tbuckley/cabot-search huggingface dataset:
Abstract 2486: A possible mechanism for plagiochiline A activity: Inhibition of cytokinesis
Authors: Nicole S. Stivers, Ashraful Islam, Lavona K. Casson, Jose C. Aponte, Gerald B. Hammond, Abraham J. Vaisberg, Paula J. Bates
Journal: Cancer Research (2010)

Abstract We recently reported on the isolation of plagiochiline A, a 2,3-secoaromadendrane-type sesquiterpenoid, from the Peruvian medicinal plant Plagiochila distichia. This compound was found to have antiproliferative activity against a variety of solid tumor cell lines, including those derived from prostate, colon, breast, lung, and cervical cancers, as well as several leukemia cell lines. Other researchers have also noted the cytotoxicity of plagiochiline A (isolated from other plant species), but the mechanism for this activity was unknown. Here, we describe new research where we have investigated the mechanism of plagiochiline A using a variety of experimental techniques. First of all, we evaluated cell cycle parameters in DU145 prostate cancer cells treated for 24 h with 4 µg/mL (11.4 µM) plagiochiline A using flow cytometry based analysis of propidium iodide-stained cells. We found that plagiochiline A caused a statistically significant increase in the percentage of cells in the G2/M phase compared to vehicle-treated cells (41.7% compared to 24.8%, based on three independent experiments). We next examined similarly treated cells stained with DAPI (a DNA intercalator) and anti-tubulin antibodies (microtubule marker) using fluorescence microscopy to evaluate the mitotic status of the cells. These experiments revealed a large number of binucleate cells, many of which had intercellular bridges evident, specifically in the plagiochiline A-treated samples. Only a few cells were observed in earlier stages of mitosis, suggesting that the accumulation of cells in G2/M is due to a defect in cytokinesis. We are currently carrying out additional research in order to test this hypothesis. We also plan to determine the effects on cells following longer treatments with plagiochiline A and to investigate possible molecular target(s) of plagiochiline A. Although many anti-mitotic compounds are in current use as anticancer agents, there are apparently only a few agents in development that specifically target cytokinesis. Therefore, we anticipate that this research may ultimately lead to novel anticancer agents and new tools to study cytokinesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2486.
PWE-246 Infliximab treatment significantly reduces inflammatory macrophage numbers while preserving regulatory macrophages in a mouse model of chronic Crohn's colitis
Authors: S Levison, M C Little, R K Grencis, J T McLaughlin, J L Pennock
Journal: Gut (2012)

<h3>Introduction</h3> Inappropriate inflammatory responses to intestinal flora, augmented by host susceptibility genetics, contribute to the pathogenesis of Crohn9s disease (CD). Transmural intestinal inflammation results from innate and adaptive immune cell infiltration, and pro-inflammatory cytokine accumulation. Activated macrophages represent a major source of TNFα production. The treatment of CD with anti-TNFα antibody (Ab) therapy has proved clinically beneficial, yet over 30% of patients fail to respond. We characterised the biological and immunological effects of Infliximab therapy in a model of experimental colitis. <h3>Methods</h3> Genetically identical mice (AKR), susceptible to chronic <i>Trichuris muris</i>-induced colitis, were infected with 300 <i>T muris</i> eggs. A single 5 mg/kg dose of Infliximab was administered intra-peritoneally once chronic colitis had established (from day 35 post-infection, p.i.). Systemic, mesenteric lymph node (MLN) and colonic effects were analysed at day 45 p.i. MLN cell cytokine bead-array and colonic gene expression (RT-qPCR) analysis were performed. Colonic histopathology, tissue Foxp3<sup>+</sup>, and macrophage recruitment and phenotype were determined. The treatment group was compared to untreated-infected, naive, and naïve AKR administered Infliximab (n=5 per group). <h3>Results</h3> Treatment did not alter worm expulsion. Anti–TNFα Ab therapy preserved colonic length compared to untreated disease (p=0.049). Colonic inflammation was less severe with Infliximab treatment (p=0.07). Reduced TNFα, CCL2, and GMCSF proteins were measured in the MLN of Infliximab treated infected AKR. Reduced colonic expression of TNFα, IL-1β, IFNγ and IL-12p40, and increased IL-13 was observed following Infliximab treated disease. Colonic Foxp3<sup>+</sup> cell numbers increased with disease but were unaltered by treatment. Infected mice treated with Infliximab demonstrated a 50% reduction in colonic F4/80<sup>+</sup> macrophages (p=0.036). A relative increase of the proportion of colonic Arg<sup>+</sup> alternatively activated macrophages (AAMФ) was observed with Infliximab treatment compared to untreated disease (29% vs 14%). <h3>Conclusion</h3> Infliximab therapy suppresses TH1-driven experimental colitis. Anti–TNFα Ab treatment reduced pro-inflammatory macrophages recruitment, and for the first time in vivo has been shown to preserve colonic tissue regulatory AAMФ. Whether a result of a fundamental alteration to macrophage recruitment, or the differentiation of a specific macrophage phenotype, requires further study. The presence of AAMФ at index biopsy, or an increase in AAMФ numbers following treatment initiation, may help to identify patient responders to Anti-TNFα Ab therapy. <h3>Competing interests</h3> None declared.
Women in medicine: Sexism is not only reason for women's “unequal status” in the workplace
Authors: Kingsley R Browne
Journal: BMJ (2004)

EDITOR—Heath expresses many misconceptions about women in the workplace.1 Women are compelled to look after their children, work part time, earn less money, and do different jobs from men. Better state support for childrearing, she implies, would produce equality in the workplace.

Many legitimate factors cause sex differences in earnings and occupations. Women earn less because they work fewer …
Nongonococcal Urethritis: the Role of Chlamydia trachomatis
Authors: NORMAN F. JACOBS
Journal: Annals of Internal Medicine (1977)

Letters1 March 1977Nongonococcal Urethritis: the Role of Chlamydia trachomatisNORMAN F. JACOBS JR., M.D., EUGENE S. ARUM, M.D., STEPHEN J. KRAUS, M.D.NORMAN F. JACOBS JR., M.D.Search for more papers by this author, EUGENE S. ARUM, M.D.Search for more papers by this author, STEPHEN J. KRAUS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-3-313 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAt present nongonococcal urethritis is more common than gonorrhea among sexually active men attending venereal disease clinics in widely separated areas of the United States (1, 2). Efforts to control this urethritis epidemic are hampered by inadequate knowledge of the origin and epidemiology of nongonococcal urethritis. Although a variety of organisms have been cultured from patients with the disease, few studies have included controls with similar levels of sexual activity (3). Recently, T-mycoplasmas (4) andChlamydia trachomatis(2) have been implicated as etiologic agents in controlled studies. However, other workers have isolatedC. trachomatisas frequently from men with...References1. JACOBSKRAUS NS: Gonococcal and nongonococcal urethritis in men. Clinical and laboratory differentiation. Ann Intern Med 82:7-12, 1975 LinkGoogle Scholar2. HOLMESHANDSFIELDWANG KHS: Etiology of nongonococcal urethritis. N Engl J Med 292:1199-1205, 1975 CrossrefMedlineGoogle Scholar3. KAUFMANWIESNER RP: Nonspecific urethritis. N Engl J Med 291:1175-1177, 1974 CrossrefMedlineGoogle Scholar4. SHEPARD M: Nongonococcal urethritis associated with human strains of "T" mycoplasmas. JAMA 211:1335-1340, 1970 CrossrefMedlineGoogle Scholar5. RICHMONDHILTONCLARKE SAS: Chlamydial infection. Role of Chlamydia subgroup A in non-gonococcal and post-gonococcal urethritis. Br J Vener Dis 48:437-444, 1972 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Venereal Disease Research Branch Center for Disease Control Public Health Service U.S. Department of Health, Education, and Welfare Atlanta, GA 30333 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAdverse Effects of Genito-urinary Infections with Particular Reference to Fertility and Pre-conceptional CareDeteccion de Chlamydia trachomatis en muestras uretrales mediante inmunofluorescencia directaPersistent and recurrent non-gonococcal urethritisNongonococcal urethritis 1 March 1977Volume 86, Issue 3Page: 313-314KeywordsChlamydia trachomatisEpidemiologyGonorrheaHuman sexual behaviorSexually transmitted diseases Issue Published: 1 March 1977 PDF DownloadLoading ...
Stable gene transfer and expression in cord blood–derived CD34+ hematopoietic stem and progenitor cells by a hyperactive Sleeping Beauty transposon system
Authors: Xingkui Xue, Xin Huang, Sonja E. Nodland, Lajos Mátés, Linan Ma, Zsuzsanna Izsvák, Zoltán Ivics, Tucker W. LeBien, R. Scott McIvor, John E. Wagner, Xianzheng Zhou
Journal: Blood (2009)
Cancer of the Nail Bed
Authors: P. M. Inlow
Journal: JAMA (1979)

<h3>To the Editor.—</h3> I agree with Long and Espiniella (239:2154,1978) that cancer of the nail bed is more frequent than the literature would indicate. I am a radiologist from a small town in Indiana (Shelbyville, population 15,000) and in 16 years of practice have had two patients, both men, with biopsy-proved squamous cell cancer of the nail bed. The men, aged 59 and 60 years, are both from this county and had had the lesion for several years. One of the patients had a growth of the left thumbnail for 25 years, which had been treated by fulguration on two previous occasions. The other patient had a lesion of the left index finger. Since there was no evidence of bone invasion, they were treated by x-ray therapy to include the interphalangeal joint of the thumb and to the proximal interphalangeal joint of the finger. They are tumor free six and
More stakeholder engagement is needed to improve quality of research, say US experts
Authors: B. Roehr
Journal: BMJ (2010)

Researchers need to overcome the evidence paradox of 18 000 randomised trials being published each year but almost every review concluding that not enough hard evidence exists to actually inform decision making, experts have said.

Sean Tunis, the founding director of the Baltimore based Center for Medical Technology Policy, which aims to improve the quality of research, warned about the lack of useful evidence at a US congressional briefing on research into comparative effectiveness on 30 July.

Dr Tunis told the briefing: “This is a structural problem, a systemic problem. It won’t be solved by doing more of the same thing. Gaps in evidence …
Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20
Authors: Melanie Bahlo, David R Booth, Simon A Broadley, Matthew A Brown, Simon J Foote, Lyn R Griffiths, Trevor J Kilpatrick, Jeanette Lechner-Scott, Pablo Moscato, Victoria M Perreau, Justin P Rubio, Rodney J Scott, Jim Stankovich, Graeme J Stewart, Bruce V Taylor, James Wiley, Glynnis Clarke, Mathew B Cox, Peter A Csurhes, Patrick Danoy, Karen Drysdale, Judith Field, Judith M Greer, Preethi Guru, Johanna Hadler, Brendan J McMorran, Cathy J Jensen, Laura J Johnson, Ruth McCallum, Marilyn Merriman, Tony Merriman, Karen Pryce, Lotfi Tajouri, Ella J Wilkins, Brian L Browning, Sharon R Browning, Devindri Perera, Simon Broadley, Helmut Butzkueven, William M Carroll, Caron Chapman, Allan G Kermode, Mark Marriott, Deborah Mason, Robert N Heard, Michael P Pender, Mark Slee, Niall Tubridy, Ernest Willoughby
Journal: Nature Genetics (2009)
Automatic activity in depolarized guinea pig ventricular myocardium. Characteristics and mechanisms.
Authors: S Imanishi, B Surawicz
Journal: Circulation Research (1976)

Membrane potential was changed uniformly in segments, 0.7-1.0 mm long, of guinea pig papillary muscles excised from the right ventricle by using extracellular polarizing current pulses applied across two electrically insulated cf preparations superfused with Tyrode's solution at maximum diastolic membrane potentials ranging from-35.2+/-7.5 (threshold) to +4.0+/-9.2 mV. The average maximum dV/dt of RAD ranged from 17.1 to 18.0 V/sec within a membrane potential range of -40 to +20 mV. Raising extracellular Ca2+ concentration [Ca2+]0 from 1.8 to 6.8 mM, or application of isoproterenol (10(-6)g/ml) enhanced the rate of RAD, but lowering [Ca2+]0 to 0.4 mM or exposure to MnCl2 (6 mM) abolished RAD. RAD were enhanced by lowering extracellular K+ concentration [K+]0 from 5.4 to 1.5 mM. RAD were suppressed in 40% of fibers by raising [K+]0 to 15.4 mM, and in all fibers by raising [K+]0 to 40.4 mM. This suppression was due to increased [K+]0 and not to K-induced depolarization because it persisted when membrane potential was held by means of a conditioning hyperpolarizing puled gradually after maximum repolarization. These observations suggest that the development of RAD in depolarized myocardium is associated with a time-dependent decrease in outward current (probably K current) and with increase in the background inward current, presumably flowing through the slow cha-nel carrying Ca or Na ions, or both.
Sample Type Bias in the Analysis of Cancer Genomes
Authors: David A. Solomon, Jung-Sik Kim, Habtom W. Ressom, Zita Sibenaller, Timothy Ryken, Walter Jean, Darell Bigner, Hai Yan, Todd Waldman
Journal: Cancer Research (2009)

Abstract There is widespread agreement that cancer gene discovery requires high-quality tumor samples. However, whether primary tumors or cultured samples are superior for cancer genomics has been a longstanding subject of debate. This debate has recently become more important because federally funded cancer genomics has been centralized under The Cancer Genome Atlas, which has chosen to focus exclusively on primary tumors. Here, we provide a data-driven “perspective” on the effect of sample type selection on cancer genomics research. We show that, in the case of glioblastoma multiforme, primary tumors and xenografts are best for the identification of amplifications, whereas xenografts and cell lines are superior for the identification of homozygous deletions. We also note that many of the most important oncogenes and tumor suppressor genes have been discovered through the use of cell lines and xenografts, and highlight the lack of published evidence supporting the dogma that ex vivo culture generates artifactual genetic lesions. Based on this analysis, we suggest that cancer genomics projects such as The Cancer Genome Atlas should include a variety of sample types such as xenografts and cell lines in their integrated genomic analysis of cancer. [Cancer Res 2009;69(14):5630–3]
A FECAL FISTULA THROUGH THE APPENDIX RESULTING FROM A PERFORATING APPENDICITIS.
Authors: J. B. EAGLESON
Journal: JAMA (1897)

The patient, Captain J. A. O'B., aged 46 years, a native of Ireland, has been well known among steamboat and shipping men on the Pacific Coast for many years. He had a slight attack of pain in the bowels in February, 1894, for which he was treated in the hospital for two days. It was thought to have been a "bilious attack." In April, 1896, he took his steamer to Cook's Inlet, Alaska, with a party of miners and shortly before his arrival he was seized with a severe pain in the right side of the abdomen, and as soon as the steamer reached her destination he placed himself in the care of Dr. B. W. Rodgers of Oakland, Cal., who happened to be at the Inlet, as surgeon for a party of prospectors. He continued to grow worse and, on April 19, Dr. Rodgers operated, with the assistance of
P15. A genetic mouse model to identify the role of the immune adapter protein MyD88 in colorectal cancer
Authors: A Holtorf, B Holzmann, KP Janssen
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Pattern recognition receptors from the Toll-like receptor (TLR) family are pivotal components of innate immunity, and have been shown to contribute to colon cancer formation. However, the molecular and cellular mechanisms underlying TLR-signaling in colon cancer remain unclear.
Mechanism of arrhythmias induced by palmitylcarnitine in guinea pig papillary muscle
Authors: K. SAKATA, H. HAYASHI, A. KOBAYASHI, N. YAMAZAKI
Journal: Cardiovascular Research (1989)

Long chain acyl carnitines, intermediates of free fatty acid metabolism, have been implicated in malignant arrhythmias occurring during myocardial ischaemia. To investigate the mechanism of arrhythmia induced by these compounds the electrophysiological effects of palmitylcarnitine (30, 100 and 300 mumol.litre-1) on guinea pig papillary muscles was examined using the microelectrode technique. Palmitylcarnitine caused a time and concentration dependent shortening of action potential duration, with an increase in both developed and resting tension. After attaining the peak value of developed tension, delayed afterdepolarisations and/or aftercontractions were observed in three out of eight muscles on exposure to 100 mumol.litre-1 palmitylcarnitine and in all 13 muscles on exposure to 300 mumol.litre-1, while arrhythmia occurred in one out of eight muscles and in seven out of 13 muscles during these exposures. The amplitude and the coupling interval of delayed afterdepolarisations were dependent on basic cycle length. Delayed afterdepolarisations, aftercontractions and arrhythmias were completely abolished by ryanodine (1 mumol.litre-1). Though low Ca2+ (0.1 mmol.litre-1) abolished these activities, verapamil (4 and 10 mumol.litre-1) did not suppress them. Palmitylcarnitine (300 mumol.litre-1) shortened action potential duration to the same degree during metabolic block of either oxidative phosphorylation or glycolysis as it did in muscles exposed to oxygenated Krebs solution. Under these conditions, delayed afterdepolarisation and/or aftercontractions appeared in all muscles. We conclude that palmitylcarnitine could cause Ca2+ overload and trigger activity due to delayed afterdepolarisations and could act on the cell membrane independently of cardiac metabolism. We suggest that palmitylcarnitine is a factor in arrhythmogenesis during myocardial ischaemia.
Changing Concepts in Lower Urinary-Tract Obstruction in Children
Authors: Frank Coleman Hamm
Journal: JAMA (1961)

Making a voiding cystourethrogram prior to cystoscopy has been found to be of great value in the diagnosis of the site of obstruction of the lower urinary tract in children. Valvular obstruction of the posterior urethra was found to be more common than had been supposed. In the past 3 years 9 cases have been diagnosed. Removal of the valves by transurethral resection was more satisfactory than open operation. Attention is drawn to the importance of considering the megacystis syndrome and fibroelastosis in the differential diagnosis of lower urinary-tract obstruction.
Bayesian Selection of Continuous-Time Markov Chain Evolutionary Models
Authors: Marc A. Suchard, Robert E. Weiss, Janet S. Sinsheimer
Journal: Molecular Biology and Evolution (2001)

We develop a reversible jump Markov chain Monte Carlo approach to estimating the posterior distribution of phylogenies based on aligned DNA/RNA sequences under several hierarchical evolutionary models. Using a proper, yet nontruncated and uninformative prior, we demonstrate the advantages of the Bayesian approach to hypothesis testing and estimation in phylogenetics by comparing different models for the infinitesimal rates of change among nucleotides, for the number of rate classes, and for the relationships among branch lengths. We compare the relative probabilities of these models and the appropriateness of a molecular clock using Bayes factors. Our most general model, first proposed by Tamura and Nei, parameterizes the infinitesimal change probabilities among nucleotides (A, G, C, T/U) into six parameters, consisting of three parameters for the nucleotide stationary distribution, two rate parameters for nucleotide transitions, and another parameter for nucleotide transversions. Nested models include the Hasegawa, Kishino, and Yano model with equal transition rates and the Kimura model with a uniform stationary distribution and equal transition rates. To illustrate our methods, we examine simulated data, 16S rRNA sequences from 15 contemporary eubacteria, halobacteria, eocytes, and eukaryotes, 9 primates, and the entire HIV genome of 11 isolates. We find that the Kimura model is too restrictive, that the Hasegawa, Kishino, and Yano model can be rejected for some data sets, that there is evidence for more than one rate class and a molecular clock among similar taxa, and that a molecular clock can be rejected for more distantly related taxa.
Toxic effects of interferon administered intrathecally.
Authors: J Ruutiainen, M Panelius, K Cantell
Journal: BMJ (1983)

Toxic effects of interferon administered intrathecallyMultiple sclerosis is a neurological disease of unknown aetiology with signs of defective immunoregulation.Studies with immunologically active agents and immunosuppressive drugs have been carried out.Interferons, of which there are at least three types (cc, 3, and y), are antiviral, cytostatic, and immunomodulatory proteins.The impaired production of interferon in patients with multiple sclerosis' has prompted follow up trials of treatment with interferon in these patients.2Since only 2-4% of interferon injected intramuscularly passes the blood-brain barrier, intrathecal administration has been used to obtain higher concentrations in the cerebrospinal fluid.Exogenous interferon-5 given intrathecally appears to be fairly non- toxic.3We report our recent experience with intrathecal administration of interferon-ac. Patients, methods, and resultsWe studied five severely disabled patients (two men, three women, mean age 34-8 years) with chronic progressive multiple sclerosis.The diagnosis was based on the criteria of Schumacher et al, and the neurological deficit of the patients was evaluated before each administration of interferon according to the scale of Fog and Raun.Lumbar puncture was done weekly and each patient received intrathecally increasing doses (0.1, 0 3, 1.0, and 3-0 X106 IU) of human leucocyte interferon-C4 diluted in 5 ml physiological saline.The duration of follow up in each patient was three months.