tbuckley/cabot-search huggingface dataset:
Expression Profiling Of Nuclear Hormone Receptors In Myeloid Leukemia Reveals Potential Novel Drug Targets For Combination Therapy
Authors: Sreeja Karathedath, Sukanya Ganesan, Wei Zhang, Ajay Abraham, Savitha Varatharajan, Bharathi M Rajamani, Shaji R Velayudhan, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
Journal: Blood (2013)
Abstract 4492: Eligibility to Percutaneous Aortic Valve Replacement in Patients at High-Risk for Surgery. Insight from PUREVALVE Registry Selection Phase
Authors: Massimo Napodano, Chiara Fraccaro, Giuseppe Tarantini, Raffaele Bonato, Gino Gerosa, Valeria Gasparetto, Sabino Iliceto, Angelo Ramondo
Journal: Circulation (2008)
A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children
Authors: David C. Brousseau, J. Paul Scott, Oluwakemi Badaki-Makun, Deepika S. Darbari, Corrie E. Chumpitazi, Gladstone E. Airewele, Angela M. Ellison, Kim Smith-Whitley, Prashant Mahajan, Sharada A. Sarnaik, T. Charles Casper, Lawrence J. Cook, J. Michael Dean, Julie Leonard, Monica L. Hulbert, Elizabeth C. Powell, Robert I. Liem, Robert Hickey, Lakshmanan Krishnamurti, Cheryl A. Hillery, Mark Nimmer, Julie A. Panepinto
Journal: Blood (2015)
Tobacco advertising
Authors: H. Kawane
Journal: BMJ (1996)

high; the standard mortality ratio was 1-42, which is much lower than that in recently published community based studies (one British,2 one American3) and similar to that in hospital based series after six years' treatment with levodopa.4Olanow and colleagues also state that the dose of levodopa was fixed in arm 2 and not adjusted to clinical need; if they read our paper's patients and methods section they will see that the dose in both arms of the trial was regulated to obtain optimum improvement.Mark T Silva and colleagues comment on the causes of death listed in table 3. Inaccuracy of death certificates is well recognised and presents particular problems in elderly people.All entries on the death certificates were coded from the
Macrophage migration inhibitory factor promotes expression of GLUT4 glucose transporter through MEF2 and Zac1 in cardiomyocytes
Authors: Yeyou Liang, Weiwei Yuan, Wensi Zhu, Jiening Zhu, Qiuxiong Lin, Xiao Zou, Chunyu Deng, Yongheng Fu, Xilong Zheng, Min Yang, Shulin Wu, Xiyong Yu, Zhixin Shan
Journal: Metabolism (2015)
Distribution Patterns of Psoriasis: Observations on Koebner Response
Authors: J C Mitchell
Journal: JAMA (1963)

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
Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer
Authors: Siker Kimbung, Ida Johansson, Anna Danielsson, Srinivas Veerla, Suzanne Egyhazi Brage, Marianne Frostvik Stolt, Lambert Skoog, Lena Carlsson, Zakaria Einbeigi, Elisabet Lidbrink, Barbro Linderholm, Niklas Loman, Per-Olof Malmström, Martin Söderberg, Thomas M. Walz, Mårten Fernö, Thomas Hatschek, Ingrid Hedenfalk
Journal: Clinical Cancer Research (2015)

The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis.A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested.Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors.Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer.
Abstract 1781: Nonprotected Left Main Stenosis: Multicenter Randomized Trial Between Total Arterial Revascularization and Interventional Treatment
Authors: Enno Boudriot, Gerhard Schuler, Thomas Walther, Volkmar Falk, Christoph Liebetrau, Holger Thiele, Peter Boeckstegers, Bruno Reichart, Tilman Pohl, Harald Mudra, Bernhard Kempkes, Florian Beier, Franz-Joseph Neumann, Elmar Eschenbruch, Michael Gick, Herzzentrum Bad Krozingen, Friedrich W Mohr
Journal: Circulation (2007)

Background: Nonprotected left main coronary stenosis is still considered an indication for bypass surgery. We conducted a multicenter prospective randomized trial to compare total arterial revascularization (CABG) with interventional treatment (PCI) in these patients. Methods and Demographics: Between 8/2003 and 5/2007 a total of 156 pts with significant stenosis of the nonprotected left main coronary artery were recruited for the study. We report the first 111 pts whith one year follow up. They were randomized to undergo CABG or PCI using drug eluting stents (Sirolimus). Additional lesions in other locations were treated concurrently. Angiographic control was performed at 12 months. Primary endpoints were death, acute myocardial infarction and re-intervention at 12 months. Out of the 111 pts 55 pts were randomized for CABG and 56 for PCI. Mean age was 65 ± 7 years, diabetes was present in 35%. There were no significant differences between both groups with respect to other baseline variables. The lesion was located at the ostium in 17%, midshaft in 11%, and distally in 72%. An average of 2.4 ± 1.1 stents were implanted, and 2.4 ± 0.6 bypass grafts were performed. Of the operated patients 70% received complete arterial revascularization. Results: Early outcome revealed a procedural success of in all 55 pts for CABG and in 53 of 56 pts for PCI , three pts assigned to PCI had to be successfully converted to CABG. Early mortality in surgery was 1.8%, no patient died early after PCI. Periprocedural NSTEMI were noted in 2 pts after PCI and in six pts after CABG, of those one pt. underwent graft revision. After 12-month follow up control angiography was performed, in 2 pts (3,5%) after CABG and in 7 pts. after PCI (13,2%) reintervention was necessary. 5 pts required target vessel revascularization (TVR). 2 pts developed a de-novo lesion. One of the PCI cohort died at 10 months. MACE rate after 12 month was comparable for CABG group with 18,1% and 17,9% for the PCI group . Conclusions: In pts with nonprotected left main stenosis both CABG and PCI using drug eluting stents can be performed with few periprocedural complications, low mortality and at 12 months mace rate and survival compare favourably, reintervention rate is higher in PCI.
The anti-apoptotic protein clusterin is induced by cancer chemotherapy, stabilized by the proteasome, and degraded by intracellular proteases
Authors: Rolf J. Craven, Melissa Ranney, Ikhlas Ahmed
Journal: Clinical Cancer Research (2006)

B20   Background: Cancer is generally treated with a combination of chemotherapy, radiation, and surgery. Highly malignant, p53-negative cancer cells are partially resistant to chemotherapy, and an important candidate mechanism is the induction of clusterin, which is strongly induced by chemotherapy and promotes drug resistance. Clusterin is capable of inhibiting apoptosis by binding to Bax or promoting apoptosis by binding to the DNA repair protein Ku70 in the nucleus. We have analyzed the regulatory pathways that control clusterin expression after chemotherapy.Experimental procedures: MDA-MB-231 human breast cancer cells were treated with doxorubicin in combination with pharmacological inhibitors the proteasome, and clusterin expression was analyzed by western blot. Clusterin expression was then suppressed by RNAi, and its effect on apoptosis was analyzed by cleavage of PARP and pro-caspase 3.Results: Clusterin expression was strongly induced by doxorubicin, as previously published. However, clusterin was degraded following treatment with doxorubicin in combination with the proteasome inhibitor epoxomicin in a dose-dependent manner, suggesting that clusterin is stabilized by proteasome activity. Thus, clusterin is similar to other anti-apoptotic proteins, such as the transcription factor NF-κB, which are inactivated by proteasome inhibitors. In contrast, clusterin levels were increased following treatment with the proteasome inhibitor MG132, either alone or in combination with doxorubicin. Using RNAi directed to the third exon of clusterin, we determined that clusterin suppressed MG132-induced apoptosis. MG132 differs from epoxomicin in that it inhibits several non-proteasome proteases. Our findings suggest a model in which MG132-sensitive proteases degrade clusterin following chemotherapy, suppressing apoptosis.Conclusions: Proteasome inhibitors are a promising class of anti-neoplastic drugs that are currently in clinical trials. Clusterin is an anti-apoptotic target protein for highly specific proteasome inhibitors, suggesting that clusterin may be a useful marker for proteasome inhibitor activity in tumors. In addition, our results are consistent with a model in which cellular proteases inhibit clusterin and promote apoptosis following chemotherapy. This protealytic activity towards clusterin is suppressed by the proteasome and by histone deacetylases (see accompanying abstract). As a result, clusterin expression may be an important parameter for individualized treatment with proteasome inhibitors.
Oliver Wolf Sacks
Authors: Geoff Watts
Journal: BMJ (2015)

Neurologist and author



Strictly speaking, Oliver Sacks was a physician who took up writing. But his authorial impact was such that it makes equal sense to think of him as a writer who happened to have a broad knowledge of medicine. He mined that knowledge for insights into what it is to be human, whether in sickness or in health. His most celebrated medical achievement was the use of L-dopa in the treatment of a group of patients affected by the epidemic of encephalitis lethargica in the 1920s. It was also this, chronicled in his 1973 book Awakenings and the subsequent film, that brought him to public attention.



Readers of his many books unfamiliar with the medical literature of years gone by may have thought Sacks had created a new genre in his writing about illness. He hadn’t, of course. What he had done was resurrect an approach that once characterised much of the content of medical journals: the case history. He modernised it, enlivened it with his literary skills, and embellished it with his own humanity.

A century or more ago—when medicine’s grasp of disease was still …
Comparison of fluticasone propionate and budesonide on phagocytosis of common respiratory pathogens in COPD patients
Authors: Catherine M.R. Thomas, Anna Miller-Larsson, Peter J. Barnes, Louise E. Donnelly
Journal: European Respiratory Journal (2011)

Background:  Inhaled corticosteroids are recommended for COPD patients with FEV 1  ≤ 50% predicted, experiencing ≥2 exacerbations in 12 months. However, post-hoc analysis of the TORCH study revealed an increased risk of pneumonia of 50% in patients taking inhaled fluticasone propionate (FP) (ERJ 2009;34:641). This contrasts with a meta-analysis of patients taking budesonide (BUD) where there was no increased risk of pneumonia (Lancet 2009;374:712). The reason for this discrepancy is unclear, however, we hypothesise that the particulate nature of FP, due to high lipophilicity and low water solubility, leads to its uptake by phagocytes resulting in impaired function.   Methods:  Neutrophils and monocytes were isolated from the blood of COPD patients (n=10). Monocyte-derived macrophages (MDM) were generated from monocytes by 12d culture in media containing GM-CSF. All cells were incubated with steroid for 1h prior to phagocytosis assays with fluorescently-labelled polystyrene beads,  Haemophilus influenzae  (HI) or  Streptococcus pneumoniae  (SP).   Results:  BUD (1μM) increased MDM phagocytosis of beads by 17% (p -10 -10 -6 M) significantly (p   Conclusions:  FP did not reduce phagocytic function of either MDM or neutrophils. BUD improved neutrophil phagocytosis of HI, which may explain differences in pneumonia incidence between FP and BUD in COPD patients.
A phase I dose-escalation study of ABT-888 (veliparib) in combination with carboplatin in HER2-negative metastatic breast cancer (MBC).
Authors: S. Viswanathan, R. Wesolowski, R. M. Layman, G. Alejandra, B. Miller, J. J. Chalmers, S. Bejastani, W. Zhao, G. Pierluigu, J. Cotrill, M. A. Phelps, L. J. Schaaf, S. M. Geyer, N. Hall, M. V. Knopp, C. L. Shapiro, M. A. Villalona-Calero, A. Chen, M. R. Grever, B. Ramaswamy
Journal: Journal of Clinical Oncology (2011)

TPS106 Background: Preclinical and clinical data demonstrate the promising activity of PARP inhibitors (PARPi) in triple negative (TN) and BRCA-1 deficient breast cancers. BRCA 1/2 are part of the Fanconi Anemia (FA) network of proteins that function in DNA damage response to maintain genomic integrity. Investigators at our institution have shown that defect in FA pathway sensitizes cells to DNA damaging agents and PARPi. We propose here to combine carboplatin and oral PARPi (ABT 888) to determine the maximum tolerated dose (MTD) on 2 differing schedules of 7 and 14 days in patients with MBC that are either TN or ER and/or PR +(HR +ve) with FA defect. Methods: Objectives: 1. To determine the MTD, toxicity and preliminary efficacy of ABT 888 in combination with carboplatin 2. To determine the biological dose-response to varying dose/schedule of ABT 888, we propose to use A. the novel imaging 3’-[F-18]Fluoro-3’-deoxythymidine Positron Emission Tomography (FLT-PET), B. obtain circulating tumor cells (CTCs) to assess induction of gamma H2Ax, and C. determine PAR levels in PBMC 3. Evaluate biomarkers in primary tumor that could predict response to PARPi such as BRCA-1/2, FANCD2 nuclear foci formation (using the FA Triple Stain Immunofluroscence test/FATSI) and expression of miR 155 (oncogenic miR that targets DNA repair genes). Eligibility: Patients with Her 2 negative MBC that are either ER/PR negative (triple negative) or HR+ with a defective FA pathway who have received no more than 3 prior chemotherapy regimens, and ECOG PS 0-2 are eligible. Prior platinum therapy is allowed. Study design: Patients with HR+ve MBC will sign a screening consent form to obtain archival tumor to test for absence of nuclear FANCD2 by FATSI and if confirmed, will be potentially eligible. All eligible patients will receive carboplatin at AUC of 6 on day 1 of a 21 day cycle and ABT 888 BID for 7 or 14 days depending on dose level. Dose-escalation: Standard 3+3 phase I trial design will be used for dose escalation and to identify MTD for -7 and 14 day schedule. Correlatives: FLT-PET scan and peripheral blood for CTCs and PAR immunoassay will be obtained at baseline and multiple time-points during the study. Funded by U01 –CA 76576
Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study.
Authors: M Housset, C Maulard, Y Chretien, B Dufour, S Delanian, J Huart, F Colardelle, P Brunel, F Baillet
Journal: Journal of Clinical Oncology (1993)

PURPOSE To improve the results obtained by cystectomy alone and to determine the possibilities of conservative treatment in invasive bladder cancer, we designed a prospective study using a combination of fluorouracil (5-FU) plus cisplatin and concomitant radiation therapy, followed by either cystectomy or additional chemoradiotherapy. PATIENTS AND METHODS Fifty-four patients with stage T2 to T4 operable untreated invasive bladder cancer were entered onto the study. Treatment was begun in all patients by transurethral resection (TUR) and followed by the 5-FU-cisplatin combination with concomitant bifractionated split-course radiation therapy. A control cystoscopy was performed 6 weeks after completion of the neoadjuvant program. Patients with persistent tumor underwent cystectomy. Complete responders were treated by either additional chemoradiotherapy (group A) or cystectomy (group B). RESULTS At control cystoscopy, 40 of 54 patients (74%) had a histologically documented complete response. Four responders developed recurrent pelvic disease after a mean follow-up time of 27 +/- 12 months (three in group A and one in group B). Metastatic disease, which developed in 16 patients, occurred more frequently in the nonresponders (71%) than in responders (15%). The disease-free survival rate at 3 years was 62%; it was significantly better in responders (77%) than in nonresponders (23%). There was no difference in survival between groups A and B. CONCLUSION This neoadjuvant chemoradiotherapy combination, easy to implement and well tolerated even in elderly patients, provides a high complete response rate. It may prove to be effective in inoperable patients and may be proposed as conservative treatment in patients with a complete response to the initial course of chemoradiation.
Corticosteroid plus long-acting beta2-agonist prevent virus-associated upregulation of B7-H1/PD-L1 on airway epithelium
Authors: Saaka Hamano, Koichiro Matsumoto, Keiko Kan-o, Satoru Fukuyama, Yukari Asai, Hiromasa Inoue, Yoichi Nakanishi
Journal: European Respiratory Journal (2013)

Background:  Airway viral infections exacerbate asthma and chronic obstructive pulmonary disease. B7-H1/PD-L1 is a coinhibitory molecule implicated in an escape mechanism of viruses from the host immune systems. This escape may induce viral persistence and lead to exacerbation of the underlying diseases. We previously showed that an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly IC), upregulated the expression of B7-H1 on airway epithelial cells, which was corticosteroid-resistant. We investigated the effects of corticosteroid plus long-acting beta 2 -agonist (LABA) on the expression of B7-H1.   Methods:  BEAS-2B cells were stimulated with poly IC or the respiratory syncytial virus. B7-H1 expression was assessed by flow cytometry.   Results:  Poly IC-induced upregulation of B7-H1 was suppressed by high-concentration fluticasone but not by salmeterol. The upregulation was suppressed by low-concentration fluticasone when used in combination with salmeterol. Similar results were obtained from experiments using other combination of corticosteroid and LABA. Their combination also suppressed the virus-induced upregulation of B7-H1. Poly IC stimulation induced the nuclear translocation of the nuclear factor kB (NF-kB). The inhibitors of NF-kB activation prevented the poly IC-induced upregulation of B7-H1. The corticosteroid in combination with LABA enhanced the  de novo  induction of IkBa, the endogenous inhibitor of NF-kB activation.   Conclusion:  Corticosteroid plus LABA attenuates virus-associated upregulation of B7-H1 on airway epithelial cells via suppression of NF-kB activation.
2-Year Clinical Outcomes After Implantation of Sirolimus-Eluting, Paclitaxel-Eluting, and Bare-Metal Coronary Stents
Authors: Anne Kaltoft, Lisette Okkels Jensen, Michael Maeng, Hans Henrik Tilsted, Per Thayssen, Morten Bøttcher, Jens Flensted Lassen, Lars Romer Krusell, Klaus Rasmussen, Knud Nørregaard Hansen, Lars Pedersen, Søren Paaske Johnsen, Henrik Toft Sørensen, Leif Thuesen
Journal: Journal of the American College of Cardiology (2009)
AVI-7288 for Marburg Virus in Nonhuman Primates and Humans
Authors: Alison E. Heald, Jay S. Charleston, Patrick L. Iversen, Travis K. Warren, Jay B. Saoud, Mohamed Al-Ibrahim, Jay Wells, Kelly L. Warfield, Dana L. Swenson, Lisa S. Welch, Peter Sazani, Michael Wong, Diane Berry, Edward M. Kaye, Sina Bavari
Journal: New England Journal of Medicine (2015)

AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its safety in humans is undetermined.We assessed the efficacy of AVI-7288 in a series of studies involving a lethal challenge with MARV in nonhuman primates. The safety of AVI-7288 was evaluated in a randomized, multiple-ascending-dose study in which 40 healthy humans (8 humans per dose group) received 14 once-daily infusions of AVI-7288 (1 mg, 4 mg, 8 mg, 12 mg, or 16 mg per kilogram of body weight) or placebo, in a 3:1 ratio. We estimated the protective dose in humans by comparing pharmacokinetic variables in infected nonhuman primates, uninfected nonhuman primates, and uninfected humans.Survival in infected nonhuman primates was dose-dependent, with survival rates of 0%, 30%, 59%, 87%, 100%, and 100% among monkeys treated with 0 mg, 3.75 mg, 7.5 mg, 15 mg, 20 mg, and 30 mg of AVI-7288 per kilogram, respectively (P<0.001 with the use of the log-rank test for the comparison of survival across groups). No safety concern was identified at doses up to 16 mg per kilogram per day in humans. No serious adverse events were reported. Drug exposure (the area under the curve) was dose-dependent in both nonhuman primates and humans; drug clearance was independent of dose but was higher in nonhuman primates than in humans. The protective dose in humans was initially estimated, on the basis of exposure, to be 9.6 mg per kilogram per day (95% confidence interval, 6.6 to 12.5) for 14 days. Monte Carlo simulations supported a dose of 11 mg per kilogram per day to match the geometric mean protective exposure in nonhuman primates.This study shows that, on the basis of efficacy in nonhuman primates and pharmacokinetic data in humans, AVI-7288 has potential as postexposure prophylaxis for MARV infection in humans. (Funded by the Department of Defense; ClinicalTrials.gov number, NCT01566877.).