tbuckley/cabot-search huggingface dataset:
Abstract 2863: Development of an AKT1-specific synbody that inhibits MOLT-4 cell growth
Authors: Chris W. Diehnelt
Journal: Cancer Research (2012)

Abstract Our group has developed bivalent peptide affinity ligands, called synbodies, to a number of proteins, including the serine / threonine kinase, AKT1. However, despite the high affinity of the synbody for AKT1 (KD = 1.5 nM), questions remain about the use of this synbody as a probe to modulate AKT1 activity within the cell due to the impermeability of most peptide ligands. In this presentation, we demonstrate that the AKT1 synbody penetrates mammalian cells and localizes with AKT1 in MOLT-4 acute lymphoblastic leukemia cells. The synbody specifically binds AKT1 but not AKT2 or AKT3 in the cytoplasm of MOLT-4 cells demonstrating a level of specificity typically only achieved by antibodies, which do not normally penetrate the cell. It was also found that after 24 hours of treatment, the synbody inhibits growth of MOLT-4 cells with an IC50 of 5 uM. FACS analysis revealed that the synbody induces apoptosis by altering the downstream activity of AKT1. We are currently confirming the mechanism of action of the synbody as well as preparing modifications to increase the activity and in vivo stability of the synbody. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2863. doi:1538-7445.AM2012-2863
A PLEA FOR ASEPTIC VACCINE VIRUS AND ASEPTIC VACCINATION, WITH A CASE IN POINT.
Authors: ROSA ENGELMANN
Journal: JAMA (1894)

On the continent every effort is made to secure aseptic lymph. Its asepticity can not be otherwise than probable, until the specific germ or tox-albumen of cowpox shall be isolated, and a laboratory product placed upon the market. However, it is not unreasonable to now require that a vaccination abrasion be treated as is any other abraded surface, viz: aseptically. Since the vitiation of bovine virus by twenty or more demonstrable germs can not as yet be excluded, added infection from skin and air can, at least, be prevented by the antiseptic preparation, operation and dressing of the arm. Should an ulcer, erysipelas, lymphangitis or phlegmon appear, treat each as you would surgical complications elsewhere. Granting them to be infectious, it follows that their invasion and effects must be minimized. In the proceedings of the Pediatrie Section of the New York Academy of Medicine, reported in the January, 1894, number
Abstract 5631: Nitric oxide-based immune response modifications: A novel paradigm in tumor vaccine development against melanoma
Authors: Samuel Y. Olson, Tamiko Konishi, Kevin W. Bruhn, Noah A. Craft, Hermes J. Garban
Journal: Cancer Research (2010)

Abstract Although of cardinal importance, the specific role of nitric oxide (NO) in the immune response to cancer remains elusive. NO is generally considered to act as a terminal effector molecule that will promote direct cell death due to its cytotoxic and/or cytostatic properties. Conversely, NO has been also found to be associated with a cytoprotective effect due to its ability to interfere with the apoptotic machinery. We have previously shown that NO is capable to immuno-sensitized tumor cells by regulating the expression of apoptosis-related genes and modifying the structure of many protein targets. Thus, we hypothesize that NO-based modification of an autologous tumor vaccine preparation may improve the immunological priming against tumor cells and potentiate the specific anti-tumor immune response. In order to test this hypothesis we used the well-characterized B16-C57BL/6 syngeneic mouse model of melanoma. B16-F0 melanoma cells were cultured in the presence or absence of a non-cytotoxic concentration of a slow rate release NO donor for 18 hours, and later homogenized into a crude lysate. These preparations were used to vaccinate mice previously challenged with B16-F0 melanoma cells on the contralateral dorsal flank one week before, in order to frame a therapeutic paradigm of treatment in cancer. Additional doses of vaccine were applied every 7 days for a period of 3 weeks and tumor volume was determined every 3 days. Our results demonstrate that the NO-modified autologous cancer vaccine decreases the rate of tumor growth by approximately 85% (p &amp;lt;0.001) by day 25 when compared with the control groups. In addition, this vaccination scheme increases the survival rate by approximately 60% (p &amp;lt;0.001) of the experimental group when compared with controls. NO can exert a myriad of modifications at the genetic, epigenetic and post-translational level in the tumor cells promoting a robust and effective therapeutic immune response against cancer cells. Currently, we are defining the molecular and immunological mechanisms responsible for the significant increase in survival and anti-tumor immune response triggered by the NO-mediated modifications of the melanoma tumor cells. Our results suggest a new role of NO as an immune response modifier that can be exploited in cancer immunotherapy and serves as a model for vaccine development. 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 5631.
Phase I and II Study of Exisulind in Combination With Capecitabine in Patients With Metastatic Breast Cancer
Authors: Lajos Pusztai, Jim Hou Zhen, Banu Arun, Edgardo Rivera, Clark Whitehead, W. Joseph Thompson, Kimberly M. Nealy, Amy Gibbs, W. Fraser Symmans, Francisco J. Esteva, Daniel Booser, James L. Murray, Vicente Valero, Terry L. Smith, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2003)

Purpose: We studied the safety and clinical activity of exisulind in combination with capecitabine in 35 patients with metastatic breast cancer (MBC). Patients and Methods: All patients had received previous anthracycline and taxane chemotherapies. Two dose levels of exisulind were explored, 125 and 250 mg orally bid as continuous daily therapy, concomitant with capecitabine 2,000 mg/m 2 for 14 days in 21-day cycles. In the phase I study, the dose-limiting toxicities were hand-foot syndrome and diarrhea. The 125-mg bid dose was selected for phase II testing. Results: The most common nonhematologic grade 2 to 3 adverse events were hand-foot syndrome (57%) and fatigue (48%). The most frequent grade 2 to 3 laboratory abnormality was granulocytopenia. No death, unexpected adverse events, or cumulative toxicity were encountered. One complete and four partial responses were achieved (objective response rate, 16%) in the 31 patients assessable for response. The median duration of response was 31 weeks; three patients experienced stable disease longer than 26 weeks. Overall clinical benefit (complete response, partial response, or stable disease &gt; 26 weeks) was 23%. Fourteen specimens were available for immunohistochemical assessment of phosphodiesterase-5 isoenzyme (PDE-5) and PDE-2 expression, which are the targets of exisulind. Eighty percent of tumors showed some expression of PDE-5 in the invasive cancer cells including 35% that showed moderate or strong staining. PDE-2 showed moderate or strong staining in 78% of tumors. There was no apparent association between tumor response and staining intensity. Conclusion: Exisulind (125 mg orally bid) in combination with capecitabine is well tolerated and the combination has anticancer activity similar to that of capecitabine alone in heavily pretreated patients with MBC.
Cardiac and pulmonary fat embolectomy for suspected fat embolus
Authors: C. S. Nelson
Journal: Thorax (1974)

<b>Nelson, C. S. (1974).</b><i>Thorax</i>, <b>29</b>, 134-137. <b>Cardiac and pulmonary fat embolectomy for suspected fat embolus.</b> There is no specific treatment of fat embolism, whether the embolism is predominantly cerebral, pulmonary, renal or mesenteric. A 46-year-old man had fractured his right femur for the third time in December 1971. Seventy hours later he suddenly developed the cardiovascular, respiratory, and cerebral manifestations of post-traumatic fat embolism. His chest radiograph at the onset of symptoms was consistent with fat embolism. He underwent cardiac and pulmonary embolectomy on 7 December 1971 and made a most dramatic recovery. His haemobronchorrhoea, dyspnoea, tachypnoea, hyperpyrexia, and profound shock disappeared at the end of the operation. His only postoperative cerebral disturbance was mild disorientation. The pathophysiological changes accompanying fat embolism are due to toxic vasculitis and fat macroglobule aggregations blockading the pulmonary arterioles and capillaries. The blockading concept is the basis for cardiac and pulmonary fat embolectomy. Only a larger series embodying a multicentre trial will show whether or not cardiopulmonary fat embolectomy is a specific treatment of massive fat embolism. The purpose of this paper is to report on the technique and result of embolectomy for a suspected fat embolus following fracture of the femur.
Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption
Authors: Laura N. Vandenberg, Maricel V. Maffini, Carlos Sonnenschein, Beverly S. Rubin, Ana M. Soto
Journal: Endocrine Reviews (2009)

In 1991, a group of 21 scientists gathered at the Wingspread Conference Center to discuss evidence of developmental alterations observed in wildlife populations after chemical exposures. There, the term "endocrine disruptor" was agreed upon to describe a class of chemicals including those that act as agonists and antagonists of the estrogen receptors (ERs), androgen receptor, thyroid hormone receptor, and others. This definition has since evolved, and the field has grown to encompass hundreds of chemicals. Despite significant advances in the study of endocrine disruptors, several controversies have sprung up and continue, including the debate over the existence of nonmonotonic dose response curves, the mechanisms of low-dose effects, and the importance of considering critical periods of exposure in experimental design. One chemical found ubiquitously in our environment, bisphenol-A (BPA), has received a tremendous amount of attention from research scientists, government panels, and the popular press. In this review, we have covered the above-mentioned controversies plus six additional issues that have divided scientists in the field of BPA research, namely: 1) mechanisms of BPA action; 2) levels of human exposure; 3) routes of human exposure; 4) pharmacokinetic models of BPA metabolism; 5) effects of BPA on exposed animals; and 6) links between BPA and cancer. Understanding these topics is essential for educating the public and medical professionals about potential risks associated with developmental exposure to BPA and other endocrine disruptors, the design of rigorously researched programs using both epidemiological and animal studies, and ultimately the development of a sound public health policy.
Citrullination is an inflammation-dependent process
Authors: D Makrygiannakis, E af Klint, I E Lundberg, R Lofberg, A-K Ulfgren, L Klareskog, A I Catrina
Journal: Annals of the Rheumatic Diseases (2006)

To study the presence of citrullinated proteins in inflammatory conditions and in clinically non-affected tissues of controls.Synovial biopsy specimens from 19 patients with rheumatoid arthritis and 10 healthy controls were investigated by immunohistochemistry. Additionally, muscle tissue from 5 patients with polymyositis and from 7 healthy controls, intestinal tissue from macroscopically affected and non-affected areas from 10 patients with inflammatory bowel disease (IBD) and tonsil tissues from 4 chronically inflamed tonsils were studied.Citrullinated proteins were present in all synovial biopsy specimens from patients with rheumatoid arthritis, whereas only three of 10 healthy synovial biopsy specimens showed scarce amounts of citrullination. Citrullination was also present in all myositis-affected muscles, whereas it was absent in the muscle tissues of controls. All tonsil biopsy specimens studied were positive for citrulline. Even though more frequently detected in the macroscopically affected colonic areas, no marked difference was observed in the pattern or extent of citrullination between the macroscopically affected and non-affected intestinal IBD tissues.Citrullination is present in a wide range of inflammatory tissues, suggesting that this process is inflammation dependent rather than disease dependent.
TCT-738 Thrombocytes And IndividuaLization Of ORal Antiplatelet Treatment After Percutaneous Coronary Intervention (TAILOR)
Authors: Nadia Paarup Dridi, Pär I. Johansson, Peter Clemmensen, Thomas Engstrøm, Maria Radu, Frants Pedersen, Henning Kelbaek, Kari Saunamäki, Erik Jørgensen, Steffen Helqvist, Lene Holmvang
Journal: Journal of the American College of Cardiology (2012)
FIBROCALCIFIC AORTIC VALVE DISEASE IN MICE IS DEPENDENT UPON BOTH ENDOTHELIAL NITRIC OXIDE SYNTHASE GENOTYPE AND VALVE CUSP NUMBER
Authors: Ramzi El Accaoui, Georges Hajj, Melissa Davis, Yi Chu, Donald Lund, Robert Brooks, Diane Kraft, Kathy Zimmerman, Donald Heistad, Robert Weiss
Journal: Journal of the American College of Cardiology (2012)
Accountability, Audit, and Reverence for the Publication Process
Authors: Drummond Rennie
Journal: JAMA (1993)

Let me begin with a few truisms, just to be sure that we are operating on a common ground of reverence for the publication process —Above all, the act of publication is an inscription under oath, a testimony. It is accepted as valid until firm evidence to the contrary is presented. There is an extremely high level of accountability for what is published under a given person's name.... It is the essential ingredient to make scientific work responsible in the sense that one cannot readily retreat from assertions that have been signed, delivered to the printer, and made available to thousands!—Joshua Lederberg<sup>1</sup> Having long subscribed to the approach that each author carries a heavy responsibility for what appears under his or her name, I had been impressed when several articles I had accepted for publication were later found by Food and Drug Administration (FDA) audit to be based on
Costs of New Treatments for Hepatitis C Infection
Authors: Ruth Lopert, Craig Welch
Journal: JAMA (2014)

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
Electrophysiologic Studies during Accelerated Idioventricular Rhythms
Authors: JOHN J. GALLAGHER, ANTHONY N. DAMATO, SUN H. LAU
Journal: Circulation (1971)

Accelerated idioventricular rhythms (AIVR) are ectopic ventricular rhythms with rates intermediate between idioventricular escape rhythms (30 to 40/min) and ventricular tachycardia (120 to 180/min). Differentiation of AIVR from supraventricular arrhythmias rests primarily on demonstration of their ventricular origin. His bundle electrograms (HBE) were recorded in four patients during AIVR. HBE verified the idioventricular nature of the ectopic rhythm and excluded supraventricular rhythm with aberration as a cause. In addition, they permitted the recognition of normally conducted sinus beats, fusion beats, and idioventricular beats. The pacemaker site for the AIVR was below the bundle of His. AIVR became manifest when the heart rate was slowed by increasing vagal tone, premature atrial stimulation, and high degree atrioventricular (A-V) block. AIVR could be suppressed and 1:1 A-V conduction established by increasing the atrial rate with atropine or by atrial pacing.
The evolution of small gene clusters: evidence for an independent origin of the maltase gene cluster in Drosophila virilis and Drosophila melanogaster
Authors: C. P. Vieira, J. Vieira, D. L. Hartl
Journal: Molecular Biology and Evolution (1997)

We analyzed a 5,770-bp genomic region of Drosophila virilis that contains a cluster of two maltase genes showing sequence similarity with genes in a cluster of three maltase genes previously identified in Drosophila melanogaster. The D. virilis maltase genes are designated Mav1 and Mav2. In addition to being different in gene number, the cluster of genes in D. virilis differs dramatically in intron-exon structure from the maltase genes in D. melanogaster, the transcriptional orientation of the genes in the cluster also differs between the species. Our findings support a model in which the maltase gene cluster in D. virilis and D. melanogaster evolved independently. Furthermore, while in D. melanogaster the maltase gene cluster lies only 10 kb distant from the larval cuticle gene cluster, the maltase and larval cuticle gene clusters in D. virilis are located very far apart and on a different chromosome than that expected from the known chromosome arm homologies between D. virilis and D. melanogaster. A region of the genome containing the maltase and larval cuticle gene clusters appears to have been relocated between nonhomologous chromosomes.
Use of nimesulide in Indian children must be stopped
Authors: K. Saha
Journal: BMJ (2003)

EDITOR—The continuing use of nimesulide for Indian children is shocking.1 Numerous studies have established the life threatening hepatotoxic effects of nimesulide. 2 3 Nimesulide is not used in the United States, and many European countries have also banned the drug because of its unacceptable rate of serious adverse reactions.

Although some studies have indicated that nimesulide may be chosen …
Effectiveness of antismoking telephone helpline: follow up survey
Authors: S. Platt, A. Tannahill, J. Watson, E. Fraser
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the effectiveness of an antismoking campaign conducted by the Health Education Board for Scotland. <b>Design:</b> Descriptive survey of adult callers to a telephone helpline (Smokeline) for stopping smoking; panel study of a random sample of adult callers; assessment of changes in prevalence of smoking in Scotland before and after introduction of the helpline <b>Setting:</b> Telephone helpline. <b>Subjects:</b> Callers to Smokeline over the initial one year period. Detailed information was collected on a 10% sample (n=8547). A cohort of adult smokers who called Smokeline (total n=848) was followed up by telephone interview three weeks, six months, and one year after the initial call. <b>Main outcome measures:</b> Numbers of adult smokers calling helpline; changes in smoking behaviour, especially stopping smoking among cohort members; and changes in prevalence of smoking in the general population. <b>Results:</b> An estimated 82 782 regular adult smokers made genuine contact with Smokeline over the year, representing about 5.9% of all adult smokers in Scotland. At one year 143 of the cohort of 848 callers (23.6%; 95% confidence interval 20.2% to 27.0%) reported that they had stopped smoking, and 534 (88.0%; 85.4% to 90.6%) reported having made some change. About 19 500 (16 700 to 22 350) adult smokers, equivalent to 1.4% (1.2% to 1.6%) of the mean adult smoking population, stopped smoking with direct help from Smokeline. During the second year of the campaign (1994) smoking prevalence among 25-65 year olds in Scotland was 6% (2.0% to 10.0%) lower than it had been before the start of the campaign. <b>Conclusion:</b> The Health Education Board for Scotland9s antismoking campaign reached a high number of adult smokers, was associated with a highly acceptable quit rate among adults given direct help through Smokeline, and contributed considerably to an accelerated decline in smoking prevalence in Scotland. <h3>Key messages</h3> There was an unprecedented response to the antismoking campaign of the Health Education Board for Scotland, with an estimated 5.9% of adult smokers in Scotland responding to the invitation to call Smokeline, a free telephone helpline, in its first year of operation A panel study of callers to Smokeline, with telephone interviewing, obtained an acceptable response rate of 71.6% at one year follow up Nearly a quarter (23.6%) of smokers who called the helpline were not smoking at the one year follow up, a success rate that exceeds a proposed standard for comparable health education and promotion interventions The Smokeline campaign contributed considerably to an accelerated (6%) reduction in smoking among people aged 25-65 in Scotland during 1992-4 The study findings provide further evidence of the efficacy of mass media antismoking initiatives with a social support component
116. The Proposed AAV Serotypes 10 and 11 Serologically Cross-React with AAV8 and AAV4
Authors: Luk H. Vandenberghe, James R. Miller, Gaung-Ping Gao, Roberto Calcedo, James M. Wilson
Journal: Molecular Therapy (2006)

Introduction: Vectors based on a variety of AAV isolates are currently being explored for application in gene therapy. This pursuit is driven by the fact that relatively subtle structural differences can dramatically affect vector biology in several ways relevant to gene therapy such as efficiency of gene transfer, tropism and interactions with the immune system of the host. Particularly, circulating neutralizing antibodies can blunt a successful gene therapy. Serological cross-reactivity between AAV isolates is not only used as a reflective measure of neutralization in vivo but also as a way of classification of primate AAVs. Recently AAV10 and AAV11 were proposed by Mori et al. (2004) as novel serotypes. AAV10 and AAV11 were found to be structurally closest to the previously described serotypes AAV8 and AAV4, respectively. Their study showed that the isolates from cynomolgus macaque were not cross-neutralized by polyclonal mouse antiserum generated against purified VP2 protein from AAV2, AAV4 or AAV8.
TWO CASES OF SYPHILITIC SPONDYLITIS
Authors: C. Abernethy
Journal: BMJ (1931)

The question -of treatment is outside the scope ofthe present-paper, and would take up too much space.The essential point is to recognize -the ankylopoietic form as early as possible and to deal with any focus of infection, to take steps to prevent the development of kyphosis, ankylosis of the hips, etc.,-by rest, supports, or by other methods, and to pay special attention to the defective calcium metabolism by correcting vitamin deficiency and other disorders of nutrition.Freund recommends treat- ment at a spa, preferring Gastein, a spa of a type well represented in this country.