Biomedical subjects
Publications and source records attributed to P Baron.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Previous studies indicated that Schwann cells in immature nerves express nerve growth factor (NGF) receptors, and that this expression is down regulated during development but re-induced by Wallerian degeneration. It was also shown that immature Schwann cells are induced to express galactocerebroside and other molecules characteristic of mature Schwann cells by either contact with an axon or treatment with the cyclic adenosine 3',5'-monophosphate (cAMP) analogues dibutyryl cAMP (dbcAMP) and 8-bromo cAMP or the adenylate cyclase activator forskolin. In the present study, NGF receptors on the surface of cultured Schwann cells were demonstrated by binding of an anti-rat NGF receptor monoclonal antibody or of radioiodinated NGF. Treatment of cultured Schwann cells with cAMP analogues or forskolin resulted in a progressive decrease in both immunoreactive NGF receptors and radioiodinated NGF binding. The cultured Schwann cells contained a polyadenylated RNA species homologous with human melanoma NGF receptor mRNA in sequence and size. The amount of this NGF mRNA was lower in cAMP analogue-treated than in untreated Schwann cells.
A common feature of Alzheimer's disease (AD) pathology is the abundance of reactive astrocytes and activated microglia in close proximity to neuritic plaques containing amyloid-beta protein (Abeta). The relationship between glial activation and neurodegeneration remains unclear, although several cytokines and inflammatory mediators produced by activated glia have the potential to initiate or exacerbate the progression of neuropathology. Assuming that glial activation plays a central role in the development and progression of AD, a prominent feature is to understand which stimuli drive this activation in senile plaques and to define their effects in vitro. There is a growing body of evidence to suggest that deposition of Abeta and expression of its associated molecules represent important trigger factors in glial activation leading to an inflammatory reaction in the brain. Thus, unraveling the mechanisms by which these proteins exert their effect on glial cells may provide significant insight into the pathophysiology of AD, and may lead to the identification of new strategies for AD treatment.
Fibrous aerosols are of great importance to industrial hygienists because of the severe health risks that may be associated with inhaling such particles. Previous studies on measurement error due to overloading of fibers and nonfibrous particles on the collected sample indicate that a 100-1300 fiber/mm2 filter area is the best filter loading density to reduce bias in fiber counts. The present study investigated the upper fiber and particle concentration limits for reliable counting and identification and the possibility of a procedure for correcting observed fiber counts to account for fiber masking due to overlapping particles or fibers. A computer-generated grid was used to simulate the light microscope graticule field. The resolution of 2000 x 2000 was found to accurately represent the shape of the fibers and nonfibrous particles. Bivariate lognormal distributions were used to describe the length and width distributions of the fibers. The capability of distinguishing particle-overlapped fibers (defined as the resolution index), the coverage of the graticule field, the filter surface loading density, size distributions of fibers and particles, and the fiber-to-particle concentration ratio were the primary parameters in this study. The counting efficiency was found to consistently decrease with increasing filter surface loading density and decreasing resolution index. The recommended upper limit of filter surface fiber density depended not only on the number concentration ratio but also on the filter surface loading densities and size distributions of fibers and particles. The advantage of using a thoracic preseparator on counting efficiency was calculated and found to improve counting efficiency significantly when the count median diameter of nonfibrous particles was close to or larger than the thoracic 50% cutoff point of 10 microm.
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To determine the feasibility of en bloc removal of the heart, lungs, liver, kidneys, and pancreas for preservation with warm blood autoperfusion, organs from 34 dogs were preserved ex vivo for periods of between 3 and 22 hours. The lungs were ventilated with a Bird Mark 7 respirator, and the heart served as the pump to perfuse all organs of the multiple organ block. In the first group of 28 animals, surgical and pharmacologic techniques were developed to permit management of the ex vivo model. The last six experiments were conducted in a standardized fashion for a period of 6 hours and evaluated on the basis of hemodynamic, biochemical, and pathologic measurements. In this group the pH level remained stable and blood gas levels remained within normal limits for inspired oxygen of 0.2. Serum and urine electrolyte levels were easily maintained within normal limits. Serum enzyme values were elevated initially after operation, and this increase persisted throughout the preservation period in most animals. Continuing refinements in surgical technique, pharmacologic management, and chamber development resulted in a dramatic reduction of the edema and organ damage seen on pathologic studies of the initial experiments. The presence of focal lymphatic congestion, however, was noted even in the animals in group II and may have been related to ligation of major lymphatic channels or to endothelial loss. These changes could contribute to the development of the pathologic changes seen in irreversible shock. Preservation of the multiple organ block by warm autoperfusion is an important step in understanding the physiology of organ preservation and has potential for permitting prolonged organ preservation. Studies are continuing to further analyze this model and prolong the time of preservation. Final assessment of the model will be transplantation of the preserved organs and evaluation of function after implantation.
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Groups of 5'-phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-acetylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene, or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonyl-phosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by the action of ammonia in methanol. All compounds were tested for inhibition of several viruses, including human herpes simplex virus type 2 and cytomegalovirus, but showed no activity. A few compounds insignificantly inhibited human immunodeficiency virus type 1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized the anti HIV action of 3'-azido-3'-deoxythymidine, thus indirectly showing that it could be partly hydrolyzed in cell culture to corresponding thymidine.