Voxel based versus region of interest analysis in diffusion tensor imaging of neurodevelopment

There are two main methods of quantitative analysis in diffusion tensor imaging (DTI) studies: manual region of interest (ROI) and automated voxel based. The purpose of this study is to compare the results of each of these methods applied to the same data set. Linear correlative analysis was performed for mean diffusivity (Trace/3 ADC) and for fractional anisotropy (FA) versus age within 8-12 years (N = 32) and within 21-27 years (N = 28), as well as a group comparison. SPM analysis identified more structures changing with age, partly due to the limited regions measured with ROI analysis. In general, ROI and voxel-based analysis methods produced comparable results for widespread reductions of Trace/3 ADC and increases of FA with age, particularly for group comparison. The discrepancies (i.e., missed regions) were likely related to problems of spatial normalization for SPM analysis, and masking localized changes by averaging all the voxels within a region of interest for ROI analysis. These two analysis methods for DTI offer complementary results, but neither one yields the complete story of neurodevelopment.     

Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons

Dopamine is believed to contribute to the degeneration of dopamine-containing neurons in the brain. However, whether dopamine affects the survival of other neuronal populations has remained unclear. Here we document that mice with persistently elevated extracellular dopamine, resulting from inactivation of the dopamine transporter gene, sporadically develop severe symptoms of dyskinesia concomitant with apoptotic death of striatal dopamine-responsive gamma-aminobutyric acidergic neurons. Chronic inhibition of dopamine synthesis prevents the appearance of motor dysfunction. The neuronal death is associated with overactivation of dopaminergic signaling as evidenced by the robust up-regulation of striatal DeltaFosB, cyclin-dependent kinase 5, and p35. Moreover, hyperphosphorylation of the tau protein, a phenomenon associated with the activation of cyclin-dependent kinase 5 in several neurodegenerative disorders, is observed in symptomatic mice. These findings provide in vivo evidence that, in addition to its proposed role in the degeneration of dopamine neurons, dopamine can also contribute to the selective death of its target neurons via a previously unappreciated mechanism.     

Complete congruence between gene diversity estimates derived from genotypic data at enzyme and random amplified polymorphic DNA loci in black spruce.

Controversy still exists over the adaptive nature of variation of enzyme loci. In conifers, random amplified polymorphic DNAs (RAPDs) represent a class of marker loci that is unlikely to fall within or be strongly linked to coding DNA. We have compared the genetic diversity in natural populations of black spruce [Picea mariana (Mill.) B.S.P.] using genotypic data at allozyme loci and RAPD loci as well as phenotypic data from inferred RAPD fingerprints. The genotypic data for both allozymes and RAPDs were obtained from at least six haploid megagametophytes for each of 75 sexually mature individuals distributed in five populations. Heterozygosities and population fixation indices were in complete agreement between allozyme loci and RAPD loci. In black spruce, it is more likely that the similar levels of variation detected at both enzyme and RAPD loci are due to such evolutionary forces as migration and the mating system, rather than to balancing selection and overdominance. Furthermore, we show that biased estimates of expected heterozygosity and among-population differentiation are obtained when using allele frequencies derived from dominant RAPD phenotypes.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Quantitative aspects of synaptogenesis in the rat barrel field cortex with special reference to GABA circuitry

The postnatal establishment of cortical connectivity was studied by estimating the number (numerical density, synapse-to-neuron ratio, and total number) of the overall synaptic population and its distribution into gamma-aminobutyric acid (GABA)-immunopositive and GABA-immunonegative synaptic contacts in the developing rat somatosensory cortex. These numerical data were obtained using the unbiased disector method in combination with GABA postembedding immunocytochemistry. The numerical density of both synaptic populations was low in the early postnatal period (postnatal days 5 and 10, P5, P10) after which it abruptly increased between P10 and P15 to approach adult values. However, since cortical volume continues to increase after this age, the number of synapses per neuron and the total number of synapses reached adult values only by P30. There was no evidence of overproduction of either GABA or non-GABA synapses. Direct comparison between the two synaptic populations revealed a similar developmental pattern with the exception of the period around P20 when the production of GABA synapses slowed down. Thus, while the formation of non-GABA synapses proceeded in a continuous manner throughout the first month of life, GABA synapse production was accomplished in two consecutive waves. We suggest that the second delayed wave of GABA synapse formation is related to the great developmental plasticity of the cortical inhibitory system. © 1996 Wiley-Liss, Inc.     

Changes in water diffusion due to Wallerian degeneration in peripheral nerve

The authors report NMR measurements of the changes in water diffusion brought about by in vivo Wallerian degeneration due to either crush- or tie-injuries in the sciatic nerve of the frog. Using a pulsed-gradient spin-echo sequence with a diffusion measurement time of 28 ms, the degree of diffusion coefficient anisotropy {D(longitudinal)/D(transverse)} 4 weeks after injury in both crush- and tie-injured nerves (2.3 ± 0.4 and 1.7 ± 0.1, respectively) is significantly less than in normal frog sciatic nerve (3.9 ± 0.4). The decrease of anisotropy in the degenerated nerves is due to both a decrease in longitudinal diffusion and an increase in transverse diffusion. The changes in diffusion coefficients are compared with the degree of axonal and myelin breakdown observed in light and electron micrographs of the nerves.     

Residual Periodontal Ligament in Extracted Teeth – Is It Associated With Indication for Extraction?

BackgroundPeriodontal disease is a major cause of tooth loss. Few studies have evaluated the residual area of the periodontal ligament in extracted teeth and, to the best of our knowledge, none from Latin America have done so regarding indications for extraction. The aim of this study was to evaluate the residual periodontal ligament (RPL) with respect to indication for extraction in a sample of teeth from a Brazilian Public Health Service district.Materials and methodsAll teeth extracted within the Public Health Service district of Santa Maria, Brazil, over a 5-month period were requested for analysis. A total of 414 teeth eligible for measurement were stained and evaluated for RPL using a stereo microscope. Participating Public Health Service dentists completed a questionnaire detailing demographic variables and indication for each extracted tooth. The percentage of RPL was determined for each tooth. Comparisons of RPL between teeth extracted on periodontal versus other indications were made using the Mann-Whitney test.ResultsRPL averaged 34.8% for teeth extracted on periodontal indications versus 79.5% for other teeth (P ≤ 0.001). When considering teeth with an RPL ≥ 30% as possible to maintain, 189 (76%) of the teeth extracted on periodontal indications could have been maintained. When RPL cut-off limits of ≥ 40% or ≥ 50% are applied, 93 (37%) and 43 (17%) teeth, respectively, could have been maintained.ConclusionThis study suggests that strictly based on RPL, a large number of teeth extracted on periodontal indications conceivably could be maintained.Key words: Cross-sectional studies, Prognosis, Tooth extraction, Tooth loss