tbuckley/cabot-search huggingface dataset:
The role of VATS in the staging of non small cell lung cancer
Authors: Reza Bagheri, Ziaollah Haghi
Journal: European Respiratory Journal (2011)

Introduction:  One of the points discussed in NSCLC always has been to use staging method with high accuracy, including boroncoscopy, CT scan, PET scan and mediastinonoscopy.  Another completing method for staging is VATS.In our study we decided to evaluat diagnostic accuracy of VATS for staging of NSCLC.   Material & methods:  The case series study was performed on 40 NSCLC patients from 2007 to 2010.After complete preoperation evaluations (history and physical exam,CXR,CT scan,broncoscopy,TTNB and mediastinoscopy if needed in some cases) patients without creiteria of inoperability have been reevaluated with VATS staging before the surgery. Thoracotomy was performed after VATS,when we didnt have any exclusion creiteria for surgical resection. we evaluated diagnostic accuracy of VATS.   Results:  40 patients were studied (M/F = 21/19), the mean age was 57 year. The most common symptom was coughing (%90). The most common finding of CT scan of the patients was mass lesion in 100% patients. The endobronchial lesion was seen in 29 patients.We performed medianoscopy on 7 patients for staging because of N2 lymph node size more than 1 cm, which was negative finding for metastatic involvement. 6 patients havent been candidated for surgical resection after performing VATS (3 patients for pleural seeding, 2 patients for N2 lymphatic involvement, and one for stellate lesion in other lobe). Thoracotomy was done on 34 patients. Operation was successful in 31 patients complete resection and failed in 3 patients due to hillar extension of tumor. The diagnosis accuracy of VATS was 92.5%.   Conclusion:  According to high diagnostic accuracy and easy to performance of VATS we recommend it to be done before surgery.
Cardiac Mechanics Revisited
Authors: Gerald Buckberg, Julien I.E. Hoffman, Aman Mahajan, Saleh Saleh, Cecil Coghlan
Journal: Circulation (2008)

The keynote to understanding cardiac function is recognizing the underlying architecture responsible for the contractile mechanisms that produce the narrowing, shortening, lengthening, widening, and twisting disclosed by echocardiographic and magnetic resonance technology. Despite background knowledge of a spiral clockwise and counterclockwise arrangement of muscle fibers, issues about the exact architecture, interrelationships, and function of the different sets of muscle fibers remain to be resolved. This report (1) details observed patterns of cardiac dynamic directional and twisting motions via multiple imaging sources; (2) summarizes the deficiencies of correlations between ventricular function and known ventricular muscle architecture; (3) correlates known cardiac motions with the functional anatomy within the helical ventricular myocardial band; and (4) defines an innovative muscular systolic mechanism that challenges the previously described concept of “isovolumic relaxation.” This new knowledge may open new doors to treating heart failure due to diastolic dysfunction.
Radiolabeled Somatostatin Analog [<sup>177</sup>Lu-DOTA<sup>0</sup>,Tyr<sup>3</sup>]Octreotate in Patients With Endocrine Gastroenteropancreatic Tumors
Authors: Dik J. Kwekkeboom, Jaap J. Teunissen, Willem H. Bakker, Peter P. Kooij, Wouter W. de Herder, Richard A. Feelders, Casper H. van Eijck, Jan-Paul Esser, Boen L. Kam, Eric P. Krenning
Journal: Journal of Clinical Oncology (2005)

Purpose There are few treatment options for patients with metastasized or inoperable endocrine gastroenteropancreatic (GEP) tumors. Chemotherapy can be effective, but the response is usually less than 1 year. Here, we present the results of treatment with a radiolabeled somatostatin analog, [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate). Patients and Methods One hundred thirty-one patients with somatostatin receptor-positive tumors were treated with up to a cumulative dose of 600 to 800 mCi (22.2 to 29.6 GBq) of 177 Lu-octreotate. Results One patient developed renal insufficiency, and another patient developed hepatorenal syndrome. Creatinine clearance did not change significantly in the other patients. WHO hematologic toxicity grade 3 or 4 occurred after less than 2% of the administrations. We observed complete remission in three patients (2%), partial remission in 32 patients (26%), minor response (tumor diameter decrease of 25% to 50%) in 24 patients (19%), stable disease (SD) in 44 patients (35%), and progressive disease (PD) in 22 patients (18%). Higher remission rates were positively correlated with high uptake on pretherapy somatostatin receptor imaging and a limited number of liver metastases, whereas PD was significantly more frequent in patients with a low performance score and extensive disease. Median time to progression in 103 patients who either had SD or tumor regression was more than 36 months. Conclusion Treatment with 177 Lu-octreotate results in tumor remission in a high percentage of patients with GEP tumors. Serious side effects are rare. The median time to progression compares favorably with chemotherapy. Results are better in patients with a limited tumor load. Therefore, early treatment, even in patients who have no PD, may be better.
THE EPHRINS AND EPH RECEPTORS IN NEURAL DEVELOPMENT
Authors: John G. Flanagan, Pierre Vanderhaeghen
Journal: Annual Review of Neuroscience (1998)

▪ Abstract The Eph receptors are the largest known family of receptor tyrosine kinases. Initially all of them were identified as orphan receptors without known ligands, and their specific functions were not well understood. During the past few years, a corresponding family of ligands has been identified, called the ephrins, and specific functions have now been identified in neural development. The ephrins and Eph receptors are implicated as positional labels that may guide the development of neural topographic maps. They have also been implicated in pathway selection by axons, the guidance of cell migration, and the establishment of regional pattern in the nervous system. The ligands are anchored to cell surfaces, and most of the functions so far identified can be interpreted as precise guidance of cell or axon movement. This large family of ligands and receptors may make a major contribution to the accurate spatial patterning of connections and cell position in the nervous system.
Airway narrowing in porcine bronchi with and without lung parenchyma
Authors: P. B. Noble, A. Sharma, P. K. McFawn, H. W. Mitchell
Journal: European Respiratory Journal (2005)

During bronchoconstriction elastic after-loads arise due to distortion of lung parenchyma by the narrowing airway. In the present study, the functional effect of parenchymal elastic after-load on airway narrowing was determined. Airway narrowing was measured in vivo over a range of transpulmonary pressures and compared with in vitro narrowing measured at corresponding transmural pressures. Bronchi were generation 10 with internal diameters of ∼4 mm. In vivo luminal narrowing was measured by videobronchoscopy in anaesthetised and ventilated pigs. In vitro luminal narrowing was measured by videoendoscopy in isolated bronchial segments. Airways were activated by maximum vagal nerve stimulation and maximum electrical field stimulation in vivo and in vitro , respectively. At 5 cmH 2 O, stimulation produced a 35.9±3.2% (n = 6) and a 36.5±2.4% (n = 11) decrease in lumen diameter in vivo and in vitro , respectively. At 30 cmH 2 O, luminal narrowing fell to 23.7±2.0% in vivo and 23.4±2.5% in vitro . There was no difference between luminal narrowing in vivo and in vitro at any pressure. In conclusion, these findings suggest that in mid-sized, cartilaginous bronchi, parenchymal elastic after-loads do not restrict airway narrowing.
A Prospective Study of Bisphosphonate Use and Risk of Colorectal Cancer
Authors: Hamed Khalili, Edward S. Huang, Shuji Ogino, Charles S. Fuchs, Andrew T. Chan
Journal: Journal of Clinical Oncology (2012)

Bisphosphonates are used for the treatment of bone metastases and have been associated with a lower risk of breast cancer. A recent case-control study showed an inverse association between bisphosphonate use and colorectal cancer. Data from prospective cohorts are lacking.We prospectively examined the relationship between bisphosphonate use and risk of colorectal cancer among 86,277 women enrolled onto the Nurses Health Study (NHS). Since 1998, participants have returned biennial questionnaires in which they were specifically queried about the regular use of bisphosphonates. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs for risk of colorectal cancer.Through 2008, we documented 801 cases of colorectal cancer over 814,406 person-years of follow-up. The age-adjusted HR for women who regularly used bisphosphonates was 0.92 (95% CI, 0.73 to 1.14) and was further attenuated after adjustment for other risk factors (multivariate HR, 1.04; 95% CI, 0.82 to 1.33). The risk was not influenced by duration of use (P(trend) = 0.79). Compared with nonusers, the multivariate-adjusted HRs of colorectal cancer were 1.24 (95% CI, 0.94 to 1.64) for women with 1 to 2 years of use, 1.16 (95% CI, 0.79 to 1.69) for 3 to 4 years of use, and 0.97 (95% CI, 0.60 to 1.56) for ≥ 5 years of use. There was no association between bisphosphonate use and colorectal cancer within strata of other risk factors.In a large prospective cohort, we did not observe an association between long-term use of bisphosphonates and risk of colorectal cancer.
Diagnosis of Deep Septic Thrombophlebitis in Cancer Patients by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Scanning: A Preliminary Report
Authors: Marisa Miceli, Rola Atoui, Ronald Walker, Tahsine Mahfouz, Nadeem Mirza, Jose Diaz, Guido Tricot, Bart Barlogie, Elias Anaissie
Journal: Journal of Clinical Oncology (2004)

To determine the role of the fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan in the diagnosis and management of deep septic thrombophlebitis (STP).We conducted a prospective observational evaluation of FDG-PET in patients with cancer and suspected STP. Retrospective evaluation of patients with cancer and deep venous thrombosis (DVT) who underwent FDG-PET and extremity duplex scan (DS) was also performed.Strong venous uptake was observed in FDG-PET of nine STP episodes versus 0 of 27 DVT episodes (P <.001). FDG-PET identified central vein STP in five patients, whereas DS and venography were negative in five and two of these patients, respectively. FDG-PET diagnosis of STP resulted in therapeutic changes in all patients. In four patients, follow-up FDG-PET confirmed resolution.In cancer patients, FDG-PET identifies STP even in areas not optimally visualized by DS or venography, distinguishes STP from DVT, and leads to significant therapeutic changes.
MRI-assessed therapeutic effects of locally administered PLGA nanoparticles loaded with anti-inflammatory siRNA in a murine arthritis model
Authors: Bernard C.M. te Boekhorst, Linda B. Jensen, Stefano Colombo, Amir K. Varkouhi, Raymond M. Schiffelers, Twan Lammers, Gert Storm, Hanne M. Nielsen, Gustav J. Strijkers, Camilla Foged, Klaas Nicolay
Journal: Journal of Controlled Release (2012)
IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines
Authors: Sophie Molet, Qutayba Hamid, Francis Davoineb, Esra Nutku, Rame Tahaa, Nathalie Pagé, Ron Olivenstein, Jack Elias, Jamila Chakir
Journal: Journal of Allergy and Clinical Immunology (2001)

Background: IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibro-blasts and macrophages for the secretion of GM-CSF, TNF-α, IL-1β, and IL-6. A number of these cytokines are involved in the airway remodeling that is observed within the lungs of asthmatic individuals. Objective: In this study, we investigated the expression of IL-17 in sputum and bronchoalveolar lavage specimens obtained from asthmatic subjects and from nonasthmatic control subjects. Methods: IL-17 was detected through use of immunocytochemistry, in situ hybridization, and Western blot. Bronchial fibroblasts were stimulated with IL-17, and cytokine production and chemokine production were detected through use of ELISA and RT-PCR. Results: Using immunocytochemistry, we demonstrated that the numbers of cells positive for IL-17 are significantly increased in sputum and bronchoalveolar lavage fluids of subjects with asthma in comparison with control subjects (P < .001 and P < .005, respectively). We demonstrated that in addition to T cells, eosinophils in sputum and bronchoalveolar lavage fluids expressed IL-17. Peripheral blood eosinophils were also positive for IL-17, and the level of IL-17 in eosinophils purified from peripheral blood was significantly higher in subjects with asthma than in controls (P < .01). To further investigate the mechanism of action of IL-17 in vivo, we examined the effect of this cytokine on fibroblasts isolated from bronchial biopsies of asthmatic and nonasthmatic subjects. IL-17 did enhance the production of pro-fibrotic cytokines (IL-6 and IL-11) by fibroblasts, and this was inhibited by dexamethasone. Similarly, IL-17 increased the level of other fibroblast-derived inflammatory mediators, such as the α-chemokines, IL-8, and growth-related oncogene-α. Conclusion: Our results, which demonstrate for the first time that eosinophils are a potential source of IL-17 within asthmatic airways, suggest that IL-17 might have the potential to amplify inflammatory responses through the release of proinflammatory mediators such as α-chemokines. (J Allergy Clin Immunol 2001;108:430-8.)
Towards a multifaceted understanding of revenge and forgiveness
Authors: Ramzi Fatfouta, Arthur Jacobs, Angela Merkl
Journal: Behavioral and Brain Sciences (2012)

We focus on two aspects: First, we argue that it is necessary to include implicit forgiveness as an additional adaptive behavioral option to the perception of interpersonal transgressions. Second, we present one possible way to investigate the cognitive-affective underpinnings of revenge and forgiveness: a functional MRI (fMRI) approach aiming at integrating forgiveness and revenge mechanisms into a single paradigm.
Elevated Plasma Ghrelin Level in Underweight Patients with Chronic Obstructive Pulmonary Disease
Authors: Takefumi Itoh, Noritoshi Nagaya, Masanori Yoshikawa, Atsuhiko Fukuoka, Hideaki Takenaka, Yoshito Shimizu, Yoshinori Haruta, Hideo Oya, Masakazu Yamagishi, Hiroshi Hosoda, Kenji Kangawa, Hiroshi Kimura
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Ghrelin, a novel growth hormone-releasing peptide, has been shown to cause a positive energy balance by reducing fat use and stimulating food intake. This study investigated whether plasma ghrelin is associated with clinical parameters in patients with chronic obstructive pulmonary disease. Plasma ghrelin was measured in 50 patients and 13 control subjects, together with anabolic and catabolic factors. Patients were divided into two groups based on body mass index: underweight patients (n = 26) or normal weight patients (n = 24). Plasma ghrelin was significantly higher in underweight patients than in normal weight patients and healthy control subjects. Circulating tumor necrosis factor-alpha, interleukin-6, and norepinephrine were significantly higher in underweight patients than in normal weight patients. Plasma ghrelin correlated negatively with body mass index and correlated positively with catabolic factors such as tumor necrosis factor-alpha and norepinephrine. In addition, plasma ghrelin correlated positively with percent predicted residual volume and residual volume-to-total lung capacity ratio. In conclusion, plasma ghrelin was elevated in underweight patients with chronic obstructive pulmonary disease, and the level was associated with a cachectic state and abnormality of pulmonary function.
Density dependence of respiratory input impedance re-evaluated with a head generator minimizing upper airway shunt
Authors: M Rotger, R Peslin, D Navajas, C Gallina, C Duvivier
Journal: European Respiratory Journal (1988)

Total respiratory impedance was assessed from 4 to 30 Hz in ten normal subjects breathing air and a helium-oxygen gas mixture using two methods of applying pressure oscillations at the airway opening: 1) the conventional method where pressure is varied at the mouth: 2) the method recently developed by Peslin et al. (J Appl Physiol, 1985, 59, 1790-1795) in which pressure is varied both at the mouth and around the head to minimize transmural pressure across upper airway walls, and the corresponding artefact. When breathing air slightly lower resistances (p less than 0.05) and considerably higher inertances (p less than 0.001) were found using the head generator. Breathing helium-oxygen reduced respiratory resistance and its frequency dependence, as well as respiratory inertance very significantly (p less than 0.001), with minor differences between the changes seen with the two methods. In contrast, the changes in respiratory compliance were small, and not in the same direction, when pressure was varied at the mouth and around the head. It is concluded that the accuracy of the conventional method may be sufficient for diagnostic purposes in subjects without gross mechanical abnormalities, i.e. for early detection of mechanical abnormalities.
The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems
Authors: Alexandre Albanese, Peter S. Tang, Warren C.W. Chan
Journal: Annual Review of Biomedical Engineering (2012)

An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.
Glutaredoxin-1 Attenuates <i>S</i>-Glutathionylation of the Death Receptor Fas and Decreases Resolution of <i>Pseudomonas aeruginosa</i> Pneumonia
Authors: Vikas Anathy, Scott W. Aesif, Sidra M. Hoffman, Jenna L. Bement, Amy S. Guala, Karolyn G. Lahue, Laurie W. Leclair, Benjamin T. Suratt, Carlyne D. Cool, Matthew J. Wargo, Yvonne M. W. Janssen-Heininger
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: The death receptor Fas is critical for bacterial clearance and survival of mice after Pseudomonas aeruginosa infection.Objectives: Fas ligand (FasL)–induced apoptosis is augmented by S-glutathionylation of Fas (Fas-SSG), which can be reversed by glutaredoxin-1 (Grx1). Therefore, the objective of this study was to investigate the interplay between Grx1 and Fas in regulating the clearance of P. aeruginosa infection.Methods: Lung samples from patients with bronchopneumonia were analyzed by immunofluorescence. Primary tracheal epithelial cells, mice lacking the gene for Grx1 (Glrx1−/−), Glrx1−/− mice treated with caspase inhibitor, or transgenic mice overexpressing Grx1 in the airway epithelium were analyzed after infection with P. aeruginosa.Measurements and Main Results: Patient lung samples positive for P. aeruginosa infection demonstrated increased Fas-SSG compared with normal lung samples. Compared with wild-type primary lung epithelial cells, infection of Glrx1−/− cells with P. aeruginosa showed enhanced caspase 8 and 3 activities and cell death in association with increases in Fas-SSG. Infection of Glrx1−/− mice with P. aeruginosa resulted in enhanced caspase activity and increased Fas-SSG as compared with wild-type littermates. Absence of Glrx1 significantly enhanced bacterial clearance, and decreased mortality postinfection with P. aeruginosa. Inhibition of caspases significantly decreased bacterial clearance postinfection with P. aeruginosa, in association with decreased Fas-SSG. In contrast, transgenic mice that overexpress Grx1 in lung epithelial cells had significantly higher lung bacterial loads, enhanced mortality, decreased caspase activation, and Fas-SSG in the lung after infection with P. aeruginosa, compared with wild-type control animals.Conclusions: These results suggest that S-glutathionylation of Fas within the lung epithelium enhances epithelial apoptosis and promotes clearance of P. aeruginosa and that glutaredoxin-1 impairs bacterial clearance and increases the severity of pneumonia in association with deglutathionylation of Fas.
Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma.
Authors: J L Baron, J A Madri, N H Ruddle, G Hashim, C A Janeway
Journal: The Journal of Experimental Medicine (1993)

Cloned CD4 T cell lines that recognize the Ac1-16 peptide of myelin basic protein bound to I-Au were isolated and used to analyze the immunopathogenesis of experimental autoimmune encephalomyelitis (EAE). T helper type 1 (Th1) clones induced disease, while Th2 clones did not. Using variants of a single cloned Th1 line, the surface expression of alpha 4 integrins (very late antigen 4 [VLA-4]) was identified as a major pathogenic factor. Encephalitogenic clones and nonencephalitogenic variants differ by 10-fold in their level of surface expression of alpha 4 integrin and in their ability to bind to endothelial cells and recombinant vascular cell adhesion molecule 1 (VCAM-1). The alpha 4 integrin-high, disease-inducing cloned Th1 T cells enter brain parenchyma in abundance, while alpha 4 integrin-low, nonencephalitogenic Th1 cells do not. Moreover, antibodies to alpha 4 integrin, its ligand VCAM-1, and intercellular adhesion molecule 1 all influence the pathogenicity of this encephalitogenic clone in vivo. The importance of the expression of VLA-4 for encephalitogenicity is not unique to cloned T cell lines, as similar results were obtained using myelin basic protein-primed lymph node T cells. alpha 4 integrin levels did not affect antigen responsiveness or production of the Th1 cytokines interleukin 2, interferon gamma, and lymphotoxin/tumor necrosis factor beta; and antibodies against alpha 4 integrin did not block antigen recognition in vitro. Thus, we conclude that surface expression of alpha 4 integrin is important in CD4 T cell entry into brain parenchyma. A general conclusion of these studies is that alpha 4 integrins may be crucial in allowing activated effector T cells to leave blood and enter the brain and other tissues to clear infections.