Associative memory function in piriform (olfactory) cortex: computational modeling and neuropharmacology.
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Biomedical subjects
Publications and source records attributed to M A Wilson.
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The cytotoxic effects of amphetamine derivatives were studied by immunocytochemistry to identify the cellular compartments affected by these drugs, to obtain morphologic evidence of neuronal degeneration, and to assess the potential for regeneration. The substituted amphetamines, MDA, MDMA, PCA, and fenfluramine, all release serotonin and cause acute depletion of 5-HT from most axon terminals in forebrain. (1) Unequivocal signs of axon degeneration were seen at 36-48 hour survivals: 5-HT axons exhibited increased caliber, huge, swollen varicosities, fragmentation, and dilated proximal axon stumps. (2) Fine 5-HT axon terminals were persistently lost after drug administration, while beaded axons and raphe cell bodies were spared. These two types of 5-HT axons, which arise from separate raphe nuclei and form distinct ascending projections, are differentially vulnerable to psychotropic drugs. (3) From 2-8 months after treatment, there was progressive serotonergic re-innervation of neocortex along a fronto-occipital gradient. Longitudinal 5-HT axons grew into layers I and VI from rostral to caudal, before sprouting into middle cortical layers; this bilaminar pattern of growth simulates perinatal development of 5-HT innervation. This study demonstrates differential vulnerability of 5-HT projections, evidence for axonal degeneration, and sprouting of 5-HT axons leading to re-innervation of forebrain. While the sprouting axons are anatomically similar to the type that was damaged, it is not known whether a normal pattern of innervation is re-established.
Kidney tissues from 20 cattle infected with Leptospira interrogans serovars hardjo, pomona, or grippotyphosa were cultured on the day of slaughter and 3, 6, and 8 days later to examine the effect of storage time on the recovery of leptospires by conventional culture methods. Leptospires were isolated from 85% of infected bovine kidney tissues cultured on day 1, and from 95%, 90%, and 90% of kidney tissues stored in transport medium at 4 C for 3, 6, and 8 days, respectively, prior to inoculation of culture media.
The epidemiology of leptospirosis in Iowa swine was examined on the basis of serologic results and herd data from 55 herds in the National Animal Health Monitoring System (NAHMS) program and culture results and histories from 578 cases of reproductive failure submitted to the Iowa Veterinary Diagnostic Laboratory during a 3-year period. Thirty-eight percent of sera from NAHMS herds contained antibodies against 1 or more of 12 leptospira antigens. Leptospires were isolated from 9 (1.6%) of 578 cases of reproductive failure. Seven (78%) of the isolates were identified as Leptospira interrogans serovar kennewicki and 2 (22%) as serovar grippotyphosa. In 7 herds from which leptospires were isolated, attack rates ranged from 1% to 84%. Clinical leptospirosis, characterized by reproductive failure and confirmed by isolation of leptospires, was sporadic. No significant differences in farrowing averages and reproductive problems were observed between vaccinated and nonvaccinated NAHMS herds or between herds with higher (43-63%) or lower (14-40%) percentages of animals that were serologically positive against serovar bratislava.
The findings of an initial investigation of variations in the thickness of the composite lute around inlays of a fine particle hybrid, light- and secondary-cured indirect composite resin inlay system are reported. The lute thickness varied between 10 microns and 90 microns, and was found to be thinnest and most uniform in the region of occlusal cavosurface margins. Although the marginal adaptation of the inlays investigated was generally considered to be satisfactory, sections of the lute were found to exhibit porosity and to contain a number of voids. It is concluded that whilst the lute thickness and marginal adaptation of composite bonded inlays of the type investigated may be found to be acceptable, further work is desirable to investigate ways to limit porosity and voids in lutes and to form and finish the cavomarginal elements of tooth-coloured inlays in such a way that the limiting layer of luting material may be better protected from the rigors of function in the oral environment.
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Benzodiazepine ligands of differing efficacy including the agonist, diazepam, the partial agonist, Ro 16-6028 and the antagonist, Ro 15-1788, were administered in vivo to rats continuously for 3 weeks. The magnitude of change in various measures of GABA sensitivity could be correlated directly with increasing agonist efficacy: maximal changes were seen following chronic treatment with diazepam, intermediate changes were seen following the partial agonist Ro 16-6028 and no changes were observed following chronic Ro 15-1788 administration. The magnitude of change could also be correlated with increasing potential for tolerance development to anticonvulsant efficacy following chronic exposure to these benzodiazepine ligands.
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The associations of physical activity, skin color, body mass difference and conspecific olfactory cues with short-term aerobic and anaerobic metabolism in paired male Anolis carolinesis were examined. Control measurements for mild laboratory manipulation (such as the movement of a metabolic chamber) yielded significant increases in the rate of oxygen consumption, but not in the lactate concentration of these animals; stronger manipulation increased both. A possible influence of conspecific olfactory cues on the metabolism of lizards introduced into empty chambers was undetected. Anolis that turned from green to brown with handling showed an increase in oxygen uptake, but an association between this color shift and total body lactate level was not detected. Elevated rates of oxygen use and glycolysis were found in pairs of males in the absence of physical activity. Lactate levels of the individuals of a pair were positively correlated with one another; the lactate concentrations of lizards placed into occupied metabolic chambers were correlated with the difference in body mass of the pair.
Molecular dynamics results are presented for the density profile of a sodium ion near the water liquid-vapor interface at 320 K. These results are compared with the predictions of a simple dielectric model for the interaction of a monovalent ion with this interface. The interfacial region described by the model profile is too narrow and the profile decreases too abruptly near the solution interface. Thus, the simple model does not provide a satisfactory description of the molecular dynamics results for ion positions within two molecular diameters from the solution interface where appreciable ion concentrations are observed. These results suggest that surfaces associated with dielectric models of ionic processes at aqueous solution interfaces should be located at least two molecular diameters inside the liquid phase. A free energy expense of about 2 kcal/mol is required to move the ion within two molecular layers of the free water liquid-vapor interface.
Immunohistochemical methods were used to analyse the distribution and morphology of serotonergic axons in normal macaque monkeys and in monkeys given (+/-)3,4-methylenedioxymethamphetamine. In untreated monkeys, we observed two morphologic classes of serotonergic axon terminals, which differ in regional and laminar distribution. These two axon types, fine and beaded, correspond to the serotonergic axon types which have been described in the rat. In 3,4-methylenedioxymethamphetamine-treated monkeys, there is a profound loss of serotonergic axon terminals, yet some are consistently spared. The surviving axon terminals are nearly all of the beaded type; in contrast, fine serotonergic axons are markedly reduced in density. There are regional differences in the magnitude of denervation, which reflect differences in the distribution of these two types of serotonergic axons in controls. The present study demonstrates that 3,4-methylenedioxymethamphetamine has differential neurotoxic effects on fine and beaded serotonergic axons. These results indicate that in the primate there are two distinct classes of serotonergic axon terminals, which differ in morphology, distribution, and vulnerability to psychotropic drugs. We hypothesize that in the primate, as demonstrated in the rat, these two classes of serotonergic axon terminals may arise from different raphe nuclei. In both rodent and primate, the dorsal and median raphe nuclei give rise to parallel ascending serotonergic projections, which are likely to have different pharmacologic properties and functions.
Tricyclic antidepressants such as imipramine interact with a membrane binding site associated with the uptake of serotonin. Ovarian hormones estradiol and progesterone were found to affect the concentration and affinity of imipramine binding sites in the hypothalamus but not the cortex of female rats. In vivo and in vitro, estradiol increased the amount of imipramine binding at physiological concentrations; at high concentrations estradiol decreased imipramine binding. Ovariectomy (OVX) had no effect on imipramine binding, consonant with the biphasic dose-response relationship for estradiol. The effects of progesterone were dependent upon the concentration of estradiol. Effects of physiological concentrations of both estradiol and progesterone on imipramine binding in an isolated membrane preparation suggest that the hormones are affecting this aspect of serotonergic neuronal function by nongenomic mechanisms.
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Complement activation by Aspergillus fumigatus may play a crucial role in stimulating binding and killing of this organism by phagocytes. We examined the amount and type of C3 deposited on resting conidia, swollen conidia, and hyphae of A. fumigatus after incubation in pooled human serum. All three life forms of A. fumigatus were potent activators of the complement cascade, with deposition on the organisms of similar amounts of C3 per unit of surface area. The rate of deposition was slowest for resting conidia, although maximal deposition was still achieved within 40 min. The roles of the alternative and classical pathways were assessed by use of serum chelated with magnesium EGTA [magnesium ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and with an alternative pathway reconstituted from the six purified alternative-pathway proteins. Complement activation by resting conidia was mediated by the alternative pathway. In contrast, there was a progressive dependence on the classical pathway as the fungal particles matured into swollen conidia and then hyphae. Treatment with hydroxylamine, which disrupts ester linkages, removed 89 to 95% of the C3 bound to all three forms of A. fumigatus. This released C3 contained a mixture of C3b and iC3b, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. These data demonstrate that although all three forms of A. fumigatus are potent activators of the complement system, the transition from resting conidia to swollen conidia to hyphae results in progressive changes in the manner in which the fungal particles interact with the complement system. The lack of participation of the classical pathway in complement activation by resting conidia may have important implications regarding their ability to effectively stimulate phagocytes.
Encapsulated Cryptococcus neoformans yeast cells are potent activators of the complement system. We examined the interaction of the yeast cells with an alternative complement pathway reconstituted from isolated factor D, factor B, factor H, factor I, C3, and properdin. Incubation of encapsulated cryptococci with the reconstituted pathway led to activation and binding of C3 fragments to the yeast cells that was quantitatively and qualitatively identical to that observed with normal human serum. Incubation with either normal serum or a mixture of isolated proteins led to binding of 4 x 10(7) to 5 x 10(7) C3 molecules to the yeast cells. The kinetics for activation and binding of C3 were identical, with maximum binding observed after a 20-min incubation. Immunoglobulin G was not needed for optimal activation kinetics. C3 fragments eluted from the yeast cells by treatment with hydroxylamine and subsequent analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated the presence primarily of iC3b on yeast cells incubated with either normal serum or the reconstituted pathway. Ultrastructural examination of the opsonized yeast cells showed that the cryptococcal capsule was the site for binding of C3 activated from normal serum or the reconstituted pathway, with a dense accumulation of C3 at the periphery of the capsule. Thus, incubation of encapsulated cryptococci in the reconstituted pathway led to deposition of opsonic complement fragments at a site that was appropriate for interaction with phagocyte receptors. Cryptococci opsonized with the reconstituted pathway showed a markedly enhanced interaction with cultured human monocytes compared with unopsonized yeast cells, indicating that the alternative pathway alone is opsonic for yeast cells. However, the results indicate that additional serum factors are needed for optimal opsonization of yeast cells because a 35% reduction in the number of cryptococci bound to macrophages was observed with cryptococci opsonized with the reconstituted pathway compared with that observed when yeast cells were opsonized with normal serum.
Triple-phase bone scans were obtained in seven patients within 48 hours of admission for frostbite injuries. Three patterns of perfusion imaging and delayed bone imaging were observed: hyperemic blood flow with normal early blood pool and normal delayed bone images; absent blood flow and absent early blood pool depiction, but depiction of bone in delayed images; and absent perfusion and absent blood pool depiction, with no bone uptake in the delayed images. The first pattern indicated mild ischemia that required no surgical treatment, the second indicated ischemia with occasional superficial tissue infarction that required minor debridement, and the third pattern indicated deep-tissue and bone infarction that required amputation. The triple-phase bone scan is a useful indicator of tissue viability as early as 2 days after cold injury and appears to have a clinical role in the evaluation of frostbite injuries. The perfusion and blood pool images demonstrate the ischemic tissue at risk, while the delayed bone scan images demonstrate the extent of deep-tissue and bone infarction.