tbuckley/cabot-search huggingface dataset:
UCSC cancer genomics browser.
Authors: J Zhu, JZ Sanborn, T Wang, F Hsu, S Benz, C Szeto, L Esserman, D Haussler
Journal: Cancer Research (2009)

Abstract Abstract #2022 As experimental techniques for a comprehensive survey of the cancer landscape mature, there is a great demand in the cancer research field to develop advanced analysis and visualization tools for the characterization and integrative analysis of the large, complex genomic datasets arising from different technology platforms.&amp;#x2028; The UCSC Cancer Genomics Browser is a suite of web-based tools designed to integrate, visualize and analyze genomic and clinical data. The secured-access browser, available at https://cancer.cse.ucsc.edu/, consists of three major components: hgHeatmap, hgFeatureSorter, and hgPathSorter. The main panel, hgHeatmap, displays a whole-genome-oriented view of genome-wide experimental measurements for individual and sets of samples/patients alongside their clinical information. hgFeatureSorter and hgPathSorter together enable investigators to order, filter, aggregate and display data interactively based on any given feature set ranging from clinical features to annotated biological pathways to user-edited collections of genes. Standard and advanced statistical tools are available to provide quantitative analysis of whole genomic data or any of its subsets. The UCSC Cancer Genomics Browser is an extension of the UCSC Genome Browser; thus it inherits and integrates the Genome Browser's existing rich set of human biology and genetics data to enhance the interpretability of cancer genomics data.&amp;#x2028; We demonstrate the UCSC Cancer Genomics Browser by integrating several independent studies on breast cancer including the I-SPY chemotherapy clinical trial and other studies focused on chemotherapeutic response or long-term survival. The types of data that are visualized and analyzed by the browser include microarray measurements of gene expression, copy number variation and phosphoprotein expression, MRI imaging measurements, and clinical parameters.&amp;#x2028; Collectively, these tools facilitate a synergistic interaction among clinicians, experimental biologists, and bioinformaticians. They enable cancer researchers to better explore the breadth and depth of the cancer genomics data resources, and to further characterize molecular pathways that influence cellular dynamics and stability in cancer. Ultimately, insights gained by applying these tools may advance our knowledge of human cancer biology and stimulate the discovery of new prognostic and diagnostic markers, as well as the development of therapeutic and prevention strategies.&amp;#x2028; Funding sources: CALGB CA31964 and CA33601, ACRIN U01 CA079778 and CA080098, NCI SPORE CA58207, California Institute for Quantitative Biosciences, NHGRI. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2022.
Case series reporting the effectiveness of mycophenolate mofetil in treatment-resistant asthma
Authors: Christopher Grainge, Nivenka Jayasekera, Patrick Dennison, Hitasha Rupani, Ramesh Kurukulaaratchy, Peter Howarth
Journal: European Respiratory Journal (2013)

Case series reporting the effectiveness of mycophenolate mofetil in treatmentresistant asthmaTo the Editor:Treatment-resistant asthma represents a significant unmet clinical need.Due to lack of therapeutic options many patients receive treatment with long-term oral steroids despite appreciation of the associated systemic adverse effects.While anti-IgE therapy with omalizumab affords benefit and there have been encouraging outcomes with monoclonal antibodies against interleukin (IL)-5 and IL-13 [1, 2], all such treatments target T-helper cell type 2 (Th2) orientated disease in a sub-population of patients.Mycophenolate mofetil (MMF) is a reversible inhibitor of inosine monophosphate dehydrogenase, an enzyme required by T-and B-cells for guanine synthesis [3].It is most commonly used to prevent transplanted organ rejection, but is increasingly prescribed to treat inflammatory disorders such as connective tissue disorders and systemic vasculitides.
Abstract P3-12-11: Provincial variation in utilization of adjuvant chemotherapy regimens in early stage breast cancer: Data from the cancer care Ontario new drug funding program (NDFP)
Authors: A Eisen, A Srikanthan, L Yeung, R Iyer, M Trudeau
Journal: Cancer Research (2013)

Abstract Objectives: Recent improvements in breast cancer mortality are partly due to increased utilization of appropriate systemic therapy in early stage disease. The objectives of this study were to 1. review utilization of the most effective adjuvant breast cancer regimens across Ontario, 2. identify regions where there are variations from best practices. Methods: We used data from the Ontario NDFP to determine the utilization of 8 drug regimens approved for early stage breast cancer in each of the 14 provincial local health integration networks (LHINs). The NDFP funds the use of new and expensive cancer drugs; over 90% of all cancer treatments are funded through this mechanism. In Ontario, there were an estimated 9000 new cases of breast cancer in 2011. The analysis was restricted to patients with early stage, Her2 negative breast cancer treated in 2011-12. Data were obtained from individual cancer clinics in each LHIN. We estimate that data collection was &amp;gt;95% complete for these regimens. Results: 3375 women were treated with an NDFP regimen. Across the province, the most commonly used regimen was FEC-D (43%), followed by TC (23%) and ddACT (21%). The remaining regimens (AC-Docetaxel, ACT q 3 wks, CEF, FEC and AC-weekly P) were used in less than 5% of cases. However, there was important regional variation. In LHIN A, ACT q 3 wks was used in 42% of cases, and no patients received FEC-D. In LHIN P, TC was used in 40% of cases. In LHIN R, only 6% of patients received FEC-D, whereas 63% received ddACT. Utilization of Adjuvant Chemo Regimens n = 3375 AC-DocetaxelddACT q2wksACT q3wksAC-weekly PCEF/FECTCFEC-DLHIN K212004109241LHIN J3417101545212LHIN Q12000640104LHIN D1530732568165LHIN V57120031027LHIN R5188390104018LHIN P2246184111115LHIN B35311182795LHIN C0588002326LHIN A0132581120LHIN H2410189109LHIN T510425466038LHIN M1011318319175263LHIN S1715004728Total (%)128 (4)708 (21)156 (5)37 (1)139 (4)766 (23)1441 (43) Conclusion: The ACT q3 wks and TC regimens are widely used. This is of concern as they are likely less effective than FEC-D or ddACT. Factors such as tumour stage, geographic distance from treatment centre and private insurance coverage for supportive care medications may also affect choice of regimen. Consensus guidelines for the adjuvant systemic therapy of breast cancer in Ontario are being developed, along with a knowledge translation strategy to disseminate the results. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-11.
Genetics of N-Methyl-N-Nitrosourea Induction of Thymic Lymphomas in AKR/J Mice: Assignment of a Susceptibility Gene to Mouse Chromosome 7
Authors: J. M. Angel, D. C. Morizot, E. R. Richie
Journal: JNCI Journal of the National Cancer Institute (1989)

Treatment of young AKR/J mice with N-methyl-N-nitrosourea (MNU) results in the induction of a high incidence of thymic lymphomas occurring between 4 and 6 months of age. The tumor incidence is higher and the latency period is shorter than that observed in other MNU-treated mouse strains. Analysis of tumor incidence in crosses of AKR/J with C57L/J mice indicates that several genes influence the incidence and latency of MNU-induced thymic lymphomas. One of these genes appears to be tightly linked to the albino locus of chromosome 7.
The Regulation of Radiopharmaceuticals
Authors: James J. Conway
Journal: JAMA (1985)

To the Editor.—  The recent editorial on the Food and Drug Administration's (FDA) role in the drug approval process is appropriate. 1 In our opinion, the FDA has shown concern about infringement upon the practice of medicine. 2 Such may not be said for the Nuclear Regulatory Commission (NRC), in its interpretation of its statutory authority to regulate the radiation safety of radiopharmaceuticals in nuclear medicine. It has adopted the FDA package insert as dogma, particularly in respect to the route of injection of the radiopharmaceutical. 3 Nuclear Regulatory Commission inspectors have cited nuclear medicine physicians for license non-compliance when they have deviated from the package insert in their practice. The irony of this situation is that one regulatory agency (FDA) issues package insert guidelines, which do not obligate the practicing physician, while another regulatory agency (NRC) adopts the guidelines as dogma in its regulation of nuclear medicine practice.  A
Charles Isadore Levene
Authors: A J Crisp
Journal: BMJ (2004)

Forde Cayley went from medical school straight into service in wartime France and then to Singapore.Captured by the Japanese, he was taken to the infamous River Kwai.The horrors he had witnessed never left him, but he believed in reconciliation, not hatred.As a postwar pioneer of drug treatment for tuberculosis, he took up the respiratory medicine post that he held until retirement.His spare time was divided between BMA activities, his work as a lay reader, and in his prolific vegetable plot.Predeceased by his wife, Eileen, he leaves two sons and three grandsons.
HIV-1 Viral Protein-R (VPR) Protects against Lethal Superantigen Challenge While Maintaining Homeostatic T Cell Levels in Vivo
Authors: Karuppiah Muthumani, Andrew Y. Choo, Daniel S. Hwang, Nathanael S. Dayes, Michael Chattergoon, Shanmugam Mayilvahanan, Khanh P. Thieu, Peter T. Buckley, Joann Emmanuel, Arumugam Premkumar, David B. Weiner
Journal: Molecular Therapy (2005)

The HIV-1 accessory protein Vpr exhibits many interesting features related to macrophage and T cell biology. As a viral protein or as a soluble molecule it can suppress immune cell activation and cytokine production in vitro in part by targeted inhibition of NF-kappaB. In this regard we sought to test its effects in vivo on an NF-kappaB-dependent immune pathway. We examined the activity of Vpr in a lethal toxin-mediated challenge model in mice. Intravenous delivery of Vpr was sufficient to protect mice from lethal challenge with staphylococcal endotoxin B (SEB). Furthermore, Vpr protected host CD4+ T cells from in vivo depletion likely by preventing induction of AICD of SEB-exposed cells in a post-toxin-binding fashion. Understanding the biology of Vpr's activities in this model may allow for new insight into potential mechanisms of hyperinflammatory disease and into Vpr pathobiology in the context of HIV infection.
Paediatric surgery should be performed by specialist surgeons
Authors: S. Mayor
Journal: BMJ (2000)

Surgery in children should be classified as a subspecialty and carried out by designated surgeons who have undergone appropriate training, recommends a report from the Royal College of Surgeons in England published last week.

The report is calling for major changes in the training and workload of surgeons carrying out paediatric surgery. It also recommends organisational changes so that inpatient surgery for children would be undertaken only by hospitals with comprehensive paediatric facilities.

Every district general hospital is being asked to develop a multidisciplinary group responsible for overseeing, improving, and integrating services for children. …
62 EVALUATION OF ANTIVIRAL ACTIVITY AND TOLERANCE OF A NOVEL SUSTAINED RELEASE INTERFERON-ALPHA-2B (IFN-ALPHA-2BXL) COMPARED TO PEGYLATED INTERFERON-ALPHA-2B (PEG-IFN-ALPHA-2B): A PHASE IB TRIAL IN HCV PATIENTS
Authors: C. Trepo, M. Guest, R. Meyrueix, R. Rouzier, C. Raffanel, H. Belhadj-Tahar, M. Maynard-Muet, F. Nicolas, Y. Donazzolo, R. Kravtzoff
Journal: Journal of Hepatology (2008)
1169-160 Systolic and diastolic strain rates by tagged magnetic resonance imaging distinguishes regions with different degrees of myocardial injury after acute myocardial infarction
Authors: Clerio F Azevedo, Luciano C Amado, Dara L Kraitchman, Bernhard L Gerber, Nael F Osman, Carlos E Rochitte, Thor Edvardsen, Joao A Lima
Journal: Journal of the American College of Cardiology (2004)
Time for action on hepatitis B immunisation.
Authors: R G Finch
Journal: BMJ (1987)

Dopamine (DA) was applied to CA1 region pyramidal cells in slices of guinea pig hippocampus maintained in vitro in order to examine its electrophysiological effect on CNS neurons. DA induced hyperpolarization of membrane potential and an increased conductance in 75% the 21 CA1 neurons to which it was applied. DA also augmented the afterhyperpolarizations and increased conductance which normally follow spike trains in these neurons. These effects were not altered by intracellular injections of Cl- but were blocked when slices were bathed in Mn2+ solutions. The Mn2+ blockade of DA-induced hyperpolarizations could be overcome when large amounts of agonists were applied. The DA effects were long lasting, were mimicked by the dopamine agonists apomorphine and Epinine, and were blocked by the dopamine antagonists flupenthixol and chlorpromazine. Extracellular or intracellular application of cyclic AMP mimicked the effects of DA. The results suggest that DA-induced hyperpolarization and conductance changes are mediated by a Ca2+-activated K+ conductance. DA may increase the intracellular Ca2+ concentration through effects on one of the Ca2+ buffering mechanisms. The long duration of these effects suggest that DA works though some intracellular intermediary, perhaps cyclic AMP, considering that the actions of cyclic AMP on membrane properties are similar to those of DA. The dopaminergic projection to the hippocampus should have a powerful inhibitory action, which would be most effective in modulating the activities of neurons exhibiting high levels of excitability, particularly cells involved in cyclical burst generation.
Watchdog inspects Cornish out of hours service after doctors complain
Authors: J. Carlowe
Journal: BMJ (2012)

England’s health and social services watchdog has confirmed that it carried out an early inspection of the out of hours GP service in Cornwall because of “rumblings of dissatisfaction” from local doctors.

A spokesman for the Care Quality Commission said that the service, which is run by the private company Serco, was “flagged up” at the point of its registration in April to be among the first wave of services inspected.

This was because of “local mood music . . . [and] rumblings of dissatisfaction in Cornwall,” said the regulator.

Among those to have contacted the CQC was Gareth Emrys-Jones, a retired BMA council member and the former chairman of the GP cooperative that used to run the out of hours service for Cornwall as a not for profit company.

Emrys-Jones told the Guardian newspaper that he had been contacted by “a significant …
Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage
Authors: D. DARR, S. COMBS, S. DUNSTON, T. MANNING, S. PINNELL
Journal: British Journal of Dermatology (1992)

Summary Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (l-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.
Cardiac Sodium Channel Gene Variants and Sudden Cardiac Death in Women
Authors: Christine M. Albert, Edwin G. Nam, Eric B. Rimm, Hong Wei Jin, Roger J. Hajjar, David J. Hunter, Calum A. MacRae, Patrick T. Ellinor
Journal: Circulation (2007)

Background— Several cardiac ion channel genes have been implicated in monogenic traits with a high risk of sudden cardiac death (SCD). Mutations or rare variants in these genes have been proposed as potential contributors to more common forms of SCD, but this hypothesis has not been assessed systematically. Methods and Results— We directly sequenced the entire coding region and splice junctions of 5 cardiac ion channel genes, SCN5A, KCNQ1, KCNH2, KCNE1, and KCNE2, in 113 SCD cases from 2 large prospective cohorts of women (Nurses’ Health Study) and men (Health Professional Follow-Up Study). Controls from the same population were then screened for the presence of mutations or rare variants identified in cases, and sequence variants without prior functional data were expressed in Xenopus oocytes to assess their biophysical consequences. No mutations or rare variants were identified in any of the 53 subjects who were men. In contrast, in 6 of 60 women (10%), we identified 5 rare missense variants in SCN5A that either had been associated previously with long-QT syndrome (A572D and G615E), had been reported to alter sodium channel function (F2004L), or had not been reported previously in control populations (A572F and W1205C). Of the 4 variants without prior functional data, 3 variants were located in the I-II linker (A572D, A572F, and G615E), and all resulted in significantly shorter recovery times from inactivation. When compared with 733 control samples from the same population, the overall frequency of these rare variants in SCN5A was significantly higher in the SCD cases (6/60, 10.0%) than in controls (12/733, 1.6%; P =0.001). Conclusion— Functionally significant mutations and rare variants in SCN5A may contribute to SCD risk among women.
Propranolol in myocardial infarction.
Authors: A. Gedeon
Journal: BMJ (1968)

neuromusculature is a highly probable sequel to persistent purging.Dr. Smith's suggestion that the sennosides have an affinity for the colonic myenteric neurones finds some support from the work of Okada, ' and Straub and Triendl,4 and if confirmed would show the sennosides to be extremely selective in their therapeutic action.However, Dr. Smith's suggestion is, we feel, likely to prove an over-simplification of the position, which must take into account such aspects as the release of the active fraction of the sennosides by interaction with colonic microflora within the gut lumen.5In the meantime, as is the case with many drugs, clinical experience of the therapeutic effects of the sennosides has far outstripped the knowledge of their pharmacology, and the immediate clinical significance of the investigation of Dr. Avery Jones and Dr. Barbara Smith is to emphasize in a new and important way the great harm which can result from the misuse of laxative drugs.Unfortunately the problem of laxative abuse by the lay public remains.-Iam, etc.,
Neurological Disease associated with Folate Deficiency
Authors: E. H. Reynolds, P. Rothfeld, J. H. Pincus
Journal: BMJ (1973)

In a general medical hospital population the neurological status of 24 patients with severe folate deficiency was compared with that of a control group of 21 patients with normal serum folate. A significant increase of organic brain syndrome and pyramidal tract damage was found in the folate-deficient group. These findings were independent of the degree of anaemia or the presence of alcoholism. These data are consistent with the view that severe folate deficiency may cause neurological deficits.
Inverted Meckel’s diverticulum presenting as iron deficiency anemia
Authors: J. Shelton, T. Newsome, K. Ford III, J. Hamilton
Journal: Endoscopy (2006)

A 48-year-old woman presented with fatigue, dyspnea on exertion, and mild abdominal bloating. Physical examination was unremarkable, with a soft nontender abdomen. Laboratory evaluation revealed iron deficiency anemia, with a hemoglobin level of 10.2 g/dl (normal range 12 - 16 g/dl) and a plasma ferritin of 8 ng/ml (normal range 10 - 291 ng/ml). As part of the investigative work-up for her anemia, colonoscopy and esophagogastroduodenoscopy with duodenal biopsies were performed and no abnormalities were found. Capsule endoscopy revealed an intraluminal mass in the distal ileum, which we suspected to be a tumor (Video 1, Figure [1]). Computed tomography was performed to further define the ileal mass, and the scan confirmed the presence of an endoluminal mass in the distal ileum (Figure [2]).
The Differential Effect of In Vivo Hydrocortisone on the Kinetics of Subpopulations of Human Peripheral Blood Thymus-Derived Lymphocytes
Authors: Barton F. Haynes, Anthony S. Fauci
Journal: Journal of Clinical Investigation (1978)

The present study was undertaken to determine the effect of in vivo hydrocortisone on the kinetics of subpopulations of normal human peripheral blood (PB) thymus-derived (T) cells. Normal volunteers received a single i.v. dose of hydrocortisone, and blood was taken just before, as well as 4, 24, and 48 h after hydrocortisone administration. T cells were purified from each specimen, and proportions and absolute numbers of T lymphocytes bearing receptors for the Fc portion of IgG (T(.G)) and for the Fc portion of IgM (T(.M)) were enumerated by rosetting T cells with bovine erythrocytes which had been coated with either antibovine erythrocyte IgG or IgM. 4 h after i.v. administration of hydrocortisone, T(.M) cells decreased from 52 (+/-5%) to 23 (+/-6%) of PB T cells (P < 0.01) and the absolute number of T(.M) cells decreased from 1,028 (+/-171) per mm(3) to 103 (+/-23) per mm(3) (P < 0.001). In contrast, relative proportion of T(.G) cells increased from 22 (+/-4%) to 66 (+/-7%), while the absolute numbers of T(.G) cells were essentially unchanged (P > 0.2). In vitro studies involving preincubation of T cells with hydrocortisone before rosette determination of T(.G) or T(.M) cells demonstrated that the decrease in absolute numbers of T(.M) cells did not represent hydrocortisone interference with T(.M) rosette formation, nor did it represent a switch of T(.M) cells to T(.G) cells. Thus, administration of hydrocortisone to normal subjects produces a selective depletion from the circulation of T lymphocytes which possess receptors for the Fc portion of IgM (T(.M) cells) and of T cells which possess no detectable F(C) receptor (T(.non-M, non-G) cells). T(.G) cells are relatively resistant to the lymphopenic effect of hydrocortisone. These data clearly demonstrate that in vivo corticosteroids have a differential effect on the kinetics of identifiable and distinct subsets of cells in the human T-cell class.
LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds
Authors: Tatsuo Kinashi, Memet Aker, Maya Sokolovsky-Eisenberg, Valentin Grabovsky, Chisato Tanaka, Revital Shamri, Sara Feigelson, Amos Etzioni, Ronen Alon
Journal: Blood (2003)