tbuckley/cabot-search huggingface dataset:
Abstract 1925: Trifluoromethylated artemisinin dimers demonstrate a potent anti-cancer activity in vitro and in vivo
Authors: Jacques Fahy, Frederic Marion, Frederic Lieby-Muller, Celine Mordant, Stephane Vispe, Viviane Brel, Bruno Gomes, Jean-Philippe Annereau, Constance Chollet, Anaïs Fournial, Benoit Crousse, Daniele Bonnet-Delpon, Anna Kruczynski, Christian Bailly, Nicolas Guilbaud
Journal: Cancer Research (2012)

Abstract Beside their widely recognised efficacy as antimalaric drugs, artemisinin derivatives are also known for their cytotoxic properties since the early nineties. More recently, artemisinin dimers (ADs) were shown to possess an increased potential as anti-cancer agents due to their ability to inhibit cancer cells proliferation in the low nanomolar range. Taking advantage of an original chemistry, we synthesized a new series of trifluoromethylated artemisnin dimers which proved to be particularly potent depending on the size and nature of the linker. Different mode of linkage were performed by either carbon 16 or carbon 10 and were tested in vitro and in vivo. Best combination was found in a hybrid linking position delivering non-symmetrical C10-C16 ADs. One of the lead compound of this series, F98458 demonstrated a moderate (but statiscally significative) anti-tumor activity in mice against a human melanoma xenograft that is, to our knowledge, the first demonstration of in vivo antitumor properties of ADs in preclinical models. Many efforts to understand the molecular origin of the cytotoxic effect of monomeric artemisinin derivatives have been undertaken. One of the aims of this study was to investigate the mechanism of action of ADs in comparison with artemisinin: the antimalaric drug artesunate, a representative monomeric derivative of artemisinin, is known to induce DNA damage and ROS generation while our ADs did not under the same experimental conditions. Moreover ADs did not induce apoptosis (caspase 3/7, annexin V), leading us to investigate cell death related to senescence and autophagy. We have also synthesized partially reduced ADs possessing only one endoperoxide functionality. These compounds did show the same potency than non reduced ADs, underlaying that a tight molecular recognition is involved in its biological response. All these observations suggest that monomeric artemisinin derivatives such as artesunate and ADs possess distinct modes of action. The high in vitro potency associated with the in vivo response led us to synthesize affinity probes in order to identify the molecular target of ADs which could provide fundamental informations for further developpement of these compounds as anti-cancer agents. This work currently underway will also be discussed. 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 1925. doi:1538-7445.AM2012-1925
Remarks on a Case of Congenital Rickets
Authors: T. C. Railton
Journal: BMJ (1894)

1299clamp was reIioved o1 .Jlanuary 29tlh.The highest tempera- ttire recor(lded i%.as a littlec ove,t-r ltHoW F., amid tlhe retovery wa.s tillevnltful.In euttimig away the uterus solmle thick, dar-k
Discounted Fees: The Past in the Present
Authors: Robert L. Martensen
Journal: JAMA (1995)

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 Journals 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
Phosphorus control in peritoneal dialysis patients
Authors: A. Yavuz, F.F. Ersoy, P.S. Passadakis, P. Tam, D.M. Evaggelos, K.P. Katopodis, Ç Özener, F. Akçiçek, T. Çamsari, K. Ateş, R. Ataman, G.J. Vlachojannis, N.A. Dombros, C. Utaş, T. Akpolat, S. Bozfakioğlu, G. Wu, I. Karayaylali, T. Arinsoy, C.P. Stathakis, M. Yavuz, D.J. Tsakiris, A.C. Dimitriades, M.E. Yilmaz, M. Gültekin, G. Süleymanlar, D.G. Oreopoulos
Journal: Kidney International (2008)
Pathology services are to be overhauled
Authors: Michael Day
Journal: BMJ (2006)

The government has announced a complete overhaul of England's pathology services.

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A candidate for privatisation?

Credit: MARK THOMAS/SPL

The move was prompted by last week's publication of a report of a review of pathology services chaired by Patrick Carter, a Labour member of the House of Lords. It concluded that pathology services were “fragmented and inefficient.” Lord Carter called for better transportation of samples and greater efficiency in …

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Genomic analysis of hepatic farnesoid X receptor binding sites reveals altered binding in obesity and direct gene repression by farnesoid X receptor in mice
Authors: Jiyoung Lee, Sunmi Seok, Pengfei Yu, Kyungsu Kim, Zachary Smith, Marcelo Rivas-Astroza, Sheng Zhong, Jongsook Kim Kemper
Journal: Hepatology (2012)

The nuclear bile acid receptor, farnesoid X receptor (FXR), is an important transcriptional regulator of liver metabolism. Despite recent advances in understanding its functions, how FXR regulates genomic targets and whether the transcriptional regulation by FXR is altered in obesity remain largely unknown. Here, we analyzed hepatic genome-wide binding sites of FXR in healthy and dietary obese mice by chromatin immunoprecipitation sequencing (ChIP-seq) analysis. A total of 15,263 and 5,272 FXR binding sites were identified in livers of healthy and obese mice, respectively, after a short 1-hour treatment with the synthetic FXR agonist, GW4064. Of these sites, 7,440 and 2,344 were detected uniquely in healthy and obese mice. FXR-binding sites were localized mostly in intergenic and intron regions at an inverted repeat 1 motif in both groups, but also clustered within 1 kilobase of transcription start sites. FXR-binding sites were detected near previously unknown target genes with novel functions, including diverse cellular signaling pathways, apoptosis, autophagy, hypoxia, inflammation, RNA processing, metabolism of amino acids, and transcriptional regulators. Further analyses of randomly selected genes from both healthy and obese mice suggested that more FXR-binding sites are likely functionally inactive in obesity. Surprisingly, occupancies of FXR, retinoid X receptor alpha, RNA polymerase II, and epigenetic gene activation and repression histone marks, and messenger RNA levels of genes examined, suggested that direct gene repression by agonist-activated FXR is common. Conclusion: Comparison of genomic FXR-binding sites in healthy and obese mice suggested that FXR transcriptional signaling is altered in dietary obese mice, which may underlie aberrant metabolism and liver function in obesity. (HEPATOLOGY 2012;56:108–117)
Myocardial potassium loss and cell depolarisation in ischaemia and hypoxia
Authors: A. A. Wilde, G. Aksnes
Journal: Cardiovascular Research (1995)

Journal Article Myocardial potassium loss and cell depolarisation in ischaemia and hypoxia Get access Arthur AM Wilde, Arthur AM Wilde * aAcademic Medical Centre, University of Amsterdam, Department of Clinical and Experimental Cardiology, PO Box 22700, 1100 DE Amsterdam, The Netherlands *Correspondence to Dr Wilde. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gunnar Aksnes Gunnar Aksnes bInstitute for Experimental Medical Research, Ulleval Hospital, University of Oslo, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 1, January 1995, Pages 1–15, https://doi.org/10.1016/S0008-6363(96)88539-7 Published: 01 January 1995 Article history Received: 31 March 1994 Accepted: 11 August 1994 Published: 01 January 1995
HLA-DR4 and Gm(1,3;5,21) are associated with U1-nRNP antibody positive connective tissue disease.
Authors: E Genth, H Zarnowski, R Mierau, D Wohltmann, P W Hartl
Journal: Annals of the Rheumatic Diseases (1987)

Patients with U1-nRNP antibodies (n = 35, 31 female, four male) were typed for HLA-A, -B, -C, and -DR antigens and IgG heavy chain allotypes G1m(1), -(2), -(3), G3m(5), and -(21). The patient group was clinically heterogeneous. Four met the American Rheumatism Association criteria for systemic lupus erythematosus, six for progressive scleroderma, and 14 for rheumatoid arthritis. Sicca syndrome was present in seven cases. Twenty three had overlapping features compatible with mixed connective tissue disease (MCTD). Healthy blood donors served as controls for HLA typing (n = 64), Gm typing (n = 228), or both (n = 56). Sixty six per cent of the patients with U1-nRNP antibodies were DR4 positive compared with 28% of the controls (relative risk = 4.9, p = 0.00053). The Gm(1,3;5,21) phenotype was found in 46% of the patients and 25% of the controls (relative risk = 2.47, p = 0.0247). Within the patient group Gm(1,3;5,21) was found only in DR4 positive individuals. The coincidence of HLA-DR4 and Gm(1,3;5,21) increases the relative risk values to 8.0 (compared with the group with neither risk factor). DR4 and Gm(1,3;5,21) primarily seem to be related to U1-nRNP antibody formation and not to disease expression. Patients with or without MCTD did not differ with respect to DR4 or Gm(1,3;5,21) frequency. Disease onset was earlier in patients with HLA-DR4/Gm(1,3;5,21) than in patients without both markers (mean 27.9 v 40.1 years; p less than 0.05).
WHO's decision not to recommend use of artemether in Africa is unethical
Authors: J. N E Ana, B. M Gana
Journal: BMJ (1996)

EDITOR,—Jacqui Wise reports that artemether, the active ingredient of a traditional Chinese remedy for fever, has been found to be as effective as quinine in severe malaria.1 She states that most deaths from malaria occur in Africa and then quotes Dr Peter Trigg, a scientist with …
Back Pain: The History and Physical Examination
Authors: Linda M. Frazier
Journal: JAMA (1993)

<h3>To the Editor.</h3> —In the excellent article by Deyo et al,<sup>1</sup>the sensitivity and specificity values provided in Tables 1 and 3 are useful. But predictive value can be even more helpful for making patient care decisions. For example, sciatica is listed by the authors as having a sensitivity (Se) of 0.95 and specificity (Sp) of 0.88 for a surgically important herniated disk. These high numbers seem to indicate that a history of sciatica is a pretty good test. But when prevalence is low, even tests with fairly high sensitivity and specificity have low predictive values. In primary care settings, for instance, a surgically important disk is present in less than 2% of patients with acute low back pain<sup>1</sup>(prevalence [P] = 0.02). The positive predictive value (+PV) of sciatica as an indicator of an important disk problem can be calculated<sup>2</sup>as +PV = (Se) (P) / (Se) (P) + (1−Sp)
Facts and Artifacts About Anemia and Preterm Delivery-Reply
Authors: Mark A. Klebanoff
Journal: JAMA (1990)

<h3>In Reply.—</h3> We appreciate the opportunity to respond to the thoughtful criticisms by Lieberman et al. These criticisms involve our interpretation of the literature, the age of the Collaborative Perinatal Project, potential nonindependence of the observations, and the possibility that women who have repeated hematocrits are different from the general population. We address each of these concerns. Our purpose in citing Nilsen et al<sup>1</sup>was to provide supporting evidence for our contention that hematocrit rises during the third trimester of a normal pregnancy, not to address the relationship between anemia and preterm birth. These investigators demonstrated that in normal pregnancies to nonsmoking, nonanemic women, the hemoglobin level rose approximately 5 g/L between 25 to 30 weeks and term. Taylor and Lind,<sup>2</sup>who studied unselected British women, noted that among those who received iron, the mean hematocrit increased from 33 percent at 26 to 30 weeks to 36 percent at
TWO FAMILIES SHOWING HEREDITARY ECTODERMAL DYSTROPHIES.
Authors: C. Hard Wick
Journal: British Journal of Dermatology (1939)

Journal Article TWO FAMILIES SHOWING HEREDITARY ECTODERMAL DYSTROPHIES. Get access C. Hard Wick, M.A., M.B. C. Hard Wick, M.A., M.B. Hospital for Sick Children, Great Ormond Street, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 51, Issue 1, 1 January 1939, Pages 24–30, https://doi.org/10.1111/j.1365-2133.1939.tb10603.x Published: 01 January 1939
Pfizer ends advertisements featuring inventor of artificial heart
Authors: Janice Hopkins Tanne
Journal: BMJ (2008)

The government has agreed in principle that the General Medical Council, the medical profession's regulator, will take over responsibility for postgraduate medical training in the United Kingdom.The move to assimilate the Postgraduate Medical and Training Board within the GMC-which will not go ahead before 2010-has been welcomed by Graeme Catto, the council's president.Sir Graeme said, "The merger will bring under one roof the regulation of all stages of medical education and will deliver real benefits for patients and the public, as well as for the medical profession."He added that the board, which was set up in autumn 2005, had made an important contribution to postgraduate medical education in the UK and promised to maintain the momentum it had generated.However, in a statement the Royal College of Surgeons of England expressed its disappointment at the slow timetable for implementing the change."We are pleased with the acceptance that PMETB [the Postgraduate Medical Education and Training Board] will become part of the GMC.However, it is disappointing that no opportunity can apparently be found to carry out this badly needed reform until 2010," it said.Altogether the government agreed (or agreed in principle) to 24 of 47 recommendations made by John Tooke in the report of his inquiry into the reform of Modernising Medical Careers (MMC), which was published in January (BMJ 2008;336:61, 12 Jan).Other proposals were put on hold for "further consideration" or were dismissed as the responsibility of other organisations.Proposals that were agreed in principle are to be evaluated as part of the next stage review, being carried out by health minister Lord Darzi and due to be published in June.Alan Johnson, the health secretary, said that his department needed more time to consider one of the late additions to the list of recommendations, the proposal to set up a new independent body, provisionally called NHS Medical Education England, GMC will take responsibility for postgraduate medical training, as advised by Tooke report UK NEWS Deaths from cancer fall after 20 years of screening in England, p 527 WorlD NEWS European Commission looks into possible restrictive practices by drug companies, p 524 bmj.com london GPs express fear over Darzi's proposals for the capital
ON CHANGE OF SIGHT AS PREMONITORY OF HARD CATARACT
Authors: W. W. Cooper
Journal: BMJ (1853)

stus on the 15th; and, in the night,a large amount was forcibly expelled, which was followed by an immense ftntid evacuation, with some bloody serum.The calomel and opium had been continued, and she had had five more ene- mata administered, the quantity of tobacco used at a time being from twelve to fifteen grains only, on account of her extreme weakness.Wine and brandy were likewise given.She nearly sank after the evacuation; but, unider the use of brandy and opium, with the injection of two drachms of compound tincture of camphor, she gradually recovered, the peritoneal covering of the abdomen being somewhat thick- ened.CASE 111.Mrs. S., a short, stout, thickset washerwoman, was seen by Mr. Payne's assistant on April 2nd, 1838, having then, after a week's constipation, been suddenly seized, at the wash tub, with violent Ipains in the abdomien.She was bled to six ounces, anid crotoii oil with a senna mixture was ordered; everything was, however, vomited.Afterwards, Mr. Payne himself saw her.The paiins were then very violent, and the sickness was excessive; the pulse was 136, full, and firm.Ile bled her to twenty-six ounces with muich relief to the paill anld the vomiting.Ile ordered two grains of caloniel and one of opium every three hours.No fluid was allowed.On April 3rd, she was again bled to faintness, the sickness and pain beinig as violent as ever, and fculent matter being ejected.This womani sank into a very feeble coinditioIn.On April 14th, after a tobacco injection, flatis escaped with a loud nioise, which was followed by stools, great faintness, and produced the flow of bloody serum.She recovered fromi this faintness under the samiie treatment as in the previous case; the peritoneum remaining also thick- ened.She had marked tenderness above the ileum on the left side; two tobacco enemata were administered, the calo- mel and opiium having been continued only up to the 6th, on account of the patient's refusal to take themn.She, as well as the second woman, often aslked for the injection.Mr. Patyne had been ied to abstain froni violent means for getting the bowels open, by having, many years ago, By W.
Tetanus vaccination during pregnancy reduces risk of neonatal mortality in India, study finds
Authors: S. Bagcchi
Journal: BMJ (2013)

British and Indian researchers have called for mandatory immunisation against tetanus for pregnant women in India, after finding that vaccination reduces neonatal mortality.

Tetanus vaccination, folic acid tablets, and antenatal visits are the major components of antenatal care in India. However, there is very little evidence that these interventions help reduce neonatal mortality. 

For the study the researchers used discrete time logistic regression models to investigate the association between …
Proposed model of early dementia screening cannot be valid
Authors: J. J. Turner
Journal: BMJ (2013)

Dementia is a threat to public health in the developed world, and pressure for screening has intensified.1 Early diagnosis is of benefit for many cancers and ischaemic heart disease, but not yet for dementia. Big Pharma, allied to patient pressure groups, have a part to play, but their overpromotion …
Intestinal Adaptation
Authors: Robin C. N. Williamson
Journal: New England Journal of Medicine (1978)

Intrinsic Regulation of Cell RenewalIn normal circumstances, the constant turnover of the small-bowel mucosa is maintained by a dynamic equilibrium between cell production at the base of the crypt and cell loss at the tip of the villus. This turnover recapitulates the embryologic development of the intestinal epithelium from undifferentiated stem cells to mature enterocytes in intimate relation to the lamina propria.171 Even in atrophic defunctioned bowel or mucosal biopsies maintained by organ culture, epithelial cells continue to replicate in the crypts and differentiate during migration onto the villi.7,48,86 The failure of mitotic inhibition by . . .
Jesse Roth: redefining diabetes by receptors
Authors: W. Check
Journal: JAMA (1979)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Calcifications in Dermatomyositis
Authors: M C Dalakas
Journal: New England Journal of Medicine (1995)

Figure 1. The elbow (Panel A) of a 33-year-old woman who had had dermatomyositis since childhood shows subcutaneous calcifications extruding through the skin. A focus of purulent inflammation within a calcium deposit is evident (arrow).An x-ray film of the patient's thigh (Panel B) shows calcifications beneath the skin and within the muscle tissue. Some lesions on the skin in this area were palpable, and others were not visible. Deposition of calcium continued in this patient despite therapy with prednisone, azathioprine, and diphosphonates.
Association of Bioavailable, Free, and Total Testosterone With Insulin Resistance
Authors: Elaine C. Tsai, Alvin M. Matsumoto, Wilfred Y. Fujimoto, Edward J. Boyko
Journal: Diabetes Care (2004)

OBJECTIVE—Previous reports of an association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markers of insulin resistance and body fat measures in 221 middle-aged nondiabetic men. RESEARCH DESIGN AND METHODS—Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07–0.1). In contrast, total testosterone correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). RESULTS—Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = −0.15 [P = 0.03], −0.14 [P = 0.03], −0.32 [P &amp;lt; 0.0001], and −0.38 [P &amp;lt; 0.0001], respectively), fasting C-peptide (r = −0.18 [P = 0.009] to −0.41 [P &amp;lt; 0.0001]), HOMA-IR (r = −0.15 [P = 0.03] to − 0.39 [P &amp;lt; 0.0001]), and body fat measures (r = −0.17 [P = 0.008] to −0.44 [P &amp;lt; 0.0001]). Only SHBG and total testosterone were significantly associated with fasting glucose (r = −0.20 [P = 0.003] to −0.21 [P = 0.002]). In multivariate analysis, bioavailable or free testosterone was significantly and inversely associated with insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG. CONCLUSIONS—The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat.