tbuckley/cabot-search huggingface dataset:
MicroRNA-195 regulates vascular smooth muscle cell phenotype and prevents neointimal formation
Authors: Yung-Song Wang, Hay-Yan J. Wang, Yi-Chu Liao, Pei-Chien Tsai, Ku-Chung Chen, Hsin-Yun Cheng, Ruey-Tay Lin, Suh-Hang Hank Juo
Journal: Cardiovascular Research (2012)

Proliferation and migration of vascular smooth muscle cells (VSMCs) can cause atherosclerosis and neointimal formation. MicroRNAs have been shown to regulate cell proliferation and phenotype transformation. We discovered abundant expression of microRNA-195 in VSMCs and conducted a series of studies to identify its function in the cardiovascular system. MicroRNA-195 expression was initially found to be altered when VSMCs were treated with oxidized low-density lipoprotein (oxLDL) in a non-replicated microRNA array experiment. Using cellular studies, we found that microRNA-195 reduced VSMC proliferation, migration, and synthesis of IL-1β, IL-6, and IL-8. Using bioinformatics prediction and experimental studies, we showed that microRNA-195 could repress the expression of Cdc42, CCND1, and FGF1 genes. Using a rat model, we found that the microRNA-195 gene, introduced by adenovirus, substantially reduced neointimal formation in a balloon-injured carotid artery. In situ hybridization confirmed the presence of microRNA-195 in the treated arteries but not in control arteries. Immunohistochemistry experiments showed abundant Cdc42 in the neointima of treated arteries. We showed that microRNA-195 plays a role in the cardiovascular system by inhibiting VSMC proliferation, migration, and proinflammatory biomarkers. MicroRNA-195 may have the potential to reduce neointimal formation in patients receiving stenting or angioplasty.
Poxviruses and Immune Evasion
Authors: Bruce T. Seet, J.B. Johnston, Craig R. Brunetti, John W. Barrett, Helen Everett, Cheryl Cameron, Joanna Sypula, Steven H. Nazarian, Alexandra Lucas, Grant McFadden
Journal: Annual Review of Immunology (2003)

Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.
Outcomes Among African-American/Non-African-American Patients With Advanced Non-Small-Cell Lung Carcinoma: Report From the Cancer and Leukemia Group B
Authors: A. W. Blackstock, J. E. Herndon, E. D. Paskett, M. C. Perry, S. L. Graziano, J. J. Muscato, M. P. Kosty, W. L. Akerley, J. Holland, S. Fleishman, M. R. Green
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Among patients diagnosed with advanced non-small-cell lung carcinoma (NSCLC), African-Americans have lower survival rates than non-African-Americans. Whether this difference is due to innate characteristics of the disease in the two ethnicities or to disparities in health care is not known. We investigated whether the disparity in survival would persist when patients were treated with similar systemic therapies (i.e., in phase II and phase III Cancer and Leukemia Group B [CALGB] trials). Methods: We assessed 504 consecutive patients (458 non-African-American and 46 African-American) receiving systemic chemotherapy in CALGB studies for advanced NSCLC during the period from 1989 through 1998. Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. Cox's proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two-sided. Results: The unadjusted 1-year survival rate was 22% (95% confidence interval [CI] = 13% to 38%) for African-American patients and 30% (95% CI = 26% to 35%) for non-African-American patients, a statistically significant difference (8%; 95% CI on the difference = 5% to 12%; P = .03). Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the worse outcome for African-American patients. However, the effect of race/ethnicity disappeared after adjustment for performance status and weight loss. African-American patients were more likely than non-African-Americans to present with a poor performance status (83% versus 60%) and substantial weight loss (41% versus 27%) and to be unmarried (59% versus 28%), disabled (31% versus 15%), unemployed (17% versus 7%), and Medicaid recipients (30% versus 8%). Conclusions: The relationship that we observed between poor performance, weight loss, and socioeconomic status suggests that social circumstances lead to African-Americans presenting with poorer prognostic features.
Evaluation of Platelet-Inhibiting Drugs in Models of Atherosclerosis
Authors: R N Saunders
Journal: The Annual Review of Pharmacology and Toxicology (1982)

Numerous methods have been described to measure platelet function or responses and alterations thereof by drugs. These techniques have con­ tributed greatly to our understanding of platelet biochemistry and mor­ phology. From these studies evolved procedures to measure the effect of platelet-inhibiting drugs in thrombotic states which have been extensively investigated. Several recent reviews (1, 2) have very adequately covered this aspect and, therefore, discussions of these test systems will be purposefully omitted from this review. The role of platelets in atherosclerosis is somewhat more controversial than their participation in thrombosis. Nevertheless, over the past decade a significant body of evidence has accumulated suggesting that platelets assume a pivotal aspect of the early vessel wall lesion development. New techniques and approaches are being formulated in which established anti­ platelet drugs may be inappropriate.
Catheter Ablation of Ventricular Tachycardia After Repair of Congenital Heart Disease
Authors: Katja Zeppenfeld, Martin J. Schalij, Margot M. Bartelings, Usha B. Tedrow, Bruce A. Koplan, Kyoko Soejima, William G. Stevenson
Journal: Circulation (2007)

Catheter ablation of ventricular tachycardia (VT) after repair of congenital heart disease can be difficult because of nonmappable VTs and complex anatomy. Insights into the relation between anatomic isthmuses identified by delineating unexcitable tissue using substrate mapping techniques and critical reentry circuit isthmuses might facilitate ablation.Sinus rhythm voltage mapping of the right ventricle was performed in 11 patients with sustained VT after repair of congenital heart disease. Unexcitable tissue from patch material, valve annulus, or dense fibrosis, identified from bipolar voltage (<0.5 mV) and pacing threshold (>10 mA), was defined as an anatomic isthmus boundary bordering 4 isthmuses between (1) the tricuspid annulus and scar/patch in the anterior right ventricular outflow, (2) the pulmonary annulus and right ventricular free wall scar/patch, (3) the pulmonary annulus and septal scar/patch, and (4) the septal scar/patch and tricuspid annulus. The reentry circuit isthmuses of all induced 15 VTs (mean cycle length, 276+/-78 ms; 73% poorly tolerated), identified by activation, entrainment, and/or pace mapping, were located in an anatomic isthmus (11 of 15 VTs in anatomic isthmus 1). Transecting the anatomic isthmuses by ablation lesions abolished all VTs. During 30.4+/-29.3 months of follow-up, 91% of patients remained free of VT.Reentry circuit isthmuses in VT late after repair of congenital heart disease are located within anatomically defined isthmuses bordered by unexcitable tissue. The boundaries can be identified with 3-dimensional substrate mapping and connected by ablation lines during sinus rhythm. These findings should facilitate catheter and surgical ablation of stable and unstable VTs.
Mid-trimester induced abortion: a review
Authors: S. Lalitkumar, M. Bygdeman, K. Gemzell-Danielsson
Journal: Human Reproduction Update (2006)

Mid-trimester abortion constitutes 10–15% of all induced abortion. The aim of this article is to provide a review of the current literature of mid-trimester methods of abortion with respect to efficacy, side effects and acceptability. There have been continuing efforts to improve the abortion technology in terms of effectiveness, technical ease of performance, acceptability and reduction of side effects and complications. During the last decade, medical methods for mid-trimester induced abortion have shown a considerable development and have become safe and more accessible. The combination of mifepristone and misoprostol is now an established and highly effective method for termination of pregnancy (TOP). Advantages and disadvantages of medical versus surgical methods are discussed. Randomized studies are lacking, and more studies on pain treatment and the safety of any method used in patients with a previous uterine scar are debated, and data are scarce. Pain management in abortion requires special attention. This review highlights the need for randomized studies to set guidelines for mid-trimester abortion methods in terms of safety and acceptability as well as for better analgesic regimens.
What Determines Asthma Phenotype? Is It the Interaction between Allergy and the Smooth Muscle?
Authors: JUDITH L. BLACK, PETER R. A. JOHNSON
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Passive sensitization provides a useful model for the examination of the effect of the allergic process on smooth muscle reactivity and growth. This technique involves the incubation of bronchial tissue segments or bronchial smooth muscle cells in culture with serum from patients with allergic asthma or, alternatively, serum from nonallergic nonasthmatic patients. The allergic serum contains a high concentration of total IgE, usually greater than 1,000 IU/ml, and is taken from patients who exhibit a positive skin test response to one or more common allergens, whereas control nonallergic serum has a total IgE concentration of less than 20 IU/ml and is derived from patients who are skin test negative (1). One of the major advantages of this model is that comparisons can then be made between tissues or cells from the one patient, thus minimizing the inevitable variability in between-patient responses so familiar to those who work with human tissue.
Impulsivity, dual diagnosis, and the structure of motivated behavior in addiction
Authors: R. Andrew Chambers
Journal: Behavioral and Brain Sciences (2008)

Abstract Defining brain mechanisms that control and adapt motivated behavior will not only advance addiction treatment. It will help society see that addiction is a disease that erodes free will, rather than representing a free will that asks for or deserves consequences of drug-use choices. This science has important implications for understanding addiction's comorbidity in mental illness and reducing associated public health and criminal justice burdens.
Unilateral increased transradiancy of the lung caused by bronchial carcinoid tumour.
Authors: S A Spitzer, I Segal, E Lubin, M Nili, M Levy
Journal: Thorax (1980)

Two patients with an intraluminal carcinoid tumour obstructing the right main bronchus in one, and the left main bronchus in the other, resulting in unilateral increased transradiancy from hypoperfusion of the lung, are described. Resection of the tumours and reconstruction of bronchial continuity was followed by return of perfusion to normal between three and 18 months after the operation. The patient in whom the diagnosis was delayed showed a much slower rate of return of perfusion and a small lung resulted. The finding of increased transradiancy of lung even in an asymptomatic patient should be an indication for bronchoscopy.
Overdiagnosis and mammography screening
Authors: H G. Welch
Journal: BMJ (2009)

The question is no longer whether, but how often, it occurs

The NHS recently scrapped its leaflet inviting women to undergo mammography in response to criticisms that it failed to mention the major harm of screening—overdiagnosis.1 In the linked systematic review (doi:10.1136/bmj.b2587), Jorgensen and Gotzsche provide evidence that screening has led to overdiagnosis of breast cancer not only in the United Kingdom, but also in Canada, Australia, Sweden, and Norway.2

Overdiagnosis refers to the detection of abnormalities that will never cause symptoms or death during a patient’s lifetime. Overdiagnosis of cancer occurs when the cancer grows so slowly that the patient dies of other causes before it produces symptoms or when the cancer remains dormant (or regresses). Because doctors don’t know which patients are overdiagnosed, we tend to treat them all. Overdiagnosis therefore results in unnecessary treatment.

With the advent of widespread efforts to diagnose cancer earlier, overdiagnosis has become an increasingly vexing problem. Overdiagnosis is a widely recognised problem in prostate cancer screening, and it …
Familial idiopathic pulmonary fibrosis in association with bone marrow hypoplasia and hepatic nodular regenerative hyperplasia: a new "trimorphic" syndrome
Authors: A Talbot-Smith, W-K Syn, G MacQuillan, D Neil, E Elias, P Ryan
Journal: Thorax (2009)

This is the first report of familial idiopathic pulmonary fibrosis associated with hepatic nodular regenerative hyperplasia and bone marrow hypoplasia. Four members of one family presented with this triad of organ dysfunction. The response to immunosuppressive treatment was poor and all four members succumbed to the disease processes. The current literature is reviewed and mechanisms that could have been involved in the development of this new syndrome are proposed.
Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury
Authors: C S Calfee, L B Ware, M D Eisner, P E Parsons, B T Thompson, N Wickersham, M A Matthay
Journal: Thorax (2008)

To determine whether baseline plasma levels of the receptor for advanced glycation end products (RAGE), a novel marker of alveolar type I cell injury, are associated with the severity and outcomes of acute lung injury, and whether plasma RAGE levels are affected by lower tidal volume ventilation.Measurement of plasma RAGE levels from 676 subjects enrolled in a large randomised controlled trial of lower tidal volume ventilation in acute lung injury.Higher baseline plasma RAGE was associated with increased severity of lung injury. In addition, higher baseline RAGE was associated with increased mortality (OR for death 1.38 (95% CI 1.13 to 1.68) per 1 log increment in RAGE; p = 0.002) and fewer ventilator free and organ failure free days in patients randomised to higher tidal volumes. These associations persisted in multivariable models that adjusted for age, gender, severity of illness and the presence of sepsis or trauma. Plasma RAGE was not associated with outcomes in the lower tidal volume group (p = 0.09 for interaction in unadjusted analysis). In both tidal volume groups, plasma RAGE levels declined over the first 3 days; however, the decline was 15% greater in the lower tidal volume group (p = 0.02; 95% CI 2.4% to 25.0%).Baseline plasma RAGE levels are strongly associated with clinical outcomes in patients with acute lung injury ventilated with higher tidal volumes. Lower tidal volume ventilation may be beneficial in part by decreasing injury to the alveolar epithelium.
Genetic insights into the causes and classification of the cerebral palsies
Authors: Andres Moreno-De-Luca, David H Ledbetter, Christa L Martin
Journal: The Lancet Neurology (2012)

Cerebral palsy-the most common physical disability of childhood-is a clinical diagnosis encompassing a heterogeneous group of neurodevelopmental disorders that cause impairments of movement and posture that persist throughout life. Despite being commonly attributed to a range of environmental factors, particularly birth asphyxia, the specific cause of cerebral palsy remains unknown in most individuals. A growing body of evidence suggests that cerebral palsy is probably caused by multiple genetic factors, similar to other neurodevelopmental disorders such as autism and intellectual disability. Recent advances in next-generation sequencing technologies have made possible rapid and cost-effective sequencing of the entire human genome. Novel cerebral palsy genes will probably be identified as more researchers and clinicians use this approach to study individuals with undiagnosed neurological disorders. As our knowledge of the underlying pathophysiological mechanisms of cerebral palsy increases, so will the possibility of developing genomically guided therapeutic interventions.
Histamine skin sensitivity in patient with drug hypersensitivity
Authors: Asem Kazangapova, Rafail Rozenson
Journal: European Respiratory Journal (2012)

One of less studied is the test of histamine serial dilutions sensitivity and exactly this test may be very important for antihistamine preparations effectiveness study.  Materials and methods: We studied 96 patients; from them 48 were patients of ENT department, who suffered from drug hypersensitivity reactions of various severity, from mild urticaria to anaphylaxis (study group). The control group consisted of 48 ENT patients with same diseases, but without drug hypersensitivity. Patients were determined into “study” and “control” group according to “case-control” principle. Seven day before histamine sensitivity tests cell antihistamine preparation were stopped. Histamine serial dilutions test was performed with standardized prick-needle. We used ten 0,1% histamine preparation. The end point was histamine dilution that caused papule ≥ 2mm in diameter.  Results and discussion: In the control group in 54,2% the end point was 10-2 histamine dilution, in 29,2% - 10-3, in 7.3% - 10-4, in 5,1% - 10-5. There were few cases, when our patients debit react by papule formation to 0,01% histamine dilution and reacted only to 0,1% of histamine. In patients with drug allergy we found an elevated skin sensitivity. Thus, the end-point 10-2 was found in 39,5% of patients, 10-3 – in 21,6%, 10-4 – in 9,9%. The difference in 10-2 dilutions and 10-3 dilutions between the control and studied group was statistically significant.  We concluded that in patients with drug allergy the increased skin sensitivity to histamine was found, and the level of this hypersensitivity should be considered in individual antihistamine preparations prescription.
Inactivation of a T cell receptor-associated GTP-binding protein by antibody-induced modulation of the T cell receptor/CD3 complex.
Authors: H Schrezenmeier, G Ahnert-Hilger, B Fleischer
Journal: The Journal of Experimental Medicine (1988)

TCR modulation induced by anti-TCR or anti-CD3 mAbs leads to a transient state of refractoriness of the T cell to all signals given via cell surface structures. To investigate the underlying mechanisms, we have used human CTL permeabilized with the alpha toxin of S. aureus. This method of permeabilization allows manipulation of the interior milieu of the cell, but maintains its functional and structural integrity. Introduction of the G protein activator GTP gamma S into permeabilized CTL leads to triggering of granule exocytosis. The G protein inactivator GDP beta S inhibited exocytosis induced by TCR triggering but not that induced by activation of protein kinase C. This indicates that the G protein that triggers exocytosis is localized after CD3 triggering but before formation of the polyphosphoinositol breakdown product diacylglycerol. In TCR-modulated CTL, GTP gamma S is no longer able to activate exocytosis. Such CTL, however, still respond to PKC activators. This demonstrates that a TCR-associated G protein has been functionally inactivated by TCR modulation.
Hepatosplenic schistosomiasis: a clinical review.
Authors: K M De Cock
Journal: Gut (1986)

<h3>ABSTRACT</h3> Macrophages, a class of tissue resident innate immune cells, are responsible for sequestering foreign objects through the process of phagocytosis, making them a promising target for immune-modulation via particulate engineering. Here, we report that nanoparticle (NP) dosing and cellular internalization via phagocytosis significantly enhances survival of <i>ex vivo</i> cultures of primary bone marrow-derived, alveolar, and peritoneal macrophages over particle-free controls. The enhanced survival is attributed to suppression of caspase-dependent apoptosis and is linked to phagocytosis and lysosomal signaling, which was also found to occur <i>in vivo</i>. Uniquely, poly(ethylene glycol)-based NP treatment does not alter macrophage polarization or lead to inflammatory effects. The enhanced survival phenomenon is also applicable to NPs of alternative chemistries, indicating the potential universality of this phenomenon with relevant drug delivery particles. These findings provide a framework for extending the lifespan of primary macrophages <i>ex vivo</i> for drug screening, vaccine studies, and cell therapies and has implications for any <i>in vivo</i> particulate immune-engineering applications.
The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins—Roles in Reproduction, Cancer, and Immune Defense
Authors: Gerard M. Gibbs, Kim Roelants, Moira K. O'Bryan
Journal: Endocrine Reviews (2008)

The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily members are found in a remarkable range of organisms spanning each of the animal kingdoms. Within humans and mice, there are 31 and 33 individual family members, respectively, and although many are poorly characterized, the majority show a notable expression bias to the reproductive tract and immune tissues or are deregulated in cancers. CAP superfamily proteins are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumor suppressor or prooncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. This review describes mammalian CAP superfamily gene expression profiles, phylogenetic relationships, protein structural properties, and biological functions, and it draws into focus their potential role in health and disease. The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. We conclude that overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters target specificity and, therefore, the biological consequences.