The specific aims of this proposal are to develop a cardiac pacemaker and an internal and external cardiac defibrillator using light instead of electric stimulation. This idea is based on the observation that light can increase the beating rate of neonatal rat and embryonic chick cardiac myocytes. With the light intensity normally used for phase contrast viewing, a 60% increase in beating rate was observed when the cells were viewed at high power (x40 objective) compared with low power (x10). Cultured atrial myocytes were similarly responsive. In studies using isolated whole adult and neonatal rat right atria, in which the spontaneous rate was measured electrocardiographically, an increase of 49% in the beating rate was obtained. The left atrium was not responsive. In addition, even after several days in culture medium, the non-beating right atrium could be stimulated to beat when specific areas were illuminated. Again, no such response was obtained from the left atrium. To achieve the stated goal, the following steps will be necessary: a) establish the wavelength that produces the maximal effect; b) determine the minimal light intensity that is required to produce the effect; c) determine the areas of the heart that are most responsive to light treatment; d) determine whether pulsed or continuous wave light is most effective; e) use a stroboscopic or continuous light source connected by a fiberoptic cable to test the response in an isolated whole heart preparation; f) examine the use of laser light to determine if short pulses of low energy light at the desired wavelength can be used without undesirable heating effects g) develop a system using short wave visible laser light for use as an automatic implantable cardiac defibrillator; and, h) develop an instrument with a higher intensity output for use in emergency medical situations. It is envisioned that with some technological advances, it should be possible to produce small, hand-held defibrillators whose light beam can be directed between the ribs at specific areas of the heart. Such a device would be relatively inexpensive, easy to transport and simple to use. It would avoid the damage done by current electric shock defibrillators and prevent the development of subsequent cardiac arrhythmias that currently occur in a large percentage of patients after defibrillation. GRANR=R01AG06348 Multiple Epstein Barr virus transformed B cell lines have been established from patients with Alzheimer's Disease (AD), Gerstmann- Straussler-Schreinker Sundrome-AD, post-stroke and multiple sclerosis and age-matched controls. Most of the cell lines secrete monoclonal or oligoclonal antibodies (Ab). A considerable number have been screened for reactivity to AD and normal brain, cell lines and cytoskeletal proteins. While a substantial numbers of Abs reacted with common cellular constituents shared by multiple tissues, thirteen Abs were found to be specific for AD brain and eight to be specific for brain. Reactive structures included neurofibrillary tangles (NFT), plaque neurites, astrocytes, filaments, and neuronal nuclei. One Ab was specific for SDS-treated isolated NFT. These Abs constitute an unique resource to explore NFT, plaques and astrocytes in AD and neurodegenerative diseases. They may identify markers for specific brain pathology. In addition, preliminary evidence from some patients has been obtained indicating the presence of circulating Abs specific for NFT and other neural structures in AD brains. The present proposal is to continue this approach to study AD.
Specific aims i nclude: 1) Continue the characterization of AD specific and brain specific Abs. Identify their reactive antigens with immunocytochemical and serological approaches. 2) Demonstrate the presence or absence of AD specific and brain specific Abs in the plasma of patients with AD, GSS-AD and Down's Syndrome and AD family members as well as in control patients including those with stroke and MS and age-matched normals. Comparison in titers and specificities between these groups will be made. 3) Continue to screen cell lines to identify additional mAbs unique to AD and brain. Attempts will be made to generate IgG secreting lines with these specificities from selected AD and GSS-AD patients. While the exact role of these Abs in the pathogenesis of AD remains to be determined, they represent a host response to neoantigens in the AD brain resulting from degenerative changes or changes due to envirorunental etiological factors. Thus, the characterization of the specificities of these Abs will provide new insights into the nature of AD.
