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Macrophage Tropism and Cytopathicity of HIV-1 Variants Isolated Sequentially from a Long-Term Survivor Infected with nef-Deleted Virus
nefPaul R. Gorry, Dale A. McPhee, Steven L. WesselinghMelissa J. Churchillnefnefnefnefnefnefnef
The Open Microbiology Journal , 2007, DOI: 10.2174/1874285800701010001]
Abstract: 1-7 Paul R. Gorry, Dale A. McPhee, Steven L. Wesselingh and Melissa J. Churchill Published Date: (25 June, 2007) Long-term survival of human immunodeficiency virus type 1 (HIV-1) infection has been noted in rare cohorts of individuals infected with nef-deleted virus. Enhanced macrophage tropism and cytopathicity contribute to pathogenicity of wild type HIV-1. To better understand the pathogenesis of nef-deleted HIV-1, we analyzed the replication capacity and macrophage cytopathicity of nef-deleted HIV-1 isolated sequentially from a long-term survivor during progression to AIDS (n=6 isolates). Compared with controls, all nef-deleted viruses replicated to low levels in peripheral blood mononuclear cells and monocyte-derived macrophages (MDM). One nef-deleted virus that was isolated on the development of AIDS caused high levels of syncytia in MDM similar to control viruses, but five viruses isolated from earlier times prior to AIDS onset caused only minimal cytopathicity. Together, these results suggest that enhanced cytopathicity of nef-deleted HIV-1 for MDM can occur independently of replication capacity, and may contribute to the pathogenesis of nef-deleted HIV-1 infection.
Flt3+ macrophage precursors commit sequentially to osteoclasts, dendritic cells and microglia
Christine Servet-Delprat, Sylvie Arnaud, Pierre Jurdic, Serge Nataf, Marie-France Grasset, Caroline Soulas, Chantal Domenget, Olivier Destaing, Aymeric Rivollier, Magali Perret, Christiane Dumontel, Daniel Hanau, Gary L Gilmore, Marie-Fran?oise Belin, Chantal Rabourdin-Combe, Guy Mouchiroud
BMC Immunology , 2002, DOI: 10.1186/1471-2172-3-15
Abstract: Mouse bone marrow cells were expanded in vitro in the presence of Flt3-ligand (FL), yielding high numbers of non-adherent cells exhibiting immature monocyte characteristics. Cells expanded for 6 days, 8 days, or 11 days (day 6-FL, day 8-FL, and day 11-FL cells, respectively) exhibited constitutive potential towards macrophage differentiation. In contrast, they showed time-dependent potential towards osteoclast, dendritic, and microglia differentiation that was detected in day 6-, day 8-, and day 11-FL cells, in response to M-CSF and receptor activator of NFκB ligand (RANKL), granulocyte-macrophage colony stimulating-factor (GM-CSF) and tumor necrosis factor-α (TNFα), and glial cell-conditioned medium (GCCM), respectively. Analysis of cell proliferation using the vital dye CFSE revealed homogenous growth in FL-stimulated cultures of bone marrow cells, demonstrating that changes in differential potential did not result from sequential outgrowth of specific precursors.We propose that macrophages, osteoclasts, dendritic cells, and microglia may arise from expansion of common progenitors undergoing sequential differentiation commitment. This study also emphasizes differentiation plasticity within the mononuclear phagocyte system. Furthermore, selective massive cell production, as shown here, would greatly facilitate investigation of the clinical potential of dendritic cells and microglia.The mononuclear phagocyte system encompasses a widely distributed family of related cells exhibiting highly specialized functions such as macrophages, osteoclasts, dendritic cells, and microglia. Resident macrophages, found in most organs and connective tissues, serve as professional phagocytes, removing pathogens or apoptotic cells [1]. Microglia represents a unique category of mononuclear phagocytes distributed throughout the central nervous system (CNS) parenchyma in both white and grey matter [2]. Microglial cells share a number of immunological markers with other mononuclear phagocy
Proteinuria inducing tubulointerstitial damage  [PDF]
Stojimirovi? Biljana B.,Petrovi? Dejan
Medicinski Pregled , 2003, DOI: 10.2298/mpns0308351s
Abstract: Introduction Glomerular basal membrane represents a mechanical and electric barrier for plasma proteins. In physiological conditions only plasma proteins of low molecular weight are completely filtered through basal membrane. Due to damages of glomerular basal membrane there is an increase in filtration of plasma proteins of moderate and high molecular weight. Proteinuria In regard to its etiology proteinuria can be prerenal, renal and postrenal. By analyzing albumin, 1-microglobulin, immunoglobulin G and 2-macroglobulin, together with total protein in urine, it is possible to detect and differentiate causes of prerenal, glomerular, tubular and postrenal proteinuria. Abnormal glomerular permeability to macromolecules results in excessive protein delivery and reabsorption in proximal tubules. Excessive reabsorption in turn may cause congestion of intracellular endocytic and biosynthetic compartments leading to NFkB-dependent and -independent gene upregulation. Among those genes, monocyte chemoattractant protein-1 (MCP-1), cytokines, osteopontin and endothelin stimulate processes of interstitial inflammation and fibroblast proliferation and are ultimately responsible for enhanced extracellular matrix deposition and renal scarring. Human tubular cells exposed to albumin and HDL increase production of endothelin-1. Endothelin-1 affects microcirculation and fibroblasts and is a monocyte chemoattractant. Specific proteins that are cytotoxic are transferrin/iron, low-density lipoprotein, and complement components, all of which appear in urine in proteinuric states. Adequate and early diagnosis and differentiation of proteinuria are of immense therapeutic importance.
On sequentially retractive inductive limits
Armando García
International Journal of Mathematics and Mathematical Sciences , 2003, DOI: 10.1155/s0161171203205202
Abstract: Every locally complete inductive limit of sequentially complete locally convex spaces, which satisfies Retakh's condition (M) is regular, sequentially complete and sequentially retractive. A quasiconverse for this theorem and a criterion for sequential retractivity of inductive limits of webbed spaces are given.
Atorvastatin Improves Plaque Stability in ApoE-Knockout Mice by Regulating Chemokines and Chemokine Receptors  [PDF]
Peng Nie, Dandan Li, Liuhua Hu, Shuxuan Jin, Ying Yu, Zhaohua Cai, Qin Shao, Jieyan Shen, Jing Yi, Hua Xiao, Linghong Shen, Ben He
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097009
Abstract: It is well documented that statins protect atherosclerotic patients from inflammatory changes and plaque instability in coronary arteries. However, the underlying mechanisms are not fully understood. Using a previously established mouse model for vulnerable atherosclerotic plaque, we investigated the effect of atorvastatin (10 mg/kg/day) on plaque morphology. Atorvastatin did not lower plasma total cholesterol levels or affect plaque progression at this dosage; however, vulnerable plaque numbers were significantly reduced in the atorvastatin-treated group compared to control. Detailed examinations revealed that atorvastatin significantly decreased macrophage infiltration and subendothelial lipid deposition, reduced intimal collagen content, and elevated collagenase activity and expression of matrix metalloproteinases (MMPs). Because vascular inflammation is largely driven by changes in monocyte/macrophage numbers in the vessel wall, we speculated that the anti-inflammatory effect of atorvastatin may partially result from decreased monocyte recruitment to the endothelium. Further experiments showed that atorvastatin downregulated expression of the chemokines monocyte chemoattractant protein (MCP)-1, chemokine (C-X3-C motif) ligand 1 (CX3CL1) and their receptors CCR2 and, CX3CR1, which are mainly responsible for monocyte recruitment. In addition, levels of the plasma inflammatory markers C-reactive protein (CRP) and tumor necrosis factor (TNF)-α were also significantly decrease in atorvastatin-treated mice. Collectively, our results demonstrate that atorvastatin can improve plaque stability in mice independent of plasma cholesterol levels. Given the profound inhibition of macrophage infiltration into atherosclerotic plaques, we propose that statins may partly exert protective effects by modulating levels of chemokines and their receptors. These findings elucidate yet another atheroprotective mechanism of statins.
Products of sequentially pseudocompact spaces  [PDF]
Paolo Lipparini
Mathematics , 2012,
Abstract: We show that the product of any number of sequentially pseudocompact topological spaces is still sequentially pseudocompact. The definition of sequential pseudocompactness can be given in (at least) two ways: we show their equivalence. Some of the results of the present note already appeared in A. Dow, J. R. Porter, R. M. Stephenson, R. G. Woods, Spaces whose pseudocompact subspaces are closed subsets, Appl. Gen. Topol. 5 (2004), 243-264.
Atorvastatin-induced pancreatitis  [cached]
Prajapati Samir,Shah Samidh,Desai Chetna,Desai Mira
Indian Journal of Pharmacology , 2010,
Abstract: Drugs account for 1-2% of all cases of pancreatitis. A 58-year-old man was prescribed atorvastatin 10 mg for 6 months for hyperlipidemia. He developed acute abdominal pain and vomiting with epigastric tenderness. Serum lipase and CT scan of the patient suggested the presence of acute pancreatitis. The patient was hospitalized; atorvastatin was stopped and treated symptomatically. He recovered completely within 10 days of drug withdrawal. The causality of the adverse drug reaction according to Naranjo and WHO-UMC Scale was probable. The exact mechanism of pancreatitis due to atorvastatin is not known. It may be a class effect of HMG CoA reductase inhibitors as it had been reported with other statins too. The definite causal relationship is difficult to establish, as rechallenge with the suspected drug was not done due to ethical consideration.
Maximal (sequentially) compact topologies  [PDF]
Hans-Peter A. Künzi,Dominic van der Zypen
Mathematics , 2003,
Abstract: We revisit the known problem whether each compact topology is contained in a maximal compact topology and collect some partial answers to this question. For instance we show that each compact topology is contained in a compact topology in which convergent sequences have unique limits. We also answer a question of D.E. Cameron by showing that each sequentially compact topology is contained in a maximal sequentially compact topology. We finally observe that each sober compact T_1-topology is contained in a maximal compact topology and that each sober compact T_1-topology which is locally compact or sequential is the infimum of a family of maximal compact topologies.
Expression of Osteopontin in Patients with Thyroid Dysfunction  [PDF]
Sara Reza, Asma Shaukat, Tariq M. Arain, Qasim Sarwar Riaz, Maria Mahmud
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056533
Abstract: Thyroid dysfunctions are common endocrine problems. They are often misdiagnosed, misunderstood, and frequently overlooked. These disorders affect almost every aspect of health. Most of them remain undetected because the clinical assessment alone lacks both sensitivity and specificity. As it is not sufficient enough we require the biochemical tests to confirm the diagnosis. As a consequence there is still great interest in new biomarkers that complement existing diagnostic tools. Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several patients with hyperthyroidism and downregulated in hypothyroid patients so it may represent a new biomarker. 100 patients with thyroid dysfunctions (50 hyperthyroid, 50 hypothyroid) and 100 normal subjects were included in the study. Osteopontin and other clinical parameters for diagnosis of thyroid disorders were measured. Osteopontin is positively correlated with T3 and T4 (r = 0.62 and r = 0.75 respectively) while it is negatively correlated with thyroid stimulating hormone (r = ?0.52) showing a significant correlation (p-value <0.001). Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with impaired thyroid function.
On Sequentially Cohen-Macaulay Modules  [PDF]
Nguyen Tu Cuong,Doan Trung Cuong
Mathematics , 2005,
Abstract: In this paper we present characterizations of sequentially Cohen-Macaulay modules in terms of systems of parameters, which are generalizations of well-known results on Cohen-Macaulay and generalized Cohen-Macaulay modules. The sequentially Cohen-Macaulayness of Stanley-Reisner rings of small embedding dimension are also examined.
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