tbuckley/cabot-search huggingface dataset:
Aberrant JMJD3 Expression Upregulates Slug to Promote Migration, Invasion, and Stem Cell–Like Behaviors in Hepatocellular Carcinoma
Authors: Bo Tang, Guangying Qi, Fang Tang, Shengguang Yuan, Zhenran Wang, Xingsi Liang, Bo Li, Shuiping Yu, Jie Liu, Qi Huang, Yangchao Wei, Run Zhai, Biao Lei, Hongping Yu, Stephen Tomlinson, Songqing He
Journal: Cancer Research (2016)

Abstract The Jumonji domain–containing chromatin remodeling factor JMJD3 has important roles in development and cancer. Here, we report a pivotal role for JMJD3 in sustaining the phenotype of aggressive hepatocellular carcinomas. Expression levels of JMJD3 in clinical specimens of hepatocellular carcinoma correlated inversely with patient survival. In hepatocellular carcinoma cells, we found that enforcing its overexpression induced epithelial–mesenchymal transition (EMT), invasive migration, stem cell–like traits, and metastatic properties. Conversely, silencing JMJD3 in hepatocellular carcinoma cells overexpressing it inhibited these aggressive phenotypes. Mechanistically, JMJD3 modulated H3K27me3 in the SLUG gene promoter, a histone mark associated with active SLUG transcription. SLUG silencing blocked JMJD3-induced EMT, stemness, and metastasis. Furthermore, SLUG expression in hepatocellular carcinoma clinical specimens correlated positively with JMJD3 expression. Our results establish JMJD3 as a critical driver of hepatocellular carcinoma stem cell–like and metastatic behaviors, with implications for prognosis and treatment. Cancer Res; 76(22); 6520–32. ©2016 AACR.
Rac GTPases Modulate Migration of Hematopoietic Progenitor Cells in an SDF-1α Dependent Manner in a Tumor Model.
Authors: Stephan Goettig, Andreas Pinter, Erika Deak, Christine Stroebele, Erhard Seifried, Jose Cancelas, David A. Williams, Jens Gille, Reinhard Henschler
Journal: Blood (2007)
The FcgRIIb gene, located in 1q21, is targeted by a t(1;22)(q21;q11) observed in malignant lymphoma
Authors: M Callanan, P Le Baccon, T Willis, S Duley, P Mossuz, Iwona Wlodarska, C Bastard, M Dyer, G Klobeck, R Rimokh, JJ Sotto, D Leroux
Journal: Blood (1998)
Does Multiorgan Failure Impact Prognosis of Liver Transplantation in Patients with End-Stage Liver Disease? Results of a French Retrospective Multicenter Case-Control Study
Authors: F. Artru, A. Louvet, I. Ruiz, E. Levesque, J. Labreuche, S. Jaber, G. Lassailly, S. Dharancy, E. Boleslawski, G. Lebuffe, E. Kipnis, P. Ichai, A. Coilly, E. De Martin, E. Vibert, A. Herrerro, D. Samuel, G.-P. Pageaux, P. Mathurin, F. Saliba
Journal: Journal of Hepatology (2016)
Clinical Validation of a Non-Invasive Lipidomic Test for the Diagnosis of Non-Alcoholic Fatty Liver Disease
Authors: P. Salvador, S. Blanco, N.M. Irazabal-Remuiñan, I. Martínez-Arranz, L.F. Eraña-Ledesma, I. Mincholé, F. Menéndez, R. Mayo, P. Ruiz, R. González-Monasterio, E. Delgado, J.I. Arenas, M. Martos, A. Otegui, G. Arregui, M.C. Eizmendi, S. Urquiola, R.S. Vicente, A. Castro, P. Ortiz, J.I. Pijoán, J. Bustamante
Journal: Journal of Hepatology (2016)
Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials
Authors: Nicholas J Viney, Julian C van Capelleveen, Richard S Geary, Shuting Xia, Joseph A Tami, Rosie Z Yu, Santica M Marcovina, Steven G Hughes, Mark J Graham, Rosanne M Crooke, Stanley T Crooke, Joseph L Witztum, Erik S Stroes, Sotirios Tsimikas
Journal: The Lancet (2016)
Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma
Authors: Inger S. Nijhof, Laurens E. Franssen, Mark-David Levin, Gerard M. J. Bos, Annemiek Broijl, Saskia K. Klein, Harry R. Koene, Andries C. Bloem, Aart Beeker, Laura M. Faber, Ellen van der Spek, Paula F. Ypma, Reinier Raymakers, Dick-Johan van Spronsen, Peter E. Westerweel, Rimke Oostvogels, Jeroen van Velzen, Berris van Kessel, Tuna Mutis, Pieter Sonneveld, Sonja Zweegman, Henk M. Lokhorst, Niels W. C. J. van de Donk
Journal: Blood (2016)
P222 Rates of hospitalisation after diagnosis of lung cancer: A linked audit and Hospital Episode Statistics study: Abstract P222 Table 1
Authors: A Khakwani, RB Hubbard, LJ Tata
Journal: Thorax (2015)

<h3></h3> Much of the research in lung cancer is concerning survival or treatment rates and little is known about the rate of hospitalisation (emergency/elective) following the diagnosis of lung cancer. Newly diagnosed English patients from the National Lung Cancer Audit database (NLCA), 2007–2011, were linked with Hospital Episode Statistics (HES) data to provide details on their subsequent hospital admissions. Hospitalisations for receipt of chemotherapy or cardiothoracic surgery were excluded to ensure only non-treatment related admissions were included. We only included patients included who survived at least 30 days after their first presentation to a physician to exclude more advanced disease. We calculated rates and rate ratios (RR) of elective and emergency admissions per person-year (ppy) by patient features including sex, age, performance status and co-morbidity. Among 92,482 patients, there were 261,121 non-treatment related hospitalisations with rate of 2.92 admissions ppy (95% CI, 2.91–2.93). Emergency admissions constituted 57% of all admissions at a rate of 1.66 admissions ppy while the elective admission rate was lower at 1.26 admission ppy. Adjusted RRs in Table 1 show that males were approximately 20% more likely than females to be admitted through either route (RR 1.17, 95% CI 1.16 – 1.18 for emergency and 1.20 (1.18–1.21) for elective). Worsening performance status, co-morbidity and advanced stage were all associated with higher emergency admissions while there was no strong association with age. For elective admissions pattern were similar yet associations were weaker and performance status did not show a linear association with admissions. Increasing socioeconomic deprivation was associated with a moderate increase emergency admission rates but a decrease elective admission rates. The rate of emergency admissions was higher than the rate of elective admissions following diagnosis of lung cancer. Sex, worsening performance status, advanced stage and co-morbidity were all independently associated with admissions with similar patterns for emergency and elective admissions. However, being from a more deprived socioeconomic class was associated with more emergency admissions and fewer elective admissions. Reason for these findings could be related to variation in receiving treatment in these groups or treatment related side effects leading to more emergency admissions.
Keratin 23 Represents a Novel Liver Injury Marker Reflecting the Severity of Ductular Reaction
Authors: N. Guldiken, G.K. Ensari, P. Lahiri, G. Couchy, C. Preisinger, C. Liedtke, H.W. Zimmermann, M. Ziol, J. Zucman-Rossi, C. Trautwein, P. Strnad
Journal: Journal of Hepatology (2016)
Prevents HBV Reactivation with Tenofovir in Anti-HBC Positive Patients with Hematologic Malignancies Treated with Rituximab. Results Final Visit 18-Months (Preblin Study)
Authors: M. Buti, M.L. Manzano, R.M. Morillas, M. García-Retortillo, L. Martín, M. Prieto, M.L. Gutiérrez, E. Suárez, F. Gil-Ares, J. López, P. Castillo, M. Rodríguez, J.M. Zozaya, M.A. Simón, L.E. Morano, J.L. Calleja, R. Esteban
Journal: Journal of Hepatology (2016)
Importance of amygdala noradrenergic activity and large-scale neural networks in regulating emotional arousal effects on perception and memory
Authors: Benno Roozendaal, Laura Luyten, Lycia D de Voogd, Erno J Hermans
Journal: Behavioral and Brain Sciences (2016)

Abstract Mather and colleagues postulate that norepinephrine promotes selective processing of emotionally salient information through local “hotspots” where norepinephrine release interacts with glutamatergic activity. However, findings in rodents and humans indicate that norepinephrine is ineffective in modulating mnemonic processes in the absence of a functional amygdala. We therefore argue that emphasis should shift toward modulatory effects of amygdala-driven changes at the network level.
HCV Reinfection Incidence and Outcomes among HIV Infected MSM in Western Europe
Authors: T.C. Martin, P. Ingiliz, A. Rodger, H.J. Stellbrink, S. Mauss, C. Boesecke, M. Mandorfer, A. Baumgarten, J. Bottero, S. Bhagani, K. Lacombe, M. Nelson, J. Rockstroh
Journal: Journal of Hepatology (2016)
TCL1 Expression in B-Cell Tumors Is Dynamically Regulated by Maturation Stage, Proliferation, and the Follicular Microenvironment.
Authors: Marco Herling, Ryuji Kobayashi, Kaushali A. Patel, Kong Chao Chang, Ellen Schlette, George Z. Rassidakis, L. Jeffrey Medeiros, Dan Jones
Journal: Blood (2004)
An Integrated Safety and Efficacy Analysis of Sofosbuvir-Based Regimens in Patients with Hereditary Bleeding Disorders
Authors: K.R. Reddy, C. Stedman, K. Workowski, J.C. Yang, L.M. Stamm, M. Lin, D.M. Brainard, J.G. McHutchison, G.P. Balba, E.J. Gane, C. Walsh
Journal: Journal of Hepatology (2016)
A phase II randomized, double-blind, placebo-controlled study to evaluate naldemedine for the treatment of opioid-induced constipation (OIC) in patients with cancer pain.
Authors: Narikazu Boku, Nobuyuki Katakami, Shiro Fujita, Koji Oda, Katsunori Tauchi, Ken Nakata, Katsunori Shinozaki, Motoyasu Okuno, Yasukazu Kawai, Hiroaki Kikukawa, Ryujiro Suzuki, Hideo Nakazawa, Hiroshi Kojima, Mitsuhiro Mizutani, Toru Hara, Takaaki Yokota, Yura Suzuki, Masaru Narabayashi
Journal: Journal of Clinical Oncology (2015)

9594 Background: While opioid analgesics play a central role in managing cancer pain, opioid-induced constipation (OIC) is one of the most common side effects. Naldemedine is a novel peripherally-acting μ-opioid receptor antagonist (PAMORA) being developed to treat OIC. Methods: This study assessed naldemedine doses of 0.1, 0.2, or 0.4 mg once-daily (QD) for 2 weeks in cancer patients with OIC. Eligibility criteria included: regular opioid use for ≥ 2 weeks, ≤ 5 spontaneous bowel movements (SBMs) during a 14-day screening period despite laxative use. The primary endpoint was the change from baseline in frequency of SBM/week during the 2-week treatment period. The SBM responder rate, defined as ≥ 3 SBMs/week and an increase from baseline of ≥ 1 SBM/week, was a secondary endpoint. Safety assessments included adverse events (AEs), Clinical Opiate Withdrawal Scale (COWS) questionnaire and 11-point Numerical Rating Scale (NRS) pain questionnaire. Patients scored bowel movement (BM) consistency using the Bristol Stool Scale; BMs with a score of 7 were to be reported as AEs of diarrhea. The primary analysis was conducted using ANCOVA with frequency of SBM/week at baseline as a covariate. The planned total sample size was 212 (53 per group) to ensure at least 80% power in the two-sample t-test with a level of significance of 0.05 (two-sided). Results: A total of 227 patients were randomized to one of three naldemedine doses or placebo (PBO). The least-squares mean of change from baseline in frequency of SBM/week was 1.50 for PBO, 3.43 for 0.1 mg (P = 0.0465), 4.75 for 0.2 mg (P = 0.0007), and 7.29 for 0.4 mg (P < 0.0001). All three groups demonstrated a significantly higher SBM responder rate vs. PBO. The most common AE was diarrhea (25.0%, 26.8%, 39.7% and 51.8% in PBO, 0.1, 0.2, 0.4 mg groups, respectively). Most AEs of diarrhea were mild. No clinically meaningful changes in NRS scores or COWS scores were observed. Conclusions: In this study naldemedine was effective and generally well tolerated in patients with cancer pain with OIC. Based on its efficacy and safety profile, 0.2 mg QD was selected as the dose for phase 3 studies. (Clinical trial information: JapicCTI-111510) Clinical trial information: JapicCTI-111510.
Central nervous system metastases (CNSm) in patients with colorectal cancer (CRC): A retrospective review.
Authors: F. Rivera, L. Calera, L. Gutierrez-Sanz, I. Hernandez-Garcia, C. López-López, N. Vega-Gil, M. Salcedo, Y. Blanco, J. I. Mayordomo, J. Sanz-Ortiz
Journal: Journal of Clinical Oncology (2010)

e14105 Background: CNSm are infrequent events in patients (pts) with CRC and only a few number of retrospective and small studies have been published in this setting. We present the results of a retrospective analysis focused on this topic. Methods: Between 1991 and 2009, clinical records from 3551 CRC pts treated at our institution were analysed: 2103 pts developed systemic metastases and 44 pts (1.2 %) developed CNSm. Results: Median age of CNSm pts was 66 years (range 23-80) and 33 pts were males (70%). Primary location: colon 27 pts (61%), rectum 17 pts (39%). ECOG: 0-1: 23 pts, 2: 13 pts, 3: 6 pts. CNS was the only metastatic site in 11 pts (25%) and in the remaining 33 pts there were also lung (22 pts), liver (20 pts), bone (6 pts) or distant lymph node (6 pts) metastases. Twelve pts (27%) presented CNSm at diagnosis of CRC and 32 pts (73%) developed CNSm after a median of 23 months (range 2-107). In 18 pts (41%) there was only one CNSm; the more frequently involved locations were the parietal lobe (8 pts, 18%) and the cerebellum (5 pts, 11%). Eleven pts (25%) suffered neurologic deficits, 8 pts (18%) seizures, 5 pts (11%) headache and 5 pts behaviour disorders. Treatment after CNSm diagnosis: 22 pts (50%) received only best supportive care, 14 pts (32%) were treated with radiotherapy, 3 pts (7%) with surgery, 2 pts (4%) with radio- surgery, 1 patient (2%) with surgery plus radiotherapy and only 1 patient was treated with chemotherapy (5FU-oxaliplatin). Three pts (7%) treated with surgery were rendered disease free and two of these pts (4%) remained alive and disease free after a follow up of 18.7 and 17.8 months. The other 42 pts have died with progressive disease and median overall survival was 2 months. Conclusions: CNSm are infrequent events in CRC pts. The prognosis of these pts is poor and their treatment remains a challenge. No significant financial relationships to disclose.
Decreased Activity of Plasma ADAMTS13 Parallels Enhanced Endotoxemia in Patients with Severe Acute Pancreatitis: Relationship to Multiorgan Failure
Authors: Chie Morioka, Masahito Uemura, Tomomi Matsuyama, Masanori Matsumoto, Masao Fujimoto, Seiji Kato, Masatoshi Ishikawa, Hiromichi Ishizashi, Tatsuhiro Tsujimoto, Hideto Kawaratani, Kazuo Okuchi, Kenji Nishio, Yoshihiro Fujimura, Hiroshi Fukui
Journal: Blood (2008)
Bringing Blood-Based Molecular Testing to the Clinic
Authors: Filip Janku, Razelle Kurzrock
Journal: Clinical Cancer Research (2016)

In cancer, plasma-derived cell-free DNA can be used for detection of oncogenic aberrations relevant for treatment selection. A cell-free DNA-based test for EGFR mutations has been approved as an alternative to tumor tissue analysis in lung cancer. Testing for other aberrations, including copy number alterations, continues to be investigated. Clin Cancer Res; 22(22); 5400-2. ©2016 AACRSee related article by Chicard et al., p. 5564.
Relationship between Baseline Hepatic Disease Severity and the Cardiometabolic and Anti-Inflammatory Effects of Elafibranor in Patients with Non-Alcoholic Steatohepatitis
Authors: S.M. Francque, S.A. Harrison, A. Sanyal, P. Bedossa, L. Serfaty, M. Romero-Gomez, J. Boursier, M. Abdelmalek, S. Caldwell, J. Drenth, Q. Anstee, D. Hum, R. Hanf, A. Roudot, S. Megnien, B. Staels, V. Ratziu
Journal: Journal of Hepatology (2016)
CYP51 Liver Knockout Mice – a New Model of Sex-Dependent Progression to Nash and Hepatocellular Carcinoma
Authors: D. Rozman, Ziga Urlep, Kaja Blagotinsek, Martina Perse, Jera Jeruc, G. Lorbek, U. Kovac, Z. Urlep, P. Juvan, M. Perse, J. Jeruc
Journal: Journal of Hepatology (2016)
Monosomal Karyotype In Myelodysplastic Syndromes, with or without Monosomy 7 or 5, Is Prognostically Worse Than An Otherwise Complex Karyotype
Authors: Mrinal M. Patnaik, Curtis A. Hanson, Janice Hodnefield, Ryan Knudson, Van Dyke L Daniel, Ayalew Tefferi
Journal: Blood (2010)
Prognostic Effect Of More Than 1 Extranodal Site Of Disease For Patients With Diffuse Large B Cell Lymphoma (DLBCL) In The Rituximab Era: Results From The UK NCRI R-CHOP 14 Versus 21 Trial
Authors: Wendi Qian, David Cunningham, FMedSci, Eliza Hawkes, Andrew Jack, Paul Smith, Paul Mouncey, Christopher Pocock, Kirit M Ardeshna, John Radford, Andrew McMillan, John Davies, Deborah Turner, Anton Kruger, Peter Johnson, Joanna Gambell, David Linch
Journal: Blood (2013)
Short-Term Outcomes following Hepatectomy in Elderly Patients with Hepatocellular Carcinoma: An Analysis of 10,805 Septuagenarians and 2,381 Octo-Nonagenarians in Japan
Authors: Hiroko Okinaga, Hideo Yasunaga, Kiyoshi Hasegawa, Kiyohide Fushimi, Norihiro Kokudo
Journal: Journal of Hepatology (2016)
IMPS-40ENHANCED VERSIONS OF THE ANTI-EGFRvIII VACCINE REVEAL A POTENTIAL NEW PARADIGM FOR ANTIGEN RECOGNITION AND VACCINE OPTIMIZATION
Authors: Albert Wong, Puja Gupta, Anin Sayana, Brandon Vu
Journal: Neuro-Oncology (2015)

An anti-EGFRvIII peptide vaccine for treating glioblastoma (Rindopepimut) has shown significant clinical potential, recently receiving Breakthrough Therapy Designation from the FDA. Interestingly, we created this vaccine before MHC binding principles were understood so the sequence was arbitrarily chosen and never optimized for immune response. X-ray diffraction of the EGFRvIII peptide reveals that it has structure, unusual for a 13 amino acid peptide, and the novel glycine at the junction, thought to be essential, is not critical for immune recognition. However, the glycine is at a hinge so we hypothesized this position is important for secondary structure. In our EGFRvIII/NIH-3T3 syngeneic tumor model, we tested substitution of the glycine by all 19 other amino acids, length variations, synthetic amino acids and deletion of the glycine (-Gly) (N = 16 or greater for 24 peptides tested). Several substitutions, including Ala, Val, Pro, show a >58% improved survival rate over Rindopepimut. Most substitutions were similar to Rindopepimut, but some, including His, Cys and -Gly, were comparable to control. All peptides elicited antibodies specific for EGFRvIII with a general trend towards high titer (>1:2x105) in the higher performing vaccines. CTL responses by Elispot revealed that the highest performing vaccines elicited a >42% increase in spots over Rindopepimut (p 19 cleavage products, including recombination to form a larger products at ∼2600Da. Rindopepimut produced ∼14 fragments with lower amounts of the 2600Da, while the poorest vaccines showed almost no cleavage and no 2600Da. Our results show that more robust vaccines against EGFRvIII can be produced, that 3D structure is important, and the vaccine shows unexpected complex processing. Further work is being performed to bring these vaccines to clinical trial.
Effect of Sofosbuvir/Daclatasvir ± Ribavirin on the Pharmacokinetics of Calcineurin Inhibitors in Liver Transplant Recipients – from the ANRS CO23 Cupilt Study
Authors: A. Barrail-Tran, C. Laforest, T. Gelé, J. Dumortier, V. Leroy, R. Anty, G.-P. Pageaux, J.-C. Duclos-Vallée, A.-M. Taburet, A. Coilly
Journal: Journal of Hepatology (2016)
Liver Stiffness Assessed by Transient Elastography can not Predict the Hemodynamic Response to Non-Selective Betablockers
Authors: S. Bota, M. Mandorfer, P. Schwabl, T. Reiberger, M. Trauner, A. Ferlitsch, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2016)
Amyloid cast tubulopathy: a unique form of immunoglobulin-induced renal disease
Authors: I-A Iliuta, A P Garneau, E Latulippe, P Isenring
Journal: Blood Cancer Journal (2016)

Excess production of monoclonal immunoglobulins (Ig) occurs in ~1% of all individuals beyond the age of 50.1 The overall prevalence of kidney disease in this condition, that is, of Ig-induced kidney disease (Ig-KD) is over 20%, and its presence is associated with a wide variety of nephropathological lesions (Table 1) as well as underlying pathogenic mechanisms.
ABSENCE OF MAJOR DELETIONS OR REARRANGEMENTS OF CARDIAC MYOSIN HEAVY-CHAIN GENES IN FAMILIAL HYPERTROPHIC CARDIOMYOPATHY
Authors: G Tanigawa, H Watkins, J A Jarcho, C C Morton, J G Seidman, C E Seidman
Journal: Circulation (1993)

Familial hypertrophic cardiomyopathy can be caused by mutation of cardiac myosin heavy chain genes. We demonstrate that major deletions or other structural rearrangements of the cardiac myosin heavy chain locus are not responsible for familial hypertrophic cardiomyopathy in most affected individuals. Cell lines from unrelated affected individuals with familial hypertrophic cardiomyopathy were analyzed, 47 by fluorescent in situ hybridization and 20 by Southern blotting with α- and β-cardiac myosin heavy chain probes. All cell lines contain two copies each of the α- and β-cardiac myosin heavy chain genes, and no rearrangements were detected. We therefore predict that missense mutations are the predominant cardiac myosin heavy chain defects that cause familial hypertrophic cardiomyopathy
Practice-Level Variation in Statin Use Among Patients With Diabetes
Authors: Yashashwi Pokharel, Kensey Gosch, Vijay Nambi, Paul S. Chan, Mikhail Kosiborod, William J. Oetgen, John A. Spertus, Christie M. Ballantyne, Laura A. Petersen, Salim S. Virani
Journal: Journal of the American College of Cardiology (2016)
The Challenge of Molecular Testing for Clinical Trials in Advanced Non-Small Cell Lung Cancer Patients: Analysis of a Prospective Database
Authors: Stefanie Lepers, Anouck Ottevaere, Christel Oyen, Liesbeth Peeters, Erik Verbeken, Christophe Dooms, Kristiaan Nackaerts, Johan Vansteenkiste
Journal: Journal of Thoracic Oncology (2015)
Land use, transport, and population health: estimating the health benefits of compact cities
Authors: Mark Stevenson, Jason Thompson, Thiago Hérick de Sá, Reid Ewing, Dinesh Mohan, Rod McClure, Ian Roberts, Geetam Tiwari, Billie Giles-Corti, Xiaoduan Sun, Mark Wallace, James Woodcock
Journal: The Lancet (2016)
S85 Pneumolysin triggers the production of platelet-activating factor by human neutrophils in vitro: Abstract S85 Table 1
Authors: R Anderson, JG Nel, AJ Theron, TJ Mitchell, C Feldman
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Pneumolysin (Ply), the major protein virulence factor of the pneumococcus, has been implicated in the pathogenesis of acute lung injury and acute coronary events, both of which are significant causes of mortality, in severe pneumococcal disease. However, the role of Ply in promoting neutrophil/platelet cross-talk, increasingly recognised as a key event in the immunopathogenesis of inflammation-mediated pulmonary and cardiovascular damage is unknown. This issue has been addressed in the current study, which is focused on the effects of exposure of isolated human blood neutrophils to Ply on the production of the platelet-targeted, pro-inflammatory lipids, platelet-activating factor (PAF) and thromboxane A<sub>2</sub> (TXA<sub>2</sub>). <h3>Methods</h3> Neutrophils, isolated from the blood of healthy, adult humans, were suspended at a concentration of 2 × 10<sup>6</sup>/ml in Hanks balanced salt solution and preincubated for 10 min at 37°C followed by addition of recombinant Ply (5–80 ng/ml), or the pneumolysoid, delta6Ply (80 ng/ml, negative control), or the calcium ionophore, A23187, (2 μM, positive control). After 5 min of incubation, the reactions were terminated and PAF and TXA<sub>2</sub> assayed in the cell-free supernatants using sandwich ELISA procedures. <h3>Results</h3> These are shown in the accompanying Table 1. Exposure of neutrophils to Ply resulted in dose-related enhancement of production of PAF, which achieved statistical significance at concentrations ≥20 ng/ml of the toxin, while delta6Ply was ineffective, and A23187 extremely potent. Similar, but less impressive effects were noted in the case of TXA<sub>2</sub>. <h3>Conclusion</h3> Ply, via its pore-forming activity, activates the production of PAF and, to a lesser extent, TXA<sub>2,</sub> by neutrophils, potentially augmenting pro-inflammatory cross-talk between these cells and platelets, an activity of the toxin which may contribute to the immunopathogenesis of lung and cardiac injury in severe pneumococcal disease.