tbuckley/cabot-search huggingface dataset:
Di-(2-ethylhexyl) Phthalate Enhances Atopic Dermatitis-Like Skin Lesionsin Mice
Authors: Hirohisa Takano, Rie Yanagisawa, Ken-ichiro Inoue, Takamichi Ichinose, Kaori Sadakane, Toshikazu Yoshikawa
Journal: Environmental Health Perspectives (2006)

Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and has become ubiquitous in the developed countries. DEHP reportedly displays an adjuvant effect on immunoglobulin production. However, it has not been elucidated whether DEHP is associated with the aggravation of atopic dermatitis. We investigated the effects of DEHP on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. NC/Nga male mice were injected intradermally with mite allergen on their right ears. In the presence of allergen, DEHP (0, 0.8, 4, 20, or 100 microg) was administered by intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the protein expression of chemokines. Exposure to DEHP at a dose of 0.8-20 microg caused deterioration of atopic dermatitis-like skin lesions related to mite allergen; this was evident from macroscopic and microscopic examinations. Furthermore, these changes were consistent with the protein expression of proinflammatory molecules such as macrophage inflammatory protein-1alpha (MIP-1alpha) and eotaxin in the ear tissue in overall trend. In contrast, 100 microg DEHP did not show the enhancing effects. These results indicate that DEHP enhances atopic dermatitis-like skin lesions at hundred-fold lower levels than the no observed adverse effect level determined on histologic changes in the liver of rodents. DEHP could be at least partly responsible for the recent increase in atopic dermatitis.
Red cell transfusions for treating anaemia in the absence of bleeding
Authors: T. S. Walsh
Journal: BMJ (2015)

Use a restrictive strategy in most patient groups

Transfusion of donated (allogeneic) red blood cells is life saving for patients with major bleeding, such as after major trauma or childbirth. However, probably less than 15% of the 85 million units of blood transfused globally each year are used to treat haemorrhagic shock; most are given to patients experiencing blood loss during surgery, or with chronic medical conditions or haematological malignancies.1 In these situations the circulating blood volume is either normal or can be restored with other fluids such as crystalloid solutions. For these patients it is uncertain when the benefits of supplementing oxygen carrying capacity by transfusing allogeneic blood outweigh the risks. In a linked updated meta-analysis Holst and colleagues (doi:10.1136/bmj.h1354) explore this issue by comparing more liberal with more restrictive transfusion practices and suggest that in many clinical situations a restrictive transfusion strategy does no harm and reduces patients’ exposure to potentially hazardous blood products.2

Red blood cells transport oxygen to cells. Non-anaemic adults transport about 1 litre of oxygen from the lungs to tissues every minute but use only 0.25 litres, creating a wide “safety margin.” When tissues acutely need more oxygen (for example during exercise), the cardiac output and the proportion of oxygen extracted from blood increase to maintain supply. The “anaerobic threshold,” …
The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling
Authors: Sari Tuupanen, Mikko Turunen, Rainer Lehtonen, Outi Hallikas, Sakari Vanharanta, Teemu Kivioja, Mikael Björklund, Gonghong Wei, Jian Yan, Iina Niittymäki, Jukka-Pekka Mecklin, Heikki Järvinen, Ari Ristimäki, Mariachiara Di-Bernardo, Phil East, Luis Carvajal-Carmona, Richard S Houlston, Ian Tomlinson, Kimmo Palin, Esko Ukkonen, Auli Karhu, Jussi Taipale, Lauri A Aaltonen
Journal: Nature Genetics (2009)
Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4–S5 linker in slow inactivation
Authors: S CASINI, H TAN, Z BHUIYAN, C BEZZINA, P BARNETT, E CERBAI, A MUGELLI, A WILDE, M VELDKAMP
Journal: Cardiovascular Research (2007)

Objective Mutations in SCN5A, the gene encoding the α-subunit of the cardiac sodium channel (Nav1.5), have been associated with various inherited arrhythmia syndromes, including Brugada syndrome (BrS). Here, we report the functional consequences of a novel missense SCN5A mutation, G1319V, identified in a BrS patient. The G1319V mutation is located in the loop connecting transmembrane segments 4 and 5 in domain III (DIIIS4–S5), a region so far considered to be exclusively involved in fast inactivation. Methods Whole-cell mutant (G1319V) and wild-type (WT) sodium currents (INa) were studied in the Human Embryonic Kidney cell line (HEK-293) transfected with Nav1.5 α-subunit cDNA (WT or mutant) together with hβ1-subunit cDNA, using the patch-clamp technique. Results Maximal peak INa and persistent sodium current were similar in WT and channel G1319V channels. The G1319V mutation shifted the potential of half-maximal (V1/2) activation towards more positive potentials (+3.7 mV), thereby increasing the degree of depolarization required for activation. The V1/2 of inactivation of G1319V channels was shifted by −6.0 mV compared to WT, resulting in a reduced channel availability. The change in the steady-state inactivation was completely due to a negative shift (−6.8 mV) of the voltage-dependence of slow inactivation, while the voltage-dependence of fast inactivation was unaffected. The fast component of recovery from inactivation of G1319V channels was slowed down. Finally, the G1319V mutation caused a two-fold increase in the propensity of the channels to enter the slow inactivated state. Reduction in INa peak amplitude on repetitive depolarizations at short interpulse intervals (40 ms) was significantly more pronounced in G1319V compared to WT. Accordingly, carriers of the G1319V mutation showed marked QRS widening upon increases in heart rate during exercise testing, pointing to enhancement of slow inactivation. Conclusions We identified the DIIIS4–S5 linker as a new region involved in slow inactivation of Nav1.5. The biophysical alterations of the G1319V mutation all contribute to a reduction in INa, in line with the proposed mechanism underlying BrS.
COMPULSORY VACCINATION; SHOULD IT BE ENFORCED BY LAW?
Authors: CLARK BELL
Journal: JAMA (1897)

This subject came recently before the Medico-Legal Society in the city of New York, introduced by a paper presented by Dr. Montague R. Leverson, in which his position was mainly an assault upon vaccination itself. Most laymen and the majority of the medical profession have been educated to accept vaccination as a reliable, safe, and the only preventive remedy, to insure against smallpox, and without especial examination the world has accepted the remedy discovered by Jenner, whose centennial has just been celebrated by all the world, even in Japan. It was not considered quite the proper way to meet the issue in a controversy pro and con, as to the merits of vaccination for this reason, and the issue was broadened and widened so as to embrace this issue: "Conceding the utility and efficacy of vaccination as a preventive against smallpox should it be made compulsory?" Owing to the recent
The rise of the British pharmaceutical industry.
Authors: J Liebenau
Journal: BMJ (1990)

The growth of the modern pharmaceutical industry took place largely in western Europe and the United States.At the beginning of the nineteenth century little distinction could be found between, on the one hand, the American corner shop that sold drugs, the British chemist's shop, or, in Germany and elsewhere, the apothecary and, on the other hand, importers, manufacturers, and wholesale drug traders.Drug exchanges operated in major trading ports, so in Philadelphia, New York, London, and Amsterdam the trade had a self governing body that helped to minimise bad business practices, especially overcharging by shippers.For the most part, however, trade consisted of representatives or proprietors of large pharmacies going to the ports when shipments came in and bargaining directly with shipping agents for bulk purchases.These purchases would typically be processed in a very preliminary fashion, cleaned, sorted, and packaged, and then enter the wholesale trade as materia medica.'3Companies such as Allen and Hanbury, Jacob Bell, and Thomas Morson, all small London operators, established standard working arrangements whereby they would conduct retail trade from their city shops and maintain warehouses with compounding rooms from which they would serve as wholesalers to retailers in south east England.Trade was well established by the early years of the century with most suppliers offering complete ranges of medicines but perhaps concentrating on the larger scale processing of a few types of items.So when
Dopamine Transporter Occupancies in the Human Brain Induced by Therapeutic Doses of Oral Methylphenidate
Authors: Nora D. Volkow, Gene.-Jack Wang, Joanna S. Fowler, Samuel J. Gatley, Jean Logan, Yu-Shin Ding, Robert Hitzemann, Naomi Pappas
Journal: American Journal of Psychiatry (1998)

Objective:The therapeutic effects of methylphenidate in the treatment of attention deficit disorder have been attributed to its ability to increase the synaptic concentration of dopamine by blocking the dopamine transporters. However, the levels of dopamine transporter blockade achieved by therapeutic doses of methylphenidate are not known. This study measured, for the first time, dopamine transporter occupancy by orally administered methylphenidate in the human brain and its rate of uptake in the brain. Method:Positron emission tomography (PET) and [11C]cocaine were used to estimate dopamine transporter occupancies after different doses of oral methylphenidate in seven normal subjects (mean age=24 years, SD=7). In addition, the pharmacokinetics of oral methylphenidate were measured in the baboon brain through use of PET and [11C]methylphenidate administered through an orogastric tube.Results:At 120 minutes after administration, oral methylphenidate produced a dose-dependent blockade of dopamine transporter; means=12% (SD=4%) for 5 mg, 40% (SD=12%) for 10 mg, 54% (SD=5%) for 20 mg, 72% (SD=3%) for 40 mg, and 74% (SD=2%) for 60 mg. The estimated dose of oral methylphenidate required to block 50% of the dopamine transporter corresponded to 0.25 mg/kg. Oral methylphenidate did not reach peak concentration in brain until 60 minutes after its administration.Conclusions:Oral methylphenidate is very effective in blocking dopamine transporters, and at the weight-adjusted doses used therapeutically (0.3 to 0.6 mg/kg), it is likely to occupy more than 50% of the dopamine transporters. The time to reach peak brain uptake for oral methylphenidate in brain corresponds well with the reported time course to reach peak behavioral effects. Am J Psychiatry 1998; 155: 1325-1331
Abstract 487: RNAi-mediated silencing of TCF7L2 sensitizes colorectal cancer cells to radiation therapy
Authors: Marian Grade, Emil Kendziorra, Georg Emons, Kerstin Ahlborn, Melanie Spitzner, Jochen Gaedcke, Margret Rave-Frank, Tobias Pukrop, Tim Beissbarth, Heinz Becker, Michael Ghadimi, Thomas Ried
Journal: Cancer Research (2010)

Abstract Background: The standard treatment for locally advanced rectal carcinomas consists of preoperative chemoradiotherapy (CT/RT), followed by radical surgery. However, the clinical response to this treatment strategy is very heterogeneous. To determine the molecular basis of disparate response, we recently profiled a series of responsive and resistant rectal cancers using gene expression microarrays and identified a set of differentially expressed genes. One gene that was significantly over-expressed in the resistant tumors was TCF7L2 (also known as TCF4), the main downstream effector of the Wnt signaling pathway. The aim of this study was to understand its role in treatment response by testing the hypothesis that RNAi-mediated silencing of TCF7L2 sensitizes tumor cells to radiation therapy. Methods: The colorectal cancer cell line SW480, which is relatively resistant to radiation, was transfected with two different shRNA-vectors targeting TCF7L2, and a non-silencing control. Subsequently, stable single cell clones were established, and knockdown efficiency was analyzed by Western blot analysis. For each vector, individual clones were irradiated at 2, 4, 6 and 8 Gy. Colonies were counted after 10 days to calculate the respective surviving fractions. Results: TCF7L2 protein levels were reduced to ∼ 34% for shRNA_1, and ∼ 29% for shRNA_2. This led to a ∼ 1.6-fold growth inhibition (plating efficiency) compared to the non-silencing control. Importantly, RNAi-mediated silencing of TCF7L2 significantly reduced colony-formation after radiation (dose reduction factors of ∼ 1.5 and ∼ 2.0 at 37% survival for shRNA_1 and shRNA_2, respectively). These results were validated in a second cell line (HT29). In addition, we analyzed global gene expression profiles after RNAi to analyze the global transcriptomic changes induced by silencing TCF7L2. Conclusion: TCF7L2 is over-expressed in rectal carcinomas resistant to chemoradiotherapy. RNAi-mediated silencing of this gene caused a significant growth inhibition and, importantly, radiosensitization of colorectal cancer cells. Thus, TCF7L2 might represent a potential molecular target to sensitize a priori resistant tumor cells. Additionally, these data provide first evidence that the Wnt signaling pathway might not only be central for the development of colorectal cancers, but also for the resistance to therapy. 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 487.
Multidrug Resistance–Associated Protein 4 Is Involved in the Urinary Excretion of Hydrochlorothiazide and Furosemide
Authors: Maki Hasegawa, Hiroyuki Kusuhara, Masashi Adachi, John D. Schuetz, Kenji Takeuchi, Yuichi Sugiyama
Journal: Journal of the American Society of Nephrology (2006)

The role of ATP-binding cassette transporters in the urinary excretion of diuretics was investigated. Significant ATP-dependent uptake of hydrochlorothiazide (HCT) and furosemide was observed in membrane vesicles that expressed multidrug resistance-associated protein 4 (MRP4) and breast cancer resistance protein (BCRP). Unlike taurocholate uptake, S-methylglutathione had no effect on the ATP-dependent uptake of both compounds by MRP4. The functional importance of MRP4 and BCRP in the urinary excretion of HCT and furosemide was investigated using gene knockout mice. The renal clearance of HCT and furosemide was reduced significantly but not abolished in Mrp4 knockout mice compared with wild-type mice (9.0 +/- 0.9 versus 15 +/- 2 ml/min per kg for HCT and 1.9 +/- 0.3 versus 2.7 +/- 0.1 ml/min per kg for furosemide), and the amount of HCT that was associated with the kidney specimens was greater in Mrp4 knockout mice (21 +/- 3 versus 13 +/- 1 nmol/g kidney). In contrast, Bcrp makes only a negligible contribution because the urinary excretion was unchanged in Bcrp knockout mice. Our results suggest that Mrp4, together with other unknown transporters, accounts for the luminal efflux of HCT and furosemide from proximal tubular epithelial cells.
The Infant Formula Controversy: An International Health Policy Paradigm
Authors: STEPHEN C. JOSEPH
Journal: Annals of Internal Medicine (1981)

Editorials1 September 1981The Infant Formula Controversy: An International Health Policy ParadigmSTEPHEN C. JOSEPH, M.D., M.P.H.STEPHEN C. JOSEPH, M.D., M.P.H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-3-383 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe details of the most recent controversy over the inappropriate promotion and use and the harmful effects of infant formula, especially in the developing countries, have been extensively publicized by the media (1, 2) and in Congressional hearings. These issues, which had been in contention for years between industry and consumer activist groups and health-and-development professionals, have suddenly gained nationwide attention. The focal point for increased interest was the adoption by the annual Assembly of the World Health Organization (WHO) of an "International Code of Marketing of Breastmilk Substitutes" in May 1981 (3). One-hundred eighteen nations of all geographic, economic,...References1. The battle of the bottle. Time. 1981; June 1: 26. Google Scholar2. The breast vs the bottle. Newsweek. 1981; June 1: 54-5. Google Scholar3. . Code of Marketing of Breastmilk Substitutes. Geneva: World Health Organization; 1981. Google Scholar4. JOSEPHBABB SE. Of babies, profit and the question of conscience. Los Angeles Times. 1981; May 24: Op-Ed page. Google Scholar5. ABRAMS E. Infant formula code: why the U.S. may stand alone. Washington Post. 1981; May 21: Op-Ed page. Google Scholar6. SHIRKEY H. Therapeutic orphans. J Pediatr. 1968;72:119. CrossrefMedlineGoogle Scholar7. DOWIE M. The corporate crime of the century. Mother Jones Magazine. 1979; November: 24, 25, 37, 38. Google Scholar8. . Report of the Select Committee on Population. Population and Development Assistance. Washington, D.C.: U. S. Government Printing Office; 1978:84-91. Google Scholar9. BAUMSLAGGRACE-MASONROESELSABIN NLCE. Breast is Best: A Bibliography on Breast Feeding and Infant Health. Washington, D.C.: U. S. Department of Health, Education, and Welfare, Office of International Health; 1979. Google Scholar10. MORLEY D. Pediatric Priorities in the Developing World. London: Butterworths; 1973:118-9. Google Scholar11. JELLIFFEJELLIFFE DE. Human Milk in the Modern World. New York: Oxford University Press; 1978:225-33. Google Scholar12. WILLIAMSJELLIFFE CD. Mother and Child Health: Delivering the Services. New York: Oxford University Press; 1972:9. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 2220 Twentieth St. NW; Washington, D.C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1981Volume 95, Issue 3Page: 383-384KeywordsGlobal healthHearingInfants Issue Published: 1 September 1981 PDF DownloadLoading ...
Early Descriptions of Closed-Chest Cardiac Massage
Authors: Joseph Shiber
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
Investigation of Genetic Variation in Scavenger Receptor Class B, Member 1 (SCARB1) and Association with Serum Carotenoids
Authors: Gareth J. McKay, Edward Loane, John M. Nolan, Christopher C. Patterson, Kristin J. Meyers, Julie A. Mares, Ekaterina Yonova-Doing, Christopher J. Hammond, Stephen Beatty, Giuliana Silvestri
Journal: Ophthalmology (2013)
Drug companies should release data from all trials of licensed drugs, say MPs
Authors: N. Hawkes
Journal: BMJ (2013)

The drug industry should be obliged to release in a publicly accessible form all the information it possesses about trials of licensed drugs, the House of Commons Health Committee has said in a new report on the functioning of the National Institute for Health and Clinical Excellence (NICE).1

It should be “neither legal nor ethical” to withhold such data, said the committee. It was concerned that failure to observe this simple principle undermined the effectiveness of NICE, because the institute was forced to appraise drugs without having access to all relevant data.

“This situation cannot be allowed to continue,” said Stephen Dorrell MP, the Conservative chairman of the Health Committee. At a press conference in London to launch the report he called for …
Stat3 is required for the development of skin cancer
Authors: Laura Pedranzini, Andrea Leitch, Jacqueline Bromberg
Journal: Journal of Clinical Investigation (2004)

Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is constitutively activated in a variety of human malignancies, including prostate, lung, brain, breast, and squamous cell carcinomas. Inhibition of activated Stat3 leads to decreased proliferation and apoptosis of many cancer-derived cell lines, while the introduction of a constitutively activated form of Stat3 into immortalized human breast epithelial cells and rodent fibroblasts results in cellular transformation. Collectively, these data suggest a role for Stat3 in oncogenesis. A new study from Chan et al. (see related article beginning on page 720) is the first to demonstrate a requirement for Stat3 in de novo epithelial carcinogenesis in vivo. Using the two-step model of chemically induced skin carcinogenesis, the authors demonstrated that mice deficient in Stat3 were completely resistant to skin tumor development.
Infusions of Donor Leukocytes to Treat Epstein-Barr Virus-Associated Lymphoproliferative Disorders after Allogeneic Bone Marrow Transplantation
Authors: Esperanza B. Papadopoulos, Marc Ladanyi, David Emanuel, Stephen Mackinnon, Farid Boulad, Matthew H. Carabasi, Hugo Castro-Malaspina, Barrett H. Childs, Alfred P. Gillio, Trudy N. Small, James W. Young, Nancy A. Kernan, Richard J. O'Reilly
Journal: New England Journal of Medicine (1994)

Lymphoma associated with Epstein-Barr virus (EBV) is a complication of bone marrow transplantation that responds poorly to standard forms of therapy. The lymphoma is usually of donor origin. We hypothesized that treatment with infusions of donor leukocytes, which contain cytotoxic T cells presensitized to EBV, might be an effective treatment.
Constant flow insufflation of oxygen as the sole mode of ventilation during out-of-hospital cardiac arrest
Authors: Catherine Bertrand, François Hemery, Pierre Carli, Patrick Goldstein, Catherine Espesson, Michel Rüttimann, Jean Michel Macher, Brigitte Raffy, Patrick Fuster, François Dolveck, Alain Rozenberg, Eric Lecarpentier, Philippe Duvaldestin, Jean-Marie Saissy, Georges Boussignac, Laurent Brochard
Journal: Intensive Care Medicine (2006)
Specificity of Serum Creatine Kinase Isoenzymes in Diagnosis of Acute Myocardial Infarction
Authors: A. Konttinen, H. Somer
Journal: BMJ (1973)

A study of the diagnostic value of serum creatine kinase (CK) isoenzymes showed that MB isoenzyme, which characterizes heart tissue, was a specific and sensitive indicator of acute myocardial infarction. In cases where the clinical picture was complicated by ventricular tachycardia, severe congestive failure, shock, or resuscitation procedures heart, liver, and muscle enzymes were increased. There was also an increase in lactate dehydrogenase isoenzyme values in these cases; indeed, the only enzyme test that correlated well with electrocardiographic and necropsy findings was the MB isoenzyme.