tbuckley/cabot-search huggingface dataset:
Aortic Dissection: New Frontiers in Diagnosis and Management
Authors: Christoph A. Nienaber, Kim A. Eagle
Journal: Circulation (2003)

C ardiovascular disease is the leading cause of death in most Western societies and is increasing steadily in many developing countries.Aortic diseases constitute an emerging share of the burden.New diagnostic imaging modalities, longer life expectancy in general, longer exposure to elevated blood pressure, and the proliferation of modern noninvasive imaging modalities have all contributed to the growing awareness of acute and chronic aortic syndromes.][3][4][5][6][7][8][9][10][11][12][13] This comprehensive review is organized in two parts, with a focus on the etiology, natural history, and classification (with vascular staging) of aortic wall disease in Part I and emphasis on therapeutic management and follow-up in Part II.Both parts may help to better integrate the complexities of acute aortic syndromes. I. Etiology of Aortic DissectionAll mechanisms weakening the aorta's media layers via micro apoplexy of the vessel wall lead to higher wall stress, which can induce aortic dilatation and aneurysm formation, eventually resulting in intramural hemorrhage, aortic dissection, or rupture (Table 1).Three major inherited connective tissue disorders are currently known to affect the arterial walls: (1) Marfan's syndrome, (2) Ehlers-Danlos syndrome, and (3) familial forms of thoracic aneurysm and dissection. Ehlers-Danlos SyndromeEhlers-Danlos syndrome (EDS) is a heterogeneous group of hereditable connective tissue disorders characterized by ar-
Pediatric Pulmonary Hypertension in the Netherlands
Authors: Rosa Laura E. van Loon, Marcus T.R. Roofthooft, Hans L. Hillege, Arend D.J. ten Harkel, Magdalena van Osch-Gevers, Tammo Delhaas, Livia Kapusta, Jan L.M. Strengers, Lukas Rammeloo, Sally-Ann B. Clur, Barbara J.M. Mulder, Rolf M.F. Berger
Journal: Circulation (2011)

Background— Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH. Methods and Results— Two registries were used to retrospectively identify children (0–17 years) with PH. Overall, 3263 pediatric patients were identified with PH due to left heart disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease (n=5; &lt;1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH. Transient PAH included persistent PH of the newborn and children with congenital heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after successful shunt correction. Progressive PAH mainly included idiopathic PAH (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial hypertension associated with CHD represented highly heterogeneous subgroups. Syndromes were frequently present, especially in progressive PAH (n=60; 39%). Survival for PAH-CHD varied depending on the subgroups, some showing better and others showing worse survival than for iPAH. Survival of children with Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH-CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4 (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies in adults, iPAH occurred less whereas PAH-CHD occurred more frequently. Conclusions— Pediatric PH is characterized by various age-specific diagnoses, the majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is lower whereas incidence of pediatric PAH-CHD is higher than reported in adults. Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical courses.
Targeting Tumor Antigens to Secreted Membrane Vesicles<i>In vivo</i>Induces Efficient Antitumor Immune Responses
Authors: Ingrid S. Zeelenberg, Matias Ostrowski, Sophie Krumeich, Angélique Bobrie, Carolina Jancic, Alexandre Boissonnas, Alain Delcayre, Jean-Bernard Le Pecq, Béhazine Combadière, Sebastian Amigorena, Clotilde Théry
Journal: Cancer Research (2008)

Abstract Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII–like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols. [Cancer Res 2008;68(4):1228–35]
Parasite infections and the risk of asthma and atopy
Authors: N. R LYNCH, J GOLDBLATT, P N LE SOUEF
Journal: Thorax (1999)

12 Since parasitic infection is endemic in the majority of the world’s population,the relationship between helminthic infection and the IgE response is highly relevant to the understanding of allergic diseases. There is a general consensus that IgE antibody is an important component of the immune resistance to helminthiasis, 5‐9 although some conflicting results have been obtained. 34 Local IgE reactions can create unfavourable conditions in the gut for intestinal parasites, and IgE can mediate the cytotoxic activity of eosinophils against parasitic larvae. These observations have led to the concept that, from an evolutionary perspective, the primary function of the allergic response may be as part of an anti-parasitic protective mechanism, and allergic disease may be the undesirable reaction towards otherwise inoVensive environmental substances. 10
Protein Kinase X Activates Ureteric Bud Branching Morphogenesis in Developing Mouse Metanephric Kidney
Authors: Xiaohong Li, Deborah P. Hyink, Katalin Polgar, G. Luca Gusella, Patricia D. Wilson, Christopher R. Burrow
Journal: Journal of the American Society of Nephrology (2005)

The human protein kinase X (PRKX) gene was identified previously as a cAMP-dependent serine/threonine kinase that is aberrantly expressed in autosomal dominant polycystic disease kidneys and normally expressed in fetal kidneys. The PRKX kinase belongs to a serine/threonine kinase family that is phylogenetically and functionally distinct from classical protein kinase A kinases. Expression of PRKX activates cAMP-dependent renal epithelial cell migration and tubular morphogenesis in cell culture, suggesting that it might regulate branching growth of the collecting duct system in the fetal kidney. With the use of a mouse embryonic kidney organ culture system that recapitulates early kidney development in vitro, it is demonstrated that lentiviral vector-driven expression of a constitutively active, cAMP-independent PRKX in the ureteric bud epithelium stimulates branching morphogenesis and results in a 2.5-fold increase in glomerular number. These results suggest that PRKX stimulates epithelial branching morphogenesis by activating cell migration and support a role for this kinase in the regulation of nephrogenesis and of collecting system development in the fetal kidney.
Ovarian disorders in domestic animals.
Authors: N J MacLachlan
Journal: Environmental Health Perspectives (1987)

The histologic appearance of the ovaries and persistence of corpora lutea vary considerably among domestic animals, particularly between spontaneous and induced ovulators. The seasonally polyestrous mare has a variety of unique characteristics in ovarian structure and general reproductive function. Among the anomalies of ovarian development is the bovine freemartin with gonads containing a mixture of male and female elements. A variety of ovarian cysts occur in domestic animals, and persistent corpora lutea with associated reproductive perturbations occur in several species. Ovarian tumors are relatively uncommon in domestic animals, with most examples described in dogs, cats, and horses. These ovarian neoplasms are generally classified as epithelial, germ cell, or sex cord-stromal tumors.
Provision of home mechanical ventilation and sleep services for England survey: Table 1
Authors: S Mandal, E Suh, M Davies, I Smith, T M Maher, M W Elliott, A C Davidson, N Hart
Journal: Thorax (2013)

The Department of Health is promoting the generation of specialist networks to manage long term ventilatory weaning and domiciliary non-invasive ventilation patients. Currently the availability of these services in England is not known. We performed a short survey to establish the prevalence of sleep and ventilation diagnostic and treatment services. The survey focussed on diagnostic services and Home Mechanical Ventilation (HMV) provision, and was divided into (a) availability of diagnostics, (b) funding, and (c) patient groups. This survey has confirmed that the majority of Home Mechanical Ventilation set-ups are currently for Obesity Related Respiratory Failure and Chronic Obstructive Pulmonary Disease. We have found that there is variable provision of diagnostic services, with the majority of units offering overnight oximetry (95%) but only 55% of responders providing a home mechanical ventilation service. Even more interestingly, less than two thirds of units charged their primary care trust for this service. These data may assist in the development of regional networks and specialist home mechanical ventilation centres.
Integrins, membrane-type matrix metalloproteinases and ADAMs: Potential implications for cardiac remodeling
Authors: A MANSO, L ELSHERIF, S KANG, R ROSS
Journal: Cardiovascular Research (2005)

The concept of myocardial remodeling links an initial pathological insult to a progressive geometric change of the ventricle. Currently, our concepts of the remodeling process have evolved to include not only changes in ventricular size and shape, but cellular and molecular remodeling, particularly as the ventricle evolves towards failure. In recent years, much attention has focused on the role of cell-extracellular matrix (ECM) connections in this process. In this review, we will specifically delineate how cell membrane-linked molecules of three classes: integrins, membrane-type matrix metalloproteinases, and ADAMs (A Disintegrin And Metalloproteinase) might play crucial roles in myocardial remodeling. These molecules are essential for cell-ECM adhesion, cell signaling, matrix modification, and proteolysis of surface receptors. Our goal is to put forth concepts on how they might interrelate to modulate the remodeling process in the heart.
Apoptosis Regulates Human Vascular Calcification In Vitro
Authors: Diane Proudfoot, Jeremy N. Skepper, Laszlo Hegyi, Martin R. Bennett, Catherine M. Shanahan, Peter L. Weissberg
Journal: Circulation Research (2000)

Abstract —The mechanisms involved in the initiation of vascular calcification are not known, but matrix vesicles, the nucleation sites for calcium crystal formation in bone, are likely candidates, because similar structures have been found in calcified arteries. The regulation of matrix vesicle production is poorly understood but is thought to be associated with apoptotic cell death. In the present study, we investigated the role of apoptosis in vascular calcification. We report that apoptosis occurs in a human vascular calcification model in which postconfluent vascular smooth muscle cell (VSMC) cultures form nodules spontaneously and calcify after ≈28 days. Apoptosis occurred before the onset of calcification in VSMC nodules and was detected by several methods, including nuclear morphology, the TUNEL technique, and external display of phosphatidyl serine. Inhibition of apoptosis with the caspase inhibitor ZVAD.fmk reduced calcification in nodules by ≈40%, as measured by the cresolphthalein method and alizarin red staining. In addition, when apoptosis was stimulated in nodular cultures with anti-Fas IgM, there was a 10-fold increase in calcification. Furthermore, incubation of VSMC-derived apoptotic bodies with 45 Ca demonstrated that, like matrix vesicles, they can concentrate calcium. These observations provide evidence that apoptosis precedes VSMC calcification and that apoptotic bodies derived from VSMCs may act as nucleating structures for calcium crystal formation.
Cost effectiveness of inhaled steroid withdrawal in outpatients with chronic obstructive pulmonary disease
Authors: J van der Palen
Journal: Thorax (2005)

<b>Background:</b> The evidence for the effectiveness and safety of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is inconclusive. This study determined the cost effectiveness of withdrawing fluticasone propionate (FP) in outpatients with COPD. <b>Methods:</b> The cost effectiveness analysis was based on a randomised, placebo controlled FP withdrawal study. After a 4 month run in period on FP, patients were randomly assigned to continue FP 500 μg twice daily or to receive placebo for 6 months. A decision analytical model evaluated the 6 month incremental cost effectiveness of the ICS versus ICS withdrawal strategy. One way sensitivity analyses and a Monte Carlo simulation were performed to evaluate the robustness of the findings. <b>Results:</b> The average patient with COPD in the FP group generated €511 in direct medical costs, including €238 for FP. The cost of the placebo strategy was €456. The higher direct drug cost of €212 per patient for the FP strategy during the 6 month follow up period compared with the placebo group was partially offset by a lower exacerbation and hospital admission cost of €157. The 6 month incremental cost effectiveness of the FP strategy compared with placebo was €110 per exacerbation prevented and €1286 per hospital admission prevented. <b>Conclusions:</b> Over a 6 month period, withdrawing FP in a pre-selected trial population of COPD patients led to absolute cost savings but with a higher rate of exacerbations and hospital admissions.
Local β-Adrenergic Stimulation Overcomes Source-Sink Mismatch to Generate Focal Arrhythmia
Authors: Rachel C. Myles, Lianguo Wang, Chaoyi Kang, Donald M. Bers, Crystal M. Ripplinger
Journal: Circulation Research (2012)

Rationale: β-Adrenergic receptor stimulation produces sarcoplasmic reticulum Ca 2+ overload and delayed afterdepolarizations in isolated ventricular myocytes. How delayed afterdepolarizations are synchronized to overcome the source-sink mismatch and produce focal arrhythmia in the intact heart remains unknown. Objective: To determine whether local β-adrenergic receptor stimulation produces spatiotemporal synchronization of delayed afterdepolarizations and to examine the effects of tissue geometry and cell-cell coupling on the induction of focal arrhythmia. Methods and Results: Simultaneous optical mapping of transmembrane potential and Ca 2+ transients was performed in normal rabbit hearts during subepicardial injections (50 μL) of norepinephrine (NE) or control (normal Tyrode's solution). Local NE produced premature ventricular complexes (PVCs) from the injection site that were dose-dependent (low-dose [30–60 μmol/L], 0.45±0.62 PVCs per injection; high-dose [125–250 μmol/L], 1.33±1.46 PVCs per injection; P &lt;0.0001) and were inhibited by propranolol. NE-induced PVCs exhibited abnormal voltage–Ca 2+ delay at the initiation site and were inhibited by either sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase inhibition or reduced perfusate [Ca 2+ ], which indicates a Ca 2+ -mediated mechanism. NE-induced PVCs were more common at right ventricular than at left ventricular sites (1.48±1.50 versus 0.55±0.89, P &lt;0.01), and this was unchanged after chemical ablation of endocardial Purkinje fibers, which suggests that source-sink interactions may contribute to the greater propensity to right ventricular PVCs. Partial gap junction uncoupling with carbenoxolone (25 μmol/L) increased focal activity (2.18±1.43 versus 1.33±1.46 PVCs per injection, P &lt;0.05), which further supports source-sink balance as a critical mediator of Ca 2+ -induced PVCs. Conclusions: These data provide the first experimental demonstration that localized β-adrenergic receptor stimulation produces spatiotemporal synchronization of sarcoplasmic reticulum Ca 2+ overload and release in the intact heart and highlight the critical nature of source-sink balance in initiating focal arrhythmias.
Preoperative Identification of a Low-Risk Group for Lymph Node Metastasis in Endometrial Cancer: A Korean Gynecologic Oncology Group Study
Authors: Sokbom Kang, Woo Dae Kang, Hyun Hoon Chung, Dae Hoon Jeong, Sang-Soo Seo, Jong-Min Lee, Jae-Kwan Lee, Jae Weon Kim, Seok-Mo Kim, Sang-Yoon Park, Ki Tae Kim
Journal: Journal of Clinical Oncology (2012)

Purpose The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with endometrial cancer and to identify a low-risk group before surgery. Patients and Methods The medical records of 360 patients with endometrial cancer who underwent surgical staging were collected from four institutions and were retrospectively reviewed. By using serum CA-125 levels, preoperative biopsy data, and magnetic resonance imaging (MRI) data, a multivariate logistic model was created. Patients whose predicted probability was less than 4% were defined as low risk. The developed model was externally validated in 180 patients from two independent institutions. Results Serum CA-125 levels and three MRI parameters (deep myometrial invasion, lymph node enlargement, and extension beyond uterine corpus) were found to be independent risk factors for nodal metastasis. The model classified 53% of patients as part of a low-risk group, and the false negative rate was 1.7%. In the validation cohort, the model classified 43% of patients as low-risk, and the false negative rate was 1.4%. The model showed good discrimination (area under the receiver operator characteristic curve = 0.85) and was calibrated well. The negative likelihood ratio of our low-risk criteria was 0.11 (95% CI, 0.04 to 0.29), which was equivalent to the false-negative rate of 1.3% (95% CI, 0.5% to 3.3%) at the assumed prevalence of nodal metastasis of 10%. Conclusion Using serum CA-125 and MRI as criteria resulted in the accurate identification of a low-risk group for lymph node metastasis among patients with endometrial cancer.
Transcriptional Repression of ATP-Binding Cassette Transporter A1 Gene in Macrophages
Authors: Yasunori Takata, Van Chu, Alan R. Collins, Christopher J. Lyon, Wei Wang, Florian Blaschke, Dennis Bruemmer, Evren Caglayan, William Daley, Jitsuo Higaki, Michael C. Fishbein, Rajendra K. Tangirala, Ronald E. Law, Willa A. Hsueh
Journal: Circulation Research (2005)

Angiotensin II (Ang II) is a powerful accelerator of atherosclerosis. Herein, we describe a novel transcription mechanism through which Ang II inhibits macrophage expression of the ATP-binding cassette transporter A1 (ABCA1), a key regulator of reverse cholesterol transport. We demonstrate that chronic Ang II infusion substantially promotes macrophage infiltration, foam cell formation, and atherosclerosis in low-density lipoprotein receptor-deficient mice and significantly reduces ABCA1 expression in peripheral macrophages. Administration of the Ang II type 1 receptor blocker valsartan inhibited Ang II-induced ABCA1 mRNA repression, macrophage cholesterol accumulation, and atherosclerosis. Ang II treatment reduced ABCA1 promoter activity of in vitro cultured mouse peritoneal macrophages, inducing fos-related antigen 2 (Fra2) protein binding to an ABCA1 promoter E-box motif, a site known to negatively regulate macrophage ABCA1 transcription. Valsartan pretreatment blocked Fra2 binding to the ABCA1 promoter, and Fra2 small interfering RNA pretreatment attenuated Ang II-mediated ABCA1 transcriptional inhibition, confirming the role of Fra2 in this process. This new evidence suggests that Ang II, a well-known proinflammatory and pro-oxidative factor, alters macrophage cholesterol homeostasis by repressing ABCA1 to promote foam cell formation and atherosclerosis.
causal relations between asymmetries at the individual level?
Authors: rebecca g. deason, david r. andresen, chad j. marsolek
Journal: Behavioral and Brain Sciences (2005)

studies with humans have failed to produce evidence that any direct causal relation exists between the asymmetry of one function in an individual and the asymmetry of a different function in that individual. without such evidence, factors external to an individual's nervous system, such as social interactions, may play crucial roles in explaining the directions of all asymmetries at all levels.
Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: Results of a pooled analysis from 3 phase-II clinical trials
Authors: Richard T Hoppe, Cameron Harrison, Mahkam Tavallaee, Sameer Bashey, Uma Sundram, Shufeng Li, Lynn Million, Bouthaina Dabaja, Pamela Gangar, Madeleine Duvic, Youn H Kim
Journal: Journal of the American Academy of Dermatology (2014)
Self-Monitoring of Blood Glucose in Patients With Type 2 Diabetes Who Are Not Using Insulin
Authors: Laura M.C. Welschen, Evelien Bloemendal, Giel Nijpels, Jacqueline M. Dekker, Robert J. Heine, Wim A.B. Stalman, Lex M. Bouter
Journal: Diabetes Care (2005)

Response to Kleefstra et al. and Davidson

In response to Kleefstra et al. (1), we will try to eliminate the confusion concerning the conclusions of our systematic reviews on self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes who are not using insulin, published in Diabetes Care (2) and the Cochrane Library (3).

In the Cochrane Library, we performed a qualitative analysis, and because of the consistency of the results of rather heterogeneous trials, we concluded …