tbuckley/cabot-search huggingface dataset:
The Cytolytically Inactive Terminal Complement Complex Activates Endothelial Cells to Express Adhesion Molecules and Tissue Factor Procoagulant Activity
Authors: Francesco Tedesco, Mario Pausa, Ermanno Nardon, Martino Introna, Alberto Mantovani, Aldo Dobrina
Journal: The Journal of Experimental Medicine (1997)

The membrane attack complex of complement (C) in sublytic concentrations stimulates endothelial cells (EC) to express adhesion molecules and to release biologically active products. We have examined the ability of a cytolytically inactive form of this complex, which is incapable of inserting into the cell membrane, to upregulate the expression of adhesion molecules and of tissue factor (TF) procoagulant activity. The inactive terminal C complex (iTCC) was prepared by mixing C5b6, C7, C8, and C9 and was purified by fast protein liquid chromatography on a Superose 12 column. Binding of this complex to EC was found to be dose dependent and was inhibited by anti-C9 antibodies, as assessed both by ELISA using an mAb anti-C9 neoantigen and by measuring cell-bound 125I-labeled iTCC. Exposure of EC to iTCC resulted in a dose- and time-dependent expression of endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 accompanied by increased levels of the corresponding mRNA, but not in the rapid expression of P-selectin. Inactive TCC also induced increased TF activity evaluated by a chromogenic assay that measures the formation of factor Xa. These effects were inhibited by anti-C9 antibodies. The data support the conclusion that iTCC may induce proinflammatory and procoagulant activities on EC.
Worsening Renal Function and Outcome in Heart Failure Patients With Preserved Ejection Fraction and the Impact of Angiotensin Receptor Blocker Treatment
Authors: Kevin Damman, Ana C. Perez, Inder S. Anand, Michel Komajda, Robert S. McKelvie, Michael R. Zile, Barrie Massie, Peter E. Carson, John J.V. McMurray
Journal: Journal of the American College of Cardiology (2014)
Occupational asthma from sensitisation to 4,4-methylene-bismorpholine in clean metalworking fluid
Authors: Gareth I. Walters, Vicky C. Moore, Alastair S. Robertson, Emmet E. McGrath, Edward Parkes, P. Sherwood Burge
Journal: European Respiratory Journal (2013)

To the Editor: 

European Respiratory Society guidelines on the management of work-related asthma recommend that occupational asthma with an allergic mechanism should be diagnosed by both identifying the workplace as the cause, and confirming sensitisation to the asthmagen by specific inhalational challenge (SIC), in the absence of any available specific IgE tests [1, 2]. Used (contaminated) metalworking fluid is the usual cause of occupational asthma in exposed workers. We present the first case of occupational asthma due to the biocide additive 4,4-methylene-bismorpholine present in clean metalworking fluid.

A 54-year-old Kenyan male presented with a 2-year history of rhinitis, wheeze, dry cough and chest tightness, which were worse at night and while at work, and improved away from work on holiday. He had had rhinitis from grass pollen, perfumes and cleaning agents intermittently for 15 years, and acne due to metalworking fluid 5 years previously. There was no childhood or family history of asthma and he had never smoked cigarettes. He had been employed as a machine tool setter operator for 22 years manufacturing car axles. For the past 6 years he had worked on an enclosed computer numerical controlled milling, drilling and boring machine, with its own oil sump, using carbide-tipped tools. It was loaded by a robot but there was no delay between the end of machining and door opening, which produced a visible mist about 3 m from his work station. The machines used …
Gut-associated microbes of Drosophila melanogaster
Authors: Nichole A. Broderick, Bruno Lemaitre
Journal: Gut Microbes (2012)

There is growing interest in using Drosophila melanogaster to elucidate mechanisms that underlie the complex relationships between a host and its microbiota. In addition to the many genetic resources and tools Drosophila provides, its associated microbiota is relatively simple (1–30 taxa), in contrast to the complex diversity associated with vertebrates (> 500 taxa). These attributes highlight the potential of this system to dissect the complex cellular and molecular interactions that occur between a host and its microbiota. In this review, we summarize what is known regarding the composition of gut-associated microbes of Drosophila and their impact on host physiology. We also discuss these interactions in the context of their natural history and ecology and describe some recent insights into mechanisms by which Drosophila and its gut microbiota interact. "Workers with Drosophila have been considered fortunate in that they deal with the first multicellular invertebrate to be cultured monoxenically (Delcourt and Guyenot, 1910); the first to be handled axenically on a semisynthetic diet (Guyenot, 1917); and the first to be grown on a defined diet (Schultz et al., 1946). This list of advantages is somewhat embarrassing, since it implies an interest in nutrition that, in reality, was only secondary. The very first studies were concerned with the reduction of variability in genetic experiments (Delcourt and Guyenot, 1910) and standardization of the nutritional environment." -James Sang, 1959 Ann NY Acad 1
Unrelated Donor Marrow Transplantation for B-Cell Chronic Lymphocytic Leukemia After Using Myeloablative Conditioning: Results From the Center for International Blood and Marrow Transplant Research
Authors: Steven Z. Pavletic, Issa F. Khouri, Michael Haagenson, Roberta J. King, Philip J. Bierman, Michael R. Bishop, Michael Carston, Sergio Giralt, Arturo Molina, Edward A. Copelan, Olle Ringdén, Vivek Roy, Karen Ballen, Douglas R. Adkins, Philip McCarthy, Daniel Weisdorf, Emili Montserrat, Claudio Anasetti
Journal: Journal of Clinical Oncology (2005)

To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL).A total of 38 CLL patients received a matched URD transplant using bone marrow procured by the National Marrow Donor Program. The median age was 45 years (range, 26 to 57 years), the median time from diagnosis was 51 months, and the median number of prior chemotherapy regimens was three. Fifty-five percent of patients were chemotherapy refractory and 89% had received fludarabine. Conditioning included total-body irradiation in 92% of patients. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate with cyclosporine or tacrolimus for 82% of patients.Twenty-one patients (58%) achieved complete response and six (17%) achieved partial response. Incidences of grades 2 to 4 acute GVHD were 45% at 100 days and incidences of chronic GVHD were 85% at 5 years. Eleven patients are alive and disease free at a median of 6 years (range, 3.0 to 9.0 years). Five-year overall survival, failure-free survival, disease progression rates, and treatment-related mortality (TRM) were 33%, 30%, 32%, and 38% respectively.These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens.
Detection of Copy Number Alterations in Metastatic Melanoma by a DNA Fluorescence<i>In situ</i>Hybridization Probe Panel and Array Comparative Genomic Hybridization: A Southwest Oncology Group Study (S9431)
Authors: Stephen R. Moore, Diane L. Persons, Jeffrey A. Sosman, Dolores Bobadilla, Victoria Bedell, David D. Smith, Sandra R. Wolman, Ralph J. Tuthill, Jim Moon, Vernon K. Sondak, Marilyn L. Slovak
Journal: Clinical Cancer Research (2008)

Gene copy number alteration (CNA) is common in malignant melanoma and is associated with tumor development and progression. The concordance between molecular cytogenetic techniques used to determine CNA has not been evaluated on a large set of loci in malignant melanoma.A panel of 16 locus-specific fluorescence in situ hybridization (FISH) probes located on eight chromosomes was used to identify CNA in touch preparations of frozen tissue samples from 19 patients with metastatic melanoma (SWOG-9431). A subset (n = 11) was analyzed using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH) of DNA isolated directly from touch-preparation slides.By FISH, most samples showed loss near or at WISP3/6p21, CCND3/6q22, and CDKN2A/9p21 (>75% of samples tested). More than one third of CDKN2A/9p21 losses were biallelic. Gains of NEDD9/6p24, MET/7q31, and MYC/8q24 were common (57%, 47%, and 41%, respectively) and CNA events involving 9p21/7p12.3 and MET were frequently coincident, suggesting gain of the whole chromosome 7. Changes were confirmed by aCGH, which also uncovered many discreet regions of change, larger than a single BAC. Overlapping segments observed in >45% of samples included many of the loci analyzed in the FISH study, in addition to other WNT pathway members, and genes associated with TP53 pathways and DNA damage response, repair, and stability.This study outlines a set of CNAs at the gene and regional level, using FISH and aCGH, which may provide a benchmark for future studies and may be important in selection of individual therapy for patients with metastatic malignant melanoma.
Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practice
Authors: J.B. Soriano, J. Vestbo, N.B. Pride, V. Kiri, C. Maden, W.C. Maier
Journal: European Respiratory Journal (2002)

Despite substantial evidence regarding the benefits of combined use of inhaled corticosteroids and long-acting β 2 -agonists in asthma, such evidence remains limited for chronic obstructive pulmonary disease (COPD). Observational data may provide an insight into the expected survival in clinical trials of fluticasone propionate (FP) and salmeterol in COPD. Newly physician-diagnosed COPD patients identified in primary care during 1990–1999 aged ≥50 yrs, of both sexes and with regular prescriptions of respiratory drugs were identified in the UK General Practice Research Database. Three-year survival in 1,045 COPD patients treated with FP and salmeterol was compared with that in 3,620 COPD patients who regularly used other bronchodilators but not inhaled corticosteroids or long-acting β 2 -agonists. Standard methods of survival analysis were used, including adjustment for possible confounders. Survival at year 3 was significantly greater in FP and/or salmeterol users (78.6%) than in the reference group (63.6%). After adjusting for confounders, the survival advantage observed was highest in combined users of FP and salmeterol (hazard ratio (HR) 0.48 (95% confidence interval 0.31–0.73)), followed by users of FP alone (HR 0.62 (0.45–0.85)) and regular users of salmeterol alone (HR 0.79 (0.58–1.07)) versus the reference group. Mortality decreased with increasing number of prescriptions of FP and/or salmeterol. In conclusion, regular use of fluticasone propionate alone or in combination with salmeterol is associated with increased survival of chronic obstructive pulmonary disease patients managed in primary care.
Possible catecholaminergie-opioidergic control of blood pressure during muscular contraction
Authors: C. A WILLIAMS, L. S BLEVINS, D. J PAUL
Journal: Cardiovascular Research (1987)

The effects of an alpha2 adrenoceptor blocker, yohimbine, and an alpha1 adrenoceptor blocker, phenoxybenzamine, and the central alpha2 adrenoceptor agonist, clonidine, on changes in arterial blood pressure and heart rate were studied during fatiguing muscular contractions to determine whether an adrenergic-opioidergic system might be involved in the mediation of cardiovascular function. Fatiguing contractions of the gastrocnemius and plantaris muscles of cats caused an increase in mean arterial blood pressure to 150-170 mmHg from resting values of 110-120 mmHg. Injection of clonidine into the cerebral aqueduct eliminated the increase in blood pressure; this effect was dose dependent. Naloxone antagonised the effects of the highest dose of clonidine (5 μg). Injections of yohimbine (1 μg) into the cerebral aqueduct had no significant effect on this pressor response. Yohimbine (1 μg) effectively counteracted the antipressor effects of clonidine when the two drugs were injected together until higher doses of clonidine (2-5 μg) were used. Phenoxybenzamine had no effect on the pressor response itself but unlike yohimbine was able to attenuate the effects of clonidine only when injected together. These data suggest that activation of muscle ergoreceptor afferent nerve fibres (group III and IV fibres) during muscular contractions may cause an increase in arterial blood pressure by interfering with an inhibitory adrenergic-endorphinergic pathway in the medullary region of the brainstem.
Inhibition of Rho-Kinase Affects Astrocytoma Morphology, Motility, and Invasion through Activation of Rac1
Authors: Bodour Salhia, Frederieke Rutten, Mitsutoshi Nakada, Christian Beaudry, Michael Berens, Allison Kwan, James T. Rutka
Journal: Cancer Research (2005)

Abstract Malignant astrocytomas are highly invasive neoplasms infiltrating diffusely into regions of normal brain. Whereas the molecular and cellular mechanisms governing astrocytoma invasion remain poorly understood, evidence in other cell systems has implicated a role for the Rho-GTPases in cell motility and invasion. Here, we examine how the inhibition or activation of Rho-kinase (ROCK) affects astrocytoma morphology, motility, and invasion. ROCK was inhibited in astrocytoma cells by using 5 to 100 μmol/L of Y27632 or by expressing the dominant-negative ROCK mutant, RB/PH TT. ROCK activation was achieved by expressing a constitutively active mutant, CAT. ROCK inhibition led to morphologic and cytoskeletal alterations characterized by an increase in the number and length of cell processes, increased membrane ruffling, and collapse of actin stress fibers. Using two-dimensional radial migration and Boyden chamber assays, we show that astrocytoma migration and invasion were increased at least 2-fold by ROCK inhibition. On the contrary, ROCK activation significantly inhibited migration and invasion of astrocytoma cells. Furthermore, using a Rac-GTP pull-down assay, we show that Rac1 is activated as a consequence of ROCK inhibition. Finally, we show that treatment of astrocytoma cells with small interfering RNA duplexes specific for Rac1-reversed stellation, prevented membrane ruffling formation and abrogated the increased motility observed following treatment with Y27632. Our data show that Rac1 plays a major role in astrocytoma morphology, motility, and invasion. These findings warrant further investigation to determine precisely how the modulation of Rac1 and ROCK can be exploited to inhibit glioma invasion.
Identification of Leptomeningeal Disease in Aggressive B-Cell Non-Hodgkin's Lymphoma: Improved Sensitivity of Flow Cytometry
Authors: Sandra Quijano, Antonio López, Juan Manuel Sancho, Carlos Panizo, Guillermo Debén, Cristina Castilla, José Antonio García-Vela, Antonio Salar, Natalia Alonso-Vence, Eva González-Barca, Francisco Javier Peñalver, Josefa Plaza-Villa, Marta Morado, José García-Marco, Jesús Arias, Javier Briones, Secundino Ferrer, Javier Capote, Concepción Nicolás, Alberto Orfao
Journal: Journal of Clinical Oncology (2009)

Here, we evaluate the sensitivity and specificity of a new 11-parameter flow cytometry (FCM) approach versus conventional cytology (CC) for detecting neoplastic cells in stabilized CSF samples from newly diagnosed aggressive B-cell non-Hodgkin's lymphoma (B-NHL) at high risk of CNS relapse, using a prospective, multicentric study design.Moreover, we compared the distribution of different subpopulations of CSF leukocytes and the clinico-biologic characteristics of CSF+ versus CSF-, patients, in an attempt to define new algorithms useful for predicting CNS disease.Overall, 27 (22%) of 123 patients showed infiltration by FCM, while CC was positive in only seven patients (6%), with three other cases being suspicious (2%). CC+/FCM+ samples typically had more than 20% neoplastic B cells and/or >or= one neoplastic B cell/microL, while FCM+/CC- samples showed lower levels (P < .0001) of infiltration. Interestingly, in Burkitt lymphoma, presence of CNS disease by FCM could be predicted with a high specificity when increased serum beta2-microglobulin and neurological symptoms coexisted, while peripheral blood involvement was the only independent parameter associated with CNS disease in diffuse large B-cell lymphoma, with low predictive value.FCM significantly improves the sensitivity of CC for the identification of leptomeningeal disease in aggressive B-NHL at higher risk of CNS disease, particularly in paucicellular samples.
Comparison of once-weekly and twice-weekly strength training in older adults
Authors: J DiFrancisco-Donoghue, W Werner, P C Douris
Journal: British Journal of Sports Medicine (2006)

Background: Strength training has been shown to benefit the health and function of older adults. Objective: To investigate whether one set of exercises performed once a week was as effective in increasing muscle strength as training twice a week. Methods: 18 subjects (7 women and 11 men) aged 65–79 years were randomly assigned to two groups. Both groups performed one set of exercises to muscular fatigue; group 1 trained 1 day/week and group 2 trained 2 days/week on three lower and three upper body exercises for 9 weeks. The data were analysed using a mixed model 2×2 analysis of variance. Results: A significant main effect of time (p&lt;0.001), but not group, on one-repetition maximum scores was observed. No significant interaction was observed between time and group and therefore no difference in strength changes between training once a week versus twice a week after 9 weeks. Conclusions: One set of exercises performed once weekly to muscle fatigue improved strength as well as twice a week in the older adult. Our results provide information that will assist in designing strength-training programmes that are more time and cost efficient in producing health and fitness benefits for older adults.
Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
Authors: K Inaba, M Inaba, N Romani, H Aya, M Deguchi, S Ikehara, S Muramatsu, R M Steinman
Journal: The Journal of Experimental Medicine (1992)

Antigen-presenting, major histocompatibility complex (MHC) class II-rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II-negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent "stroma." At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since &amp;gt; 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type.
How to diagnose spondyloarthritis early? Accuracy of peripheral enthesitis detection by power Doppler ultrasonography
Authors: M. A. D'Agostino, P. Aegerter, K. Bechara, C. Salliot, O. Judet, M. S. Chimenti, D. Monnet, J.-M. Le Parc, P. Landais, M. Breban
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Early diagnosis of spondyloarthritis (SpA) is sometimes difficult owing to the lack of reliable diagnostic criteria. The objective of this study was to determine the diagnostic accuracy of detecting enthesitis by power Doppler ultrasonography (PDUS) in patients with suspected SpA. <h3>Methods</h3> A prospective single-centre cohort study was performed in patients with symptoms suggestive of SpA (inflammatory back pain, arthritis, enthesitis or dactylitis, HLAB27+ uveitis) who underwent clinical examination, pelvic x-ray, MRI of lumbar spine/sacroiliac joints, HLA-B typing and other tests judged useful for diagnosis. Blinded PDUS examination of seven sites of enthesitis was performed at baseline. The gold standard was the diagnosis made by the referring rheumatologist according to the development of symptoms and findings, blinded to PDUS results, during routine follow-up for up to 2 years. <h3>Results</h3> Between November 2002 and October 2004, 118 patients were included in the study. After 2 years a definite diagnosis was retained for 99 patients (51 SpA and 48 non-SpA). PDUS detection of at least one vascularised enthesis provided good predictive value for diagnosing SpA (sensitivity 76.5%; specificity 81.3%; positive likelihood ratio 4.1; OR 14.1; p&lt;0.0001). Vascularised enthesitis detected by PDUS and Amor9s criteria were the only independent contributors to a diagnosis of SpA in multivariate logistic regression (c-index=0.87). Alternatively, CART analysis resulted in a highly sensitive and specific diagnostic tree by combining PDUS with Amor9s criteria. <h3>Conclusions</h3> PDUS appears to be a valuable first-line diagnostic tool to confirm a diagnosis of SpA.
Use of Analytic Morphomics of Liver, Spleen, and Body Composition to Identify Patients at Risk for Cirrhosis
Authors: Venkat Krishnamurthy, Peng Zhang, Sampath Ethiraj, Binu Enchakalody, Akbar K. Waljee, Lu Wang, Stewart C. Wang, Grace L. Su
Journal: Clinical Gastroenterology and Hepatology (2014)