tbuckley/cabot-search huggingface dataset:
Fibroblast Hepatocyte Growth Factor Promotes Invasion of Human Mammary Ductal Carcinoma <i>In situ</i>
Authors: Christopher Jedeszko, Bernadette C. Victor, Izabela Podgorski, Bonnie F. Sloane
Journal: Cancer Research (2009)

Abstract Stromal-derived hepatocyte growth factor (HGF) acting through its specific proto-oncogene receptor c-Met has been suggested to play a paracrine role in the regulation of tumor cell migration and invasion. The transition from preinvasive ductal carcinoma in situ (DCIS) to invasive breast carcinoma is marked by infiltration of stromal fibroblasts and the loss of basement membrane. We hypothesized that HGF produced by the infiltrating fibroblasts may alter proteolytic pathways in DCIS cells, and, to study this hypothesis, established three-dimensional reconstituted basement membrane overlay cocultures with two human DCIS cell lines, MCF10.DCIS and SUM102. Both cell lines formed large dysplastic structures in three-dimensional cultures that resembled DCIS in vivo and occasionally developed invasive outgrowths. In coculture with HGF-secreting mammary fibroblasts, the percentage of DCIS structures with invasive outgrowths was increased. Activation of c-Met with conditioned medium from HGF-secreting fibroblasts or with recombinant HGF increased the percentage of DCIS structures with invasive outgrowths, their degradation of collagen IV, and their secretion of urokinase-type plasminogen activator and its receptor. In agreement with the in vitro findings, coinjection with HGF-secreting fibroblasts increased invasiveness of MCF10.DCIS xenografts in severe combined immunodeficient mice. Our study shows that paracrine HGF/c-Met signaling between fibroblasts and preinvasive DCIS cells enhances the transition to invasive carcinomas and suggests that three-dimensional cocultures are appropriate models for testing therapeutics that target tumor microenvironment-enhanced invasiveness. [Cancer Res 2009;69(23):9148–55]
Interleukin 2 activates extracellular signal-regulated protein kinase 2.
Authors: G R Perkins, J Marvel, M K Collins
Journal: The Journal of Experimental Medicine (1993)

Interleukin 2 (IL-2) stimulated activation of the 42-kD extracellular signal-regulated kinase 2 (Erk2) in murine IL-3-dependent cells, expressing either high or intermediate affinity IL-2 receptors. Activation was both rapid, occurring within 5 min of IL-2 addition, and prolonged, remaining elevated for 30 min. Activation of Erk2 appeared to be necessary for IL-2 stimulation of proliferation, as deletion of a region of the cytoplasmic domain of the IL-2 receptor beta chain, essential for IL-2 stimulation of proliferation, abolished Erk2 activation by IL-2. Furthermore, cells that had been deprived of cytokine for 24 h were then refractory to IL-2 stimulation of both Erk2 activity and proliferation. However, elevation of Erk2 activity was not sufficient to stimulate proliferation, as protein kinase C activation stimulated Erk2 activity but not DNA synthesis. Also, cells exposed to IL-2 in the presence of rapamycin showed full Erk2 activation but not DNA synthesis. These data suggest that IL-2 must stimulate both Erk2 activity and a further pathway(s) to trigger cell proliferation.
Arachidonic acid metabolism by polymorphonuclear leukocytes in psoriasis
Authors: T. Ruzicka
Journal: British Journal of Dermatology (1986)

Journal Article Arachidonic acid metabolism by polymorphonuclear leukocytes in psoriasis Get access T. Ruzicka T. Ruzicka Department of Dermatology, University of Munich, Federal Republic of Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 4, 1 October 1986, Pages 517–518, https://doi.org/10.1111/j.1365-2133.1986.tb06254.x Published: 01 October 1986
P179 Lung-based assessment in Anderson Fabry Disease (AFD) demonstrates differential galactosidase a enzyme (GLA) activity at blood and tissue sites
Authors: N. T. Shafi, D. A. Hughes, R. Baker, C. Smith, J. Hurst, A. Mehta, M. Lipman
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> AFD is an X-linked lysosomal storage disorder caused by mutations of the GLA gene. Lack of enzyme results in storage material accumulation within lysosomes, leading to multi-organ pathology. Airflow obstruction has been reported, though there has been no systematic assessment of lung enzyme activity in affected individuals. We therefore undertook a controlled cohort review of UK AFD patients focussing in particular on the relationship between airway and blood intra- and extracellular GLA, and lung pathology. <h3>Methods</h3> Study subjects and controls were recruited following local Ethics Committee approval. All underwent systematic pulmonary investigation, including lung function testing and sputum induction with 40 ml of 4% hypertonic saline over 20 min via an ultrasonic nebuliser. GLA activity was measured from AFD patients and healthy controls in induced sputum (IS) cells and supernatant using a fluorometric assay. In addition, in AFD patients, GLA activity was measured simultaneously in blood leucocytes and plasma. <h3>Results</h3> 45 AFD patients with variable severity extra-pulmonary disease were recruited (20 males, 10 smokers). The population had a mean FEV1 of 89% predicted. 20 of 45 (44%) (13 males, 6 smokers) had evidence of airflow obstruction with FEV1/FVC ratio &lt;70%. IS intra- and extracellular GLA activity was lower in AFD affected males compared to controls (n=18 and 13, median enzyme activity 18.8 vs 41.7 nmol/h/mg protein and 0.9 vs 10.0 nmol/h/ml, p&lt;0.001 and p&lt;0.01, respectively). No similar difference was found in females. Paired blood and sputum data from 22 AFD patients (13 males, 18 on enzyme replacement therapy) demonstrated greater GLA activity intracellularly in IS than peripheral blood, p=0.001 (see Abstract P179 Figure 1), and extracellularly in IS supernatant versus plasma in males alone (p&lt;0.05). <h3>Conclusions</h3> Sputum GLA activity is lower in male AFD patients than controls. However AFD subjects had significantly higher GLA activity in lung than blood. Measured airway obstruction in AFD was mild, though common. We speculate that the higher levels of lung enzyme found in AFD patients, on or off enzyme replacement, may contribute to the relative preservation of pulmonary function compared to other organ systems.
SPONTANEOUS AND ACQUIRED ACTIVE IMMUNITY TO THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES
Authors: Gregory Shwartzman
Journal: The Journal of Experimental Medicine (1932)

Spontaneous active immunity to the phenomenon of local skin reactivity to bacterial filtrates has been demonstrated. In one experiment, the immunity was non-specific, while in others it appeared limited to one or two bacterial species. Intradermal vaccination of rabbits with bacterial filtrates induced active immunity to the phenomenon. The specificity of this immunity was tested with graded amounts of toxic factors. The combined intradermal and intravenous immunization in these experiments elicited two types of response:- 1. Specific immunity, which was obtained in rabbits highly susceptible to the phenomenon (i.e., showing reactions with 1 reacting unit). 2. Non-specific immunity which was elicited in rabbits with partial spontaneous immunity (i.e. showing no reactions with 1 reacting unit, but susceptible to 15 units 1 week later). Comparative studies on the reacting potency of "agar washings" and disintegrates (Besredka's method, freezing and thawing method) showed that the first washings of bacterial cells are considerably stronger than subsequent washings and disintegrates. These facts demonstrate once again the extracellular nature of the material necessary for the phenomenon. Tentative explanations of the mechanisms involved in the specific and non-specific immunity to the phenomenon are discussed.
Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population
Authors: Angeline S. Andrew, David A. Jewell, Rebecca A. Mason, Michael L. Whitfield, Jason H. Moore, Margaret R. Karagas
Journal: Environmental Health Perspectives (2008)

Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 microg/L in the northeastern, western, and north central regions of the United States.
Resistance to lamivudine therapy: is there more than meets the eye?
Authors: G Dusheiko
Journal: Gut (2004)

A CD8+ T cell response to lamivudine resistant polymerase cytotoxic T lymphocyte (CTL) epitope influences the response to lamivudine treatment for chronic hepatitis B and may indicate an important aspect of the role of T cell responsiveness in lamivudine therapy

The goals of treatment of hepatitis B are to prevent progression of the disease or to slow the disease process. Hepatitis B virus (HBV) is a DNA virus which integrates into the host genome. Thus it is difficult to eradicate viraemia. However, it is possible, albeit in a minority, to reduce levels of viraemia to relatively low threshold levels after finite courses of treatment with either interferon alpha or nucleoside analogues, and to lessen the induced necroinflammatory and immune response.1 Two major forms of active chronic hepatitis B are recognised: wild-type (or hepatitis B e antigen (HBeAg) positive chronic HBV infection) and anti-HBe positive or precore mutant disease. The latter disease is caused by variants of HBV that contain nucleotide substitutions in the core promoter/precore regions of the viral genome.2

Wild-type (HBeAg positive) chronic hepatitis B can be treated with either interferon alpha or nucleoside analogues. Loss of HBeAg and associated suppression of viral replication with pegylated interferon alpha and new nucleoside analogues such as lamivudine, adefovir, tenofovir, telbuvidine, entecavir, and emtricitabine leads to biochemical remission, histological improvement, and in a small percentage, loss of HBsAg.3–5 Durable responses can occur. Continuous therapy is frequently required for the majority of anti-HBe positive patients with chronic hepatitis B. Thus in most patients, longer term therapy is required to suppress viral replication and …
Thoracic Duct-to-Pulmonary Vein Shunt in the Treatment of Experimental Right Heart Failure
Authors: WILLIAM R. COLE, MARLYS HEARST WITTE, STEPHEN L. KASH, MALCOLM RODGER, VIRGIL R. BLEISCH, GERHARD H. MUELHEIMS
Journal: Circulation (1967)

Elevated venous pressure in right heart failure leads not only to an increase in lymph formation but also to progressive resistance in the neck to the return of lymph to the circulation via the thoracic duct. Sequestration of fluid behind the failing heart tends to protect the circulation but at the same time leads to the clinical manifestations of heart failure. The present study was performed on 40 dogs with combined tricuspid insufficiency and pulmonary stenosis. Thoracic duct lymph flow was greatly increased. Pressure was considerably greater in the systemic veins than in the pulmonary vein beyond the right heart obstruction. Lymph flow was substantially enhanced when the thoracic duct was connected to the lower pressure pulmonary veins. Furthermore, direct anastomosis of the thoracic duct to the pulmonary vein resulted in fall in systemic venous pressure, increase in renal excretion of salt and water, and reduction in ascites. These results indicate that alterations in the flow of thoracic duct lymph have important bearing on the manifestations and treatment of right heart failure.
Clinical and epidemiological assessment of steroid-resistant nephrotic syndrome associated with the NPHS2 R229Q variant
Authors: Eduardo Machuca, Aurélie Hummel, Fabien Nevo, Jacques Dantal, Frank Martinez, Essam Al-Sabban, Véronique Baudouin, Laurent Abel, Jean-Pierre Grünfeld, Corinne Antignac
Journal: Kidney International (2009)
Management of Clinically Relevant Bleeding Following Endoscopic Sphincterotomy
Authors: J. Boujaoudé, G. Pelletier, J. Fritsch, A. Choury, J. F. Lefebvre, A. Roche, C. Frouge, C. Liguory, J. P. Etienne
Journal: Endoscopy (1994)

We report here on our experience of clinically relevant bleeding after endoscopic sphincterotomy (ES). Relevant bleeding was defined by the occurrence of (a) hematemesis or melena and (b) at least a two-point drop in hemoglobin, with no other bleeding source on endoscopy. These two criteria were met in 16 patients between 1983 and 1992. They represented 0.65% of all ES procedures performed during this period. Bleeding occurred immediately after ES in five cases, and was delayed in 11 cases from one to eight days (mean two days). Patients were retrospectively classified into three groups according to the severity of bleeding and subsequent clinical management. In six cases (group 1), bleeding developed slowly without shock and stopped spontaneously. In five cases (group 2), bleeding developed rapidly with melena and a drop in hemoglobin, but without shock. These patients were successfully managed with sclerotherapy without any further complications. The five patients in Group 3 had brisk bleeding with hematemesis and shock. Endoscopic hemostasis could not be performed; emergency arteriography disclosed active bleeding in four patients, and embolization of the gastroduodenal artery was performed. Bleeding stopped in all patients. Billroth II anastomosis appeared to be the only factor associated with an increased risk of clinically relevant bleeding. It was possible to control bleeding following ES using endoscopic or angiographic hemostasis, surgery being avoided in all cases.
Epicardial Adipose Tissue Thickness in Normotensive and Prehypertensive Subjects
Authors: Osman Turak, Fırat ÖzcanUğur Canpolat, Mehmet A Mendi, Fatih Öksüz, Derya Tok, Fatma N Başar, Kumral Çağlı, Sinan Aydoğdu
Journal: Journal of the American College of Cardiology (2013)
Science for Sale: The Perils, Rewards, and Delusions of Campus Capitalism
Authors: Xavier Bosch
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
Shared Treatment Decision Making Improves Adherence and Outcomes in Poorly Controlled Asthma
Authors: Sandra R. Wilson, Peg Strub, A. Sonia Buist, Sarah B. Knowles, Philip W. Lavori, Jodi Lapidus, William M. Vollmer
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Poor adherence to asthma controller medications results in poor treatment outcomes.
Critical soft‐tissue dimensions with dental implants and treatment concepts
Authors: Daniel S. Thoma, Sven Mühlemann, Ronald E. Jung
Journal: Periodontology 2000 (2014)

Abstract Dental implants have proven to be a successful treatment option in fully and partially edentulous patients, rendering long‐term functional and esthetic outcomes. Various factors are crucial for predictable long‐term peri‐implant tissue stability, including the biologic width; the papilla height and the mucosal soft‐tissue level; the amounts of soft‐tissue volume and keratinized tissue; and the biotype of the mucosa. The biotype of the mucosa is congenitally set, whereas many other parameters can, to some extent, be influenced by the treatment itself. Clinically, the choice of the dental implant and the position in a vertical and horizontal direction can substantially influence the establishment of the biologic width and subsequently the location of the buccal mucosa and the papilla height. Current treatment concepts predominantly focus on providing optimized peri‐implant soft‐tissue conditions before the start of the prosthetic phase and insertion of the final reconstruction. These include refined surgical techniques and the use of materials from autogenous and xenogenic origins to augment soft‐tissue volume and keratinized tissue around dental implants, thereby mimicking the appearance of natural teeth.
Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients
Authors: Manisha Talim
Journal: Diabetes Care (2007)

I read with interest the articles by Targher et al. (1), which shows that nonalcoholic fatty liver disease (NAFLD) is extremely common in type 2 diabetes and is associated with a higher prevalence of cardiovascular disease (CVD), and by Hu et al. (2), which shows that type 2 diabetes is associated with an increased risk of Parkinson's disease. Neither is surprising, considering society's excessive use of polyunsaturated n-6–rich vegetable oils (a source of linoleic acid, a short-chain n-6 polyunsaturated fatty acid [PUFA]) in place of saturated fats, in addition …
Tobacco funding for academics
Authors: D. Carnall
Journal: BMJ (1996)

Most people would agree that Cambridge University would be ill advised to launder money for a Colombian cocaine cartel. While the pounds sterling1.5 million that the university proposes to accept from BAT (British American Tobacco) Industries to fund a new chair in international relations may be legal, it is hard to make a moral distinction between the tobacco industry and the drug cartels.1 Both supply and promote an addictive substance with the intention of maximising their profits, in spite of the resultant human suffering.

Selling tobacco is certainly profitable: BAT Industries' profits went up 56% to a record pounds sterling1.56 billion in 1995. Most of this growth came from selling 100 …
Abstract 1926: The changing incidence of primary central nervous system lymphoma (PCNSL) in the United States (US): A surveillance, epidemiology and end results (SEER) study
Authors: Christina Tieu, James R. Cerhan, Brian Patrick O'Neill
Journal: Cancer Research (2011)

Abstract Introduction. Up to now PCNSL incidence in the US was presumed to be increasing in all age groups independent of changes in nosology, new diagnostic techniques, and HIV infection. The intent of our study was, firstly, to extend our prior study of PCNSL incidence in the US (Olson et al, Cancer 2002;95:1504-10) with an additional decade of SEER data; and, secondly, to determine time trends during the HAART era in the US. Methods. PCNSL age-adjusted incidence rates from 1973-2007 were obtained from the nine SEER registries used in the Olson et al. study. Similarly, the same exclusion criteria were used to remove PCNSL most likely associated with HIV (never married males and females; persons of unknown marital status; all cases reported in the San Francisco registry). To assess the accuracy of the criteria in removing HIV associated cases, incidence rates of Kaposi sarcoma (KS) were assessed with and without the use of the same exclusion criteria. Results. The incidence of PCNSL in the general population decreased from 1995 to 2000. Following this decrease, the incidence stabilized and is now beginning to increase in the last 5 years. Stratifying the incidence rate by age group and employing the exclusion criteria, PCNSL incidence has remained stable in the 20-64 year old population, but has steadily increased in the 65+ population. Removing the exclusion criteria did not alter the data for the 65+ population but demonstrated a sharp drop in incidence after 1996 for the 20-64 year old population. Applying the same HIV exclusion criteria the incidence of KS resulted in no appreciable change in incidence rates over the same time frame. Conclusion. The incidence rate of PCNSL is increasing. This increase is driven by a continued increase in incidence among the 65+ population while the incidence for those aged 20-64 has stabilized during the same time frame. An effect of HAART on PCNSL incidence in the US is suggested by the decline in the incidence among the 20-64 year old population without the HIV exclusion criteria. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1926. doi:10.1158/1538-7445.AM2011-1926
S22 The Effect Of Cigarette Smoke On Important Pathogens In Copd Lung Infection
Authors: K. McGown, M. Tunney, S. McGrath, J. Elborn, D. Gilpin
Journal: Thorax (2014)

<h3>Introduction</h3> The leading cause of COPD in developed nations is exposure to tobacco smoke. COPD is characterised by acute periods of exacerbation, which are often bacterial in aetiology. The direct effect of cigarette smoke on bacteria present in the COPD lung, and how this may drive disease progression, has not been determined. This preliminary study aimed to determine the effect of cigarette smoke extract (CSE) on the growth and antibiotic susceptibility of COPD bacterial lung pathogens. <h3>Methods</h3> CSE was prepared as described previously. Briefly, smoke from one, two, three or four cigarettes was bubbled through 100 mls growth medium. Bacterial type strains (<i>Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pneumoniae, Prevotella </i>spp and <i>Haemophilus influenzae</i>) were inoculated into growth medium +/- CSE and incubated either aerobically or anaerobically (<i>Prevotella</i> spp). Total viable counts (TVC cfu/ml) were estimated from 0–48 hrs (aerobes) and 0–72 hrs (<i>Prevotella </i>spp). Changes in minimum inhibitory concentration (MIC) of antibiotics used in the treatment of respiratory infections were determined by E-Test®, in bacterial cultures exposed daily to CSE over 12 days. <h3>Results</h3> The growth of <i>P.aeruginosa, S. pneumoniae </i>and <i>H. influenzae</i> were not completely inhibited by any concentration of CSE; however a reduction in growth rate at higher concentrations was observed. <i>M. catarrhalis</i> growth was completely inhibited by two cigarettes/100 ml growth medium. No difference in growth was observed between <i>Prevotella</i> spp +/- CSE. A marked increase in <i>P.aeruginosa</i> resistance to tetracycline and doxycycline was observed after repeated CSE exposure: resistance to tetracycline and doxycycline increased from 24 to &gt;256 μg/ml, and 48- &gt;256 μg/ml, respectively. <h3>Conclusions</h3> The growth of principal bacteria isolated from COPD patients were not affected by concentrations of CSE utilised in this study, but changes in the susceptibility of <i>P. aeruginosa </i>to tetracyclines was observed. This increase in resistance may be mediated by efflux pump up-regulation, and may lead to cross-resistance with other antibiotics. Work currently underway aims to determine whether CSE induces other key phenotypic changes (virulence factor expression and/or biofilm production) which might enhance the pathogenicity of these bacteria in the presence of CSE and result in poorer outcomes for patients with COPD.