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Search Results: 1 - 10 of 464227 matches for " Dennis A. Steindler "
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Purification of Immature Neuronal Cells from Neural Stem Cell Progeny
Hassan Azari, Geoffrey W. Osborne, Takahiro Yasuda, Mohammad G. Golmohammadi, Maryam Rahman, Loic P. Deleyrolle, Ebrahim Esfandiari, David J. Adams, Bjorn Scheffler, Dennis A. Steindler, Brent A. Reynolds
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020941
Abstract: Large-scale proliferation and multi-lineage differentiation capabilities make neural stem cells (NSCs) a promising renewable source of cells for therapeutic applications. However, the practical application for neuronal cell replacement is limited by heterogeneity of NSC progeny, relatively low yield of neurons, predominance of astrocytes, poor survival of donor cells following transplantation and the potential for uncontrolled proliferation of precursor cells. To address these impediments, we have developed a method for the generation of highly enriched immature neurons from murine NSC progeny. Adaptation of the standard differentiation procedure in concert with flow cytometry selection, using scattered light and positive fluorescent light selection based on cell surface antibody binding, provided a near pure (97%) immature neuron population. Using the purified neurons, we screened a panel of growth factors and found that bone morphogenetic protein-4 (BMP-4) demonstrated a strong survival effect on the cells in vitro, and enhanced their functional maturity. This effect was maintained following transplantation into the adult mouse striatum where we observed a 2-fold increase in the survival of the implanted cells and a 3-fold increase in NeuN expression. Additionally, based on the neural-colony forming cell assay (N-CFCA), we noted a 64 fold reduction of the bona fide NSC frequency in neuronal cell population and that implanted donor cells showed no signs of excessive or uncontrolled proliferation. The ability to provide defined neural cell populations from renewable sources such as NSC may find application for cell replacement therapies in the central nervous system.
A Preclinical Assessment of Neural Stem Cells as Delivery Vehicles for Anti-Amyloid Therapeutics
eMalick G. Njie, Svetlana Kantorovich, Garrett W. Astary, Cameron Green, Tong Zheng, Susan L. Semple-Rowland, Dennis A. Steindler, Malisa Sarntinoranont, Wolfgang J. Streit, David R. Borchelt
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034097
Abstract: Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated Aβ peptides that are the major constituents of the senile plaques. Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered. We found that our injection methods led to cells largely distributing to white matter tracts, which are anisotropic conduits for fluids that facilitate rapid distribution within the CNS. Third, with regard to MMP9 as a therapeutic to remove senile plaques, we observed high concentrations of endogenous metalloproteinases around amyloid plaques in the mouse models used for these preclinical tests with no evidence that the NSC-delivered enzymes elevated these activities or had any impact. Interestingly, MMP9-expressing NSCs formed substantially larger grafts. Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.
Increased Precursor Cell Proliferation after Deep Brain Stimulation for Parkinson's Disease: A Human Study
Vinata Vedam-Mai, Bronwen Gardner, Michael S. Okun, Florian A. Siebzehnrubl, Monica Kam, Palingu Aponso, Dennis A. Steindler, Anthony T. Yachnis, Dan Neal, Brittany U. Oliver, Sean J. Rath, Richard L. M. Faull, Brent A. Reynolds, Maurice A. Curtis
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088770
Abstract: Objective Deep brain stimulation (DBS) has been used for more than a decade to treat Parkinson's disease (PD); however, its mechanism of action remains unknown. Given the close proximity of the electrode trajectory to areas of the brain known as the “germinal niches,” we sought to explore the possibility that DBS influences neural stem cell proliferation locally, as well as more distantly. Methods We studied the brains of a total of 12 idiopathic Parkinson's disease patients that were treated with DBS (the electrode placement occurred 0.5–6 years before death), and who subsequently died of unrelated illnesses. These were compared to the brains of 10 control individuals without CNS disease, and those of 5 PD patients with no DBS. Results Immunohistochemical analyses of the subventricular zone (SVZ) of the lateral ventricles, the third ventricle lining, and the tissue surrounding the DBS lead revealed significantly greater numbers of proliferating cells expressing markers of the cell cycle, plasticity, and neural precursor cells in PD-DBS tissue compared with both normal brain tissue and tissue from PD patients not treated with DBS. The level of cell proliferation in the SVZ in PD-DBS brains was 2–6 fold greater than that in normal and untreated PD brains. Conclusions Our data suggest that DBS is capable of increasing cellular plasticity in the brain, and we hypothesize that it may have more widespread effects beyond the electrode location. It is unclear whether these effects of DBS have any symptomatic or other beneficial influences on PD.
Neurotrophin-Induced Migration and Neuronal Differentiation of Multipotent Astrocytic Stem Cells In Vitro
Martha Douglas-Escobar, Candace Rossignol, Dennis Steindler, Tong Zheng, Michael D. Weiss
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0051706
Abstract: Hypoxic ischemic encephalopathy (HIE) affects 2–3 per 1000 full-term neonates. Up to 75% of newborns with severe HIE die or have severe neurological handicaps. Stem cell therapy offers the potential to replace HIE-damaged cells and enhances the autoregeneration process. Our laboratory implanted Multipotent Astrocytic Stem Cells (MASCs) into a neonatal rat model of hypoxia-ischemia (HI) and demonstrated that MASCs move to areas of injury in the cortex and hippocampus. However, only a small proportion of the implanted MASCs differentiated into neurons. MASCs injected into control pups did not move into the cortex or differentiate into neurons. We do not know the mechanism by which the MASCs moved from the site of injection to the injured cortex. We found neurotrophins present after the hypoxic-ischemic milieu and hypothesized that neurotrophins could enhance the migration and differentiation of MASCs. Using a Boyden chamber device, we demonstrated that neurotrophins potentiate the in vitro migration of stem cells. NGF, GDNF, BDNF and NT-3 increased stem cell migration when compared to a chemokinesis control. Also, MASCs had increased differentiation toward neuronal phenotypes when these neurotrophins were added to MASC culture tissue. Due to this finding, we believed neurotrophins could guide migration and differentiation of stem cell transplants after brain injury.
The Use of Life Narrative and Living Standard Measurement Survey Data in the Study of Poverty in the Caribbean: A Resolution of Conflicting Epistemologies  [PDF]
Dennis A. V. Brown
Sociology Mind (SM) , 2013, DOI: 10.4236/sm.2013.33030

The paper examines the compatibility or usefulness of fit between epistemologically disparate quantitative survey data and qualitative life narrative data gleaned in the study of poverty in the Caribbean. It aims to find out whether or not the different approaches to the understanding of reality on which the two methodologies are based preclude the integration of their findings as a means of furthering understanding of the dynamics of Caribbean poverty. The analysis draws on Country Poverty Studies conducted in the territory of Grenada in the Eastern Caribbean. It is centered on the demographic measure of fertility, a measure of chronic illnesses by socioeconomic status and life narrative interviews conducted around the themes of poverty, family and life experiences with select poor households across the country. Fertility was measured using parity of women aged <15 - 30+. Statistical analyses were done using cross tabulations. The findings indicate that the hermeneutic understanding of the life narratives, and the causal explanatory accounts provided by the positivist quantitative data, allow for understanding of negative health seeking behaviour on the part of the poor, not provided by the quantitative data by themselves. They also provide insight into the synergy between family, reproductive behaviour, labour market status and chronic poverty in the Caribbean region that would not have been possible through the use of the positivist quantitative method by itself.

Presence of the Potato Late Blight Resistance Gene RB Does Not Promote Adaptive Parasitism of Phytophthora infestans  [PDF]
Dennis A. Halterman, Gail Middleton
American Journal of Plant Sciences (AJPS) , 2012, DOI: 10.4236/ajps.2012.33043
Abstract: The gene RB is derived from the wild potato species S. bulbocastanum and confers partial resistance to late blight, caused by the oomycete pathogen Phytophthora infestans. In order to investigate whether a single strain of P. infestans can adapt to overcome this partial resistance source, we subjected RB containing leaflets to multiple rounds of infection with P. infestans, with a culture isolated from a lesion used to infect the next leaflet (a passage). A parallel line of passages was done using susceptible leaflets as hosts. At the end of the experiment, P. infestans strains passaged through resistant or susceptible leaflets were compared for infection efficiency and lesion size. Variants of the P. infestans effector family IPI-O, some of which are recognized by the RB protein to elicit resistance, were cloned and sequenced to determine whether variation occurred during selection on the partially resistant host. Our results show that after 20 rounds of selection, no breakdown in RB resistance took place. In fact, the strain that was continually passaged through the partially resistant host produced smaller lesions on susceptible leaflets and had a lower infection frequency than the strain passaged through susceptible cultivar Katahdin. No changes within IPI-O coding regions were detected after selection on the hosts with RB. Our results indicate that individual strains of P. infestans are not capable of rapidly overcoming RB resistance even when it is the only host available.
Il teatro di Edna Mazya: dal dramma famigliare a quello storico-politico
Gabriella Steindler Moscati
Altre Modernità , 2011,
Abstract: A macroscopic trend in contemporary Israeli literature concerns the growing success and increase of women writers. Even in theatre - a genre which, in current Jewish culture, is new in many aspects -, many women dramatists are gaining considerable achievements. The incidence of this phenomenon may be valued in the light of some innovative contributions, such as the elaboration of various female - or feminist - themes. The dramatic writings of Edna Mazya are particularly eloquent if read according to this analysis. In this article we will deal with some of her literary topics, which recur especially in her drama Herod (May 2000): on the one hand, the biblical inspiration and the actualization of biblical features and Mazya's leitmotif, i.e. the representation of marginalized characters and their stories in contrast to the “main stream”.
Disease Cycle, Development and Management of Sclerotinia Stem Rot of Potato  [PDF]
Dennis A. Johnson, Zahi K. Atallah
American Journal of Plant Sciences (AJPS) , 2014, DOI: 10.4236/ajps.2014.525388
Potato is severely affected by Sclerotinia sclerotiorum in the US Pacific Northwest (PNW) and satisfactory disease management has not been achieved until recently. Recent research has given a better understanding of key epidemiological factors which has resulted in improved disease management in the PNW. This work reviews the epidemiology of Sclerotinia stem rot and highlights information that has led to the better management of the disease on potato. The primary source of inoculum of Sclerotinia sclerotiorum for potato in the Columbia Basin of the PNW are ascospores produced within potato fields or carried by wind currents from neighboring fields planted to winter cereals or other crops. Ascospores are ejected from apothecia and disseminated throughout the Columbia Basin over an extended time period. Immature apothecia generally first emerge at or shortly after row closure in potato fields in the Columbia Basin. Ascospores of S. sclerotiorum are incapable of direct infection of intact green potato tissues, and flower blossoms are crucial for infection and development of the disease in potato. Airborne ascospores are deposited on open potato blossoms still attached to the canopy. Infested flowers fall and are trapped on stems, usually leaf axils, or fall on the ground, and fungal mycelia then rapidly colonize the blossoms when humidity is high in the plant canopy. Ascospores are also deposited on senescent and dead plant material on the ground, germinate, and produce mycelium. Infection occurs shortly after contaminated blossoms become lodged on stems in the plant canopy, or after stems come in contact with contaminated fallen blossoms or decomposing plant tissues on the ground. Infection can occur within 3 days after contact of contaminated blossoms with green tissue. Lesions initially appear on potato stems 14 to 30 days after row closure and 12 to 20 days following full bloom of primary inflorescences of potato in the Columbia Basin. Significant levels of outcrossing sexual recombination have been found in the homothallic S. sclerotiorum population in the Pacific Northwest. Sclerotinia stem rot of potato is best managed by using an integrated approach of combining cultural practices that produce optimum plant foliar development without producing an excessive crop canopy, irrigation management to avoid excessive amounts of irrigation water, and timely applications of fungicides. Contaminated flower blossoms served as a bridge for infection and fungicides applied
Role of Community Health Practitioners in National Development: The Nigeria Situation  [PDF]
Asiton-a Solomon Ibama, Pauline Dennis
International Journal of Clinical Medicine (IJCM) , 2016, DOI: 10.4236/ijcm.2016.77056
Abstract: This is a review paper that brings to focus, concepts of Community Health Practice that connect Community Health Practitioners’ Roles to National development in view of its composite index improvement measure of social welfare services provision among others for the citizens of a country over time, with particular emphasis on medical care component of such index aimed at reduction in diseases and poverty in the population. The objective of the review work is to determine the extent to which Community Health Practice, particularly by Community Health Practitioners is capable of ensuring National Development in democratic governance or otherwise, in the context of our country, Nigeria. The methodology applied was traditional review of published literatures concerning the subject and findings of operational research of programme implemented by Community Health Practitioners at the Primary Health Care facilities and household level in the communities. This paper emphasizes on Primary Health Care services delivery contribution to National Development, since it is the level where Community Health Practitioners are mainly commissioned to render their services. Home-Based Care Strategy for Integrated Maternal, Newborn and Child Health piloted in three (3) local government areas (Ahoada West, Etche and Oyigbo) in Rivers State, Nigeria, in 2012 and implemented by Community Health Practitioners, aimed at reducing maternal, newborn and child morbidity and mortality by 20% by 2015 in line with the United Nations (UN) Millennium Development Goals 4 and 5, had been shown to achieve an average of 26% improvement in utilization of maternal and newborn health services, an average of 27% overall reduction in maternal malnutrition status, an average of 14% overall improvement in under 5 years malnutrition status among others in 2013 on comparing with baseline indicators. Nigeria also attained 80% coverage in routine immunization in most vaccine preventable diseases except Tetanus Toxiod (TT) 2 (54%) in 2013 to achieve herd immunity of the community to prevent transmission of disease pathogen to cause a disease. Community Health Practitioners are the frontline Primary Health Care Professionals charged with the responsibility of implementation of immunization programmes in Nigeria and therefore contributing significantly to the prevention and control of targeted vaccine preventable diseases in Nigeria Health System. Our findings on factors militating against Community Health Practitioners’ Roles in National Development as elicited in this paper may form basis for empirical
Role of Rheumatoid Factor B Cells in Normal and Pathologic Antigen Presentation
Dennis A Carson
Arthritis Research & Therapy , 1999, DOI: 10.1186/ar25
Abstract: The results of our investigations have shown that genes encoding rheumatoid factor autoantibodies are present in the germ line of most people. Their immunoglobulin products greatly potentiate the presentation of tiny amounts of antigen during secondary immune responses, and also may provide bystander help for T cell activation. The development of high-affinity pathogenic lgG rheumatoid factors is normally prevented by an antigen-specific deletion mechanism. This mechanism fails in RA.HLA-DR4 molecules contain a short peptide sequence, `the shared epitope,' that is duplicated in the dnaJ class of heat shock proteins in bacteria and in the gp 120 capsid protein of EBV. Patients with early RA, but not normal subjects, have circulating Th1-type T lymphocytes that respond to these exogenous antigens but not to autologous HLA-DR4 molecules.The synovium has a rich blood supply and macrophage lining. Consequently, exogenous antigens easily become trapped there. Although rheumatoid factors and HLA-DR4 molecules normally protect the host from infection, they may promote the conversion of a low-grade, nonspecific synovitis into the chronic granulation tissue characteristic of RA.
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