tbuckley/cabot-search huggingface dataset:
Randomized placebo-controlled clinical trial of high-dose interleukin-2 in combination with a soluble p75 tumor necrosis factor receptor immunoglobulin G chimera in patients with advanced melanoma and renal cell carcinoma.
Authors: J S Du Bois, E G Trehu, J W Mier, L Shapiro, M Epstein, M Klempner, C Dinarello, K Kappler, L Ronayne, W Rand, M B Atkins
Journal: Journal of Clinical Oncology (1997)

PURPOSE A randomized, double-blind, placebo-controlled trial was performed to compare the toxicity and biologic effects of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus the recombinant human soluble p75 tumor necrosis factor (TNF) receptor immunoglobulin G (IgG) chimera (rhuTNFR:Fc) with high-dose IL-2 alone in patients with advanced melanoma and renal cell carcinoma. PATIENTS AND METHODS Twenty patients with advanced melanoma or renal cell carcinoma were randomized to receive IL-2 (Chiron, Emeryville, CA) 600,000 IU/kg every 8 hours on days 1 to 5 and 15 to 19 (maximum, 28 doses) combined with placebo or the rhuTNFR:Fc fusion protein (Immunex, Seattle, WA) 10 mg/m2 on days 1 and 15 and 5 mg/m2 on days 3, 5, 17, and 19. The impact of rhuTNFR:Fc on IL-2 toxicity and biologic effects was evaluated. RESULTS No clinically significant difference in toxicity was observed in the two treatment arms. The adjusted median number of IL-2 doses administered during cycle 1 was 24.5 (range, seven to 28) and 21.5 (range, five to 27) for the placebo and rhuTNFR:Fc arms, respectively (P = .544). IL-2-induced TNF bioactivity, neutrophil chemotactic defect, and serum IL-6, IL-8, and IL-1 receptor antagonist (IL-1RA) induction were suppressed by rhuTNFR:Fc. Two of nine assessable patients (22%) on IL-2/placebo and three of 10 patients (30%) on IL-2/rhuTNFR:Fc responded. CONCLUSION Despite evidence of in vitro neutralization of TNF functional activity and partial inhibition of other secondary biologic effects of IL-2, rhuTNFR:Fc does not reduce the clinical toxicity associated with high-dose IL-2 therapy. These results suggest that the toxicity and antitumor effects of IL-2 treatment are independent of circulating TNF.
ROLE OF THE THYMUS IN TOLERANCE
Authors: Katarina Isaković, Stanley B. Smith, Byron H. Waksman
Journal: The Journal of Experimental Medicine (1965)

Rats thymectomized and irradiated as adults were restored to immunologic reactivity by grafts of normal adult rat thymus and bone marrow. Reactivity of the delayed (cellular) type and formation of mercaptoethanol-sensitive (MES) and mercaptoethanol-resistant (MER) antibody returned within 3 weeks, while Arthus reactivity remained subnormal till 9 weeks after irradiation and grafting. When the thymus donor was tolerant to BGG, the recipient showed specific non-reactivity to this antigen 3 weeks and, to a much lesser extent, 6 weeks after grafting. This non-reactivity affected delayed responses and MER antibody. No effect was noted on Arthus reactivity and a slight effect on MES antibody. Controls showed that the non-reactivity was not due to transfer of free antigen at the time of grafting. It was concluded that different source organs are responsible for different immune functions and that specific immunologic tolerance may be induced within such an organ as the thymus.
LSC 2011 Abstract: Changes in the proteome upon dermal sensitization in a mouse model of chemical-induced asthma
Authors: Steven Haenen, Elke Clynen, Vanessa De Vooght, Peter Hoet, Ben Nemery, Jeroen Vanoirbeek
Journal: European Respiratory Journal (2011)

In follow up of our studies on proteomic changes in a validated mouse model of immunologically mediated chemical-induced asthma, using toluene-2,4-diisocyanate (TDI) as a sensitizer [1 we evaluated the temporal changes at early time points following dermal sensitization. The identification of biomarkers of sensitization could help to move diagnosis to an earlier (pre-clinical) stage. We explored the proteome of the auricular lymph nodes and serum of mice dermally sensitized to TDI.  Mice were treated once (day 1) or twice (day 1 and 8) with TDI or with the vehicle (acetone-olive oil, 2:3, control) on both ears. Auricular lymph nodes and serum were collected three days later. Two-dimensional difference gel electrophoresis was used to analyze the differential proteins (p  Proteome analyses of the auricular lymph nodes resulted in 39 and 86 differential proteins and of serum in 7 and 16 differential proteins, after 1 and 2 sensitizations, respectively. Identification (MALDI-TOF MS) of these proteins mainly showed structural (e.g. vimentin), immune related (e.g. lymphocyte specific protein-1) and oxidative stress related proteins (e.g. peroxiredoxin 6) in both the lymph nodes and the serum.  Now, a software based pathway analysis of the differential proteins is performed (Ariadne Genomics). This will give more insight in the cellular and molecular events involved in early sensitization, leading to chemical-induced asthma. Possible biomarkers among the differential proteins will be validated.  Reference:  1Haenen S, Vanoirbeek JA, De Vooght V, Maes E, Schoofs L, Nemery B, Hoet PH, Clynen E. J Proteome Res. 2010;9(11):5868-76.
Incidence and seroprevalence of tularaemia in Finland, 1995 to 2013: regional epidemics with cyclic pattern
Authors: H Rossow, J Ollgren, J Hytönen, H Rissanen, O Huitu, H Henttonen, M Kuusi, O Vapalahti
Journal: Eurosurveillance (2015)

Binary file ES_Abstracts_Final_ECDC.txt matches
Transmission of cancer with cadaveric donor organs.
Authors: P J Conlon, S R Smith
Journal: Journal of the American Society of Nephrology (1995)

A case is presented in which each of the recipients of a pair of cadaveric kidneys developed metastatic carcinoma. One of the recipients died, and the other demonstrated involution of metastatic deposits after graft nephrectomy and withdrawal of immunosuppression. By the use of polymerase chain reaction of minisatellite regions of donor and recipient DNA, the donor origin of the tumor was conclusively demonstrated. Although a relatively uncommon complication of cadaveric renal transplantation, the transmission of cancer with cadaveric organs may become more frequent as older donors are accepted for organ donation.
Coronary Artery Reperfusion
Authors: P. R. Maroko, P. Libby, W. R. Ginks, C. M. Bloor, W. E. Shell, B. E. Sobel, J. Ross
Journal: Journal of Clinical Investigation (1972)

The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue.
Parity as a Prognostic Factor in Young Breast Cancer Patients&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M M Black, B F Hankey, T H Barclay
Journal: JNCI Journal of the National Cancer Institute (1983)

Data were analyzed concerning 219 female breast cancer patients less than 36 years of age who were diagnosed and treated in the Province of Saskatchewan, Canada, during 1946–72. Pathology slides were available for review on 171 of these patients, and invasive breast cancer could be confirmed in 136. Nulliparous patients had more favorable age-adjusted survival rates than parous patients for the total patient group and for those patients whose tumor was verified to be invasive cancer on pathologic review. Adjustment for potential confounding factors indicated that differences in survival among parity groups could be explained to a substantial degree by differences in distribution over node status and the nuclear grade of the primary tumor. Because these factors relate to the biologic behavior of breast cancer and because the distributions of these factors were significantly associated with the parity categories utilized in the analysis, the data provide some evidence that parity influences the behavior of breast cancer in young women.
Higher-level snake phylogeny inferred from mitochondrial DNA sequences of 12S rRNA and 16S rRNA genes.
Authors: P J Heise, L R Maxson, H G Dowling, S B Hedges
Journal: Molecular Biology and Evolution (1995)

Portions of two mitochondrial genes (12S and 16S ribosomal RNA) were sequenced to determine the phylogenetic relationships among the major clades of snakes. Thirty-six species, representing nearly all extant families, were examined and compared with sequences of a tuatara and three families of lizards. Snakes were found to constitute a monophyletic group (confidence probability [CP] = 96%), with the scolecophidians (blind snakes) as the most basal lineages (CP = 99%). This finding supports the hypothesis that snakes underwent a subterranean period early in their evolution. Caenophidians (advanced snakes), excluding Acrochordus, were found to be monophyletic (CP = 99%). Among the caenophidians, viperids were monophyletic (CP = 98%) and formed the sister group to the elapids plus colubrids (CP = 94%). Within the viperids, two monophyletic groups were identified: true vipers (CP = 98%) and pit vipers plus Azemiops (CP = 99%). The elapids plus Atractaspis formed a monophyletic clade (CP = 99%). Within the paraphyletic Colubridae, the largely Holarctic Colubrinae was found to be a monophyletic assemblage (CP = 98%), and the Xenodontinae was found to be polyphyletic (CP = 91%). Monophyly of the henophidians (primitive snakes) was neither supported nor rejected because of the weak resolution of relationships among those taxa, except for the clustering of Calabaria with a uropeltid, Rhinophis (CP = 94%).
Study Using the NCCN Guidelines for Palliative Care to Screen Patients for Palliative Care Needs and Referral to Palliative Care Specialists
Authors: Paul Glare, Kathy Plakovic, Anna Schloms, Barbara Egan, Andrew S. Epstein, David Kelsen, Leonard Saltz
Journal: Journal of the National Comprehensive Cancer Network (2013)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Palliative Care recommend screening all patients for palliative care (PC) needs and to call a PC consult when referral criteria are met. The goal of this pilot project was to evaluate the feasibility of implementing the screening and referral components of the NCCN Guidelines for Palliative Care in patients admitted to the Gastrointestinal Oncology Service (GIOS) at a comprehensive cancer center (CCC). Floor nurses performed the initial screening of all patients admitted to the 2 teams—Team A and Team B—of the GIOS on one floor of Memorial Hospital for 3 months. In addition, only the patients admitted to Team A were evaluated according to the referral criteria, triggering a PC consult if results were positive. Nurses were surveyed regarding satisfaction with and the acceptability of screening. During the study period, 229 (90%) total admissions were screened, with 169 (73%) having positive results. Of the Team A admissions, 72 (64%) met the referral criteria. More consults occurred for patients in Team A (47 vs 15; P=.001). In 30% of the referral criteria-triggered consults, the PC needs were manageable by the primary team. Nurses reported screening to be easy and quick (<5 minutes per patient) but only somewhat helpful. Being unfamiliar with many patients and families, floor nurses often felt unable to screen them accurately for some issues. In conclusion, screening was feasible, increasing access to PC, but accuracy and usefulness are concerns. With a consult indicated in 64% patients, yet with 30% being manageable by the primary team, the current criteria may be too sensitive for the inpatient environment of a CCC. More evaluation is needed before widespread implementation can be recommended.
COPD airway epithelium secretion attracts and activates neutrophils
Authors: Lucie Knabe, Aurélie Petit, Nicolas Molinari, Anne-Sophie Gamez, Isabelle Vachier, Arnaud Bourdin
Journal: European Respiratory Journal (2014)

Background: 

Sustained neutrophilic airway inflammation may promote Chronic Obstructive Pulmonary Disease (COPD) progression. To which extent the airway epithelium is involved remains unclear. We investigated neutrophil chemotaxis and activation induced by supernatants of fully differentiated air liquid interface (ALI) epithelial cultures.

Methods: 

Supernatants were collected at day 28 from ALI cultures of human airway epithelial cells differentiated from COPD patients, smokers and control subjects'biopsies taken during bronchoscopy two months earlier. Neutrophils obtained by venipuncture from normal non smoker volunteers were purified using percoll gradient. Neutrophil elastase secretion and activity were evaluated respectively by ELISA and colorimetric assay. The migratory dynamic of neutrophils was assessed using Dunn's Chamber where three parameters were monitored: cell speed, chemotaxis and chemotactic index.

Results: 

ALI supernatants of COPD and smokers increased elastase secretion and activity after 24 hours of neutrophil incubations. Moreover, these supernatants induced velocity and chemotaxis were increased compared to control supernatants. In addition, neutrophil chemotactic indexes were significantly higher in presence of COPD and smoker ALI-supernatants.

Conclusion: 

The airway epithelium of COPD patients reconstituted in ALI sustains increased neutrophilic chemotaxis and neutrophil elastase release and activity. Whether CXCL-8 is involved will be the next step. Interfering with this pathway may be a useful strategy for controlling neutrophilic airway inflammation.
Phosphorylation of Eukaryotic Translation Initiation Factor 2Bε by Glycogen Synthase Kinase-3β Regulates β-Adrenergic Cardiac Myocyte Hypertrophy
Authors: Stefan E. Hardt, Hideharu Tomita, Hugo A. Katus, Junichi Sadoshima
Journal: Circulation Research (2004)

Glycogen synthase kinase 3β (GSK-3β) negatively regulates cardiac hypertrophy. A potential target mediating the antihypertrophic effect of GSK-3β is eukaryotic translation initiation factor 2Bε (eIF2Bε). Overexpression of GSK-3β increased the cellular kinase activity toward GST-eIF2Bε in neonatal rat cardiac myocytes, whereas LiCl (10 mmol/L) or isoproterenol (ISO) (10 μmol/L), a treatment known to inhibit GSK-3β, decreased it. Immunoblot analyses using anti-S535 phosphospecific eIF2Bε antibody showed that S535 phosphorylation of endogenous eIF2Bε was decreased by LiCl or ISO, suggesting that GSK-3β is the predominant kinase regulating phosphorylation of eIF2Bε-S535 in cardiac myocytes. Decreases in eIF2Bε-S535 phosphorylation were also observed in a rat model of cardiac hypertrophy in vivo. Overexpression of wild-type eIF2Bε alone moderately increased cell size (+31±11%; P &lt;0.05 versus control), whereas treatment of eIF2Bε-transduced myocytes with LiCl (+73±22% versus eIF2Bε only; P &lt;0.05) or ISO (+84±33% versus eIF2Bε only; P &lt;0.05) enhanced the effect of eIF2Bε. Overexpression of eIF2Bε-S535A, which is not phosphorylated by GSK-3β, increased cell size (+107±35%) as strongly as ISO (+95±25%), and abolished antihypertrophic effects of GSK-3β, indicating that S535 phosphorylation of eIF2Bε critically mediates antihypertrophic effects of GSK-3β. Furthermore, expression of eIF2Bε-F259L, a dominant-negative mutant, inhibited ISO-induced hypertrophy, indicating that eIF2Bε is required for β-adrenergic hypertrophy. Interestingly, expression of eIF2Bε-S535A partially increased cytoskeletal reorganization, whereas it did not increase expression of atrial natriuretic factor gene. These results suggest that GSK-3β is the predominant kinase mediating phosphorylation of eIF2Bε-S535 in cardiac myocytes, which in turn plays an important role in regulating cardiac hypertrophy primarily through protein synthesis.
Hand-foot skin reaction in patients treated with sorafenib: a clinicopathological study of cutaneous manifestations due to multitargeted kinase inhibitor therapy
Authors: C-H. Yang, W-C. Lin, C-K. Chuang, Y-C. Chang, S-T. Pang, Y-C. Lin, T-T. Kuo, J-J. Hsieh, J.W.C. Chang
Journal: British Journal of Dermatology (2007)

Hand-foot skin reaction is a distinctive cutaneous side-effect of antineoplastic kinase inhibitor-targeted therapy. Severe hand-foot skin reaction requires postponement of treatment or dose reduction. Histopathological studies of skin toxicity associated with kinase inhibitors are currently unavailable.To report the clinical and histopathological findings of hand-foot skin reaction produced by the multikinase inhibitor sorafenib.Nine patients with metastatic carcinoma-seven with renal cell carcinoma (RCC), one with melanoma and one with hepatocellular carcinoma (HCC)-received continuous, oral sorafenib 400 mg twice daily. Hand-foot skin reaction was defined and graded according to National Cancer Institute Common Toxicity Criteria 3.0. Biopsies from lesions of erythematous scaly or blistering skin were obtained from five cases (four RCC and one HCC).Seven of the nine (78%) patients developed hand-foot skin reaction characterized by well-demarcated, tender, erythematous papules and plaques with greyish blisters or hyperkeratotic, callus-like formations on palmoplantar surfaces and distal phalanges. Skin biopsy of hand-foot skin reaction lesions revealed epidermal acanthosis, papillomatosis, parakeratosis, dispersed dyskeratotic cells and keratinocyte vacuolar degeneration. Other skin toxicities included angular cheilitis, seborrhoeic dermatitis and perianal dermatitis.The clinical manifestations and histopathological features of sorafenib-induced skin reactions are unique. The most relevant histopathological findings of hand-foot skin reaction include keratinocyte vacuolar degeneration, the presence of intracytoplasmic eosinophilic bodies, and intraepidermal blisters in the stratum malpighii. Further studies are warranted to elucidate the mechanisms of this novel multitargeted kinase inhibitor-associated skin reaction.
Fluticasone propionate in clinically suspected asthma patients with negative methacholine challenge test
Authors: Hamidreza Abtahi, Soheil Peiman
Journal: European Respiratory Journal (2013)

Objective  : Despite response to steroid inhaler in some clinically suspected asthma patients with negative methacholine challenge test (CSA/ MCT−), asthma treatment in these patients has not been prospectively studied. We studied the role of a course of inhaled fluticasone trial in CSA/ MCT− patients.    Method  : After a 2 week run-in period, CSA/ MCT− patients were treated with 12 weeks of Fluticasone inhaler 500 µg BID. Pre- and post-treatment Asthma Control Test (ACT) and numeric cough score (NCS) were recorded.    Results  : 26 of 34 patients completed the study. Mean pretreatment ACT score (pACT) was significantly increased after treatment (15.5±3.3 to 20.8±3.2, P  5, wheeze disappeared and 66% of them did not use bronchodilator for symptom.    Conclusion  : A significant portion of CSA/ MCT− patients respond to high dose fluticasone inhaler in terms of symptoms, wheeze disappearance and bronchodilator use. In view of its safety profile, we suggest a course of steroid inhaler trial especially in CSA/ MCT−patients with pretreatment ACT score
Bioavailability of vascular endothelial growth factor (VEGF)? A role in pulmonary fibrosis?
Authors: Shaney Barratt, Caroline Jarrett, Gavin Welsh, David Bates, Ann Millar
Journal: European Respiratory Journal (2012)

Vascular endothelial growth factor (VEGF) is both a growth factor and permeability factor, involved in tissue repair and as such, has been proposed to have a role in the pathogenesis of pulmonary fibrosis. VEGF is generated as multiple isoforms of two families, VEGF xxx  and VEGF xxx b and mediates its effects through specific receptors, VEGFR-1 and VEGFR-2 and co-receptors, neuropilin-1 and neuropilin-2. We hypothesised that these receptors, co-receptors and isoforms would be differentially expressed in normal versus fibrotic fibroblasts.  Normal fibroblasts (NF) and fibrotic fibroblasts (FF) (from patients with proven UIP) were extracted from lung samples using the explant method. Expression of VEGFR-1, 2 and NRP1-1, NRP2 and VEGF isoforms was established at the protein level using western blotting whilst receptor expression was confirmed with immunofluorescence staining of cells in culture.  Both NF and FF expressed VEGFR1 and 2, NRP-1 and 2 and VEGF xxx / xxx b isoforms. No significant differences in VEGFR-2 and NRP-1 expression between NF and FF fibroblast were detected, however both VEGFR-1 and NRP-2 were significantly reduced in FF versus NF (p  VEGF receptors, co-receptors and isoforms are expressed differentially in NF and FF. This suggests a potential role for changes in VEGF bioactivity in the development of pulmonary fibrosis.
Circulating and exhaled vascular endothelial growth factor in asthmatic pregnancy
Authors: Andras Bikov, Aniko Bohacs, Noemi Eszes, Zsoka Weiszhar, Istvan Ivancso, Veronika Muller, Janos Rigo, Gyorgy Losonczy, Lilla Tamasi, Ildiko Horvath
Journal: European Respiratory Journal (2013)

Introduction: It is well known that vascular endothelial growth factor (VEGF) plays an important role in asthma and pathological pregnancies. However, VEGF has not been investigated in pregnant asthmatics before.  Aims: In this study we aimed to analyse systemic and airway levels of VEGF in asthmatic pregnant individuals by measuring this mediator in plasma and exhaled breath condensate (EBC) samples, respectively.  Methods: 32 asthmatic pregnant, 29 asthmatic non-pregnant, 28 healthy pregnant and 22 healthy non-pregnant women were enrolled. Plasma VEGF was measured in all subjects and additional EBC was collected in 57 volunteers for VEGF measurements. Furthermore, plasma soluble VEGF receptor, the fms-like tyrosine kinase 1 (sFlt1) was also determined in 86 subjects.  Results: Significant differences were observed in plasma VEGF and sFlt1 among the four groups (p 0.05). In the majority of the EBC samples VEGF levels were undetectable. Neither VEGF nor sFlt1 correlated with clinical variables (lung function, exhaled NO, asthma control, neonatal birth weight) in any group.  Conclusions: Our results suggest that concomitant asthma does not affect plasma VEGF during pregnancy.  The study was supported by Hungarian Respiratory Society and Hungarian National Research Fund (OTKA 68808).
Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease: An Analysis of Clinical Benefit As Determined By Number Needed to Treat (NNT) to Achieve Complete Response and to Improve Survival
Authors: Paul G. Richardson, Nancy A. Kernan, Stephan A. Grupp, Paul L. Martin, Robert J. Soiffer, Richard Martin, Alison L. Hannah, Kathleen F. Villa
Journal: Blood (2014)