tbuckley/cabot-search huggingface dataset:
GnRH antagonists are safer than agonists: an update of a Cochrane review
Authors: H. G. Al-Inany, M. A. F. M. Youssef, M. Aboulghar, F. Broekmans, M. Sterrenburg, J. Smit, A. M. Abou-Setta
Journal: Human Reproduction Update (2011)

A NUTSHELL GnRH antagonists are safer than agonists: an update of a Cochrane review Background GnRH agonists or antagonists can be used to prevent LH surges during ovarian stimulation for assisted reproduction.GnRH agonists downregulate GnRH pituitary receptors.GnRH antagonists directly and rapidly inhibit gonadotrophin release.In a 2006 systematic review involving 29 trials, the average clinical pregnancy rate was 4.7% lower with GnRH antagonist treatment and the incidence of ovarian hyperstimulation syndrome (OHSS) was 2% lower compared with GnRH agonist treatment (Al-Inany et al., 2006).The current update includes 45 trials which addressed live birth or ongoing pregnancy rate (OPR) in GnRH antagonist and GnRH agonist protocols among women undergoing assisted reproduction treatment (Youssef et al., 2011). MethodsThe authors searched electronic databases including MEDLINE, EMBASE and the Cochrane Library, proceedings of major reproductive medicine conferences and reference lists of retrieved articles, until April 2010.Eligible reports were randomized trials comparing GnRH agonist and GnRH antagonist protocols in women undergoing IVF or ICSI cycles.The primary outcome was live birth.Secondary outcomes included OPR and OHSS rates.The meta-analysis calculated summary average rates, rate differences and rate ratios in the individual trials using the inverse variance procedure, or in case of heterogeneity, random effects models (Deeks et al., 2001).
THE IMMUNOLOGY OF EXPERIMENTAL CHAGAS' DISEASE
Authors: Charles A. Santos-Buch, Antonio R. L. Teixeira
Journal: The Journal of Experimental Medicine (1974)

Experiments that consisted of incubation of Trypanosoma cruzi-sensitized lymphocytes derived from chronically infected rabbits and from rabbits repeatedly immunized with a small particle or membrane fraction derived from homogenates of T. cruzi forms, showed destruction of allogeneic, parasitized and nonparasitized heart cells in vitro. Mononuclear cells collected from peripheral blood were incubated for 1 h at 37°C to isolate the lymphocytes. Following incubation, over 99% of the cells in the supernate were lymphocytes, which were utilized in these experiments. At the start of these experiments, 70–80% of the sensitized lymphocytes were unattached, small and round, with sparse filipodia. In the ensuing hours, marked heart cell destruction, similar to that seen in an active lesion when lymphocytes invade heart tissue, were observed. After 18 h incubation, about 65–70% of the lymphocytes were attached, larger, and rough surfaced. Inhibition of monocyte migration tests, each in the presence of the antigens of subcellular fractions of T. cruzi organisms and of allogeneic heart myofibers, indicated the presence of a cross-reacting antigen common to both the parasite and the heart in the small particle or membrane fractions. The particulate antigens of the 30,000 g, 35-min fraction of heart muscle gave rise to inhibition of monocyte migration as did the counterpart fraction derived from T. cruzi organisms. The destruction of nonparasitized target heart cells by T. cruzi-sensitized lymphocytes is an in vitro model of the chronic myocarditis of Chagas' disease, and the recognition of cross-reactive antigens of the host cell by T. cruzi-sensitized lymphocytes is believed to be the pathogenic basis for subsequent tissue injury in the chronic phase of this disease.
Development of glucose intolerance in male transgenic mice overexpressing human glycogen synthase kinase-3β on a muscle-specific promoter
Authors: Nigel J. Pearce, Jonathan R.S. Arch, John C. Clapham, Matthew P. Coghlan, Stacey L. Corcoran, Carolyn A. Lister, Andrea Llano, Gary B. Moore, Gregory J. Murphy, Stephen A. Smith, Colleen M. Taylor, John W. Yates, Alastair D. Morrison, Alexander J. Harper, Lynne Roxbee-Cox, Alejandro Abuin, Ed Wargent, Julie C. Holder
Journal: Metabolism (2004)
A Propensity Analysis of Late Versus Early Nephrologist Referral and Mortality on Dialysis
Authors: Wolfgang C. Winkelmayer, William F. Owen, Raisa Levin, Jerry Avorn
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Previous studies have analyzed the association between late versus early nephrologist referral (LR, ER) and poor clinical outcomes in patients with end-stage renal disease. We sought to determine whether these poor outcomes were causally related to LR, or whether LR was a proxy for poorer access to health care in general. An inception cohort of incident dialysis patients enrolled in the New Jersey Medicare or Medicaid programs was identified. Using a large number of demographic, clinical, and health care utilization covariates, propensity scores (PS) were then calculated to predict whether a given patient had been seen by a nephrologist at 90 d before first dialysis. Cox proportional hazards models were then built to test the association between timing of nephrologist referral and mortality during the first year of dialysis, using PS adjustment and matching to determine whether this association was confounded by other measures of reduced healthcare utilization. Neither adjustment for PS (HR = 1.31; 95% CI, 1.17 to 1.47) nor matching (HR = 1.40; 95% CI, 1.23 to 1.59) materially changed the initial 36% excess mortality in LR compared with ER patients (HR = 1.36; 95% CI, 1.22 to 1.51). Excess mortality among LR was limited to the first 3 mo of dialysis (HR = 1.75; 95% CI, 1.48 to 2.08) but not present thereafter (HR = 1.03; 95% CI, 0.84 to 1.25). Late nephrologist referral is an independent risk factor for early death on dialysis, even after controlling for other indicators of healthcare utilization. Further research is needed to identify patients at particular risk so that interventions to prevent early deaths on dialysis in LR patients can be developed and tested. E-mail: [email protected]
Clinical significance of residual pulmonary vein potentials after pulmonary vein isolation in patients with paroxysmal atrial fibrillation
Authors: Hakan Oral, Hiroshi Tada, Mehmet Ozaydin, Sohail Hassan, Christoph Scharf, Aman Chugh, Radmira Greenstein, Frank Pelosi, Bradley P. Knight, S.Adam Strickberger, Fred Morady
Journal: Journal of the American College of Cardiology (2002)
Nox4 is a Novel Inducible Source of Reactive Oxygen Species in Monocytes and Macrophages and Mediates Oxidized Low Density Lipoprotein–Induced Macrophage Death
Authors: Chi Fung Lee, Mu Qiao, Katrin Schröder, Qingwei Zhao, Reto Asmis
Journal: Circulation Research (2010)

The enhanced formation of intracellular reactive oxygen species (ROS) induced by oxidized low-density lipoprotein (OxLDL) promotes macrophage death, a process likely to contribute to the formation of necrotic cores and the progression of atherosclerotic lesions. Yet macrophage deficiency of phagocytic NADPH oxidase (Nox2), the primary source of ROS in macrophages, does not reduce atherosclerotic lesion development in mice. This suggests an as yet unidentified NADPH oxidase may be present in macrophages and responsible for the intracellular ROS formation induced by OxLDL.The aim of this study was to identify the source of intracellular ROS involved in macrophage death.Nox4 was expressed in human monocytes and mature macrophages, and was localized to the endoplasmic reticulum and to defined foci within the nucleus. Nox4 colocalized with p22(phox), and both proteins were upregulated in response to OxLDL stimulation, whereas Nox2/gp91(phox) levels remained unchanged. Induction of Nox4 expression, intracellular ROS formation and macrophage cytotoxicity induced by OxLDL were blocked by MEK1/2 inhibition, but not by inhibitors of p38-MAPK (mitogen-activated protein kinase), JNK (Jun N-terminal kinase), or JAK2 (Janus kinase 2). Small interfering RNA knockdown of Nox4 inhibited both intracellular ROS production and macrophage cytotoxicity induced by OxLDL, whereas Nox4 overexpression enhanced both OxLDL-stimulated ROS formation and macrophage death.Nox4 is a novel source of intracellular ROS in human monocytes and macrophages. Induction of Nox4 by OxLDL is mediated by the MEK1/ERK pathway and required for OxLDL cytotoxicity in human macrophages, implicating monocytic Nox4 in atherogenesis.
Deleted in Liver Cancer 1 Controls Cell Migration through a Dia1-Dependent Signaling Pathway
Authors: Gerlinde Holeiter, Johanna Heering, Patrik Erlmann, Simone Schmid, Ruth Jähne, Monilola A. Olayioye
Journal: Cancer Research (2008)

Deleted in liver cancer (DLC) 1 and 2 are Rho GTPase-activating proteins that are frequently down-regulated in various types of cancer. Ectopic expression in carcinoma cell lines lacking these proteins has been shown to inhibit cell migration and invasion. However, whether the loss of DLC1 or DLC2 is the cause of aberrant Rho signaling in transformed cells has not been investigated. Here, we have down-regulated DLC1 and DLC2 expression in breast cancer cells using a RNA interference approach. Silencing of DLC1 led to the stabilization of stress fibers and focal adhesions and enhanced cell motility in wound-healing as well as chemotactic Transwell assays. We provide evidence that enhanced migration of cells lacking DLC1 is dependent on the Rho effector protein Dia1 but does not require the activity of Rho kinase. By contrast, DLC2 knockdown failed to affect the migratory behavior of cells, suggesting that the two proteins have distinct functions. This is most likely due to their differential subcellular localizations, with DLC1 found in focal adhesions and DLC2 being mainly cytosolic. Collectively, our data show that DLC1 is critically involved in the control of Rho signaling and actin cytoskeleton remodeling and that its cellular loss is sufficient for the acquisition of a more migratory phenotype of breast cancer cells.
Survival of Bacterial Enteropathogens in the Ice of Popular Drinks
Authors: D. Lynn Dickens, Herbert L. DuPont, Philip C. Johnson
Journal: JAMA (1985)

We examined the survival of four bacterial enteropathogens frozen in ice and subsequently allowed to melt in various popular drinks. The counts of all the organisms were markedly lowered by freezing alone, and the numbers were further decreased by exposure to some of the drinks. Nevertheless, none of the organisms were completely eliminated as a result of freezing for 24 hours followed by melting in any of the test drinks, even when the drink was 86-proof tequila.
Onset and Duration of Action of Concomitant administration of Mometasone Furoate Nasal Spray with Oxymetazoline Nasal Spray Versus Either Drug Alone and placebo in Subjects With Seasonal Allergic Rhinitis
Authors: B.Q. Lanier, E.O. Meltzer, D. Gates, T. Shekar, A. Teper
Journal: Journal of Allergy and Clinical Immunology (2010)
TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II–infused mice
Authors: Yu Wang, Hafid Ait-Oufella, Olivier Herbin, Philippe Bonnin, Bhama Ramkhelawon, Soraya Taleb, Jin Huang, Georges Offenstadt, Christophe Combadière, Laurent Rénia, Jason L. Johnson, Pierre-Louis Tharaux, Alain Tedgui, Ziad Mallat
Journal: Journal of Clinical Investigation (2010)

Complicated abdominal aortic aneurysm (AAA) is a major cause of mortality in elderly men. Ang II–dependent TGF-β activity promotes aortic aneurysm progression in experimental Marfan syndrome. However, the role of TGF-β in experimental models of AAA has not been comprehensively assessed. Here, we show that systemic neutralization of TGF-β activity breaks the resistance of normocholesterolemic C57BL/6 mice to Ang II–induced AAA formation and markedly increases their susceptibility to the disease. These aneurysms displayed a large spectrum of complications on echography, including fissuration, double channel formation, and rupture, leading to death from aneurysm complications. The disease was refractory to inhibition of IFN-γ, IL-4, IL-6, or TNF-α signaling. Genetic deletion of T and B cells or inhibition of the CX3CR1 pathway resulted in partial protection. Interestingly, neutralization of TGF-β activity enhanced monocyte invasiveness, and monocyte depletion markedly inhibited aneurysm progression and complications. Finally, TGF-β neutralization increased MMP-12 activity, and MMP-12 deficiency prevented aneurysm rupture. These results clearly identify a critical role for TGF-β in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome.
Peripheral Deletion of Autoreactive CD8 T Cells by Cross Presentation of Self-Antigen Occurs by a Bcl-2–inhibitable Pathway Mediated by Bim
Authors: Gayle M. Davey, Christian Kurts, Jacques F.A.P. Miller, Philippe Bouillet, Andreas Strasser, Andrew G. Brooks, Francis R. Carbone, William R. Heath
Journal: The Journal of Experimental Medicine (2002)

By transgenic expression of ovalbumin (OVA) as a model self antigen in the β cells of the pancreas, we have shown that self tolerance can be maintained by the cross-presentation of this antigen on dendritic cells in the draining lymph nodes. Such cross-presentation causes initial activation of OVA-specific CD8 T cells, which proliferate but are ultimately deleted; a process referred to as cross-tolerance. Here, we investigated the molecular basis of cross-tolerance. Deletion of CD8 T cells was prevented by overexpression of Bcl-2, indicating that cross-tolerance was mediated by a Bcl-2 inhibitable pathway. Recently, Bim, a pro-apoptotic Bcl-2 family member whose function can be inhibited by Bcl-2, was found to play a critical role in the deletion of autoreactive thymocytes, leading us to examine its role in cross-tolerance. Bim-deficient T cells were not deleted in response to cross-presented self-antigen, strongly implicating Bim as the pro-apoptotic mediator of cross-tolerance.
GENebu Project: home nebulizer use and maintenance in Italy
Authors: A.S. Melani, P. Sestini, S. Aiolfi, N. Barbato, P. Canessa, G. De Angelis, D. Zanchetta, R. De Tullio, C. Cinti, M. Neri
Journal: European Respiratory Journal (2001)

Due to the lack of information on this topic, the Educational Group of the Italian Association of Hospital Pneumologists performed an open, multicentre, observational survey to evaluate home nebulizer practices in Italy. From May-December 1999, all patients attending one of the 27 participating chest clinics throughout Italy and who were or had been using a home nebulizer in the previous 6 months were consecutively enrolled. All patients completed a self-administered questionnaire on their current practices of home nebulization. Of the 1,721 questionnaires delivered, 1,257 were returned with an overall response rate of 73%. Most patients (82.8%) reported using their nebulizer for bronchopulmonary symptoms and the remaining patients only used theirs for upper respiratory tract diseases. Subjects using their nebulizer for lower respiratory symptoms were older (p<0.001), predominantly female (p<0.001) and used their nebulizer more frequently (p<0.001). Forty per cent of patients >60 yrs old used their nebulizer regularly, at least once a day. More than 60% of respondents never received any information from healthcare workers on the correct usage of their nebulizer, and >75% received no information on nebulizer hygiene and care. Patients who received information on the use and maintenance of their nebulizer from caregivers more commonly attended to these practices (p<0.01). The present survey suggests that home nebulizer use and maintenance in Italy are heterogeneous, and there is the need to implement better nebulizer practice.
PRESSOR SUBSTANCES IN ARTERIAL HYPERTENSION
Authors: Henry A. Schroeder, Norman S. Olsen
Journal: The Journal of Experimental Medicine (1950)

Pherentasin, a highly active pressor substance producing a prolonged effect in the rat, has been obtained in a fairly pure form from the arterial blood of patients with hypertension. Its presence has been demonstrated by two biological methods. It was rarely found in normotensive blood. The blood of patients with renal or nephrogenic hypertension, either primary or secondary, consistently yielded this material. The blood of patients exhibiting neurogenic hypertension and the endocrine hypertensive syndrome had smaller amounts of it. Little or none was found in malignant hypertension. Perhaps pherentasin has a causal relation to the existence of arterial hypertension.
Phase II trial of galiximab (anti-CD80 monoclonal antibody) plus rituximab (CALGB 50402): Follicular Lymphoma International Prognostic Index (FLIPI) score is predictive of upfront immunotherapy responsiveness
Authors: M.S. Czuczman, J.P. Leonard, S. Jung, J.L. Johnson, E.D. Hsi, J.C. Byrd, B.D. Cheson
Journal: Annals of Oncology (2012)
Phylogenetic relationships among prokaryotic and eukaryotic catalases
Authors: M. G. Klotz, G. R. Klassen, P. C. Loewen
Journal: Molecular Biology and Evolution (1997)

Seventy-four catalase protein sequences, including 29 bacterial, 8 fungal, 7 animal, and 30 plant sequences, were compiled, and 70 were used for phylogenetic reconstruction. The core of the resulting tree revealed unique, separate groups of plant and animal catalases, two groups of fungal catalases, and three groups of bacterial catalases. The only overlap of kingdoms occurred within one branch and involved fungal and bacterial large-subunit enzymes. The other fungal branch was closely linked to the group of animal enzymes. Group I bacterial catalases were more closely related to the plant enzymes and contained such diverse taxa as the Gram-positive Listeria seeligeri, Deinocococcus radiodurans, and gamma-proteobacteria. Group III bacterial sequences were more closely related to fungal and animal sequences and included enzymes from a broad range of bacteria including high- and low-GC Gram positives, proteobacteria, and a bacteroides species. Group II was composed of large-subunit catalases from diverse sources including Gram positives (low-GC Bacilli and high-GC Mycobacteria), proteobacteria, and species of the filamentous fungus Aspergillus. These data can be interpreted in terms of two gene duplication events that produced a minimum of three catalase gene family members that subsequently evolved in response to environmental demands. Horizontal gene transfer may have been responsible for the group II mixture of bacterial and fungal large-subunit catalases.
Augmentation of Therapeutic Responses in Melanoma by Inhibition of IRAK-1,-4
Authors: Ratika Srivastava, Degui Geng, Yingjia Liu, Liqin Zheng, Zhaoyang Li, Mary Ann Joseph, Colleen McKenna, Navneeta Bansal, Augusto Ochoa, Eduardo Davila
Journal: Cancer Research (2012)

Abstract Toll-like receptors (TLR) are expressed by a variety of cancers, including melanoma, but their functional contributions in cancer cells are uncertain. To approach this question, we evaluated the effects of stimulating or inhibiting the TLR/IL-1 receptor-associated kinases IRAK-1 and IRAK-4 in melanoma cells where their functions are largely unexplored. TLRs and TLR-related proteins were variably expressed in melanoma cell lines, with 42% expressing activated phospho-IRAK-1 constitutively and 85% expressing high levels of phospho-IRAK-4 in the absence of TLR stimulation. Immunohistochemical evaluation of melanoma tumor biopsies (n = 242) revealed two distinct patient populations, one that expressed p-IRAK-4 levels similar to normal skin (55%) and one with significantly higher levels than normal skin (45%). Levels of p-IRAK-4 levels did not correlate with clinical stage, gender, or age, but attenuated IRAK-1,-4 signaling with pharmacologic inhibitors or siRNA-enhanced cell death in vitro in combination with vinblastine. Moreover, in a xenograft mouse model of melanoma, the combined pharmacologic treatment delayed tumor growth and prolonged survival compared with subjects receiving single agent therapy. We propose p-IRAK-4 as a novel inflammation and prosurvival marker in melanoma with the potential to serve as a therapeutic target to enhance chemotherapeutic responses. Cancer Res; 72(23); 6209–16. ©2012 AACR.
High resolution computed tomography as a predictor of lung histology in systemic sclerosis.
Authors: A U Wells, D M Hansell, B Corrin, N K Harrison, P Goldstraw, C M Black, R M du Bois
Journal: Thorax (1992)

BACKGROUND: The relative proportions of fibrosis and inflammation seen by open lung biopsy examination is a predictor of disease outcome in fibrosing alveolitis. This study was designed to assess the ability of high resolution computed tomography to predict the histological appearance of open lung biopsy specimens from patients with systemic sclerosis. METHODS: Twenty abnormal biopsy specimens from 12 patients were assessed; abnormalities were categorised as fibrotic (fibrosis exceeding inflammation) or inflammatory (inflammation equal to or exceeding fibrosis). Computed tomography appearances were scored for the lobe from which the biopsy specimen was taken; scans were graded from parenchymal opacification alone through to a reticular pattern alone. RESULTS: Two lobar appearances were identified on computed tomograms: amorphous parenchymal opacification equal in extent to reticulation (grade 3) and a predominantly reticular pattern (grade 4). There was a significant association between a fibrotic histological appearance and a grade 4 computed tomogram, and between an inflammatory histological appearance and a grade 3 computed tomogram. Computed tomography grade 4 was associated with a fibrotic histological appearance in 12 out of 13 lobes, and grade 3 with an inflammatory histological appearance in four out of seven lobes. CONCLUSION: Computed tomography discriminated between biopsy specimens that were predominantly fibrotic and a smaller group with a larger amount of inflammation.
A SCANNING AND TRANSMISSION ELECTRON MICROSCOPE STUDY OF ANTIGEN-BINDING SITES ON ROSETTE-FORMING CELLS
Authors: Fred G. Gudat, W. Villiger
Journal: The Journal of Experimental Medicine (1973)

The ultrastructure of binding sites in rosette-forming cells of mice after immunization with sheep red cells was studied by means of scanning and transmission electron microscopy. It was found that the red cells were bound to the lymphocyte surface in circumscribed, immunoglobulin-containing areas, consistent with a spotlike or patchy distribution of antigen-binding immunoglobulin receptors. In these contact areas the cell membranes formed a gap of 80 A (range 75-90 A) which exhibited electron-opaque bridges at high magnification. These results are discussed in the light of the recent recognition of the formation of immunoglobulin spots on the lymphocyte surface after antigen contact. Morphological details suggest that the same mechanism is operating in rosette formation, possibly including the movement of the contact areas on the lymphocyte membrane.