tbuckley/cabot-search huggingface dataset:
RbAp48 Regulates Cytoskeletal Organization and Morphology by Increasing K-Ras Activity and Signaling through Mitogen-Activated Protein Kinase
Authors: Anna Scuto, Hongling Zhang, Haiyan Zhao, Maria Rivera, Timothy J. Yeatman, Richard Jove, Javier F. Torres-Roca
Journal: Cancer Research (2007)

Abstract RbAp48 is a WD-40 protein that plays an important role in chromatin metabolism and regulates Ras signaling. Here, we report that RbAp48 is involved in the regulation of cytoskeletal organization, a novel function. First, we show that transfection of RbAp48 into Hs-578T breast cancer cells (Hs-RbAp48-hi) leads to cell size reduction, a rounded cell shape, decreased cellular protrusions, and a higher nuclear/cytoplasmic ratio. Furthermore, we observed cytoskeletal F-actin organization disruption with loss of actin stress fibers and formation of membranous F-actin rings in Hs-RbAp48-hi cells. These morphologic changes were partially reversed by RbAp48 knockdown. Interestingly, mitogen-activated protein kinase (MAPK) was activated in Hs-RbAp48-hi cells, and this activity was also partly reversed by RbAp48 down-regulation. Furthermore, pharmacologic inhibition of MAPK led to the reappearance of organized actin fibers and focal contacts, suggesting MAPK as the effector pathway. Moreover, we show an increase in total Ras activity in Hs-RbAp48-hi cells with K-Ras-GTP becoming the dominant isoform. This reverted to baseline activity levels on RbAp48 small interfering RNA transfection, thus suggesting a direct role for RbAp48 in Ras regulation. Finally, we tested the model in transformed 3T3-K-Ras-G12V fibroblasts. As expected, RbAp48 knockdown in 3T3-K-Ras-hi fibroblasts resulted in reappearance of an organized cytoskeleton and shutdown of K-Ras activity. In conclusion, our data support a model whereby RbAp48 regulates cellular morphology and cytoskeletal organization by increasing K-Ras activity and signaling through MAPK. [Cancer Res 2007;67(20):10317–24]
15d-PGJ2 Primes Eotaxin-induced Eosinophil Chemotaxis Through PPAR-Gamma Ligation
Authors: S. Ueki, Y. Kobayashi, G. Mahemuti, T. Chiba, N. Saito, A. Kanda, H. Kayaba, K. Ohta, J. Chihara
Journal: Journal of Allergy and Clinical Immunology (2006)
250. Correction of Hunter Syndrome in the Ids-Knock-Out Mouse Model by r-AVV Mediated Gene Therapy
Authors: Monica Cardone, Vinicia Polito, Alessandra D'Azzo, Joseph Muenzer, Alberto Auricchio, Andrea Ballabio, Maria Pia Cosma
Journal: Molecular Therapy (2005)

Mucopolyssaccharidosis type II (Hunter syndrome) is a lysosomal storage disorder due to deficiency of iduronate 2-sulfatase (IDS[). Sulfatases are a family of proteins that cleave sulfate ester from a wide range of substrates as glycosaminoglycans, sulfolipid, and steroid sulfates. The Hunter mouse model exhibits many of the characteristics of MPSII, including skeleton abnormalities, coarse facies, macrodactlya, and elevated accumulation of GAGs in the urine and many organs. Generally the major treatment for MPSII syndrome is the enzyme replacement therapy (ERT) and BMT. However there is no effective treatment for MPSII up to now and gene therapy is an attractive approach to cure the MPSII syndrome. After cloning of the hIds cDNA, under the control of the liver-specific promoter (TBG promoter), in a type -2 adeno-associated viral genome, and packaging into the AVV8 serotype (liver-specific), the viral particles were administrated intravenously (IV) to adult Ids-knock-out mice. Plasma levels of IDS enzyme were increased in all treated mice. Two months later the mice were sacrificed and all tissues collected for IDS enzyme assay, GAGs analysis and histopathology. Complete GAGs clearance was found in all tissues examined since the level of Ids enzymatic activity was significantly increased. Microscopically, there was a marked reduction in vacuolization in all of the organs examined. We characterized the CNS defects of the MPSII mice and found degeneration of Purkinje cells and GAGs accumulation in the choroid plexus. Our goal is to rescue the central nervous system phenotype by delivering hIDS adeno-associated vector (AVV2/5CMVhIDS) in the cerebrospinal fluid after intraventricular injection (i.c.). These results demonstrate possibility and the efficacy of gene therapy by rAAV in the Ids knock-out mouse model.
THE VALUE OF ENTEROSTOMY IN SELECTED CASES OF PERITONITIS.
Authors: F. B. LUND
Journal: JAMA (1903)

Among the many serious aspects in which that protean disease, appendicitis, is presented to the surgeon, there is none more alarming than the types in which diffuse peritonitis is attended with intestinal paralysis and distention of the abdomen. Here we have in addition to the already severe septicemia due to absorption from the peritoneum, a toxemia from absorption of the poisonous products of stagnating feces in the intestine, and the great depression produced by gaseous distention of the bowel. The mechanical interference with the descent of the diaphragm renders respiration feeble and shallow, interferes with the aëration of the blood, and adds the grave complication of asphyxia to tax the failing strength of a patient already almost exhausted. It is hard to conceive of a more certainly fatal form of assault on the organism. We all, as surgeons, are familiar with the insidious and dangerous character of those cases of
Video games and health
Authors: Mark Griffiths
Journal: BMJ (2005)

<h3>Background and objective</h3> High calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini, and whether dietary or intraperitoneal magnesium administration affects the onset and course of experimental pancreatitis. <h3>Methods</h3> Pancreatic acini were incubated with up to 10 mM magnesium; [Ca<sup>2+</sup>]<sub>i</sub> (fura-2AM) and intracellular protease activation (fluorogenic substrates) were determined over 60 min. Wistar rats received chow either supplemented or depleted for magnesium (&lt;300 ppm to 30 000 ppm) over two weeks before pancreatitis induction (intravenous caerulein 10 µg/kg/h/4 h); controls received 1 µg/kg/h caerulein or saline. C57BL6/J mice received four intraperitoneal doses of magnesium (NaCl, Mg<sup>2+</sup> 55 192 or 384 mg/kg bodyweight) over 72 h, then pancreatitis was induced by up to eight hourly supramaximal caerulein applications. Pancreatic enzyme activities, protease activation, morphological changes and the immune response were investigated. <h3>Results</h3> Increasing extracellular Mg<sup>2+</sup> concentration significantly reduced [Ca<sup>2+</sup>]<sub>i</sub> peaks and frequency of [Ca<sup>2+</sup>]<sub>i</sub> oscillations as well as intracellular trypsin and elastase activity. Magnesium administration reduced pancreatic enzyme activities, oedema, tissue necrosis and inflammation and somewhat increased Foxp3-positiv T-cells during experimental pancreatitis. Protease activation was found in animals fed magnesium-deficient chow—even with low caerulein concentrations that normally cause no damage. <h3>Conclusions</h3> Magnesium supplementation significantly reduces premature protease activation and the severity of pancreatitis, and antagonises pathological [Ca<sup>2+</sup>]<sub>i</sub> signals. Nutritional magnesium deficiency increases the susceptibility of the pancreas towards pathological stimuli. These data have prompted two clinical trials on the use of magnesium in patients at risk for pancreatitis.
Interactive effects of the ACE DD polymorphism with the NOS III homozygous G849T (Glu298-Asp) variant in determining endothelial function in coronary artery disease
Authors: Michael A. Schmidt, Anjan Chakrabarti, Dana Pfeninnger, Nico Kacirotti, Claire Duvernoy, Anthony Killeen, Robert D. Brook, Sanjay Rajagopalan
Journal: Journal of the American College of Cardiology (2003)
Occupational cancer in Spain.
Authors: C A González, A Agudo
Journal: Environmental Health Perspectives (1999)

The knowledge of specific problems of occupational cancer in Spain is scarce. The environment of the workplace has improved over the last few years after a long period distinguished by bad working conditions, incomplete legislation, and insufficient safety measures and control. It has been estimated that 3,083,479 workers (25.4% of employees) were exposed to carcinogens. The most common occupational exposures to carcinogenic agents were solar radiation, environmental tobacco smoke, silica, and wood dust. The highest number of employees were exposed to silica crystalline (404,729), diesel engine exhaust (274,321), rubber products (99,804), benzene (89,932), ethylene dibromide (81,336), agents used in furniture and cabinet making (72,068), and formaldehyde (71,189). The percentage of total cancer deaths attributed to occupational exposure was 4% (6% in men, 0.9% in women). Compared with other European countries, the incidence of lung cancer and leukemia in Spain are one of the lowest, but it is rapidly increasing. The incidence of urinary bladder and larynx cancer, on the contrary, are one of the highest. Few studies on occupational cancer have been conducted in Spain. The main problems are the availability of death certificates and the quality of the information on occupation in mortality of statistics. It is necessary to improve methods of assessment of exposures using expert hygienists and biologic markers of exposure and diseases. Reduction of cancer by limiting or avoiding exposure to known occupational carcinogens is still necessary.
CHANGES IN PLASMA VOLUME
Authors: William A. Evans
Journal: JAMA (1941)

To the Editor:—  In studying the behavior of the plasma volume during diuresis it is apparent that changes in the plasma volume will depend for their magnitude on the intensity of the diuresis in proportion to the volume of the plasma. To illustrate the superiority of the edematous dog to the edematous cardiac patient for experimental purposes in this respect, I give the following approximate average values taken from the recently published paper of Swigert and Fitz (The Journal, Nov. 23, 1940, p. 1786) and the papers of Bryan, Evans, Fulton and Stead (Arch. Int. Med.55:735 [May] 1935) and Evans and Gibson (Am. J. Physiol.118:251 [Feb.] 1937):    It may be inferred that trebling the flow of urine when the plasma volume is 3,000 cc. may place no burden on the equilibrium between the tissue fluids and the blood, whereas increasing the flow of urine fourteen fold and to a higher rate with a plasma volume of only 1,000 cc. would affect that equilibrium and produce demonstrable and consistent changes in the plasma volume.
A Single Therapeutic Echo Endoscope Used for Combined Transgastric and Transpapillary Drainage of a Pancreatic Abscess
Authors: M. Benyoumes, P. H. Deprez
Journal: Endoscopy (2006)

The design of endoscopic ultrasound (EUS) instruments has been improved to provide a wide therapeutic channel and an elevator to facilitate the movement of needles and medical devices. These improvements make it possible to carry out combined ultrasound and endoscopic approaches in the pancreas and duodenal papilla, with ultrasound examination of surrounding fluid collections [1] [2] [3] [4] [5]. Cystogastrostomy is a particularly interesting field for therapeutic endosonography, with major advantages over conventional therapeutic endoscopy - including increased safety, access to distant collections, and differentiation of cystic lesions [5]. Although cystoenterostomy is an effective form of treatment, it does not provide treatment for impaired ductal drainage [3]. We report here on the use of a combined EUS and endoscopic retrograde cholangiopancreatography procedure using a single echo endoscope.
A Diagnosis of Dismobility—Giving Mobility Clinical Visibility
Authors: Steven R. Cummings, Stephanie Studenski, Luigi Ferrucci
Journal: JAMA (2014)

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
Chronic Arsenic Exposure and Oxidative Stress: <i>OGG1</i> Expression and Arsenic Exposure, Nail Selenium, and Skin Hyperkeratosis in Inner Mongolia
Authors: Jinyao Mo, Yajuan Xia, Timothy J. Wade, Michael Schmitt, X. Chris Le, Runhe Dang, Judy L. Mumford
Journal: Environmental Health Perspectives (2006)

Arsenic, a human carcinogen, is known to induce oxidative damage to DNA. In this study we investigated oxidative stress and As exposure by determining gene expression of OGG1, which codes for an enzyme, 8-oxoguanine DNA glycosylase, involved in removing 8-oxoguanine in As-exposed individuals. Bayingnormen (Ba Men) residents in Inner Mongolia are chronically exposed to As via drinking water. Water, toenail, and blood samples were collected from 299 Ba Men residents exposed to 0.34-826 microg/L As. RNA was isolated from blood, and mRNA levels of OGG1 were determined using real-time polymerase chain reaction. OGG1 expression levels were linked to As concentrations in drinking water and nails, selenium concentrations in nails, and skin hyperkeratosis. OGG1 expression was strongly associated with water As concentrations (p < 0.0001). Addition of the quadratic term significantly improved the fit compared with the linear model (p = 0.05) . The maximal OGG1 response was at the water As concentration of 149 microg/L. OGG1 expression was also significantly associated with toenail As concentrations (p = 0.015) but inversely associated with nail Se concentrations (p = 0.0095) . We found no significant differences in the As-induced OGG1 expression due to sex, smoking, or age even though the oldest group showed the strongest OGG1 response (p = 0.0001) . OGG1 expression showed a dose-dependent increased risk of skin hyperkeratosis in males (trend analysis, p = 0.02) , but the trend was not statistically significant in females. The results from this study provide a linkage between oxidative stress and As exposure in humans. OGG1 expression may be useful as a biomarker for assessing oxidative stress from As exposure.
Chronic Fatigue and the Chronic Fatigue Syndrome: Prevalence in a Pacific Northwest Health Care System
Authors: Dedra Buchwald
Journal: Annals of Internal Medicine (1995)

Objectives: To investigate the point prevalence of the chronic fatigue syndrome and unexplained debilitating chronic fatigue in a community-based sample of persons and to describe demographic, clinical, and psychosocial differences among those with the chronic fatigue syndrome, those with chronic fatigue, and healthy controls. Design: Prospective cohort study. Setting: A health maintenance organization in Seattle, Washington. Participants: A random sample of 4000 members of the health maintenance organization was surveyed by mail for the presence of chronic fatigue. Measurements: Persons with chronic fatigue were evaluated using a questionnaire that requested information about medical history and fatigue and related symptoms; validated measures of functional status and psychological distress; a physical examination; and standardized blood tests. A structured psychiatric interview was done in persons who appeared to meet the original Centers for Disease Control and Prevention (CDC) criteria for the chronic fatigue syndrome. Participants completed self-report measures at 12 and 24 months. Those with chronic fatigue were reevaluated in person 1 year after study enrollment. Results: 3066 (77%) of the 4000 members surveyed responded. Chronic fatigue was reported by 590 persons (19%). Of these, 388 (66%) had a medical or psychiatric condition that could account for the fatigue. Of the 74 persons (37%) with chronic fatigue who were enrolled in the study, only 3 met the CDC criteria for the chronic fatigue syndrome. The remaining 71 persons were designated as having chronic fatigue alone. Seventy-four healthy, age- and sex-matched controls who were drawn from the same sample but who denied having chronic fatigue were also studied. Demographic characteristics were similar in persons with the chronic fatigue syndrome, persons with chronic fatigue alone, and controls. Those with the chronic fatigue syndrome or chronic fatigue alone had more frequent cervical and axillary adenopathy, poorer functional status, and greater psychological distress than controls. Women and minorities were not overrepresented among cases with chronic fatigue. Conclusions: Using different assumptions about the likelihood that persons who did not participate in the study had the chronic fatigue syndrome, the estimated crude point prevalence of the syndrome in this community ranged from 75 to 267 cases per 100 000 persons. The point prevalence of chronic fatigue alone was strikingly higher; it ranged from 1775 to 6321 cases per 100 000 persons.
Registering herbalists will improve patients' safety, says health secretary
Authors: Z. Kmietowicz
Journal: BMJ (2010)

Practitioners in the United Kingdom who supply unlicensed herbal products, including Chinese medicines, will have to register with the Complementary and Natural Healthcare Council under new plans from the Department of Health.

The health secretary for England, Andy Burnham, said that ensuring registration of herbal practitioners would help prevent unscrupulous practices in the sale of herbal remedies to the public in high street shops and private clinics.

The move follows a consultation with the scientific community and the public in all four countries of the UK last year. It will become law as soon as parliamentary time allows, said a health department spokeswoman.

Mr Burnham said, “Emerging evidence clearly demonstrates that the public needs better protection …
GMC issues new guidance on clinical research
Authors: S. Mayor
Journal: BMJ (2002)

The General Medical Council—the body that registers doctors in the UK—has issued new guidance on the standards expected for research in the NHS, universities, and the private sector.

Trust between participants in research and healthcare professionals is emphasised as the central principle in conducting ethical clinical research. The guidance warns: “Doctors involved in research have an ethical duty to show respect for human life and respect peoples’ autonomy. Partnership between participants and the health care team is essential to good research practice and such partnerships are based on trust. You must respect patients’ and volunteers’ rights to make decisions about their involvement in research.”

Sir Cyril Chantler, chairman of the GMC standards …
Ablation of C/EBP Homologous Protein Attenuates Endoplasmic Reticulum–Mediated Apoptosis and Cardiac Dysfunction Induced by Pressure Overload
Authors: Hai Ying Fu, Ken-ichiro Okada, Yulin Liao, Osamu Tsukamoto, Tadashi Isomura, Mitsutoshi Asai, Tamaki Sawada, Keiji Okuda, Yoshihiro Asano, Shoji Sanada, Hiroshi Asanuma, Masanori Asakura, Seiji Takashima, Issei Komuro, Masafumi Kitakaze, Tetsuo Minamino
Journal: Circulation (2010)

Apoptosis may contribute to the development of heart failure, but the role of apoptotic signaling initiated by the endoplasmic reticulum in this condition has not been well clarified.In myocardial samples from patients with heart failure, quantitative real-time polymerase chain reaction revealed an increase in messenger RNA for C/EBP homologous protein (CHOP), a transcriptional factor that mediates endoplasmic reticulum-initiated apoptotic cell death. We performed transverse aortic constriction or sham operation on wild-type (WT) and CHOP-deficient mice. The CHOP-deficient mice showed less cardiac hypertrophy, fibrosis, and cardiac dysfunction compared with WT mice at 4 weeks after transverse aortic constriction, although the contractility of isolated cardiomyocytes from CHOP-deficient mice was not significantly different from that in the WT mice. In the hearts of CHOP-deficient mice, phosphorylation of eukaryotic translation initiation factor 2alpha, which may reduce protein translation, was enhanced compared with WT mice. In the hearts of WT mice, CHOP-increased apoptotic cell death with activation of caspase-3 was observed at 4 weeks after transverse aortic constriction. In contrast, CHOP-deficient mice had less apoptotic cell death and lower caspase-3 activation at 4 weeks after transverse aortic constriction. Furthermore, the Bcl2/Bax ratio was decreased in WT mice, whereas this change was significantly blunted in CHOP-deficient mice. Real-time polymerase chain reaction microarray analysis revealed that CHOP could regulate several Bcl2 family members in failing hearts.We propose the novel concept that CHOP, which may modify protein translation and mediate endoplasmic reticulum-initiated apoptotic cell death, contributes to development of cardiac hypertrophy and failure induced by pressure overload.
Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction
Authors: Itsuro Morishima, Takahito Sone, Kenji Okumura, Hideyuki Tsuboi, Junichiro Kondo, Hiroaki Mukawa, Hideo Matsui, Yukio Toki, Takayuki Ito, Tetsuo Hayakawa
Journal: Journal of the American College of Cardiology (2000)
Cathepsin D Expression in Renal Cell Cancer–Clinical Implications
Authors: Axel S. Merseburger, Joerg Hennenlotter, Perikles Simon, Petra A. Ohneseit, Ursula Kuehs, Stephan Kruck, Eva Koch, Ulrich Vogel, Arnulf Stenzl, Markus A. Kuczyk
Journal: European Urology (2005)
Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B
Authors: A Penna, G Del Prete, A Cavalli, A Bertoletti, M M D'Elios, R Sorrentino, M D'Amato, C Boni, M Pilli, F Fiaccadori, C Ferrari
Journal: Hepatology (1997)

The cytokine pattern secreted by T cells on viral antigen recognition is believed to exert a profound influence on both the type of disease caused by the infecting agent and the final outcome of the viral infection. To characterize the cytokine pattern associated with spontaneous resolution of acute hepatitis B, we analyzed interferon gamma (IFN-γ), interleukin (IL)-4, and IL-5 production by a wide series of hepatitis B virus (HBV) nucleocapsid-specific T-cell lines (34 lines) and T-cell clones (71 clones) derived from the peripheral blood of 13 patients during the acute or recovery phase of hepatitis B (2 and 7 of them were studied only in the recovery or the acute phase, respectively, and 4 during both). Most T-cell lines (67%) and clones (77%) isolated during the acute phase of infection expressed a T-helper (Th) 1 cytokine profile dominated by the production of IFN-γ. A larger proportion (74%) of T-cell lines produced several years after resolution of hepatitis was able to secrete not only IFN-γ, but also IL-4 and IL-5 (Th0-like cells). Results indicate that the antigen-specific fraction of peripheral blood T cells in acute self-limited hepatitis B selectively secrete Th1-type eytokines, suggesting that Th1-mediated effects may contribute not only to liver cell injury, but probably also to recovery from disease and successful control of infection.