tbuckley/cabot-search huggingface dataset:
Mechanisms and time course of beta1 adrenoceptor desensitisation in mammalian cardiac myocytes
Authors: J. S KARLINER, P. C SIMPSON, N. HONBO, W. WOLOSZYN
Journal: Cardiovascular Research (1986)

Journal Article Mechanisms and time course of beta1 adrenoceptor desensitisation in mammalian cardiac myocytes Get access JOEL S KARLINER, JOEL S KARLINER From the Cardiology Section, Veterans Administration Medical Center; and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar PAUL C SIMPSON, PAUL C SIMPSON From the Cardiology Section, Veterans Administration Medical Center; and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar NORMAN HONBO, NORMAN HONBO From the Cardiology Section, Veterans Administration Medical Center; and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar WANDA WOLOSZYN WANDA WOLOSZYN From the Cardiology Section, Veterans Administration Medical Center; and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 20, Issue 3, March 1986, Pages 221–228, https://doi.org/10.1093/cvr/20.3.221 Published: 01 March 1986
Essentials of Dermatology.
Authors: Norman. Tobias
Journal: JAMA (1952)

The fifth edition of Tobias' "Essentials of Dermatology," like the previous editions, is difficult to assess. For the most part it is a good book, with emphasis on the practical aspects of dermatology designed to benefit practitioners. The plan of the book is similar to that of the previous editions; basic aspects of dermatology, as the physiological and biochemical, are omitted; the book is profusely illustrated; the diagnosis, differential diagnosis, and treatment are given in simple manner. The latter includes useful notes on nursing care and some helpful instructions to patients with diseases such as acne, pruritus ani, eczema, etc. An entire chapter is devoted to the troublesome hand eczema. Throughout, the descriptions of the diseases and the recommended treatments are acceptable. Of less importance but regrettable are the following: Too many of the illustrations are not as clear as they might be; the author's definition of acantholysis is not
Detection of bacterial DNA in sterile serum and ascitic fluid from patients with cirrhosis. Preliminary data
Authors: J. Such, R.F. Frances, C. Munoz, J.A. Casellas, S. Pascual, J. Sola-Vera, P. Zapater, P. Saez, P. Griño, M. Perez-Mateo
Journal: Journal of Hepatology (2001)
P3-16-06: Phase II Trial of TS-1 in Combination with Oxaliplatin (SOX) in Patients with Metastatic Breast Cancer (MBC) Previously Treated with Anthracycline and Taxane Chemotherapy [TORCH] [Korean Cancer Study Group (KCSG) BR07-03].
Authors: S-A Im, D-Y Oh, KS Lee, J-H Ahn, J Shon, JS Ahn, JH Kim, SW Han, MH Lee, KE Lee, K Lee, HJ Kim, B Keam, S-Y Kim, SB Kim, YH Im, J Ro, H-S Park
Journal: Cancer Research (2011)

Abstract Background Oxaliplatin, a platinum analogue, is an active drug in advanced anthracycline and taxane-pretreated breast cancer patients as a single agent and with 5-fluorouracil (5-FU) combination. TS-1 was developed by the scientific theory of both potentiating antitumor activity of 5-FU and reducing gastrointestinal toxicity. This trial was performed to evaluate the efficacy and safety of TS-1 in combination with oxaliplatin in metastatic breast cancer (MBC) patients previously treated with anthracycline and taxane chemotherapy. Methods: Between October 2007 and October 2009, MBC patients were enrolled in this prospective multicenter trial. Eligible criteria included age ≥18 years, at least one measurable lesion, prior treatment with anthracycline and taxane chemotherapy, and ECOG Performance Status 0–2. TS-1 40 mg/m2 b.i.d. on days 1–14 with oxaliplatin 130 mg/m2 on day 1 were administered every 3 weeks till disease progression. Primary end-point was response rate, and secondary end-points were time-to-progression (TTP), overall survival (OS), duration of response (DOR) and toxicities. Response was evaluated every 6 weeks according to the RECIST criteria v. 1.0 and toxicity was assessed with NCICTCAE v.3.0.(ClinicalTrials.gov identifier NCT00527930). Results: A total of 87 patients were enrolled. Median age was 48 years (range 30–71 years). Nineteen patients (21.8%) had de novo stage IV and 68 patients (78.2%) had recurrent disease. Thirty-five patients (40.2%) received two-lines of prior chemotherapy in palliative setting. Forty-eight patients (55.2%) had ≥ 3 disease sites. Fifty-four patients (62.1%) were hormone receptor positive, and 25 patients (28.7%) were triple negative. Five patients received prior anti-HER2 therapy. A total of 525 cycles were administered (median 6 cycles, range: 1 ∼ 22+ cycle). In per-protocol analysis, overall response rate was 38.5% (95% CI: 27.7−49.3) (CR 0%, PR 38.5%) and disease control rate (CR, PR, and SD) was 67.9% (95% CI: 57.5−78.3). Median TTP, OS, and DOR were 6.0 months (95% CI: 5.1−6.9 months), 19.4 months (95% CI: not estimated), 6.6 months (95% CI: 3.7−9.6 months), respectively. RR was not different by triple negativity (39.1% in TNBC vs. 38.2% in non-TNBC, P=0.361). TTP was not different according to the number of prior chemotherapy regimens. Reported grade 3 or 4 toxicities (per cycle) were neutropenia (10.3%), thrombocytopenia (5.5%), diarrhea (1.9%), vomiting (1.9%), and stomatitis (0.2%). There was no treatment-related death. Conclusions: SOX is an effective regimen in anthracycline and taxane pretreated MBC patients with manageable toxicities. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-06.
Psychological impact of alopecia
Authors: Diana M Amor
Journal: BMJ (2005)

Endovascular repair is not worse than open repair of abdominal aortic aneurysmsEditor-The title and interpretation of the EVAR trial results in the POEM are misleading and incorrect. 1Mortality figures were quoted both as aneurysm related and all cause deaths.The 30 day mortality was 1.7% in the EVAR group, which is significantly lower than 4.7% in the open repair group.Surprisingly, the POEM somehow interpreted 30 day mortality to be less than 1% for both groups, which is clearly an error.The confidence intervals (odds ratio 0.35, 95% confidence interval 0.16 to 0.77, P = 0.009) make type I error unlikely.If preintervention deaths are added to the figures 30 day mortality was calculated at 3.5% for endovascular repair and 7.1% for open surgery. 2 The advantage of endovascular repair is sustained at four years, with 4% aneurysm related deaths in the EVAR group compared with 7% in the open repair group.This confers a 3% absolute reduction in aneurysm related mortality.The all cause mortality rate was comparable in both groups at four years.Endovascular repair offers a 30 day lower risk treatment compared with open surgery in patients who are medically fit with an abdominal aortic aneurysm.Compared with open repair, endovascular repair offers no advantage with respect to all cause mortality and health related quality of life; and is more expensive; however, it confers a 3% improved aneurysm related survival which persists at four years.The POEM's message that endovascular repair is worse than open repair is inaccurate and not evidence based.
Korean Ethnicity as Compared with White Ethnicity Is an Independent Favorable Prognostic Factor for Overall Survival in Non-small Cell Lung Cancer before and after the Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Era
Authors: Myung-Ju Ahn, Jeeyun Lee, Yun-Hee Park, Jin-Seok Ahn, Argyrios Ziogas, Jason A. Zell, Keunchil Park, Sai-Hong Ignatius Ou
Journal: Journal of Thoracic Oncology (2010)
Evidence for Unique Mechanisms of Estrogen Receptor Degradation Elicited by Estradiol and ICI 182,780 (Fulvestrant).
Authors: A. Casa, A. Casa, Z. Lazard, C. Thorne, M. Ouspenskia, P. Zhang, A. Lee, A. Lee, A. Lee
Journal: Cancer Research (2009)

Abstract Selective estrogen receptor down-regulators (SERDs), such as ICI 182780 (Fulvestrant), comprise a class of drugs that has been developed to inhibit estrogen receptor alpha (ER) activity in breast cancer. ICI is a pure antagonist that competitively binds to the ligand-binding domain of ER. The binding of ICI is thought to reduce the receptor's half-life by increasing protein turnover. However, the exact mechanism of ICI action, including whether or not receptor degradation is actually required for its antiestrogenic action, is currently unknown. Our laboratory has shown that a cytoplasmic ER mutant (ERΔNLS) lacking a nuclear localization sequence (NLS) is completely resistant to ICI-mediated degradation in both MCF-7 breast cancer cells and their ER-negative derivatives, C4-12 cells. Immunofluorescence and confocal microscopy were performed to assess localization of all ER proteins. These cells were also treated for different lengths of time with varying concentrations of both estradiol (E2) and ICI. Immunoblotting was performed to determine levels of ER protein. A competitive radioligand binding assay was also conducted to assess the ligand-binding capability of the ERΔNLS mutant receptor. Immunofluorescence and confocal imaging of stably transfected C4-12 cells has confirmed distinct subcellular localization of each ER protein. Wild-type ER localizes mainly to the nucleus, while ERΔNLS is cytoplasmic. As expected, treatment of either wild-type MCF-7 cells or C4-12 cells expressing wild-type ER with E2 or ICI caused degradation of ER protein. Treatment of MCF-7/ ERΔNLS or C4-12/ ERΔNLS cells with E2 caused degradation of ERΔNLS protein. In stark contrast, increasing concentrations of ICI failed to cause degradation of ERΔNLS. Furthermore, experiments performed in the presence of cycloheximide have shown that ICI does not modulate ERΔNLS half-life. The inability of ICI to degrade ERΔNLS is not due to an inability of ERΔNLS to bind ligand, since results from competitive radioligand binding assays show that the affinity of ERΔNLS for both E2 and ICI is equal to the affinity of wild-type ER for both ligands. We have recently cloned the SV40-NLS onto ERΔNLS, and confocal microscopy has confirmed that the SV40-NLS is sufficient to force ERΔNLS into the nucleus. I am currently using this construct to determine if it is the NLS domain itself or merely subcellular localization of ER that is important for ICI-mediated degradation. In conclusion, ER is a critical marker for response to antiestrogen therapy. Treatment with ICI is not without its shortcomings. A better understanding of the mechanism by which ICI degrades ER may lead to the development of better antiestrogen therapies to inhibit ER action with less toxicity and greater specificity. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4137.
Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study
Authors: Abbas Dehghan, Anna Köttgen, Qiong Yang, Shih-Jen Hwang, WH Linda Kao, Fernando Rivadeneira, Eric Boerwinkle, Daniel Levy, Albert Hofman, Brad C Astor, Emelia J Benjamin, Cornelia M van Duijn, Jacqueline C Witteman, Josef Coresh, Caroline S Fox
Journal: The Lancet (2008)
Research misconduct: Dr Grethe Støa Birketvedt not guilty of scientific misconduct
Authors: Jon Florholmen, Anthony R Leeds
Journal: Journal of the Royal Society of Medicine (2010)

In May 2006, you published a review ‘Research misconduct: poisoning the well’ by former editor of the British Medical Journal Richard Smith1 in which the problem of identifying scientific fraud was discussed and a general failure to develop methods for examination of possible cases was noted. He stated that, unlike many other countries, the Nordic countries had developed processes yet chose to highlight a case from Norway in which he, as editor of the BMJ, had successfully asked an author's employer to investigate. That investigation at the University of Oslo found that ‘there was not a problem with the work’. The paper by Norwegian general practitioner Dr Grethe Stoa Birketvedt was published in the BMJ2 with a ‘sceptical’ commentary from Professor John Garrow.3

The matter might have rested there had Dr Smith not added ‘I am not sure if the work was fraudulent, but I am left with severe doubts’ in his 2006 JRSM article, 13 years after the first misconduct investigation in Oslo. This damaging comment published in the JRSM and repeated in Dr Smith's book has led to professional difficulties for the investigator formerly under suspicion and ultimately led to a re-examination of the case all over again, this time by the ethical committee of the University of Tromso where she had received a PhD in 1995 [JF was the supervisor, ARL was the principal external examiner]. In August 2009, the University of Tromso announced that, following a very thorough enquiry into the issue, the Research Ethics Committee concluded that allegations of scientific misconduct were unfounded [including an identity confirmation from University Director, University of Tromso],4 yet no effort has been made to publicize this finding of ‘not guilty’.

While we support every effort to identify cases of fraud and withdraw papers presenting fraudulent claims, we feel that scientific journals have an equally strong moral obligation to make a clear statement when a suspect investigator has been found not guilty.
Redefining overweight and obesity in rheumatoid arthritis patients
Authors: A. Stavropoulos-Kalinoglou, G. S Metsios, Y. Koutedakis, A. M Nevill, K. M Douglas, A. Jamurtas, J. J C S V. van Zanten, M. Labib, G. D Kitas
Journal: Annals of the Rheumatic Diseases (2007)

To assess whether body mass index (BMI) and body fat (BF) differ between rheumatoid arthritis (RA) patients, patients with non-inflammatory arthritis (osteoarthritis, OA) and healthy individuals, and whether disease specific measures of adiposity are required to accurately reflect BF in these groups.641 individuals were assessed for BMI (kg/m(2)) and BF (bioelectrical impedance). Of them, 299 (174 RA, 43 OA and 82 healthy controls (HC)) formed the observation group and 342 (all RA) the validation group. RA disease characteristics were collected.ANOVA revealed significant differences between disease groups for BMI (p<0.05) and BF (p<0.001). ANCOVA showed that age accounted for the differences in BMI (F(1,294) = 5.10, p<0.05); age (F(1,293) = 22.43, p<0.001), sex (F(1,293) = 380.90, p<0.001) and disease (F(2, 293) = 18.7, p<0.001) accounted for the differences in BF. For a given BF, patients with RA exhibited BMI levels reduced by 1.83 kg/m(2) (p<0.001) compared to HC; there were no significant differences between OA and HC. A predictive model for BF was developed (R(2) = 0.769, p<0.001) and validated using limits of agreement Analysis against measured BF in the validation group (95%LIM(AG) = 6.17; CV = 8.94).In individuals with RA, BMI cut-off points should be reduced by 2 kg/m(2) (that is, to 23 kg/m(2) for overweight and 28 kg/m(2) for obesity). The equation developed can be used to accurately predict BF from BMI in RA patients. These findings may be important in the context of the cardiovascular comorbidity of RA.
Next generation sequencing of the Ago2 interacting transcriptome identified chemokine family members as novel targets of neuronal microRNAs in hepatic stellate cells
Authors: Andrea Noetel, Natalia Elfimova, Janine Altmüller, Christian Becker, Diana Becker, Wolfgang Lahr, Peter Nürnberg, Hermann Wasmuth, Andreas Teufel, Reinhard Büttner, Hans Peter Dienes, Margarete Odenthal
Journal: Journal of Hepatology (2012)
Opioid antagonist diprenorphine microinjected into parabrachial nucleus selectively inhibits vasopressin response to hypovolemic stimuli in the rat.
Authors: Y Iwasaki, M B Gaskill, R Fu, C B Saper, G L Robertson
Journal: Journal of Clinical Investigation (1993)

Subcutaneous injection of the potent, nonselective opioid antagonist diprenorphine inhibits the vasopressin response to acute hypovolemia. To determine if this inhibition is due to antagonism of opioid receptors in brain pathways that mediate volume control, we determined the vasopressin response to different stimuli when diprenorphine or other opiates were injected into the cerebral ventricles, the nucleus tractus solitarius (NTS), or the lateral parabrachial nucleus (PBN) of rats. We found that the vasopressin response to hypovolemia was inhibited by injection of diprenorphine into the cerebral ventricles at a dose too low to be effective when given subcutaneously. This response also was inhibited when a 20-fold lower dose of diprenorphine was injected into the PBN but not when it was injected into the NTS. The inhibitory effect of diprenorphine in the PBN was not attributable to a decrease in osmotic or hypovolemic stimulation and did not occur with osmotic or hypotensive stimuli. Injecting the PBN with equimolar doses of the mu antagonist naloxone, the delta antagonist ICI-154,129 or the kappa-1 agonist U-50,488H had no effect on basal or volume-stimulated vasopressin. We conclude that the inhibition of vasopressin by diprenorphine is due partially to action at a novel class of opioid receptors that transmit volume stimuli through the PBN.
Abstract 3231: A small molecule inhibitor of glucose transporter 1 (Glut1) down-regulates glycolysis, induces cell cycle arrest, and inhibits cancer cell growth <i>in vitro</i> and <i>in vivo</i>
Authors: Yi Liu, Yanyan Cao, Weihe Zhang, Stephen Bergmeier, Yanrong Qian, Huzoor Akbar, Robert Colvin, Juan Ding, Lingying Tong, Shiyong Wu, Jennifer Hines, Xiaozhuo Chen
Journal: Cancer Research (2012)

Abstract Increased dependence on glycolysis and glucose metabolism, known as the Warburg effect, is a near-universal hallmark of cancer. The functional and therapeutic importance of the effect has been increasingly recognized and glycolysis has become a new target of anticancer strategies. We recently reported the identification of a group of novel small compounds that inhibit basal glucose transport and reduce cancer cell growth by using a glucose deprivation-like mechanism. Based on these and other results, we hypothesized that the compounds inhibit cancer growth by targeting Glut1 and they are efficacious in vivo as anticancer agents. Here we report that the representative and novel compound WZB117 not only inhibited cancer cell growth in multiple cancer cell lines but also inhibited cancer growth in a nude mouse model. Daily intraperitoneal (ip) injection of WZB117 at a dose of 10 mg/kg resulted in an over 70% reduction in the average size of xenografted tumor of human lung cancer A549 cell origin. Compound target study showed that WZB117 inhibited glucose transport in human red blood cells (RBC) and RBC-derived vesicles, both of which express Glut1 as their sole glucose transporter. Docking studies of WZB117-Glut1 interaction also demonstrate and support the binding of WZB117 to Glut1. Mechanism studies using multiple cancer cell lines revealed that treatment of WZB117 led to an induction of glycolytic enzymes, such as hexokinase, PKM2 and PGAM1; and then a decline of glycolysis as indicated by reduced lactate production with changes in Akt, AMPK and mTOR, protein factors in energy sensitive signaling pathways. These resulted in ER stress, followed by cell cycle arrest mediated through downregulation of cyclin E and Rb. Taken together, cell cycle arrest at G1/S phase plays major roles in the WZB117-induced inhibition of cancer cell growth while apoptosis is secondary. WZB117 can serve as a prototypic compound for further development of Glut1 inhibitors into novel anticancer therapeutics targeting glucose transport and glucose metabolism. 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 3231. doi:1538-7445.AM2012-3231
CASE OF ABORTION, WITH FLOODING, IN WHICH A NEW UTERO-VAGINAL PLUG WAS SUCCESSFULLY EMPLOYED
Authors: W. F. Cleveland
Journal: BMJ (1856)

histoe of a lage number of cas, I have come to the cnlusion that whatever may be the seat of disease in the horse, these glands are seldom or ever affected in man.A very interesting inquiry arises, whether this disease did occur in man previous to the commencement of the preent century, or whether it was overlooked, in conse- quence of the presumed impossibility of its transmission.supposing it to be a new disease, to what extent is it likely to prevail if greater precautions are not exercised by those more immediately exposed to the contagion: farriers and grooms being still in a state of ignorance as to the risks they necessarily run from the incautious handling of glandered horses.That Mr. W. died of glanders, I think I have fully proved; and that the disease was decidedly produced from contagion, I have no reason whatever to doubt. EXPERIMENT.Nov. 19th, 7 P.x.With pus taken from the abscess of the right ankle on the preceding day, I inoculated a jack- ass on the septum of the left nostril and the ala of the right.I also rubbed some of the pus on the conjunctiva of both eyes.Nov. 20th, 4 P.M.A slight discharge, clear and watery, was running from both nostrils and from both eyes; the
A Second Opinion: Rescuing America's Health Care
Authors: Robert J. Caswell
Journal: Annals of Internal Medicine (2008)

Medical Writings: Book Notes6 May 2008A Second Opinion: Rescuing America's Health CareRobert J. Caswell, PhDRobert J. Caswell, PhDFrom Ohio State University College of Public Health, Columbus, Ohio.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-9-200805060-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail A Second Opinion: Rescuing America's Health CareRelman AS. 224 pages. New York: PublicAffairs; 2007. $24.00. ISBN 9781586484811. Order at www.publicaffairsbooks.com.Field of medicine: Health policy and management.Format: Hardcover book.Audience: Anyone interested in health policy and health reform, especially those in the medical profession.Purpose: To provide “a ‘second opinion’ about the state of our health care system and the major reforms it requires. It is in essence a personal manifesto.”Content: This brief book presents the author's analysis of the principal causes of the current crisis in the U.S. health care system and his recommended solution. He ... Author, Article, and Disclosure InformationAffiliations: From Ohio State University College of Public Health, Columbus, Ohio. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 May 2008Volume 148, Issue 9Page: 716KeywordsHealth careHealth care providersHealth information technologyPrevention, policy, and public healthSoftware tools ePublished: 6 May 2008 Issue Published: 6 May 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A Surgical Approach to Ebstein's Disease
Authors: L. P. SCOTT III, J. J. DEMPSEY, H. H. TIMMIS, J. E. MCCLENATHAN
Journal: Circulation (1963)

Ebstein's disease in a severely cyanotic 7-year-old boy was successfully treated by anastomosing the superior vena cava to the right pulmonary artery. A discussion of impaired right heart function in Ebstein's disease is presented emphasizing the inefficiency of right atrial contraction as a consequence of the "atrialization" of the right ventricle. It is our belief that right heart bypass with a superior vena cava to right pulmonary artery anastomosis is the surgical procedure of choice in patients severely ill from Ebstein's disease.