tbuckley/cabot-search huggingface dataset:
Characterization of Right Ventricular Diastolic Performance After Complete Repair of Tetralogy of Fallot
Authors: Seamus Cullen, Darryl Shore, Andrew Redington
Journal: Circulation (1995)

Prolonged postoperative recovery caused by a low cardiac output state occurs in some patients after complete repair of tetralogy of Fallot. Biventricular systolic function is usually well preserved in these patients. The contribution of impaired diastolic function, particularly of the right ventricle, has not been studied in detail; therefore, we performed a prospective study of right ventricular diastolic function in this patient group.We studied biventricular systolic and diastolic function using Doppler echocardiographic examination. Tricuspid valve, superior vena caval, pulmonary arterial, and mitral valve Doppler spectrals were obtained during the first postoperative day in 35 patients aged 6 months to 45 years who underwent complete repair of tetralogy of Fallot. Biventricular systolic function was grossly normal in all patients. Isolated restrictive right ventricular physiology characterized by pulmonary arterial antegrade flow coincident with atrial systole and associated with prominent retrograde superior vena caval flow was seen in 17 of the 35 patients (group 1). This flow was augmented during the expiratory phase of positive pressure ventilation and abolished or greatly diminished during the inspiratory phase (P < .001). An increase in the duration of pulmonary regurgitation occurred during the inspiratory phase of positive pressure ventilation in these patients (P < .01). All patients with right ventricular restriction had a clinical picture compatible with a low cardiac output state, requiring prolonged stays in intensive care and the hospital. Clinical improvement was mirrored by resolution of the Doppler markers of right ventricular restriction in most of the patients.Isolated right ventricular restriction is characterized by antegrade diastolic pulmonary arterial flow on Doppler echocardiography and is responsible for the slower postoperative course and clinical evidence of low cardiac output state in some patients after complete repair of tetralogy of Fallot.
Effects of asbestos and smoking on the levels and rates of change of lung function in a crocidolite exposed cohort in Western Australia
Authors: H S Alfonso
Journal: Thorax (2004)

Increased rates of death from asbestos related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom, Western Australia. Exposure to asbestos is associated with reduced static lung volumes, gas transfer and lung compliance, and a restrictive ventilatory abnormality.The effects of crocidolite exposure and smoking history on levels and rates of change of lung function were evaluated using a linear mixed model. Lung function was measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC.Cumulative doses of asbestos and the presence of radiographic asbestosis were associated with lower levels of FEV1 and FVC and a steeper decline during the period of observation. Subjects exposed to asbestos at a younger age had lower levels of FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung function than never smokers. No significant interactions between crocidolite exposure and smoking on the levels or rates of change of lung function were found.The deleterious effects of crocidolite exposure on lung function persist in this population, despite asbestos exposure having ceased more than 30 years ago. No significant interactions were found in this population between asbestos and smoking at the first visit or longitudinally.
Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate tumor development by promoting M2 polarization
Authors: Min Yang, Jingwei Liu, Jianghua Shao, Yanwen Qin, Qunsheng Ji, Xiaolin Zhang, Jie Du
Journal: Molecular Cancer (2014)

Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes influenced by the microenvironment surrounding tumor tissues, but relatively little is known about the key molecular in these cells that contribute to malignant phenotypes. Autophagic activity is a critical factor in tumor development that contributes to enhancing cellular fitness and survival in the hostile tumor microenvironment. However, the molecular basis and relations between autophagy and TAMs polarization remain unclear. Cathepsin S (Cat S) expression was analyzed in human colon carcinoma and normal colon tissues. In vivo effects were evaluated using PancO2 subcutaneous tumor model and SL4 hepatic metastasis model. Immunofluorescence staining, flow cytometry and real-time PCR were done to examine TAMs polarization. Western blotting assay, transmission electron microscopy, mCherry-GFP-LC3 transfection and DQ-BSA degradation assays were carried out to determine its role in regulating autophagy. In the present study, we showed that the enhanced expression of Cat S correlated with the severity of histologic grade as well as clinical stage, metastasis, and recurrence, which are known indicators of a relatively poor prognosis of human colon carcinoma. Cat S knockout led to decreased tumor growth and metastasis. Moreover, Cat S knockout inhibited M2 macrophage polarization during tumor development. We further demonstrated that Cat S was required for not only autophagic flux but also the fusion processes of autophagosomes and lysosomes in TAMs. Importantly, we found that Cat S contributed to tumor development by regulating the M2 phenotype of TAMs through the activation of autophagy. These results indicated that Cat S-mediated autophagic flux is an important mechanism for inducing M2-type polarization of TAMs, which leads to tumor development. These data provide strong evidence for a tumor-promoting role of autophagy in TAMs and suggest Cat S could be a potential target for cancer therapy.
Postoperative Adjuvant Dendritic Cell–Based Immunotherapy in Patients with Relapsed Glioblastoma Multiforme
Authors: Steven De Vleeschouwer, Steffen Fieuws, Stefan Rutkowski, Frank Van Calenbergh, Johannes Van Loon, Jan Goffin, Raf Sciot, Guido Wilms, Philippe Demaerel, Monika Warmuth-Metz, Niels Soerensen, Johannes E.A. Wolff, Sabine Wagner, Eckhart Kaempgen, Stefaan W. Van Gool
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse. Experimental Design: Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis. Results: Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event. Conclusion: Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.
Effect of ventilation strategy and surfactant on inflammation in experimental pneumonia
Authors: A. H. L. C. van Kaam, R. Lutter, R. A. Lachmann, J. J. Haitsma, E. Herting, M. Snoek, A. De Jaegere, J. H. Kok, B. Lachmann
Journal: European Respiratory Journal (2005)

This study explored, the inflammatory response during experimental pneumonia in surfactant-depleted animals as a function of ventilation strategies and surfactant treatment. Following intratracheal instillation of Group B streptococci (GBS), surfactant-depleted piglets were treated with conventional (positive-end expiratory pressure (PEEP) of 5 cmH 2 O, tidal volume 7 mL·kg −1 ) or open lung ventilation. During the latter, collapsed alveoli were recruited by applying high peak inspiratory pressures for a short period of time, combined with high levels of PEEP and the smallest possible pressure amplitude. Subgroups in both ventilation arms also received exogenous surfactant. Conventionally ventilated healthy animals receiving GBS and surfactant-depleted animals receiving saline served as controls. In contrast with both control groups, surfactant-depleted animals challenged with GBS and conventional ventilation showed high levels of interleukin (IL)-8, tumour necrosis factor (TNF)-α and myeloperoxidase in bronchoalveolar lavage fluid after 5 h of ventilation. Open lung ventilation attenuated this inflammatory response, but exogenous surfactant did not. Systemic dissemination of the inflammatory response was minimal, as indicated by low serum levels of IL-8 and TNF-α. In conclusion, the current study indicates that the ventilation strategy, but not exogenous surfactant, is an important modulator of the inflammation during Group B streptococci pneumonia in mechanically ventilated surfactant-depleted animals.
Matrix metalloproteinases as mediators of tissue injury in different forms of cutaneous lupus erythematosus
Authors: T.M. Järvinen, P. Kanninen, L. Jeskanen, S. Koskenmies, J. Panelius, T. Hasan, A. Ranki, U. Saarialho-Kere
Journal: British Journal of Dermatology (2007)

Matrix metalloproteinases (MMPs) contribute to tissue destruction, regeneration, inflammation and apoptosis and several of them are upregulated by ultraviolet (UV) radiation in skin. Although some MMPs associate with organ manifestations of systemic lupus erythematosus (SLE), their role in cutaneous lupus erythematosus (LE) is elusive.Our aim was to evaluate the expression of MMPs in SLE, subacute cutaneous LE (SCLE) and discoid LE (DLE) skin lesions and their relation to apoptosis and epidermal changes.Lesional skin biopsies from 20 patients with SLE, 20 with DLE and 17 with SCLE, and from UVA/UVB-photoprovoked skin of healthy volunteers were immunostained using antibodies to multiple MMPs and tissue inhibitors of metalloproteinases (TIMPs). The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling) method was used for detection of apoptosis.MMP-3, -10, -19 and -26 were abundantly expressed by keratinocytes in SLE, DLE and SCLE skin samples. MMP-7 was detected in keratinocytes in regions of oedema and vacuolization especially in SLE and SCLE, while MMP-14 was only occasionally observed in keratinocytes. Photoprovocation did not induce MMP-10 or -26 expression in skin of healthy volunteers. Epithelial TIMP-1 expression was low while occasional positive fibroblasts were seen in the dermis. TIMP-3 was abundantly expressed in the epidermis, endothelial cells and macrophages.Different subtypes of cutaneous LE are fairly similar in their MMP expression profile. MMP-3 and -10 mediate both epidermal changes and dermal tissue remodelling but are not present in lymphocytes. Low expression of TIMP-1 suggests that lupus skin is characterized by proteolytic events, and targeted action using selective MMP inhibitors may reduce lupus-induced damage in inflamed tissues.
Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice
Authors: Takahisa Murata, Michelle I. Lin, Yan Huang, Jun Yu, Phillip Michael Bauer, Frank J. Giordano, William C. Sessa
Journal: The Journal of Experimental Medicine (2007)

Caveolin-1 (Cav-1) is the principal structural component of caveolae organelles in smooth muscle cells, adipocytes, fibroblasts, epithelial cells, and endothelial cells (ECs). Cav-1–deficient (Cav-1 knockout [KO]) mice are viable and show increases of nitric oxide (NO) production in vasculature, cardiomyopathy, and pulmonary dysfunction. In this study, we generated EC-specific Cav-1–reconstituted (Cav-1 RC) mice and reexamined vascular, cardiac, and pulmonary phenotypes. Cav-1 KO pulmonary arteries had decreased smooth muscle contractility and increased endothelial NO synthase activation and hypotension; the latter two effects were rescued completely in Cav-1 RC mice. Cav-1 KO mice exhibited myocardial hypertrophy, pulmonary hypertension, and alveolar cell hyperproliferation caused by constitutive activation of p42/44 mitogen-activated protein kinase and Akt. Interestingly, in Cav-1 RC mice, cardiac hypertrophy and pulmonary hypertension were completely rescued, whereas alveolar hyperplasia was partially recovered because of the lack of rescue of Cav-1 in bronchiolar epithelial cells. These results provide clear physiological evidence supporting the important role of cell type–specific Cav-1 expression governing multiple phenotypes in the vasculature, heart, and lung.
Pediatric gastrointestinal disease: Pathophysiology, diagnosis, management. Edited by W.A. Walker, P.R. Durie, J.R. Hamilton, JA. Walker-Smith and J.B. Watkins, 1,785 pp., 2 vol. Philadelphia: B C Decker Inc., 1991. $298
Authors: Janna C. Collins
Journal: Hepatology (1991)
Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice
Authors: Christophe Viret, Stéphane Leung-Theung-Long, Laurent Serre, Camille Lamare, Dario A.A. Vignali, Bernard Malissen, Alice Carrier, Sylvie Guerder
Journal: Journal of Clinical Investigation (2011)

Type 1 diabetes is a chronic autoimmune disease in which genetic predispositions affect the immune system, leading to a loss of T cell tolerance to β cells and consequent T cell-mediated destruction of insulin-producing islet cells. Genetic studies have suggested that PRSS16 is linked to a diabetes susceptibility locus of the extended HLA class I region in humans. PRSS16 encodes what we believe to be a novel protease, thymus-specific serine protease (TSSP), which shows predominant expression in thymic epithelial cells and is suspected to have a restricted role in the class II presentation pathway. Consistently, Tssp is necessary for the intrathymic selection of few class II-restricted T cell receptor specificities in B6 mice. To directly assess the role of Tssp in autoimmune diabetes, we generated Tssp-deficient (Tssp°) NOD mice. While remaining immunocompetent, Tssp° NOD mice were protected from diabetes and severe insulitis. Diabetes resistance of Tssp° NOD mice was a property of the CD4 T cell compartment that is acquired during thymic selection and correlated with an impaired selection of CD4 T cells specific for islet antigens. Hence, in the NOD mouse, Tssp is a critical regulator of diabetes development through the selection of the autoreactive CD4 T cell repertoire.
The Association of Bronchial Carcinoid and Pluriglandular Adenomatosis
Authors: E. D. Williams, L. R. Celestin
Journal: Thorax (1962)

The syndrome of multiple endocrine adenomas in which pituitary, parathyroid, pancreatic islets, and adrenals may be involved has received much attention recently, mainly because of its intricate relationship to the Zollinger-Ellison syndrome, which associates non-beta pancreatic islet tumours with recurrent peptic ulceration. One of the interesting facets of pluriglandular adenomatosis is its association with other unusual tumours; in the case reported here a bronchial carcinoid was present. It is also one more example of a patient in whom the diagnosis of Zollinger-Ellison syndrome was considered during life, and who at necropsy had multiple endocrine tumours.
CHEMICAL STUDIES IN HOST-VIRUS INTERACTIONS
Authors: Catherine B. Fowler, Seymour S. Cohen
Journal: The Journal of Experimental Medicine (1948)

Using the one-step growth technique the production of the virus T2 in its host, measured by latent period and burst size, was shown to depend on the nutritional environment of the host cell. When E. coli, grown in broth, was transferred to a simple medium, single organic compounds such as some amino acids and nucleosides were found to increase or accelerate the synthesis of virus. An antimetabolite of glutamic acid, an amino acid important for virus synthesis, was shown to be inhibitory. Several naturally occurring amino acids, leucine, serine, and cysteine, inhibited virus synthesis in the simple medium. A chemically defined mixture was found which supported a rate of virus synthesis very nearly comparable to that found for host cells in nutrient broth.
Debating the Oncologist's Role in Defining the Value of Cancer Care: We Have a Duty to Society
Authors: Reshma Jagsi
Journal: Journal of Clinical Oncology (2014)

Unsustainable Increases in Health Care Spending The rising costs of health care in general and cancer care in particular have prompted increasing concern in recent years. Data from the Organisation for Economic Co-operation and Development suggest that health care expenditure as a percent of gross domestic product is not only higher in the United States than in other developed nations but is also rising at a steeper rate. In 2011, the United States spent a staggering 18% of gross domestic product—$2.7 trillion— on health care. Although some have been optimistic that the rate of growth is finally slowing, perhaps reflecting the impact of payment reforms and the Affordable Care Act, experts warn that the evidence is more consistent with the effects of the recent recession and one-time changes that will not ultimately result in a long-term flattening of the cost curve. Cancer care accounts for a substantial share of health care spending and appears to be growing even faster than health care costs overall; US expenditures for cancer care were $72B in 2004 and $126B by 2010. Evidence suggests that this increase reflects not only those advances in early detection, prevention, and treatment that have led to improvements in cancer mortality but also the increasing use of aggressive therapy near the end of life, raising concerns that increases in cost have not been accompanied by commensurate improvements in quality. Although we as oncologists recognize that measures such as expenditures in the last months of life are imperfect, most of us also have direct experiences that validate the underlying concern that we do not always direct scarce resources optimally. Many have voiced concerns about the potential impact of this pattern of health care spending on economic stability and, somewhat ironically, population health within the United States. The substantial and increasing share of resources devoted toward health care inevitably crowds out other types of essential spending. This includes education and social services which, like health care, have an important impact on population health.
The response to combination therapy treatment regimens in severe/difficult-to-treat asthma
Authors: J. D. Campbell, L. Borish, T. Haselkorn, L. Rasouliyan, J. H. Lee, S. E. Wenzel, S. D. Sullivan
Journal: European Respiratory Journal (2008)

The aim of the present study was to assess the response of high-dose salmeterol/fluticasone combination (SFC) and low-dose SFC compared with regimens without inhaled corticosteroid (ICS) plus long-acting β-agonist (LABA) in a large cohort with severe or difficult-to-treat asthma. Subjects were administered low-dose SFC (100/50 or 250/50 μg) or high-dose SFC (500/50 μg), and a control group received medications that could include ICS or LABA but not both. The present authors calculated unadjusted and propensity score-adjusted differences in outcomes consistent with components of asthma control, comparing high-dose and low-dose SFC cohorts with controls. The low-dose SFC cohort had higher asthma-related quality of life and fewer asthma control problems compared with controls. The high-dose SFC cohort had higher forced expiratory volume in one second but higher odds of having severe asthma compared with controls. The present results support the evidence that some asthmatics achieve better outcomes while receiving a low-dose salmeterol/fluticasone combination, but also suggest that those on a high-dose salmeterol/fluticasone combination fail to achieve significant improvement in many control-related health outcomes as compared with similar patients not receiving salmeterol/fluticasone combination. These findings suggest a limited value of high-dose salmeterol/fluticasone combination compared with the alternatives. While additional studies are needed, the present findings call for alternative therapeutic approaches in severe/difficult-to-treat asthma for those unable to attain asthma control with or without salmeterol/fluticasone combination.
Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial
Authors: RF van Vollenhoven, S Ernestam, P Geborek, IF Petersson, L Cöster, E Waltbrand, A Zickert, J Theander, Å Thörner, H Hellström, A Teleman, C Dackhammar, F Akre, K Forslind, L Ljung, R Oding, A Chatzidionysiou, M Wörnert, J Bratt
Journal: The Lancet (2009)
Evidence for the synthesis and release of strongly immunosuppressive, noncytotoxic substances by Streptococcus intermedius.
Authors: M P Arala-Chaves, T B Higerd, M T Porto, J Munoz, J M Goust, H H Fudenberg, C B Loadholt
Journal: Journal of Clinical Investigation (1979)

Products secreted by Streptococcus intermedius were studied for their effects on the immune response. Three different preparations of crude extracellular products from S. intermedius (CEP-Si) were found to have powerful suppressor activity in vitro as shown by inhibition of human lymphocyte proliferation (uptake of [3H]thymidine) and protein synthesis in response to a wide variety of stimulants, including mitogens and antigens, and suppression of plaque formation by human cells in response to sheep erythrocytes. CEP-Si was noncytotoxic, because cells incubated with high concentrations of CEP-Si and subsequently washed were viable and recovered their ability to respond to mitogens, and because leukocyte migration was not inhibited by CEP-Si, nor was the release of leukocyte migration inhibitory factor from sensitized lymphocytes. The possibility of antigen or mitogen competition was excluded. The effects of CEP-Si in vitro were time dependent and did not require the presence of monocytes. Cells pretreated with CEP-Si and then washed suppressed plaque formation by fresh autologous cells in highly stimulated cultures. CEP-Si injected into C57BL/6 mice also strongly suppressed their immune response to sheep erythrocytes, and the in vivo suppression was correlated with the effects of CEP-Si in vitro.