tbuckley/cabot-search huggingface dataset:
Biodegradable CpG DNA hydrogels for sustained delivery of doxorubicin and immunostimulatory signals in tumor-bearing mice
Authors: Makiya Nishikawa, Yumiko Mizuno, Kohta Mohri, Nao Matsuoka, Sakulrat Rattanakiat, Yuki Takahashi, Hisakage Funabashi, Dan Luo, Yoshinobu Takakura
Journal: Biomaterials (2010)
A novel brain-enriched E3 ubiquitin ligase RNF182 is up regulated in the brains of Alzheimer's patients and targets ATP6V0C for degradation
Authors: Qing Liu, Joy X Lei, Marianna Sikorska, Rugao Liu
Journal: Molecular Neurodegeneration (2008)

Alterations in multiple cellular pathways contribute to the development of chronic neurodegeneration such as a sporadic Alzheimer's disease (AD). These, in turn, involve changes in gene expression, amongst which are genes regulating protein processing and turnover such as the components of the ubiquitin-proteosome system. Recently, we have identified a cDNA whose expression was altered in AD brains. It contained an open reading frame of 247 amino acids and represented a novel RING finger protein, RNF182. Here we examined its biochemical properties and putative role in brain cells.RNF182 is a low abundance cytoplasmic protein expressed preferentially in the brain. Its expression was elevated in post-mortem AD brain tissue and the gene could be up regulated in vitro in cultured neurons subjected to cell death-inducing injuries. Subsequently, we have established that RNF182 protein possessed an E3 ubiquitin ligase activity and stimulated the E2-dependent polyubiquitination in vitro. Yeast two-hybrid screening, overexpression and co-precipitation approaches revealed, both in vitro and in vivo, an interaction between RNF182 and ATP6V0C, known for its role in the formation of gap junction complexes and neurotransmitter release channels. The data indicated that RNF182 targeted ATP6V0C for degradation by the ubiquitin-proteosome pathway. Overexpression of RNF182 reduced cell viability and it would appear that by itself the gene can disrupt cellular homeostasis.Taken together, we have identified a novel brain-enriched RING finger E3 ligase, which was up regulated in AD brains and neuronal cells exposed to injurious insults. It interacted with ATP6V0C protein suggesting that it may play a very specific role in controlling the turnover of an essential component of neurotransmitter release machinery.
Lenalidomide in multiple myeloma: Current status and future potential
Authors: Hang Quach, Anna Kalff, Andrew Spencer
Journal: American Journal of Hematology (2012)

Abstract The clinical development of lenalidomide (Revlimid™), then pomalidomide (Actimid™) as members of immunomodulatory drugs (IMiDs) for the treatment of multiple myeloma (MM), exemplifies how insight into disease biology can lead to design of effective therapeutic agents. Increased experience and understanding of IMiD's diverse biological effects has lead to rational design of lenalidomide‐based treatment‐regimens over recent years. However, much about lenalidomide is yet to be understood and fully exploited. Here, we review what is known of lenalidomide's biological effects, clinical certainties and uncertainties in the treatment of MM, and explore its future potential with other synergistic therapeutic agents. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Residency Training in Primary Care Internal Medicine
Authors: ALLAN H. GOROLL
Journal: Annals of Internal Medicine (1975)

The Primary Care Program at the Massachusetts General Hospital is designed to develop competence in the full range of problems encountered by general internists delivering primary care. House staff spend 3 years in the program, which starts with internship, includes a senior residency, and fulfills the requirements for board eligibility in internal medicine. Half of the training is provided in outpatient care settings. House staff assume responsibility for organization and operation of an ambulatory medical unit. In addition, there is supervised instruction in office gynecology, orthopedics, ear, nose and throat, dermatology, and psychiatry. Close integration with the traditional inpatient-oriented training program is maintained to ensure commensurate growth and competence in management of acute, life-threatening disease.
P1212 USE OF BASELINE FIBROSCAN TO PREDICT EFFICACY AND SAFETY OF TREATMENT FOR 1143 PATIENTS IN THE TELAPREVIR EARLY ACCESS PROGRAMME
Authors: H. Wedemeyer, M. Colombo, S.I. Strasser, P.A. Ferreira, P. Urbanek, I. Fernandez, D. Abdurakhmanov, A. Streinu-Cercel, F. Beeldens, W. Iraqi, R. Demasi, A. Hill, I. Lonjon-Domanec, C. Moreno
Journal: Journal of Hepatology (2014)
Incompetent Hospital Management.
Authors: Lucy L. Flower
Journal: JAMA (1902)

Chicago, Oct. 15, 1902. <h3>To the Editor:</h3> —My attention has been called to an article in your number of October 11 [pages 918 and 920] speaking of one of our nurses who was concerned in the late accident at the Presbyterian Hospital and stating that the nurse had been dismissed. This is not correct. She has not been dismissed, nor have we the slightest intention of dismissing her. She went home because she was very much disturbed and unstrung, as was perfectly natural, though the chief blame did not rest on her, but on the person who sent 1 gr. strychnin tablets to the ward, where the only ones usual and permitted are 1/60 grain. The fault of the nurse was only in the fact that she assumed that the tablets were the usual ones, and did not read the full label to see. Her career is not ended; she
Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis
Authors: Yue Zhang, Faezeh Vasheghani, Ying-hua Li, Meryem Blati, Kayla Simeone, Hassan Fahmi, Bertrand Lussier, Peter Roughley, David Lagares, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Mohit Kapoor
Journal: Annals of the Rheumatic Diseases (2014)

Objectives Mammalian target of rapamycin (mTOR) (a serine/threonine protein kinase) is a major repressor of autophagy, a cell survival mechanism. The specific in vivo mechanism of mTOR signalling in OA pathophysiology is not fully characterised. We determined the expression of mTOR and known autophagy genes in human OA cartilage as well as mouse and dog models of experimental OA. We created cartilage-specific mTOR knockout (KO) mice to determine the specific role of mTOR in OA pathophysiology and autophagy signalling in vivo. Methods Inducible cartilage-specific mTOR KO mice were generated and subjected to mouse model of OA. Human OA chondrocytes were treated with rapamycin and transfected with Unc-51–like kinase 1 (ULK1) siRNA to determine mTOR signalling. Results mTOR is overexpressed in human OA cartilage as well as mouse and dog experimental OA. Upregulation of mTOR expression co-relates with increased chondrocyte apoptosis and reduced expression of key autophagy genes during OA. Subsequently, we show for the first time that cartilage-specific ablation of mTOR results in increased autophagy signalling and a significant protection from destabilisation of medial meniscus (DMM)-induced OA associated with a significant reduction in the articular cartilage degradation, apoptosis and synovial fibrosis. Furthermore, we show that regulation of ULK1/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway by mTOR may in part be responsible for regulating autophagy signalling and the balance between catabolic and anabolic factors in the articular cartilage. Conclusions This study provides a direct evidence of the role of mTOR and its downstream modulation of autophagy in articular cartilage homeostasis.
Challenges in Using Observational Studies to Evaluate Adverse Effects of Treatment
Authors: Michael D. Hughes, Paige L. Williams
Journal: New England Journal of Medicine (2007)

In this issue of the Journal, Friis-Møller and colleagues (pages 1723–1735) report on results from a prospective observational study involving more than 23,000 patients infected with HIV. The study, called the Data Collection on Adverse Effects of Anti-HIV Drugs (DAD) trial, identified a possible increased risk of myocardial infarction associated with exposure to protease inhibitors but not to nonnucleoside reverse-transcriptase inhibitors. Because randomized studies are rarely well powered for evaluating adverse effects of treatment, well-designed observational studies are important.1 However, such studies raise complex questions concerning both the potential confounding of risk associations and the mechanisms by which treatment might . . .
TCT-261 Five-Year Clinical Outcomes of the OLIVUS-Ex (Impact of OLmesartan on progression of coronary atherosclerosis: Evaluation by IntraVascular UltraSound Extension) Trial
Authors: Atsushi Hirohata, Eiki Hirose, Yuhei Kobayashi, Minako Ohara, Tohru Ohe, Fumihiko Sano, Hiroya Takafuji, Hiroyuki Takinami, Keizo Yamamoto, Ryo Yoshioka
Journal: Journal of the American College of Cardiology (2012)
Abstract A35: SMARCE1 mutations cause inherited multiple spinal meningiomas
Authors: Miriam J. Smith, James O'Sullivan, Sanjeev S. Bhaskar, Kristen D. Hadfield, Gemma Poke, John Caird, Saba Sharif, Diana Eccles, David FitzPatrick, Daniel Rawluk, Daniel du Plessis, William G. Newman, D. Gareth Evans
Journal: Cancer Research (2013)

Abstract Meningiomas represent approximately one third of all primary central nervous system tumors in adults. Multiple meningiomas are usually associated with neurofibromatosis type 2 (NF2) disease, which is caused by mutations in the NF2 gene. Recent reports have also shown multiple meningiomas to be associated with schwannomatosis disease, which is caused by mutations in the SWI/SNF chromatin remodeling complex subunit, SMARCB1. In a subset of individuals, multiple meningioma disease is a discrete entity, inherited in an autosomal dominant manner unrelated to NF2 or SMARCB1 mutations. We sought to discover novel genes associated with a predisposition to meningioma development by exome sequencing of germline DNA three unrelated individuals with familial multiple spinal meningiomas, who did not have germline NF2 or SMARCB1 mutations. Two of these three individuals harbored heterozygous novel loss-of-function mutations in the SWI/SNF complex subunit, SMARCE1. Sanger sequencing of SMARCE1 in lymphocyte DNA from six additional individuals with spinal meningiomas identified another two novel heterozygous loss-of-function mutations. Tumors from individuals with germline SMARCE1 mutations were demonstrated a clear cell histological subtype and all demonstrated loss of SMARCE1 protein consistent with a tumor suppressor mechanism. Our findings define multiple spinal meningioma disease as a novel discrete entity and implicate the SWI/SNF chromatin remodeling complex in the pathogenesis of meningiomas and tumors with clear cell histology. Citation Format: Miriam J. Smith, James O'Sullivan, Sanjeev S. Bhaskar, Kristen D. Hadfield, Gemma Poke, John Caird, Saba Sharif, Diana Eccles, David FitzPatrick, Daniel Rawluk, Daniel du Plessis, William G. Newman, D. Gareth Evans. SMARCE1 mutations cause inherited multiple spinal meningiomas. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A35.
Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas
Authors: Hans-Peter Gerber, May Kung-Sutherland, Ivan Stone, Carol Morris-Tilden, Jamie Miyamoto, Renee McCormick, Stephen C. Alley, Nicole Okeley, Brad Hayes, Francisco J. Hernandez-Ilizaliturri, Charlotte F. McDonagh, Paul J. Carter, Dennis Benjamin, Iqbal S. Grewal
Journal: Blood (2009)
Prospects for Vaccines to Protect Against AIDS, Tuberculosis, and Malaria
Authors: Norman L. Letvin
Journal: JAMA (2001)

Given the scope of the worldwide health problems caused by the acquired immunodeficiency syndrome, tuberculosis, and malaria, it is imperative that vaccines be developed to prevent these infections. Recent advances in the understanding of these diseases suggest that T-lymphocyte–mediated immunity is important in containing these infections. The application of novel vaccine technologies for eliciting this type of immunity promises to provide successful vaccines for controlling the spread of these deadly infections.
Criteria for Authors
Authors: ALFRED D. STEINBERG
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 January 1983Criteria for AuthorsALFRED D. STEINBERG, M.D.ALFRED D. STEINBERG, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-1-108_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Burman (1) has managed to add another paper to his bibliography and reduce the percentage of multiauthored papers. However, he seems naive about the difficulty of deciding who should be an author or in what order.As a laboratory head, I may have a technician who produces 96.3% of the data for a project, but less than 0.5% of the work in terms of design, analysis, and writing the papers. Without the technician, the project would not get done; should the technician be excluded? If so, how is this person to be motivated for the next project?...References1. BURMAN K. Hanging from the masthead: reflections on authorship. Ann Intern Med. 1982;97:602-5. LinkGoogle Scholar2. STEINBERG A. Myxedema and coronary artery disease—a comparative autopsy study. Ann Intern Med. 1968;68:338-44. LinkGoogle Scholar1. BURMAN K. Hanging from the masthead: reflections on authorship. Ann Intern Med. 1982;97:602-5. LinkGoogle Scholar2. HUTH E. Authorship from the reader's side [Editorial]. Ann Intern Med. 1982;97:613-4. LinkGoogle Scholar3. MASURMICHELISWORMSER HMG. Opportunistic infection in previously healthy women: initial manifestations of a community-acquired cellular immunodeficiency. Ann Intern Med. 1982;97:533-9. LinkGoogle Scholar4. GREENESIDHULEWIN JGS. Mycobacterium avium-intracellulare: a cause of disseminated life-threatening infection in homosexuals and drug abusers. Ann Intern Med. 1982;97:539-46. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1983Volume 98, Issue 1Page: 108-109KeywordsResearch laboratoriesTechnicians Issue Published: 1 January 1983 PDF downloadLoading ...
Effects of Undersized Mitral Annuloplasty on Regional Transmural Left Ventricular Wall Strains and Wall Thickening Mechanisms
Authors: Allen Cheng, Tom C. Nguyen, Marcin Malinowski, David Liang, George T. Daughters, Neil B. Ingels, D. Craig Miller
Journal: Circulation (2006)

Undersized mitral annuloplasty, widely used for ischemic and functional mitral regurgitation (MR), has been proposed as an "annular solution to a ventricular problem." Beyond relief of MR, it is thought to improve global left ventricular (LV) shape, hence potentially reducing myocardial stress and promoting beneficial reverse LV remodeling. We previously observed that undersized annuloplasty inhibited systolic wall thickening at the LV base near the mitral annulus. In this study, we measured the effects of undersized annuloplasty on regional transmural LV wall fiber and sheet strains and wall thickening mechanisms.Nine sheep had transmural radiopaque beadsets surgically inserted into anterobasal and lateral equatorial LV regions, with additional markers silhouetting the LV and mitral annulus. 4-Dimensional marker dynamics were studied with biplane videofluoroscopy before and after tightening an adjustable Paneth-type mitral annuloplasty suture. Transmural circumferential, longitudinal, and radial systolic and remodeling strains in the subepicardium (20% depth), midwall (50%), and subendocardium (80%) in both regions were computed. Fiber and sheet angles from quantitative regional histology allowed transformation of these strains into local fiber (f), sheet (s), and sheet-normal (n) coordinates. Further analysis calculated the transmural contributions of sheet extension (E(ssc)), sheet thickening (E(nnc)), and sheet shear (E(snc)) to systolic wall thickening (E(33)). In the anterobasal region, undersized annuloplasty reduced systolic wall thickening (E33) by &50% at all transmural depths by inhibiting: (1) subendocardial systolic fiber shortening (-0.10+/-0.05 versus -0.04+/-0.05; P<0.05); (2) subepicardial (0.16+/-0.15 versus 0.09+/-0.08; P<0.05) and subendocardial (0.45+/-0.40 versus 0.19+/-0.18; P<0.05) systolic sheet thickening; (3) midwall sheet extension (0.22+/-0.12 versus 0.11+/-0.06; P<0.05); and (4) transmural sheet shear (subepicardium, -0.14+/-0.07 versus -0.08+/-0.07; midwall, 0.21+/-0.12 versus 0.10+/-0.11; subendocardium, -0.19+/-0.23 versus -0.11+/-0.16; P<0.05). In the remote lateral equatorial region, fiber-sheet strains and E33 were unchanged.In this acute animal study, undersized annuloplasty inhibited systolic wall thickening in the anterobasal region by reducing subendocardial systolic fiber shortening and laminar sheet wall thickening, but had no effects in a more distant LV region. This suggests that undersized mitral annuloplasty may have potentially deleterious effects on local myocardial mechanics.
Maternal Smoking during Pregnancy, Prematurity and Recurrent Wheezing in Early Childhood
Authors: R.G. Robison, R. Kumar, L.M. Arguelles, X. Hong, A. Bonzagni, S. Apollon, K. Ortiz, C. Pearson, H. Bauchner, J.A. Pongracic
Journal: Journal of Allergy and Clinical Immunology (2011)
Human and porcine early kidney precursors as a new source for transplantation
Authors: Benjamin Dekel, Tatyana Burakova, Fabian D. Arditti, Shlomit Reich-Zeliger, Oren Milstein, Sarit Aviel-Ronen, Gideon Rechavi, Nir Friedman, Naftali Kaminski, Justen H. Passwell, Yair Reisner
Journal: Nature Medicine (2002)
Starting Insulin Therapy in Patients With Type 2 Diabetes
Authors: Rodney A. Hayward
Journal: JAMA (1997)

<h3>Context.</h3> —Although experimental studies show that insulin therapy can be safe and efficacious in improving glycemic control in type 2 diabetes under optimal conditions (ie, using patient volunteers with close monitoring under strict study protocols), little is known about its effectiveness, complication rates, and associated resource utilization in actual clinical practice. <h3>Design.</h3> —Cohort study. <h3>Setting.</h3> —Large staff-model health maintenance organization. <h3>Participants.</h3> —A total of 8668 patients with type 2 diabetes cared for by generalist physicians from 1990 through 1993. <h3>Outcome Measures.</h3> —Resource use (hospitalizations, outpatient visits, laboratory testing, and home glucose monitoring) and glycemic control were evaluated using combined clinical, survey, and administrative information systems data. Detailed clinical case-mix data, including a newly validated case-mix method, the Total Illness Burden Index, were collected on a subsample of 1738 patients. <h3>Results.</h3> —Among patients starting insulin therapy, hemoglobin A<sub>1c</sub>(HbA<sub>1c</sub>) decreased by 0.9 percentage point (95% confidence interval, 0.7-1.0) at 1 year compared with those receiving stable medication regimens; however, 2 years after starting insulin therapy, 60% still had HbA<sub>1c</sub>levels of 8% or greater. There was no evidence that some primary care physicians achieved better results than other primary care physicians when starting insulin therapy in their patients. Patients with the poorest baseline glycemic control achieved substantially greater HbA<sub>1c</sub>reductions; those with a baseline HbA<sub>1c</sub>level of 13% had a 3-fold greater decline in HbA<sub>1c</sub>than those whose baseline HbA<sub>1c</sub>level was 9%. For a subset of all patients for whom detailed clinical case-mix data were obtained, those taking insulin had higher resource use than those taking sulfonylureas, independent of illness severity. After adjusting for age, sex, race, socioeconomic status, disease duration, and severity of diabetes and comorbidities, insulin users had slightly more laboratory tests performed, 2.4 more outpatient visits per year, and almost 300 more fingersticks for home glucose testing per year compared with sulfonylurea users (all<i>P</i>&lt;.01). Although 15% of patients receiving insulin therapy reported weekly symptoms of hypoglycemia, insulin therapy was not associated with an increase in emergency department visits (after case-mix adjustment) and resulted in only 0.5 hypoglycemia-related hospitalizations per 100 patient-years. <h3>Conclusions.</h3> —For patients with type 2 diabetes who were cared for by generalist physicians, starting insulin therapy was generally safe and effective in achieving moderate glycemic control in patients who initially had poor glycemic control. However, insulin therapy was associated with increases in resource use and was rarely effective in achieving tight glycemic control, even for those with moderate control.
Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension
Authors: Spilios Manolakopoulos, Christos Triantos, Jiannis Theodoropoulos, Jiannis Vlachogiannakos, Anastasios Kougioumtzan, George Papatheodoridis, Dimitrios Tzourmakliotis, Dimitrios Karamanolis, Andrew K. Burroughs, Athanasios Archimandritis, Sotirios Raptis, Alec Avgerinos
Journal: Journal of Hepatology (2009)
Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3
Authors: Mark P Purdue, Mattias Johansson, Diana Zelenika, Jorge R Toro, Ghislaine Scelo, Lee E Moore, Egor Prokhortchouk, Xifeng Wu, Lambertus A Kiemeney, Valerie Gaborieau, Kevin B Jacobs, Wong-Ho Chow, David Zaridze, Vsevolod Matveev, Jan Lubinski, Joanna Trubicka, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Péter Rudnai, Eleonora Fabianova, Alexandru Bucur, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Paolo Boffetta, Joanne S Colt, Faith G Davis, Kendra L Schwartz, Rosamonde E Banks, Peter J Selby, Patricia Harnden, Christine D Berg, Ann W Hsing, Robert L Grubb, Heiner Boeing, Paolo Vineis, Françoise Clavel-Chapelon, Domenico Palli, Rosario Tumino, Vittorio Krogh, Salvatore Panico, Eric J Duell, José Ramón Quirós, Maria-José Sanchez, Carmen Navarro, Eva Ardanaz, Miren Dorronsoro, Kay-Tee Khaw, Naomi E Allen, H Bas Bueno-de-Mesquita, Petra H M Peeters, Dimitrios Trichopoulos, Jakob Linseisen, Börje Ljungberg, Kim Overvad, Anne Tjønneland, Isabelle Romieu, Elio Riboli, Anush Mukeria, Oxana Shangina, Victoria L Stevens, Michael J Thun, W Ryan Diver, Susan M Gapstur, Paul D Pharoah, Douglas F Easton, Demetrius Albanes, Stephanie J Weinstein, Jarmo Virtamo, Lars Vatten, Kristian Hveem, Inger Njølstad, Grethe S Tell, Camilla Stoltenberg, Rajiv Kumar, Kvetoslava Koppova, Olivier Cussenot, Simone Benhamou, Egbert Oosterwijk, Sita H Vermeulen, Katja K H Aben, Saskia L van der Marel, Yuanqing Ye, Christopher G Wood, Xia Pu, Alexander M Mazur, Eugenia S Boulygina, Nikolai N Chekanov, Mario Foglio, Doris Lechner, Ivo Gut, Simon Heath, Hélène Blanche, Amy Hutchinson, Gilles Thomas, Zhaoming Wang, Meredith Yeager, Joseph F Fraumeni, Konstantin G Skryabin, James D McKay, Nathaniel Rothman, Stephen J Chanock, Mark Lathrop, Paul Brennan
Journal: Nature Genetics (2010)