tbuckley/cabot-search huggingface dataset:
Melanoma Cells Inhibit Natural Killer Cell Function by Modulating the Expression of Activating Receptors and Cytolytic Activity
Authors: Gabriella Pietra, Claudia Manzini, Silvia Rivara, Massimo Vitale, Claudia Cantoni, Andrea Petretto, Mirna Balsamo, Romana Conte, Roberto Benelli, Simona Minghelli, Nicola Solari, Marina Gualco, Paola Queirolo, Lorenzo Moretta, Maria Cristina Mingari
Journal: Cancer Research (2012)

Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function. We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2). Together, our findings suggest that immunosuppressive barriers erected by tumors greatly hamper the antitumor activity of human NK cells, thereby favoring tumor outgrowth and progression.
Excessive fibrinolysis in suspected amyloidosis: Demonstration of plasmin‐α2‐plasmin inhibitor complex and von Willebrand factor fragment in plasma
Authors: Hoyu Takahashi, Tadashi Koike, Nobuhiko Yoshida, Osamu Kitahara, Masaharu Hanano, Akira Shibata, Nobuo Aoki
Journal: American Journal of Hematology (1986)

We performed a hemostatic evaluation in detail in a patient with suspected amyloidosis who was suffering from several bleeding episodes. He had a shortened euglobulin clot lysis time, decreased alpha 2-plasmin inhibitor (alpha 2-PI), decreased plasminogen, elevated tissue-type plasminogen activator (t-PA), elevated plasmin-alpha 2-PI complex, and decreased ratio of ristocetin cofactor to von Willebrand factor (vWF) antigen. Fibrinogen and fibrin/fibrinogen degradation products levels fluctuated, with abnormal values on several occasions. On crossed immunoelectrophoresis, plasmin-alpha 2-PI complex and vWF fragment were demonstrated in the patient plasma. These abnormal findings and bleeding symptoms improved following the administration of tranexamic acid. Discontinuation of tranexamic acid resulted in deterioration of these parameters. These observations indicate that pathologic fibrinolysis (continuous intravascular plasmin generation) characterized by the consumption of alpha 2-PI and plasminogen, formation of plasmin-alpha 2-PI complex, and fragmentation of vWF contributed to the bleeding in this patient. It is important to recognize excessive fibrinolysis as the underlying cause of bleeding in these patients, since specific treatment with antifibrinolytic agents is effective in controlling the bleeding.
Contrast ultrasound molecular imaging of inflammation in cardiovascular disease
Authors: J. R. Lindner
Journal: Cardiovascular Research (2009)

The cellular immune response plays an important role in almost every major form of cardiovascular disease. The ability to image the key aspects of the immune response in the clinical setting could be used to improve diagnostic information, to provide important prognostic or risk information, and to customize therapy according to disease phenotype. Accordingly, targeted imaging probes for assessing inflammation have been developed for essentially all forms of medical imaging. Molecular imaging of inflammation with contrast ultrasound relies on the detection of targeted microbubble or other gas-filled particle contrast agents. These agents are confined to the vascular space and, hence, have been targeted to either activated leucocytes or endothelial cell adhesion molecules that are upregulated in inflammation and mediate leucocyte recruitment and adhesion. This review focuses on the inflammation-targeting strategies for ultrasound contrast agents and how they have been matched to cardiovascular disease states such as myocardial ischaemia, infarction, atherosclerosis, transplant rejection, and arteriogenesis.
What is the cause of the carcinoid flush?
Authors: D G Grahame-Smith
Journal: Gut (1987)

Leading articleWhat is the cause of the carcinoid flush?Between 1952 and 1954 the constellation of clinical signs and symptoms in patients with carcinoid tumours became known as the carcinoid syndrome.'In 1953, Lembeck' isolated 5-hydroxytryptamine (5-HT, serotonin) from a carcinoid tumour.Initially it was thought that the carcinoid flush was the result of 5-HT which was known to have pharmacological vascular actions.But it is not as simple as that.Clinical observation shows there are various types of flush'-namely, a diffuse erythematous flush affecting mainly the face, neck and upper anterior chest, but often spreading over the skin of the back and affecting the abdomen and palms.This flush is usually paroxysmal and short, lasting two to five minutes.Patients with this type of flush often look normal between flushes.The second type of flush has a violatious tinge to it.It affects the same areas, but lasts longer.The nose is often shining and purple during the flush, which frequently occurs on a background of permanent cyanotic flushing.These patients usually have a very high urinary 5HIAA output.The third type of flush is usually associated with bronchial carcinoid tumours.The flushes often last several hours and may even last days.The skin becomes red and often slightly purplish and body areas other than the usual flushing areas are involved.There is profuse lacrimation and the conjunctivae are suffused.The facial skin swells and the normal facial creases become exaggerated into deep folds.This type of flushing is extremely distressing.The fourth type of flush is bright red and patchy, the red flush is a particularly vivid red and the white patches seem particularly brightly white.Patchiness is most evident around the root of the neck.This type of flushing is usually associated with gastric carcinoid tumours and excess production of histamine.These different types of flushing must have a different pharmacology and are likely to be because of different substances alone, or in concert affecting different parts of the vascular bed of the skin.Robertson et al showed that 5-HT could not be the sole substance responsible for flushing.Quite simply 5-HT did not produce a true carcinoid flush when given intra- venously, nor did its concentrations usually rise in arterial plasma during a flush.Oates et al continued the search for the carcinoid flushing substance.In a series of investigations they found that the tumour contained kallikrein and that the hepatic venous blood draining carcinoid liver metastases contained a bradykinin like substance during an induced flush.They did, however, have some patients who did not release bradykinin into the circulation during flushing attacks.At that time the bradykinin was isolated and identified by various extraction techniques and bioassays.My colleagues and 1I measured arterial blood bradykinin concentrations during provoked carcinoid flush and in some patients the concentrations clearly increased, but plasma bradykinin 1413 on August 19,
Prognosis of ventilator-associated pneumonia: what lies beneath
Authors: S. Krüger, D. Frechen, S. Ewig
Journal: European Respiratory Journal (2011)

<h3>Background</h3> Applying the Australasian Triage Scale to pregnant women presenting to emergency departments (EDs) is difficult as the descriptors may not reflect the urgency of the obstetric condition. This study aimed to examine whether condition-specific algorithms and triage education improved triage assessment and documentation of pregnant women presenting to the ED. <h3>Method</h3> Algorithms with a decision aid for triage with minimum agreed descriptors were developed to triage two pregnancy conditions (pre-eclampsia and antepartum haemorrhage). Triage documentation was then audited before (n=50) and after (n=50) a triage education programme which introduced algorithms for both conditions. Significant differences were examined using χ<sup>2</sup> test with significance set at p&lt;0.05. <h3>Results</h3> The quality of documentation of specific clinically significant symptoms of pre-eclampsia improved considerably, including the presence of headache from 58% pre-education to 80% post-education (p=0.002), visual disturbances from 58% to 90% (p&lt;0.001), epigastric pain from 24% to 80% (p=0.002) and the presence of fetal movements from 62% to 90% (p=0.001). Documentation of descriptors for vaginal bleeding &gt;20 weeks gestation improved for estimation of blood loss from 54% to 86% (p&lt;0.001), patient ‘appearance’ from 32% to 62% (p=0.003) and, importantly, descriptions of patient9s own assessment of their well-being from 8% to 28% (p=0.009). <h3>Conclusion</h3> The introduction of triage education and condition-specific decision aids for triage markedly improved triage assessment and documentation. The application of algorithms may reduce clinical risk resulting from suboptimal triage of pregnant women presenting to EDs.
Effect of chest physiotherapy on blood gases of neonates treated by intermittent positive pressure respiration
Authors: R. Holloway, E. B. Adams, S. D. Desai, A. K. Thambiran
Journal: Thorax (1969)

The effect of standardized chest physiotherapy and hyperinflation on the blood gases of neonates being treated for tetanus by intermittent positive pressure respiration was investigated. It was found that physiotherapy and suction to remove secretions did not improve oxygen pressures but produced a small drop in both Paco<sub>2</sub> and Pao<sub>2</sub>. This was associated with a widening of the alveolar to arterial gradient for oxygen. During the hour that followed, blood oxygen pressure slowly returned to pre-physiotherapy levels. This could be hastened by hyperinflation (increasing the pressure delivered to the baby) after physiotherapy. Although hyperinflation restored blood oxygen pressures, it did so by a mechanism which left alveolar to arterial oxygen gradients unchanged. Moderate hyperinflation without physiotherapy produced small increases in blood oxygen tension, but also failed to restore completely arterial oxygen pressures of neonates on I.P.P.R. The results are discussed.
RESULTS OF IRRADIATING STAPHYLOCOCCUS AUREUS BACTERIOPHAGE WITH MONOCHROMATIC ULTRAVIOLET LIGHT
Authors: Frederick L. Gates
Journal: The Journal of Experimental Medicine (1934)

The incident energies required to kill Staphylococcus aureus or to inactivate its homologous bacteriophage have been measured at the various wave-lengths of the quartz mercury vapor arc between 238 and 302 mmicro and found to run strictly parallel, the readings for the S. aureus phage being obtained at a uniformly higher energy level. This difference in levels is of less significance than the striking similarity in the shapes of the energy curves, which indicate that in both instances the same organic structures are absorbing the radiations. The results are open to three interpretations. The most obvious is that the bacteriophage is a submicroscopic organism. Again, it is possible that the bacteriophage is a product of its own lytic action on the homologous bacterium and contains the essential structural units which in S. aureus also are destroyed by ultraviolet light and thus cause the death of the organism. A third, more remote explanation is that the phage, of wholly unknown nature, is absorbed on S. aureus material in so intimate a bond that the alteration of this material by irradiation renders the phage incapable of further lytic activity.
Early intervention studies in infants and preschool children with cystic fibrosis: are we ready?
Authors: Stephen Stick, Harm Tiddens, Paul Aurora, Per Gustafsson, Sarath Ranganathan, Paul Robinson, Margaret Rosenfeld, Peter Sly, Felix Ratjen
Journal: European Respiratory Journal (2013)

Cystic fibrosis (CF) lung disease starts early in life and progresses even in the absence of clinical symptoms. Therefore, sensitive outcome measures to quantify and track these early abnormalities in infants and young children are needed; both for clinical care and interventional trials. Currently, the efficacy of most therapeutic interventions in CF has not been tested in children under the age of 6 years and drug development programmes have focused on assessing safety rather than efficacy in this age group. This article summarises the current status for outcome measures that can be utilised in clinical trials in infants and children with CF. Two methodologies are specifically highlighted in this review; chest computed tomography to assess structural damage of the lung and multiple breath washout as a technique to quantify ventilation inhomogeneity. While not all questions regarding the utility of these outcome measures in infants and young children have been resolved, significant advances have been made and it now appears feasible to design and conduct adequately powered efficacy studies in this age group. This could be a crucial step to further improve outcomes in CF patients as initiating effective treatment early is considered essential to prevent permanent lung damage.
Influence of development and joint pathology on stromelysin enzyme activity in equine synovial fluid
Authors: P A J Brama
Journal: Annals of the Rheumatic Diseases (2000)

To investigate the role of stromelysin (MMP-3) activity in synovial fluid (SF) at different stages of development and in common joint disorders in the horse.Stromelysin activity was determined with a fluorogenic enzyme activity assay in SF of normal joints of fetal, juvenile and adult horses, and in SF of horses suffering from the developmental orthopaedic disease osteochondrosis (OC) or osteoarthritis (OA). Additionally, MMP-3 activity was expressed as a ratio of previously reported general MMP activity in the same SF samples.The levels of active stromelysin were 30-fold to 80-fold higher in SF from fetal horses than in SF from juvenile and mature animals (p<0.001). Juvenile horses (5 and 11 months of age) showed a twofold to threefold higher stromelysin activity than adult horses ( p<0.05). In OC joints, stromelysin activity was not significantly different from the activity in normal, age matched, control joints. In OA joints the activity was about four times higher than in normal joints (p<0.001). The ratio MMP-3 activity/general MMP activity did not change with age in normal, healthy joints. This ratio was more then twofold increased in OA joints compared with normal joints, indicating selective upregulation of gene expression or activation of proMMP-3, or both, in OA pathology.The significantly higher stromelysin activity in young individuals parallels the higher metabolic activity occurring at rapid growth and differentiation at early age. In OC, MMP-3 mediated matrix degradation appears to be not different from normal joints. The increased stromelysin activity in OA joints is in agreement with pathological matrix degradation. In these joints MMP-3 activity is selectively increased compared with normal joints.
PTU-010 Computational model predicts that portosystemic shunting is key to the development of hyperammonaemia in liver cirrhosis
Authors: L Noiret, S Baigent, M Jover Cobos, R Jalan
Journal: Gut (2012)

<h3>Introduction</h3> Hyperammonaemia occurs in patients with advanced cirrhosis, which is also associated with a major redistribution of blood flow (hyperdynamic circulation). Previous investigations have sought to explain hyperammonaemia on the basis of metabolic adaptation (enzymatic derangements). We hypothesised that hyperammonaemia is centrally linked to the haemodynamic disturbances caused by portal hypertension. To test this hypothesis, we developed a theoretical model, which predicted arterial ammonia levels when organ blood flow is modulated. <h3>Methods</h3> Assumptions on individual organ fluxes of ammonia (across the gut, liver, muscle, brain and kidney) were based on published arterio-venous differences and tracer kinetic data. In order to study the role of organ blood flow in isolation, we assumed that hepatic detoxification function and ammonia production were normal. A wide range of conditions was investigated (increased cardiac output, splanchnic vasodilation, low to high porto-systemic shunt fraction). In addition, we used scenarios of organ blood flow corresponding to Child Pugh A, B and C. Finally, we considered the effect of lowering ammonia release in the renal vein. <h3>Results</h3> Hyperammonaemia developed when the fraction of gastrointestinal blood shunted was more than 65%. The influence of redistribution of organ blood flow accounted for &lt;10% of the increase in arterial levels. Decrease in ammonia release in the renal vein may be sufficient to compensate for the increase in arterial ammonia due to shunted flow in Child Pugh A and B, but is insufficient in stage C. <h3>Conclusion</h3> Portosystemic shunting may be centrally involved in the generation of hyperammonaemia in liver cirrhosis. This can be partially attenuated by increased urinary ammonia excretion. In patients with cirrhosis, decreased hepatic functions and metabolic changes may further increase the arterial ammonia levels. <h3>Competing interests</h3> None declared.
HG-16 * THE ANTI-APOPTOTIC PROTEIN ARC IS OVER-EXPRESSED IN MALIGNANT GLIOMA AND CORRELATES WITH PATIENT OUTCOME
Authors: A. Kankean, M. Tsoli, J. Tsang, A. Chitranjan, S. Maleki, K. McDonald, D. Ziegler
Journal: Neuro-Oncology (2015)

BACKGROUND: Glioblastoma multiforme (GBM) is among the most malignant of cancers with poor long term survival. ARC is an anti-apoptotic protein that we have previously examined published microarray data sets and found that ARC is overexpressed in malignant gliomas with higher mRNA levels correlating with poor survival. We hypothesised that ARC expression on immunohistochemistry may be a novel prognostic marker, that ARC may engender tumour resistance to conventional and targeted therapies. METHODS: We analysed a tissue bank of 94 grade 2-4 gliomas and performed immunohistochemistry (IHC) to assess ARC protein levels in high grade gliomas and correlation with patient outcomes. To assess the biological role of ARC in GBM we used siRNA and shRNA to suppress ARC expression and used an ARC plasmid to induce over-expression in U87 and U118 GBM cells. Following lenti-viral knock down, ARC expression was measured by western blot and PCR on the U87 VIII cells with non-silencing, empty vector and 2 shRNA variants. The biological effects of ARC silencing or overexpression, either alone or in combination with radiotherapy was measured using cell proliferation, clonogenic, caspase 3/7 activity and scratch assays. RESULTS: The IHC analysis of 94 glioma specimens showed that ARC protein levels in malignant gliomas specimens increased significantly with higher tumour grade. Increased protein levels of ARC in all high grade gliomas and separately in GBM, corresponded with reduced patient survival. Functional studies showed no impact on cell proliferation, colony formation, caspase 3/7 activity or sensitivity to radiation therapy or other cytotoxic therapies. CONCLUSION: Our findings indicate that ARC expression by IHC correlates with tumour grade and is a potential prognostic indicator and marker of higher grade malignant tumours. Functional studies showed no impact of ARC expression on tumour progression, apoptosis or treatment sensitivity indicating that increased ARC expression is likely a secondary phenomenon.
Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fasligand system in patients with chronic heart failure
Authors: Stamatis Adamopoulos, John Parissis, Dimitrios Karatzas, Christos Kroupis, Michael Georgiadis, George Karavolias, John Paraskevaidis, Katerina Koniavitou, Andrew J.S Coats, Dimitrios Th Kremastinos
Journal: Journal of the American College of Cardiology (2002)
Analysis of Apoptosis Protein Expression in Early-Stage Colorectal Cancer Suggests Opportunities for New Prognostic Biomarkers
Authors: Maryla Krajewska, Hoguen Kim, Chul Kim, Haeyoun Kang, Kate Welsh, Shu-ichi Matsuzawa, Michelle Tsukamoto, Ronald G. Thomas, Nuria Assa-Munt, Zhe Piao, Koichi Suzuki, Manuel Perucho, Stan Krajewski, John C. Reed
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Although most stage II colon cancers are potentially curable by surgery alone, ∼20% of patients relapse, suggesting a need for establishing prognostic markers that can identify patients who may benefit from adjuvant chemotherapy. We tested the hypothesis that differences in expression of apoptosis-regulating proteins account for differences in clinical outcome among patients with early-stage colorectal cancer. Experimental Design: Tissue microarray technology was employed to assay the expression of apoptosis-regulating proteins by immunohistochemistry in 106 archival stage II colorectal cancers, making correlations with disease-specific survival. The influence of microsatellite instability (MSI), tumor location (left versus right side), patient age, and gender was also examined. Results: Elevated expression of several apoptosis regulators significantly correlated with either shorter (cIAP2; TUCAN) or longer (Apaf1; Bcl-2) overall survival in univariate and multivariate analyses. These biomarkers retained prognostic significance when adjusting for MSI, tumor location, patient age, and gender. Moreover, certain combinations of apoptosis biomarkers were highly predictive of death risk from cancer. For example, 97% of patients with favorable tumor phenotype of cIAP2low plus TUCANlow were alive at 5 years compared with 60% of other patients (P = 0.00003). In contrast, only 37% of patients with adverse biomarkers (Apaf1low plus TUCANhigh) survived compared with 83% of others at 5 years after diagnosis (P&amp;lt; 0.0001). Conclusions: Immunohistochemical assays directed at detection of certain combinations of apoptosis proteins may provide prognostic information for patients with early-stage colorectal cancer, and therefore could help to identify patients who might benefit from adjuvant chemotherapy or who should be spared it.
Measuring intracellular pH in the heart using hyperpolarized carbon dioxide and bicarbonate: a 13C and 31P magnetic resonance spectroscopy study
Authors: Marie A. Schroeder, Pawel Swietach, Helen J. Atherton, Ferdia A. Gallagher, Phillip Lee, George K. Radda, Kieran Clarke, Damian J. Tyler
Journal: Cardiovascular Research (2009)

Technological limitations have restricted in vivo assessment of intracellular pH (pHi) in the myocardium. The aim of this study was to evaluate the potential of hyperpolarized [1-13C]pyruvate, coupled with 13C magnetic resonance spectroscopy (MRS), to measure pHi in the healthy and diseased heart. Hyperpolarized [1-13C]pyruvate was infused into isolated rat hearts before and immediately after ischaemia, and the formation of 13CO2 and H13CO3− was monitored using 13C MRS. The HCO3−/CO2 ratio was used in the Henderson–Hasselbalch equation to estimate pHi. We tested the validity of this approach by comparing 13C-based pHi measurements with 31P MRS measurements of pHi. There was good agreement between the pHi measured using 13C and 31P MRS in control hearts, being 7.12 ± 0.10 and 7.07 ± 0.02, respectively. In reperfused hearts, 13C and 31P measurements of pHi also agreed, although 13C equilibration limited observation of myocardial recovery from acidosis. In hearts pre-treated with the carbonic anhydrase (CA) inhibitor, 6-ethoxyzolamide, the 13C measurement underestimated the 31P-measured pHi by 0.80 pH units. Mathematical modelling predicted that the validity of measuring pHi from the H13CO3−/13CO2 ratio depended on CA activity, and may give an incorrect measure of pHi under conditions in which CA was inhibited, such as in acidosis. Hyperpolarized [1-13C]pyruvate was also infused into healthy living rats, where in vivo pHi from the H13CO3−/13CO2 ratio was measured to be 7.20 ± 0.03. Metabolically generated 13CO2 and H13CO3− can be used as a marker of cardiac pHiin vivo, provided that CA activity is at normal levels.