tbuckley/cabot-search huggingface dataset:
Comparison of Aorta and Pulmonary Artery
Authors: Dawn C. Schwenke
Journal: Circulation Research (1997)

Abstract The pulmonary artery and the aorta are similarly susceptible to atherosclerosis in rabbits. However, the mechanism(s) that accounts for this is not yet known. This study investigated the hypothesis that one or more aspects of arterial low-density lipoprotein (LDL) transport and metabolism might explain the similar susceptibility of the aortic arch and pulmonary artery to atherosclerosis and the increased susceptibility of these arterial regions compared with the descending thoracic aorta. We determined permeability to LDL, rates of LDL degradation, and concentrations of undegraded LDL for the intima-media of normal rabbits and those fed cholesterol for ≈8 days. Intima-media permeability did not differ between corresponding arterial regions of normal rabbits and rabbits fed cholesterol for 8 days and was similar for the aortic arch and pulmonary artery. Rates of LDL degradation and concentrations of undegraded LDL for the intima-media were influenced by cholesterol feeding. These measures were reduced in fractional terms but increased in absolute terms as a result of hypercholesterolemia, without differences between corresponding parameters for the pulmonary artery and aortic arch. However, permeability to LDL, rates of LDL degradation, and concentrations of undegraded LDL were increased for the intima-media of the aortic arch compared with the descending thoracic aorta. Similar, although not always significant, trends were evident for the comparison of the pulmonary artery and descending thoracic aorta. Differences in LDL transport and metabolism and changes after feeding cholesterol for 8 days parallel the relative susceptibility to atherosclerosis for the three arterial regions studied. These results support the role of arterial LDL transport and metabolism in atherogenesis and potentially provide a mechanistic explanation for the differences in susceptibility to atherosclerosis for these three arterial regions.
Mesothelioma in Cyprus: the role of tremolite.
Authors: K McConnochie, L Simonato, P Mavrides, P Christofides, F D Pooley, J C Wagner
Journal: Thorax (1987)

There is a chrysotile mine in the central mountains of Cyprus but no other appreciable source of industrial asbestos. Hence the island was thought to offer ideal conditions to seek pure chrysotile induced mesothelioma. The first reported case was a village woman whose lung tissue contained amphibole asbestos fibres, which were later identified as tremolite. This began a search for the origin of her exposure to asbestos. Our studies have shown that tremolite is widespread, being found, along with chrysotile, in domestic and environmental dust samples. Other cases of mesothelioma have been diagnosed, and the pattern of their distribution suggests that the mine is not the major source of disease. Exposure to tremolite is equally, if not more, important.
Glucose and Prednisolone Alter Basic Fibroblast Growth Factor Expression in Peritoneal Mesothelial Cells and Fibroblasts
Authors: Satoshi Ogata, Noriaki Yorioka, Nobuoki Kohno
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. The mechanism of peritoneal fibrosis in patients on continuous ambulatory peritoneal dialysis is poorly understood. The production of basic fibroblast growth factor (bFGF) by human peritoneal mesothelial cells cultured in high glucose medium was investigated, and the behavior of peritoneal fibroblasts, as well as the inhibitory effect of prednisolone, was assessed. Reverse transcriptase-PCR and immunocytochemistry showed the expression of glucocorticoid receptors in mesothelial cells. The semiquantitative reverse transcriptase-PCR showed that high glucose medium (4.0%) increased bFGF mRNA by 2.5-fold relative to control medium (0.1% glucose), with 83% suppression of the increase by 1 μM prednisolone. The bFGF protein level in culture supernatant was also increased by 1.5-fold in high glucose medium, with this change showing 45% suppression by 1 μM prednisolone. These effects of prednisolone were prevented by a glucocorticoid receptor antagonist (RU486) in a concentration-dependent manner. The proliferation of peritoneal fibroblasts was increased 1.9-fold by the supernatant of mesothelial cells cultured in high glucose medium, with 85% suppression by 1 μM prednisolone and suppression to 16% below basal proliferation by an anti-bFGF neutralizing antibody (10 μg/ml), whereas proliferation showed a concentration-dependent increase on addition of an anti-transforming growth factor beta-neutralizing antibody. Recombinant bFGF (50 to 1000 pg/ml) likewise caused a concentration-dependent increase of peritoneal fibroblast proliferation and fibronectin release by these cells was also increased (at 50 to 5000 pg/ml). These results suggest the potential importance of bFGF for initiation of peritoneal fibrosis and the possible efficacy of glucocorticoids for preventing such fibrosis in patients receiving peritoneal dialysis.
In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor
Authors: Alexandre Boissonnas, Luc Fetler, Ingrid S. Zeelenberg, Stéphanie Hugues, Sebastian Amigorena
Journal: The Journal of Experimental Medicine (2007)

Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8+ cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.
Nomogram for the Prediction of Having Four or More Involved Nodes for Sentinel Lymph Node–Positive Breast Cancer
Authors: Angela Katz, Barbara L. Smith, Mehra Golshan, Andrzej Niemierko, Wendy Kobayashi, Rita Abi Raad, Alexandra Kelada, Levi Rizk, Julia S. Wong, Jennifer R. Bellon, Michele Gadd, Michelle Specht, Alphonse G. Taghian
Journal: Journal of Clinical Oncology (2008)

The standard of care for patients with a positive (+) sentinel lymph node (SLN) is axillary dissection; however, for various reasons, some SLN+ patients do not undergo dissection. The purpose of this study was to define possible predictors of having four or more involved nodes to provide information for clinicians and patients making decisions about adjuvant chemotherapy and radiation.We reviewed the records of 402 patients with invasive breast cancer and one to three involved SLNs who underwent completion axillary dissection at two academic cancer centers. None of these patients received neoadjuvant chemotherapy. Factors associated with having four or more involved axillary nodes (SLNs and non-SLNs) were evaluated by univariate and multivariate logistic regression analysis.Eighty-seven patients had four or more positive nodes. On multivariate analysis, having four or more SLNs was associated with tumor histology, primary tumor size, lymphovascular space invasion, extranodal extension, the number of involved SLNs, the number of uninvolved SLNs, and the size of the largest SLN metastasis. A nomogram to predict the probability of having four or more nodes based on patients' pathologic data was developed from the multivariate logistic regression model. A separate previously published data set of 206 SLN+ patients treated at a community hospital in another city was used to validate this model.Patients with a low probability of having four or more nodes can be identified from known pathologic features. The nomogram developed will be helpful to clinicians making adjuvant treatment recommendations.
Extracellular Superoxide Dismutase Protects against Proteinuric Kidney Disease
Authors: Roderick J. Tan, Dong Zhou, Liangxiang Xiao, Lili Zhou, Yingjian Li, Sheldon I. Bastacky, Tim D. Oury, Youhua Liu
Journal: Journal of the American Society of Nephrology (2015)

Extracellular superoxide dismutase (EC-SOD), also known as SOD3, is an antioxidant expressed at high levels in normal adult kidneys. Because oxidative stress contributes to a variety of kidney injuries, we hypothesized that EC-SOD may be protective in CKD progression. To study this hypothesis, we used a murine model of ADR nephropathy characterized by albuminuria and renal dysfunction. We found that levels of EC-SOD diminished throughout the course of disease progression and were associated with increased levels of NADPH oxidase and oxidative stress markers. EC-SOD null mice were sensitized to ADR injury, as evidenced by increases in albuminuria, serum creatinine, histologic damage, and oxidative stress. The absence of EC-SOD led to increased levels of NADPH oxidase and an increase in β-catenin signaling, which has been shown to be pathologic in a variety of kidney injuries. Exposure of EC-SOD null mice to either chronic angiotensin II infusion or to daily albumin injections also caused increased proteinuria. In contrast, EC-SOD null mice subjected to nonproteinuric CKD induced by unilateral ureteral obstruction exhibited no differences compared with wild-type mice. Finally, we also found a decrease in EC-SOD in human CKD biopsy samples, similar to our findings in mice. Therefore, we conclude that EC-SOD is protective in CKDs characterized by proteinuria.
Adopting Clean Fuels and Technologies on School Buses. Pollution and Health Impacts in Children
Authors: Sara D. Adar, Jennifer D’Souza, Lianne Sheppard, Joel D. Kaufman, Teal S. Hallstrand, Mark E. Davey, James R. Sullivan, Jordan Jahnke, Jane Koenig, Timothy V. Larson, L. J. Sally Liu
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

More than 25 million American children breathe polluted air on diesel school buses. Emission reduction policies exist, but the health impacts to individual children have not been evaluated.Using a natural experiment, we characterized the exposures and health of 275 school bus riders before, during, and after the adoption of clean technologies and fuels between 2005 and 2009. Air pollution was measured during 597 trips on 188 school buses. Repeated measures of exhaled nitric oxide (FeNO), lung function (FEV1, FVC), and absenteeism were also collected monthly (1,768 visits). Mixed-effects models longitudinally related the adoption of diesel oxidation catalysts (DOCs), closed crankcase ventilation systems (CCVs), ultralow-sulfur diesel (ULSD), or biodiesel with exposures and health.Fine and ultrafine particle concentrations were 10-50% lower on buses using ULSD, DOCs, and/or CCVs. ULSD adoption was also associated with reduced FeNO (-16% [95% confidence interval (CI), -21 to -10%]), greater changes in FVC and FEV1 (0.02 [95% CI, 0.003 to 0.05] and 0.01 [95% CI, -0.006 to 0.03] L/yr, respectively), and lower absenteeism (-8% [95% CI, -16.0 to -0.7%]), with stronger associations among patients with asthma. DOCs, and to a lesser extent CCVs, also were associated with improved FeNO, FVC growth, and absenteeism, but these findings were primarily restricted to patients with persistent asthma and were often sensitive to control for ULSD. No health benefits were noted for biodiesel. Extrapolating to the U.S. population, changed fuel/technologies likely reduced absenteeism by more than 14 million/yr.National and local diesel policies appear to have reduced children's exposures and improved health.
Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
Authors: Hans-Reimer Rodewald, Claudia Waskow, Corinne Haller
Journal: The Journal of Experimental Medicine (2001)

The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor γ chain (γc) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferation, survival, or differentiation, but the contribution of each receptor to distinct intracellular signaling cascades is only poorly defined. Here, we have examined whether enforced expression of Bcl-2 can rescue thymocyte development in c-kit and γc single or double mutant mice. A bcl-2 transgene (Eμ-bcl-2-25; expressed in the T cell lineage) was introduced into (a) c-kit and γc wild-type (c-kit+γc+bcl+), (b) c-kit–deficient (c-kit−γc+bcl+), (c) γc-deficient (c-kit+γc−bcl+), or (d) c-kit and γc double-deficient mice (c-kit−γc−bcl+). The bcl-2 transgene was functionally active in wild-type and c-kit or γc single mutants, as it promoted survival of ex vivo isolated thymocytes, including pro-T cells. In vivo, however, transgenic Bcl-2 did not release T cell precursors from their phenotypic block and failed to increase progenitor or total thymocyte cellularity in c-kit or γc single or double mutants. These data argue strongly against a role for Bcl-2 as a key mediator in signaling pathways linked to cytokine and growth factor receptors driving early thymocyte development.
Local Targeting of Malignant Gliomas by the Diffusible Peptidic Vector 1,4,7,10-Tetraazacyclododecane-1-Glutaric Acid-4,7,10-Triacetic Acid-Substance P
Authors: Stefan Kneifel, Dominik Cordier, Stephan Good, Mihai C.S. Ionescu, Anthony Ghaffari, Silvia Hofer, Martin Kretzschmar, Markus Tolnay, Christos Apostolidis, Beatrice Waser, Marlene Arnold, Jan Mueller-Brand, Helmut R. Maecke, Jean Claude Reubi, Adrian Merlo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Malignant glial brain tumors consistently overexpress neurokinin type 1 receptors. In classic seed-based brachytherapy, one to several rigid 125I seeds are inserted, mainly for the treatment of small low-grade gliomas. The complex geometry of rapidly proliferating high-grade gliomas requires a diffusible system targeting tumor-associated surface structures to saturate the tumor, including its margins. Experimental Design: We developed a new targeting vector by conjugating the chelator 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid to Arg1 of substance P, generating a radiopharmaceutical with a molecular weight of 1,806 Da and an IC50 of 0.88 ± 0.34 nmol/L. Cell biological studies were done with glioblastoma cell lines. neurokinin type-1 receptor (NK1R) autoradiography was done with 58 tumor biopsies. For labeling, 90Y was mostly used. To reduce the “cross-fire effect” in critically located tumors, 177Lut and 213Bi were used instead. In a pilot study, we assessed feasibility, biodistribution, and early and long-term toxicity following i.t. injection of radiolabeled 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid substance P in 14 glioblastoma and six glioma patients of WHO grades 2 to 3. Results: Autoradiography disclosed overexpression of NK1R in 55 of 58 gliomas of WHO grades 2 to 4. Internalization of the peptidic vector was found to be specific. Clinically, the radiopharmeutical was distributed according to tumor geometry. Only transient toxicity was seen as symptomatic radiogenic edema in one patient (observation period, 7-66 months). Disease stabilization and/or improved neurologic status was observed in 13 of 20 patients. Secondary resection disclosed widespread radiation necrosis with improved demarcation. Conclusions: Targeted radiotherapy using diffusible peptidic vectors represents an innovative strategy for local control of malignant gliomas, which will be further assessed as a neoadjuvant approach.
Lung function measurement in awake young children
Authors: H Bisgaard, B Klug
Journal: European Respiratory Journal (1995)

The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint) and transcutaneous measurements of oxygen tension (Ptc,O2) were compared with concomitant measurements of specific airway resistance (sRaw) and forced expiratory volume in one second (FEV1) by whole body plethysmography and spirometry, respectively, during methacholine challenge in 21 young children aged 4-6 yrs, with suspected asthma. Measurements with each technique were repeated after each challenge step. A special face-mask was developed with an integrated mouthpiece which ensured mouth breathing during the measurements. The order of sensitivity of the techniques to assess methacholine-induced changes in lung function was ZIOS > sRaw > Ptc,O2 > FEV1 > Rint. ZIOS was significantly more sensitive than all subsequent methods, and Ptc,O2 was significantly more sensitive than FEV1. ZIOS, sRaw and Rint, but not Ptc,O2 and FEV1, detected the subclinical increase in bronchial muscle tone in the children during baseline, which was revealed by the significantly reduced airway obstruction after inhalation of a beta 2-agonist as compared to baseline. It is concluded that ZIOS, Rint and Ptc,O2 change in parallel with sRaw and FEV1 and with a comparable sensitivity during simultanoeous measurements of the response to methacholine in young children aged 4-6 yrs. This implies that ZIOS, Rint and Ptc,O2 provide convenient indices of changes in lung function. Their combined use will be useful for monitoring airway diseases of young children.
Incidental Appendectomies
Authors: Robert J. Hays
Journal: JAMA (1977)

INCIDENTAL appendectomy continues to be highly controversial. Opinions about this operation vary widely, ranging from the view that the appendix should be removed virtually every time the peritoneal cavity is opened to the belief that incidental appendectomy is a meddlesome and dangerous operation that should never be performed. Because of this diversity of opinion, a study was undertaken to determine the current teaching regarding incidental appendectomy in all approved residency training programs in general surgery and obstetrics-gynecology in the United States today.  From 1975 to 1976, all directors of approved residencies in general surgery and in obstetrics-gynecology in the United States, listed in the American Medical Association Directory of Approved Internships and Residencies, were sent a questionnaire.  The directors of 467 surgical programs were asked to give an unqualified yes or no to the question: Do you recommend incidental appendectomy in uncomplicated (1) intra-abdominal operations in which the gastrointestinal tract
Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Myeloma
Authors: Lotfi Benboubker, Meletios A. Dimopoulos, Angela Dispenzieri, John Catalano, Andrew R. Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier de la Rubia, Lugui Qiu, Darrell J. White, Daniel Binder, Kenneth Anderson, Jean-Paul Fermand, Philippe Moreau, Michel Attal, Robert Knight, Guang Chen, Jason Van Oostendorp, Christian Jacques, Annette Ervin-Haynes, Hervé Avet-Loiseau, Cyrille Hulin, Thierry Facon
Journal: New England Journal of Medicine (2014)

The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches.We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT.The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers.As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. (Funded by Intergroupe, Francophone du Myélome and Celgene; FIRST ClinicalTrials.gov number, NCT00689936; European Union Drug Regulating Authorities Clinical Trials number, 2007-004823-39.).
Response to acute ozone exposure in healthy men. Results of a screening procedure.
Authors: G G Weinmann, S M Bowes, M W Gerbase, A W Kimball, R Frank
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We screened 64 healthy, nonsmoking men, 18 to 35 yr old, for their sensitivity to 0.35 ppm ozone (O3) administered for 130 to 150 min with intermittent exercise. The changes in FVC, FEV1, AND FEF25-75 (p < 0.0001) immediately after O3 exposure varied widely among subjects. Histograms of the percentage changes in FVC and FEV1 did not differ from a unimodal, skewed (gamma) distribution (p = 0.99 and p = 0.17, respectively); the changes in FEF25-75 tended to deviate from a gamma distribution (p = 0.055). To adjust FEF25-75 for the confounding effects of O3 on FVC, we used multiple linear regression analysis with contemporaneous FVC as a covariable, analysis of a subgroup of nine subjects whose O3-induced FVC changes were < or = 5%, and volume correction of FEF25-75 for any changes in FVC after exposure. These analyses showed reductions in FEF25-75 unexplained by and following a different time course than the O3-induced changes in FVC. In 26 subjects also exposed to filtered air, significant effects of O3 on respiratory frequency (p < 0.004) and tidal volume (p < 0.0007) correlated weakly with FVC changes. The results confirm the wide variability in spirometric responsiveness among individuals to O3 and suggest that intrinsic narrowing of the small airways may be a significant component of the functional response.