tbuckley/cabot-search huggingface dataset:
Histamine release in immediate-type hypersensitivity reactions in intact human skin measured by microdialysis.
Authors: L.J. Petersen, P. Stahl Skov, C. Bindslev‐Jensen, J. Søndergaard
Journal: Allergy (1992)

The purpose of this study was to evaluate the application of a microdialysis technique for measurement of interstitial histamine levels in intact human skin. Three allergic subjects were investigated. Single dialysis fibers were glued to nylon tubings and inserted in forearm skin by means of a fine cannula. Dialysis fibers were inserted in triplicate and perfused with isotonic saline at a rate of 3 μl/min. After a period of 2 h a 60‐μl base‐line period was established. Then the patients were skin prick tested (SPT) with allergen in duplicate and a single saline control. Dialysate was collected in consecutive 30 μl fractions. Histamine concentration in the dialysate was analyzed with a glass fiber fluorescence assay. Median base‐line histamine level was 4 (range 4–7) ng/ml. Following allergen SPT, dialysate histamine concentration increased to 81 ng/ml (74–128), with maximum values 10–20 min after SPT. Intraindividual coefficient of variation on peak histamine levels was 18.9%. No histamine increase was seen following saline SPT. We consider microdialysis to be a valuable method for assessment of allergic mechanisms in intact human skin.
Nasal Sinusitis in Children
Authors: W. K. Hughes
Journal: BMJ (1940)

1.<h3>Abstract</h3> Among viruses, human immunodeficiency virus (HIV) presents the greatest challenge to humans. Here, we retrieved genome sequences from NCBI and were then run through LALIGN bioinformatics software to compute the E value, bit score, Waterman eggert score, and percent identity, which are four important indicators of how similar the sequences are. The E value was 3.1 x 10^-9, the percent identity was 54.4 percent, and the bit score was 51.9. It was also sensed that bases 1600 to 1990 in HIV and bases 800 to 910 in FIV have a higher than normal similarity. This reflects that while the DNA sequences of the gag region of both the HIV and FIV genomes are rather similar, it is unlikely that this similarity is due to random chance; therefore, there are a noticeable number of differences. A better understanding of the level of similarity and differences in the gag region of the genome sequence would facilitate our understanding of structural and cellular behavioral differences between FIV and HIV, and in the long term, it will provide new insights into the differences observed in previous studies or even facilitate the development of an effective HIV treatment.
Artificial neural network is superior to MELD in predicting mortality of patients with end-stage liver disease
Authors: A Cucchetti, M Vivarelli, N D Heaton, S Phillips, F Piscaglia, L Bolondi, G La Barba, M R Foxton, M Rela, J O'Grady, A D Pinna
Journal: Gut (2006)

<b>Background:</b> Despite its accuracy, the model for end-stage liver disease (MELD), currently adopted to determine the prognosis of patients with liver cirrhosis, guide referral to transplant programmes and prioritise the allocation of donor organs, fails to predict mortality in a considerable proportion of patients. <b>Aims:</b> To evaluate the possibility to better predict 3-month liver disease-related mortality of patients awaiting liver transplantation using an artificial neural network (ANN). <b>Patients and methods:</b> The ANN was constructed using data from 251 consecutive people with cirrhosis listed for liver transplantation at the Liver Transplant Unit, Bologna, Italy. The ANN was trained to predict 3-month survival on 188 patients, tested on the remaining 63 (internal validation group) unknown by the system and finally on 137 patients listed for liver transplantation at the King's College Hospital, London, UK (external cohort). Predictions of survival obtained with ANN and MELD on the same datasets were compared using areas under receiver-operating characteristic (ROC) curves (AUC). <b>Results:</b> The ANN performed significantly better than MELD both in the internal validation group (AUC = 0.95 <i>v</i> 0.85; p = 0.032) and in the external cohort (AUC = 0.96 <i>v</i> 0.86; p = 0.044). <b>Conclusions:</b> The ANN measured the mortality risk of patients with cirrhosis more accurately than MELD and could better prioritise liver transplant candidates, thus reducing mortality in the waiting list.
Effect of smoking on the lipid composition of lung lining fluid and relationship between immunostimulatory lipids, inflammatory cells and foamy macrophages in extrinsic allergic alveolitis
Authors: DA Hughes, PL Haslam
Journal: European Respiratory Journal (1990)

Normal lung lining fluid suppresses lymphoproliferative responses. This effect is mediated by the major phospholipid components, but minor lipid components can stimulate lymphocyte proliferation. The aim of this study was to discover whether the changes in lung lipid composition reported in patients with extrinsic allergic alveolitis (EAA) might influence the levels of lymphocytes which occur in the lungs of these patients. Since cigarette smokers are less susceptible to EAA, we also investigated the effect of smoking on the lipid composition of lung lining fluid. Lung lining fluid was sampled by bronchoalveolar lavage (BAL) from 15 patients with EAA, and 9 non-smokers and 13 smokers without lung disease. The smoking controls had increases in phosphatidylethanolamine, sphingomyelin and phosphatidylglycerol, but lower levels of cholesterol and cholesterol:total phospholipid ratios compared with the nonsmoking controls. By contrast, the patients with EAA had increases in total phospholipid and sphingomyelin; there were no smoking related decreases in cholesterol; and several patients had levels of cholesterol and cholesterol:total phospholipid ratios above the upper limit for the controls. In the BAL fluids of the EAA patients, the levels.ml-1 of the immunostimulatory lipids sphingomyelin, phosphatidylethanolamine, cholesterol and cholesterol esters correlated with the number.ml-1 of lymphocytes, mast cells, neutrophils and "foamy" macrophages. Cholesterol levels (rs = 0.82) and lymphocyte counts (rs = 0.90) correlated most closely with "foamy" macrophages (p less than 0.001), suggesting that uptake of cholesterol by macrophages may enhance antigen-presenting function. These observations provide some support for the hypothesis that inflammatory reactions in the lungs might be influenced by the local lipid environment.
The early reduction of leukemic blasts in bone marrow on day 6 of induction treatment is predictive for complete remission rate and survival in adult acute myeloid leukemia; The results of multicenter, prospective Polish adult leukemia group study
Authors: Sebastian Grosicki, Jerzy Holowiecki, Sebastian Giebel, Slawomira Kyrcz‐Krzemien, Kazimierz Kuliczkowski, Marek Kielbinski, Aleksander B. Skotnicki, Beata Piatkowska‐Jakubas, Andrzej Hellmann, Agnieszka Wierzbowska, Beata Stella‐Holowiecka, Barbara Zdziarska, Malgorzata Calbecka
Journal: American Journal of Hematology (2011)

The aim of this study was to prospectively evaluate the impact of early bone marrow response on complete remission (CR) rate and long-term outcome in adults with acute myeloid leukemia. Bone marrow cytology was assessed on day 6 of induction treatment in 164 patients, revealing the presence of ≥5% blasts in 61 cases. In this subgroup the CR rate was significantly lower compared to the remaining patients (P < 0.00001) resulting in decrease of the overall survival (P = 0.002). Persistence of ≥5% blasts in bone marrow on day 6 of induction is an easily available surrogate marker to be used for treatment decisions.
Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial
Authors: Philip A Poole-Wilson, Jacobus Lubsen, Bridget-Anne Kirwan, Fred J van Dalen, Gilbert Wagener, Nicolas Danchin, Hanjörg Just, Keith AA Fox, Stuart J Pocock, Tim C Clayton, Michael Motro, John D Parker, Martial G Bourassa, Anthony M Dart, Per Hildebrandt, Åke Hjalmarson, Johannes A Kragten, G Peter Molhoek, Jan-Erik Otterstad, Ricardo Seabra-Gomes, Jordi Soler-Soler, Simon Weber
Journal: The Lancet (2004)
Pooled Analysis of Fluorouracil-Based Adjuvant Therapy for Stage II and III Colon Cancer: Who Benefits and by How Much?
Authors: Sharlene Gill, Charles L. Loprinzi, Daniel J. Sargent, Stephan D. Thomé, Steven R. Alberts, Daniel G. Haller, Jacqueline Benedetti, Guido Francini, Lois E. Shepherd, Jean Francois Seitz, Roberto Labianca, Wei Chen, Stephen S. Cha, Michael P. Heldebrant, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2004)

Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain.Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets.Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients.Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs. This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.
Aging Mesenchymal Stem Cells Fail to Protect Because of Impaired Migration and Antiinflammatory Response
Authors: Martha L. Bustos, Luai Huleihel, Maria G. Kapetanaki, Christian L. Lino-Cardenas, Lyle Mroz, Bryon M. Ellis, Bryan J. McVerry, Thomas J. Richards, Naftali Kaminski, Nayra Cerdenes, Ana L. Mora, Mauricio Rojas
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Aging is characterized by functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. With age, there is an increase in the incidence and severity of chronic and acute lung diseases. However, the relationship between age and the lung’s reduced ability to repair is far from established and necessitates further research in the field.Objectives: Little is currently known about age-related phenomena in mesenchymal stem cells (MSCs). On account of their ability to protect the endothelium and the alveolar epithelium through multiple paracrine mechanisms, we looked for adverse effects that aging might cause in MSC biology. Such age-related changes might partly account for the increased susceptibility of the aging lung to injury.Measurements and Main Results: We demonstrated that old mice have more inflammation in response to acute lung injury. To investigate the causes, we compared the global gene expression of aged and young bone marrow–derived MSCs (B-MSCs). Our results revealed that the expression levels of inflammatory response genes depended on the age of the B-MSCs. We demonstrated that the age-dependent decrease in expression of several cytokine and chemokine receptors is important for the migration and activation of B-MSCs. Finally, we showed by adoptive transfer of aged B-MSCs to young endotoxemic mice that aged cells lacked the antiinflammatory protective effect of their young counterparts.Conclusions: Taken together, the decreased expression of cytokine and chemokine receptors in aged B-MSCs compromises their protective role by perturbing the potential of B-MSCs to become activated and mobilize to the site of injury.
<i>Trypanosoma cruzi</i> –Infected Cardiomyocytes Produce Chemokines and Cytokines That Trigger Potent Nitric Oxide–Dependent Trypanocidal Activity
Authors: Fabiana S. Machado, Gislâine A. Martins, Júlio C. S. Aliberti, Fabiola L. A. C. Mestriner, Fernando Q. Cunha, João S. Silva
Journal: Circulation (2000)

The pathogenesis of myocarditis that occurs in Trypanosoma cruzi-infected mice is still poorly understood. Therefore, it is important to know the mediators that trigger leukocyte migration to the heart as well as the cellular source of these possible mediators. In this study, we investigated (1) NO synthase (NOS) induction, (2) NO synthesis, (3) trypanocidal activity, and (4) chemokine and cytokine mRNA expression by isolated cardiomyocytes infected with T cruzi.Mouse cardiomyocytes were isolated, infected with T cruzi, and evaluated for induction of inducible NOS (iNOS), nitrite production, trypanocidal activity, and cytokine and chemokine mRNA expression. We found that T cruzi-infected murine embryonic cardiomyocytes produced nitrite and expressed mRNAs for the chemokines chemokine growth-related oncogene, monokine induced by interferon-gamma, macrophage inflammatory protein-2, interferon-gamma-inducible protein, RANTES, and monocyte chemotactic protein, for iNOS, and for the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Separate addition of IL-1beta, interferon-gamma, TNF-alpha or monocyte chemotactic protein, macrophage inflammatory protein-2, and interferon-gamma-inducible protein, to cultured cardiomyocytes resulted in NO production but low trypanocidal activity. However, simultaneous addition of IL-1beta, interferon-gamma, and TNF-alpha or the chemokines to cultures resulted in the induction of iNOS, high levels of nitrite, and a marked trypanocidal activity. The iNOS/L-arginine pathway mediated the latter activity, inasmuch as it was inhibited by treatment with N:(G)-monomethyl-L-arginine.These results indicate that iNOS activation and the proinflammatory cytokines and chemokines produced by cardiomyocytes are likely to control parasite growth and cell influx, thus contributing to the pathogenesis of chagasic cardiomyopathy seen in T cruzi-infected mice.
Report of an international working group to standardize response criteria for myelodysplastic syndromes
Authors: B. D. Cheson, J. M. Bennett, Hagop M Kantarjian, A. Pinto, C. A. Schiffer, S. D. Nimer, B. Lowenberg, M. Beran, T. M. De Witte, R. M. Stone, M. Mittelman, G. F. Sanz, P. W. Wijermans, S. Gore, P. L. Greenberg
Journal: Blood (2000)
Diagnostic value of confocal laser endomicroscopy for gastric superficial cancerous lesions
Authors: W.-B. Li, X.-L. Zuo, C.-Q. Li, F. Zuo, X.-M. Gu, T. Yu, C.-L. Chu, T.-G. Zhang, Y.-Q. Li
Journal: Gut (2010)

<h3>Background</h3> The identification of gastric superficial cancerous lesions based on conventional white-light endoscopy (WLE) is challenging, and histological analysis remains the 'gold standard' for the final diagnosis. Confocal laser endomicroscopy (CLE) can provide in vivo histological observation without the need for biopsy. <h3>Objective</h3> To develop and evaluate CLE imaging criteria for gastric superficial cancerous lesions and to compare the diagnostic value of real-time integrated CLE (iCLE) and WLE alone in distinguishing gastric superficial cancerous lesions. <h3>Design</h3> Prospective study. <h3>Setting</h3> Qilu Hospital, Shandong University, Jinan, China. <h3>Patients</h3> A total of 182 patients were enrolled into phase I and 1786 patients were enrolled into phase II. <h3>Interventions</h3> CLE images were blindly evaluated after endoscopy in phase I, and real-time iCLE diagnosis during endoscopy was compared with WLE diagnosis by using histopathology as a gold standard in phase II. <h3>Main outcome measurements</h3> The validity and reliability of the CLE diagnosis for identifying gastric superficial cancerous lesions. <h3>Results</h3> Off-line CLE diagnosis for early gastric cancers had a high sensitivity (88.1%) and specificity (98.6%). When the two-tiered CLE classification of non-cancerous lesions and cancer/high-grade intraepithelial neoplasia (HGIN) lesions was introduced, CLE diagnosis led to a higher sensitivity (90.2%) and specificity (98.5%) (phase I). Real-time iCLE diagnosis had a higher sensitivity (88.9%), specificity (99.3%) and accuracy (98.8%) for gastric superficial cancer/HGIN lesions than WLE diagnosis (sensitivity, 72.2%; specificity, 95.1%; and accuracy, 94.1%) (p&lt;0.05) (phase II). <h3>Limitations</h3> This was a single-centre study. <h3>Conclusions</h3> CLE can be used to identify gastric superficial cancer/HGIN lesions with high validity and reliability.
KRas Induces a Src/PEAK1/ErbB2 Kinase Amplification Loop That Drives Metastatic Growth and Therapy Resistance in Pancreatic Cancer
Authors: Jonathan A. Kelber, Theresa Reno, Sharmeela Kaushal, Cristina Metildi, Tracy Wright, Konstantin Stoletov, Jessica M. Weems, Frederick D. Park, Evangeline Mose, Yingchun Wang, Robert M. Hoffman, Andrew M. Lowy, Michael Bouvet, Richard L. Klemke
Journal: Cancer Research (2012)

Early biomarkers and effective therapeutic strategies are desperately needed to treat pancreatic ductal adenocarcinoma (PDAC), which has a dismal 5-year patient survival rate. Here, we report that the novel tyrosine kinase PEAK1 is upregulated in human malignancies, including human PDACs and pancreatic intraepithelial neoplasia (PanIN). Oncogenic KRas induced a PEAK1-dependent kinase amplification loop between Src, PEAK1, and ErbB2 to drive PDAC tumor growth and metastasis in vivo. Surprisingly, blockade of ErbB2 expression increased Src-dependent PEAK1 expression, PEAK1-dependent Src activation, and tumor growth in vivo, suggesting a mechanism for the observed resistance of patients with PDACs to therapeutic intervention. Importantly, PEAK1 inactivation sensitized PDAC cells to trastuzumab and gemcitabine therapy. Our findings, therefore, suggest that PEAK1 is a novel biomarker, critical signaling hub, and new therapeutic target in PDACs.
Epigenome-wide Association Study of Breast Cancer Using Prospectively Collected Sister Study Samples
Authors: Zongli Xu, Sophia C.E. Bolick, Lisa A. DeRoo, Clarice R. Weinberg, Dale P. Sandler, Jack A. Taylor
Journal: JNCI Journal of the National Cancer Institute (2013)

Previous studies have suggested DNA methylation in blood is a potential epigenetic marker of cancer risk, but this has not been evaluated on a genome-wide scale in prospective studies for breast cancer. We measured DNA methylation at 27578 CpGs in blood samples from 298 women who developed breast cancer 0 to 5 years after enrollment in the Sister Study cohort and compared them with a random sample of 612 cohort women who remained cancer free. We also genotyped women for nine common polymorphisms associated with breast cancer. We identified 250 differentially methylated CpGs (dmCpGs) between case subjects and noncase subjects (false discovery rate [FDR] Q < 0.05). Of these dmCpGs, 75.2% were undermethylated in case subjects relative to noncase subjects. Women diagnosed within 1 year of blood draw had small but consistently greater divergence from noncase subjects than did women diagnosed at more than 1 year. Gene set enrichment analysis identified Kyoto Encyclopedia of Genes and Genomes cancer pathways at the recommended FDR of Q less than 0.25. Receiver operating characteristic analysis estimated a prediction accuracy of 65.8% (95% confidence interval = 61.0% to 70.5%) for methylation, compared with 56.0% for the Gail model and 58.8% for genome-wide association study polymorphisms. The prediction accuracy of just five dmCpGs (64.1%) was almost as good as the larger panel and was similar (63.1%) when replicated in a small sample of 81 women with diverse ethnic backgrounds. Methylation profiling of blood holds promise for breast cancer detection and risk prediction.
Cytochrome P-450 Content and the Ability of Liver Microsomes From Patients Undergoing Abdominal Surgery to Alter the Mutagenicity of a Primary and a Secondary Carcinogen2
Authors: Peter Czygan, Helmut Greim, Anthony J. Garro, Ferenc Hutterer, Jack Rudick, Fenton Schaffner, Hans Popper
Journal: JNCI Journal of the National Cancer Institute (1973)

The capacity of microsomes isolated from patients undergoing abdominal surgery to alter the mutagenicity of a primary and a secondary carcinogen was investigated and related to the cytochrome P-450 content of the liver. Such microsomes activated the mutagenic effect on bacteria of the secondary carcinogen dimethylnitrosamine and inactivated that of the primary carcinogen N-methyl-N- nitro-N-nitrosoguanidine. The differential ability of microsomes to alter mutagenicity varied in parallel with cytochrome P-450 content. This suggests great variability in the capacity of patients, examined to metabolize carcinogens by their microsomes.
Detection of interleukin-2 in addition to interferon-γ discriminates active tuberculosis patients, latently infected individuals, and controls
Authors: R. Biselli, S. Mariotti, V. Sargentini, I. Sauzullo, M. Lastilla, F. Mengoni, V. Vanini, E. Girardi, D. Goletti, R. D’ Amelio, R. Nisini
Journal: Clinical Microbiology and Infection (2009)