tbuckley/cabot-search huggingface dataset:
Abstract IA9-1: Is taxol resistance related to tubulin isotypes?
Authors: Susan Band Horwitz
Journal: Clinical Cancer Research (2010)

Abstract Microtubules are an important component of the euraryotic cytoskeleton and are essential for normal cell division. They are also a validated target for antitumor drugs, such as taxol, that bind to the – tubulin subunit in the microtubule polymer. Endogenous resistance or the development of drug resistance during treatment with taxol is a serious clinical problem. Understanding the emergence of taxol resistance and being able to predict patient response would enhance the efficacy of the drug. A number of mechanisms, such as overexpression of P-glycoprotein that acts as an ATP-dependent drug-efflux pump, or mutations in the drug-binding site in tubulin, have been described. Of particular interest to our research, is the aberrant expression of β-tubulin isotypes in cancer. Tubulin is composed of α- and β-tubulin subunits that exist as heterodimers. In humans, there are seven β-tubulins and eight β-tubulins, each the product of a distinct gene located on different chromosomes. Each isotype can undergo extensive posttranslational modifications such as acetylation, phosphorylation, polyglutamylation, polyglycylation and reversible tyrosination, all of which add to the complexity of the tubulin/microtubule system. Most of the divergence between the isotypes is found in the last 15-20 amino acids at the carboxyl end of tubulin and in addition, most posttranslational modifications of tubulin occur in this region. For the most part, tubulin isotypes have been detected at the mRNA level or at the protein level with isotype-specific antibodies. Our laboratory has developed proteomic methods, including highresolution isoelectrofocusing, CNBr cleavage and mass spectrometry that allow us to determine the isotype content and posttranslational modifications of tubulin in cells and tissues in a single experiment. We have utilized taxol, which enhances tubulin polymerization, to isolate sufficient tubulin from cells and are developing methods to quantify tubulin isotype expression by mass spectrometry. The overexpression of βIII-tubulin has been associated with resistance to taxanes in a range of tumor types and in taxol-resistant cells generated in our laboratory. βIII-tubulin is normally expressed only in neuronal cells. However, it is aberrantly expressed in numerous malignant tissues and could be a meaningful prognostic factor for treatment outcome. As has been shown by others in different tumors, in our laboratory an immunohistochemical analysis of 47 tumor specimens from head and neck patients determined that overexpression of β-III tubulin was highly prognostic of survival. Citation Information: Clin Cancer Res 2010;16(14 Suppl):IA9-1.
STAT3 is constitutively phosphorylated on serine 727 residues, binds DNA, and activates transcription in CLL cells
Authors: Inbal Hazan-Halevy, David Harris, Zhiming Liu, Jie Liu, Ping Li, Xiaomin Chen, Sreejesh Shanker, Alessandra Ferrajoli, Michael J. Keating, Zeev Estrov
Journal: Blood (2010)
One in seven beds could go in the Netherlands
Authors: T Sheldon
Journal: BMJ (1994)

One in seven acute hospital beds in the Netherlands should be lost by 2000 and more space should be given to outpatient departments, said a government advisory body last week. These adjustments in hospital planning reflect changes in the use of the Dutch health service. During the 1980s the average length of hospital stays dropped 2.5% every year, while first visits to outpatient departments shot up from three million to nearly six million a year.

Six months ago Health Minister Hans Simons asked the National Board for Hospital Facilities to reconsider the …
Serum Antibody to Inner Ear Proteins in Patients With Progressive Hearing Loss
Authors: Richard A. Moscicki
Journal: JAMA (1994)

To test whether detection of serum antibody to a 68-kd inner ear protein distinguishes among different causes of sensorineural hearing loss, and identifies patients with active disease and those likely to respond to corticosteroid therapy.Serum samples were tested by Western blot using bovine inner ear extract as antigen, and results were correlated with patient information obtained by chart review.Referral center.Serum samples were obtained from patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPBSNHL) (n = 72) otosclerosis (n = 11), Cogan's syndrome (n = 8), patients with positive tests for antinuclear antibodies (n = 10), and normal controls (n = 53).Detection of serum antibody to a 68-kd inner ear protein.Serum from 42 to 72 patients with IPBSNHL reacted with a 68-kd protein constituent of inner ear extract. This reactivity was not detected in serum from 11 of 11 patients with otosclerosis, or in eight of eight with Cogan's syndrome. It was found in serum from one of 10 patients with a positive test for antinuclear antibody and in one of 53 normal controls. Antibody to the 68-kd protein was detected in serum from 89% of patients with actively progressing IPBSNHL and none of the 25 patients with inactive disease (P < .001). Patients who were antibody-positive responded to steroid treatment more frequently than did those who were antibody-negative (P < .001).These results indicate that the presence of circulating antibody to a 68-kd constituent of bovine inner ear extract serves as a marker for IPBSNHL and that its presence correlates with disease activity and responsiveness to corticosteroid treatment.
P3-125: Similar characteristics of responders treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) Gefitinib and Erlotinib for advanced non small cell lung cancer (NSCLC) in a single Canadian institution.
Authors: Shannon Otsuka, Bruce Musgrave, Salina Chan, Tony Magliocco, Cynthia Card, Desiree Hao, Don Morris, Gwyn Bebb
Journal: Journal of Thoracic Oncology (2007)
Treating major depression in children and adolescents
Authors: Kenneth D Shenderey
Journal: BMJ (2004)

Screening without evidence of efficacy Thyroid ultrasonography is another exampleEditor-I agree with Law's view of screening, that screening of unproved value should not be advocated. 1 As a clinical endocrinologist I often have to deal with patients' anxieties about non-palpable incidental findings on thyroid ultrasonography, often performed for wrong or unjustified reasons.Sometimes patients arrive with already established surgical complications after unnecessary thyroid operations.Although a substantial number of incidental thyroid nodules may be histologically malignant, 2 their clinical importance has never been proved.A recent preliminary study indicates that the progression rate of non-palpable proved thyroid malignant nodules to clinically significant lesions may be very low. 3 Thyroid ultrasonography is an additional example of an often used, often non-efficacious screening modality that may lead to "cascade iatrogenesis." 4
A6.7 Evaluation of<i>porphyromonas gingivalis</i>serology in rheumatic and non-rheumatic inflammatory disease
Authors: M Rinaudo-Gaujous, A Moreau, V Blasco-Baque, X Roblin, C Genin, T Thomas, S Paul, H Marotte
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) interest for RA development disease is growing fast since it is the only bacteria able to citrullinate peptides and may induce autoimmune response through development of ACPA. However, few studies have reported its presence in others inflammatory diseases. The aim of this study is to evaluate the specificity of <i>P. gingivalis</i> and <i>Prevotella intermedia</i> (<i>P. intermedia</i>) serology in patients with rheumatic diseases including rheumatoid arthritis (RA) and spondylarthritis (SA) compared to controls (healthy subjects or patients with inflammatory bowel disease (IBD)). <h3>Methods</h3> We enrolled in this study 79 RA patients, 56 SA patients and 39 IBD patients requiring infliximab therapy, as well as 30 healthy controls. Anti-<i>P. intermedia</i> antibodies and anti-<i>P. gingivalis </i>LPS specific and whole extract antibodies were determined by ELISA. Specificity of these antibodies was evaluated by the search for antibodies against a commensal bacterium of the intestinal tract: <i>Escherichia Coli (E. coli).</i> <h3>Results</h3> Anti-<i>P. gingivalis</i> antibody titers determined by LPS and whole extract were well correlated together (P &lt; 0.0001) as well as antibody titers against the two oral bacteria (<i>P. gingivalis</i> and <i>P. intermedia</i>) (P &lt; 0.0001). By using LPS from <i>E. coli</i>, no cross reaction was observed as high anti-<i>P. gingivalis</i> antibody titers were negative for anti-<i>E. coli</i> antibody and <i>vice versa.</i> Anti-P. gingivalis antibodies titers were higher in RA and SA patients than in healthy subjects (P &lt; 0.0001) or in IBD patients (P&lt; 0.0001). Moreover, there was a trend for higher titers in RA patients than in SA patients (Fig 1A). Same results were found with anti-<i>P. intermedia</i> antibody titers which were higher in RA and SA patients than in healthy controls (P &lt; 0.0001) or IBD patients (P &lt; 0.0001) (Fig 1B). <h3>Conclusions</h3> <i>P. gingivalis</i> and <i>P. intermedia</i> are oral bacteria having an important role in rheumatic diseases, especially in RA, compared to another inflammatory disease as shown by higher titers of antibodies found in both RA and SA.
Role of nitric oxide, muscarinic receptors, and the ATP-sensitive K+ channel in mediating the effects of acetylcholine to mimic preconditioning in dogs.
Authors: Z Yao, G J Gross
Journal: Circulation Research (1993)

The aims of the current study were to examine the efficacy of acetylcholine (ACh) to mimic ischemic preconditioning in dogs and to determine the role of nitric oxide (NO), muscarinic receptors, and ATP-sensitive K+ (KATP) channels in mediating its effects. Barbital-anesthetized open-chest dogs were subjected to 60 minutes of left anterior descending coronary artery (LAD) occlusion followed by 4 hours of reperfusion. Preconditioning was elicited by 10 minutes of LAD occlusion followed by 10 minutes of reperfusion before the 60-minute occlusion period. ACh (3 or 10 micrograms/min) or an equivalent volume of saline was infused into the LAD for 10 minutes, followed by a 10-minute drug-free period before the 60-minute ischemic insult. In other groups, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA, 4 mg/min), the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 3 mg/min), or the specific KATP channel blocker 5-hydroxydecanoate (5-HD, 3 mg/min) was infused with ACh into the LAD for 10 minutes. The infusion of L-NAME, L-NMMA, or 5-HD was started 2 minutes before ACh infusion. Transmural myocardial blood flow was measured at 5 minutes of occlusion, and infarct size was determined by triphenyltetrazolium staining and expressed as a percentage of the area at risk. There were no significant differences in collateral blood flow or the area at risk between groups. Preconditioning produced a marked reduction (P &lt; .05) in infarct size (6.2 +/- 3.0% versus 26.1 +/- 5.7% in the control group).(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory Tests: Bills and Costs
Authors: MICHAEL B. SIMSON
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 November 1971Laboratory Tests: Bills and CostsMICHAEL B. SIMSON, M.D.MICHAEL B. SIMSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-5-803_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the analysis of laboratory costs by Drs. Griner and Liptzin (Ann Intern Med 75:157-163, 1971) they do not distinguish between charges made to the patient and actual expense to the hospital. A wide discrepancy typically exists between these two figures. For example, the expense to the Hospital of the University of Pennsylvania for the entire process of measuring serum electrolytes, blood urea nitrogen, and glucose, from venipuncture by a technician to computer reporting, is roughly $3.00. The inpatient is billed $74.40.If one calculates from patient bills, one will seriously overestimate the contribution to total hospital... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hospital of the University of Pennsylvania Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1971Volume 75, Issue 5Page: 803-804KeywordsBlood urea nitrogenComputersGlucoseInpatientsLaboratory testsPhlebotomyResearch laboratoriesSaltsTechnicians Issue Published: 1 November 1971 PDF DownloadLoading ...
3,3′-Diindolylmethane Is a Novel Mitochondrial H+-ATP Synthase Inhibitor that Can Induce p21Cip1/Waf1 Expression by Induction of Oxidative Stress in Human Breast Cancer Cells
Authors: Yixuan Gong, Heesook Sohn, Ling Xue, Gary L. Firestone, Leonard F. Bjeldanes
Journal: Cancer Research (2006)

Abstract Epidemiologic evidence suggests that high dietary intake of Brassica vegetables, such as broccoli, cabbage, and Brussels sprouts, protects against tumorigenesis in multiple organs. 3,3′-Diindolylmethane, one of the active products derived from Brassica vegetables, is a promising antitumor agent. Previous studies in our laboratory showed that 3,3′-diindolylmethane induced a G1 cell cycle arrest in human breast cancer MCF-7 cells by a mechanism that included increased expression of p21. In the present study, the upstream events leading to p21 overexpression were further investigated. We show for the first time that 3,3′-diindolylmethane is a strong mitochondrial H+-ATPase inhibitor (IC50∼20 μmol/L). 3,3′-Diindolylmethane treatment induced hyperpolarization of mitochondrial inner membrane, decreased cellular ATP level, and significantly stimulated mitochondrial reactive oxygen species (ROS) production. ROS production, in turn, led to the activation of stress-activated pathways involving p38 and c-Jun NH2-terminal kinase. Using specific kinase inhibitors (SB203580 and SP600125), we showed the central role of p38 and c-Jun NH2-terminal kinase (JNK) pathways in 3,3′-diindolylmethane-induced p21 mRNA transcription. In addition, antioxidants significantly attenuated 3,3′-diindolylmethane-induced activation of p38 and JNK and induction of p21, indicating that oxidative stress is the major trigger of these events. To further support the role of ROS in 3,3′-diindolylmethane-induced p21 overexpression, we showed that 3,3′-diindolylmethane failed to induce p21 overexpression in mitochondrial respiratory chain deficient ρ0 MCF-7 cells, in which 3,3′-diindolylmethane did not stimulate ROS production. Thus, we have established the critical role of enhanced mitochondrial ROS release in 3,3′-diindolylmethane-induced p21 up-regulation in human breast cancer cells. (Cancer Res 2006; 66(9): 4880-7)
Mutations in GATA2 cause human NK cell deficiency with specific loss of the CD56bright subset
Authors: Emily M. Mace, Amy P. Hsu, Linda Monaco-Shawver, George Makedonas, Joshua B. Rosen, Lesia Dropulic, Jeffrey I. Cohen, Eugene P. Frenkel, John C. Bagwell, John L. Sullivan, Christine A. Biron, Christine Spalding, Christa S. Zerbe, Gulbu Uzel, Steven M. Holland, Jordan S. Orange
Journal: Blood (2013)
Transureteral Phonocatheter Recording of the Renal Arterial Pulse.
Authors: Herbert L. Tanenbaum
Journal: Annals of Internal Medicine (1964)

s1 April 1964Transureteral Phonocatheter Recording of the Renal Arterial Pulse.Herbert L. Tanenbaum, M.D. (Associate), William S. Kiser, M.D.Herbert L. Tanenbaum, M.D. (Associate)Search for more papers by this author, William S. Kiser, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-739_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptHypertensive patients suspected of having renal vascular lesions are frequently studied by splitrenal function tests requiring bilateral ureteral catheterization. These studies intend to demonstrate increased water reabsorption by the ischemic kidney. The present study extends the information obtained during the retrograde ureteral catheterization by passing small phonocatheters, used in cardiac catheterization technics, into each ureter. The renal arterial pulse may be recorded indirectly with a phonocatheter tip in the respective renal pelvis. The pulse tracings from each kidney are compared as to relative amplitude and the presence or absence of bruits.In patients with renal vascular occlusions, there was a... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe Phonorenogram: Transureteral Phonocatheter Recording of the Renal Artery Pulse in the Diagnosis of Renal Vascular Disease 1 April 1964Volume 60, Issue 4Page: 739-739KeywordsCatheterizationHeart rateKidneysLesionsPelvisUreter Issue Published: 1 April 1964 PDF DownloadLoading ...
Coordinating health research to promote action: the Tanzanian experience
Authors: A. Y Kitua
Journal: BMJ (2000)

Developing countries carry 90% of the global burden of disease. Infections such as malaria and HIV are debilitating their economies by killing the young and economically productive workforce. Research is essential for health development, yet less than 10% of the annual global expenditure on health research is allocated to addressing developing countries' problems.1 Poor countries must face this challenge seriously. It is essential that they create strong national research infrastructures so that they can define priorities for health research priorities; influence national, regional, and global health agendas; and lobby for a more equitable allocation of resources. This paper discusses some of the barriers to establishing coordinated health research programmes in developing countries and describes how Tanzania has developed a new research model to try and overcome these.

#### Summary points

The failure of the malaria eradication programme in some developing countries illustrates the failure of those countries to coordinate their health research activities

Coordination is needed to use scarce resources effectively but also to identify priorities and communicate these to policymakers and the public

After years of Tanzanian health research institutions failing to collaborate they have now joined in a national health forum

Already the forum has identified research priorities and is setting out an ethical framework for research

Lack of a strong research infrastructure is a common feature of many developing countries and is a major hindrance to effective health research. Health resources are often used inefficiently. There is also duplication of effort and little sharing of knowledge and skill. Institutional rivalry and intellectual dependence on the “North” often results in research institutions in the “South” employing external research consultants at high cost when appropriate expertise is available locally.

Although a colonial past and financial dependence on rich donor countries are undeniably important factors behind the failure to establish effective well …
Abstract 3376: Human arrest defective 1 protein suppresses cancer cell metastasis by binding PIX/Cool proteins and inhibiting Cdc42/Rac1 activity
Authors: Kuo-Tai Hua, Michael Hsiao, Min-Liang Kuo
Journal: Cancer Research (2010)

Abstract Human arrest defective 1 protein, ARD1, is an N-acetyltransferase known to be involved in cell cycle control. We found that ARD1 is highly expressed in the early stage of the cell cycle and less highly expressed in a variety of human malignancies that metastasize to lymph nodes. ARD1 expression favors survival in patients. ARD1 significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, ARD1 binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activities and decreased cell migration. Forced expression of PIX in ARD1-transfected tumor cells restored the migration and metastasis ability. We suggest that ARD1 functions as a novel tumor metastasis suppressor by disrupting the migratory complex, GIT-PIX-Paxillin, in cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3376.
Predicting and preparing for pandemic flu
Authors: F. Godlee
Journal: BMJ (2009)

“Never make predictions,” said the American baseball player Casey Stengel, “especially about the future.” But we have to forecast if we are to plan. For more accurate forecasting in this flu pandemic, it’s essential for us to refine our methods and to understand their limitations. This is what Tini Garske and colleagues seek to do in their fast tracked article in this week’s journal (doi:10.1136/bmj.b2840).

The world needs to know how many people are likely to die from the new flu virus. Data emerging from different countries offer widely different pictures. The initial reports from Mexico suggested high fatality ratios among those infected, sparking a sense of …
Fatal Free-Floating Left Atrial Thrombus
Authors: Tamás Tornóczky, Zeno Ajtay
Journal: New England Journal of Medicine (2004)

This 68-year-old woman was resuscitated after cardiac arrest. Echocardiography showed a dilated left atrium and severe mitral-valve stenosis. A free-floating thrombus caused intermittent occlusion of the mitral valve.
SH2-containing inositol phosphatase (SHIP-1) transiently translocates to raft domains and modulates CD16-mediated cytotoxicity in human NK cells
Authors: Ricciarda Galandrini, Ilaria Tassi, Gianfranco Mattia, Luisa Lenti, Mario Piccoli, Luigi Frati, Angela Santoni
Journal: Blood (2002)
The Attacks on the American Medical Association.
Authors: Leartus Connor
Journal: JAMA (1906)

Detroit, Sept. 14, 1906. <h3>To the Editor:</h3> —As a contribution to a correct estimate of the criticisms in Association management, the following observations are presented: 1. There has always been criticism of the American Medical Association management, a criticism varying with its prosperity. In this it falls under the general law of powerful organizations. Someone is always ready, with a club, to hit the head of anyone who rises above mediocrity, so as to reduce him to the general level. Hence, no friend of the American Medical Association need be disturbed by wild criticism, criticism inspired by hostility to its fundamental principles. 2. The medical profession has never learned cheerful submission to the guidance of its leaders. Many are restive under any regulation essential to effective organization, criticising both the committees who make and the officers who enforce them. It seems an American characteristic to be "agin the givernment." Very
A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1
Authors: Jochen Hampe, Andre Franke, Philip Rosenstiel, Andreas Till, Markus Teuber, Klaus Huse, Mario Albrecht, Gabriele Mayr, Francisco M De La Vega, Jason Briggs, Simone Günther, Natalie J Prescott, Clive M Onnie, Robert Häsler, Bence Sipos, Ulrich R Fölsch, Thomas Lengauer, Matthias Platzer, Christopher G Mathew, Michael Krawczak, Stefan Schreiber
Journal: Nature Genetics (2006)