Limited benefit of CT scans in tuberculosis contact tracing

ObjectiveThe detection of abnormal findings on computed tomography (CT) scans of tuberculosis contacts combined with normal plain radiographs contributes to the early detection of tuberculosis. However, the benefit of the early detection of abnormalities for the prevention of active tuberculosis during follow-up requires evaluation.MethodWe conducted retrospective comparison of the existence of CT scans of tuberculosis contacts without findings of active tuberculosis on plain radiographs at a hospital in Japan. Results: Among 243 contacts without CT scans, five developed tuberculosis during follow-up. Among 229 contacts with CT scans, 24 were judged as targets of multi-drug therapy since their CT findings were suggestive of active tuberculosis at the time of the CT screening. Among 205 contacts judged as having latent tuberculous infection with CT screening, three developed tuberculosis diseases during follow-up. Conclusion: CT scans detected abnormal findings among contacts without abnormalities of plain radiographs but there were some contacts that developed tuberculosis diseases among those with contact investigation including CT scan. The value of CT is equivocal considering the balance of true treatment, overtreatment and harm of radiation.     

Central nervous system and peripheral cell labeling by vascular endothelial cadherin-driven lineage tracing in adult mice

Understanding the contribution of endothelial cells to the progenitor pools of adult tissues has the potential to inform therapies for human disease.To address whether endothelial cells transdifferentiate into non-vascular cell types,we performed cell lineage tracing analysis using transgenic mice engineered to express a fluorescent marker following activation by tamoxifen in vascular endothelial cadherin promoter-expressing cells(VEcad-CreERT2;B6 Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze).Activation of target-cell labeling following 1.5 months of ad libitum feeding with tamoxifen-laden chow in 4–5 month-old mice resulted in the tracing of central nervous system and peripheral cells that include:cerebellar granule neurons,ependymal cells,skeletal myocytes,pancreatic beta cells,pancreatic acinar cells,tubular cells in the renal cortex,duodenal crypt cells,ileal crypt cells,and hair follicle stem cells.As Nestin expression has been reported in a subset of endothelial cells,Nes-CreERT2 mice were also utilized in these conditions.The tracing of cells in adult Nes-CreERT2 mice revealed the labeling of canonical progeny cell types such as hippocampal and olfactory granule neurons as well as ependymal cells.Interestingly,Nestin tracing also labeled skeletal myocytes,ileal crypt cells,and sparsely marked cerebellar granule neurons.Our findings provide support for endothelial cells as active contributors to adult tissue progenitor pools.This information could be of particular significance for the intravenous delivery of therapeutics to downstream endothelial-derived cellular targets.The animal experiments were approved by the Boise State University Institute Animal Care and Use Committee(approval No.006-AC15-018)on October 31,2018.     

Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transportedPhaseolus vulgaris leucoagglutinin

The present paper deals with a detailed analysis of cortical projections from the magnocellular basal nucleus (MBN) and horizontal limb of the diagonal band of Broca (HDB) in the rat. The MBN and HDB were injected iontophoretically with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). After immunocytochemical visualization of labeled efferents, the distribution of projections over the cortical mantle, olfactory regions and amygdala were studied by light microscopy. Based on differences in cortical projection patterns, the MBN was subdivided in anterior, intermediate and posterior portions (MBNa, MBNi and MBNp). All subdivisions maintain neocortical projections and are subject to an anterior to posterior topographic arrangement. In the overall pattern, however, the frontal cortex is the chief target. Furthermore, all MBN parts project to various regions of meso- and allocortex, which are progressively more dense when the tracer injection is more anteriorly placed. The most conspicuous finding, however, was a ventrolateral to dorsomedial cortical projection pattern as the PHA-L injection site moved from posterior to anterior. Thus, the posterior MBN projects predominantly to lateral neo- and mesocortex while the anterior MBN sends more fibers to the medial cortical regions. Furthermore, the MBNa is a source of considerable afferent input to the olfactory nuclei and as such should be regarded as a transition to the HDB. The HDB, apart from projecting densely to olfactory bulb and related nuclei, maintains a substantial output to the medial prefrontal cortical regions and entorhinal cortex, as well. Comparison of young vs aged cases indicate that aging does not appear to have a profound influence on cortical innervation patterns, at least as studied with the PHA-L method.     

Lesion-induced synapse reorganization in the hippocampus of cats: sprouting of entorhinal, commissural/associational, and mossy fiber projections after unilateral entorhinal cortex lesions, with comments on the normal organization of these pathways.

This study evaluates whether three forms of sprouting occur in the hippocampus of the cat following unilateral entorhinal cortex (EC) lesions: (1) sprouting of projections from the EC contralateral to the lesion; (2) sprouting of the commissural/associational system; and (3) sprouting of mossy fibers. Tract tracing techniques were used to define the normal organization of the entorhinal cortical projection system, the commissural/associational (C/A) systems, and the mossy fiber projections in normal cats. The same techniques were then used to evaluate whether there were changes in these projections in animals with long-standing unilateral EC lesions. The projections from the entorhinal cortex were evaluated autoradiographically following injections of 3H proline into the entorhinal area. The projections of the C/A system were traced using the Fink-Heimer technique after lesions of the hippocampal commissures, and by using autoradiographic techniques after injections of 3H proline into the hippocampus. The distribution of mossy fibers was evaluated using the Timm's stain. The results reveal that unilateral lesions of the EC in cats lead to the same sorts of sprouting that have been described in rats. There is: (1) an increase in the density of the crossed projection from the surviving EC to the contralateral dentate gyrus that had been deprived of its normal EC inputs; (2) an expansion of the terminal field of the C/A projection system into portions of the molecular layer of the dentate gyrus normally occupied by EC projections; and (3) an increase in supragranular mossy fibers in some animals. The mossy fiber sprouting was especially prominent when the lesions encroached upon the hippocampus. The studies also reveal additional details about the normal organization of hippocampal pathways in cats. The most important points are: (1) there is a crossed projection from the entorhinal cortex to the contralateral dentate gyrus; and (2) there is a complex laminar organization of the commissural and associational terminal fields in the molecular layer of the dentate gyrus that appears to be related to the point of origin of the projections along the septotemporal axis of the hippocampus. This heretofore unrecognized aspect of the laminar organization of C/A terminations has important implications for the temporal competition hypothesis, which has been advanced to account for the development of these afferent systems.     

Expression of tyrosine hydroxylase and neuropeptide tyrosine in mouse sympathetic airway-specific neurons under normal situation and allergic airway inflammation

BACKGROUND: The traditional neurotransmitter catecholamine and the neuropeptide tyrosine in sympathetic airway nerves have been proposed to be involved in the pathogenesis of airway diseases. OBJECTIVE: The aim of the present study was to investigate the effect of allergic airway inflammation on the expression of catecholamine enzyme tyrosine hydroxylase (TH), neuropeptide tyrosine (NPY) and tachykinins in mouse sympathetic airway ganglia. METHODS: Using neuronal tracing in combination with immunohistochemistry, the present study was designed to characterize TH, NPY and tachykinin profiles of superior cervical (SCG) and stellate ganglia after allergen challenge. RESULTS: The vast majority of fast blue-labelled SCG neurons (allergen: 97.5+/-1.22% (mean+/-SEM) vs. controls: 94.5+/-1.48%, P=0.18) and stellate neurons (allergen: 95.3+/-1.01% vs. controls: 93.6+/-1.33%, P=0.34) were immunoreactive for TH. Of the TH immunoreactive and fast blue-labelled SCG neurons, 52.0+/-1.01% allergen vs. 51.2+/-3.58% controls (P=0.83) and stellate neurons, 57.3%+/-0.97 allergen vs. 56.4+/-1.65% controls (P=0.64) were positive for TH only but not NPY, whereas 45.3+/-1.05% allergen vs. 43.3+/-1.18% controls (P=0.47) of fast blue-labelled SCG neurons and 37.9+/-0.86% allergen vs. 37.1+/-1.24% controls (P=0.62) of fast blue-labelled stellate neurons were immunoreactive for both TH and NPY immunoreactivities. There was a trend of an increase, but not significant one, in the percentage of TH-/NPY-immunoreactive and fast blue-labelled neurons in allergen-treated animals in comparison with the controls. Tachykinins, however, were not expressed by sympathetic neurons and were also not induced in sympathetic neurons after allergen challenge. CONCLUSION: The present study indicates that allergic airway inflammation does not alter the expression of noradrenalin and NPY in sympathetic ganglia and also shows that sympathetic neurons do not respond to allergic airway inflammation with tachykinins induction. However, a participation of catecholamine and NPY in the pathogenesis of allergic airway inflammation cannot be excluded in the present study as a higher neurotransmitter output per neuron following allergen challenge could be possible.     

A liquid-scintillation-based primary standardization of Pb

A new radioactivity solution standard of ²¹⁰Pb has been developed and will be disseminated by the National Institute of Standards and Technology (NIST) as standard reference material (SRM) 4337. This new ²¹⁰Pb solution standard is contained in a 5 mL flame-sealed borosilicate glass ampoule, consists of (5.133±0.002) g of a nominal 1 mol L⁻¹ nitric acid solution, has a density of (1.028±0.002) g mL⁻¹ at 20 °C, has carrier ion concentrations of about 11 μg Pb²⁺ and 21 μg Bi³⁺ per gram of solution, and is certified to contain a massic activity (9.037±0.22) kBq g⁻¹ as of the reference time 1200 EST, 15 June 2006. All of the uncertainties cited above correspond to standard uncertainties multiplied by a coverage factor k=2. The standardization for the ²¹⁰Pb content of the solution was based on 4πβ liquid scintillation (LS) measurements using CIEMAT/NIST ³H-standard efficiency tracing (CNET). Confirmatory determinations were also performed by high-resolution HPGe γ-ray spectrometry, by 2π spectrometry with a Si surface barrier detector of separated ²¹⁰Po, and by 4πβ(LS)–γ(NaI) anticoincidence counting.     

The Dubbelman eye model analysed by ray tracing through aspheric surfaces

Dubbelman and co-workers have determined intraocular spacings and surface shapes in living eyes by means of corrected Scheimpflug images in a large number of subjects of different age at several levels of accommodation. They give relationships for key anterior segment parameters as a function of age and level of accommodation. These are used in this paper to build a schematic eye incorporating aspheric surfaces. This eye model is analysed by means of ray tracing with a technique developed for use with a common spreadsheet computer program. The Dubbelman eye model appears to be well corrected for spherical aberration. Compared with measurements on real eyes it agrees well in general, but spherical aberration is negative, while in real eyes it tends to be positive.     

Neuronal migration and dendritic maturation of the medial cerebellar nucleus in rat embryos: an HRP in vitro study using cerebellar slabs

The morphological maturation of medial nuclear neurons of fetal rat cerebella was studied using an in vitro assay. Neurons of this nucleus were identified in isolated preparations of rhombencephalon between embryonic days 16 and 20 (E16-E20) by the intracerebellar decussation of their outgrowing axons within the uncinate fascicle. A small crystal of horseradish peroxidase (HRP) applied either in the region containing the inferior cerebellar peduncle or, preferably, in the lateral cerebellum retrogradely labeled contralateral medial nuclear neurons. In the youngest embryos (E16-E17), HRP-marked neurons were situated rostrally at the dorsal surface of the cerebellum. By E18, the cell mass containing labeled neurons had shifted in a rostrocaudal and dorsoventral direction and finally reached the adult position in E19-E20 embryos. Dendritic differentiation of these neurons followed a similar positional gradient, closely corresponding to the pattern of temporal development. From the most immature monopolar forms located dorsally to the virtually adult stellate neurons in a ventral position, it was possible to trace a continuum of intermediary forms grouped into six well-defined stages. Immature monopolar cells first became transversely bipolar. Then, they changed orientation, assuming a longitudinal radial direction. During this stage, neurons sank into the cerebellar parenchyma. As they reached their final destination, these neurons gradually developed dendrites which radiated from the cell body in an adult-like pattern. It is concluded that the medial nuclear neurons occupy a superficial dorsal position in early phases of cerebellar ontogeny, thereafter undergoing a second, inward migration. The main stages of neuronal dendritic differentiation occur between E16 and E20, indicating that the ingrowth of afferent in puts to the medial nucleus most probably occurs rather early and is concomitant with dendritic development.     

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity.

The organization of the thalamostriatal projections arising from the centromedian (CM) and parafascicular (Pf) thalamic nuclei in the squirrel monkey (Saimiri sciureus) was studied at both light and electron microscopic levels. Following selective injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the CM or Pf, patterns of terminal arborization within the striatum were compared to the biochemical heterogeneity of the striatum as revealed by immunohistochemical staining for the calcium-binding protein calbindin D-28k (CaBP), and histochemical staining for the enzymes acetylcholinesterase (AChE) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase). The PHA-L-labeled axon terminals within the striatum were further analyzed at the ultrastructural level to characterize their pattern of synaptic organization. Dense and heterogeneous terminal fields occur in the "sensorimotor" territory of the striatum after CM injections, or in the "associative" striatal territory following Pf injections. In the associative territory labeled axons arborize in a diffuse manner predominantly within areas enriched with CaBP, AChE, or NADPH-diaphorase, representing the matrix compartment, and tend to avoid areas poor in these substances, corresponding to the patch/striosome compartment. In the sensorimotor territory labeled axons form bands that occupy a subregion of the NADPH-diaphorase-rich zone in the putamen. The terminal pattern of the CM-striatal projection suggests the existence of a more complex mosaic organization within the sensorimotor territory. Ultrastructural analysis of PHA-L-labeled elements within the striatum reveals that both CM and Pf projections form asymmetric synapses upon dendrites and spines of striatal cells. A total of 339 PHA-L-labeled boutons were examined after CM injections and compared to 293 boutons following Pf injections. After CM injections, 29% of PHA-L-labeled terminals form synapses on dendritic spines and 66% on dendritic shafts, whereas after Pf injections only 12% of synapses occur on dendritic spines compared to 81% on dendritic shafts. Labeled terminals forming axosomatic or axoaxonic synapses were not seen within the striatum following either CM or Pf injections. It is concluded that in the squirrel monkey: 1) Pf-striatal fibers profusely arborize within the matrix compartment of the associative territory, 2) CM-striatal fibers form bands that occupy a subregion of the NADPH-diaphorase-rich zone within the sensorimotor territory, and 3) that both Pf- and CM-striatal projections establish asymmetric synapses with dendrites and spines of medium-sized spiny cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Functional organization of mustached bat inferior colliculus: II. Connections of the FM2 region

Echolocating bats estimate target distance by analyzing the time delay between frequency-modulated portions of their emitted ultrasonic vocalizations and the resultant echoes. In the companion paper we investigated, in the central nucleus of the inferior colliculus, the representation of the predominant second-harmonic frequency-modulated component (FM2) of the mustached bat biosonar signal (O'Neill et al.: J. Comp. Neurol. 283:000-000,'89). In the present paper we report the connections of this part of the colliculus, as determined by focal, iontophoretic injections of HRP following single-unit mapping of the FM2 representation. It was found that the major inputs to the FM2 region of the inferior colliculus come from the contralateral cochlear nucleus; ipsilaterally from the medial superior olive, periolivary nuclei, and ventral and intermediate nuclei of the lateral lemniscus; and bilaterally from the lateral superior olive and dorsal nucleus of the lateral lemniscus. This study identifies for the first time those specific regions of brainstem nuclei providing input to the central nucleus of the inferior colliculus that process FM2 information in the mustached bat. The primary outputs of the FM2 region project to the medial and dorsal divisions of the medial geniculate body. In sharp contrast to other mammals, we found little evidence of connections to the ventral division of the medial geniculate. Other regions receiving significant inputs from the FM2 area include the deep superior colliculus ipsilaterally and the ipsilateral lateral pontine nuclei. Some fibers also terminated near the midline in the dorsal midbrain periaqueductal gray. Sparse intrinsic connections were also seen to the ipsilateral dorsoposterior division of the central nucleus and to the contralateral inferior colliculus at a location homologous to the injection site in the anterolateral division. The finding that FM2 projections to the medial geniculate heavily favor the medial and dorsal divisions is consistent with the location of "FM-FM" delay-dependent facilitation neurons found by Olsen (Processing of Biosonar Information by the Medical Geniculate Body of the Mustached Bat, Pteronotus parnellii. Dissertation, Washington Univ., St. Louis, '86) in these divisions, and with thalamocortical projection patterns in this species. These findings demonstrate that for the FM portions of the biosonar signal, a transformation from a tonotopic form of processing to a more specialized, convergent pattern of organization occurs at the level of the inferior colliculus outputs.