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High-probability grants
According to our matching algorithm, Ladislav Volicer is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
1986 — 1988 |
Volicer, Ladislav |
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. |
Monoamines in Alzheimer's Disease/Coulometric Detection @ Boston University Medical Campus
Despite recent advances in our understanding of dementia of Alzheimer type (DAT) its etiology is still unknown. It is not known if the cholinergic deficit, detected in most DAT patients, is the primary pathological process or a consequence of other processes. There is considerable evidence indicating involvement of neurotransmitters other than acetylcholine in DAT. We have found a strong evidence for involvement of the dopaminergic and serotoninergic systems and would like to continue this investigation. This work will include application of a new approach to electrochemical detection of substances in cerebrospinal fluid (CSF). This detection involves use of multiple coulometric electrodes which are set at different voltages. We have a preliminary evidence indicating that liquid chromatography using amperometric detection leads to erroneously high estimates of CSF concentrations of DOPAC, HVA, MHPG, 5-HT and 5-HIAA. This error is due to presence of co-eluting interfering compounds which are indistinguishable by the amperometric method but can be differentiated from the authentic monoamine metabolites by the use of coulometric gates and multiple sensors. In addition to the coulometric method is more sensitive than the amperometric one and allows detection of norepinephrine, epinephrine and dopamine in CSF. Investigation with a 6-sensor system coulometric system also indicated presence of 5-HTP and 5-HT in a form which had already undergone oxidation of the 5-hydroxy group, presumably to the quinone. The partially oxidized 5-HT (5-HT-e) in DAT CSF is not metabolized by monomine oxidase. This could explain the aberrant relationship of 5-HT and 5-HIAA levels in rostral fraction of DAT CSF found by us previously. It is possible that 5-HT-e- participates in pathogenesis of DAT, since the neurotoxic effect of 6-hydroxy-dopamine is mediated by formation of a quinone intermediate. In this project we will investigate monoamines and their metabolites, as well as the abnormal form of 5-HT and other interfering substances, using an advanced version of the multidetector coulometric system. We plan to investigate these compounds and compare them in CSF from controls and DAT patients. The presence of a specific change of monoamine concentration or a specific interfering compound would provide not only a diagnostic procedure for DAT but it would give us also a clue for the pathogenesis of DAT. The possible role of 5-HT-e- in DAT will be tested by measuring 5-HT-e- in DAT brains and by investigation of 5-HT-e-neurotoxicity.
|
0.931 |
1996 — 2000 |
Volicer, Ladislav |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Core--Clinical @ Boston University Medical Campus
The Clinical Core will define the neuropsychological and neurological attributes of the two patient populations enrolled in the Boston University Alzheimer's Disease Research Center (BU ADCC). The Bedford VA Medical Center is a source of institutionalized patients with late stage Alzheimer's disease (AD) and ambulatory patients with earlier stages of dementia. Unlike the typical Alzheimer clinic in an acute hospital setting, patients are not lost to follow up and close contact is maintained with caregivers throughout all stages of the disease. This close relationship is a patient/family and provider partnership that has facilitated the recruitment of patients and caregivers into several research projects and has sustained an autopsy rate of 75% over the past 6 years. This exemplary standard of care and research will be applied to characterize the racially, ethnically and culturally diverse poor urban population served by the Boston University Home Medical Service (HMS). In contrast to the population served at the Bedford VA Medical Center, which is homogenous and middle class, about 40% of HMS patients are not caucasian, 60% are on Medicaid and 72% are female. All HMS patients receive a complete medical evaluation which will be reviewed to identify early stage or presymptomatic patients for enrollment in the clinical core. Enrolled subjects at the Bedford VA and the HMS will undergo a standardized, validated one hour neuropsychological evaluation every 6 months and an annual neurological evaluation and blood drawing. DNA will be extracted and stored and Apo E genotype will be determined. In selected cases, lymphoblastic cell lines will be created. All data collected will be entered into a standardized database. In conjunction with a major aim of the Education Core, patients and control subjects will be encouraged to donate their brains for research purposes. Family caregivers will be enrolled and a standardized assessment of caregiver burden will be performed annually. This database will provide a foundation for future research on interventions to reduce caregiver burden and studies concerning the emotional and financial impact of AD.
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0.931 |