tbuckley/cabot-search huggingface dataset:
Abstract IA16: Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress
Authors: Regina Young, Daniel Ackerman, Zachary Quinn, Anthony Mancuso, Michaela Gruber, Liping Liu, Dionysios Giannoukos, Ekaterina Bobovnikova-Marjon, J. Alan Diehl, Brian Keith, M. Celeste Simon
Journal: Cancer Research (2013)

Abstract Solid tumors exhibit heterogeneous microenvironments, often characterized by limiting concentrations of oxygen (O2), glucose, and other nutrients. How oncogenic mutations alter stress response pathways, metabolism, and cell survival in the face of these challenges is incompletely understood. Here we report that constitutive mTORC1 activity renders hypoxic cells dependent on exogenous desaturated lipids, as levels of de novo synthesized unsaturated fatty acids are reduced under low O2. Specifically, we demonstrate that hypoxic Tsc2-/- cells deprived of serum lipids exhibit a magnified UPR response, but fail to appropriately expand their ER, leading to IRE1-dependent cell death that can be reversed by the addition of unsaturated lipids. UPR activation and apoptosis were also detected in Tsc2-deficient kidney tumors. Importantly, we observe this phenotype in multiple human cancer lines and suggest that cells committed to unregulated growth within ischemic tumor microenvironments are unable to balance lipid and protein synthesis due to a critical limitation in desaturated lipids. Citation Format: Regina Young, Daniel Ackerman, Zachary Quinn, Anthony Mancuso, Michaela Gruber, Liping Liu, Dionysios Giannoukos, Ekaterina Bobovnikova-Marjon, J. Alan Diehl, Brian Keith, M. Celeste Simon. Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr IA16.
Diagnostic and predictive factors of significant liver fibrosis and minimal lesions in patients with persistent unexplained elevated transaminases. A prospective multicenter study
Authors: Victor de Lédinghen, Vlad Ratziu, Xavier Causse, Brigitte Le Bail, Dominique Capron, Christophe Renou, Christophe Pilette, Valérie Oules, Eve Gelsi, Frédéric Oberti, Anaïs Vallet-Pichard, Nicolas Le Provost, Jean-François Cadranel
Journal: Journal of Hepatology (2006)
Loss of Cav1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness
Authors: Shahid M Baig, Alexandra Koschak, Andreas Lieb, Mathias Gebhart, Claudia Dafinger, Gudrun Nürnberg, Amjad Ali, Ilyas Ahmad, Martina J Sinnegger-Brauns, Niels Brandt, Jutta Engel, Matteo E Mangoni, Muhammad Farooq, Habib U Khan, Peter Nürnberg, Jörg Striessnig, Hanno J Bolz
Journal: Nature Neuroscience (2010)
Interferon alfa plus ribavirin in chronic hepatitis C relapsers and non-responders to previous interferon alfa course
Authors: J. Salmerón, R. Martín Vivaldi, M. De la Mata, M. Romero, J. Perez Moreno, J. Aguilar, A. Palacios, F. Nogueras, M. Vignote, R. Alcántara, E. Suarez, R. Andrade, L. Rodriguez, H. Sanchez, D. Quintero
Journal: Journal of Hepatology (2000)
P332L162V PPAR-alpha gene polymorphism, A603G tissue factor gene polymorphism and markers of endothelial dysfunction in coronary heart disease patients in Russian population
Authors: Z Ionova, E Sergeeva, A Kostareva, O Galkina, E Bogdanova
Journal: Cardiovascular Research (2014)

Purpose. The goal of this study is to determine the effect of structural polymorphism L162V of peroxisome proliferator-activated receptors type α (PPAR-α)gene and structural polymorphism of A603G of TF gene on the molecular markers of endothelial dysfunction in patients with coronary heart disease. Methods. The L162V PPAR-α and A603G TF gene genotypes were determined in a sample of 212 Russian men with CHD and 55 healthy men by a polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based method. Vascular cell adhesion molecule-1 (VCAM-1), IL-8, IFN-γ, IL-6 plasma levels were studied by ELISA (Bender Medsystems). ANOVa analysis, exact Fisher test and Odds-Ratio calculation were performed. Results. The frequency of L162V genotype of PPAR-α gene in coronary heart disease patients was higher than in the group of healthy people (30 from 212 and 2 from 55, p=0.016). The frequency of TF G603G genotype in CHD patients was higher than in the group of healthy people (72 from 212 and 11 from 55, p=0,017). VCAM-1 level of blood plasma in CHD patients was higher than in healthy individuals: 991.6+ 42.3 ng/ml and 657.1+47.4 ng/ml respectively, p<0.01. In the group of patients with BMI >29.9kg/m^2­ the level of VCAM-1 accounted 1080+66.5 ng/ml that is significantly higher than in patients with BMI <=29.9kg/m^2 (885+48 ng/ml, p<0.01). Significant positive correlation has been found between VCAM-1 level and IL-6 content in blood plasma: r =0.25, p<0.05. CHD patients - L162V genotype carriers of PPAR-α gene - have revealed elevated VCAM-1 level of blood plasma compared to patients - L162L genotype carriers ­­(1054+129 ng/ml and 965+48 ng/ml respectively, p<0.05). IL-8 content in CHD patients with L162V genotype was higher than in L162L genotype carriers and healthy people - 2208+90.4 pkg/ml, 484.0+57.2 pkg/ml (p<0.001) and 472.1+128 pkg/ml (p<0.001) respectively. IL-8 content in CHD patients with G603G TF gene genotype were higher, than in A603A genotype carriers (981,3±214 pkg/ml and 308,1±59,2 pkg/ml respectively, p<0,05) The same tendencies were revealed in IFN-γ plasma content (1,58±0,251 pkg/ml in G603G tissue factor gene carriers and 0,99±0,205 pkg/ml in A603A genotype carriers. Conclusions. L162V PPAR-α and G603G tissue factor gene genotypes are associated with elevated levels of endothelial dysfunction markers in coronary heart disease patients in Russian population.
340 GPO10, a collagen mimetic effectively promotes activation of collagen-bound pro-matrix-metalloproteinase-2 in fibrotic liver tissue
Authors: M. Ruehl, C. Freise, M. Seja, U. Erben, D. Schuppan, R. Famdale, M. Zeitz, R. Somasundaram
Journal: Journal of Hepatology (2006)
Prospective study of cigarette smoking and adult glioma: Dosage, duration, and latency
Authors: Crystal N. Holick, Edward L. Giovannucci, Bernard Rosner, Meir J. Stampfer, Dominique S. Michaud
Journal: Neuro-Oncology (2007)

Tobacco products are major contributors of exogenous N-nitroso compounds, a group of potent neurocarcinogens. Overall results from studies of smoking and brain tumors have been null, but have provided little information on duration, age at smoking initiation, and latency. We prospectively examined the relation between cigarette smoking and glioma risk among men and women in three large U.S. cohort studies: the Health Professionals Follow-up Study (HPFS), the Nurses' Health Study I (NHS), and NHS II. Information on smoking history was obtained at baseline (1986 for HPFS, 1976 for NHS, and 1989 for NHS II) and updated biennially through 2002 in the HPFS and the NHS and 2003 in the NHS II. We confirmed 110 incident gliomas among men and 255 gliomas among women during 667,673 and 4,388,515 person-years of follow-up, respectively. Cox proportional hazard models were used to estimate incidence rate ratios and 95% confidence intervals between smoking and glioma risk adjusting for age, total meat intake, and alcohol and coffee consumption. Estimates from each cohort were pooled using a random-effects model after determining that there was no heterogeneity by sex. No association with glioma risk was observed between baseline or updated smoking status, intensity, duration, or age at smoking initiation among men and women. Furthermore, no association with glioma risk was observed after allowing for an induction period between smoking and glioma diagnosis. These findings provide strong evidence that cigarette smoking is not associated with an appreciably elevated risk of adult glioma.
Analysis of natural killer–cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease
Authors: Stefania Marcenaro, Federico Gallo, Stefania Martini, Alessandra Santoro, Gillian M. Griffiths, Maurizio Aricó, Lorenzo Moretta, Daniela Pende
Journal: Blood (2006)
A Randomized Phase II Trial of First-Line Treatment with Gemcitabine, Erlotinib, or Gemcitabine and Erlotinib in Elderly Patients (Age ≥70 Years) with Stage IIIB/IV Non-small Cell Lung Cancer
Authors: Thomas E. Stinchcombe, Amy H. Peterman, Carrie B. Lee, Dominic T. Moore, Jennifer L. Beaumont, Daniel S. Bradford, Kamal Bakri, Mark Taylor, Jeffrey M. Crane, Garry Schwartz, Thomas A. Hensing, Edwin McElroy, Harvey B. Niell, Harry D. Harper, Sridhar Pal, Mark A. Socinski
Journal: Journal of Thoracic Oncology (2011)
THE CAUSE OF DEATH IN PNEUMONIA
Authors: HARLOW BROOKS
Journal: JAMA (1934)

My purpose in this study was to investigate the immediate cause of death in pneumonia, both from a clinical and from an anatomic standpoint. The material consists of 200 consecutive cases of pneumonia, which were studied clinically and which finally came to autopsy in the Fourth Medical Service at Bellevue Hospital.  The autopsies were performed by various members of the pathologic staff under the chief pathologist, who has permitted me to utilize the material in this manner. The clinical studies were based on the usual records of the cases under the regular attending physicians and their associates of the division, with additional notes when possible of the immediate manner of death.  During the war as chief of medical service at the Camp Upton Base Hospital, as senior consultant in medicine to the Second Army, A. E. F., 1918-1919, and finally after the armistice attached to the army laboratory at Dijon,
Effect of airplane travel on women treated for breast cancer.
Authors: S Kilbreath, L Ward, K Lane, M McNeely, E Williams, D McKenzie, K Refshauge, C Peddle, K Battersby
Journal: Cancer Research (2009)

Abstract Abstract #1119 Background: Many patient materials promulgate lifestyle adaptations purported to minimize risk of lymphedema. One factor often mentioned is development or exacerbation of lymphedema due to airplane travel. The aim of this study was to describe prospectively the effect of airplane travel on women treated for breast cancer, traveling to Caloundra, Qld., Australia to attend a dragon boat regatta.&amp;#x2028; Methods: Pre and post data were obtained from 63 women traveling from Canada to Australia, and from 12 women traveling within Australia. 54% were treated for breast cancer on their dominant side, 63% underwent mastectomy with or without reconstruction, 77% underwent axillary node dissection, and 21% wore a compression sleeve during flight; 94% trained at a moderate to vigorous intensity for the regatta. Single frequency bioimpedance analysis (BIA; XCA; Impedimed Inc.®) was used to determine the inter-limb difference in upper limb extracellular fluid. BIA is highly reliable and has high sensitivity and specificity for increased extracellular fluid accumulation. Change in ratio &amp;gt;0.05 for women without lymphoedema is of clinical significance. Women were measured within 2 weeks of their flight to Caloundra, immediately on arrival in Caloundra, and for 46 women, within 6 weeks of return to Canada.&amp;#x2028; Results: Airplane travel did not have a significant effect on the upper limb BIA ratio, either between the pre and post flight (t75= -0.355; p=0.72) or between the pre and follow-up measures (t44=.241; p=0.811).&amp;#x2028; &amp;#x2028; Overall, the BIA post ratio increased from the pre measure by ≤0.02 in 48 women; 0.02 to &amp;lt;0.05 in 12 women; 0.05 to &amp;lt;0.10 in 10 women; and &amp;gt;0.10 in 5 women (Fig 1). In Figure 1, symbols in grey-shaded area represents women who did not have lymphedema prior to flight but presented with it post flight and the dashed lines indicate previously established cut-offs for criteria for detection of lymphedema. Dotted line on each graph is the line of agreement. The 6 symbols in the grey shaded area (Fig 1) represent women from the international group; their change in BIA ranged from 0.05 to 0.28. Follow-up measures were available on 5 of these women, and indicated that 4 were below the cut-offs for lymphedema. All 6 women had undergone mastectomy and axillary clearance of their lymph nodes and for 5, surgery was on their dominant side. Only 3 of the women wore a compressive sleeve on the plane.&amp;#x2028; Discussion: For the majority of women who undertake moderate to vigorous upper limb exercise, airplane travel did not have a significant impact on extracellular fluid ratio. Acknowledgment: Impedimed for funding and equipment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1119.
COMMON DNA POLYMORPHISM WITHIN CODING SEQUENCE OF APOLIPOPROTEIN B GENE ASSOCIATED WITH ALTERED LIPID LEVELS
Authors: A. Law, L.M. Powell, H. Brunt, T.J. Knott, D.G. Altman, T. Rajput, S.C. Wallis, R.J. Pease, L.M. Priestley, J. Scott, G.J. Miller, N.E. Miller
Journal: The Lancet (1986)
Effects of intensive application of retinoic acid on human skin
Authors: KAYS H. KAIDBEY, ALBERT M. KLIGMAN, HIKOTARO YOSHIDA
Journal: British Journal of Dermatology (1975)

The daily application of 0-3% retinoic acid to the back produced an acute irritant dermatitis which resolved to a near-normal clinical appearance within 40 days despite continued daily exposure. Hardened skin was markedly altered physiologically. The responses to DMSO, histamine and the histamine liberator, compound 48/80, were sharply enhanced. This reflected enhanced permeability resulting from reduction of the horny layer to less than one-half its normal thickness. Phototoxic and irritant substances produced exaggerated reactions owing to greater penetration. A paradoxical decrease in delayed sinsitivity to streptodornase-streptokinase was attributed to enhanced clearance of the antigen.
Characterization of membrane homing receptors in two cloned murine hemopoietic progenitor cell lines.
Authors: T Matsuoka, C Hardy, M Tavassoli
Journal: Journal of Clinical Investigation (1989)

To characterize homing receptors that are responsible for the recognition and specific binding of hemopoietic progenitor cells to the stroma, we synthesized and 125I-labeled a number of neoglycoproteins. We used these neoglycoproteins as ligand to detect receptors on the membrane of two cloned murine hemopoietic progenitor cell lines, B6SUT and FDCP-1. Both cell lines demonstrated membrane receptors with galactosyl and mannosyl, but not fucosyl, specificities. B6SUT galactosyl receptors showed a single receptor population with a Kd of about 2.3 X 10(-7) M and 10(6) receptors per cell. Mannosyl receptors demonstrated two components with high and low affinities respectively with Kd of about 2.5 X 10(-8) M and 1.0 X 10(-7) M, and respectively about 7.4 X 10(5) and 3.7 X 10(5) receptors per cell. Comparable data were also obtained for FDCP-1. Displacement experiments indicated that radioactive ligands bound to receptors could be increasingly displaced by homologous cold ligand giving typical sigmoid-shaped curves. Cold mannosyl probe could also displace radioactive galactosyl probe in a similar manner, but cold galactosyl probe displaced radioactive mannosyl ligand with a curve demonstrating two phases, further suggesting two receptor components for the mannosyl ligand. Mature murine neutrophils and red cells as well as human neutrophils, monocytes, and red cells showed no receptors. The functional significance of these receptors in binding to stromal cells was demonstrated by quantitation of the binding of 51Cr-labeled progenitor cells to the cloned stromal cell line, D2X, before and after enzymatic removal of various carbohydrate residues of membrane glycoconjugates. Enzymatic removal of galactosyl and mannosyl, but not fucosyl, residues almost totally eliminated the binding. The findings strongly suggest that these homing receptors are present on the surface of early hemopoietic progenitor cells. With maturation the cells lose their receptors, so that mature cells can be released into the blood stream.
Stem Cell Research: A Target Article Collection Part I - Jordan's Banks, A View from the First Years of Human Embryonic Stem Cell Research
Authors: Laurie Zoloth
Journal: The American Journal of Bioethics (2002)

This essay will address the ethical issues that have emerged in the first considerations of the newly emerging stem cell technology. Many of us in the field of bioethics were deliberating related issues as we first learned of the new science and confronted the ethical issues it raised. In this essay, I will draw on the work of colleagues who were asked to reflect on early stages of the research (members of the IRBs, the Geron Ethicist Advisory Board, and the National Bioethics Advisory Commission) as the field debated the issues of consent, moral status, use of animal tissues, abortion, use of fetal tissue, and the nature and goals of entrepreneurial research. In this new capacity, ethicists weighed the problem of privacy, the role of justice considerations, and the issues of the marketplace in science. At this point, it is clear that far more issues remain unresolved than are settled, that there is largely unexplored territory ahead, and that the single most important task that faces us as a field is a steady call for ongoing conversation and public debate.
Postexcisional melanocytic regrowth extending beyond the initial scar: a novel clinical sign of melanoma
Authors: J.W. Kelly, S. Shen, Y. Pan, J. Dowling, C.A. McLean
Journal: British Journal of Dermatology (2013)

Recurrent naevi are widely recognized to occur commonly following incomplete removal of melanocytic lesions. These lesions have been generally understood as representing benign imitators of melanoma.To provide a formal description of the clinical findings of postexcisional melanocytic regrowth.We examined all cases of recurrent pigmentation adjacent to scars from previous excisional biopsies of melanocytic naevi treated at a private dermatology practice from 1995 to 2012.We report nine cases of recurrence of melanocytic lesions that were melanomas. The most suspicious clinical feature for melanoma in these cases was the growth of the lesion beyond the confines of the initial scar, into the surrounding normal skin.This pattern of recurrence of a melanocytic lesion represents a little recognized and distinctive clinical presenting sign of melanoma.
Child Psychiatrists Address Problem of Youth Violence
Authors: Stephen Lurie
Journal: JAMA (1999)

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Short-term recovery of mental efficiency after anaesthesia.
Authors: P G Cutler
Journal: BMJ (1976)

Myasthenic syndrome during treatment with practolol SIR,-The myasthenic syndrome during treat- ment with large doses of practolol described by Drs R 0 Hughes and F J Zacharias (21 February, p 460) appears to be a clinical manifestation of the effect of 3-adrenoceptor blocking agents on the neuromuscular junction observed in animals.Like other members of this group of drugs' 2 practolol has a curare- like action, as shown in sciatic nerve- gastrocnemius preparations of the cat:' and frog and in the frog sciatic nerve-sartorius preparation and rectus abdominis muscle.2 4 The dosage required to depress neuromuscular transmission was larger for practolol than for propranolol.Though the patient's electromyogram, presumably taken in the resting state, was normai, it would be of great interest to know whether in the myasthenic state repetitive nerve stimulation evoked a gradually declining response of the muscle and whether even in the absence of the myasthenic syndrome the patient was particularly prone to fatigue.As in experimental animals the neuromuscular effects of '3-adrenoceptor blockers are readily reversible the risk of a relapse of the myas- thenic syndrome seems to be remote.How- ever, the patient may be hypersensitive to D-tubocurarine and related agents and also to drugs with a local anaesthetic action, like quinidine.
Aspirin (5 mmol/L) Inhibits Leukocyte Attack and Triggered Reactive Cell Proliferation in a 3D Human Coronary In Vitro Model
Authors: Rainer Voisard, Robert Fischer, Markus Oßwald, Sami Voglic, Regine Baur, Milorat Susa, Wolfgang Koenig, Vinzenz Hombach
Journal: Circulation (2001)

Background —Leukocyte attack (LA) and the triggered reactive proliferation of smooth muscle cells (SMCs) are key events for the development of early atherosclerosis and restenosis. In the present study, we used a 3D human coronary in vitro model of LA (3DLA model) to examine the effect of high-dose aspirin on the adhesion and chemotaxis of leukocytes and the reactive proliferative response of SMCs. Methods and Results —For dose-finding, the effect of aspirin (1, 2, 5, and 10 mmol/L) on the tumor necrosis factor-α–induced upregulation of intercellular adhesion molecule-1 was analyzed in monocultures of human coronary endothelial cells (HCAEC) and the SMCs of the human coronary media (HCMSMC). In cytoflow and Northern blot experiments, the expression of intercellular adhesion molecule-1 was slightly reduced after incubation with 5 mmol/L aspirin, and strong inhibition was found after incubation with 10 mmol/L. In 3DLA models, HCAECs and HCMSMCs were cultured on both sides of a porous filter. For LA, human monocytes or CD4 + lymphocytes were seeded on the HCAEC side of the 3DLA unit. A dose of 5 mmol/L aspirin inhibited the adherence of monocytes or CD4 + lymphocytes by 50% ( P &lt;0.01) and the chemotaxis of monocytes by 90% ( P &lt;0.01). The reactive proliferative response of cocultured HCMSMCs after LA, as measured by the uptake of bromodeoxyuridine, was significantly reduced by 83% after selective monocyte attack ( P &lt;0.001) and by 42% after selective CD4 + lymphocyte attack ( P &lt;0.05). Conclusions —A local concentration of 5 mmol/L aspirin should be accepted as the lowest rational concentration for the beneficial in vitro effects of high-dose aspirin to be reproduced in clinical studies.