tbuckley/cabot-search huggingface dataset:
Noninvasive assessment of airway inflammation in children: induced sputum, exhaled nitric oxide, and breath condensate
Authors: P G Gibson, R L Henry, P Thomas
Journal: European Respiratory Journal (2000)

Noninvasive markers of airway inflammation are needed for use in research and clinical practice in childhood asthma. Induced sputum and exhaled nitric oxide are well established as direct markers of inflammation for use in asthma research. Sputum can be induced from children of &gt;6 yrs using inhalation of hypertonic saline, and, if appropriate, can be combined with an assessment of airway responsiveness to hypertonic saline. The success rate of sputum induction in children is 68-100%. Most studies have processed sputum using the plug selection method, and show that the dominant cell in sputum from normal children is the macrophage, and that the upper normal limit for sputum eosinophils in children is 2.5%. The inflammatory response in childhood asthma is characterized by elevated numbers of sputum eosinophils, and eosinophil cationic protein concentration, as well as increased nitric oxide and hydrogen peroxide levels in exhaled breath. Sputum eosinophils correlate with objective markers of disease severity in steroid-naive children with asthma, and in severe asthma. Inflammatory marker levels are lower in children using glucocorticosteroids. Induced sputum and exhaled gases are important markers of inflammation in childhood asthma. The clinical utility of these markers warrants further study.
Correlation of CXCL10, Tumor Necrosis Factor Receptor Type II, and Galectin 9 With Disease Activity in Juvenile Dermatomyositis
Authors: F. Bellutti Enders, F. van Wijk, R. Scholman, M. Hofer, B. J. Prakken, A. van Royen‐Kerkhof, W. de Jager
Journal: Arthritis & Rheumatology (2014)

Objective Juvenile dermatomyositis (DM) is a systemic autoimmune disorder of unknown immunopathogenesis in which the immune system targets the microvasculature of skeletal muscles, skin, and other organs. The current mainstay of therapy is a steroid regimen in combination with other immunosuppressive treatments. To date, no validated markers for monitoring disease activity have been identified, which hampers personalized treatment. This study was undertaken to identify a panel of proteins specifically related to active disease in juvenile DM. Methods We performed a multiplex immunoassay for plasma levels of 45 proteins related to inflammation in 25 patients with juvenile DM in 4 clinically well‐defined groups, as determined by clinical activity and treatment. We compared them to 14 age‐matched healthy children and 8 age‐matched children with nonautoimmune muscle disease. Results Cluster analysis of circulating proteins showed distinct profiles for juvenile DM patients and controls based on a group of 10 proteins. In addition to CXCL10, tumor necrosis factor receptor type II (TNFRII) and galectin 9 were significantly increased in active juvenile DM. The levels of these 3 proteins were tightly linked to active disease and correlated with clinical scores (as measured by the Childhood Myositis Assessment Scale and physician's global assessment of disease activity on a visual analog scale). Conclusion Our findings indicate that CXCL10, TNFRII, and galectin 9 correspond to disease status in juvenile DM and thus could be helpful in monitoring disease activity and guiding treatment. Furthermore, they might provide new knowledge about the pathogenesis of this autoimmune disease.
PRODUCTION OF A RABBIT ANTIMOUSE EOSINOPHIL SERUM WITH NO CROSS-REACTIVITY TO NEUTROPHILS
Authors: Adel A. F. Mahmoud, Kenneth S. Warren, Dov L. Boros
Journal: The Journal of Experimental Medicine (1973)

Antieosinophil serum (AES), obtained by immunizing rabbits with a highly purified suspension of mouse eosinophils, contains high titers of specific agglutinating and cytotoxic antibodies to eosinophils. Absorption with macrophages, lymphocytes, and neutrophils does not affect the antieosinophilic activity while it is markedly lowered by absorption with eosinophils. One dose of AES (0.1 ml) injected into mice with schistosomiasis mansoni caused a mean decrease in circulating eosinophils of 90% within 1 h which was maintained for 5 days, followed by gradual recovery. No other changes in the total or differential white cell counts were noted. In normal mice AES markedly depressed exudation of eosinophils in the peritoneal cavity after repeated saline stimulation. Some of the immunological and clinical implications of a monospecific AES are discussed.
Macrophage Migration Inhibitory Factor Promotes Tumor Invasion and Metastasis via the Rho-Dependent Pathway
Authors: Bailong Sun, Jun Nishihira, Takashi Yoshiki, Masao Kondo, Yuji Sato, Fumiaki Sasaki, Satoru Todo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Macrophage migration inhibitory factor (MIF) plays an important role not only in the immune system but also in tumorigenesis. In this study, we investigated the potential role of MIF in association with tumor invasion and metastasis. Methods: To assess the function of MIF, we knocked down the MIF mRNA using small interfering RNA (siRNA). Twenty-one base siRNA specific for the mRNA sequence of mouse MIF was introduced to a murine colon cancer cell line, colon 26. Tumor cell invasion was evaluated using a transwell method (8-μm pores) coated with Matrigel on the upperside membrane and with fibronectin on the underside membrane. Moreover, we investigated the signal transduction of lysophosphatidic acid (LPA) relevant to the Rho-dependent pathway and further examined the effect of MIF siRNA on this signal transduction system. In vivo, the tumor cells were pretreated with MIF siRNA and injected into the portal vein, and the effects on metastasis to the liver were evaluated. Results: We found that MIF siRNA markedly reduced the invasion of the cells from the upperside to lowerside membranes. We revealed that the Rho-dependent pathway activated by LPA was suppressed by MIF siRNA. Next, we found that the tyrosine-phosphorylation of focal adhesion kinase and LPA-induced expressions of integrin β1 were significantly suppressed by MIF siRNA. In vivo, metastasis to the liver was significantly inhibited by pretreatment of the cells with MIF siRNA. Conclusion: Taken together, these results suggest that MIF promotes tumor invasion and metastasis via the Rho-dependent pathway.
Significance of changes in endurance shuttle walking performance
Authors: V. Pepin, L. Laviolette, C. Brouillard, L. Sewell, S. J. Singh, S. M. Revill, Y. Lacasse, F. Maltais
Journal: Thorax (2010)

The endurance shuttle walking test (ESWT) has shown good responsiveness to interventions in patients with chronic obstructive pulmonary disease (COPD). However, the minimal important difference (MID) for this test remains unknown, therefore limiting its interpretability.Patients with COPD who completed two or more ESWTs following pulmonary rehabilitation (n=132; forced expiratory volume in 1 s (FEV1) 48 ± 22%) or bronchodilation (n=69; FEV1 50 ± 12%) rated their performance of the day in comparison with their previous performance on a 7-point scale ranging from -3 (large deterioration) to +3 (large improvement). The relationship between subjective perception of changes and objective changes in performance during the shuttle walk was evaluated.Following pulmonary rehabilitation, the anchor-based approach did not allow a valid estimation of the MID in the ESWT performance to be obtained. After bronchodilation, patient ratings of change correlated significantly with the difference in walking distance (r=0.53, p<0.001) and endurance time (r=0.55, p<0.001). For the pharmacotherapy data, regression analysis indicated that a 65 s (95% CI 45 to 85) change in endurance time and a 95 m (95% CI 60 to 115) change in walking distance were associated with a 1-point change in the rating of change scale. These changes represented 13-15% of the baseline values.A change in endurance shuttle walking performance of 45-85 s (or 60-115 m) after bronchodilation is likely to be perceived by patients. This MID value may be specific to the intervention from which it was derived.
Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity
Authors: Ingunn M Stromnes, J Scott Brockenbrough, Kamel Izeradjene, Markus A Carlson, Carlos Cuevas, Randi M Simmons, Philip D Greenberg, Sunil R Hingorani
Journal: Gut (2014)

Pancreatic ductal adenocarcinoma (PDA) is characterised by a robust desmoplasia, including the notable accumulation of immunosuppressive cells that shield neoplastic cells from immune detection. Immune evasion may be further enhanced if the malignant cells fail to express high levels of antigens that are sufficiently immunogenic to engender an effector T cell response.To investigate the predominant subsets of immunosuppressive cancer-conditioned myeloid cells that chronicle and shape the progression of pancreas cancer. We show that selective depletion of one subset of myeloid-derived suppressor cells (MDSC) in an autochthonous, genetically engineered mouse model (GEMM) of PDA unmasks the ability of the adaptive immune response to engage and target tumour epithelial cells.A combination of in vivo and in vitro studies were performed employing a GEMM that faithfully recapitulates the cardinal features of human PDA. The predominant cancer-conditioned myeloid cell subpopulation was specifically targeted in vivo and the biological outcomes determined.PDA orchestrates the induction of distinct subsets of cancer-associated myeloid cells through the production of factors known to influence myelopoiesis. These immature myeloid cells inhibit the proliferation and induce apoptosis of activated T cells. Targeted depletion of granulocytic MDSC (Gr-MDSC) in autochthonous PDA increases the intratumoral accumulation of activated CD8 T cells and apoptosis of tumour epithelial cells and also remodels the tumour stroma.Neoplastic ductal cells of the pancreas induce distinct myeloid cell subsets that promote tumour cell survival and accumulation. Targeted depletion of a single myeloid subset, the Gr-MDSC, can unmask an endogenous T cell response, disclosing an unexpected latent immunity and invoking targeting of Gr-MDSC as a potential strategy to exploit for treating this highly lethal disease.
Role of Cell Cycle in Epidermal Growth Factor Receptor Inhibitor-Mediated Radiosensitization
Authors: Aarif Ahsan, Susan M. Hiniker, Mary A. Davis, Theodore S. Lawrence, Mukesh K. Nyati
Journal: Cancer Research (2009)

Epidermal growth factor receptor (EGFR) inhibitors are increasingly used in combination with radiotherapy in the treatment of various EGFR-overexpressing cancers. However, little is known about the effects of cell cycle status on EGFR inhibitor-mediated radiosensitization. Using EGFR-overexpressing A431 and UMSCC-1 cells in culture, we found that radiation activated the EGFR and extracellular signal-regulated kinase pathways in quiescent cells, leading to progression of cells from G(1) to S, but this activation and progression did not occur in proliferating cells. Inhibition of this activation blocked S-phase progression and protected quiescent cells from radiation-induced death. To determine if these effects were caused by EGFR expression, we transfected Chinese hamster ovary (CHO) cells, which lack EGFR expression, with EGFR expression vector. EGFR expressed in CHO cells also became activated in quiescent cells but not in proliferating cells after irradiation. Moreover, quiescent cells expressing EGFR underwent increased radiation-induced clonogenic death compared with both proliferating CHO cells expressing EGFR and quiescent wild-type CHO cells. Our data show that radiation-induced enhancement of cell death in quiescent cells involves activation of the EGFR and extracellular signal-regulated kinase pathways. Furthermore, they suggest that EGFR inhibitors may protect quiescent tumor cells, whereas radiosensitization of proliferating cells may be caused by downstream effects such as cell cycle redistribution. These findings emphasize the need for careful scheduling of treatment with the combination of EGFR inhibitors and radiation and suggest that EGFR inhibitors might best be given after radiation in order to optimize clinical outcome.
Cyclooxygenase-2 Induces EP1- and HER-2/Neu-Dependent Vascular Endothelial Growth Factor-C Up-Regulation
Authors: Jen-Liang Su, Jin-Yuan Shih, Men-Luh Yen, Yung-Ming Jeng, Cheng-Chi Chang, Chang-Yao Hsieh, Lin-Hung Wei, Pan-Chyr Yang, Min-Liang Kuo
Journal: Cancer Research (2004)

Abstract Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin H synthase, has been implicated in the progression of human lung adenocarcinoma. However, the mechanism underlying COX-2’s effect on tumor progression remains largely unknown. Lymphangiogenesis, the formation of new lymphatic vessels, has recently received considerable attention and become a new frontier of tumor metastasis research. Here, we study the interaction between COX-2 and the lymphangiogenic factor, vascular endothelial growth factor (VEGF)-C, in human lung cancer cells and their implication in patient outcomes. We developed an isopropyl-β-d-thiogalactopyranoside-inducible COX-2 gene expression system in human lung adenocarcinoma CL1.0 cells. We found that VEGF-C gene expression but not VEGF-D was significantly elevated in cells overexpressing COX-2. COX-2-mediated VEGF-C up-regulation was commonly observed in a broad array of non-small cell lung cancer cell lines. The use of pharmacological inhibitors or activators and genetic inhibition by EP receptor-antisense oligonucleotides revealed that prostaglandin EP1 receptor but not other prostaglandin receptors is involved in COX-2-mediated VEGF-C up-regulation. At the mechanistic level, we found that COX-2 expression or prostaglandin E2 (PGE2) treatment could activate the HER-2/Neu tyrosine kinase receptor through the EP1 receptor-dependent pathway and that this activation was essential for VEGF-C induction. The transactivation of HER-2/Neu by PGE2 was inhibited by way of blocking the Src kinase signaling using the specific Src family inhibitor, PP1, or transfection with the mutant dominant negative src plasmid. Src kinase was involved in not only the HER-2/Neu transactivation but also the following VEGF-C up-regulation by PGE2 treatment. In addition, immunohistochemical staining of 59 lung adenocarcinoma specimens showed that COX-2 level was highly correlated with VEGF-C, lymphatic vessels density, and other clinicopathological parameters. Taken together, our results provided evidence that COX-2 up-regulated VEGF-C and promotes lymphangiogenesis in human lung adenocarcinoma via the EP1/Src/HER-2/Neu signaling pathway.
Mesenteric vasculitis associated with Sezary syndrome.
Authors: R D Ellis, C H Smith, J R Goodlad, N P Smith, R P Thompson
Journal: Gut (1996)

A 71 year old lady with Sézary syndrome presented with chronic diarrhoea and cramping abdominal pains. A small bowel meal x ray examination showed two mid-ileal strictures. At laparotomy the small intestine was found to be sub-acutely obstructed and resection of a 15 cm ileal stricture and stricturoplasty of a second, 10 cm stricture were performed. Histological examination of the stricture revealed a mesenteric vasculitis with secondary ischaemic changes in the small bowel wall. Mesenteric vasculitis causing small bowel stricture may be associated with Sézary syndrome.
Clinical value of left atrial appendage flow for prediction of long-term sinus rhythm maintenance in patients with nonvalvular atrial fibrillation
Authors: Emanuele Antonielli, Alfredo Pizzuti, Attila Pálinkás, Mattia Tanga, N.oèmi Gruber, Claudio Michelassi, Albert Varga, Alessandro Bonzano, Nicola Gandolfo, L.ászló Halmai, Antonia Bassignana, Muhammad Babar Imran, Fabrizio Delnevo, Miklós Csanády, Eugenio Picano
Journal: Journal of the American College of Cardiology (2002)
Fibrinolytic response to tumor necrosis factor in healthy subjects.
Authors: T van der Poll, M Levi, H R Büller, S J van Deventer, J P de Boer, C E Hack, J W ten Cate
Journal: The Journal of Experimental Medicine (1991)

Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men, investigating the effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2) on the stimulation and inhibition of plasminogen activation as well as on plasmin activity and inhibition. TNF induced a brief fourfold increase in the overall plasma plasminogen activator (PA) activity peaking after 1 h (p less than 0.0001), which was associated with rises in the antigenic levels of urokinase-type plasminogen activator (p less than 0.0001) and tissue-type plasminogen activator (p less than 0.0001). Plasminogen activator inhibitor type I antigen remained unchanged in the first hour, but showed a rapid eightfold increase thereafter (p less than 0.0001), which coincided with the decrease in PA activity. Generation of plasmin activity in the first hour was signified by an 11-fold rise in D-dimer levels (p less than 0.0001); inhibition of plasmin was reflected by a 36-fold rise in plasmin-alpha 2 antiplasmin complexes (p less than 0.0001), as well as by a transient 16% decrease in alpha 2-antiplasmin activity (p less than 0.01). In conclusion, TNF induced an early activation of the fibrinolytic system becoming maximal in 1 h, with a rapid inhibition thereafter. Earlier observations in the same subjects showed sustained coagulation activation for 6-12 h. The observed disbalance between the procoagulant and fibrinolytic mechanisms after TNF injection confirms the in vivo relevance of the effects of TNF on vascular endothelium in vitro and may explain the tendency towards microvascular thrombosis in septicemia.
Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice
Authors: Maria Febbraio, Eugene A. Podrez, Jonathan D. Smith, David P. Hajjar, Stanley L. Hazen, Henry F. Hoff, Kavita Sharma, Roy L. Silverstein
Journal: Journal of Clinical Investigation (2000)

Macrophage scavenger receptors have been implicated as key players in the pathogenesis of atherosclerosis. To assess the role of the class B scavenger receptor CD36 in atherogenesis, we crossed a CD36-null strain with the atherogenic apo E–null strain and quantified lesion development. There was a 76.5% decrease in aortic tree lesion area (Western diet) and a 45% decrease in aortic sinus lesion area (normal chow) in the CD36-apo E double-null mice when compared with controls, despite alterations in lipoprotein profiles that often correlate with increased atherogenicity. Macrophages derived from CD36-apo E double-null mice bound and internalized more than 60% less copper-oxidized LDL and LDL modified by monocyte-generated reactive nitrogen species. A similar inhibition of in vitro lipid accumulation and foam cell formation after exposure to these ligands was seen. These results support a major role for CD36 in atherosclerotic lesion development in vivo and suggest that blockade of CD36 can be protective even in more extreme proatherogenic circumstances.
Endoscopic ultrasound in the follow up and response assessment of patients with primary gastric lymphoma
Authors: A Püspök, M Raderer, A Chott, B Dragosics, A Gangl, R Schöfl
Journal: Gut (2002)

Endoscopic ultrasound (EUS) is considered the best technique for local staging of primary gastric lymphomas. Its role in the follow up of patients with gastric lymphoma following organ conserving strategies has not been established.To compare endosonographic response assessment with results of histological evaluation.Thirty three patients with primary gastric lymphomas underwent pretreatment EUS and were followed endosonographically every 3-6 months after administration of organ conserving treatment modalities. A wall thickness of <or=4 mm with preserved five layer structure and the absence of suspicious lymph nodes was defined as endosonographic remission. Decrease in wall thickness, increase in echogenicity, and regression of lymph nodes were tested for their value to predict histological remission.A total of 158 endosonographies were performed (median 4; range 2-12). Within a median follow up period of 15 months (range 3-48), 27 (82%) patients achieved complete histological remission while endosonographic remission was found in 21 (64%) patients. Eighteen patients achieved both forms of remission, with endosonographic remission occurring later (35.1 (11-212.9) weeks v 17.6 (11-97.9) weeks; median (range); p<0.02) than histological remission. A further three patients demonstrated a false negative remission on EUS. Histological relapse was paralleled by endosonographic relapse in only one of five patients. None of the tested endosonographic parameters was able to predict histological remission.In view of the inferior accuracy of EUS when compared with histology, gastroscopy with biopsy seems sufficient for the routine follow up of patients with gastric lymphoma.
The TOPGAME-study: effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy
Authors: J Zwerver, I van den Akker-Scheek, F Hartgens, H van de Worp, E Verhagen, R L Diercks
Journal: British Journal of Sports Medicine (2011)

Background Patellar tendinopathy is a common and often difficult-to-treat knee injury in jumping athletes. Extracorporeal shockwave therapy (ESWT) appears to be a promising treatment but its effectiveness has not been studied in athletes who keep playing sports. Objective To determine the effectiveness of ESWT in athletes with patellar tendinopathy with short duration of symptoms who are still in training and competition. Design Multicenter two armed randomized controlled trial with blinded participants and outcome assessors. Setting and participants Non-elite athletes aged 18–35. 57 volleyball, one handball and four basketball players with patellar tendinopathy (symptoms 3–12 months). Of these, 57 completed the study Intervention of three focused ESWT treatments (or placebo) at a weekly interval. Main outcome measurements VISA-P score at 1, 12 and 22 weeks after the final treatment, when athletes were still in competition. Results The mean VISA-P scores before and after treatment are summarized below. There was a significant effect for time (p&lt;0.01) but no effect for treatment×time (p=0.82). One week after treatment more patients in the treatment group compared to patients in the placebo group evaluated the treatment as being beneficial (67% vs 37%, χ 2 =5.00 p=0.03). Mean VISA-P scores ESWT Placebo Before 59.4±11.7 62.4±13.4 After 1 week 66.8±16.2 66.3±19.0 After 12 week 66.7±17.5 68.9±20.3 After 22 week 70.5±18.9 72.7±8.0 Conclusions There was no effect of ESWT treatment protocol on the course of symptomatic patellar tendinopathy in jumping athletes who continued to train and compete.