Area:
Neuroscience Biology
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High-probability grants
According to our matching algorithm, Stephen J. Kish is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
1988 — 1990 |
Kish, Stephen John |
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. |
Neurobehavioral Neurochemistry &Histology of Opca
Although much evidence circumstantially implicates the brain cholinergic system in Alzheimer's disease (AD) dementia, the degree to which the cholinergic dysfunction can explain the features of the cognitive impairment is not known. We propose that examination of non-AD individuals also having brain cholinergic dysfunction is likely to significantly increase our understanding of the role of the brain cholinergic system in dementia. In this regard our MAJOR OBJECTIVE is to conduct a combined brain neurochemical, neuropathological, and behavioral study of 31 individuals from four well-studied families afflicted with a hereditary cerebellar disorder (dominantly-inherited olivopontocerebellar atrophy, OPCA). A preliminary neurochemical study of several members of each family revealed a cortical cholinergic deficiency as severe as that observed in end-stage AD. Surprisingly, none of the OPCA patients at last examination appeared grossly to have any clinically significant dementia. Our SPECIFIC AIMS are: 1) to assess carefully, once a year the cognitive (using a test battery approach) and neurological status of the 31 affected patients; 2) to examine systematically and extensively the behavioral of the major neurotrasnmitter systems (esp. cholinergic) in brain of the OPCA patients as they come to autopsy; and 3) to perform the first detailed neuropathological examination of extracerebellar brain areas in OPCA with special attention devoted to the quantitative assessment of the basal forebrain cholinergic nuclei. As shown below, all personnel have demonstrated expertise in their individual areas of research. An essential and special feature of this proposal will be the collaboration with Drs. Schut and Currier, who will arrange all patient contact with the investigators. Much effort is now being directed to the pharmacological restoration of cholinergic function in AD brain in an attempt to normalize cognitive process. A crucial question, which is directly related to the likelihood of success of this approach is whether the brain cholinergic degeneration in AD is in fact related to any clinically significant extent to the mental deterioration. We suggest that results of our intensive and careful examination of OPCA individuals may have profound implications with respect to 1) the actual role of the brain cholinergic system in human cognition and 2) prospects of successful cholinergic therapy in dementia disorders.
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1 |
1991 — 1993 |
Kish, Stephen John |
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. |
Is Chronic Cocaine Abuse Toxic to the Human Brain?
Despite the explosive increase in cocaine abuse, little information is available with respect to the effects, in human brain, of long-term exposure to this drug. The major objective of our study is to conduct, for the first time, a systematic and comprehensive examination of the behaviour of the major neurotransmitter systems in autopsied brain of cocaine abusers. We propose to test the Specific Hypothesis that chronic cocaine abuse will be associated with long-lasting depletion in autopsied human brain in the markers for the monoamine neurotransmitters as assessed by HPLC, quantitative autoradiography, receptor binding, and photoaffinity labelling procedures. Autopsied cocaine-abused brain (n=10 per year for the next three years) will be carefully selected from over 250 possible autopsies at one Canadian (Toronto) and two U.S. (Minneapolis; Bronx, N.Y.) centers. The obtained neurochemical data will be compared with biochemical findings obtained in two drug (chronic heroin; alcohol) and one non-neurological group. All of the applicants have demonstrated expertise in the relevant human brain dissection, neurochemical, and neuropathological components of this investigation. Much effort is now being directed to experimental animal studies designed to understand the biochemical basis of cocaine addiction and the long-term changes in brain following chronic cocaine abuse. We argue that such studies should more appropriately be conducted in the human brain. We suggest that the results of our intensive study will provide, for the first time, baseline information with respect to the potential long-term pharmacologic/neurotoxicological efforts of cocaine as well as a springboard for formulating new treatment strategies for the human cocaine abuser.
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1 |
1991 — 1993 |
Kish, Stephen John |
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. |
Neurobehavior Neurochemistry and Neuropathology of Opca
The LONG-TERM GOAL of our proposal is to understand both the physiologic and etiological bases of the neurobehavioural changes of patients with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder. This will be accomplished through neurobehavioural and brain neurochemical and neuropathological examination of 30 patients from five U.S. OPCA families. The four specific aims of our interdisciplinary study are the following: 1) to understand in OPCA the role of the brain cholinergic system and the,cerebellum in the cognitive deficits typical of patients with frontal lobe damage; 2) to provide a biochemical explanation for the excitatory amino acid and phospholipid metabolite changes in OPCA brain; 3) to investigate the possibility of a "dying-back" phenomenon involving the OPCA nigrostriatal dopamine neurone; and 4) to improve the quality of life of our OPCA patients through dysphagia intervention. The SPECIAL FEATURES of our proposal include the unique ability of the applicants to follow prospectively and carefully patients from five U.S. OPCA families with annual neurobehavioural assessment until autopsy, and the demonstrated expertise of each of the applicants in the relevant neurobehavioural assessment, dysphagia intervention, and human brain neurochemical and neuropathological techniques. We suggest that the information to be obtained is important in its own right for characterizing aspects of a disorder which have been relatively neglected by the scientific community and, more generally, is likely to lead to new brain-behavioural correlations relevant to our understanding of both normal and abnormal brain functioning.
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1 |