tbuckley/cabot-search huggingface dataset:
Insulin therapy in burn patients does not contribute to hepatic triglyceride production.
Authors: A Aarsland, D L Chinkes, Y Sakurai, T T Nguyen, D N Herndon, R R Wolfe
Journal: Journal of Clinical Investigation (1998)

Lipid kinetics were studied in six severely burned patients who were treated with a high dose of exogenous insulin plus glucose to promote protein metabolism. The patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned. They were studied in a randomized order (a) in the fed state on the seventh day of a control period (C) of continuous high-carbohydrate enteral feeding alone, and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite a glucose delivery rate approximately 100% in excess of energy requirements, the following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]), (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]), and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63 mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis. In association with the doubling of the secretion rate of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P > 0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/-8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4% to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68 mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater potential for hepatic lipid accumulation in burn patients than the endogenous hepatic fat synthesis, even during excessive carbohydrate intake in conjunction with insulin therapy.
Long-term study of indolent adult T-cell leukemia-lymphoma
Authors: Yumi Takasaki, Masako Iwanaga, Yoshitaka Imaizumi, Masayuki Tawara, Tatsuro Joh, Tomoko Kohno, Yasuaki Yamada, Shimeru Kamihira, Schuichi Ikeda, Yasushi Miyazaki, Masao Tomonaga, Kunihiro Tsukasaki
Journal: Blood (2010)
XII. Polarity and Amplitude of the U Wave of the Electrocardiogram in Relation to that of the T Wave
Authors: BORYS SURAWICZ, ROBERT L. KEMP, SAMUEL BELLET
Journal: Circulation (1957)

The ratio of the amplitude of the QRS complex to the amplitude of the U wave varies in different leads of the same electrocardiogram. In the majority of electrocardiograms, the U wave has the same polarity as the T wave and the ratio of the U wave and T wave amplitude is relatively constant in all leads. The tallest positive U wave is usually observed in the area of leads V 2 to V 4 . The deepest negative U wave is usually observed in the area of leads V 5 to V 6 . Secondary changes of the T wave are very frequently accompanied by similar changes of the U wave. T-wave changes caused by myocardial infarction and digitalis are usually not accompanied by changes of the polarity of the U wave. The electrocardiograms of 297 cases of hypertension were divided into 6 groups on the basis of the relationship between the polarity of the T wave and the U wave. Both waves were positive in all precordial leads in 48.1 per cent of the cases. Negative U waves were found in 21.8 per cent of the cases and these were predominantly in the leads with negative T waves. A negative T wave in the left precordial leads was accompanied most frequently by a negative, less frequently by an isoelectric, and least frequently by a positive, U wave. An inverted U wave in the presence of an upright T wave was found in only 2.8 per cent of the cases. A change from a negative to a positive or isoelectric U wave was observed after slowing of the heart rate, a drop in blood pressure, and nitroglycerin administration.
Abstract 2488: Novel candidate protein biomarkers for cisplatin response prediction in non-small cell lung cancer.
Authors: Tieneke B M Schaaij-Visser, Remco Nagel, Inge de Reus, Sander R. Piersma, Thang V. Pham, Egbert F. Smit, Frederik B. Thunnissen, Ruud H. Brakenhoff, Anton Berns, Connie R. Jimenez
Journal: Cancer Research (2013)

Abstract The five-year survival rate for non-small cell lung cancer (NSCLC) is still less than twenty percent in part due to treatment failure and lack of biomarkers for personalized therapy. Most NSCLC patients are treated by chemotherapy and cisplatin is still the major component of most chemotherapy regimens. However, resistance to cisplatin is a common phenomenon. Aim of this study was to identify protein biomarkers that can be used for cisplatin response prediction. The proteomes and secretomes1 of a series of human NSCLC cell lines with a range of IC50-values for cisplatin (1.5 - 15 μM) were analyzed by label-free proteomics based on GeLC-MS/MS and quantified by spectral counting. Significant differential expression of proteins was determined by the in-house developed beta-binomial statistical test2. Network and gene ontology analysis was performed, with STRING and DAVID respectively, to reveal cellular and molecular functions associated with the differential proteins. In total, 2885 and 2342 proteins were detected in the cell lysates and secretomes, respectively. The proteins with significantly higher expression in the resistant cell lines were associated RNA processing and vesicle transport, while the proteins with higher expression in the sensitive cell lines were known to be involved in RNA splicing, DNA damage repair and extracellular matrix organization. The most promising candidates are being validated in tissues and sputum of patients with known response to cisplatin. 1 Piersma SR et al. J Proteome Res. 2010 Apr 5;9(4):1913-22. 2 Pham TV et al. Bioinformatics. 2010 Feb 1;26(3):363-9. Citation Format: Tieneke B M Schaaij-Visser, Remco Nagel, Inge de Reus, Sander R. Piersma, Thang V. Pham, Egbert F. Smit, Frederik B. Thunnissen, Ruud H. Brakenhoff, Anton Berns, Connie R. Jimenez. Novel candidate protein biomarkers for cisplatin response prediction in non-small cell lung cancer. [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 2488. doi:10.1158/1538-7445.AM2013-2488
KRAS-LCS6 Genotype as a Prognostic Marker in Early-Stage CRC–Letter
Authors: Bríd M. Ryan, Ana I. Robles, Curtis C. Harris
Journal: Clinical Cancer Research (2012)

In their recently published study (1), Smits and colleagues reported an association between rs61764370 and colorectal cancer (CRC) survival of early-stage tumors. Similarly, in our study of 678 (441 controls and 237 cases; Table 1), we found that rs61764370 was also associated with a reduced risk of mortality, albeit in late-stage tumors [HRTG/GG vs. TT, 0.38; 95% confidence interval (CI), 0.16–0.88; n = 124] (Fig. 1 and Table 2). Neither study found an association with risk (Table 1).There are some key differences between the two studies that could explain the differential findings. The first of these relates to the ethnicity of the cohorts. Our study was based upon both African Americans and European Americans, whereas that of Smits and colleagues focused on a European population. While we lose power upon stratification, we still observe the same association in European Americans and survival of late-stage tumors (HRTG/GG vs. TT, 0.46; 95% CI, 0.18–1.16; n = 78).We believe a more likely explanation lies in the differences between KRAS mutation status among the two cohorts. In our study, 70% of the cancers with a KRAS mutation were diagnosed as either stage III or IV. In Smits and colleagues, only 33.5% of stage III and 43.5% of stage IV tumors were KRAS-mutant. We also noted that there were no deaths among patients who carried rs61764370 and whose tumors were mutant for KRAS. This could therefore suggest that the presence of KRAS mutation is a more important factor in determining the relationship between rs61764370 and survival than stage. In addition, it helps to explain the differences between the studies' findings and clarify why our association was primarily seen in late-stage tumors.Another possible difference that could confound these reports is the predictive properties of the rs61764370 single-nucleotide polymorphism (SNP). Zhang and colleagues previously reported that the variant G allele predicts response to single-agent cetuximab monotherapy in refractory CRCs, particularly in patients whose tumors are KRAS wild-type (2). Intriguingly, Graziano and colleagues reported that the same genotype was predictive of poor outcome in patients treated with both cetuximab and irinotecan (3). Collectively, these results suggest that both KRAS mutation status and therapy modulate the impact of this SNP. Smits and colleagues did not describe the treatment details of their cohort, and where data are available, our cohort primarily received 5-fluorouracil. Collectively, we find that this SNP is not predictive of risk. Rather, an association with survival has again emerged. However, larger studies that take KRAS, BRAF, and treatment status (1–5) into account are needed to more accurately and completely define the role of this SNP in CRCs and its potential to contribute to individualized and personalized treatment.See the Response, p. 3489No potential conflicts of interest were disclosed.
Monoclonal rat anti-major histocompatibility complex antibodies display specificity for rat, mouse, and human target cells.
Authors: D E Smilek, H C Boyd, D B Wilson, C M Zmijewski, F W Fitch, T J McKearn
Journal: The Journal of Experimental Medicine (1980)

24 monoclonal rat antibodies are described that are reactive with determinants encoded by the major histocompatibility complex (MHC) of the rat. These hybridoma antibodies were derived by fusing mutant mouse myeloma cells to spleen cells from Lewis rats immunized with allogeneic Brown Norway cells. All 24 antibodies are cytotoxic for both Brown Norway target cells and target cells from the appropriate MHC congenic rats. Pattern of cytotoxicity and hemagglutination strongly suggest reactivity against class I (K or D equivalent) rat MHC determinants. Cytotoxic cross-reactivity patterns were generated for each monoclonal antibody on a panel of rat and mouse lymphoid cells and human peripheral T lymphocytes. A high degree of interspecies cross-reactivity was noted with approximately one-half of the antibodies positive on human and/or mouse target cells. 11 antibodies recognized polymorphic determinants in the mouse, and, by using target cells from MHC congenic mouse strains, it was shown that these determinants are encoded by genes within the H-2 complex. Finally, by considering the overall reactivity patterns of these monclonal antibodies on all target cells, one can show that these 24 antibodies represent a minimum of 14 antibody specificities.
Poisoning: Toxicology, Symptoms, Treatments
Authors: Joseph R. Dipalma
Journal: JAMA (1970)

This is the second edition of a book which has established itself as the bible for those who are responsible for diagnosing and treating poisoning cases. Much enlarged and updated, it now contains many new tables and subjects which make it even more useful. Primarily the text is designed for the practicing physician. It deals first with general consideration of diagnosis and therapy of poisoning, at the same time indicating the incidence of the major types likely to be encountered. Specific sections are then devoted to such topics as insecticides, industrial hazards, and poisonous plants and animals. A very large section aptly deals with the drugs of medical practice and iatrogenic disease. Very few items likely to be toxic are omitted. Extremely useful are the generous use of tables of diagnostic symptoms and treatments. All the Poison Control Centers in the United States are listed, together with their phone numbers.
NICE guidelines urge local authorities to "spend to save" on public health
Authors: H. Mooney
Journal: BMJ (2013)

The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically trained individuals to recognise the signs and symptoms of possible sport-related concussion and provides guidance for removing an athlete from play/sport and to seek medical attention. This paper presents the development of the CRT5 and highlights the differences between the CRT5 and prior versions of the instrument.
Abstract 2165: Identification of a novel pathway of castrate resistant prostate cancer (CRPCa) growth
Authors: Farideh Mehraein-Ghomi, Hirak S. Basu, Shigeki Miyamoto, George Wilding
Journal: Cancer Research (2011)

Abstract Development of an effective therapy to prevent PCa occurrence, recurrence and/or progression remains an unmet medical need. This is mainly due to a poor understanding of the mechanism of PCa occurrence and progression. There is accumulating evidence that ROS (Reactive Oxygen Species) such as hydrogen peroxide, superoxide, hydroxyl radical, etc. that are produced in high amounts in PCa cells may be a major factor in PCa occurrence and its progression to androgen-independence. One of the ROS (H2O2) plays a key role in triggering growth signals and expression of transcription factors to sustain growth of androgen-dependent PCa cells in the absence of androgen. One such factor is Nuclear Factor κB (NF-κB) that may sustain cell survival by preventing apoptosis and inducing cell proliferation. NF-κB activation kinetically correlates with androgen-induced ROS production in cultured LNCaP human PCa cells. This activation is also seen in resected PCa tissues from patients, who subsequently progressed to CRPCa. Our published data show that androgen induces an up-regulation of spermidine/spermine acetyl transferase (SSAT) mRNA as well as enzyme activity that initiates polyamine oxidation in LNCaP cells after 72 h exposure. Because of the unusually high polyamine levels in the PCa cells, polyamine oxidation causes a large increase in ROS production that is abrogated by silencing SSAT expression in PCa cells stably transfected with shRNA against SSAT (siSSAT). To determine whether SSAT is required for NF-κB activation following prolonged androgen stimulus, we transfected 3xκB-luciferase vector containing NF-κB consensus binding sites-luciferase reporter construct along with a β-gal expression vector (to control for the transfection efficiency) into both wild type LNCaP cells and its siSSAT clones. While 72 h androgen exposure causes an over 30-fold induction of luciferase activity in wild type LNCaP cells, no activation of NF-κB was observed in the siSSAT clones. These data clearly show a strong SSAT induction is required for a robust activation of NF-κB in androgen-treated PCa cells. Multiple published reports show that NF-κB can also induce SSAT in several human cancer cells. Thus, our data suggest an intriguing mechanism of CRPCa progression, where androgen induced SSAT expression and consequent upregulation of NF-κB can set up an autocrine feed forward loop of SSAT-ROS-NFκB-SSAT that can sustain PCa cell proliferation in the absence of androgen that can lead to CRPCa growth. 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 2165. doi:10.1158/1538-7445.AM2011-2165
Modeling exposure routes to man of trace metals associated with acid precipitation.
Authors: B G Bennett
Journal: Environmental Health Perspectives (1985)

Pollutant metals released to the environment disperse and interact in various ways before arriving at sensitive receptors. Modeling of pollutant behavior may be by time-dependent or time-independent means. The time-independent, exposure commitment method requires a less extensive data base and can begin with general associations between environmental concentrations or fluxes. Such assessments for representative background conditions have been performed for most of the metals associated with acid precipitation. Examples are given here for cadmium and mercury. These overviews are only the beginning stage of relating pollutant releases to environmental effects.
SAFE: Design Takes on Risk
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

An exhibition at the Museum of Modern Art, 11 West 53rd Street, New York, NY 10019, until 2 January 2006. Admission $20 www.moma.org/exhibitions/2005/safe.html Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> For doctors and others who convey risk to the public, the most important document from this exhibition is a free handout. The card uses ever larger dots to show the risk from venomous snakes and lizards (invisible), from non-opioid analgesics, antipyretics, and antirheumatics (a teeny dot), to air and space transport crashes (a slightly bigger dot), to exposure to forces of nature (a good sized dot). Then we hit the big time risk dots: motorcycling, poisoning, drowning or submersion, or being the occupant of a pickup truck or van, or a pedestrian. And the biggest dot, the most dangerous risk: being the occupant of a car. The show, at the large, pure white, glassy, and newly expanded Museum of Modern Art … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Assessment of cleaning to control lead dust in homes of children with moderate lead poisoning: treatment of lead-exposed children trial.
Authors: Adrienne S Ettinger, Robert L Bornschein, Mark Farfel, Carla Campbell, N Beth Ragan, George G Rhoads, Merrill Brophy, Sherry Wilkens, Douglas W Dockery
Journal: Environmental Health Perspectives (2002)

In this article we describe the assessment and control of lead dust exposure in the Treatment of Lead-exposed Children (TLC) Trial, a clinical trial of the effects of oral chelation on developmental end points in urban children with moderately elevated blood lead levels. To reduce potential lead exposure from settled dust or deteriorated paint during the drug treatment phase of the trial, the homes of 765 (98%) of the randomized children (both active and placebo drug treatment groups) were professionally cleaned. Lead dust measurements were made in a sample of 213 homes before and after cleaning. Geometric mean dust lead loadings before cleaning were 43, 29, 308, and 707 micro g/ft2 in the kitchen floor, playroom floor, playroom windowsill, and playroom window well samples respectively. Following cleaning, floor dust lead loadings were reduced on average 32% for paired floor samples (p < 0.0001), 66% for windowsills (p < 0.0001), and 93% for window wells (p < 0.0001). Cleaning was most effective for 146 homes with precleaning dust lead levels above the recommended clearance levels, with average reductions of 44%, 74%, and 93% for floors (p < 0.0001), windowsills (p < 0.0001), and window wells (p < 0.0001), respectively. Despite these substantial reductions in dust lead loadings, a single professional cleaning did not reduce the lead loadings of all dust samples to levels below current federal standards for lead in residential dust. Attainment of dust levels below current standards will require more intensive cleaning and lead hazard reduction strategies.
Inhibiting Systemic Autophagy during Interleukin 2 Immunotherapy Promotes Long-term Tumor Regression
Authors: Xiaoyan Liang, Michael E. De Vera, William J. Buchser, Antonio Romo de Vivar Chavez, Patricia Loughran, Donna Beer Stolz, Per Basse, Tao Wang, Bennett Van Houten, Herbert J. Zeh, Michael T. Lotze
Journal: Cancer Research (2012)

Abstract Administration of high-dose interleukin-2 (HDIL-2) has durable antitumor effects in 5% to 10% of patients with melanoma and renal cell carcinoma. However, treatment is often limited by side effects, including reversible, multiorgan dysfunction characterized by a cytokine-induced systemic autophagic syndrome. Here, we hypothesized that the autophagy inhibitor chloroquine would enhance IL-2 immunotherapeutic efficacy and limit toxicity. In an advanced murine metastatic liver tumor model, IL-2 inhibited tumor growth in a dose-dependent fashion. These antitumor effects were significantly enhanced upon addition of chloroquine. The combination of IL-2 with chloroquine increased long-term survival, decreased toxicity associated with vascular leakage, and enhanced immune cell proliferation and infiltration in the liver and spleen. HDIL-2 alone increased serum levels of HMGB1, IFN-γ, IL-6, and IL-18 and also induced autophagy within the liver and translocation of HMGB1 from the nucleus to the cytosol in hepatocytes, effects that were inhibited by combined administration with chloroquine. In tumor cells, chloroquine increased autophagic vacuoles and LC3-II levels inhibited oxidative phosphorylation and ATP production and promoted apoptosis, which was associated with increased Annexin-V+/propidium iodide (PI)− cells, cleaved PARP, cleaved caspase-3, and cytochrome c release from mitochondria. Taken together, our findings provide a novel clinical strategy to enhance the efficacy of HDIL-2 immunotherapy for patients with cancer. Cancer Res; 72(11); 2791–801. ©2012 AACR.
An Unusual Complication of Support with a Continuous-Flow Cardiac Assist Device
Authors: Mitesh V. Badiwala, Heather J. Ross, Vivek Rao
Journal: New England Journal of Medicine (2007)

To the Editor: A 61-year-old man in cardiogenic shock was recently transferred to our hospital. Angiography revealed total occlusion of the left anterior descending coronary artery and an 80% ostia...
Some GP commissioners pay twice as much for IVF as others, review finds
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Background/Aim: Anti-apoptotic proteins, including Bcl-2 and Bcl-xL, hinder cancer treatment, and several drugs targeting these molecules have been developed. One is ABT-263 (navitoclax), which targets Bcl-2, Bcl-xL, and Bcl-w. On the other hand, hydroxychloroquine (HCQ) has been used as a drug for malaria infection and autoimmune disease. HCQ can exert a similar effect as chloroquine with fewer adverse events. In addition, HCQ exerts antitumor activity. In the present study, the effects of HCQ on ABT-263-induced antitumor activities were examined using three human pancreatic cancer cell lines (PANC-1, MiaPaCa-2, and BxPC-3). Materials and Methods: In vitro effects of HCQ and ABT-263 were examined by cell viability, colony-forming assays, and flow cytometry. Protein expression was determined by immunoblotting. In vivo effects of HCQ and ABT-263 were examined by a xenograft mice model. Results: Combined treatment with HCQ and ABT-263 synergistically decreased the viability of only BxPC-3 cells. This synergistic effect was not observed when HCQ was combined with ABT-199, an inhibitor specific to Bcl-2. The combination of HCQ and ABT-263 induced caspase-dependent apoptosis. Protein expression of Bcl-xL was more highly expressed in BxPC-3 cells than in the other two cell lines, and the combination of HCQ with a Bcl-xL inhibitor or siRNA-mediated knockdown of Bcl-xL induced apoptosis in BxPC-3 cells. Combination therapy with HCQ and ABT 737, an ABT-263 analogue, suppressed the in vivo growth of BxPC-3 with transient body-weight loss. Conclusion: HCQ effectively promotes Bcl-xL inhibition-induced apoptosis in BxPC-3 human pancreatic cancer cells.