tbuckley/cabot-search huggingface dataset:
Abstract 1550: Small molecule inhibitors of ezrin as anti-metastatic agents in osteosarcoma
Authors: Gulay Bulut, Kevin Chen, Eric Glasgow, Sung-Hyeok Hong, Hyun-Shik Lee, George Kosturko, Jeffrey A. Toretsky, Ira Daar, Chand Khanna, Aykut Uren
Journal: Cancer Research (2010)

Abstract Osteosarcoma (OS) is the most common type of primary bone cancer and the third most common cancer in children and adolescents. Current combination modalities have improved OS treatment, but did not have a major improvement on patient survival. Thus targeting underlying molecular events can provide dramatic benefits especially for the treatment of patients with fatal metastatic disease. Recently it is shown in a mouse model of OS that high ezrin expression is linked to pulmonary metastasis, providing an early survival advantage for cancer cells reaching the lung. Ezrin, a member of the ERM (Ezrin/Radixin/Moesin) family is conserved through evolution both structurally and functionally. By regulating membrane-cytoskeleton complexes, it plays key roles in normal cellular processes like maintenance of membrane dynamics, survival, adhesion, motility, cytokinesis, phagocytosis and integration of membrane transport with signaling pathways. Due to its critical role in these cellular functions and relevance to metastasis, ezrin is a validated molecular target for prevention of metastasis in OS. In order to identify small molecules that directly interact with recombinant ezrin protein, we screened a small molecule library by surface plasmon resonance technology (Biacore). Initial hits from this primary screen were then evaluated in functional assays. We tested our small molecules for inhibiting ezrin mediated chemotaxis in cell culture, mimicking ezrin morpholino phenotype in zebrafish development, inhibiting ezrin phosphorylation and ezrin-actin interaction, effecting xenopus embryo development and inhibiting lung metastasis of osteosarcoma cells in a mouse lung organ culture assay. Results from these secondary functional assays, binding kinetics values from Biacore experiments and drugability of the chemical structures allowed us to pick two lead compounds. In summary, we discovered two lead compounds that directly bind to ezrin protein with ∼10uM affinity and inhibit its function in multiple independent assays. These molecules form the foundation of new potential therapeutic agents for osteosarcoma metastasis. 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 1550.
In Vivo Enhanced Expression of Patched Dampens the Sonic Hedgehog Pathway
Authors: Ivan Bergstein, Philip L Leopold, Noboru Sato, Andrei A Panteleyev, Angela M Christiano, Ronald G Crystal
Journal: Molecular Therapy (2002)

The sonic hedgehog (SHH)–patched (PTCH) pathway functions in normal embryonic development of the brain, musculoskeletal system, and hair follicles, and in normal post-natal control of hair follicles. Dysregulation of the pathway has been implicated in a variety of neoplasias, including those of skin and brain. Based on the knowledge that generalized, prolonged PTCH expression can inhibit the effects of SHH signaling, we tested the hypothesis that localized transient overexpression of PTCH would inhibit the phenotype of SHH-induced accelerated growth of hair follicles. Adenovirus (Ad)-mediated transient over-expression of Shh (AdShh) in telogen (8 weeks) mouse skin induced anagen hair growth as demonstrated by histology and gross appearance. Strikingly, local intradermal administration of a Ptch-expressing adenovirus (AdPtch), but not a Null control adenovirus (AdNull), 18 hours before AdShh injection, significantly blocked this phenotype, with 100% of AdPtch+AdShh mice failing to advance to anagen compared with AdNull+AdShh mice and AdShh mice (30% and 45% failing to advance to anagen, respectively). Thus, PTCH expression mediated by gene transfer can modulate the SHH signaling pathway in the adult mammal and may serve as a starting point for therapies relevant to clinical conditions resulting from dysregulation of this pathway as well as for strategies to suppress normal SHH-dependent processes, such as hair growth. The sonic hedgehog (SHH)–patched (PTCH) pathway functions in normal embryonic development of the brain, musculoskeletal system, and hair follicles, and in normal post-natal control of hair follicles. Dysregulation of the pathway has been implicated in a variety of neoplasias, including those of skin and brain. Based on the knowledge that generalized, prolonged PTCH expression can inhibit the effects of SHH signaling, we tested the hypothesis that localized transient overexpression of PTCH would inhibit the phenotype of SHH-induced accelerated growth of hair follicles. Adenovirus (Ad)-mediated transient over-expression of Shh (AdShh) in telogen (8 weeks) mouse skin induced anagen hair growth as demonstrated by histology and gross appearance. Strikingly, local intradermal administration of a Ptch-expressing adenovirus (AdPtch), but not a Null control adenovirus (AdNull), 18 hours before AdShh injection, significantly blocked this phenotype, with 100% of AdPtch+AdShh mice failing to advance to anagen compared with AdNull+AdShh mice and AdShh mice (30% and 45% failing to advance to anagen, respectively). Thus, PTCH expression mediated by gene transfer can modulate the SHH signaling pathway in the adult mammal and may serve as a starting point for therapies relevant to clinical conditions resulting from dysregulation of this pathway as well as for strategies to suppress normal SHH-dependent processes, such as hair growth.
Letter: Skin contact pressures.
Authors: P A Isherwood, A Rossi, J E Druett, J C Robertson
Journal: BMJ (1976)

While rarely heard of nowadays except in Dr Apley's metaphorical sense, a tooth-comb was in the past an essential weapon in the battle against head-lice.Perhaps its apparently superfluous prefix was suggested by the pain caused by its being dragged across the scalp and through tangled hair in the search for the elusive nit.-Ep,BM7.
DETERMINATION OF THE NORMAL TEMPERATURE OF THE CLOSED INGUINAL FOLD OF A CHILD, AND ITS CLINICAL SIGNIFICANCE.
Authors: ALBERT H. PARKS
Journal: JAMA (1906)

<h3>HISTORY.</h3> The practitioner of medicine is constantly looking to science and research for methods he may use in his routine work. Most practitioners seek methods which combine two characteristics, accuracy and practicability, but these are often diametrically opposed. I have attempted to solve a problem in a manner that shall yield results at the same time accurate and easy of application to the clinical case. Normal and pathologic conditions in the animal body are very intimately connected with, and in fact dependent on, the production, the distribution and the variation of that phenomenon called animal heat. Medical and scientific literature is replete with all phases of this subject, and I intend to touch on only those points of measurement which may be included in the term thermometry. The practitioner usually adopts the practice of taking the patient's temperature as one of the first steps in his routine examination. Two methods
Exercise-Related Hematuria
Authors: Philip L. Hooper
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The provocative study by Siegel et al (241:391, 1979) found that after running the Boston Marathon, subjects with hematuria had no RBC casts in their urine. The authors suggested that absence of formed elements argued against a glomerular origin. They further cite 21 cases of exercise-related hematuria in which no upper urinary tract cause was found. The following case demonstrates that the appearance of bloody urine after running may arise from the upper urinary tract. <h3>Report of a Case.—</h3> A 17-year-old high school cross-country runner ran a 3.2-km race at a local golf course. He ran his best time ever (11 minutes, 23 s), and for the first time in his life, he ran barefoot. Three hours later he painlessly voided dark red, burgundy-colored urine. Sixteen hours later an intravenous pylelogram showed a large filling defect in the right renal pelvis, which suggested a blood clot. No
Amantadine hydrochloride. Analysis of data related to its proposed use for prevention of A2 influenza virus disease in human beings
Authors: A. B. Sabin
Journal: JAMA (1967)

The control of viral respiratory disease by safe and effective drugs is an important research goal, but the usefulness of potential candidates must be evaluated with great care. E. I. Du Pont de Nemours &amp; Company, Wilmington, Del, has recently proposed that amantadine hydrochloride (1-adamantanamine hydrochloride) be used for the prophylaxis of A2 influenza virus disease in human beings. This proposal, based to a large extent on unpublished studies on human beings, led to the present analysis of both the published data and the unpublished reports; the investigators who carried out the studies have given permission to refer to the unpublished data in this communication. <h3>Studies in Tissue Cultures, Eggs, and Experimental Animals</h3><h3>Tissue Culture Studies.—</h3> Investigators<sup>1-3</sup>at the Du Pont laboratories reported that amantadine hydrochloride has an inhibitory effect on the influenza A, Al, and A2 strains that were tested and also on influenza C, the Sendai strain
Use and outcome of liver transplantation in acetaminophen-induced acute liver failure
Authors: William Bernal, Julia Wendon, Mohamed Rela, Nigel Heaton, Roger Williams
Journal: Hepatology (1998)

Once defined clinical criteria are fulfilled in acetaminophen-induced hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be very poor. In the present study, we examined the application and outcome of OLT in 548 patients admitted to a single center between 1990 and 1996. Four hundred twenty-four (77%) of the patients studied did not fulfill transplantation criteria, and 396 of these (93%) survived. The majority of the 28 nonsurvivors (7%) in this group fulfilled two of three combined criteria, and the finding of a high APACHE III score could be used as an indicator for the need for OLT. Of the 56 patients (45%) not listed, in only a small proportion was this caused by psychiatric reasons, and in the majority, it was a consequence of the rapid development of multiple organ failure and cerebral edema. This also applied to 24 (35%) of the 68 listed patients in whom the rapidity of clinical deterioration, reflected in increasing APACHE III scores, was such that even with the prompt availability of donor organs, OLT was not possible. In the final event, only 44 (35%) of those who fulfilled criteria underwent OLT, of whom 33 (75%) survived to leave the hospital. Survival was greatest in those receiving unreduced grafts, and markers of early graft function differed significantly between survivors and nonsurvivors. Liver transplantation is an effective treatment in a relatively small number of patients with acetaminophen-induced hepatotoxicity, and for a substantial proportion, transplantation was never an option because of the rapidity of clinical deterioration. APACHE III scoring may be of value in decision making and in better defining patients in clinical trials.
NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951
Authors: E Clappier, S Collette, N Grardel, S Girard, L Suarez, G Brunie, S Kaltenbach, K Yakouben, F Mazingue, A Robert, P Boutard, D Plantaz, P Rohrlich, P van Vlierberghe, C Preudhomme, J Otten, F Speleman, N Dastugue, S Suciu, Y Benoit, Y Bertrand, H Cavé
Journal: Leukemia (2010)
Practical Advancement of Multipollutant Scientific and Risk Assessment Approaches for Ambient Air Pollution
Authors: Douglas O. Johns, Lindsay Wichers Stanek, Katherine Walker, Souad Benromdhane, Bryan Hubbell, Mary Ross, Robert B. Devlin, Daniel L. Costa, Daniel S. Greenbaum
Journal: Environmental Health Perspectives (2012)

The U.S. Environmental Protection Agency is working toward gaining a better understanding of the human health impacts of exposure to complex air pollutant mixtures and the key features that drive the toxicity of these mixtures, which can then be used for future scientific and risk assessments.A public workshop was held in Chapel Hill, North Carolina, 22-24 February 2011, to discuss scientific issues and data gaps related to adopting multipollutant science and risk assessment approaches, with a particular focus on the criteria air pollutants. Expert panelists in the fields of epidemiology, toxicology, and atmospheric and exposure sciences led open discussions to encourage workshop participants to think broadly about available and emerging scientific evidence related to multipollutant approaches to evaluating the health effects of air pollution.Although there is clearly a need for novel research and analytical approaches to better characterize the health effects of multipollutant exposures, much progress can be made by using existing scientific information and statistical methods to evaluate the effects of single pollutants in a multipollutant context. This work will have a direct impact on the development of a multipollutant science assessment and a conceptual framework for conducting multipollutant risk assessments.Transitioning to a multipollutant paradigm can be aided through the adoption of a framework for multipollutant science and risk assessment that encompasses well-studied and ubiquitous air pollutants. Successfully advancing methods for conducting these assessments will require collaborative and parallel efforts between the scientific and environmental regulatory and policy communities.
Psychiatric Treatment of Eczema: A Controlled Trial
Authors: D. G. Brown, F. R. Bettley
Journal: BMJ (1971)

Seventy-two patients with eczema were randomly allotted to one of two treatment groups: A, those receiving dermatological treatment only, and B, those receiving the same dermatological treatment plus psychiatric treatment, limited where possible to four months. Cases were followed up at six-monthly dermatological assessments, 57 (79%) for 18 months. The findings suggest that in the presence of overt emotional disturbance, of new psychological or psychophysiological symptoms preceding the rash by up to a year, and of high motivation for it, brief psychiatric treatment improves the outcome in eczema (the proportion clear at 18 months was about doubled), whereas in their absence such treatment may worsen it, especially in the short term.
A117: Demonstration of Antibodies to Multiple Citrullinated Epitopes in the Sera of Patients With Juvenile Idiopathic Arthritis
Authors: Lance Feller, Brooke Gilliam, Esperanza Cleland, Reema H. Syed, Peri H. Pepmueller, Terry L. Moore
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified in the sera of juvenile idiopathic arthritis (JIA) patients and have been associated with more destructive disease. The identity of the target proteins of the citrullinated modification has remained elusive. We attempted to determine the prevalence and significance of different citrullinated epitopes.



Methods:

We evaluated serum from 96 patients with various subtypes of JIA for the presence of antideiminated (citrullinated) fibrinogen, anti-citrullinated α-enolase, anti-citrullinated and native type II collagen, and anti-vimentin (vim1–16 and vim 59–74) antibodies by enzyme-linked immunosorbent assays. We correlated the presence of the antibodies with anti-CCP and rheumatoid factor (RF) isotypes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels.



Results:

31 JIA patients (32%) demonstrated reactivity to anti-citrullinated fibrinogen, 23 (24%) to anti-citrullinated type II collagen, 10 (10.5%) to anticitrullinated vimentin I-16, 9 (9%) to anti-citrullinated α-enolase, and 7 (7.4%) to anti-citrullinated vimentin 59–74 antibodies. One IgM RF positive JIA patient was positive for all 6 of the citrullinated autobodies assayed. The reactivity was higher in those JIA patients positive for IgM RF and IgG/IgM anti-CCP antibodies.



Conclusion:

The study demonstrates that antibodies to multiple citrullinated epitopes are present in the sera of patients with JIA. A higher percentage of antibodies reacted with citrullinated fibrinogen and citrullinated type II collagen. The more widespread the positivity correlates with more severe disease.
Girls Like Us: Fighting for a World Where Girls Are Not for Sale, an Activist Finds Her Calling and Heals Herself
Authors: Tina Kelley
Journal: JAMA Pediatrics (2013)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis: results from the WHO World Health Survey
Authors: Carmen Moreno, Roberto Nuevo, Somnath Chatterji, Emese Verdes, Celso Arango, José Luis Ayuso-Mateos
Journal: World Psychiatry (2013)

This study explored whether physical health problems are related to psychotic symptoms independently of a mental disorder diagnosis. A total of 224,254 subjects recruited for the World Health Organization World Health Survey were subdivided into those with both a lifetime diagnosis of psychosis and at least one psychotic symptom in the 12 months prior to the evaluation, those with at least one psychotic symptom in the past 12 months but no lifetime diagnosis of psychosis, and those without psychotic symptoms in the past 12 months and without a lifetime diagnosis of psychosis. The three groups were compared for the presence of medical conditions, health problems, and access to health care. Medical conditions and health problems (angina, asthma, arthritis, tuberculosis, vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking, and accidents), medication consumption, and hospital admissions (but not regular health care visits) were more frequent in individuals with psychotic symptoms but no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The number of medical conditions increased with the number of psychotic symptoms. Given the sample analyzed, this trend seems to be independent from the socio-economic development of the country or the specific health care system.
Basic Splinting Techniques
Authors: Michael T Fitch, Bret A Nicks, Manoj Pariyadath, Henderson D McGinnis, David E Manthey
Journal: New England Journal of Medicine (2008)

Basic Splinting Techniques Indications Patients frequently present to primary care offices, urgent care, and emergency departments with musculoskeletal injuries, such as fractures, sprains, and dislocations. Many distal-extremity injuries can be initially managed in an outpatient setting using basic splinting techniques. Splinting immobilizes injured extremities and prevents further injury, decreases pain and bleeding, and allows healing to begin. While there are many indications for splinting an extremity, three main types of injuries are commonly treated in outpatient settings: Fractures: Splinting is used to stabilize fractures of the upper and lower extremity, providing patient comfort and maintaining proper bone alignment. Dislocations: After . . . .
Hypothetical Questions in a Suit for Malpractice.
Authors: James L. Tracy
Journal: JAMA (1900)

Toledo, Ohio, June 8, 1900. <h3>To the Editor:</h3> —Recently in this city, in a malpractice suit, the following questions were asked: Assuming that upon a surgical operation, through the usual incision for appendicitis, a surgeon finds the appendix normal, and the condition of the surrounding parts so satisfactory that he returns the appendix to its former position, and permanently closes the incision without drainage, by through-and-through silk-worm gut sutures, reinforced by buried kangaroo tendons, through the peritoneal parts, and immediately thereafter makes an incision in the median line, and removes a ruptured tubal pregnancy, leaving the surrounding parts in such condition that he permanently closes the latter incision without drainage, with through-and-through silk-worm gut sutures, reinforced by buried kangaroo tendons, through the peritoneal parts, and within ten days thereafter, preceded by great abdominal pains, pus forces its way through the first incision in such quantities that a cotton pad one
Probing the role of stearoyl-CoA desaturase_1 in hepatic insulin resistance
Authors: M. T. Flowers
Journal: Journal of Clinical Investigation (2006)

Previous studies using stearoyl-CoA desaturase–1–deficient (SCD1-deficient) mice have shown that this enzyme plays an important role in many diseases of altered cellular metabolism including obesity, insulin resistance, and dyslipidemia. Although SCD1 activity is highest in lipogenic tissues such as the liver and adipose tissue, it is also present at lower levels in most tissues. To better understand the role of SCD1 in liver metabolism it is necessary to explore SCD1 deficiency in a more focused, tissue-specific manner. This commentary focuses on 2 recent studies published in the JCI that address this question using antisense oligonucleotide inhibition of SCD1. First, Jiang et al. have previously reported that long-term inhibition of SCD1 prevents the development of high-fat diet–induced obesity and hepatic steatosis. Second, Gutiérrez-Juárez et al. show in this issue that short-term inhibition of hepatic SCD1 is sufficient to prevent diet-induced hepatic insulin resistance, signifying an important role of hepatic SCD1 in liver insulin sensitivity (see related article beginning on page 1686).