tbuckley/cabot-search huggingface dataset:
Serum pepsinogens in blood transfusion donors.
Authors: R J Loffeld, E E Tobberingh, J W Arends
Journal: Gut (1992)

<h3>Aims and objectives</h3> The involvement of patients in the design and conduct of research is increasingly promoted by policy and research bodies. The experiences of individuals who become involved in research in this way are not well understood. This study aims to describe the experiences of people9s participation in patient and public involvement (PPI) in supportive and palliative care research, specifically with respect to the benefits and challenges of participation for the individuals and the broader research support structures. <h3>Methods</h3> In this qualitative exploratory study, semistructured interviews were undertaken with individuals who had a cancer diagnosis and were involved in a supportive and palliative care research collaborative over a period of 6 years. Recruitment was through the host university organisations involved in the research collaborative. A thematic analysis was undertaken to identify commonalities and differences across their experiences. <h3>Findings</h3> The eight participants in the study were highly motivated and undertook PPI in research alongside other voluntary activities. They identified a number of research and personal benefits: bringing a lay perspective into research, making a difference and personal gains. Personal gains concerned support, new knowledge and skills and greater confidence. The challenges to participation that were identified included the emotional and practical nature of the work, issues of language and identifying the difference made. <h3>Conclusions</h3> Involvement in supportive and palliative care research is valued by people with a cancer diagnosis, but there are ongoing issues of emotional support and good communication through the use of appropriate language in documentation.
Audit Commission tells trusts to improve if they want to survive
Authors: Nadeeja Koralage
Journal: BMJ (2004)

Most primary care trusts will have to “raise their game” if they are to survive changes in the system for paying doctors, says the author of a report from the Audit Commission.

The message comes as primary care trusts move towards a “payment by results” system—paying doctors for work done according to a set tariff, taking into account regional variations in cost and complexity of individual cases.

The report attacked primary care trusts over their “inadequate” financial management capabilities, adding that some NHS bodies would “struggle to meet these new challenges.”

Emma Knowles, the author of Achieving First-Class Financial Management in the NHS …
Russian Physicians In an Era of Reform and Revolution, 1856-1905
Authors: Frederick Butzen
Journal: JAMA (1982)

<i>Russian Physicians in an Era of Reform and Revolution</i>is the fascinating and disturbing story of the development of the medical profession in Russia between the Crimean War and the revolution of 1905. Historian Nancy Mandelker Frieden describes how the social changes and the science of the period affected the evolution of medicine as a profession and led many physicians to conclude that they could execute their professional duties only through political radicalism. The experience of Russian physicians can throw light on problems that US physicians may face in the future. Since de Tocqueville, historians have commented on the resemblance between Russia and the United States. Growing up at opposite ends of the earth, each flooded across relatively primitive regions to become the first modern empire-nations. As one Russian foreign minister commented in the 1860s, the United States and Russia have "a natural community of interests and sympathies." However, the
Preoperative Serum CA-125 Levels in Patients With Surgical Stage I Invasive Ovarian Adenocarcinoma
Authors: W. J. Mann, B. Patsner, H. Cohen, M. Loesch
Journal: JNCI Journal of the National Cancer Institute (1988)

Preoperative serum CA-125 levels were elevated in only three of 13 patients (23%) with a pelvic mass who were found to have surgical stage I invasive ovarian adenocarcinoma. This low incidence is surprising, since elevated levels have been found in greater than 80% of patients with advanced ovarian cancer. This suggests serious limitations for using serum CA-125 levels as a screening test for ovarian cancer.
TREATMENT OF GANGRENE DUE TO THROMBO-ANGIITIS OBLITERANS
Authors: SAUL S. SAMUELS
Journal: JAMA (1931)

The past decade has witnessed radical changes in the treatment of thrombo-angiitis obliterans.<sup>1</sup>Former teachings concerning this disease gave rise to the impression that the ultimate outcome in almost every case of thrombo-angiitis obliterans was amputation of one or more extremities because of the inevitable occurrence of gangrene. This erroneous idea has been so impressed on physicians that patients, even in the early stages of the disease, are often looked on as hopeless, and doomed to a future minus legs and arms. I have known of instances in which immediate amputation of both legs was advised because of the presence of incipient thrombo-angiitis obliterans, without ulceration or gangrene. A still larger number of cases of thrombo-angiitis obliterans are submitted to high amputation because of the presence of a small area of gangrene limited to one toe. In many textbooks the disease is described as a progressive series of amputations,
HYPERIDROSIS PEDUM AND ITS TREATMENT BY BATHS OF PERMANGANATE OF POTASH.
Authors: LUDWIG WEISS
Journal: JAMA (1904)

<h3>DEFINITION.</h3> By hyperidrosis we understand an excessive production of sweat due primarily to anomalies of the nerve centers influencing the sweat secretion; and secondarily, to circulatory disturbances depending on the altered state of the vasomotor nerves. The definition tries to embrace the two main central causes of overactivity of the sudoriparous glands. It will be shown later that there are also peripheral causes for hyperidrosis. It is impossible to determine how much the other follicular secretions—those of the sebaceous glands and the hair follicles—contribute to the volume of exuded material. We have no reliable method of separating both kinds of secretions from each other. Already Meissner<sup>1</sup>maintained that the coil glands serve as fatty lubricators, and more recently Unna<sup>2</sup>tried to prove that the sebaceous glands contribute only in a small degree to the function of lubricating the skin with fatty material, and that the coil glands mainly perform this
Extracorporeal membrane oxygenation as a rescue of intractable ventricular fibrillation and bridge to heart transplantation
Authors: Thomas Fux, Peter Svenarud, Karl‐Henrik Grinnemo, Anders Albåge, Fredrik Bredin, Jan van der Linden, Inger Hagerman, Anders Gabrielsen, Lars H. Lund
Journal: European Journal of Heart Failure (2010)
Oncolytic Viruses Targeting Tumor Stem Cells
Authors: E. Antonio Chiocca, Donald Blair, R. Allan Mufson
Journal: Cancer Research (2014)

A workshop "Targeting Oncolytic Viruses to Tumor Stem Cells," organized by the Division of Cancer Biology, NCI, NIH, was held on September 6, 2013 in Rockville, MD. Seventeen invited experts presented an overview of their current research in this area and discussed the state of current research on the use of oncolytic viruses targeted to stem cells as a potential cancer therapy. The goal was to evaluate the evidence that this approach might increase the efficacy of oncolytic virus therapy and to identify gaps in knowledge that have retarded progress in this area.
The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor TRAF6
Authors: Shi Jiao, Zhen Zhang, Chuanchuan Li, Min Huang, Zhubing Shi, Yanyan Wang, Xiaomin Song, Heng Liu, Chunyang Li, Min Chen, Wenjia Wang, Yun Zhao, Zhengfan Jiang, Hongyan Wang, Catherine C L Wong, Chen Wang, Zhaocai Zhou
Journal: Nature Immunology (2015)
Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular Events
Authors: Caroline Schmidt-Lucke, Lothar Rössig, Stephan Fichtlscherer, Mariuca Vasa, Martina Britten, Ulrike Kämper, Stefanie Dimmeler, Andreas M. Zeiher
Journal: Circulation (2005)

Background— The maintenance of endothelial integrity plays a critical role in preventing atherosclerotic disease progression. Endothelial progenitor cells (EPCs) were experimentally shown to incorporate into sites of neovascularization and home to sites of endothelial denudation. Circulating EPCs may thus provide an endogenous repair mechanism to counteract ongoing risk factor–induced endothelial injury and to replace dysfunctional endothelium. Methods and Results— In 120 individuals (43 control subjects, 44 patients with stable coronary artery disease, and 33 patients with acute coronary syndromes), circulating EPCs were defined by the surface markers CD34 + KDR + and analyzed by flow cytometry. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, PTCA, CABG, or ischemic stroke) served as outcome variables over a median follow-up period of 10 months. Patients suffering from cardiovascular events had significantly lower numbers of EPCs ( P &lt;0.05). Reduced numbers of EPCs were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis ( P =0.0009). By multivariate analysis, reduced EPC levels were a significant, independent predictor of poor prognosis, even after adjustment for traditional cardiovascular risk factors and disease activity (hazard ratio, 3.9; P &lt;0.05). Conclusions— Reduced levels of circulating EPCs independently predict atherosclerotic disease progression, thus supporting an important role for endogenous vascular repair to modulate the clinical course of coronary artery disease.
Association between serum uric acid level and chronic liver disease in the United States
Authors: Anita Afzali, Noel S. Weiss, Edward J. Boyko, George N. Ioannou
Journal: Hepatology (2010)

Elevated serum uric acid (UA) levels strongly reflect and may even cause oxidative stress, insulin resistance, and metabolic syndrome, which are risk factors for the progression of liver disease. We sought to determine whether serum UA levels are associated with the development of cirrhosis or the presence of elevated serum liver enzymes. We used cohort data from the first National Health and Nutrition Examination Survey (NHANES I) to determine whether the baseline serum UA level was associated with the incidence of hospitalization or death due to cirrhosis among 5518 participants during a mean follow-up of 12.9 years (range = 4-21 years) after the exclusion of the first 4 years of follow-up. We also used cross-sectional data from NHANES 1988-1994 (n = 10,993) and NHANES 1999-2006 (n = 6186) to determine whether the serum UA level was associated with elevated serum alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT), two markers of hepatic necroinflammation. Compared to persons in the lower third of the distribution of serum UA (<4.8 mg/dL), those in the top third (>6 mg/dL) had a higher risk of cirrhosis-related hospitalization or death [adjusted hazard ratio (AHR) = 2.8, 95% confidence interval (CI) =1.3-5.7], whereas the risk was not substantially increased in persons within the middle third (serum UA level = 2.6-4.8 mg/dL, AHR = 1.3, 95% CI = 0.6-2.7). A higher serum UA level was associated with greater mean serum ALT and GGT levels and a greater probability of elevated serum ALT and GGT.The serum UA level is associated with the development of cirrhosis and the presence of elevated serum liver enzymes after adjustments for important causes and risk factors of chronic liver disease.
Highlights on the Cholesterol-Fats, Diets and Atherosclerosis Problem
Authors: Grace A. Goldsmith
Journal: JAMA (1961)

Many dietary substances, including fats and numerous other factors, influence serum lipid concentrations. Serum lipids which may be related in some way to atherogenesis include cholesterol, specific triglycerides, phospholipids, fatty acids, or the whole spectrum of beta lipoproteins. A direct causal relationship between dietary fats, serum lipid concentrations, and atherosclerosis or coronary artery disease remains unproved. Many endogenous and exogenous factors other than diet influence atherogenesis. Obesity, hypertension, and hypercholesterolemia are associated with a high incidence of coronary artery disease. A therapeutic attempt to reduce high concentrations of cholesterol and other lipids in serum should be made as an experimental procedure. Neither the proportions of the fatty acid mixture nor the total amount of dietary fat which may be desirable for the maintenance of health has been determined.
Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion
Authors: Vanessa M. Freitas, Jônatas Bussador do Amaral, Thaiomara Alves Silva, Emerson de Souza Santos, Flávia R. Mangone, João de Jesus Pinheiro, Ruy Gastaldoni Jaeger, Maria A. Nagai, Gláucia Maria Machado-Santelli
Journal: Molecular Cancer (2013)

ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells.
Abstract 4887: Genetic analyses of chromatin remodelers in cancer
Authors: Laia S. Riudalbas, Sónia A. Melo, Anna Portela Mestres, Manel Esteller
Journal: Cancer Research (2010)

Abstract Genetic analyses of chromatin remodelers in cancer Laia S. Riudalbas1, Sónia A. Melo, Anna Portela &amp; Manel Esteller. 1Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08907 L'Hospitalet, Barcelona, Catalonia, Spain Chromatin remodelers are ATP dependent proteins that enable dynamic access to packaged DNA and tailor nucleosome composition in chromosomal regions. These protein complexes have been shown to regulate a wide range of cellular processes, including transcription regulation, DNA-damage response and DNA replication. Being that some components of this remodeler machinery were already characterized as tumor suppressor genes and/or oncogenic, we can hypothesize that the dysregulation of any of these molecules in tumor cells with microsatellite instability (MSI+), that show a higher rate of insertions and deletions, can lead to neoplastic transformation. For that we decided to screen all the exonic mononucleotide repeats of some of the most important chromatin remodelers with ATPase activity in colorectal, gastric and endometrial cancer cell lines, on the search for frameshift mutations that could alter protein function. We have mainly analyzed the catalytic subunits of remodeling complexes because any alteration of these crucial proteins could drive into a tumorigenic process. Until now no alteration was found in the cancer cell lines studied. This could be underscoring the importance of these genes to normal cellular functioning being that their disruption could impair cell viability. This work was supported by Grants SAF2007-00027-65134, FIS PI08-0517, Consolider CSD2006-49, and CANCERDIP FP7-200620. L.S.R. is a research fellow of FIS - Instituto de Salud Carlos III, FI09/00218. 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 4887.
Mobilization-competent Lentiviral Vector–mediated Sustained Transcriptional Modulation of HIV-1 Expression
Authors: Anne-Marie W Turner, Justin De La Cruz, Kevin V Morris
Journal: Molecular Therapy (2008)

Current anti-HIV-1 strategies reduce replication through targeting of viral proteins and RNA; meanwhile, targeting at the level of the integrated provirus has been less explored. We show here that mobilization-competent vectors containing small noncoding RNAs targeted to transcriptionally active regions of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) can take advantage of integrated virus and modulate HIV-1 replication. Transcriptional silencing of HIV-1 correlates with an increase in silent-state epigenetic marks including histone and DNA methylation, a loss of nuclear factor-κB (NF-κB) recruitment, and requires Argonaute 1 (Ago-1), histone deacetylase 1 (HDAC-1), and DNA methyltransferase 3a (DNMT3a) localization to the LTR. Long-term suppression of the virus was observed for 1 month with no evidence of viral resistance. These data show that RNA-directed transcriptional silencing of HIV-1 can be delivered by a mobilization-competent vector, suggesting that this system could be used to target long-term selective pressures on conserved promoter elements to evolve less pathogenic variants of HIV-1. Current anti-HIV-1 strategies reduce replication through targeting of viral proteins and RNA; meanwhile, targeting at the level of the integrated provirus has been less explored. We show here that mobilization-competent vectors containing small noncoding RNAs targeted to transcriptionally active regions of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) can take advantage of integrated virus and modulate HIV-1 replication. Transcriptional silencing of HIV-1 correlates with an increase in silent-state epigenetic marks including histone and DNA methylation, a loss of nuclear factor-κB (NF-κB) recruitment, and requires Argonaute 1 (Ago-1), histone deacetylase 1 (HDAC-1), and DNA methyltransferase 3a (DNMT3a) localization to the LTR. Long-term suppression of the virus was observed for 1 month with no evidence of viral resistance. These data show that RNA-directed transcriptional silencing of HIV-1 can be delivered by a mobilization-competent vector, suggesting that this system could be used to target long-term selective pressures on conserved promoter elements to evolve less pathogenic variants of HIV-1.
Palisaded neutrophilic and granulomatous dermatitis in an adolescent girl with perinuclear antineutrophil cytoplasmic antibody–positive pauci-immune glomerulonephritis and arthritis
Authors: Raegan D. Hunt, Rachael D. Hartman, Vered Molho-Pessach, Henry J. Votava, Julie V. Schaffer
Journal: Journal of the American Academy of Dermatology (2012)
Endotoxin uptake in mouse liver is blocked by endotoxin pretreatment through a suppressor of cytokine signaling-1-dependent mechanism
Authors: Melanie J. Scott, Shubing Liu, Richard A. Shapiro, Yoram Vodovotz, Timothy R. Billiar
Journal: Hepatology (2009)

Abstract The liver is the main organ that clears lipopolysaccharide (LPS) and hepatocytes are a major cell-type involved in LPS uptake. LPS tolerance, or desensitization, is important in negative regulation of responses to LPS, but little is known about its mechanisms in hepatocytes. Primary isolated C57BL/6 hepatocytes, and liver in vivo , internalized fluorescent LPS, and this was dependent on Toll-like receptor 4 (TLR4) at the cell surface but not on TLR4-TIR signaling through MyD88. LPS clearance from plasma was also TLR4-dependent. Pretreatment of C57BL/6 hepatocytes with LPS prevented uptake of LPS 24 hours later and this LPS-mediated suppression was dependent on TLR4 signaling through MyD88. Many regulators of TLR4 signaling have been identified and implicated in LPS desensitization, including suppressor of cytokine signaling 1 (SOCS1). SOCS1 mRNA and protein expression increased after LPS stimulation in hepatocytes and in whole liver. LPS uptake in hepatocytes and liver was significantly reduced following infection with adenoviral vectors overexpressing SOCS1. Similarly, inhibition of SOCS1 using small interfering (si)RNA-mediated knockdown prevented LPS desensitization in hepatocytes. SOCS1 is known to interact with Toll/IL-1 receptor associated protein (TIRAP) and cause TIRAP ubiquitination and degradation, which regulates TLR signaling. We have also shown previously that TIRAP regulates LPS uptake in hepatocytes. SOCS1 coimmunoprecipitated with TIRAP in wild type hepatocyte cell lysates up to 8 hours after LPS stimulation, but not at later times. In the same samples, ubiquitinated TIRAP was detected after 4 hours and up to 8 hours after LPS stimulation, but not at later times. Conclusion: These data indicate hepatocytes are desensitized by LPS in a TLR4 signaling-dependent manner. LPS-induced SOCS1 upregulation increases degradation of TIRAP and prevents subsequent LPS uptake. The exploitation of these mechanisms of LPS desensitization in the liver may be important in future sepsis therapies. (Hepatology 2009.)
Dose- and time-dependent oval cell reaction in acetaminophen-induced murine liver injury
Authors: Alexander V. Kofman, Glyn Morgan, Adam Kirschenbaum, Jon Osbeck, Mehboob Hussain, Scott Swenson, Neil D. Theise
Journal: Hepatology (2005)

We examined the response of murine oval cells, that is, the putative liver progenitor cells, to acetaminophen. Female C57BL/6J mice were injected intraperitoneally with varying doses of N-acetyl-paraaminophen (APAP) (250, 500, 750, and 1,000 mg/kg of weight) and sacrificed at 3, 6, 9, 24, and 48 hours. In preliminary studies, we showed that anticytokeratin antibodies detected A6-positive cells with a sensitivity and specificity of greater than 99%. The oval cell reaction was quantified, on immunostaining for biliary-type cytokeratins, as both number and density of oval cells per portal tract, analyzed by size of portal tract. Acetaminophen injury was followed by periportal oval cell accumulation displaying a moderate degree of morphological homogeneity. Oval cell response was biphasic, not temporally correlating with the single wave of injury seen histologically. Increases in oval cells were largely confined to the smallest portal tracts, in keeping with their primary derivation from the canals of Hering, and increased in a dose-dependent fashion. The timing of the two peaks of the oval cell reaction also changed with increasing dose, the first becoming earlier and the second later. In conclusion, our studies indicate a marked oval cell activation during the height of hepatic injury. Oval cells appear to be resistant to acetaminophen injury. The close fidelity of mechanism and histology of acetaminophen injury between mouse and human livers makes it a useful model for investigating liver regeneration and the participation of stem/progenitor cells in that process. (HEPATOLOGY 2005.)