2014)
Critical Appraisal in Clinical Practice: Sometimes Irrelevant, Occasionally Invalid
Authors: Aravinthan Coomarasamy, Pallavi Latthe, Spyros Papaioannou, Mary Publicover, Harry Gee, Khalid S Khan
Journal: Journal of the Royal Society of Medicine (2001)

A core activity of evidence-based practice is the search for and appraisal of evidence on specific clinical issues. Clinicians vary in their competence in this process; we therefore developed a 16-item checklist for quality of content (relevance and validity) and presentation (useability, attribution, currency and contact details). This was applied to a set of 55 consecutive appraisals conducted by clinicians and posted at a web-based medical journal club site. Questions were well formulated in 51/55 (92%) of the appraisals. However, 22% of appraisals missed the most relevant articles to answer the clinical question. Validity of articles was well appraised, with methodological information and data accurately extracted in 84% and accurate conversion to clinically meaningful summary statistics in 87%. The appraisals were presented in a useable way with appropriate and clear bottom-lines stated in 95%. The weakest link in production of good-quality critical appraisals was identification of relevant articles. This should be a focus for evidence-based medicine and critical appraisal skills.
Opportunities for Enhancing the FDA Guidance on Pharmacovigilance
Authors: Bruce M. Psaty
Journal: JAMA (2008)

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
Obesity increases the risk of incident asthma among adults
Authors: E. Ronmark
Journal: European Respiratory Journal (2005)

The annual incidence of asthma in adults in northern Sweden has been estimated at 2.3 per thousand population. Risk factors for incident asthma among adults were studied in a case–referent study based on incident cases of asthma during 1995–1999. The healthcare providers reported suspected cases of incident asthma. After clinical examination, 309 (65% female) of 473 reported subjects were included. Inclusion criteria were a history of incident asthma (onset &lt;12 months) and verified bronchial variability. Referents were randomly selected and stratified by age, sex and area of residence. The significant risk factors were hay fever, a family history of asthma, ex-smoking status and elevated body mass index (25.0–29.9 and ≥30). The risk factor pattern was similar for females and males, and increased body mass index was a significant risk factor for both males and females, as well as for allergic and nonallergic subjects. In conclusion, in addition to hay fever, a family history of asthma, allergic sensitisation and ex-smoking status, increased body mass index was a significant risk factor for incident asthma independent of sex and allergic status.
American Surgery and the Affordable Care Act
Authors: Steven C. Stain, David B. Hoyt, John G. Hunter, Geoffrey Joyce, Jonathan R. Hiatt
Journal: JAMA Surgery (2014)

The Affordable Care Act (ACA) attempts to change the way we finance and deliver health care by coordinating the delivery of primary, specialty, and hospital services in accountable care organizations. The ways in which accountable care organizations will develop and evolve is unclear; however, the effects on surgeons and their patients will be substantial. High-value care in the ACA emphasizes quality, safety, resource use and appropriateness, and the patient's experience of care. Payment will be linked to these principles. Department chairs overseeing a clinical enterprise in academic medical centers now must add financial and quality measures to the traditional missions of education, research, and clinical service. At a time when surgical training is in dramatic evolution, with work hour limitations for residents and an emphasis on quality, productivity, and increasing oversight of trainees for faculty, residency programs will need to meet the increasing demands of an aging population and newly insured patients under the ACA. The American College of Surgeons, with its century-long commitment to quality improvement, research-based standards, and performance measurement and verification, has begun its Inspiring Quality Campaign, is developing new educational tools, and is preparing proposals for payment reform based on surgeons' participation in quality programs.
Deposits of alpha 2M in the rheumatoid synovial membrane.
Authors: E D Flory, B J Clarris, K D Muirden
Journal: Annals of the Rheumatic Diseases (1982)

Synovial tissue from patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and having menisectomies was examined by immunofluorescence for deposits of alpha-2-macroglobulin (alpha 2M). In inflammed tissues, alpha 2M was found in the synovial lining cells and in perivascular cells. The amount of alpha 2M correlated with the degree of inflammation. Similarly, free lining cells obtained by trypsination of the intact synovial membrane contained identical inclusions. alpha 2M was not detected in the menisectomy cases and in the less inflammatory osteoarthritic specimens. In-vitro studies demonstrated uptake of alpha 2M-trypsin complexes but not of native alpha 2M by most of the cultured synovial cells whether they came from rheumatoid patients or controls. The internalised complexes disappeared within 12 hours of culture. The results suggest that alpha 2M-proteinase complexes formed in the joint are taken up by phagocytic and perivascular cells in a similar way to immune complexes.
A Minimal Ksp-Cadherin Promoter Linked to a Green Fluorescent Protein Reporter Gene Exhibits Tissue-Specific Expression in the Developing Kidney and Genitourinary Tract
Authors: Xinli Shao, Jane E. Johnson, James A. Richardson, Thomas Hiesberger, Peter Igarashi
Journal: Journal of the American Society of Nephrology (2002)

Ksp-cadherin is a unique, tissue-specific member of the cadherin family of cell adhesion molecules that is expressed exclusively in tubular epithelial cells in the kidney and developing genitourinary (GU) tract. Transgenic mice carrying 3425 bp of the Ksp-cadherin 5' flanking region linked to a lacZ reporter gene express beta-galactosidase exclusively in the kidney, although the expression pattern is incomplete (Am J Physiol 277: F599-F610, 1999). To further define the region that mediates tissue-specific expression, transgenic mice carrying 1341 bp or 324 bp of the 5' flanking region linked to a green fluorescent protein (GFP) reporter gene were produced. Transgenic mice carrying 1341 bp of the 5' flanking region expressed GFP in all embryonic tissues that endogenously express Ksp-cadherin, including the ureteric bud, Wolffian duct, Müllerian duct, and developing tubules in the mesonephros and metanephros. In the adult kidney, GFP was highly expressed in thick ascending limbs of Henle's loops and collecting ducts and weakly expressed in proximal tubules and Bowman's capsules. Transgenic mice carrying 324 bp of the 5' flanking region exhibited expression exclusively in tubular epithelial cells in the developing kidney and GU tract. Immunoblot analysis showed that the expression of GFP was restricted to the kidney in adult mice. Taken together, these results demonstrate that 324 bp of the Ksp-cadherin 5' flanking region is sufficient to direct epithelial-specific expression in the developing kidney and GU tract. Transgenic mice that express GFP in the mesonephros, metanephros, ureteric bud, and sex ducts may be useful for cell lineage studies.
Ileal Crohn's disease is best treated by surgery
Authors: A C J Windsor
Journal: Gut (2002)

<h3>Aim</h3> To investigate the impact of newspaper use in a year of increased coverage of litigation against the tobacco industry on youths9 beliefs about the health risks of ‘light’ cigarettes, and examine relations between inaccurate beliefs about ‘lights’, perceptions of risk and intentions to quit smoking. <h3>Participants</h3> The data come from the 2004 National Annenberg Survey of Youth, a representative random digit dial telephone survey of youths aged 14–22 years in the USA (n=1501; current smokers, n=305; ‘lights’ smokers, n=112). <h3>Design</h3> All youths were asked about newspaper use and beliefs regarding ‘light’ cigarettes (riskiness, addictiveness, ease of quitting). Smokers reported on risk perceptions and quitting intentions. We also examined changes in newspaper coverage related to ‘lights’ from January 2001 to April 2004. <h3>Results</h3> Newspaper coverage related to ‘lights’ increased in the first months of 2003, and continued into 2004. Logistic regression analyses suggest that ‘lights’ smokers with lower levels of newspaper use were most likely to hold inaccurate beliefs about ‘lights’ (OR=5.93, 95% CI 1.48 to 23.77). Smokers of ‘lights’ with inaccurate beliefs were less likely to perceive their smoking as risky (OR=0.29, 95% CI 0.11 to 0.87), and smokers with inaccurate beliefs were less likely to have strong quitting intentions (OR=0.52, 95% CI 0.28 to 0.96). <h3>Conclusions</h3> Inaccurate beliefs about the risks of ‘lights’ were negatively related to youth smokers9 perceptions of risk and intentions to quit smoking. News coverage surrounding the tobacco industry9s failure to disclose these risks might help reduce these inaccurate, and potentially dangerous, beliefs.