1986 — 1988 |
Long, John F |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Dietary Induced Aluminum Encephalopathy
The ultimate objective is to identify environmental factors and physiologic states, of relevance to humans, whereby toxic levels of aluminum are able to breach the normal barriers and gain entrance to the nervous system. The specific long-term objective of this study is to determine whether factors exist, under naturally occurring conditions, whereby dietary aluminum is able to breach the gut-epithelial barrier and blood-brain-barrier in sufficient quantity to produce toxicity of the nervous system, using the rabbit as a model. To accomplish this, it is necesary to test these barriers individually. This will entail use of agents which, based on preliminary data, are postulated to have an enhancing effect on dietary aluminum absorption. The specific objectives are: 1. To determine whether or not a relationship exists between continuous calcitriol (1,25(OH)2D3) and parathyroid hormone administration (by Alzet osmotic pump) and subsequent levels of serum and bone aluminum (thus demonstrating whether or not these agents enable dietary aluminum to breach the gut-epithelial barrier). 2. To determine whether or not the incomplete blood-brain-barrier of the fetus permits aluminum from elevated plasma aluminum from the pregnant dam (or via the milk aluminum in the neonate) to breach this barrier in the neonatal brain. 3. To determine the risk of aluminum-induced encephalopathy in adult and neonatal rabbits exposed to high dietary aluminum under the above conditions. 4. To describe and define the morphologic and chemical changes in the nervous system of animals under the above regimens, utilizing techniques of silver carbonate impregnation; transmission (TEM) and scanning transmission (STEM) electron microscopy; X-ray microanalysis for aluminum, and serum and brain tissue quantitative aluminum analayis by atomic absorption spectroscopy. The information obtained from the above studies should contribute to the understanding of the significance of aluminum in certain encephalopathies of humans, including dialysis dementia and Alzheimer disease. It would also provide some comparative insight into the recently described aluminum loading in infants receiving intravenous therapy. This model, once developed, should facilitate the correlation of aluminum-induced neuronal degenerations with abnormalities of cholinergic function.
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0.911 |
1987 — 1989 |
Long, John P |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cardiovascular Properties of 5-Ht 1 Receptor Agonists
5-HT1-receptor agonists are potent, long acting agents that lower arterial pressure and induce bradycardia in cats, dogs, and rats. 8-OH-2-di-n propylaminotetralin (8-OH DPAT) will serve as the reference chemical and will be compared with newly-synthesized apomorphine derivatives in which the 10-OH group is substituted with CH3, CH2OH, H, etc., as well as altering substitution on nitrogen (aporphines). Preliminary studies ahve demonstrated that the 10-CH3, N-CH3 aporphine derivative parallels closely the behavorial and cardiovascular changes-induced by 8-OH DPAT, a selective 5-HT1A receptor agonist. The aporphine compound has no interaction with DA2-receptors and our hypothesis is that alkyl substitutions in the 10-position of apomorphine introduce potent 5-HT1-receptor agonist properties. The experimental procedures will evaluate possible central and peripheral sites for the hypotensive and bradycardic responses induced by these series of compounds, investigate reflex activations of the sympathetic and parasympathetic nervous systems, and determine receptor selectively and specificity using various radioligand binding and bioassay procedures. Direct goals of this research include: (1) determine the role of 5- HT1 -receptors for control of the cardiovascular system, (2) evaluate present hypothesis is that these agents are potent 5-HT- receptor agonists, and both of these series of agents are very potent in blocking cardiovascular responses to bilateral carotid occlusion, inducing bradycardia and hypotension, (3) identifying agonists for serotonin-receptor subtypes; this is certainly needed to help define physiological roles of this receptor, and (4) since we have no selective antagonists for 5-HT1 receptors, an active agent is clearly needed and this research will identify antagonists for 5-HT1 receptor subtypes. This research will combine chemical and biological experimental procedures to advance our understanding of the role of 5-HT1 receptors in cardiovascular pharmacology.
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0.922 |
2013 — 2014 |
Danos, Nicole (co-PI) [⬀] Azizi, Emanuel (co-PI) [⬀] Long, John Summers, Adam [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Meeting: International Congress of Vertebrate Morphology, July 8-12, Barcelona, Spain @ University of Washington
This award will support participation of students, postdocs, and early-career faculty in the 10th International Congress of Vertebrate Morphology, Barcelona, Spain, July 8th -12th, 2013. Morphology, the study of form or shape, is the foundational field for a diversity of areas of biological research including developmental biology, biomechanics, paleontology and evolutionary biology. Symposium topics are forward looking and interdisciplinary, and include sessions on Hominin evolution, the function and evolution of the nose, the function of non-contractile components of muscle and the curation and analysis of 3-D data. The Congress will bring together leaders in the field from around the world, students and post-doctoral fellows, and integrative scientists from related disciplines. The international nature of the meeting is an excellent opportunity for students, postdoctoral researchers and junior faculty to develop productive collaborations with non-US researchers and to gain new insights and perspectives about the conduct of scientific research and infrastructure in different countries. The funding will be used to partially offset the travel and registration costs for 25 presenters at the meeting. Travel support provided through this award will be aimed at broadening participation in the meeting ensuring that greater numbers of women and members of underrepresented groups of US researchers will be able to attend. Among other broader impacts of the Congress will be the (1) integration and communication of research, (2) enhancement of research infrastructure through the encouragement of partnerships and collaborations, and (3) broad dissemination of research through publication of abstracts and posters. The posters will be available through the open source Faculty of 1000 web site.
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0.954 |