tbuckley/cabot-search huggingface dataset:
Restored insulin-sensitivity in IRS-1–deficient mice treated by adenovirus-mediated gene therapy
Authors: Kohjiro Ueki, Toshimasa Yamauchi, Hiroyuki Tamemoto, Kazuyuki Tobe, Ritsuko Yamamoto-Honda, Yasushi Kaburagi, Yasuo Akanuma, Yoshio Yazaki, Sininchi Aizawa, Ryozo Nagai, Takashi Kadowaki
Journal: Journal of Clinical Investigation (2000)

Insulin resistance is commonly observed both in overt diabetes and in individuals prone to, but not yet manifesting, diabetes. Hence the maintenance or restoration of insulin sensitivity may prevent the onset of this disease. We previously showed that homozygous disruption of insulin receptor substrate-1 (IRS-1) in mice resulted in insulin resistance but not diabetes. Here, we have explored the mechanism of systemic insulin resistance in these mice and used adenovirus-mediated gene therapy to restore their insulin sensitivity. Mice expressing the IRS-1transgene showed almost normal insulin sensitivity. Expression of an IRS-1 mutant (IRS-1Δp85) lacking the binding site for the p85 subunit of phosphatidylinositol 3-kinase (PI3K) also restored insulin sensitivity, although PI3K is known to play a crucial role in insulin’s metabolic responses. Protein kinase B (PKB) activity in liver was decreased in null mice compared with the wild-type and the null mice expressing IRS-1 or IRS-1Δp85. In primary hepatocytes isolated from null mice, expression of IRS-1 enhanced both PI3K and PKB activities, but expression of IRS-1Δp85 enhanced only PKB. These data suggest that PKB in liver plays a pivotal role in systemic glucose homeostasis and that PKB activation might be sufficient for reducing insulin resistance even without full activation of PI3K.
Environmental and Occupational Interventions for Primary Prevention of Cancer: A Cross-Sectorial Policy Framework
Authors: Carolina Espina, Miquel Porta, Joachim Schüz, Ildefonso Hernández Aguado, Robert V. Percival, Carlos Dora, Terry Slevin, Julietta Rodriguez Guzman, Tim Meredith, Philip J. Landrigan, Maria Neira
Journal: Environmental Health Perspectives (2013)

Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low- and middle-income countries. A substantial proportion of all cancers are attributable to carcinogenic exposures in the environment and the workplace.We aimed to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer.We identified relevant studies through PubMed by using combinations of the search terms "environmental," "occupational," "exposure," "cancer," "primary prevention," and "interventions." To supplement the literature review, we convened an international conference titled "Environmental and Occupational Determinants of Cancer: Interventions for Primary Prevention" under the auspices of the World Health Organization, in Asturias, Spain, on 17-18 March 2011.Many cancers of environmental and occupational origin could be prevented. Prevention is most effectively achieved through primary prevention policies that reduce or eliminate involuntary exposures to proven and probable carcinogens. Such strategies can be implemented in a straightforward and cost-effective way based on current knowledge, and they have the added benefit of synergistically reducing risks for other noncommunicable diseases by reducing exposures to shared risk factors.Opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens.
Plasma Angiopoietin-2 Predicts the Onset of Acute Lung Injury in Critically Ill Patients
Authors: Ashish Agrawal, Michael A. Matthay, Kirsten N. Kangelaris, John Stein, Jeffrey C. Chu, Brandon M. Imp, Alfredo Cortez, Jason Abbott, Kathleen D. Liu, Carolyn S. Calfee
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Current clinical prediction scores for acute lung injury (ALI) have limited positive predictive value. No studies have evaluated predictive plasma biomarkers in a broad population of critically ill patients or as an adjunct to clinical prediction scores.To determine whether plasma angiopoietin-2 (Ang-2), von Willebrand factor (vWF), interleukin-8 (IL-8), and/or receptor for advanced glycation end products (sRAGE) predict ALI in critically ill patients.Plasma samples were drawn from critically ill patients (n = 230) identified in the emergency department. Patients who had ALI at baseline or in the subsequent 6 hours were excluded, and the remaining patients were followed for development of ALI.Nineteen patients developed ALI at least 6 hours after the sample draw. Higher levels of Ang-2 and IL-8 were significantly associated with increased development of ALI (P = 0.0008, 0.004, respectively). The association between Ang-2 and subsequent development of ALI was robust to adjustment for sepsis and vasopressor use. Ang-2 and the Lung Injury Prediction Score each independently discriminated well between those who developed ALI and those who did not (area under the receiver operating characteristic curve, 0.74 for each), and using the two together improved the area under the curve to 0.84 (vs. 0.74, P = 0.05). In contrast, plasma levels of sRAGE and vWF were not predictive of ALI.Plasma biomarkers such as Ang-2 can improve clinical prediction scores and identify patients at high risk for ALI. In addition, the early rise of Ang-2 emphasizes the importance of endothelial injury in the early pathogenesis of ALI.
Serendipitous Detection of a Mallory-Weiss Tear on Hepatic Imaging
Authors: LAWRENCE C. SWAYNE, MICHAEL SAMACH
Journal: Clinical Nuclear Medicine (1986)

A case of a bleeding Mallory-Weiss tear was detected by liver imaging and verified at endoscopy. Delayed imaging demonstrated small bowel visualization, confirming the impression of faint gastric activity observed on the initial routine scan.
Anthracycline-Induced Cardiotoxicity
Authors: Herman O. Klein
Journal: Annals of Internal Medicine (1997)

Letters15 May 1997Anthracycline-Induced CardiotoxicityHerman O. Klein, MDHerman O. Klein, MDMeir Hospital, Kfar-Saba, IsraelSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-10-199705150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Missing from Shan and colleagues' interesting review of anthracycline-induced cardiotoxicity [1] is any reference to the potential use of L-carnitine to prevent adriamycin cardiotoxicity. Can the authors express their opinion? The beneficial effects of L-carnitine were reported by Anselmi and colleagues at the 31st Annual Meeting of the European Association of Pediatric Cardiologists.REFERENCE1. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med. 1996; 125:47-58. Google Scholar Author, Article, and Disclosure InformationAuthors: Herman O. Klein, MDAffiliations: Meir Hospital, Kfar-Saba, Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEntwurf eines integrativen Erfolgsmanagementkonzeptes 15 May 1997Volume 126, Issue 10Page: 827 ePublished: 15 August 2000 Issue Published: 15 May 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Americans retreat on SI units.
Authors: M. Nylenna, R. Smith
Journal: BMJ (1992)

that the test had not been correctly performed.In the case of the false negative result the subject would also have to show that loss or damage had been sustained as a result of the delayed diagnosis.A health authority might also be judged negligent if substandard laboratory reagents or techniques resulted in an incorrect result or if staff failed to respond appropriately to a positive result.Screening has an intuitive appeal.Nevertheless, health authorities may be reluctant to continue or embark on screening programmes that have not been adequately researched or that expose them to a risk of litigation.They must consider what might go wrong with a screening programme, how a court might react in the event of a mishap, how informed consent can best be obtained, and how hazards can be minimised.At the same time they should remember that, though failure to provide and promote a particular health care measure is not necessarily actionable, it might become so if a substantial body of medical opinion came to believe that such a measure was necessary.
Preventing postoperative nausea and vomiting: Prevention in context
Authors: J. B Carlisle
Journal: BMJ (2006)

EDITOR—Metoclopramide is one of the drugs that we reviewed in our recent Cochrane meta-analysis.1 We also found that metoclopramide was effective. We found that, compared with placebo, the average relative risk for postoperative nausea and vomiting was 0.76 for all doses of metoclopramide, which compares to 0.89, 0.75, and 0.63 for 10 mg, 25 mg, and 50 mg of metoclopramide in the study reported by Wallenborn et al.2 We would like to comment on the useful information that Wallenborn's study provides in this context.

Wallenborn et al provided the most …
Infants with Food Protein-Induced Enterocolitis Syndrome (FPIES) Can Be Classified Into Two Distinct Subgroups Based On the Presence or Absence of Bloody Stool and Their Antigen-Specific Cytokine Production Profiles
Authors: Hideaki Morita, Ichiro Nomura, Tetsuo Shoda, Hirotoshi Unno, Akio Matsuda, Hirohisa Saito, Kenji Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2013)
Sexual Intercourse and Urinary Infections
Authors: Ronald G. Evens
Journal: New England Journal of Medicine (1978)

The common belief that there is a close association between sexual intercourse and urinary-tract infection in young women is largely based on anecdotal information and clinical impressions. "Honeymoon cystitis" and "pyelitis of pregnancy" are rather dramatic events that are often preceded by a history of urinary infection. These disorders, as well as a history of antecedent sexual activity reported by patients with acute urinary-tract infection, have strengthened the theory that the two events are closely linked. Despite the attractiveness of the hypothesis, there is as yet no clear-cut study that has adequately defined a causal relation.My own study with . . .
Abstract 4989: Selective inhibitors of the inositol-requiring enzyme 1 kinase domain
Authors: Carly Griffin, Ayome Abibi, Ratheesh Subramaniam, Hassan S. Zaidi, Richard Marcellus, Gennadiy Poda, Michael Prakesch, David Uehling, Marella Canny, David Chiovitti, Dan Durocher, Frank Sicheri, Rima Al-awar
Journal: Cancer Research (2012)

Abstract Inositol-requiring enzyme 1 (IRE1) is a key player in endoplasmic reticulum (ER) stress conditions. IRE1 is a highly conserved ER-membrane protein activated by the unfolded protein response (UPR) or other ER-stressors, such as hypoxia and glucose deprivation. Stress causes IRE1 to undergo oligomerization and autophosphorylation, which triggers nonconventional splicing of XBP-1 mRNA by its cytosolic endonuclease domain. The resulting spliced XBP-1 protein (XBP-1s) is a transcription factor that serves to increase the protein folding capacity and ultimately restore homeostasis of the ER. Thus, sustained IRE1 activity promotes cell survival and inhibition of IRE1 may be a potential therapeutic target for diseases associated with chronic ER-stress, such as neurodegenerative disorders, diabetes, and cancer. Proper RNase function of IRE1 is dependent upon autophosphorylation of the kinase domain. We therefore screened a library of 380 known kinase inhibitors, consisting of tool compounds and compounds already in clinical use, for those with activity against the human IRE1 kinase domain. As a result, a number of compounds were found that potently inhibit phosphorylation of a biotin-STK peptide substrate in the presence of human IRE1 (IC50 &amp;lt; 1 μM), as determined by HTRF (homogeneous time-resolved fluorescence). The lead compounds were then screened in cell-based assays. Several ATP-mimetic compounds with diverse chemotypes were found to inhibit expression of XBP-1s in human cancer cells under pharmacologically-induced acute ER-stress. Furthermore, transcriptional targets of XBP-1s and phosphorylation of IRE1 were also negatively affected by these compounds. Interestingly one compound in particular, a known ROCK1 (Rho-associated coiled-coil containing protein kinase 1) inhibitor (OICR000287A), was significantly more toxic to cells under acute ER-stress than to unstressed cells. This study suggests that development of ATP-competitive inhibitors of human IRE1 is a promising therapeutic strategy for ER-stress related diseases including myeloma, pancreatic and other secretory cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4989. doi:1538-7445.AM2012-4989
Informing the Debate: Rates of Kidney Transplantation in Nations With Presumed Consent
Authors: Lucy D. Horvat, Meaghan S. Cuerden, S. Joseph Kim, John J. Koval, Ann Young, Amit X. Garg
Journal: Annals of Internal Medicine (2010)

Background: The kidney is the most common transplanted organ, accounting for almost all living donor transplantations and most deceased donor organ transplantations. The organ shortage has caused policymakers in many nations to debate the merits of adopting presumed consent legislation as a way to increase donor organ donation from deceased donors. Objective: To compare characteristics and kidney transplantation rates for countries with presumed consent for deceased organ donation with countries with explicit consent. Design: A longitudinal study of international kidney transplantation from 1997 to 2007. Setting: 44 nations performing kidney transplantation. Patients: Recipients of deceased and living kidney donor transplants. Measurements: Rates of transplantation of kidneys from deceased and living donors. Results: National characteristics, such as population size, proportion of the population self-identified as Catholic, per capita gross domestic product, health expenditures, and physician density, varied widely for the 22 nations with presumed consent and the 22 nations with explicit consent. Deceased donor kidney transplantation rates were higher in nations with presumed consent (median, 22.6 transplantations per million population [pmp]; interquartile range [IQR], 9.3 to 33.8) versus nations with explicit consent (median, 13.9 transplantations pmp; IQR, 3.6 to 23.1). Living donor kidney transplantation rates were lower in nations with presumed consent (median, 2.4 transplantations pmp; IQR, 1.7 to 4.3) versus nations with explicit consent (median, 5.9 transplantations pmp; IQR, 2.3 to 12.2). The findings were consistent when nations were classified according to per capita gross domestic product, health expenditures, and physician density. Limitation: As with any observational study, associations may not be causal. Conclusion: Nations with presumed consent have higher rates of deceased donor kidney transplantation than nations with explicit consent. Any nation deciding to adopt presumed consent should carefully consider and reduce any negative effect on rates of living donation. Primary Funding Source: Canadian Institutes of Health Research and Lawson Health Research Institute.
Classification vs Typology
Authors: Kurt A. Hoehne
Journal: JAMA (1980)

THERE are two principal approaches with which we try to order in our mind the infinite variety of manifestations of the world around us. Without going into historical and epistemological details, 1 I shall confine discussion to the implications these two approaches have for the study of man in general and the work of the clinician in particular.  Definition  The simplest method of arriving at some kind of logical order is to select or to measure an easily obtainable variable by which we can subdivide a group into welldefined sections or classes. For studying people such a variable could be height, weight, age, color of skin, language, or religion. We will call this method classification.  The second method does not appear at first to be particularly systematic or scientific but nonetheless is of considerable heuristic importance. It consists basically of the intuitive identification of a characteristic and meaningful constellation of
Saphenous Vein Arteriovenous Fistulas
Authors: Curt A. Ries
Journal: JAMA (1973)

Subcutaneous arteriovenous fistulas were successfully constructed, using autologous saphenous vein grafts, in two patients with hemophilia. Neither patient had remaining arm veins suitable for infusions of factor VIII. The fistulas have been functioning well for 10 and 13 months.
Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates
Authors: Abdelmajid Sabile, Gabriel Perlemuter, Fulvia Bono, Kyoko Kohara, France Demaugre, Michinori Kohara, Yoshiharu Matsuura, Tatsuo Miyamura, Christian Bréchot, Giovanna Barba
Journal: Hepatology (1999)

Several lines of evidence suggest that hepatitis C virus (HCV) core protein may modulate cellular transduction signals and alter lipid metabolism. We have investigated the binding of HCV core protein to cellular proteins by combining 2 yeast hybrid, confocal, and surface plasmon resonance assays. Our results show the direct binding of the viral protein to apolipoprotein AII (apoAII) and map the interaction domain to the C-terminal of HCV core protein. To investigate the biological relevance of the interaction between HCV core and lipid metabolism, we took advantage of the well-established increase in apoAII expression caused by fibrates in HepG2 cells. After fenofibric acid treatment, we show a parallel increase in apoAII and core protein secretion, this effect being abolished by brefeldin A. Our study identifies apoAII as one of the cellular targets for HCV core protein. We also show that the intervention of fenofibric acid in cellular lipid metabolism directly affects the expression pattern of HCV core protein.
Megestrol for AIDS-Related Anorexia
Authors: Mathew Maurer
Journal: Annals of Internal Medicine (1995)

Letters1 June 1995Megestrol for AIDS-Related AnorexiaMathew MaurerMathew MaurerSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-11-199506010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As a resident in internal medicine in New York City, I treat many patients with AIDS. I was pleased to read two well-done studies describing a beneficial effect of megestrol on weight gain in patients with AIDS-related cachexia [1, 2]. My optimism is limited, however, by an encounter with a patient for whom I prescribed megestrol. Oster and colleagues [1] state that “because megestrol acetate is a derivative of progesterone, concern exists about the potential effect of megestrol on the endocrine system.” This concern is well illustrated by the case of a 29-year-old woman with AIDS who ...References1. Oster MH, Enders SR, Samuels SJ, Cone LA, Hooton TM, Browder HP, et al. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med. 1994; 121:400-8. Google Scholar2. Von Roenn JH, Armstrong D, Kotler DP, Cohn DI, Klimas NG, Tchekmedyian NS, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med. 1994; 121:393-9. Google Scholar3. Leinung M, Miller C. Adrenal suppression due to megestrol acetate (Megace) (Abstract). 76th Annual Meeting of Endocrine Society. Anaheim, California; June 1994. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdrenal function in cystic fibrosisMegestrol acetate therapy and secondary adrenal suppression 1 June 1995Volume 122, Issue 11Page: 879-881KeywordsAIDSAdrenocorticotropic hormoneCortisolPatientsPneumocystis carinii pneumoniaProgesteroneResuscitationThyroidWeight gainWeight loss ePublished: 15 August 2000 Issue Published: 1 June 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury
Authors: Florentia Papastefanaki, Igor Jakovcevski, Nafsika Poulia, Nevena Djogo, Florian Schulz, Tamara Martinovic, Darko Ciric, Gabrielle Loers, Tobias Vossmeyer, Horst Weller, Melitta Schachner, Rebecca Matsas
Journal: Molecular Therapy (2015)

Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.
Intrathoracic vagus nerve neurofibroma and sudden death in a patient with neurofibromatosis.
Authors: L T Chow, B S Shum, W H Chow
Journal: Thorax (1993)

A 21 year old man with type 1 neurofibromatosis was found dead in the middle of the night. Postmortem examination revealed a large neurofibroma arising from the right intrathoracic vagus nerve, which might have contributed to his sudden death.
COMPARISON OF TRANS-FEMORAL TRANSCATHETER AORTIC VALVE IMPLANTATION (TAVI) PERFORMED WITH EDWARDS SAPIEN OR COREVALVE IMPLANTATION
Authors: Cosmo Godino, Alaide Chieffo, Francesco Maisano, Matteo Montorfano, Azeem Latib, Alfonso Ielasi, Micaela Cioni, Marco Mussardo, Paolo Denti, Andrea Giacomini, Maurizio Taramasso, Irina Arendar, Antonio Grimaldi, Pietro Spagnolo, Giovanni La Canna, Ottavio Alfieri, Antonio Colombo
Journal: Journal of the American College of Cardiology (2011)
Stage IV Chronic Kidney Disease
Authors: Hanna Abboud, William L. Henrich
Journal: New England Journal of Medicine (2010)

A 54-year-old woman with type 2 diabetes presents for care. Her creatinine level has increased from 1.1 mg per deciliter (97 μmol per liter) 4 years ago to 3.1 mg per deciliter (274 μmol per liter) at the most recent measurement (estimated glomerular filtration rate, 26 ml per minute per 1.73 m2 of body-surface area). Her urinary protein excretion is 2.8 g per 24 hours. Her blood pressure is 155/90 mm Hg, and the glycated hemoglobin level is 7.6 mg per deciliter. Her current medications include an oral hypoglycemic agent, an angiotensin-converting–enzyme inhibitor, a statin, and a thiazide diuretic. How should her case be managed?