tbuckley/cabot-search huggingface dataset:
Comparative gene expression profiling of post-natal and post-pneumonectomy lung growth
Authors: J-C. Wolff, J. Wilhelm, L. Fink, W. Seeger, R. Voswinckel
Journal: European Respiratory Journal (2009)

Although increasing numbers of patients suffer from chronic destructive lung diseases, there are no effective therapeutic options apart from transplantation. Understanding the mechanisms of physiological and regenerative alveolar septation is prerequisite for the development of regenerative therapies for the lung. We compared lung gene expression in the phase of induction of post-natal and post-pneumonectomy alveolarisation to identify regulatory genes involved in both processes. We performed genome-wide microarray screenings of newborn and pneumonectomised mouse lungs 1 and 3 days after birth or surgery. Selected candidates were validated by real-time PCR, Western blot and <i>in situ</i> hybridisation. We found 58 genes to be regulated in both models with 40 candidates being changed likewise. Many of these genes participated in growth and differentiation processes. Additionally, immune system, structural molecules, respiratory chain, signal transduction and metabolism were involved. Some candidates were not yet linked to specific functions. The highest regulatory concordance was observed for various isoforms of (pro-)collagen molecules, elastin and the elastin-associated protein fibrillin1 being corporately upregulated. Our findings do not definitively support a common regulating mechanism for induction of post-natal and adult alveolarisation, but some candidates in the intersection of both models are promising for further investigations.
Immunization of Stage IV Melanoma Patients with Melan-A/MART-1 and gp100 Peptides plus IFN-α Results in the Activation of Specific CD8+ T Cells and Monocyte/Dendritic Cell Precursors
Authors: Tiziana Di Pucchio, Lorenzo Pilla, Imerio Capone, Maria Ferrantini, Enrica Montefiore, Francesca Urbani, Roberto Patuzzo, Elisabetta Pennacchioli, Mario Santinami, Agata Cova, Gloria Sovena, Flavio Arienti, Claudia Lombardo, Arianna Lombardi, Patrizia Caporaso, Stefania D'Atri, Paolo Marchetti, Enzo Bonmassar, Giorgio Parmiani, Filippo Belardelli, Licia Rivoltini
Journal: Cancer Research (2006)

Abstract The use of IFN-α in clinical oncology has generally been based on the rationale of exploiting its antiproliferative and antiangiogenic activities. However, IFN-α also exhibits enhancing effects on T-cell and dendritic cell functions, which may suggest a novel use as a vaccine adjuvant. We have carried out a pilot phase I-II trial to determine the effects of IFN-α, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients. In five of the seven evaluable patients, a consistent enhancement of CD8+ T cells recognizing modified and native MART-1 and gp100 peptides and MART-1+gp100+ melanoma cells was observed. Moreover, vaccination induced an increase in CD8+ T-cell binding to HLA tetramers containing the relevant peptides and an increased frequency of CD45RA+CCR7− (terminally differentiated effectors) and CD45RA−CCR7− (effector memory) cells. In all patients, treatment augmented significantly the percentage of CD14+ monocytes and particularly of the CD14+CD16+ cell fraction. An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed. Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8+ T cells. Although further clinical studies are needed to show the adjuvant activity of IFN-α, the present data represent an important starting point for considering a new clinical use of IFN-α and new immunologic end points, potentially predictive of clinical response. (Cancer Res 2006; 66(9): 4943-51)
Can lung function measurements be used to predict which patients will be at risk of developing interstitial pneumonitis after bone marrow transplantation?
Authors: H J Milburn, H G Prentice, R M du Bois
Journal: Thorax (1992)

Lung function often deteriorates after bone marrow transplantation for haematological malignancies. Whether pulmonary function measurements are useful for monitoring patients' progress after transplantation and for alerting clinicians to the development of pneumonitis is uncertain.Serial pulmonary function measurements were made in 39 patients with a haematological malignancy, and the values from 18 recipients of T cell depleted allogeneic (n = 17) or autologous (n = 1) bone marrow transplants who developed interstitial pneumonitis were compared retrospectively with values from 21 recipients of allogeneic (n = 17) or autologous (n = 4) transplants who did not develop pneumonitis. Lung function was measured at the onset of a further 18 episodes of pneumonitis.Measurements made before transplantation showed no difference in forced expiratory volume in one second (FEV1), transfer factor for carbon monoxide (TLCO), or total lung capacity between the two groups, but the forced vital capacity (FVC) was slightly higher in those who developed pneumonitis (mean (SD)% predicted 104 (12)) than in those who did not (93 (17%)). Six weeks and three months after transplantation all pulmonary function measurements had fallen slightly in both groups but TLCO had fallen considerably more in those who later developed pneumonitis, being 71% (SD 11%) and 77% (7%) of pretransplant values in patients who later developed pneumonitis compared with 109% (38%) and 96% (26%) in those who did not. All lung function measurements were significantly lower at the onset of pneumonitis than three months after transplantation, even in patients with no abnormal signs and a normal chest radiograph.Serial measurements of gas transfer before and after bone marrow transplantation may be useful for predicting which patients will be at risk of developing pneumonitis and may help to diagnose pneumonitis in breathless patients with no abnormal signs.
Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy
Authors: Felix Klug, Hridayesh Prakash, Peter E. Huber, Tobias Seibel, Noemi Bender, Niels Halama, Christina Pfirschke, Ralf Holger Voss, Carmen Timke, Ludmila Umansky, Kay Klapproth, Knut Schäkel, Natalio Garbi, Dirk Jäger, Jürgen Weitz, Hubertus Schmitz-Winnenthal, Günter J. Hämmerling, Philipp Beckhove
Journal: Cancer Cell (2013)
Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema
Authors: G. Peces-Barba, J. Ruiz-Cabello, Y. Cremillieux, I. Rodríguez, D. Dupuich, V. Callot, M. Ortega, M.L. Rubio Arbo, M. Cortijo, N. Gonzalez-Mangado
Journal: European Respiratory Journal (2003)

Hyperpolarised gases have been most recently used in magnetic resonance imaging to demonstrate new image-derived pulmonary function parameters. One of these parameters is the apparent diffusion coefficient, which reflects the sizes of the structures that compartmentalise gas within the lung ( i.e. alveolar space). In the present study, noninvasive parameters were compared to microscopic measurements (mean linear intercept and mean alveolar internal area). Nonselective helium‐3 gas density coronal ex vivo images and apparent diffusion maps were acquired in control and elastase-induced panacinar emphysema rats. Total lung capacity was considered the reference for both imaging experiments and lung fixation. A mild degree of emphysema was found based on mean linear intercept (134±25 µm) versus control (85±14 µm). The apparent diffusion coefficients were significantly different between the two groups (0.18±0.02 and 0.15±0.01 cm 2 ·s −1 for elastase and control, respectively). A significant correlation between the apparent diffusion coefficient and corresponding morphometric parameters in mild emphysema was demonstrated for the first time. This study opens the possibility of estimating absolute airspace size using noninvasive techniques.
Surfactant protein-A deficiency in a primate model of bronchopulmonary dysplasia.
Authors: R J King, J J Coalson, R A deLemos, D R Gerstmann, S R Seidner
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Pathophysiologic and biochemical (surfactant protein and phospholipid) features were studied in a baboon model of hyperoxia-induced bronchopulmonary dysplasia (BPD) and superimposed infection. A total of 20 baboons were delivered by hysterotomy at 76% of gestation (140 d of gestational age) and were randomized into four groups, consisting of two control and two injury groups. Animals constituting a group that was managed on a pro re nata (PRN) basis were ventilated with clinically appropriate oxygen for the 16-d experimental period and served as ventilatory controls. They underwent an initial period of 42 h during which they demonstrated evidence of hyaline membrane disease (HMD), but began recovery at 42 h and by Day 6 appeared to have maximally recovered. At the time of these animals' killing, concentrations of surfactant proteins, messenger ribonucleic acids (mRNAs), and phospholipids were similar to those of normal adult baboons. Gestational control animals were delivered and killed without ventilation at 156 d gestational age. Surfactant protein-A (SP-A) and phospholipid concentrations in these animals' lavage fluids were about 10% of those in the PRN animals. Animals with BPD were subjected to positive-pressure ventilation and an FIO2 of 1.0 for 11 d, followed by 5 d of an FIO2 sufficient to maintain PaO2 at 40 to 50 mm Hg. The animals with BPD and infection were treated in the same way as the BPD group, except that 10(8) Escherichia coli were instilled intratracheally on Day 11, concomitantly with the reduction in FIO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Abnormal Expression of Fcγ Receptors by Human Bone Marrow Mast Cells in Systemic Mastocitosis
Authors: L.B. Sanchez-Muñoz, A. Prados, R. Nuñez, C. Ruiz, C. Teodosio, A. Lopez, M. Jara, J. Almeida, A. Orfao, L. Escribano
Journal: Journal of Allergy and Clinical Immunology (2007)
Alternating gemcitabine and cisplatin with gemcitabine and radiation in stage IV squamous cell carcinoma of the head and neck
Authors: M. Benasso, R. Corvò, A. Ponzanelli, G. Sanguineti, I. Ricci, E. Pallestrini, A. Santelli, V. Vitale, R. Rosso
Journal: Annals of Oncology (2004)
Systematic Review of Pretreatment Prostate-Specific Antigen Velocity and Doubling Time As Predictors for Prostate Cancer
Authors: Andrew J. Vickers, Caroline Savage, M. Frank O'Brien, Hans Lilja
Journal: Journal of Clinical Oncology (2008)

Pretreatment prostate-specific antigen (PSA) dynamics (PSA velocity and PSA doubling time) are widely advocated as useful prognostic markers in prostate cancer. We aimed to assess the published evidence for the clinical utility of PSA dynamics in this population.We conducted a systematic review of studies published before March 2007 in which a PSA dynamic (velocity or doubling time) was calculated in patients before definitive treatment, a subsequent event (such as biopsy or recurrence) was ascertained, and the association between the two was analyzed. Our principal end point was the type of analysis reported, particularly whether the predictive accuracy of a statistical model that included both absolute PSA level and a PSA dynamic was compared with that of a model that included only PSA.Eighty-seven articles were eligible for analysis. The most common end points were biopsy (42 articles), and either recurrence (14 articles) or metastases or death (14 articles) after definitive therapy. Although PSA dynamics were generally found to be associated with outcome, only one article compared predictive accuracy of models with and without a PSA dynamic: this reported that PSA velocity improved prediction slightly (from 0.81 to 0.83), but was subject to verification bias. No article used decision analytic methods to examine the clinical impact of PSA dynamics.There is little evidence that calculation of PSA velocity or doubling time in untreated patients provides predictive information beyond that provided by absolute PSA level alone. We see no justification for the use of PSA dynamics in clinical decision making before treatment in early-stage prostate cancer.
Tiotropium as a first maintenance drug in COPD: secondary analysis of the UPLIFT(R) trial
Authors: T. Troosters, B. Celli, T. Lystig, S. Kesten, S. Mehra, D.P. Tashkin, M. Decramer
Journal: European Respiratory Journal (2010)

The aim of the present study was investigate the long-term effect of tiotropium as first maintenance respiratory medication in chronic obstructive pulmonary disease (COPD). A 4-yr, randomised, multicentre, double-blind, parallel-group, placebo-controlled trial (Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®)) was conducted. Analysis focused on the effect of tiotropium versus matching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting β-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation. Spirometry, health-related quality of life (St George’s Respiratory Questionnaire (SGRQ) score), exacerbations of COPD and mortality were also analysed. 403 patients (mean± sd age 63±8 yrs, post-bronchodilator forced expiratory volume in 1 s (FEV 1 ) 53±12% predicted) received tiotropium and 407 (64±8 yrs of age, post-bronchodilator FEV 1 51±12% pred) received placebo. Post-bronchodilator FEV 1 decline was 42±4 mL·yr −1 in the tiotropium group and 53±4 mL·yr −1 in the placebo group (p = 0.026). At 48 months, the morning pre-dose FEV 1 was 134 mL higher in the tiotropium group compared to the placebo group (p&lt;0.001). SGRQ total score declined more slowly in the tiotropium group (difference of 1.05±0.34 units·yr −1 ; p = 0.002). This was particularly significant for the impact (difference of 1.08±0.37 units·yr −1 ; p = 0.004) and activity (1.44±0.40 units·yr −1 ; p&lt;0.001) domains, but not for symptoms (0.26±0.50 units·yr −1 ; p = 0.6). At 48 months, the difference in total score was 4.6 units (p&lt;0.001) with tiotropium compared to placebo. In patients with COPD who are not on maintenance therapy, tiotropium is associated with significant benefits in disease progression.
Preoperative Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal Cancer
Authors: Ellen Kapiteijn, Corrie A.M. Marijnen, Iris D. Nagtegaal, Hein Putter, Willem H. Steup, Theo Wiggers, Harm J.T. Rutten, Lars Pahlman, Bengt Glimelius, J. Han J.M. van Krieken, Jan W.H. Leer, Cornelis J.H. van de Velde
Journal: New England Journal of Medicine (2001)

Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer. We conducted a multicenter, randomized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision.We randomly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision (924 patients) or to total mesorectal excision alone (937 patients). The trial was conducted with the use of standardization and quality-control measures to ensure the consistency of the radiotherapy, surgery, and pathological techniques.Of the 1861 patients randomly assigned to one of the two treatment groups, 1805 were eligible to participate. The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone (P=0.84). Among the 1748 patients who underwent a macroscopically complete local resection, the rate of local recurrence at two years was 5.3 percent. The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group (P<0.001).Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a standardized total mesorectal excision.
Energy Intake and Response to Infection with Influenza
Authors: Elizabeth M. Gardner, Eleni Beli, Jonathan F. Clinthorne, David M. Duriancik
Journal: Annual Review of Nutrition (2011)

Influenza is a worldwide public health concern, particularly with emerging new strains of influenza to which vaccines are ineffective, limited, or unavailable. In addition, the relationship between adequate nutrition and immune function has been repeatedly demonstrated. Mouse models provide strong evidence that energy extremes, including energy restriction (ER) and diet-induced obesity (DIO), have deleterious effects on the immune response to influenza infection. Both ER and DIO mice demonstrate increased susceptibility and mortality to influenza infection. The effects of ER are more pronounced during innate responses to influenza infection, whereas the effects of DIO are evidenced during innate and adaptive responses to both primary and secondary infection. There are striking similarities between ER and DIO during influenza infection, including impaired natural killer cell function and altered inflammation. Future studies must develop effective nutritional paradigms to offset the effects of these energy extremes on the immune response to an acute infection.
High-Density Functional Gastrin Releasing Peptide Receptors on Primate Cells
Authors: D. C. Heimbrook, J. W. Wallen, N. L. Balishin, A. Friedman, A. Oliff
Journal: JNCI Journal of the National Cancer Institute (1990)

Gastrin releasing peptide (GRP) is a 27 amino acid hormone that elicits a variety of biological effects. Receptor-binding antagonists of GRP may have therapeutic use in several pathologic conditions including cancer. The identification and characterization of GRP receptor antagonists have been aided by the use of murine 3T3 cells that possess functional GRP receptors. However, no human or primate cell lines that possess high-density GRP receptors and exhibit a biochemical or biological response to GRP have been described. To address this problem, we examined a series of cell lines and found that GRP specifically binds to Cos-7 monkey cells and stimulates elevation of intracellular calcium in these cells. Cos-7 cells exhibit a single class of high-affinity (dissociation constant = 0.13 nM) GRP binding sites (35,000/cell). Cross-linking experiments that use radiolabeled GRP identified two species of putative GRP receptor proteins (relative molecular mass, 90,000 and 22,000). Competitive binding inhibition studies indicate that Cos-7 cells tightly bind GRP-specific receptor antagonists. These antagonists block the binding of radiolabeled GRP to Cos-7 cells and inhibit GRP-stimulated elevation of intracellular calcium. These properties make Cos-7 cells a useful reagent for the study of GRP receptor antagonists.
Effect of Annular Shape on Leaflet Curvature in Reducing Mitral Leaflet Stress
Authors: Ivan S. Salgo, Joseph H. Gorman, Robert C. Gorman, Benjamin M. Jackson, Frank W. Bowen, Theodore Plappert, Martin G. St John Sutton, L. Henry Edmunds
Journal: Circulation (2002)

Background — Leaflet curvature is known to reduce mechanical stress. There are 2 major components that contribute to this curvature. Leaflet billowing introduces the most obvious form of leaflet curvature. The saddle shape of the mitral annulus imparts a more subtle form of leaflet curvature. This study explores the relative contributions of leaflet billowing and annular shape on leaflet curvature and stress distribution. Methods and Results — Both numerical simulation and experimental data were used. The simulation consisted of an array of numerically generated mitral annular phantoms encompassing flat to markedly saddle-shaped annular heights. Highest peak leaflet stresses occurred for the flat annulus. As saddle height increased, peak stresses decreased. The minimum peak leaflet stress occurred at an annular height to commissural width ratio of 15% to 25%. The second phase involved data acquisition for the annulus from 3 humans by 3D echocardiography, 3 sheep by sonomicrometry array localization, 2 sheep by 3D echocardiography, and 2 baboons by 3D echocardiography. All 3 species imaged had annuli of a similar shape, with an annular height to commissural width ratio of 10% to 15%. Conclusion — The saddle shape of the mitral annulus confers a mechanical advantage to the leaflets by adding curvature. This may be valuable when leaflet curvature becomes reduced due to diminished leaflet billowing caused by annular dilatation. The fact that the saddle shape is conserved across mammalian species provides indirect evidence of the advantages it confers. This analysis of mitral annular contour may prove applicable in developing the next generation of mitral annular prostheses.
A5.18 Carotid ultrasonography: usefullness to evaluate cardiovascular risk in patients with systemic lupus erythematosus: Abstract A5.18 Table 1
Authors: R Martinez Perez, ML Velloso Feijoo, J Uceda Montañes, JL Marenco de la Fuente
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The frequency of stroke in SLE patients between 18–44 years is 2 times the frequency in general population of the same age and sex. Clinical atherosclerosis is detected in 6%–12% of patients with SLE. Some researchers have suggested that the development of atherosclerosis may be related to the systemic inflammation. The objetive of our study is to assess cardiovascular risk in patients with SLE by measuring carotid intima-media thickness and identifying the presence of plaques. <h3>Material and methods</h3> Cross-sectional study on a series of 10 SLE patients without dyslipidemia. The presence of plaques and/or an intima-media thickness higher than 0.9 mm, evaluated with a high-resolution B mode ultrasound, reflect high cardiovascular risk. <h3>Results</h3> Of the 10 patients, 8 were women. The mean age was 36 ± 1.2 years and the mean age at diagnosis of the disease 23.2 ± 7.37 years. The patient's characteristics and analytical data are shown in table 1. Mean intima-media thickness in the right carotid was 580.72 ± 103.83 mm and in the left 544.76 ± 202.17 mm. Of the 10 patients, 3 had plaques, 2 of them were smokers and had been treated with Rituximab after unsuccessfully treatment with several immunosuppressants. <h3>Conclusions</h3> The 30% of our patients had plaques, even without having classical cardiovascular risk factors. The use of carotid ultrasound may predict cardiovascular events. Carotid study may be considered for assessing the existence of subclinical aterosclerosis in SLE patients and treating with statins when necessary.