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Biomedical subjects

M A Moran

Publications and source records attributed to M A Moran.

5 recordsLinked to original sources

Ultrastructural localization of acetylcholinesterase in neurofibrillary tangles, neuropil threads and senile plaques in aged and Alzheimer's brain.

Acetylcholinesterase (AChE) histochemistry was used to evaluate the accumulation of this enzyme in senile plaques, neurofibrillary tangles and neuropil threads using light and electron microscopy in Alzheimer's disease as well as non-demented aged brains. Under the electron microscope, a crystalline-like AChE precipitate was localized over paired helical filaments and straight filaments in both neurofibrillary tangles and neuropil threads. AChE reaction product also decorated the amyloid fibrils in diffuse plaques as well as the halo and the heavy accumulation of amyloid which forms the core of classical plaques. In both diffuse plaques and the halo of classical plaques, we found AChE-positive structures resembling cell processes, which in some cases appeared to contain amyloid fibrils. The possible origin and significance of AChE localized over paired helical filaments, straight filaments and amyloid is discussed.

Acetylcholinesterase

Adaptation of model genetically engineered microorganisms to lake water: growth rate enhancements and plasmid loss.

When a genetically engineered microorganism (GEM) is released into a natural ecosystem, its survival, and hence its potential environmental impact, depends on its genetic stability and potential for growth under highly oligotrophic conditions. In this study, we compared plasmid stability and potential for growth on low concentrations of organic nutrients of strains of Pseudomonas putida serving as model GEMs. Plasmid-free and plasmid-bearing (NAH7) prototrophic isogenic strains and two amino-acid auxotrophs, all containing antibiotic resistance markers, were held physically separate from but in chemical contact with lake water containing the natural bacterium-sized microbial populations. Cells were reisolated at intervals over a 2-month period to determine the percent retaining the plasmid and the specific growth rate on various media. Plasmid stability in lake water was strongly strain specific; the NAH7 plasmid was stably maintained by the prototrophic strain for the duration of the test but was lost within 24 h by both of the auxotrophs. Specific growth rates of reisolates, compared with those of the corresponding non-lake water-exposed strains (i.e., parental strains), were not different when measured in rich medium (Luria-Bertani broth). However, specific growth rates were 42, 55, and 63% higher in reisolates of auxotrophs and the plasmid-free prototroph, respectively, when measured in 10-fold-diluted medium after exposure of 15 days or longer to lake water. Moreover, lake water-exposed strains grew actively when reintroduced into sterile lake water (28- to 33-fold increase in numbers over 7 days), while the corresponding unadapted parental strains exhibited no growth over the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Biological

Significantly improved peripheral intravenous catheter performance in neonates: insertion ease, dwell time, complication rate, and costs.

A prospective, randomized, controlled study was performed in neonates in an intensive care nursery to compare the performance of a peripheral intravenous catheter made of Aquavene material (test catheter) with that of a conventional peripheral catheter made of Teflon material (control catheter). Aquavene is a newly developed biomaterial that softens and expands on contact with body fluids. A total of 105 catheters (50 test and 55 control) were inserted in 63 neonates. The median time to a catheter-related complication was 3.60 days for the test catheters and 1.75 days for the control catheters (p = 0.0007). Infiltration rate for the test catheters was 56% as compared with 78% for the control catheters (p = 0.03). The test catheters provided fewer catheter-related complications (p = 0.006), with 34% of the test catheters reaching end of therapy as compared with 9% of the control catheters (p = 0.004). On average, 1.8 test catheters were used per insertion versus 2.3 control catheters (p = 0.08). The test catheters were rated easier to insert (p = 0.05), with a shorter time required for insertion. Because of improved performance, cost savings were realized with the test catheters after the first day of therapy, even though the per unit cost of the test catheter was greater. These data indicate that the test catheter, made of Aquavene material, is superior to the Teflon catheter for peripheral intravenous therapy in neonates.

Biocompatible Materials

The immunosuppressive properties of enisoprost and a 5-lipoxygenase inhibitor (SC-45662).

Metabolic derivatives of arachidonic acid such as prostaglandins and leukotrienes may alter immune responses. Enisoprost (ENO), a synthetic prostaglandin E analog, inhibited the response of human peripheral blood mononuclear cells to phytohemagglutinin in a concentration-dependent fashion: .1, 1.0, and 10 micrograms/ml yielding 4.0, 21.7, and 74.3% inhibition, respectively. ENO also potently inhibited both IL-2 production (measured by ELISA) and IL-2 responsiveness (measured by CTLL-2 response to IL-2) in a concentration-dependent manner, yet did not inhibit acquisition of IL-2 receptors. ENO similarly diminished efferent immune function in a concentration-dependent fashion, as measured by inhibition of cytotoxic T cell and natural killer effector function. A 5-lipoxygenase inhibitor (5-LO), SC-45662, also inhibited mononuclear cell response to PHA in a concentration-dependent manner: 0.1, 1.0, and 10 micrograms/ml yielding 5.0, 9.7, and 79.7% inhibition, respectively. Although 5-LO potently inhibited IL-2 production, it had no effect on IL-2 responsiveness or IL-2 receptor acquisition. Like ENO, 5-LO impaired CTL and NK effector function yet was not as potent in inhibiting CTL effector function. In summary, ENO and 5-LO inhibit afferent and efferent immune function. The inhibitory effects of these drugs are not related to cytotoxicity as cell viability is maintained for 72 hr in the presence of these drugs, and the inhibitory effect is reversible when the drugs are removed. The 5-LO does not inhibit mononuclear cell responses simply by shunting the formation of arachidonic acid precursors to form inhibitory prostaglandins, since it does not impair IL-2 responsiveness in a manner similar to ENO. These two compounds may prove to have clinical utility in organ transplantation if safely achieved serum concentrations of these drugs yield in vivo immunosuppression parallel to our in vitro results.

Acetates