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The privileged immunity of immune privileged organs: the case of the eye
Inbal Benhar,Anat London,Michal Schwartz
Frontiers in Immunology , 2012, DOI: 10.3389/fimmu.2012.00296
Abstract: Understanding of ocular diseases and the search for their cure have been based on the common assumption that the eye is an immune privileged site, and the consequent conclusion that entry of immune cells to this organ is forbidden. Accordingly, it was assumed that when immune cell entry does occur, this reflects an undesired outcome of breached barriers. However, studies spanning more than a decade have demonstrated that acute insults to the retina, or chronic conditions resulting in retinal ganglion cell loss, such as in glaucoma, result in an inferior outcome in immunocompromised mice; likewise, steroidal treatment was found to be detrimental under these conditions. Moreover, even conditions that are associated with inflammation, such as age-related macular degeneration, are not currently believed to require immune suppression for treatment, but rather, are thought to benefit from immune modulation. Here, we propose that the immune privilege of the eye is its ability to enable, upon need, the entry of selected immune cells for its repair and healing, rather than to altogether prevent immune cell entry. The implications for acute and chronic degenerative diseases, as well as for infection and inflammatory diseases, are discussed.
The Glial Scar-Monocyte Interplay: A Pivotal Resolution Phase in Spinal Cord Repair
Ravid Shechter, Catarina Raposo, Anat London, Irit Sagi, Michal Schwartz
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027969
Abstract: The inflammatory response in the injured spinal cord, an immune privileged site, has been mainly associated with the poor prognosis. However, recent data demonstrated that, in fact, some leukocytes, namely monocytes, are pivotal for repair due to their alternative anti-inflammatory phenotype. Given the pro-inflammatory milieu within the traumatized spinal cord, known to skew monocytes towards a classical phenotype, a pertinent question is how parenchymal-invading monocytes acquire resolving properties essential for healing, under such unfavorable conditions. In light of the spatial association between resolving (interleukin (IL)-10 producing) monocytes and the glial scar matrix chondroitin sulfate proteoglycan (CSPG), in this study we examined the mutual relationship between these two components. By inhibiting the de novo production of CSPG following spinal cord injury, we demonstrated that this extracellular matrix, mainly known for its ability to inhibit axonal growth, serves as a critical template skewing the entering monocytes towards the resolving phenotype. In vitro cell culture studies demonstrated that this matrix alone is sufficient to induce such monocyte polarization. Reciprocal conditional ablation of the monocyte-derived macrophages concentrated at the lesion margins, using diphtheria toxin, revealed that these cells have scar matrix-resolving properties. Replenishment of monocytic cell populations to the ablated mice demonstrated that this extracellular remodeling ability of the infiltrating monocytes requires their expression of the matrix-degrading enzyme, matrix metalloproteinase 13 (MMP-13), a property that was found here to be crucial for functional recovery. Altogether, this study demonstrates that the glial scar-matrix, a known obstacle to regeneration, is a critical component skewing the encountering monocytes towards a resolving phenotype. In an apparent feedback loop, monocytes were found to regulate scar resolution. This cross-regulation between the glial scar and monocytes primes the resolution of this interim phase of spinal cord repair, thereby providing a fundamental platform for the dynamic healing response.
Air pollution attributable postneonatal infant mortality in U.S. metropolitan areas: a risk assessment study
Reinhard Kaiser, Isabelle Romieu, Sylvia Medina, Joel Schwartz, Michal Krzyzanowski, Nino Künzli
Environmental Health , 2004, DOI: 10.1186/1476-069x-3-4
Abstract: Based on exposure-response functions from a U.S. cohort study, we assessed the attributable risk of postneonatal infant mortality in 23 U.S. metropolitan areas related to particulate matter <10 μm in diameter (PM10) as a surrogate of total air pollution.The estimated proportion of all cause mortality, sudden infant death syndrome (normal birth weight infants only) and respiratory disease mortality (normal birth weight) attributable to PM10 above a chosen reference value of 12.0 μg/m3 PM10 was 6% (95% confidence interval 3–11%), 16% (95% confidence interval 9–23%) and 24% (95% confidence interval 7–44%), respectively. The expected number of infant deaths per year in the selected areas was 106 (95% confidence interval 53–185), 79 (95% confidence interval 46–111) and 15 (95% confidence interval 5–27), respectively. Approximately 75% of cases were from areas where the current levels are at or below the new U.S. PM2.5 standard of 15 μg/m3 (equivalent to 25 μg/m3 PM10). In a country where infant mortality rates and air pollution levels are relatively low, ambient air pollution as measured by particulate matter contributes to a substantial fraction of infant death, especially for those due to sudden infant death syndrome and respiratory disease. Even if all counties would comply to the new PM2.5 standard, the majority of the estimated burden would remain.Given the inherent limitations of risk assessments, further studies are needed to support and quantify the relationship between infant mortality and air pollution.Research conducted during the last 10 to 20 years confirms that outdoor air pollution contributes to illness and death in adults and children [1]. The quantification of this public health problem and the benefits of its regulation, however, has been the subject of debates [2,3]. Such impact assessments usually rely on extrapolations of data from various fields with partly unknown uncertainties [4], as it is rather rare to base the assessment on direct interventio
The Rhetoric of Begin: Leadership in Changing Times  [PDF]
David Schwartz
Open Journal of Leadership (OJL) , 2016, DOI: 10.4236/ojl.2016.53008
A precise examination of Menachem Begin’s speeches and history over the years reveals that Begin’s rhetoric constituted a political instrument that he knew to change according to the circumstances. Begin’s rhetoric was controversial, as he went from the leader of a terrorist organization, was awarded a Nobel Peace Prize, and was the Prime Minister who signed the peace treaty with Egypt. This quality study claims that begin’s rhetoric is integral part of his personality and of his leadership. The assumption is that like a typical politician his leadership changed according the winds of times. His charisma and transformational leadership made him a great leader. His rhetoric constituted just instrument for justification his political actions. Begin was revealed to be pragmatic, in contrast to the militant images that his political rivals attempted to affix to him.
The Social Doctrine of Zeev Jabotinsky, from the Fathers of Zionism  [PDF]
David Schwartz
Open Journal of Political Science (OJPS) , 2016, DOI: 10.4236/ojps.2016.64034
Abstract: Zeev Jabotinsky, in contrast to the conservative economic approach that characterizes the right parties around the world, in essence supports a social democratic approach in the economic dimension, at least in the stage of the establishment of the Jewish state that will be established. Jabotinsky considered the topic of the need to protect the person’s individualism to be very important, since “every individual is a king” and he also supports the idea of the welfare state. The state has to give the individuals there basic needs, but the new Jew has to pay contribution to building the Hebrew new nation and new society. His approach was mixed of liberalism and nationalism, and he adopted the universal attitude of the famous Russian writer Tolstoy to the human suffer, and admired Garibaldi the leader that united Italy. After the second world war and the rise of the Fascists dictatorship of Germany and the communist revolution, Jabotinsky emphasized his belief in the values of liberalism like the American approach of Abram Linkolen that gave freedom to the slaves. Jabotinsky died in New York in the United States, the land of freedom and liberalism as refugee, far away from Russian culture that he was born to.
The 2nd Step by Step International Spinal Cord Repair—Combining research Step by Step into multi-pronged approaches for spinal cord repair  [PDF]
Maria Teresa Moreno-Flores, Francois Ferón, Victor Arvanian, Armin Blesch, Armin Curt, David J. Fink, Marina Mata, Kinichi Nakashima, Xavier Navarro, Francisco Javier Rodríguez, Michal Schwartz, Mikael Svensson, Erik Sundstrom, Joan Romero, Filip Lim
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.67A2003
Abstract: On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting research including clinical trials which show promise for treatments for this devastating disorder. This meeting brought together clinicians, clinical scientists and molecular biologists from more than 10 countries to evaluate current knowledge on clinical, cellular, and biomolecular aspects of spinal cord injury. A major goal of the conference in advancing the translation of research data to the clinic was to promote multi-pronged approaches for therapy of this complex problem.
Abnormal Changes in NKT Cells, the IGF-1 Axis, and Liver Pathology in an Animal Model of ALS
Arseny Finkelstein, Gilad Kunis, Akop Seksenyan, Ayal Ronen, Tamara Berkutzki, David Azoulay, Maya Koronyo-Hamaoui, Michal Schwartz
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022374
Abstract: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing fatal neurodegenerative disorder characterized by the selective death of motor neurons (MN) in the spinal cord, and is associated with local neuroinflammation. Circulating CD4+ T cells are required for controlling the local detrimental inflammation in neurodegenerative diseases, and for supporting neuronal survival, including that of MN. T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it. Here, we show that in the mutant superoxide dismutase 1 G93A (mSOD1) mouse model of ALS, the levels of natural killer T (NKT) cells increased dramatically, and T-cell distribution was altered both in lymphoid organs and in the spinal cord relative to wild-type mice. The most significant elevation of NKT cells was observed in the liver, concomitant with organ atrophy. Hepatic expression levels of insulin-like growth factor (IGF)-1 decreased, while the expression of IGF binding protein (IGFBP)-1 was augmented by more than 20-fold in mSOD1 mice relative to wild-type animals. Moreover, hepatic lymphocytes of pre-symptomatic mSOD1 mice were found to secrete significantly higher levels of cytokines when stimulated with an NKT ligand, ex-vivo. Immunomodulation of NKT cells using an analogue of α-galactosyl ceramide (α-GalCer), in a specific regimen, diminished the number of these cells in the periphery, and induced recruitment of T cells into the affected spinal cord, leading to a modest but significant prolongation of life span of mSOD1 mice. These results identify NKT cells as potential players in ALS, and the liver as an additional site of major pathology in this disease, thereby emphasizing that ALS is not only a non-cell autonomous, but a non-tissue autonomous disease, as well. Moreover, the results suggest potential new therapeutic targets such as the liver for immunomodulatory intervention for modifying the disease, in addition to MN-based neuroprotection and systemic treatments aimed at reducing oxidative stress.
Theoretical and Practical Notes on Vending Strategies  [PDF]
Gustav Cepciansky, Ladislav Schwartz
iBusiness (IB) , 2011, DOI: 10.4236/ib.2011.31001
Abstract: The paper deals with an application of theory of mass servicing on some cases in vending strategies. The aim of the paper is to show how the theory which is apparently applicable for scientific problems can also be utilised in practical use. First, the necessary theoretical background will have been done and then some examples applied on vending practises will be given.
Tariffication Strategies and Charging Effectivity  [PDF]
Gustav Cepciansky, Ladislav Schwartz
iBusiness (IB) , 2011, DOI: 10.4236/ib.2011.33041
Abstract: The effort of all service providers is to maximize their revenues. The ideal case would be, when a service provider obtained payment for entire services provided. But it is not always possible. Some services may not be paid for. Distribution companies (electricity power, gas, and water), transport companies (airlines, railways, buses, and taxis), telecommunication companies and companies established by the government (e.g. cash of road tax) represent such type of enterprises. Their clients pay for the volume of drawn media, distance of transmission, service duration, amount of transmitted information or travelled distance. Most services are charged fully, but certain services are only charged partly or not at all. An appropriate theory concerning the service provision effectivity and charging policy will be done on examples from telecommunication business and from road tax cashing.
Concatenated Processes in Commercial Business and in Global Economy  [PDF]
Gustav Cepciansky, Ladislav Schwartz
iBusiness (IB) , 2012, DOI: 10.4236/ib.2012.44037
Abstract: The paper deals with an application of theory stochastic processes on business practices and with consequences which the concatenated economic co-operation may have on the future economic growth. The aim of the paper is also to draw attention how the theory which is apparently applicable for solution of scientific problems can also be utilised in practical commercial and economic use. First, the necessary theoretical background will have been done and then some application examples will be given.
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