tbuckley/cabot-search huggingface dataset:
Combinations of Physiologic Estrogens with Xenoestrogens Alter ERK Phosphorylation Profiles in Rat Pituitary Cells
Authors: Yow-Jiun Jeng, Cheryl S. Watson
Journal: Environmental Health Perspectives (2010)

BackgroundEstrogens are potent nongenomic phospho-activators of extracellular-signal–regulated kinases (ERKs). A major concern about the toxicity of xenoestrogens (XEs) is potential alteration of responses to physiologic estrogens when XEs are present simultaneously.ObjectivesWe examined estrogen-induced ERK activation, comparing the abilities of structurally related XEs (alkylphenols and bisphenol A) to alter ERK responses induced by physiologic concentrations (1 nM) of estradiol (E2), estrone (E1), and estriol (E3).MethodsWe quantified hormone/mimetic-induced ERK phosphorylations in the GH3/B6/F10 rat pituitary cell line using a plate immunoassay, comparing effects with those on cell proliferation and by estrogen receptor subtype-selective ligands.ResultsAlone, these structurally related XEs activate ERKs in an oscillating temporal pattern similar (but not identical) to that with physiologic estrogens. The potency of all estrogens was similar (active between femtomolar and nanomolar concentrations). XEs potently disrupted physiologic estrogen signaling at low, environmentally relevant concentrations. Generally, XEs potentiated (at the lowest, subpicomolar concentrations) and attenuated (at the highest, picomolar to 100 nM concentrations) the actions of the physiologic estrogens. Some XEs showed pronounced nonmonotonic responses/inhibitions. The phosphorylated ERK and proliferative responses to receptor-selective ligands were only partially correlated.ConclusionsXEs are both imperfect potent estrogens and endocrine disruptors; the more efficacious an XE, the more it disrupts actions of physiologic estrogens. This ability to disrupt physiologic estrogen signaling suggests that XEs may disturb normal functioning at life stages where actions of particular estrogens are important (e.g., development, reproductive cycling, pregnancy, menopause).
The Heroic Age of Science: The Conception, Ideals, and Methods of Science Among the Ancient Greeks.
Authors: William Arthur Heidel
Journal: JAMA (1933)

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
COMPARISON OF A VIRUS OBTAINED BY KOBAYASHI FROM CASES OF EPIDEMIC ENCEPHALITIS WITH THE VIRUS OF RABIES
Authors: E. V. Cowdry
Journal: The Journal of Experimental Medicine (1927)

Since the symptoms produced in experimental animals by the encephalitic virus of Kobayashi and by the virus of rabies are similar, and are accompanied by lesions which are indistinguishable, and since a cross-immunity is demonstrable between the two viruses, the conclusion is advanced that the specimen of so called encephalitis virus isolated by Kobayashi is in reality a specimen of rabic virus.
Pain in the Lower Extremity
Authors: David Lee
Journal: JAMA (1963)

<h3>To the Editor:</h3> —I should like to comment briefly on the answer by Dr. Evan Calkins to the question on<i>Pain in Lower Extremity</i>, which appeared in the June 2 issue ofThe Journal(<b>180</b>:795). I think it improper to dismiss this question without some mention of peripheral vascular disorder. Nocturnal pain in a great toe is very suggestive of thromboangiitis obliterans (Buerger's disease) which should be considered in any heavy smoker. Oscillometric examination cannot rule out the presence of this disease. Galvanometric temperature readings taken before and after the patient has smoked several cigarettes constitute a very effective test. One should not overlook the fact that organic disease can occur simultaneously with psychosomatic disease such as hysteria, and in the face of the bewildering array of symptoms which anxious patients bring to the physician, one is often inclined to explain glibly the bizarre syndromes on a psychogenic basis.
Prevalence and clinical features of cryoglobulinaemia in multitransfused beta -thalassaemia patients
Authors: R Perniola, C De Rinaldis, E Accogli, G Lobreglio
Journal: Annals of the Rheumatic Diseases (1999)

The aim of the study was to determine the prevalence of cryoglobulinaemia and its clinical features among beta-thalassaemia patients.Eighty eight multitransfused beta-thalassaemia patients were studied. They were physically examined and asked about the presence of cryoglobulinaemia related symptoms. Hepatitis C virus (HCV) serology, HCV-RNA, HCV subtypes, viraemia, serum ferritin, liver and kidney function tests, rheumatoid factor (RF), circulating immune complexes (CIC), complement levels and autoantibodies were all evaluated. The patients were divided into four groups: HCV-RNA positive patients with and without cryoglobulinaemia (groups A and B), HCV-Ab positive/HCV-RNA negative patients (group C), HCV-Ab negative patients (group D).Cryoglobulinaemia was present in 35 of 53 (66.0%) patients with chronic HCV infection. They had higher viraemia than non-cryoglobulinaemic viral carriers, but no statistical difference relating to sex or HCV subtypes was found. In comparison with the other groups, group A patients were older, had undergone transfusion therapy for a longer period, had received a higher number of transfusions, and had increased levels of RF and CIC, as well as consumption of C4; in addition, they had a higher prevalence of cirrhosis. Cutaneous lesions (purpura, Raynaud's phenomenon, nodules and leg rash), peripheral neuropathy and sicca syndrome symptoms were present only in group A. Musculoskeletal symptoms (bone pain, arthralgia and myalgia), weakness, splenomegaly, lymphadenopathy, skin ulcers and proteinuria were also commoner in group A, but the difference did not reach statistical significance, possibly because of partial overlap between cryoglobulinaemia and beta-thalassaemia syndromes.Because of its high prevalence in multitransfused beta-thalassaemia patients, cryoglobulinaemia needs to be systematically studied and considered in the differential diagnosis of various beta-thalassaemia manifestations.
ABC of mental health: Addiction and dependence I: Illicit drugs
Authors: C. Gerada, M. Ashworth
Journal: BMJ (1997)

About 30% of adults in Britain have used illicit drugs at some time in their lives, but misuse of prescription drugs (such as benzodiazepines and barbiturates) is probably even more widespread. Cannabis is the most commonly used illicit drug. About 100 000 people misuse heroin (diamorphine), and an unknown but increasing number use other drugs such as ecstasy and amphetamines.



Numbers of drug addicts notified to the Home Office during 1982-92



While the number of new drug users continues to rise, the number who inject drugs is falling, possibly as a result of health education about risks of HIV transmission. The highest number of addicts are found in London and the north west of England.

What determines whether drug use becomes continuous and problematic includes

Personality factors determine how a person copes once addicted and the mechanisms he or she may use to seek help.



Factors influencing misuse of drugs



Common drugs of misuse tend to cause dependence and euphoria.



Snorting heroin (picture reproduced with subject's permission)



### Benzodiazepines

This is the largest category of drug misuse. The most commonly misused drugs, temazepam and diazepam, usually originate from legal prescriptions or thefts from pharmacies. They may be taken alone as the drug of choice, to supplement opioids, or as a last resort when supply of opioids fails. Tolerance to benzodiazepines can occur, with daily doses escalating to 50-100 mg of diazepam. Intravenous injection of the viscous gel within temazepam capsules can cause catastrophic embolic damage to limbs and digits: temazepam is now a controlled drug.

A withdrawal syndrome can occur after only three …
REGULATION OF CHOLESTEROL SYNTHESIS IN THE LIVER: THE INFLUENCE OF DIETARY FATS
Authors: José M. Linazasoro, R. Hill, François Chevallier, I. L. Chaikoff
Journal: The Journal of Experimental Medicine (1958)

Rats were fed, for 3 days, four synthetic diets, all of which contained the same proportion of carbohydrate (50 per cent) and were of equal caloric value per gram. These diets contained either 0 or 15 per cent fat. The fats used were lard, corn oil, Wesson oil, and a hydrogenated vegetable oil. The feeding of the fat-containing diet for 3 days increased the liver's capacity for incorporating acetate carbon to cholesterol. The fats tested were of about equal value in stimulating hepatic cholesterogenesis. The various diets fed had no effect on the lipide or glycogen content of the liver nor on the lipide content of plasma.
Abstract 2491: Dynamics changes in antigen-autoantibody profiles involving glycolysis and spliceosome proteins precede a diagnosis of ER+ and triple negative breast cancer among post-menopausal women.
Authors: Jon Ladd, Melissa Johnson, Timothy Chao, Alice Chin, Sharon Pitteri, Jianning Mao, Lynn M. Amon, Martin McIntosh, Paul Lampe, Christopher Li, Ross Prentice, Nora Disis, Samir Hanash
Journal: Cancer Research (2013)

Abstract We assessed the circulating autoantibody repertoire in breast cancer using genetically engineered mouse models and human plasmas collected at a pre-clinical time point and at the time of clinical diagnosis of breast cancer. We aimed to identify common pathways, networks and protein families associated with the humoral response to tumors and to elucidate the dynamic nature of tumor antigens and autoantibody interactions in ER+ and triple negative breast cancer. Lysate proteins from immortalized mouse cell lines from MMTV-neu and C3(1)-T mouse models and from the MCF7 and MDA-MB-231 human breast cancer cell lines were spotted onto nitrocellulose microarrays and hybridized with mouse and human plasma samples, respectively. Ig-based plasma immunoreactivity against glycolysis and spliceosome proteins was a predominant feature observed both in MMTV-neu tumor bearing mice and in pre-diagnostic ER+ human samples. A cytoskeletal signature was uniquely observed in C3(1)-T mice and in human patients with triple negative breast cancer. We provide evidence for dynamic changes in autoantibody reactivity and in antigen-antibody interactions with tumor development and progression. Citation Format: Jon Ladd, Melissa Johnson, Timothy Chao, Alice Chin, Sharon Pitteri, Jianning Mao, Lynn M. Amon, Martin McIntosh, Paul Lampe, Christopher Li, Ross Prentice, Nora Disis, Samir Hanash. Dynamics changes in antigen-autoantibody profiles involving glycolysis and spliceosome proteins precede a diagnosis of ER+ and triple negative breast cancer among post-menopausal women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2491. doi:10.1158/1538-7445.AM2013-2491
Sodium restriction improves the gustatory threshold for salty taste in patients with chronic kidney disease
Authors: Tetsuro Kusaba, Yasukiyo Mori, Okagaki Masami, Neriya Hiroko, Takaomi Adachi, Chikako Sugishita, Kazuhiro Sonomura, Taikou Kimura, Noriko Kishimoto, Hisako Nakagawa, Mitsuhiko Okigaki, Tsuguru Hatta, Hiroaki Matsubara
Journal: Kidney International (2009)
Focal lymphocytic aggregates in chronic hepatitis C: Occurrence, immunohistochemical characterization, and relation to markers of autoimmunity
Authors: Maria Antonietta Freni, Domenica Artuso, Guido Gerken, Cesarina Spanti, Teresa Marafioti, Nunziata Alessi, Aldo Spadaro, Antonino Ajello, Oscar Ferrau
Journal: Hepatology (1995)

Intrahepatic lymphocytic aggregates are observed in chronic hepatitis C as well as in autoimmune chronic hepatitis. Autoantibodies and autoimmune manifestations may occur in hepatitis C. It has been suggested that the lymphocytic aggregates play a role in the liver injury of chronic hepatitis C by an immune-mediated mechanism. We studied the occurrence of intrahepatic lymphocytic aggregates and of autoantibodies in a consecutive series of 128 patients with chronic hepatitis C. For the phenotypic characterization of the lymphocytic aggregates cryostat sections and microwaved paraffin embedded sections were immunostained with monoclonal antibodies directed against T cell subsets, B cells, killer/natural killer cells, follicular dendritic cells, and macrophages. Autoantibodies were tested by immunofluorescence (antinuclear, anti-smooth muscle, antimitochondrial) and by enzyme-linked immunosorbent assay (anti-soluble liver antigen, anti-liver/kidney microsome, anti-human receptor for asialoglycoprotein). Focal lymphocytic aggregates in portal tracts were observed in 76 of 128 (59%) patients. The cellular composition of the aggregates was constant: a core of B cells mixed with many T helper/inducer lymphocytes, and an outer ring was prominently formed by T suppressor/cytotoxic lymphocytes. A germinal center was rarely identifiable. The presence of lymphocytic aggregates was inversely correlated with the degree of fibrosis. Lymphocytic aggregates appeared more frequently in chronic persistent and chronic active hepatitis in comparison with cirrhosis and in the presence of bile duct damage. No correlation was found between lymphocytic aggregates and autoantibodies or other markers of autoimmunity. The lymphocytic aggregates are frequent in chronic hepatitis C. Their cellular composition is similar to that of primary lymphoid follicles in lymph nodes. Their presence does not seem to be correlated with features of autoimmunity. (Hepatology 1995; 22:389-394.)
Persistent benefit of coronary artery stenting versus balloon angioplasty for isolated stenosis of proximal left anterior descending coronary artery: Five-year clinical follow-up
Authors: Francesco Versaci, Achille Gaspardone, Igino Proietti, Fabrizio Tomai, Jacob Zeitani, Anna De Fazio, Filippo Crea, Francesco Romeo, Pier Agostino Gioffrè, Luigi Chiariello
Journal: Journal of the American College of Cardiology (2003)
Action of a Sympathomimetic Drug and of Theophylline Ethylene Diamine on the Pulmonary Circulation
Authors: GWENDA R. BARER, A. J. GUNNING
Journal: Circulation Research (1959)

The action of two drugs, β-(2,5-diethoxyphenyl)-β-hydroxy-isopropylamine (BW 45/50) and theophylline ethylene diamine, on the pulmonary circulation of dogs and cats was tested. These experiments were made on intact animals, or animals with open chests, or on isolated perfused lungs. BW 45/50 reduced pulmonary arterial pressure in cats and dogs probably because of a fall in cardiac output; pulmonary vascular resistance was usually increased. Theophylline ethylene diamine caused a decrease in pulmonary vascular resistance; its value in pulmonary embolism is suggested.
Human recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3 cause basophil histamine release.
Authors: M Haak-Frendscho, N Arai, K Arai, M L Baeza, A Finn, A P Kaplan
Journal: Journal of Clinical Investigation (1988)

Histamine-releasing factors (HRFs) have been shown to be released from a variety of human cells, including T lymphocytes and alveolar macrophages. We considered the possibility that known cytokines might possess such activity on human basophils and/or mast cells and therefore tested preparations of human recombinant IL 3, IL 4, IL 5, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upon a panel of basophil donors. IL 3 and GM-CSF possessed significant histamine-releasing activity in 8 of 10 and 12 of 14 subjects, respectively. In each instance, a dose response could be demonstrated. IL 4 and G-CSF had no such activity, whereas IL 5 had activity in only 2 of 14 donors tested. We conclude that IL 3 and GM-CSF represent two effective HRFs, and suggest that HRF, as isolated based upon histamine-releasing activity, is likely to be heterogeneous in terms of molecular identity. Whether previously described HRFs relate specifically to IL 3 or GM-CSF must await primary sequence analysis of HRF and/or studies with monospecific antisera.
BMA calls special representative meeting to discuss concerns over reforms
Authors: Z. Kmietowicz
Journal: BMJ (2011)

The BMA has called a Special Representative Meeting to debate the NHS reforms in England.

The BMA Council said it was appropriate to discuss the planned changes to the NHS now that the Health and Social Care Bill has been laid before parliament. The meeting will take place on 15 March. Representatives were last called to a special meeting in 1992 when John Major’s Conservative government was attempting to introduce NHS reforms whose central feature was the separation of purchasers from providers ( BMJ 1992:304:920-21). 

The council sets out its concerns over the reforms in a briefing published on 26 January. It calls for several amendments to the bill and says the government should halt all further implementation of the reforms while the legislation makes it way through parliament.

In particular the BMA says it is concerned about the enforcement of competition through Monitor’s new role as the economic regulator for the NHS and the “inappropriate” introduction of price competition between providers.

“Commissioning consortia should be able to place contracts with the most suitable providers without fear of being accused of anti-competitive behaviour,” says the briefing. “They should be free to design new clinical pathways built around integration of services, inclusivity and partnership.”

The risk is that price competition will “damage the ability of the NHS to provide services in the most efficient and cost-effective way. It will destabilise provision, and increase transaction costs, and will threaten the provision of essential local services.”

The BMA is also opposed to the idea that all NHS trusts should be forced to become foundation trusts by 1 April 2014—a move which it says “could distort priorities and drive trusts to place the achievement of this target above all others, including safe patient care.”

On the same day …
Intravenous L-Thyroxine
Authors: ROBERT F. KLEIN
Journal: Annals of Internal Medicine (1973)

Letters, Comments, and Corrections1 February 1973Intravenous L-ThyroxineROBERT F. KLEIN, M.D.ROBERT F. KLEIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-2-306_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The paper, "Acute Metabolic Responses in Myxedema to Large Doses of Intravenous L-Thyroxine" (Ann Intern Med77:549-555, 1972), by Ridgway and colleagues has raised a question about the management of patients with newly discovered myxedema. It has been my practice to start therapy with small doses of whatever thyroid substance is used, to avoid ischemic myocardial effects. The authors have used large doses intravenously (without qualms?) and noted not one complication in 14 patients. They failed to mention the implications of this finding for the practicing internist. Could they do so for me?...Reference1. HOLVEYGOODNERNICOLOFF DCJ: Treatment of myxedema coma with intravenous thyroxine. Arch Intern Med 113:89-96, 1964 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug Action, Reaction, and Interaction 1 February 1973Volume 78, Issue 2Page: 306-306KeywordsThyroidThyroxine Issue Published: 1 February 1973 PDF downloadLoading ...
Increased Age at Diagnosis Has a Significantly Negative Effect on Outcome in Children With Down Syndrome and Acute Myeloid Leukemia: A Report From the Children’s Cancer Group Study 2891
Authors: Alan S. Gamis, William G. Woods, Todd A. Alonzo, Allen Buxton, Beverly Lange, Dorothy R. Barnard, Stuart Gold, Franklin O. Smith
Journal: Journal of Clinical Oncology (2003)

To determine the outcome of children with Down syndrome (DS) and acute myeloid leukemia (AML) receiving standard timing chemotherapy without bone marrow transplantation (BMT), with determination of prognostic factors.Children with DS and newly diagnosed AML or myelodysplasia were prospectively enrolled on Children's Cancer Group study 2891 (N = 161) and treated uniformly with four standard timing induction courses of dexamethasone, cytarabine arabinoside, 6-thioguanine, etoposide, daunorubicin (DCTER) followed by intensively timed high-dose cytarabine.Children with DS were significantly younger at diagnosis than those without (median age, 1.8 v 7.5 years, respectively; P <.001), with more megakaryocytic leukemia (70% v 6%; P <.001). Higher complete remission rates (91%) were achieved in children with DS than among those without DS (75%; P <.001). Equivalent grade 3 to 4 toxicity (29% v 30%; P =.84) was seen, though children with DS had greater pulmonary toxicity (P <.01) during induction and mucositis during intensification (P =.12). Children with DS had significantly better 8-year event-free survival (EFS; 77% v 21% standard and 40% intensive induction; P <.0001). Multivariate analysis in children with DS revealed that only age at diagnosis of 2 years or older was a risk factor for greater relapse risk (odds ratio, 4.9; P =.006) and worse survival. Children between ages 0 to 2 years (n = 94) had a 6-year EFS of 86%; those from 2 to 4 years (n = 58), 70%; and those older than 4 years (n = 9), 28%. Remission failures were the primary reason for worse 6-year EFSs (1% in those 0 to 2 years v 14% if >2 years; P =.002).Outcome for children with DS and AML is excellent with standard induction therapy, but declines with increasing age.