tbuckley/cabot-search huggingface dataset:
Intracellular Signaling Pathways Involved in Acetaldehyde–Induced Collagen and Fibronectin Gene Expression in Human Hepatic Stellate Cells
Authors: Gianluca Svegliati-Baroni, Francesco Ridolfi, Antonio Di Sario, Stefania Saccomanno, Emanuele Bendia, Antonio Benedetti, Patricia Greenwel
Journal: Hepatology (2001)

Ethanol induces liver fibrosis by several means that include, among others, the direct fibrogenic action of acetaldehyde on hepatic stellate cells (HSC). However the mechanisms responsible for this effect are not well understood. In this communication we investigated signal transduction pathways triggered by acetaldehyde leading to upregulation of α2(I) collagen and fibronectin gene expression in human HSC. Run–on assays showed that acetaldehyde–enhanced transcription of these 2 genes as early as 2 hours, via de novo protein synthesis–independent and –dependent mechanisms. It also stimulated a time–dependent induction in phosphorylation of pp70 S6K and extracellular–regulated kinase ½ (ERK½). These effects were completely prevented by calphostin C, a protein kinase C inhibitor. As expected, acetaldehyde–elicited ERK½ phosphorylation was inhibited by PD98059, a MEK inhibitor, but not by wortmannin, a PI3K inhibitor. On the other hand, both of these inhibitors partially inhibited phosphorylation of pp70 S6K induced by acetaldehyde suggesting that its activation is ERK½– and PI3K–dependent. Acetaldehyde–elicited fibronectin and α2(I) collagen upregulation was inhibited by calphostin C. However, while PD98059, wortmannin and rapamycin (a pp70 S6K inhibitor) completely abrogated α2(I) collagen upregulation, they had no effect on fibronectin expression. Overall, these data suggest that protein kinase C is an upstream component from which acetaldehyde signals are transduced to other pathways such as PI3K and ERK½. In addition, differential activation of these pathways is needed for the increase in fibronectin and α2(I) collagen gene expression induced by acetaldehyde in human HSC.
Intestinal Carcinoma in the Peutz-Jeghers Syndrome
Authors: John D. Reid
Journal: JAMA (1974)

IN 1949, Jeghers et al<sup>1</sup>published their classic account of the syndrome of generalized intestinal polyposis and melanin spots of the oral mucosa, lips, and digits, and wrote that "the well-known tendency for multiple polyposis of the colon to develop malignancy apparently holds to some degree for the small-bowel polyps in cases of this syndrome." This conclusion, which has practical implications favoring preventive surgery, was supported in subsequent early reports. In 1957, Bailey<sup>2</sup>found the risk of cancer to be as high as 24%, on the basis of reviews of all 67 cases published to that time. Contrary opinions began to appear in the same year, asserting that there was no increased incidence of malignant neoplasms, and justifying surgical conservatism. Dormandy,<sup>3</sup>reporting on 21 patients, thought that malignant neoplasm degeneration in the small intestine was exceedingly rare if it ever occurred. Despite several histologic diagnoses of carcinoma,
Ventricular refractory period extension caused by defibrillation shocks.
Authors: R J Sweeney, R M Gill, M I Steinberg, P R Reid
Journal: Circulation (1990)

In pentobarbital-anesthetized dogs, transcardiac shocks of up to 30 J or pacing stimuli were delivered to myocardial tissue at different times in the electrical cycle. When delivered midway or later into electrical systole, shocks, but not pacing stimuli, greatly extended the refractory period as determined by left ventricular pacing. There was a positive correlation between both the shock energy and timing and the amount of delay. A 30-J shock given 10 msec before the end of the refractory period extended the refractory period by 63 +/- 15 msec (p less than 0.001), whereas the same shock given 40 msec earlier produced only 25 +/- 10 msec (p less than 0.001) of extension. By comparison, a 5-J shock given at those times produced 36 +/- 18 (p less than 0.005) and 10 +/- 8 msec (p less than 0.001) of extension, respectively. When delivered early into electrical systole, both a pacing stimulus and a shock had no substantial effect on the tissue refractory period. Because the tissue that is late in electrical systole would otherwise be the first to repolarize if no shock were given, the selective refractory period extension may create a period after the shock during which no tissue is repolarized to a level sufficient for wavefront propagation. Thus, the energy- and time-dependent refractory period extension may help explain the mechanism by which ventricular defibrillation occurs during transcardiac shocks.
Cold Urticaria in Infectious Mononucleosis
Authors: Robert F. Lemanske
Journal: JAMA (1982)

URTICARIA and angioedema are common disorders. Although the specific cause of these disorders frequently is not known, certain underlying diseases and physical stimuli have been shown to produce these conditions and need to be evaluated. Viral infections such as hepatitis B and infectious mononucleosis (IM) may be associated with urticaria. In some patients, cryoprecipitates have been demonstrated<sup>1</sup>in which the presence of viral particles, antibodies, and complement components suggests a pathogenic role for immune complexes and complement activation. Physical stimuli such as cold exposure may produce urticaria on exposed body surfaces of affected persons. The precise mechanisms by which cold temperatures produce these symptoms is unknown but may involve IgE antibody,<sup>2</sup>cryofibrinogens,<sup>3</sup>cold hemolysins,<sup>3</sup>various chemical mediators,<sup>4</sup>and cryoglobulins that are capable of complement activation.<sup>5</sup> Although IM has been associated with cryoprecipitates<sup>6</sup>and, to a lesser extent, cryoprecipitates have been associated with cold urticaria,
Serum alkaline phosphatase in hypophosphatasia
Authors: Joseph B. Warshaw, John W. Littlefield, William H. Fishman, Norma R. Inglis, Leo L. Stolbach
Journal: Journal of Clinical Investigation (1971)

It is recognized that serum alkaline phosphatase may reflect enzyme contributions from bone, liver, and intestine. We have investigated serum alkaline phosphatases in two siblings with hypophosphatasia. After administration of long-chain triglycerides, the major alkaline phosphatase component of their sera was shown to be of intestinal origin on the basis of inhibition by l-phenylalanine. Starch block electrophoresis suggested that there were other regions of l-phenylalanine-sensitive alkaline phosphatase in addition to the major slow-moving intestinal band. Medium-chain triglycerides which are absorbed by the portal route did not cause a similar augmentation of intestinal alkaline phosphatase activity. These studies indicate that serum levels of intestinal alkaline phosphatase are increased normally after long-chain fat feeding in hypophosphatasia and may be the major component of total serum alkaline phosphatase activity.
Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial
Authors: Guillaume Debaty, Maxime Maignan, Dominique Savary, François-xavier Koch, Stéphane Ruckly, Michel Durand, Julien Picard, Christophe Escallier, Renaud Chouquer, Charles Santre, Clemence Minet, Dorra Guergour, Laure Hammer, Hélène Bouvaist, Loic Belle, Christophe Adrie, Jean-François Payen, Françoise Carpentier, Pierre-Yves Gueugniaud, Vincent Danel, Jean-François Timsit
Journal: Intensive Care Medicine (2014)
The Usefulness of Argon Plasma Coagulation in the Treatment of Gastric Adenoma Known as a Premalignant Lesion of Stomach Cancer : Compare with the Endoscopic Submucosal Dissection Group
Authors: W.K. Bae, J.W. Kim, T.J. Song, N.H. Kim, K.A. Kim, J.S. Lee
Journal: Annals of Oncology (2014)
David John Thornberry
Authors: C. S Perkins, E A. Thornberry
Journal: BMJ (2009)

After house jobs, David John Thornberry pursued a career in surgery, passing the FRCS in 1980. A diagnosis of multiple sclerosis made while he was working as a registrar in orthopaedic surgery prompted a change of career direction. Subsequent training as a medical officer in the artificial limb and appliance service at …
Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats.
Authors: R Hirschberg, J D Kopple
Journal: Journal of Clinical Investigation (1989)

The mechanisms whereby growth hormone may increase renal plasma flow (RPF) and GFR are not known, but circumstantial evidence has implicated insulin-like growth factor I (IGF-I) as a mediator of this effect. This study examined whether an infusion of IGF-I will increase RPF and GFR, whether this effect occurs quickly, and if this effect is dependent on eicosanoids or peptide hormones known to affect renal function. Rats fasted for 3 d to reduce IGF-I and IGF-I plasma binding proteins were anesthetized; then the rats received an intravenous injection of 25 micrograms/kg IGF-I, and an infusion of 25 micrograms/kg IGF-I within 20 min. Controls received infusion of the vehicle. RPF (para-aminohippurate clearances), GFR (inulin clearances), renal vascular resistance (RVR), mean arterial blood pressure (MABP), plasma IGF-I, and glucose concentrations were measured repeatedly. At the end of the 20-min infusion, plasma IGF-I tended to be increased in the animals that received IGF-I (P = 0.069), but did not increase in the control rats. IGF-I induced a significant and sustained fall in RVR and rise in RPF and GFR without any change in MABP. A small, transient, but significant decrease in plasma glucose concentrations was observed during IGF-I but not during vehicle infusion. Indomethacin, but not somatostatin, blocked the renal response to IGF-I infusion. Thus, IGF-I infusion increases RPF and GFR and reduces RVR in fasted rats. This effect requires the presence of eicosanoids but does not seem to require other peptide hormones suppressed by somatostatin.
The C-CURE Randomized Clinical Trial (Cardiopoietic stem Cell therapy in heart failURE)
Authors: Jozef Bartunek, Atta Behfar, Dariouch Dolatabadi, Marc Vanderheyden, Miodrag Ostojic, Jo Dens, Badih El Nakadi, Marko Banovic, Branko Beleslin, Mathias Vrolix, Victor Legrand, Christian Vrints, Jean Louis Vanoverschelde, Ruben Crespo-Diaz, Christian Homsy, Michal Tendera, Scott Waldman, William Wijns, Andre Terzic
Journal: Journal of the American College of Cardiology (2013)
TGFβ in the differentiation of embryonic stem cells
Authors: M PUCEAT
Journal: Cardiovascular Research (2006)

The biology of embryonic stem (ES) cell lines has opened new avenues both in the biology of pathophysiological development and in potential regenerative medicine. The transforming growth factor (TGF)-beta superfamily plays a major role in the development of organisms. The family comprises a variety of growth factors that feature disparate functions in the biology of ES cells. These factors regulate both stemness and various cell differentiation pathways. Despite intensive work, the role of this family of growth factors in the function of ES cells is still unclear. More specifically, mouse and human ES cells differentially respond to these factors. Inspired by the biology of development, this review summarizes the current knowledge on the pleiotropic effects of these growth factors on the fate of ES cells.
FEMORAL ACCESS METHODS AND OUTCOMES: UNDERSTANDING THE STRATEGY (FAMOUS) TRIAL
Authors: Ramesh Babu Daggubati, Hutton Brantley, Sundeep Adusumalli, Lakshmi Sindhura Kakani, Poonam Paruchuri, Hassan Ismail, Brian Cabarrus
Journal: Journal of the American College of Cardiology (2011)
Proposed genetic database on Tongans opposed
Authors: B. Burton
Journal: BMJ (2002)

A proposal by a Melbourne based biotechnology company, Autogen, to establish a database of genetic information on the population of Tonga in the South Pacific is floundering after opposition from church and pro-democracy groups.

In November 2000 Autogen triumphantly announced to the Australian Stock Exchange that it had signed an agreement with the Tongan health ministry to undertake a project “aimed at identifying genes that cause common diseases using the unique population resources in the Kingdom of Tonga.”

The project is the product of an alliance between Autogen and Merck Lipha, a subsidiary of the German pharmaceutical giant Merck. Merck holds a 15% stake in Autogen and …
Complex <i>N</i>-Glycan and Metabolic Control in Tumor Cells
Authors: Richard Mendelsohn, Pam Cheung, Lloyd Berger, Emily Partridge, Ken Lau, Alessandro Datti, Judy Pawling, James W. Dennis
Journal: Cancer Research (2007)

Abstract Golgi β1,6N-acetylglucosaminyltransferase V (Mgat5) produces β1,6GlcNAc-branched complex N-glycans on cell surface glycoproteins that bind to galectins and promote surface residency of glycoproteins, including cytokine receptors. Carcinoma cells from polyomavirus middle T (PyMT) transgenic mice on a Mgat5−/− background have reduced surface levels of epidermal growth factor (EGF) and transforming growth factor-β (TGF-β) receptors and are less sensitive to acute stimulation by cytokines in vitro compared with PyMT Mgat5+/+ tumor cells but are nonetheless tumorigenic when injected into mice. Here, we report that PyMT Mgat5−/− cells are reduced in size, checkpoint impaired, and following serum withdrawal, fail to down-regulate glucose transport, protein synthesis, reactive oxygen species (ROS), and activation of Akt and extracellular signal-regulated kinase. To further characterize Mgat5+/+ and Mgat5−/− tumor cells, a screen of pharmacologically active compounds was done. Mgat5−/− tumor cells were comparatively hypersensitive to the ROS inducer 2,3-dimethoxy-1,4-naphthoquinone, hyposensitive to tyrosine kinase inhibitors, to Golgi disruption by brefeldin A, and to mitotic arrest by colcemid, hydroxyurea, and camptothecin. Finally, regulation of ROS, glucose uptake, and sensitivities to EGF and TGF-β were rescued by Mgat5 expression or by hexosamine supplementation to complex N-glycan biosynthesis in Mgat5−/− cells. Our results suggest that complex N-glycans sensitize tumor cells to growth factors, and Mgat5 is required to balance responsiveness to growth and arrest cues downstream of metabolic flux. [Cancer Res 2007;67(20):9771–80]
Appearance of a Common Catheter in an Uncommon Location
Authors: S. M. GANDHI, S. MATTOX, J. SCHEINER, L. S. ZUCKIER
Journal: Clinical Nuclear Medicine (1996)

GANDHI, S. M. M.D.*; MATTOX, S. M.D.†; SCHEINER, J. M.D.†; ZUCKIER, L. S. M.D.*† Author Information
The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat
Authors: Yiqun Ling, Junlan Zhang, Bao Luo, Daisheng Song, Lichuan Liu, Liping Tang, Cecil R. Stockard, William E. Grizzle, David D. Ku, Michael B. Fallon
Journal: Hepatology (2004)

Endothelin-1 (ET-1) stimulation of endothelial nitric oxide synthase (eNOS) via pulmonary endothelial endothelin B (ET B ) receptors and pulmonary intravascular macrophage accumulation with expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are implicated in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Our aim was to evaluate the role of ET-1 in the development of experimental HPS. The time course of molecular and physiological changes of HPS and the effects of selective endothelin receptor antagonists in vivo were assessed after CBDL. Effects of ET-1 on intralobar pulmonary vascular segment reactivity and on eNOS expression and activity in rat pulmonary microvascular endothelial cells (RPMVECs) were also evaluated. Hepatic and plasma ET-1 levels increased 1 week after CBDL in association with a subsequent increase in pulmonary microvascular eNOS and ET B receptor levels and the onset of HPS. Selective ET B receptor inhibition in vivo significantly decreased pulmonary eNOS and ET B receptor levels and ameliorated HPS. CBDL pulmonary artery segments had markedly increased ET B receptor mediated, nitric oxide dependent vasodilatory responses to ET-1 compared with controls and ET-1 triggered an ET B receptor dependent stimulation of eNOS in RPMVECs. Pulmonary intravascular macrophages also accumulated after CBDL and expressed HO-1 and iNOS at 3 weeks. Selective ET B receptor blockade also decreased macrophage accumulation and iNOS production. In conclusion , ET-1 plays a central role in modulating pulmonary micovascular tone in experimental HPS. (Hepatology 2004;39:1593-1602.)
Rib cage distortion in a canine model of flail chest.
Authors: M Cappello, C Yuehua, A De Troyer
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Although blunt chest injuries frequently lead to respiratory failure, the effects of flail chest on the mechanics of breathing have not been evaluated. In the present studies, we have measured the respiratory displacements of the ribs and sternum and the electromyograms (EMG) of the parasternal and external intercostal muscles in eight supine, anesthetized, spontaneously breathing dogs before and after the third to sixth ribs on the right side of the chest were fractured both dorsally and ventrally. After flail, the fractured ribs moved inward, rather than outward, during inspiration, but their inspiratory cranial displacement remained unchanged. The inspiratory outward and caudal displacement of the sternum, the inspiratory EMG activity of the parasternal intercostals, the pattern of breathing, and the arterial blood gases were also unaltered. However, the inspiratory EMG activity recorded from the external intercostals increased consistently to 327 +/- 101% of control (p < 0.05). These observations indicate that with flail chest, the disconnected segment of the rib cage shows paradoxical motion exclusively along the lateral axis; the increased external intercostal activation may account, at least in part, for the persistent inspiratory cranial motion of the ribs. These observations also suggest that the harmful effects of blunt chest injuries are related to pulmonary contusion and pain, rather than to flail chest per se.
Non-capsulate Haemophilus influenzae: a neglected pathogen in adults.
Authors: P Ispahani, E R Youngs
Journal: BMJ (1985)

We recommend that starter regimens can therefore be abandoned when elemental as well as polymeric diets are administered naso- gastrically over 24 hours.1 Jones BJM, Lees R, Andrews J, Frost P, Silk DBA.Comparison of an elemental and polymeric enteral diet in patients with normal gastrointestinal function.
Human Preleukemia
Authors: David W. Golde, Martin J. Cline
Journal: New England Journal of Medicine (1973)

The proliferation and maturation of bone-marrow cells from four patients with preleukemia were studied in vitro with the use of a liquid culture technic. Viable cell counts and 3H-thymidine labeling indexes were similar in preleukemia, acute myelogenous leukemia and normal marrow cultures. Cellular maturation, however, was delayed in the patients with preleukemia and delayed or absent in acute leukemia, resulting in the appearance of a morphologically homogeneous population of immature cells early in culture. Maturation was normal in cultures of bone marrow from three patients with refractory anemia and from three with chronic myelocytic leukemia. These data provide evidence supporting a concept of acute myelogenous leukemia as a primary disturbance of cellular maturation. The technic of bone-marrow culture in liquid medium may be useful in identifying the preleukemic state in man. (N Engl J Med 288:1083–1086, 1973)
THE MECHANICAL ETIOLOGY OF OPTIC NEURITIS
Authors: M. Mamourian, C. J. Smith
Journal: BMJ (1911)

Another aid to diagnosis is oblique illumination combined with the use of a magnifying lens or corneal loup.By this method it is often possible to recognize signs of iritis, which otherwise might be difficult, for fine deposits -on the anterior capsule of the lens con thus be detected.This method is extremely useful to see the punctate deposits on the posterior surface of the cornea, which are -sometimes the only signs of cyclitis, and which may be so faint that it may be impossible to see them with the unaided eye.These deposits are due to inflammatory exudates from the ciliary processes, and, owing to gravitation, are usually situated on the lower part of the -cornea.Yellow oxide of mercury, or Pagenstecher's ointment, is extremely valuable in suitable cases, but if indiscriminately used it can do much harm.I am afraid that in some -quarters it is almost looked upon as a panacea for diseases of the eye.The suitable cases for its use are phlyctenular conjunctivitis, strumous or superficial keratitis, blepharitis, and to aid in the clearing up of corneal opacities, when the eye is free from inflammation.There is a tendency to think that, if any ointment is to be used to the eyes, -it must be the yellow oxide, and that if any drops are -necessary they must be atropin drops.In conclusion, I wish to insist on the importance of 'being able to tell whether the tension of an eye is raised.'Take every opportunity of testing the tension; if in doubt -as to what normal tension is, try your own eyes.Unless you are able to appreciate difference in tension you will fail to diagnrose many cases of glaucoma.When house.-surgeon, I saw admitted into an infirmary two spinster sisters almost completely blind through chronic glauooma.Their medical attendant had diagnosed cataract, and had not sent them in till he thought the cataracts must be ready for extraction, as they came from a considerable distance.Nothing could be done at this late stage to ;avert complete blindness.
Regulation of Cardiac MicroRNAs by Bone Marrow Mononuclear Cell Therapy in Myocardial Infarction
Authors: Kazuma Iekushi, Florian Seeger, Birgit Assmus, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2012)

Cell therapy with bone marrow-derived mononuclear cells (BMCs) can improve recovery of cardiac function after ischemia; however, the molecular mechanisms are not yet fully understood. MicroRNAs (miRNAs) are key regulators of gene expression and modulate the pathophysiology of cardiovascular diseases.We demonstrated that intramyocardial delivery of BMCs in infarcted mice regulates the expression of cardiac miRNAs and significantly downregulates the proapoptotic miR-34a. In vitro studies confirmed that the supernatant of BMC inhibited the expression of H(2)O(2)-induced miR-34a and cardiomyocytes apoptosis. These effects were blocked by neutralizing antibodies directed against insulin-like growth factor-1 (IGF-1). Indeed, IGF-1 significantly inhibited H(2)O(2)-induced miR-34a expression, and miR-34a overexpression abolished the antiapoptotic effect of IGF-1. Likewise, inhibition of IGF-1 signaling in vivo abolished the BMC-mediated inhibition of miR-34 expression and the protective effect on cardiac function and increased apoptosis and cardiac fibrosis. IGF-1 specifically blocked the expression of the precursor and the mature miR-34a, but did not interfere with the transcription of the primary miR-34a demonstrating that IGF-1 blocks the processing of miR-34a.Together, our data demonstrate that the paracrine regulation of cardiac miRNAs by transplanted BMCs contributes to the protective effects of cell therapy. BMCs release IGF-1, which inhibits the processing of miR-34a, thereby blocking cardiomyocyte apoptosis.