Search PubMed⌕ Search

Biomedical subjects

M A Wilson

Publications and source records attributed to M A Wilson.

At least 253 records · Page 14Linked to original sources

Evaluation of multivalent Leptospira fluorescent antibody conjugates for general diagnostic use.

Four lots of conjugate were evaluated for optimal dilution and degree of fluorescence produced with reference cultures and bovine and porcine leptospira isolates. One lot that uniformly produced better fluorescence was evaluated for sensitivity and specificity with reference cultures, isolates, culture-positive tissues, and 13 other bacterial species. Further evaluation of the conjugates was done with bovine, porcine, and ovine specimens submitted to a diagnostic laboratory. Leptospires were detected with the fluorescent antibody test (FAT) in 9 of 21 culture-positive bovine kidneys and were detected in diluted cultures when present at concentrations of 10(2)-10(3) organisms/ml. With the exception of Treponema hyodysenteriae, FAT's of other bacterial cultures produced minimal fluorescence or were negative. Positives were characterized by moderate to brilliant fluorescence of typical cell forms, and most nonspecific fluorescence was eliminated with a flazo-orange counterstain. The results indicated that the FAT utilizing multivalent conjugates could be used successfully as an additional method for diagnosis of leptospira infections.

Animals↗

Responses of substantia nigra pars reticulata neurons to benzodiazepine ligands after acute and prolonged diazepam exposure. I. Modulation of gamma-aminobutyric acid sensitivity.

We have examined the ability of the benzodiazepine inverse agonist, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), and the antagonist, Ro15-1788, to modulate gamma-amino-butyric acid (GABA) sensitivity of reticulata neurons after chronic (3 week) and acute (1 hr) diazepam exposure. Sensitivity to GABA was analyzed by monitoring single unit responses to microiontophoretically applied GABA. The inverse agonist DMCM decreased GABA sensitivity of reticulata neurons to similar levels in control, chronic diazepam and acute diazepam-treated groups. Ro15-1788 administration reversed the effects of DMCM on GABA sensitivity and also resulted in comparable levels of GABA sensitivity in all treatment groups. Thus, the ability of the inverse agonist DMCM and the antagonist Ro15-1788 to alter GABA sensitivity of reticulata neurons was not altered by diazepam treatment. However, reticulata GABA sensitivity in the absence of additional benzodiazepine ligands was enhanced in both acute and chronic diazepam groups when compared to control values. The similarity in reticulata responses after both chronic (3 week) and acute (1 hr) diazepam treatments suggests that the enhanced sensitivity to GABA merely reflects the presence of diazepam. Thus, the ability of diazepam to potentiate reticulata GABA responses does not show time-dependent changes with prolonged benzodiazepine exposure.

Animals↗

Responses of substantia nigra pars reticulata neurons to benzodiazepine ligands after acute and prolonged diazepam exposure. II. Modulation of firing rate.

We have examined the effects of chronic (3 week) and acute (1 hr) exposure to diazepam on firing rate responses of reticulata neurons to the inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and the benzodiazepine antagonist Ro15-1788. The ability of DMCM and Ro15-1788 to alter firing rate were tested in control, chronic diazepam and acute diazepam-treated rats. In controls, DMCM increased firing rate of reticulata neurons. This effect was reversed by Ro15-1788, which had no effect on firing rate when administered alone. In acute and chronic diazepam-treated groups, low doses of DMCM were less effective in increasing firing than in controls. However, the administration of high doses of DMCM to diazepam-treated animals increased firing rates above the rates observed in control animals after the same compounds. Administration of Ro15-1788 also increased reticulata firing rates above control levels in both acute and chronic diazepam-treated groups. The similarity in reticulata responses after chronic (3 week) and acute (1 hr) diazepam treatments suggests that the altered properties of the benzodiazepine ligands observed after chronic exposure could reflect the presence of diazepam. This may indicate that reticulata neurons themselves do not show changes in sensitivity to benzodiazepine ligands after chronic benzodiazepine exposure. We propose that the altered responses to DMCM and Ro15-1788 in diazepam-treated rats reflect a compensatory change which occurs by 1 hr and maintains reticulata activity at a constant level throughout the period of prolonged exposure to the agonist.

Animals↗

GABAergic subsensitivity of dorsal raphe neurons in vitro after chronic benzodiazepine treatment in vivo.

Previous studies have shown that chronic benzodiazepine treatment reduces the in vivo sensitivity of dorsal raphe neurons (DRN) to microiontophoretically applied gamma-aminobutyric acid (GABA). We have examined sensitivity of DRN in vitro using a modified midbrain slice technique which allows side-by-side analysis of slices from control and chronic diazepam-treated rats. GABA sensitivity of raphe neurons was reduced in slices from rats treated for 3 weeks with diazepam, compared to control sensitivity. Thus, GABA subsensitivity following chronic diazepam treatment appears to be dependent on changes intrinsic to the midbrain area.

Action Potentials↗

(+/-)3,4-Methylenedioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates.

(+/-)3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has been proposed to be useful as an adjunct to psychotherapy. This study assessed the neurotoxic potential of MDMA in nonhuman primates. Monkeys were repeatedly administered doses (2.50, 3.75, and 5.00 mg/kg) of MDMA subcutaneously and analyzed for regional brain content of serotonin and 5-hydroxyindoleacetic acid two weeks later. In all regions of the monkey brain examined, MDMA produced a selective dose-related depletion of serotonin and 5-hydroxyindoleacetic acid. These neurochemical deficits were associated with evidence of structural damage to serotonergic nerve fibers. In addition, MDMA produced pathological changes in nerve cell bodies in the dorsal, but not median, raphe nucleus. These results indicate that MDMA is a selective serotonergic neurotoxin in nonhuman primates and that humans using this drug may be at risk for incurring central serotonergic neuronal damage.

3,4-Methylenedioxyamphetamine↗

Surface potential of the water liquid-vapor interface.

The surface potential of the water liquid-vapor interface is studied by molecular dynamics using the TIP4P model. The surface potential predicted by this empirical model is -(130 +/- 50) mV. This value for the surface potential is of reasonable magnitude but of opposite sign to the expectations derived from laboratory experiments. The electrostatic potential displays a nonmonotonic variation with depth into the liquid. This nonmonotonic variation is explained on the basis of the nondipolar charge distribution of the H2O molecule and the observation that the more probable molecular orientations in the interfacial region place the molecular symmetry axis near the plane of the interface. It is shown that minor changes in the assumed molecular charge distribution can bring the computed surface potential into agreement with experimental expectations without qualitatively altering the nonmonotonic variation of the electrostatic potential through the interfacial region. Computed quantum mechanical descriptions of the electron distribution of the isolated H2O molecule are not compatible with the surface structure predicted by the TIP4P model and the experimental expectation that the surface potential of the water liquid-vapor interface is small, roughly of the of order of 10-100 mV. The surface potential is sensitive to details in the large distance wings of the molecular electron distribution. It is hypothesized that the surface environment qualitatively alters the wings of the distribution from the result obtained by a superposition of the isolated molecule electron densities.

Gases↗

A developmental and ultrastructural study of the optic chiasma in Xenopus.

The structure of the optic chiasma in Xenopus tadpoles has been investigated by light and electron microscopy. Where the optic nerve approaches the chiasma, a tongue of cells protrudes from the periventricular cell mass into the dorsal part of the nerve. Glial processes from this tongue of cells ensheath fascicles of optic axons as they enter the brain. Coincident with this partitioning, the annular arrangement of axons in the optic nerve changes to the laminar organization of the optic tract. Beyond the site of this rearrangement, all newly growing axons accumulate in the ventral-most part of the nerve and pass into the region between the periventricular cells and pia which we have called the 'bridge'. This region is characterized by a loose meshwork of glial cell processes, intercellular spaces and the presence of both optic and nonoptic axons. In the bridge, putative growth cones of retinal ganglion cell axons are found in the intercellular spaces in contact with both the glia and with other axons. The newly growing axons from each eye cross in the bridge at the midline and pass into the superficial layers of the contralateral optic tracts. As the system continues to grow, previous generations of axon, which initially crossed in the existing bridge, are displaced dorsally and caudally, forming the deeper layers of the chiasma. At their point of crossing in the deeper layers, these fascicles of axons from each eye interweave in an intimate fashion. There is no glial segregation of the older axons as they interweave within the chiasma.

Animals↗

Osteosarcoma arising in Paget's disease of the calvarium.

Paget's disease of the bone occasionally transforms into sarcomatous tumors such as osteosarcoma. While Paget's disease demonstrates markedly increased uptake of bone scanning radiopharmaceutical, osteosarcomas complicating this condition often show decreased uptake. An unusual scan appearance of the osteosarcoma is presented in which the tumor showed intense uptake of the tracer on the bone scan. The extent of the sarcoma as delineated by the bone scan corresponded closely to the size of the lesion as seen on computerized tomography and magnetic resonance imaging and was confirmed at surgery.

Aged↗

Comparison of the structure of harmonic aqueous glasses and liquid water.

Glassy structures of water were generated by rapidly quenching configurations of 64 and 343 molecules of liquid water. The potential energy was then expanded through quadratic order around local minima generated this way and properties of the resulting harmonic system were calculated. The results were used to test the extent to which the structure of liquid water is similar to that of a harmonic aqueous glass. The radial distribution functions for the glass are remarkably similar to those of the liquid. The vibrational density of states for the glassy water exhibits a gap between 300 and 400 cm-1. The normal modes below 300 cm-1 correspond to molecular translations while the modes above 400 cm-1 are ascribed to molecular librations. Translational modes are almost entirely responsible for the broadening of oxygen-oxygen radial distribution function of the quenched configuration. They are also primarily responsible for the broadening of other radial distribution functions. Vibrational density of states leads to classical and quantum free energies for the harmonic system equal -9.62 +/- 0.12 and -8.89 +/- 0.12 kcal/mol, respectively, at T = 300 K. Both free energies were found to be insensitive to sample size and to the configurational differences between the quenched structures.

Computer Simulation↗

Effects of chronic diazepam exposure on GABA sensitivity and on benzodiazepine potentiation of GABA-mediated responses of substantia nigra pars reticulata neurons of rats.

This study examined the effects of chronic diazepam treatment on GABA sensitivity of substantia nigra pars reticulata neurons and on the ability of benzodiazepines to enhance GABAergic responses of these neurons in rats. Chronic diazepam exposure failed to significantly alter the sensitivity of reticulata neurons to microiontophoretically applied GABA. However, following chronic diazepam treatment for 1 day, or 1, 3 or 7-11 weeks, reticulata neurons showed tolerance to additional systemically or iontophoretically applied benzodiazepines and displayed an increased firing rate following injection of Ro 15-1788. These changes were not apparent 24 h after cessation of chronic treatment. Thus, tolerance to the effects of benzodiazepines on reticulata neurons appeared to develop after a single day of diazepam exposure and to dissipate by 24 h after cessation of treatment. When compared to our previous studies on dorsal raphe neurons, these results demonstrate regional differences in neuronal responses to chronic diazepam exposure, which may help elucidate neural systems which are involved in tolerance to the various functional aspects of benzodiazepines.

Animals↗