tbuckley/cabot-search huggingface dataset:
Abstract 1442: Expression of miRNA processing factor Dicer in cutaneous melanoma and its role in cell invasion
Authors: Seyed Mehdi Jafarnejad Shourkaei, Mazyar Ghaffari, Magdalena Martinka, Michael Cox, Gang Li
Journal: Cancer Research (2011)

Abstract Deregulated expression of miRNAs is a hallmark of various human cancers. One potential mechanism for the aberrant expression of miRNAs in cancers is their abnormal processing due to altered expression or function of their processing factors such as Dicer and Drosha. Although altered expression of several miRNAs have been reported in melanoma, the expression profile of miRNA processing factors in this cancer is unknown. In this study we examined the expression of Dicer protein in different stages of melanocytic lesions. Using tissue microarray and immunohistochemistry, we evaluated cytoplasmic Dicer expression in 32 dysplastic nevi, 77 primary melanomas, and 48 metastatic melanomas. Our data revealed that expression of Dicer has a significant but inverse correlation with progression of melanoma (P &amp;lt; 0.001). Accordingly, the number of samples with moderate-strong staining for Dicer was reduced from 81.2% in dysplastic nevi to 67.5% in primary melanoma and 40.8% in metastatic melanoma. The expression of Dicer was also negatively correlated with the American Joint Committee on Cancer (AJCC) staging of the melanoma samples (p=0.019). Moreover, the reduced Dicer expression was correlated with a poorer disease-specific 5-year survival of melanoma patients (P = 0.026). Multivariate Cox regression analysis revealed that reduced nuclear Dicer expression is an independent prognostic factor to predict patient outcome (P = 0.030). We also knocked down Dicer expression and used Boyden chamber migration assay to study its role in the invasion ability of MMRU human melanoma cells. Interestingly, knockdown of Dicer enhanced the invasion ability of MMRU cells by 2-fold. Our results demonstrate the critical role of miRNA machinery in the progression of melanoma, suggesting that Dicer may be a suitable prognostic marker for human melanoma patients as well as a potential therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1442. doi:10.1158/1538-7445.AM2011-1442
PHYSICAL PROPERTIES OF OINTMENT BASES.
Authors: P. B. MUMFORD, R. M. MUMFORD
Journal: British Journal of Dermatology (1941)

Journal Article PHYSICAL PROPERTIES OF OINTMENT BASES. Get access P. B. MUMFORD, M.D., F.R.C.P., P. B. MUMFORD, M.D., F.R.C.P. Hon. Dermatologist, Manchester Royal Infirmary; Hon. Physician, Manchester and Salford Skin Hospital; Hon. Consulting Dermatologist, Christic Cancer Hospital and Holt Radium Institute Search for other works by this author on: Oxford Academic Google Scholar R. M. MUMFORD, B.A., B.Sc.Oxon. R. M. MUMFORD, B.A., B.Sc.Oxon. Royal Air Force Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 53, Issue 2, 1 February 1941, Pages 45–51, https://doi.org/10.1111/j.1365-2133.1941.tb10497.x Published: 01 February 1941
Lowering Cardiac Risk in Noncardiac Surgery
Authors: Lee A. Fleisher, Kim A. Eagle
Journal: New England Journal of Medicine (2001)

A 65-year-old man requires resection of an abdominal aortic aneurysm. He has a remote history of myocardial infarction and rare episodes of angina. Recent coronary angiography revealed more than 70 percent stenosis of the left circumflex artery. What can be done to minimize this patient's risk of perioperative cardiac complications?
Medical Reform in West Germany
Authors: Norman B. Roberg
Journal: JAMA (1967)

Systems of education reflect the sociopolitical histories of their countries, and the German and American educational systems have been as different as their historical heritages. For six centuries the character of a German university was a contract between an absolute ruler, who needed educated men for his kingdom, and the faculties, which tried to insure their academic freedom against royal intrusion. Now, since 1949, the universities are the responsibility of the 11 states of the West German Republic, but the fundamental organization has not changed. Because all German universities are state institutions, there are no private medical schools. An appointed state minister of education is responsible for education, and he selects the new head of a department from a list of three candidates submitted by the faculty. There is no board of trustees which represents the public interest.  The internal organization of the faculty is democratic but ineffectual. Although the
THE LOCAL MEDICAL SOCIETY AND PUBLIC HEALTH
Authors: A. CARPENTER
Journal: JAMA (1928)

"Today medicine—and particularly preventive medicine— is the property of all mankind. A progressive physician must be aware of his relationships to the civic and economic problems of the community and the nation."<sup>1</sup> This is the record of the active participation of a local medical society in the organization and guidance of a community health program. In the fall of 1922 a group of physicians in Fargo, Cass County, North Dakota, was successful in stimulating representatives of various civic bodies to consider the possibility of providing for the community an adequate health program in which the medical profession, the dental profession, public and private schools, the Red Cross, the tuberculosis society and the city government would all be asked to cooperate. This movement received its original impetus from the announcement of the Commonwealth Fund that it would establish its first child health demonstration in some suitable city in the upper
P1313 NGM282, A NOVEL SPECIFIC INHIBITOR OF CYP7A1-MEDIATED BILE ACID SYNTHESIS, IS SAFE AND WELL TOLERATED WITH PREDICTABLE PHARMACOKINETICS IN HEALTHY HUMAN SUBJECTS
Authors: S. Rossi, K. Allamneni, M. Elliott, K. Byrnes-Blake, J. Luo, L. Ling, H. Tian, A. De Paoli
Journal: Journal of Hepatology (2014)
Triiodothyronine, Thyroxine, and Iodine in Purified Thyroglobulin from Patients with Graves' Disease
Authors: M. Izumi, P. Reed Larsen
Journal: Journal of Clinical Investigation (1977)

Previous studies have suggested that there is an overproduction of triiodothyronine (T(3)) relative to thyroxine (T(4)) in patients with thyrotoxicosis associated with Graves' disease. To evaluate whether or not an increased ratio of T(3) to T(4) in thyroidal secretion could be contributing to this relative T(3) hyperproduction, T(3), T(4), and iodine were measured in thyroglobulin (Tg) from controls and patients with Graves' disease who had been treated either with propranolol only or with antithyroid drugs plus iodide before surgery. To avoid possible artifacts associated with pulse labeling and chromatography, T(3) and T(4) were determined by radioimmunoassay of Pronase hydrolysates of purified Tg. Results of analyses of Tg from six control patients and seven with Graves' disease, not receiving thiourea drugs or iodide, showed that the iodine content of Graves' disease Tg was not different from normal. Both contained 3.4 residues of T(4)/molecule Tg, but there was 0.39+/-0.08 (mean+/-SD) residue of T(3)/molecule Tg in Graves' Tg as opposed to 0.23+/-0.07 residue T(3) molecule Tg in controls matched for iodine content (P < 0.01). This difference resulted in a significantly lower T(4)/T(3) molar ratio (9+/-2) in Graves' Tg as opposed to control (15+/-2, P < 0.001). In Tg from patients with treated Graves' disease, iodine, T(3), and T(4) were reduced, but the reduction in the latter was more substantial, resulting in a T(4)/T(3) molar ratio of 3.4+/-1. Fractionation of Tg from all groups by RbCl density gradient ultracentrifugation indicated that at physiological levels of Tg iodination, the molar ratio of T(3)/Tg was consistently higher in Graves' disease. The specific mechanism for this difference is not known, but it is not due to iodine deficiency. If T(3) and T(4) are secreted in this altered ratio in patients with Graves' disease, the magnitude of the difference could explain the relative T(3) hyperproduction which is characteristic of this state.
Low-Dose Prednisone Therapy for Patients with Early Active Rheumatoid Arthritis: Clinical Efficacy, Disease-Modifying Properties, and Side Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Amalia A. van Everdingen, Johannes W.G. Jacobs, Dirk R. Siewertsz van Reesema, Johannes W.J. Bijlsma
Journal: Annals of Internal Medicine (2002)

Background: Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis. Objective: To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis. Design: 2-year randomized, double-blind, placebo-controlled clinical trial. Setting: 2 outpatient rheumatology clinics. Patients: 81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs. Intervention: 41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti-inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication. Measurements: Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months. Results: In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group. Conclusions: Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.
Clinical Nuclear Cardiology
Authors: Samuel Zoneraich
Journal: JAMA (1979)

The book reflects the dramatic increase that has occurred in the number of nuclear studies in diagnosing coronary artery disease. The authorship of this book is a constellation of authorities in the field of nuclear cardiology. The text includes discussions of theory, equipment, and technique, as well as considerations of clinical applications. Chapters on the more sophisticated diagnostic techniques are excellent and include myocardial blood-flow measurements, myocardial perfusion imaging, myocardial scintigraphic techniques, combined hot-spot technetium Tc 99m and cold-spot thallium 201 imaging, transmission and emission computerized tomography of the heart, qualitative blood-pool imaging, and assessment of myocardial function using radionuclide techniques, among others. The book contains two separate excellent chapters on scintigraphic methods for sizing myocardial infarction and on the pathophysiology of myocardial scintigraphy. The tables and diagrams in the book are concise. The illustrations are abundant and are of good quality. The general physician or the internist, however, would
Respiratory Stimulation with Intravenous Doxapram in Respiratory Failure
Authors: Kenneth M. Moser, Peter C. Luchsinger, James S. Adamson, Samuel M. McMahon, Donald P. Schlueter, Martin Spivack, John G. Weg
Journal: New England Journal of Medicine (1973)

The ability of a respiratory stimulant (doxapram) to maintain arterial carbon dioxide tension and pH within narrow limits during oxygen administration was assessed in a double-blind study of 78 patients with chronic obstructive lung disease admitted to hospitals for management of acute respiratory failure. The first two hours after admission constituted the study period, with either doxapram or placebo being given intravenously (2 to 3 mg per minute). During the two-hour period, oxygen administration was associated with elevation of carbon dioxide tension or decline in pH (or both) beyond the desired range in 36.8 per cent of the patients receiving placebo, but in only 17.5 per cent of those receiving doxapram. The results suggest that doxapram may prove a useful adjunct in the management of patients in whom oxygen therapy may be expected to exaggerate hypercapnia and acidosis.
Abstract 2449: The bromodomain inhibitor JQ1 blocks growth of pancreatic cancer cells in 3D collagen.
Authors: Vaibhav Sahai, Krishan Kumar, Kazumi Ebine, Halla Nimeiri, Hidayatullah G. Munshi
Journal: Cancer Research (2013)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. We have found that the collagen microenvironment promotes expression of histone acetyltransferases (HATs) and thereby promotes chemo-resistance; however, HATs have proven to be difficult ‘druggable’ targets. Bromodomain proteins are chromatin readers that can bind to acetylated histones and thereby regulate gene expression. JQ1, an inhibitor of BET class of human bromodomains, was shown to have efficacy against leukemia and lymphoma cell lines. Thus, we examined the effect of JQ1 on a panel of PDAC cells grown in 3D collagen. AsPC1, CD18 and Panc02.03 cells were particularly sensitive to the effects of JQ1, while Panc1 cells were relatively resistant to JQ1 treatment. JQ1 decreased myc mRNA and increased p21 mRNA in CD18 cells, but not in Panc1 cells. JQ1 also decreased growth of chemo-resistant CD18 cells grown in 3D collagen, and blocked EGF and TGF-β1-induced growth and scattering of Panc1 and CD18 cells in 3D collagen. The MEK1/2 inhibitor U0126 and JQ1 synergistically attenuated growth of CD18 and Panc1 cells in 3D collagen. In addition, EGFR inhibitors (AG1478 and PD153035) and JQ1 also synergistically attenuated the growth of CD18 and Panc1 cells in 3D collagen. In contrast, the p38 MAPK inhibitor SB202190 did not attenuate the effect of JQ1 on growth of CD18 and Panc1 cells in 3D collagen. Finally, JQ1 potentiated the effect of gemcitabine on the growth of CD18 and Panc1 cells in 3D collagen. Overall, these results suggest that JQ1 and other bromodomain inhibitors are potential therapeutic agents for the treatment of pancreatic cancer. Citation Format: Vaibhav Sahai, Krishan Kumar, Kazumi Ebine, Halla Nimeiri, Hidayatullah G. Munshi. The bromodomain inhibitor JQ1 blocks growth of pancreatic cancer cells in 3D collagen. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2449. doi:10.1158/1538-7445.AM2013-2449
Alteration of splicing signals in a genomic/cDNA hybrid VEGF gene to modify the ratio of expressed VEGF isoforms enhances safety of angiogenic gene therapy
Authors: Hideki Amano, Neil R. Hackett, Robert J. Kaner, Paul Whitlock, Todd K. Rosengart, Ronald G. Crystal
Journal: Molecular Therapy (2005)

Vascular endothelial growth factor (VEGF)-mediated physiological angiogenesis results from the concerted action of three major VEGF isoforms (VEGF121, 165, 189), which arise from alternate splicing. We have previously shown that expression of a mixture of VEGF isoforms via gene transfer is considerably more potent than expression of a single VEGF isoform. To test the hypothesis that different mixtures of VEGF isoforms may offer the same therapeutic benefit with a better safety profile, we compared the efficacy and safety of an adenovirus gene transfer vector expressing the three major VEGF isoforms (AdVEGF-All) in the normal ratio to those of AdVEGF-All6A+, in which the splicing sequences for exon 6A were altered to promote expression of VEGF189 at the expense of VEGF121. Both vectors were equally potent in mediating recovery of hind-limb blood flow following experimental ischemia. By contrast, intravenous administration of AdVEGF-All6A+ yielded enhanced survival and a lower capacity to support tumor growth compared to AdVEGF-All, and intratracheal administration of AdVEGF-All6A+ resulted in less pulmonary edema than that of AdVEGF-All. We conclude that AdVEGF-All and AdVEGF-All6A+ are similar in potency but that AdVEGF-All6A+ is safer. This suggests that AdVEGF-All6A+ may be the preferred candidate for clinical development.
Long‐Term Survival of Allograft Murine Islets Coated via Covalently Stabilized Polymers
Authors: Hernán R. Rengifo, Jaime A. Giraldo, Irayme Labrada, Cherie L. Stabler
Journal: Advanced Healthcare Materials (2014)

Clinical islet transplantation (CIT) has emerged as a promising treatment option for type 1 diabetes mellitus (T1DM); however, the antirejection drug regimen necessary to mitigate allograft islet rejection is undesirable. The use of polymeric coatings to immunocamouflage the transplant from host immune attack has great potential. Alginate and poly(ethylene glycol) (PEG)‐based polymers, functionalized with azide and phosphine, respectively, which form spontaneous and chemoselective crosslinks via the bioorthogonal Staudinger ligation scheme, were recently developed. Here, the utility of these polymers to form immunoprotective, ultrathin coatings on murine primary pancreatic islets is explored. Resulting coatings are nontoxic, with unimpaired glucose stimulated insulin secretion. Transplantation of coated BALB/c (H‐2 d ) islets into streptozotozin‐induced diabetic C57BL/6 (H‐2 b ) results in prompt achievement of normoglycemia, at a rate comparable to controls. A significant subset of animals receiving coated islets (57%) exhibits long‐term (&gt;100 d) function, with robust islets observed upon explantation. Control islets rejected after 15 d (±9 d). Results illustrate the capacity of chemoselectively functionalized polymers to form coatings on islets, imparting no detrimental effect to the underlying cells, with resulting coatings exhibiting significant protective effects in an allograft murine model.
5′-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication
Authors: Maria M Simile, Sebastiano Banni, Elisabetta Angioni, Gianfranca Carta, Maria R De Miglio, Maria R Muroni, Diego F Calvisi, Angelo Carru, Rosa M Pascale, Francesco Feo
Journal: Journal of Hepatology (2001)
Insulin-producing Surrogate β-cells From Embryonic Stem Cells: Are We There Yet?
Authors: Ortwin Naujok, Chris Burns, Peter M Jones, Sigurd Lenzen
Journal: Molecular Therapy (2011)

Embryonic stem cells (ESCs) harbor the potential to generate every cell type of the body by differentiation. The use of hESCs holds great promise for potential cell replacement therapies for degenerative diseases including diabetes mellitus. The recently discovered induced pluripotent stem cells (iPSCs) exhibit immense potential for regenerative medicine as they allow the generation of autologous cells tailored to the patients' immune system. Research for insulin-producing surrogate cells from ESCs has yielded highly controversial results, because many steps and factors in the differentiation process are currently still unknown. Thus, there is no consensus on common standard protocols. The protocols presently used established the differentiation from pluripotent cells toward pancreatic progenitor cells. However, none of the differentiation protocols reported to date have generated by exclusive in vitro differentiation sufficient numbers of insulin-producing cells meeting all essential criteria of a β-cell. The cells often lack the crucial function of regulated insulin secretion upon glucose stimulation. This review focuses on past and current approaches to the generation of insulin-producing cells from pluripotent sources, such as ESCs and iPSCs, and critically discusses the hurdles to be taken before insulin-secreting surrogate cells derived from these stem cells will be of clinical use in humans. Embryonic stem cells (ESCs) harbor the potential to generate every cell type of the body by differentiation. The use of hESCs holds great promise for potential cell replacement therapies for degenerative diseases including diabetes mellitus. The recently discovered induced pluripotent stem cells (iPSCs) exhibit immense potential for regenerative medicine as they allow the generation of autologous cells tailored to the patients' immune system. Research for insulin-producing surrogate cells from ESCs has yielded highly controversial results, because many steps and factors in the differentiation process are currently still unknown. Thus, there is no consensus on common standard protocols. The protocols presently used established the differentiation from pluripotent cells toward pancreatic progenitor cells. However, none of the differentiation protocols reported to date have generated by exclusive in vitro differentiation sufficient numbers of insulin-producing cells meeting all essential criteria of a β-cell. The cells often lack the crucial function of regulated insulin secretion upon glucose stimulation. This review focuses on past and current approaches to the generation of insulin-producing cells from pluripotent sources, such as ESCs and iPSCs, and critically discusses the hurdles to be taken before insulin-secreting surrogate cells derived from these stem cells will be of clinical use in humans.
Relationships with the drug industry: Focus on better information
Authors: R. Tiner
Journal: BMJ (2009)

The relationship between the drug industry, academia, healthcare professionals, and patients has reached an all time low and few doubt that it is in the interests of all parties to improve it. A recent report from the Royal College of Physicians attempts to define a path towards achieving a more productive relationship. Here we set out five contrasting views on what the ideal relationship between industry and prescribers and patients should be and what steps need to be taken to achieve it (doi:10.1136/bmj.b222, doi:10.1136/bmj.b211, doi:10.1136/bmj.b252, doi:10.1136/bmj.b232)
Reasons for doctors' career choice and change of choice
Authors: J Parkhouse, D J Ellin
Journal: BMJ (1988)

In a study of doctors who qualified from British medical schools in 1974 and 1977, which was carried out five to 11 years after graduation, frequent changes of career choice were found. Most of these changes occurred at a relatively early stage. There was a shift of choices towards general practice, and to a lesser extent other specialties, predominantly from medicine, surgery, and paediatrics. Great importance was attached to self evaluation of aptitude and ability as a factor in determining the choice of career and also to awareness of promotion prospects and difficulties. The absence of or failure of careers advice to influence choice of career was notable as was the little importance attached to financial circumstances. Domestic circumstances were an important determinant, particularly for general practice and for women doctors. Among those who qualified in 1980 and 1983, at the preregistration stage, domestic circumstances were less important than they were for slightly older doctors, but undergraduate experience had a greater influence. Contact with a particular teacher or department was not, however, a notable element in this.