tbuckley/cabot-search huggingface dataset:
Renal Effects of Natriuretic Peptide Receptor Blockade in Cirrhotic Rats With Ascites
Authors: Paolo Angeli, Wladimiro Jiménez, Vicente Arroyo, Harald S. Mackenzie, Ping L. Zhang, Joan Clária, Francisca Rivera, Barry M. Brenner, Joan Rodés
Journal: Hepatology (1994)

The aim of this study was to assess the effect of HS–142–1, a recently discovered specific antagonist of endogenous natriuretic peptides, on systemic hemodynamics, renal function, and the renin–aldosterone system in rats with cirrhosis and ascites. The study consisted of three protocols, each including 10 conscious control rats and 10 conscious rats with carbontetrachloride–induced cirrhosis with ascites. In protocol 1, HS–142–1 administration (by intravenous bolus of 20 mg · kg-1 body weight in all protocols) was not associated with significant changes in mean arterial pressure, heart rate, cardiac output or total peripheral resistance in the two groups of animals. In protocol 2, HS–142–1 induced a significant reduction in glomerular filtration rate (from 4.2 ± 0.5 to 2.6 ± 0.3 ml/min, p &lt; 0.025) in control animals. A decrease in renal plasma flow and an increase in renal vascular resistance also occurred, but these changes were not statistically significant. In cirrhotic rats, HS–142–1 resulted in a significant decrease in renal plasma flow (from 10.9 ± 0.7 to 4.3 ± 0.6 ml/min, p &lt; 0.001) and a significant increase in renal vascular resistance (from 6.0 ± 0.6 to 16.3 ± 2.7 mm Hg · min · ml-1, p &lt; 0.025). Glomerular filtration rate decreased more in cirrhotic rats with ascites than in control rats (from 3.8 ± 0.3 to 1.3 ± 0.2 ml/min, p &lt; 0.001). Changes in urine flow rate and urinary sodium excretion rate paralleled those of glomerular filtration rate in both groups of animals. In protocol 3, HS–142–1 administration was associated with a marked increase in plasma renin activity (from 17 ± 3 to 39 ± 9 ng · ml-1 ± hr-1, p &lt; 0.01) and plasma aldosterone concentration (from 130 ± 12 to 268 ± 48 pg · ml-1, p &lt; 0.025) in cirrhotic rats with ascites. This association was not observed in control animals (plasma renin activity from 1.6 ± 0.3 to 1.6 ± 0.5 ng ± ml·1 · hr-1, aldosterone from 45 ± 15 to 44 ± 16 pg · ml-1). These findings indicate that endogenous natriuretic peptides play a critical role in the maintenance of renal function and in the regulation of the renin–aldosterone system in cirrhosis with ascites. These peptides, however, are not critical to arterial pressure homeostasis under the conditions studied. (Hepatology 1994;20:948-954).
Prolonged Hemolysis from Overheated Dialysate
Authors: STEPHEN L. BERKES
Journal: Annals of Internal Medicine (1975)

A patient with chronic renal failure exposed to overheated dialysate (50 °C) for 20 minutes developed evidence of delayed and protracted hemolysis, which continued for several days. By contrast, in the only previously reported similar case, sudden gross hemolysis followed by cardiac arrest occurred. It is emphasized that the rapidity and severity of hemolysis due to thermal injury to erythrocytes are dependent upon the duration of exposure and the height of temperature to which extracorporeal blood is exposed. Methods of preventing such incidents and therapeutic approaches are outlined.
A Novel Small-Molecule Inhibitor of Protein Kinase Cι Blocks Transformed Growth of Non–Small-Cell Lung Cancer Cells
Authors: Melody Stallings-Mann, Lee Jamieson, Roderick P. Regala, Capella Weems, Nicole R. Murray, Alan P. Fields
Journal: Cancer Research (2006)

Abstract We recently showed that atypical protein kinase Cι (PKCι) is required for transformed growth of human non–small-cell lung cancer (NSCLC) cells by activating Rac1. Genetic disruption of PKCι signaling blocks Rac1 activity and transformed growth, indicating that PKCι is a viable target for development of novel therapeutics for NSCLC. Here, we designed and implemented a novel fluorescence resonance energy transfer–based assay to identify inhibitors of oncogenic PKCι signaling. This assay was used to identify compounds that disrupt the interaction between PKCι and its downstream effector Par6, which links PKCι to Rac1. We identified aurothioglucose (ATG), a gold compound used clinically to treat rheumatoid arthritis, and the related compound, aurothiomalate (ATM), as potent inhibitors of PKCι-Par6 interactions in vitro (IC50 ∼1 μmol/L). ATG blocks PKCι-dependent signaling to Rac1 and inhibits transformed growth of NSCLC cells. ATG-mediated inhibition of transformation is relieved by expression of constitutively active Rac1, consistent with a mechanism at the level of the interaction between PKCι and Par6. ATG inhibits A549 cell tumor growth in nude mice, showing efficacy against NSCLC in a relevant preclinical model. Our data show the utility of targeting protein-protein interactions involving PKCι for antitumor drug development and provide proof of concept that chemical disruption of PKCι signaling can be an effective treatment for NSCLC. ATG and ATM will be useful reagents for studying PKCι function in transformation and represent promising new agents for the clinical treatment of NSCLC. (Cancer Res 2006; 66(3): 1767-74)
German hospital doctors temporarily halt strike but vow to continue
Authors: Annette Tuffs
Journal: BMJ (2006)

Doctors in 25 German university hospitals and 14 state psychiatric hospitals are determined to continue with their strike of more than nine weeks to achieve better pay and working conditions.

They will not accept an agreement that was reached last week between state employees and the Tarifgemeinschaft der Lander (TdL) group, representing the state employers, because it does not satisfy their demands, said a spokesperson from the hospital doctors' union, the Marburger Bund.

However, the strike has been called off for a week so that the thousands of …
Abstract 119: Stabilization of hypoxia-inducible factor-1α by the human rhomboid family-1 gene product RHBDF1
Authors: Zhuan Zhou, Luyuan Li
Journal: Cancer Research (2010)

Abstract Hypoxia inducible factor 1α (HIF1α) is a key transcription factor in the maintenance of oxygen and energy homoeostasis. Increased levels of HIF1α in cancer cells are often associated with increased tumor angiogenesis, metastasis, drug resistance, and poor prognosis. We reported recently that the human rhomboid family-1 gene (RHBDF1) plays a critical role in facilitating tumor growth. Here, we show that RHBDF1 interacts with and stabilizes HIF1α. RHBDF1 gene-silencing with siRNA leads to markedly decreased HIF1α protein stability and down-regulation of HIF1α-targeted genes. However, HIF1α gene transcription and translation is unaffected. RACK1 and HSP90 are protein factors that compete for binding to HIF1α, causing either oxygen-independent degradation or stabilization of the latter. Protection of HIF1α from degradation by RHBDF1 is the result of a switch of HIF1α binding from RACK1 to HSP90. Stabilization of HIF1a can be abolished by using 17-allylaminogeldanamycin, an inhibitor of HSP90. Moreover, engineered over-expression of RHBDF1 leads to hypoxia-induced resistance of cancer cells to apoptosis-inducing agent Etoposide, an anticancer drug, apparently due to high HIF1α levels. These findings are consistent with the view that RHBDF1 may function as a chaperone to maintain HIF-1α stability. 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 119.
Effective Humanitarian Aid
Authors: James C. Cobey
Journal: JAMA (1993)

Despite the dissolution of the Soviet Union and other totalitarian regimes, the world has yet to see a "peace dividend." Instead of two superpowers competing for sole possession of the best economic and political system, we now see numerous ethnic groups trying to found nations, define separate identities, and vent long-standing resentments. These seemingly sudden and unprecedented conflicts have centuries-old historical roots.<sup>1</sup> Today, of approximately 130 armed conflicts in the world, 32 have each produced more than 1000 battlefield deaths, the majority occurring within the boundaries of individual countries. Since World War II, the number of civilian deaths has surpassed military fatalities in most wars and conflicts.<sup>2</sup>In Cambodia, for example, half the land mine casualties in 1991 were civilian.<sup>3</sup>The International Human Rights Law Institute of DePaul University, Chicago, Ill, estimates that there have been 140 000 to 150 000 war fatalities in the former Yugoslavia
Medical Education a la Mode
Authors: James A. Brussel
Journal: JAMA (1966)

To the Editor:—  On returning from Europe, I plunged into the accumulated backlog of medical journals. In JAMA ( 197 , Sept 5, 1966, adv p 9) I find the corniest piece of propaganda ever.  In AMAgrams of this issue is a picture of Miss America boning up on requirements for admission to medical school with the help of AMA's paperback, Horizons Unlimited . Since when does a student study in elbow-length evening gloves, a jeweled diadem, an evening gown, and a metallic-threaded shoulder wrap? Who's kidding whom?
Glyoxalase-1 overexpression in bone marrow cells reverses defective neovascularization in STZ-induced diabetic mice
Authors: Branka Vulesevic, Brian McNeill, Michele Geoffrion, Drew Kuraitis, Joanne E. McBane, Marina Lochhead, Barbara C. Vanderhyden, Gregory S. Korbutt, Ross W. Milne, Erik J. Suuronen
Journal: Cardiovascular Research (2013)

Methylglyoxal (MG) accumulates in diabetes and impairs neovascularization. This study assessed whether overexpressing the MG-metabolizing enzyme glyoxalase-1 (GLO1) in only bone marrow cells (BMCs) could restore neovascularization in ischaemic tissue of streptozotocin-induced diabetic mice. After 24 h of hyperglycaemic and hypoxic culture, BMCs from GLO1 overexpressing and wild-type (WT) diabetic mice were compared for migratory potential, viability, and mRNA expression of anti-apoptotic genes (Bcl-2 and Bcl-XL). In vivo, BMCs from enhanced green fluorescent protein (eGFP) mice that overexpress GLO1 were used to reconstitute the BM of diabetic mice (GLO1-diabetics). Diabetic and non-diabetic recipients of WT GFP+ BM served as controls (WT-diabetics and non-diabetics, respectively). Following hindlimb ischaemia, the mobilization of BMCs was measured by flow cytometry. In hindlimbs, the presence of BM-derived angiogenic (GFP+CXCR4+) and endothelial (GFP+vWF+) cells and also arteriole density were determined by immunohistochemistry. Hindlimb perfusion was measured using laser Doppler. GLO1-BMCs had superior migratory potential, increased viability, and greater Bcl-2 and Bcl-XL expression, compared with WT BMCs. In vivo, the mobilization of pro-angiogenic BMCs (CXCR4+, c-kit+, and Flk+) was enhanced post-ischaemia in GLO1-diabetics compared to WT-diabetics. A greater number of GFP+CXCR4+ and GFP+vWF+ BMCs incorporated into the hindlimb tissue of GLO1-diabetics and non-diabetics than in WT-diabetics. Arteriole and capillary density and perfusion were also greater in GLO1-diabetics and non-diabetics. This study demonstrates that protection from MG uniquely in BM is sufficient to restore BMC function and neovascularization of ischaemic tissue in diabetes and identifies GLO1 as a potential therapeutic target.
Problems in Differential Diagnosis of Non-Langerhans Cell Histiocytosis with Pituitary Involvement: Case Report and Review of Literature
Authors: Rene Mahnel, Khing Hiong Tan, Rudolf Fahlbusch, Benedikt Volk, Dieter Lüdecke, Hans-Gerhard Nagel, Cornelia Jaursch-Hancke
Journal: Endocrine Pathology (2002)
Androgen Receptor Promotes Sex-Independent Angiogenesis in Response to Ischemia and Is Required for Activation of Vascular Endothelial Growth Factor Receptor Signaling
Authors: Sumiko Yoshida, Ken-ichi Aihara, Yasumasa Ikeda, Yuka Sumitomo-Ueda, Ryoko Uemoto, Kazue Ishikawa, Takayuki Ise, Shusuke Yagi, Takashi Iwase, Yasuhiro Mouri, Matomo Sakari, Takahiro Matsumoto, Ken-ichi Takeyama, Masashi Akaike, Mitsuru Matsumoto, Masataka Sata, Kenneth Walsh, Shigeaki Kato, Toshio Matsumoto
Journal: Circulation (2013)

Background— Hypoandrogenemia is associated with an increased risk of ischemic diseases. Because actions of androgens are exerted through androgen receptor (AR) activation, we studied hind-limb ischemia in AR knockout mice to elucidate the role of AR in response to ischemia. Methods and Results— Both male and female AR knockout mice exhibited impaired blood flow recovery, more cellular apoptosis, and a higher incidence of autoamputation after ischemia. In ex vivo and in vivo angiogenesis studies, AR-deficient vascular endothelial cells showed reduced angiogenic capability. In ischemic limbs of AR knockout mice, reductions in the phosphorylation of the Akt protein kinase and endothelial nitric oxide synthase were observed despite a robust increase in hypoxia-inducible factor 1α and vascular endothelial cell growth factor ( VEGF ) gene expression. In in vitro studies, siRNA-mediated ablation of AR in vascular endothelial cells blunted VEGF-stimulated phosphorylation of Akt and endothelial nitric oxide synthase. Immunoprecipitation experiments documented an association between AR and kinase insert domain protein receptor that promoted the recruitment of downstream signaling components. Conclusions— These results document a physiological role of AR in sex-independent angiogenic potency and provide evidence of novel cross-talk between the androgen/AR signaling and VEGF/kinase insert domain protein receptor signaling pathways.
The Kardashian index: a measure of discrepant social media profile for scientists
Authors: Neil Hall
Journal: Genome biology (2014)

In the era of social media there are now many different ways that a scientist can build their public profile; the publication of high-quality scientific papers being just one. While social media is a valuable tool for outreach and the sharing of ideas, there is a danger that this form of communication is gaining too high a value and that we are losing sight of key metrics of scientific value, such as citation indices. To help quantify this, I propose the 'Kardashian Index', a measure of discrepancy between a scientist's social media profile and publication record based on the direct comparison of numbers of citations and Twitter followers.
ADRENOCORTICOTROPHIC HORMONE AND ERYTHROPOIETIN
Authors: JULIA H. HAUGER-KLEVENE
Journal: Annals of Internal Medicine (1967)

Letters and Comments1 May 1967ADRENOCORTICOTROPHIC HORMONE AND ERYTHROPOIETINJULIA H. HAUGER-KLEVENE, M.D.JULIA H. HAUGER-KLEVENE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1024_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:In the article entitled "Hypothalamic Control of Red Cell Production" by Dr. Allan J. Erslev that appeared in the October 1966 ANNALS(p. 862), it was stated that the tissue tension of oxygen in the kidneys themselves controls the rate of red cell production. However, Seip, Halvorsen, Andersen, and Kaada (1) and Halvorsen (2) have reported that hypothalamic stimulation increases the rate of red cell production and that hypothalamic ablation interferes with normal erythropoietic response to hypoxia. Richards and Sayers (3) have reported that in rats relatively large amounts of injected adrenocorticotrophic hormone (ACTH) accumulate in the...References1. SEIPHALVORSENANDERSENKAADA MSPBR: Effects of hypothalamic stimulation on erythropoiesis in rabbits. Scand. J. Clin. Lab. Invest. 13: 553, 1961. CrossrefMedlineGoogle Scholar2. HALVORSEN S: Effects of hypothalamic lesions on the erythropoietic response to hypoxia in rabbits. Acta Physiol. Scand. 61: 1, 1964. CrossrefMedlineGoogle Scholar3. RICHARDSSAYERS JBGF: Excretion of adrenocorticotrophic hormone. Proc. Soc. Exp. Biol. Med. 77: 87, 1951. CrossrefMedlineGoogle Scholar4. MARKSGARBERMCCOY BHBGFW: The juxtaglomerular apparatus as an extraadrenal site of ACTH action. Proc. Soc. Exp. Biol. Med. 105: 593, 1960. CrossrefMedlineGoogle Scholar5. HAUGER-KLEVENECOLE JHVW: Plasma renin activity and aldosterone secretion(abtract). Southern Society Clinical Research Meeting, New Orleans, January 1967. Google Scholar6. HAUGER-KLEVENE JH: Personal observations. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JULIA H. HAUGER-KLEVENE, M.D.Affiliations: Department of Medicine M. D. Anderson Hospital and Tumor Institute The University of Texas Houston, Tex. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1024-1024KeywordsAdrenocorticotropic hormoneErythropoietinHypoxiaKidneysOxygen ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Estimation of stroke volume changes by ultrasonic doppler.
Authors: J S Colocousis, L L Huntsman, P W Curreri
Journal: Circulation (1977)

The purpose of this study was to conduct a controlled evaluation of the continuous-wave Doppler technique for the estimation of stroke volume changes. Six anesthetized dogs were studied. Aortic blood velocity was recorded from the suprasternal notch by a special continuous-wave Doppler unit. Cardiac output was varied by fluid infusion and exsanguination, and over 300 simultaneous records of aortic blood velocity and thermodilution cardiac output were taken. Average stroke volume and average systolic velocity integral (SVI), the area under the Doppler velocity curve were calculated. The relationship of SVI to stroke volume was evaluated for each animal using linear regression. Average results were: correlation coefficient 0.95 +/- 0.04 SD; y-intercept 0.38 +/- 0.14 cm(SD); standare error of fit 0.29 +/- 0.03 cm (SD). These data show that the systolic integral of aortic blood velocity was essentially directly proportional to stroke volume, even over a six-fold range. Thus, this technique will provide an accurate non-invasive estimate of changes in stroke volume.
Gastric Cytoprotection: A Clinician's Guide
Authors: Robert A. Levine
Journal: JAMA (1990)

This book fills an important void that is not customarily addressed in gastroenterology texts. The editors' goal, as stated in their preface, is "to bridge the gap between the research laboratory and medical practice," and in this respect it succeeds remarkably well. The book is clinically directed rather than basic science oriented. It is more of a "handbook" than a textbook and should be of great interest to those who would like an introduction to gastric cytoprotection. Thus, it supercedes the only other treatise on this subject, a collection of papers presented at an international meeting.<sup>1</sup> The book begins with an introductory discussion on "Cytoprotection for the Clinician" (three chapters), which is the most easily readable for the practitioner. It then proceeds to a more extensive section on "Defensive Mechanisms of the Stomach" (six chapters). The roles of mucus and bicarbonate secretion, mucosal blood flow, and microvascular and epithelial
Recurrent aphthous ulceration and jejunal biopsy.
Authors: J D Rose, D M Smith, F G Allan, W Sircus
Journal: BMJ (1978)

Background/Aim: To evaluate outcomes and toxicities of chemoradiation with a less intensive paclitaxel regimen for locally recurrent bladder cancer. Patients and Methods: Three elderly patients received simultaneous chemoradiation for recurrent muscle-invasive bladder cancer. Chemotherapy included two courses (three times 25 mg/m<sup>2</sup> over 1.5 weeks) of paclitaxel. Radiotherapy doses were 59.4 Gy to the bladder and 50.4 Gy to regional lymph nodes. Survival, local control and toxicities were retrospectively evaluated. Results: One patient died after 71 months, two were alive after 69 and 98 months, respectively. No local recurrence was not observed. Five-year survival and local control rates were 100%. Two patients experienced grade 1 acute dysuria, one patient grade 1 diarrhea. Late toxicities were also mild; two patients had grade 1 dysuria. Conclusion: Chemoradiation with a less intensive paclitaxel regimen resulted in excellent 5-year results and was very well tolerated. It may be a reasonable option for elderly patients who cannot tolerate more intensive approaches.
Detection of Intracolonic Lesion by Barium Contrast Enema
Authors: Carl O. Knutson
Journal: JAMA (1979)

Frequently, the clinical significance of the barium contrast enema is minimal because of inadequate colon preparation prior to examination. The frequency of false-positive routine barium enemas was 17% in 230 consecutive patients who underwent colonoscopy for removal of specific radiographically identified polypoid colon lesions. Initial barium enema inaccuracies were documented with postendoscopic air-contrast radiography in colons that were endoscopically proved to be mechanically clean following a two-day colon preparation. These results suggest that more emphasis on a two-day colon preparation, before the initial barium contrast enema, would substantially reduce the frequency of false-positive interpretations.
Placebo reactions in double‐blind, placebo‐controlled food challenges in children
Authors: B. J. Vlieg‐Boerstra, S. Van Der Heide, C. M. A. Bijleveld, J. Kukler, E. J. Duiverman, A. E. J. Dubois
Journal: Allergy (2007)

Background: A cardinal feature of the double‐blind, placebo‐controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented. Objective: To analyse the occurrence and features of placebo events in DBPCFCs and to assess their contribution to the diagnostic accuracy of the DBPCFC in children. Methods: The study population consisted of 132 challenges in 105 sensitized children (age range 0.7–16.6 years, median 5.3 years), who underwent DBPCFCs with cow’s milk, egg, peanut, hazelnut and soy. Placebo and active food challenges were performed on different days. Results: A total number of 17 (12.9%) positive placebo events occurred, which could be classified as immediate (9/17), late‐onset (8/17), objective (11/17) or subjective (6/17). Four of 74 (5.4%) positive active food challenges were revealed to be false positive by administration of a placebo challenge. This is 3% (4/132) of all challenges. When computed by a statistical model, the false positive rate was 0.129 (12.9% of all challenges). Conclusion: Placebo events with diverse clinical characteristics occur in DBPCFCs in a significant number of children. The diagnostic significance of the administration of a placebo challenge is first, to identify false positive diagnoses in DBPCFCs by refuting false positive tests in individual patients. Secondly, to allow for blinding of the active food challenge. Thirdly, applying a statistical model demonstrates that some positive challenges may be false positive and that the test may need to be repeated in selected cases.
So be good for goodness' sake
Authors: John Hartung
Journal: Behavioral and Brain Sciences (2002)

Altruism is traditionally encouraged by promoting a goal, for example, going to heaven. In contrast, Rachlin argues that altruistic behavior can be sufficiently reinforced by the abstract intrinsic reward that comes from maintaining an unbroken pattern of altruistic behavior. In my experience, there are very few people for whom this is true. For fellow atheists and anti-theists, I suggest an alternative.