tbuckley/cabot-search huggingface dataset:
Critical role of the CD40 CD40-ligand pathway in regulating mucosal inflammation-driven angiogenesis in inflammatory bowel disease
Authors: S Danese, F Scaldaferri, S Vetrano, T Stefanelli, C Graziani, A Repici, R Ricci, G Straface, A Sgambato, A Malesci, C Fiocchi, S Rutella
Journal: Gut (2007)

Angiogenesis is a novel component in inflammatory bowel disease (IBD) pathogenesis. We have previously shown that immune-nonimmune interactions through the CD40-CD40-ligand (CD40L) pathway might sustain gut inflammation, although their effect on regulating inflammation-driven angiogenesis is unknown. The present study evaluated the role of the CD40-CD40L interaction in the promotion of immune-mediated angiogenesis in IBD.Human nonimmune cells of colonic origin-namely, human intestinal fibroblasts (HIFs) and human intestinal microvascular endothelial cells (HIMECs)-were activated with either soluble CD40L (sCD40L), or CD40(+) D1.1 cells or CD40L-activated lamina propria T (LPT) cells before measuring pro-angiogenic cytokine release. Blocking antibodies to either CD40 or CD40L were used to disrupt the CD40-CD40L interaction. The dextran sodium sulphate (DSS) model of experimental colitis in CD40 and CD40L knockout mice was established to assess whether the CD40-CD40L pathway was implicated in controlling inflammation-driven angiogenesis in vivo.Engagement of CD40 on HIFs promoted the release of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and hepatocyte growth factor (HGF). LPT cells were potent inducers of pro-angiogenic cytokine secretion by HIFs. Supernatants from sCD40L-activated HIFs induced migration of HIMECs and tubule formation, both of which were inhibited by blocking antibodies to either VEGF, IL-8 or HGF. Both CD40- and CD40L-deficient mice were protected from DSS-induced colitis and displayed a significant impairment of gut inflammation-driven angiogenesis, as assessed by microvascular density.The CD40-CD40L pathway appears to be crucially involved in regulating inflammation-driven angiogenesis, suggesting that strategies aimed at blocking CD40-CD40L interactions might be beneficial in acute and chronic intestinal injury.
Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)
Authors: P Emery, P Durez, M Dougados, C W Legerton, J-C Becker, G Vratsanos, H K Genant, C Peterfy, P Mitra, S Overfield, K Qi, R Westhovens
Journal: Annals of the Rheumatic Diseases (2009)

Background Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA. Objective To determine the impact of T-cell costimulation modulation in patients with UA or very early RA. Methods In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept (∼10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years. Results At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) −20.5% (−47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group. Conclusion Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.
Magnetically Targeted Nanocapsules for PAA‐Cisplatin‐Conjugated Cores in PVA/SPIO Shells via Surfactant‐Free Emulsion for Reduced Nephrotoxicity and Enhanced Lung Cancer Therapy
Authors: Chih‐Sheng Chiang, Yi‐Hsuan Tseng, Bang‐Jie Liao, San Yuan Chen
Journal: Advanced Healthcare Materials (2015)

Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is one of the most potent chemotherapy agents, but its side effects toward normal tissues, particularly toxicity in the kidney and nonspecific biodistribution, limit its ability to have significant clinical activity against a variety of solid tumors. A magnetic CDDP-encapsulated nanocapsule (CDDP-PAA-NC) with CDDP-polyacrylic acid (PAA) core in amphiphilic polyvinyl alcohol/superparamagnetic iron oxide nanoparticles shell is synthesized through a double emulsion to provide both high loading efficiency and controlled drug release. The CDDP-PAA-NCs significantly increase the blood circulation time of CDDP in vivo, with nearly 100-fold higher concentration, and drastically reduce side effects, including nephrotoxicity and hepatotoxicity, compared with the delivery of free CDDP. Furthermore, with a magnetic targeting effect, the CDDP-PAA-NCs show ninefold higher level accumulation in tumor tissue than the free CDDP treatment when administered at the equivalent dose, and mice treated with the CDDP-PAA-NCs display approximately 3.5-fold lower tumor volume than those of the control group on day 24. This result demonstrates that the magnetic CDDP-PAA-NCs, which are synthesized using a facile emulsion process, can significantly reduce toxicity and exhibit anticancer activity in A549-tumor bearing mice with negligible side effects.
Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability
Authors: Huixing Wu, Alexander Kuzmenko, Sijue Wan, Lyndsay Schaffer, Alison Weiss, James H. Fisher, Kwang Sik Kim, Francis X. McCormack
Journal: Journal of Clinical Investigation (2003)

The pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), have been reported to bind lipopolysaccharide (LPS), opsonize microorganisms, and enhance the clearance of lung pathogens. In this study, we examined the effect of SP-A and SP-D on the growth and viability of Gram-negative bacteria. The pulmonary clearance of Escherichia coli K12 was reduced in SP-A–null mice and was increased in SP-D–overexpressing mice, compared with strain-matched wild-type controls. Purified SP-A and SP-D inhibited bacterial synthetic functions of several, but not all, strains of E. coli, Klebsiella pneumoniae, and Enterobacter aerogenes. In general, rough E. coli strains were more susceptible than smooth strains, and collectin-mediated growth inhibition was partially blocked by coincubation with rough LPS vesicles. Although both SP-A and SP-D agglutinated E. coli K12 in a calcium-dependent manner, microbial growth inhibition was independent of bacterial aggregation. At least part of the antimicrobial activity of SP-A and SP-D was localized to their C-terminal domains using truncated recombinant proteins. Incubation of E. coli K12 with SP-A or SP-D increased bacterial permeability. Deletion of the E. coli OmpA gene from a collectin-resistant smooth E. coli strain enhanced SP-A and SP-D–mediated growth inhibition. These data indicate that SP-A and SP-D are antimicrobial proteins that directly inhibit the proliferation of Gram-negative bacteria in a macrophage- and aggregation-independent manner by increasing the permeability of the microbial cell membrane.
The number needed to treat provides additional insight on the performance of detection points of asthma exacerbations in self-management plans: authors’ response on behalf of the BIOAIR consortium
Authors: Maciej Kupczyk, Sven-Erik Dahlen
Journal: Thorax (2013)

We would like to thank Drs Honkoop and Sont for their interesting comments regarding our paper.1 We much appreciate the value of their original contribution on the early detection of asthma exacerbations.2 

In our study, in the BIOAIR asthma cohort, we have proven that among several studied variables, peak expiratory flow (PEF) and day symptoms provide the highest sensitivity and specificity for the detection of severe asthma exacerbations. This confirms that the selection of action points in the study by Honkoop et al 2 was optimal. However, data on other possible variables (eg, rescue medication use) are not discussed. We look forward to whether future studies confirm our finding that the use of short-acting β-agonists is no longer of value for the prediction of an exacerbation.

We agree that the …
MicroRNA Regulation of Oncolytic Herpes Simplex Virus-1 for Selective Killing of Prostate Cancer Cells
Authors: Cleo Y. F. Lee, Paul S. Rennie, William W.G. Jia
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Advanced castration-resistant prostate cancer, for which there are few treatment options, remains one of the leading causes of cancer death. MicroRNAs (miRNA) have provided a new opportunity for more stringent regulation of tumor-specific viral replication. The purpose of this study was to provide a proof-of-principle that miRNA-regulated oncolytic herpes simplex virus-1 (HSV-1) virus can selectively target cancer cells with reduced toxicity to normal tissues. Experimental Design: We incorporated multiple copies of miRNA complementary target sequences (for miR-143 or miR-145) into the 3′-untranslated region (3′-UTR) of an HSV-1 essential viral gene, ICP4, to create CMV-ICP4-143T and CMV-ICP4-145T amplicon viruses and tested their targeting specificity and efficacy both in vitro and in vivo. Results: Although miR-143 and miR-145 are highly expressed in normal tissues, they are significantly down-regulated in prostate cancer cells. We further showed that miR-143 and miR-145 inhibited the expression of the ICP4 gene at the translational level by targeting the corresponding 3′-UTR in a dose-dependent manner. This enabled selective viral replication in prostate cancer cells. When mice bearing LNCaP human prostate tumors were treated with these miRNA-regulated oncolytic viruses, a &amp;gt;80% reduction in tumor volume was observed, with significantly attenuated virulence to normal tissues in comparison with control amplicon viruses not carrying these 3′-UTR sequences. Conclusion: Our study is the first to show that inclusion of specific miRNA target sequences into the 3′-UTR of an essential HSV-1 gene is a viable strategy for restricting viral replication and oncolysis to cancer cells while sparing normal tissues. (Clin Cancer Res 2009;15(16):5126–35)
Clinical and laboratory features distinguishing pandemic H1N1 influenza-related pneumonia from interpandemic community-acquired pneumonia in adults
Authors: T. Bewick, P. Myles, S. Greenwood, J. S. Nguyen-Van-Tam, S. J. Brett, M. G. Semple, P. J. Openshaw, B. Bannister, R. C. Read, B. L. Taylor, J. McMenamin, J. E. Enstone, K. G. Nicholson, W. S. Lim
Journal: Thorax (2011)

<h3>Background</h3> Early identification of patients with H1N1 influenza-related pneumonia is desirable for the early instigation of antiviral agents. A study was undertaken to investigate whether adults admitted to hospital with H1N1 influenza-related pneumonia could be distinguished clinically from patients with non-H1N1 community-acquired pneumonia (CAP). <h3>Methods</h3> Between May 2009 and January 2010, clinical and epidemiological data of patients with confirmed H1N1 influenza infection admitted to 75 hospitals in the UK were collected by the Influenza Clinical Information Network (FLU-CIN). Adults with H1N1 influenza-related pneumonia were identified and compared with a prospective study cohort of adults with CAP hospitalised between September 2008 and June 2010, excluding those admitted during the period of the pandemic. <h3>Results</h3> Of 1046 adults with confirmed H1N1 influenza infection in the FLU-CIN cohort, 254 (25%) had H1N1 influenza-related pneumonia on admission to hospital. In-hospital mortality of these patients was 11.4% compared with 14.0% in patients with inter-pandemic CAP (n=648). A multivariate logistic regression model was generated by assigning one point for each of five clinical criteria: age ≤65 years, mental orientation, temperature ≥38°C, leucocyte count ≤12×10<sup>9</sup>/l and bilateral radiographic consolidation. A score of 4 or 5 predicted H1N1 influenza-related pneumonia with a positive likelihood ratio of 9.0. A score of 0 or 1 had a positive likelihood ratio of 75.7 for excluding it. <h3>Conclusion</h3> There are substantial clinical differences between H1N1 influenza-related pneumonia and inter-pandemic CAP. A model based on five simple clinical criteria enables the early identification of adults admitted with H1N1 influenza-related pneumonia.
Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages.
Authors: J A Martinez, S Prevot, B Nordlinger, T M Nguyen, Y Lacarriere, A Munier, I Lascu, J C Vaillant, J Capeau, M L Lacombe
Journal: Gut (1995)

Although a reduced expression of nm23 has been shown to correlate with a high metastatic potential in some human cancers, in colorectal cancers, conflicting data have been reported. As there are two homologous genes, nm23-H1 and nm23-H2, which encode the A and B subunits of nucleoside diphosphate kinase, efficient and simplified techniques were designed to selectively study nm23-H1 and -H2 expression in 35 colorectal cancers at both the protein and mRNA levels by immunoblotting, immunohistochemistry, and reverse transcription polymerase chain reaction (RT PCR) using specific antibodies and primers. Nm23-H1 and Nm23-H2 proteins were overexpressed in tumours compared with adjacent mucosa. This overexpression was lost, however, in some advanced cases: 89% and 81% of TNM (tumour, node, metastases) stages 0-II showed Nm23-H1 and -H2 overexpression, respectively, which significantly differed from 47% and 38% of stage III-IV tumours. Similar results were seen with nm23-H1 mRNA. Heterogenous labelling of tumoral cells was seen by immunohistological staining. This suggests a dichotomy: an overexpression of nm23-H1 and -H2 linked to early stages of cancer and a loss of nm23-H1 overexpression seen in more advanced stages. Therefore specific nm23-H1 determination should be evaluated as a prognostic factor in human colorectal carcinoma.
Randomized Clinical Trial of Abciximab in Diabetic Patients Undergoing Elective Percutaneous Coronary Interventions After Treatment With a High Loading Dose of Clopidogrel
Authors: Julinda Mehilli, Adnan Kastrati, Helmut Schühlen, Alban Dibra, Franz Dotzer, Nicolas von Beckerath, Hildegard Bollwein, Jürgen Pache, Josef Dirschinger, Peter P. Berger, Albert Schömig
Journal: Circulation (2004)

Diabetic patients are at increased risk of adverse outcomes after percutaneous coronary interventions. Although subset analyses suggest particular benefit from the administration of abciximab in diabetic patients, no dedicated large randomized trials have been performed in diabetic patients undergoing percutaneous coronary intervention, and certainly not after pretreatment with a high loading dose of clopidogrel.This study (Intracoronary Stenting and Antithrombotic Regimen: Is Abciximab a Superior Way to Eliminate Elevated Thrombotic Risk in Diabetics [ISAR-SWEET] Study) enrolled 701 diabetic patients with coronary artery disease who underwent an elective percutaneous coronary intervention after pretreatment with a 600-mg dose of clopidogrel >2 hours before the procedure: 351 patients were randomly assigned to abciximab and 350 patients to placebo. The primary end point of the trial was the composite incidence of death and myocardial infarction at 1 year. The frequency of angiographic restenosis (diameter stenosis > or =50%) was the secondary end point. The incidence of death or myocardial infarction was 8.3% in the abciximab group and 8.6% in the placebo group (P=0.91), with a relative risk of 0.97 (95% CI, 0.58 to 1.62). The incidence of angiographic restenosis was 28.9% in the abciximab group and 37.8% in the placebo group (P=0.01), with a relative risk of 0.76 (95% CI, 0.62 to 0.94). The incidence of target lesion revascularization was 23.2% in the abciximab group and 30.4% in the placebo group (P=0.03).The findings of this study do not support a significant impact of abciximab on the risk of death and myocardial infarction in diabetic patients undergoing percutaneous coronary interventions after pretreatment with a 600-mg loading dose of clopidogrel at least 2 hours before the procedure. The present findings suggest, however, that abciximab reduces the risk of restenosis in diabetic patients receiving coronary bare metal stents.
Test-retest reliability of the sport concussion assessment tool 2 (SCAT2) for uninjured children and young adults
Authors: Monica Chan, Jannick Vicky Vielleuse, Stephanie Vokaty, Matthew Ari Wener, Isabelle Pearson, Isabelle Gagnon
Journal: British Journal of Sports Medicine (2013)

Objective To establish test-retest reliability of the Sport Concussion Assessment Tool 2 (SCAT2) in healthy elementary school children and young adults. Design Repeated-measures design. Setting Elementary Schools in the Montreal area (children) and McGill University Athletics Department (adults). Participants Twenty-two children (14 females and eight males; mean age 10.3±0.5 years) and 73 young adults (42 female, 31 males; mean age 22.6±1.8 years) from University students participated in this study. Intervention None. Main Outcome Measurements Participants were tested using the Sport Concussion Assessment Tool-2 (SCAT2) on two occasions, 1-week apart (6.4±2.7 days). The SCAT2 measures several domains of functioning such as delayed memory, balance and post-concussion symptoms. Test-retest reliability was assessed for the total SCAT2 score as well as for the SCAT2 components separately. Results Intraclass Correlation Coefficients for the total SCAT2 score were only fair for both groups of participants (ICC=0.367 for young adults and 0.446 for children). The ICCs were also below 0.5 for individual components of the SCAT2 in young adults. In children, individual components yielded better reliability than the total score (Balance ICC=0.725; SAC ICC=0.523; symptom severity ICC=0.488). Conclusions The results indicate that in view of the low levels of test-retest reliability achieved for the total SCAT2 score, professionals should be cautious when using change in score over time for clinical decisions. Recommending the use of the SCAT2 as a standard of care to diagnose a concussion or to ascertain recovery from one may be premature at this time. Acknowledgments Participants and their families, The Priory School, Gardenview Elementary School for allowing testing within their institutions, Fonds de recherche du Québec-Santé, School of Physical and Occupational Therapy McGill University. Competing interests None.
Systemic Administration of Serotonin 2A/2C Agonist Improves Upper Airway Stability in Zucker Rats
Authors: Toshiyuki Ogasa, Andrew D. Ray, Charles P. Michlin, Gaspar A. Farkas, Brydon J. B. Grant, Ulysses J. Magalang
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The effects of [±]-2,5-dimethoxy-4-iodoaminophentamine, a serotonin2A/2C receptor agonist, on pharyngeal airflow mechanics were examined in isoflurane-anesthetized lean and obese Zucker rats. The pharyngeal pressure associated with flow limitation, maximum inspiratory flow, oronasal resistance, genioglossus muscle activity, and arterial blood pressure (BP) were measured before and after the intravenous administration of the agonist. A robust activation of the genioglossus muscle in all lean and obese rats was associated with decreased upper airway (UA) collapsibility (p < 0.05), unchanged maximum flow, and increased oronasal resistance (p < 0.05) in both groups. The changes in UA mechanics and BP after the drug were similar in lean and obese rats. The serotonin agonist had no effect on UA mechanics in a group of paralyzed (pancuronium bromide) rats, despite similar elevations in BP. There was a smaller decrease (p < 0.05) in UA collapsibility that was also associated with increased upstream resistance when the drug was administered after bilateral hypoglossal nerve transection. We conclude that systemic administration of a serotonin2A/2C receptor agonist improves UA collapsibility predominantly, but not exclusively, via stimulation of the hypoglossal nerves and also increases upstream resistance, at least in part, through activation of nonhypoglossal motoneuronal pools innervating the UA muscles.
Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles
Authors: C.A. Venetis, E.M. Kolibianakis, J.K. Bosdou, B.C. Tarlatzis
Journal: Human Reproduction Update (2013)

BACKGROUNDThe aim of this meta-analysis was to evaluate the association of progesterone elevation (PE) on the day of hCG administration with the probability of pregnancy in fresh, frozen–thawed and donor/recipient IVF cycles.
Antipsychotic Drugs: Comparison in Animal Models of Efficacy, Neurotransmitter Regulation, and Neuroprotection
Authors: Jeffrey A. Lieberman, Frank P. Bymaster, Herbert Y. Meltzer, Ariel Y. Deutch, Gary E. Duncan, Christine E. Marx, June R. Aprille, Donard S. Dwyer, Xin-Min Li, Sahebarao P. Mahadik, Ronald S. Duman, Joseph H. Porter, Josephine S. Modica-Napolitano, Samuel S. Newton, John G. Csernansky
Journal: Pharmacological Reviews (2008)

Various lines of evidence indicate the presence of progressive pathophysiological processes occurring within the brains of patients with schizophrenia. By modulating chemical neurotransmission, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and have the potential for neuroprotection. This article reviews the current literature describing preclinical and clinical studies that evaluate the efficacy of antipsychotic drugs, their mechanism of action and the potential of first- and second-generation antipsychotic drugs to exert effects on cellular processes that may be neuroprotective in schizophrenia. The evidence to date suggests that although all antipsychotic drugs have the ability to reduce psychotic symptoms via D<sub>2</sub> receptor antagonism, some antipsychotics may differ in other pharmacological properties and their capacities to mitigate and possibly reverse cellular processes that may underlie the pathophysiology of schizophrenia.
Treatment of myocardial ischaemia
Authors: G. R. Royston
Journal: BMJ (1967)

October, p. 129) restates the interesting association between the teratogenic and carcinogenic action of trypan blue.In fact observations which could account for the teratogenic action of the trypan blue group of compounds (acid bisazo dyes) have recently been made,' and it is interesting to speculate whether the same cellular disturbances might not also be related to some aspects of the oncogenic process.In rats trypan blue and related compounds are actively phagocytesed by macrophages and by certain extra-embryonic membranes, sub- sequently entering the vacuolar apparatus of the cells.They accumulate in hetero- lysosomes, and in this situation actively in- hibit the hydrolytic enzymes found in these organelles.In the context of placental function the short-term effect would appear to be an inhibition of embryotrophic nutrition leading to congenital malformation.Investigations to see whether lysosomal enzyme inhibition is in itself associated with carcino- genesis and whether such a cellular event could account for the development of reticu- loses are currently under way.-Weare, etc.,