tbuckley/cabot-search huggingface dataset:
Abstract A17: A role for the endocytic regulators Rab25 and Rab coupling protein (RCP) in K-Ras dependent colorectal cancer cells
Authors: Claire Rooney, Simon Barry
Journal: Clinical Cancer Research (2010)

Abstract Endocytic transport impacts a wide range of cellular functions, including growth factor signaling, cell polarity, and cell-cell and cellmatrix adhesion. As such, deregulated endocytosis is emerging as a key feature of tumorigenesis. Growth factors and their receptors are important regulators of normal cell survival and proliferation and aberrant growth factor signaling is one of the fundamental elements of tumor growth and progression. Upon activation at the plasma membrane, growth factor receptors are internalized and either trafficked to the lysosome for degradation, or returned to the cell surface via the process of endosomal recycling. Furthermore, growth factor receptors can signal from endocytic compartments en route to the lysosome, and throughout the recycling process. Downstream of growth factor stimulation, signaling from Ras GTPases to effectors such as the mitogen activated protein kinase (MAPK) pathway has also been shown to occur at endocytic compartments. Elucidation of the key regulators of the endocytic process therefore presents a novel opportunity to target certain growth factor signaling pathways. Two such key regulators are the small GTPase Rab25, and its interacting partner Rab coupling protein (RCP). Rab25 and RCP are amplified in certain breast and ovarian cancers, and this amplification is associated with increased aggressiveness of these cancers. Additionally, in mutant p53 cells RCP has been implicated in enhanced EGFR and integrin signaling, resulting in increased invasion. Here, we provide evidence for the importance of Rab25 and RCP in colorectal cancer (CRC) cell lines. Using siRNA to specifically knockdown RCP and Rab25 in a panel of CRC cell lines we have found that RCP and Rab25 knockdown significantly impacts on the proliferation of these lines. Within the panel of CRC cell lines, we have identified subpopulations of K-Ras dependent and K-Ras independent lines. K-Ras dependency appeared to be independent of K-Ras mutation status, and those lines which depend on K-Ras for proliferation also require RCP and Rab25. We are currently investigating the consequences of RCP knockdown on growth factor receptor signaling and subsequent Ras activation. These findings highlight the importance of the regulation of recycling endocytosis in colorectal cancer, and indicate a dependence of colorectal cancer cells on this process. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A17.
Serum Concentrations of Soluble Vascular Cell Adhesion Molecule-1 and E-Selectin Are Elevated in Insulin-Resistant Patients With Type 2 Diabetes
Authors: Kazunari Matsumoto, Yasunori Sera, Yasuyo Abe, Yukitaka Ueki, Seibei Miyake
Journal: Diabetes Care (2001)

It is well known that soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) levels are elevated in patients with type 2 diabetes (1,2,3). Previous studies suggest that hyperglycemia, hyperinsulinemia, or insulin resistance may be responsible for the elevation of adhesion molecules (4,5,6). However, to our knowledge, the relation between soluble adhesion molecules and directly measured insulin sensitivity has not been studied in patients with type 2 diabetes. To investigate the direct association between insulin resistance and the elevation of soluble adhesion molecules, we performed a case-control study. Serum concentrations of sICAM-1, sVCAM-1, and sE-selectin were compared in insulin-sensitive and insulin-resistant …
Why Doctor Can't Write (Yet Again)
Authors: Michael A. Kowal
Journal: JAMA (1985)

<h3>To the Editor.—</h3> May I bring to the attention of those who read this journal an irksome, significant, and correctable problem: illegible handwriting. I am a physical therapist practicing at the Veterans Administration Medical Center in Milwaukee, a large teaching institution. Other staff members and I waste considerable time trying to decipher illegible orders and notes written by doctors. As a result, care of the patient is usually delayed and encumbered. Why should this be the case? (1) Doctors have not attended grammar school and, as a result, have no training in handwriting skills. (2) Doctors are supposed to write illegibly. (3) It is not important for doctors to communicate with staff. The chart serves only as a device for papercompliance with regulations. (4) Doctors are not really confident about what they are doing or writing. People are less likely to criticize and judge them, or less likely to lose
Four Cases of Typhus Fever in Britain
Authors: H. L. W. Beach, J. K. Rennie
Journal: BMJ (1945)

height from which it falls should be such that it forms a ring when it enters the fluid.If cups or umbrellas are formed the apparent specific gravities will be higher; if the pipette is not steady fluffy rings will be formed and the apparent specific gravity found will be less.SummaryThe copper sulphate method for measuring specific gravity of serum gives satisfactory and consistent estimates of the protein concentration.The apparent specific gravities found by this method are less than the true specific gravity.The equation recommended for calculating the protein concentra- tion from the apparent specific gravity is P = 364 (S -1.006).For satisfactory and consistent measurements of serum protein by the Kjeldahl method, selenium dioxide should be used as a catalyst and digestion should be continued for at least one hour, and preferably for 3{ hours.We wish to express our thanks to Prof.
Identification of patients with sustained ventricular tachycardia by frequency analysis of signal-averaged electrocardiograms despite the presence of bundle branch block.
Authors: B D Lindsay, J Markham, K B Schechtman, H D Ambos, M E Cain
Journal: Circulation (1988)

Previously, we have demonstrated distinguishing features in the fast Fourier transform (FFT) of signal-averaged electrocardiograms (ECGs) obtained during sinus rhythm in the absence of bundle branch block that differentiate patients with from those without sustained ventricular tachycardia (VT). The ECGs during sinus rhythm from many patients with sustained VT, however, exhibit intraventricular conduction abnormalities. Accordingly, this study was performed to determine whether the presence of bundle branch block during sinus rhythm precluded accurate identification of patients with sustained VT. Studies were performed in 28 normal subjects (group I) and 141 patients with organic heart disease grouped according to clinical characteristics. Group II comprised 40 patients without VT in whom the QRS duration during sinus rhythm was less than 120 msec. Group III included 21 patients without VT in whom the QRS duration during sinus rhythm was 120 msec or greater. Group IV comprised 43 patients with sustained VT having ECGs during sinus rhythm with QRS durations less than 120 msec. Group V included 37 patients with sustained VT in whom the QRS duration during sinus rhythm was 120 msec or greater. FFTs of the terminal QRS and ST segment of signal-averaged X, Y, and Z ECGs were computed. Transformed data were expressed as an FFT magnitude and the relative contribution and peak magnitudes of 20 to 50 Hz frequencies determined after first demonstrating that this FFT method was more appropriate, when compared with the energy spectrum, for analyzing ECG signals having a broad range of ST segment durations.(ABSTRACT TRUNCATED AT 250 WORDS)
Pre-eclamptic Toxemia and Degenerative Vascular Disease: A Prospective Study of 158 Patients.
Authors: Cheves M. Smythe
Journal: Annals of Internal Medicine (1966)

s1 May 1966Pre-eclamptic Toxemia and Degenerative Vascular Disease: A Prospective Study of 158 Patients.Cheves M. Smythe, M.D., F.A.C.P., E. J. Dennis III, M.D., F. A. McIver, M.D.Cheves M. Smythe, M.D., F.A.C.P.Search for more papers by this author, E. J. Dennis III, M.D.Search for more papers by this author, F. A. McIver, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1157_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA 4½-year prospective study of 158 patients, 86 with pre-eclampsia, 23 with eclampsia, 6 with hypertensive vascular disease, and 43 normal controls re-emphasizes with the passage of every year the role of toxemia of pregnancy in both the genesis and advance of degenerative vascular disease. Of the 67 (78%) adequately followed pre-eclamptics, hypertension has reappeared in 48% of those patients with subsequent pregnancies, in 34% of all subsequent pregnancies, and 19% have become permanently hypertensive. Only 47% have had no subsequent trouble. For the 21 (87%) followed eclamptics, the corresponding figures are 62% hypertensive in subsequent pregnancies, 52% of all... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Cheves M. Smythe, M.D., F.A.C.P.; E. J. DennisIII, M.D.; F. A. McIver, M.D.Affiliations: Charleston, South Carolina PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1157-1157KeywordsEclampsiaHypertensionPregnancyProspective studiesVascular diseases ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
Direct evidence for the absence of active Na+ reabsorption in hamster ascending thin limb of Henle's loop.
Authors: Y Kondo, K Abe, Y Igarashi, K Kudo, K Tada, K Yoshinaga
Journal: Journal of Clinical Investigation (1993)

The mechanisms of Na+ transport across cell membranes were investigated in the in vitro microperfused hamster ascending thin limb (ATL) of Henle's loop using a fluorescent Na+ indicator sodium-binding benzofuran isophthalate. The intracellular Na+ concentration ([Na+]i) of the ATL cells was 17.1 +/- 1.7 mM (n = 22) when the ATL was microperfused in vitro with Hepes-buffered solution containing 204 mM Na+. Elimination of metabolites such as glucose and alanine from the basolateral solution increased [Na+]i. Applying either 5 mM cyanide or 5 mM iodoacetic acid to the bath also increased [Na+]i. The elimination of K+ and the addition of 10(-4) M ouabain in the bath increased [Na+]i by 25.0 +/- 5.0 mM (n = 5) in 3 min and by 10.7 +/- 2.4 mM (n = 4), respectively. The elimination of luminal and basolateral Na+ resulted in a decrease in [Na+]i, indicating Na+ permeability of both the luminal and basolateral cell membranes. The luminal Na+ permeability was not affected by furosemide. The presence of luminal Na+ permeability and the basolateral Na+/K+ ATPase suggests the presence of net active reabsorption of Na+, which is not a physiologically important amount, in our estimation.
THE DISCOVERER OF STREPTOMYCIN
Authors: D. V. Hubble
Journal: BMJ (1958)

<h3>Summary</h3> Fc fragment, indistinguishable from papain Fc, was demonstrated in concentrated normal human urine. F′c was found, in addition, in 20 urines tested. Urinary F′c was demonstrated to be antigenically deficient to urinary Fc, papain Fc and 7 S γG, and identical to esterase induced F′c. Heterogeneity in size of urinary F′c was suggested by density gradient and analytical ultracentrifugation, polyacrylamide and immuno-electrophoresis and gel filtration. Urinary F′c may have a molecular weight range of 18,000 to 60,000: some urinary F′c has a sedimentation coefficient of 1·3 S. On the basis of <i>in vitro</i> incubation experiments of radiolabeled 7 S γG and papain Fc with normal human urine, it is concluded that native 7 S γG is not easily degraded by urinary enzymes, whereas papain Fc breaks down to form the F′c fragment. The significance of these findings in relation to possible <i>in vivo</i> mechanisms is discussed.
SOME PROBLEMS IN PUBLIC HEALTH ADMINISTRATION
Authors: MATTHIAS NICOLL
Journal: JAMA (1925)

When we take into consideration the comparatively short time that official care of the public health has been recognized in America, with certain noteworthy local exceptions, as a problem of fundamental importance to the citizenry, it is not surprising that the rapid strides that have taken place in this field, especially during the last decade, should be accompanied by difficulties inherent in any widespread campaign that seeks the adoption of a program frequently opposed to customs and habits of life inherited from individualistic forebears. Today the American people as a whole, when the value of rules and regulations affecting public and personal health habits have been convincingly demonstrated, show remarkable willingness to comply with their provisions, even though such compliance may entail a good deal of discomfort and not infrequently physical and mental suffering. There are no other countries in which the almost autocratic powers of constituted health authorities are
Chlamydia, Smoking, and Heart Disease
Authors: David L. Hahn
Journal: Annals of Internal Medicine (1992)

Letters15 July 1992Chlamydia, Smoking, and Heart DiseaseDavid L. Hahn, MDDavid L. Hahn, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-117-2-171_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: Saikku and colleagues (1) present evidence of an association between chronic Chlamydia pneumoniae infection and the development of coronary heart disease in the Helsinki Heart Study. This association, if confirmed, could have a profound effect on the prevention and management of coronary heart disease. The odds ratios associating evidence of C. pneumoniae infection and coronary heart disease were attenuated (from 2.7 to 2.3 for immunoglobulin A [IgA] titers, 2.1 to 1.8 for immune complexes, and 2.9 to 2.6 for the presence of both factors). There was no statistical difference for IgA titers and immune complexes after controlling...Reference1. SaikkuLeinonenTenkanenLinnanmäkiEkmanManninen PMLEMV. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med. 1992;116:273-8. LinkGoogle Scholar1. HoltKeast PD. Environmentally induced changes in immunological function: acute and chronic effects of inhalation of tobacco smoke and other atmospheric contaminants in man and experimental animals. Bacteriol Rev. 1977;41:205-16. CrossrefMedlineGoogle Scholar2. SaikkuLeinonenTenkanenLinnenmäkiEkmanManninen PMLEMV. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med. 1992;116:273-8. LinkGoogle Scholar3. SaikkuLeinonenMattilaEkmanNieminenMäkelä PMKMMP. Serologic evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet. 1988;2:983-5. CrossrefMedlineGoogle Scholar4. LeinonenLinnanmäkiMattilaNieminenValtonenLeirisalo-Repo MEKMVM. Circulating immune complexes containing chlamydial lipopolysaccharide in acute myocardial infarction. Microb Pathog. 1990;9:67-73. CrossrefMedlineGoogle Scholar5. FrickEloHaapaHeinonenHeinsalmiHelo MOKOPP. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317:1237-45. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAntibiotika zur ReokklusionsprophylaxeChlamydia Pneumoniae and Coronary Heart Disease 15 July 1992Volume 117, Issue 2Page: 171-171KeywordsCOVID-19Cardiovascular therapyChlamydiaChlamydia infectionCoronary heart diseaseImmune complexInfectious disease immunologyInfectious diseasesLongitudinal studiesOdds ratio Issue Published: 15 July 1992 PDF downloadLoading ...
Power Shortage: Clinical Trials Testing the “Homocysteine Hypothesis” against a Background of Folic Acid–Fortified Cereal Grain Flour
Authors: Andrew G. Bostom, Jacob Selhub, Paul F. Jacques, Irwin H. Rosenberg
Journal: Annals of Internal Medicine (2001)

Large randomized, controlled trials of total homocysteine-lowering therapy for the potential reduction of cardiovascular disease outcomes are ongoing in the United States and Canada. These trials are the Vitamin Intervention for Stroke Prevention (VISP) trial, the Women's Antioxidant Cardiovascular Disease Study (WACS), and the Heart Outcomes Prevention Evaluation (HOPE-2). However, the dramatic effect of policies mandating fortification of cereal grain flour products with folic acid may reduce the statistical power of these trials. All three trials assume that the active treatment groups will achieve the same mean effects of total homocysteine-lowering therapy as those reported in the absence of folic acid-fortified cereal grain flour. This paper examines this assumption using data from studies of total homocysteine-lowering therapy in U.S. and Canadian patients with cardiovascular disease who were exposed to products made with folic acid-fortified cereal grain flour. These data showed that the VISP trial, HOPE-2, and WACS will probably achieve only approximately 20% to 25% of the projected treatment effects of mean total homocysteine-lowering therapy (1.0 to 1.5 micromol/L vs. 4.0 to 6.0 micromol/L). As a result, all three trials will be substantially underpowered to test the specific hypotheses of total homocysteine-lowering therapy identified a priori. In contrast, renal transplant recipients have a persistent excess prevalence of hyperhomocysteinemia in the era of fortification but remain very responsive to supraphysiologic doses of folic acid-based supplementation (mean reduction in total homocysteine level, 5.0 to 6.0 micromol/L). Therefore, unlike other populations with normal renal function that are at high risk for cardiovascular disease but are profoundly affected by fortification efforts, renal transplant recipients continue to merit serious consideration for a controlled trial of the "homocysteine hypothesis."
The Renin-Angiotensin System
Authors: Suzanne Oparil, Edgar Haber
Journal: New England Journal of Medicine (1974)

TIGERSTEDT and Bergman established a role for the kidney in blood-pressure regulation at the close of the 19th century. In a classic experiment, they produced hypertension in dogs by injecting a crude extract of kidney, which they called renin.1 Goldblatt called the attention of modern investigators to renal mechanisms of blood-pressure control by producing hypertension in the dog by clamping the renal artery.2 This experiment suggested the release of a pressor substance from the kidney when its circulation was impaired. Since that time, a cascade of enzymes, peptide and steroid hormones and cofactors belonging to the renin–angiotensin–aldosterone system have been . . .
Connie Adler, MD
Authors: Fitzhugh Mullan
Journal: JAMA (1998)

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
Aberrant aquaporin 5 expression in the sweat gland in aquagenic wrinkling of the palms
Authors: Kenji Kabashima, Takatoshi Shimauchi, Miwa Kobayashi, Shoko Fukamachi, Chika Kawakami, Makiko Ogata, Rieko Kabashima, Tomoko Mori, Tomoko Ota, Satoshi Fukushima, Mariko Hara-Chikuma, Yoshiki Tokura
Journal: Journal of the American Academy of Dermatology (2008)
Vasopressin/nitroglycerin infusion vs. esophageal tamponade in the treatment of acute variceal bleeding: A randomized controlled trial
Authors: Josep Teres, Ramon Planas, Julia Panes, Joan Manel Salmeron, Antoni Mas, Jaime Bosch, Covadonga Llorente, Josep Viver, Faust Feu, Joan Rodés
Journal: Hepatology (1990)

Vasopressin infusion and esophageal tamponade are still widely used to arrest variceal bleeding, but no objective evidence exists on the superiority of either of the two procedures. In this study, 108 cirrhotic patients bleeding from varices were included in a prospective, randomized trial to investigate the comparative effectiveness and safety of balloon tamponade (using the Sengstaken–Blakemore tube for esophageal varices and the Linton–Nachlas tube for gastric varices) (n = 52) and intravenous vasopressin infusion (0.4 to 0.8 μ/min) plus intravenous nitroglyeerin infusion (40 to 400 μg/min) (n = 56). Both treatments were maintained for 24–hr. The hemostatic efficacy according to the intention to treat was 86.5% for tamponade and 66% for pharmacological therapy (p &lt; 0.01). No significant differences were found with respect to rebleeding during the first 72 hr after treatment, mortality rate or side effects. These results suggest that esophageal tamponade is more effective than vasopressin/nitroglycerin infusion in the treatment of variceal bleeding in cirrhotic patients.(HEPATOLOGY 1990;11:964–968.).
Influence of Subsalicylate Bismuth on Absorption of Doxycycline
Authors: Charles D. Ericsson, Stuart Feldman, Larry K. Pickering, Thomas G. Cleary
Journal: JAMA (1982)

The influence of a typical 60-mL dose of subsalicylate bismuth (Pepto-Bismol) on the absorption of 200 mg of orally administered doxycycline hyclate was studied. Bioavailability of doxycycline was significantly reduced by 37% and 51%, respectively, when subsalicylate bismuth was given simultaneously and as a multiple-dose regimen before doxycycline. Peak serum concentrations of doxycycline were significantly decreased when subsalicylate bismuth was given two hours before doxycycline but not when given two hours after doxycycline. Subsalicylate bismuth should not be taken when doxycycline is used for therapeutic purposes, and we suggest travelers should not take the agents together in an effort to prevent diarrhea.