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Effect of yoga-based and forced uninostril breathing on the autonomic nervous system.

Some reports have described the effects of forced uninostril breathing on autonomic activity as sex-specific, while other reports described selective effects of breathing through a specific nostril on the two divisions of the autonomic nervous system, irrespective of sex. There are also yoga breathing techniques which involve voluntary uninostril breathing. These techniques also influenced the autonomic activity based on the patent nostril rather than sex. These descriptions were in line with experiential observations of the ancient sages described in classical yoga texts. This paper summarizes these perspectives on uninostril breathing.

Adult↗

Opposing effects of low and high-dose clozapine on survival of transgenic amyotrophic lateral sclerosis mice.

Clozapine is a potent atypical neuroleptic or antipsychotic agent used to relieve symptoms of early-diagnosed schizophrenia. Aside from well-described dopamine and serotonin receptor blockade effects, clozapine may also be neuroprotective through its modulation of the p75 neurotrophin receptor (p75(NTR)) and superoxide dismutase 1 (SOD1) expression. The death-signalling activities of both p75(NTR) and mutant SOD1 are implicated in motor neuron degeneration in humans and transgenic mice with amyotrophic lateral sclerosis (ALS). We therefore investigated the effects of clozapine in cell culture and mouse models of ALS. Clozapine dose-dependently inhibited full-length and cleaved p75(NTR) but not SOD1 protein expression in the motor neuron-like (NSC-34) cell line. Furthermore, low concentrations of clozapine protected NSC-34 cells from paraquat-mediated superoxide toxicity, nerve growth factor (NGF)-induced death signalling, and serum deprivation, whereas high concentrations potentiated death. Systemic thrice-weekly administration of low and high-dose clozapine to mutant superoxide dismutase 1 (SOD1(G93A)) mice produced differential effects on disease onset and survival. Low-dose treatment was associated with delayed locomotor impairment and death, compared to high-dose clozapine, which accelerated paralysis and mortality (P < 0.05). Increased death was not attributable to toxicity, as clozapine-induced agranulocytosis was not detected from blood analysis. High-dose clozapine, however, produced extrapyramidal symptoms in mice manifest by hindlimb rigidity, despite reducing spinal cord p75(NTR) levels overall. These results suggest that although clozapine may exert p75(NTR)-mediated neuroprotective activity in vitro, its profound antagonistic effects on dopaminergic and serotonergic systems in vivo at high doses may exacerbate the phenotype of transgenic ALS mice.

Amyotrophic Lateral Sclerosis↗

European experience with a system for bifurcated stent-graft insertion.

PURPOSE: To test an endovascular aneurysm exclusion system in the presence of a wide range of challenging anatomic features. METHODS: Bifurcated endovascular stent-grafts were inserted in 52 patients and followed with serial computed tomography for up to 3 years. The device underwent several modifications during this time, the most significant of which represent the difference between the homemade (n = 42) and industry-made (n = 10) versions. RESULTS: The initial procedural success rate was 92% in the homemade group and 100% in the industry-made group. In the 3 years of follow-up, the long-term success rate was 64% in the homemade group and 90% in the industry-made group. The primary reasons for failure in the homemade group were graft thrombosis due to kinking early in the series and proximal stent migration later in our experience. All cases of migration occurred when the neck was < 15 mm in length, the neck was lined with thrombus, or the stent was implanted > 15 mm from the renal arteries. Kinking was subsequently overcome by implanting Wallstents throughout the graft limbs. The sole failure in the industry-made group was a case in which collateral perfusion reached the aneurysm through patent lumbar arteries. CONCLUSIONS: The fruits of this experience are a better technique, a better device, and, most importantly, a better understanding of the system's limits, as reflected in the current selection criteria.

Angiography↗

Automatic-controlled information processing and error detection in a simulated pharmacy-verification task.

The relationships between attentional variables and information-processing demands of pharmacy dispensing tasks that contribute to difficulties in cognitive performance are not well-known. In the present study, a psychological approach to medical dispensing errors, the cognitive-systems performance model of Grasha, was employed to evaluate the contributions of individual differences in attention and alterations in visual task information on simulated pharmacy-verification performance, perceived workload, and self-reported stress. 73 college-age volunteers completed a pretest battery containing psychological measures of automatic and controlled information processing, and one-week later spent 265 min. completing the end visual-inspection process for 200 simulated prescriptions, 27% of which contained artificially inserted errors. Evidence suggesting that both automatic and controlled processes underlie performance of a simulated pharmacy-verification task was obtained. Individual differences in controlled information processing were mildly predictive of detection accuracy, while contrary to expectations, automatic processing scores did not produce significant relationships. Detection associated with experimental alterations in font size (12-pt. vs 6-pt.) of critical prescription label information was partially in line with expectations from the cognitive-systems performance model, while additional visual enhancements via a magnification/illumination device yielded mixed results. Finally, reports of perceived workload (NASA Task Load Index) and specific patterns of self-reported stress (Dundee Stress State Questionnaire) were consistent with a three-tier behavioral framework offered recently by Matthews, Davies, Westerman, and Stammers for predicting behaviors along the automatic-controlled continuum.

Adult↗

Postnatal localization and morphogenesis of cells expressing the dopaminergic D2 receptor gene in rat brain: expression in non-neuronal cells.

The cellular localization of the dopaminergic D2 receptor (D2R) mRNA and protein was determined during postnatal development, from birth to 35 days, in the rat neostriatum by in situ hybridization histochemistry and immunohistochemistry. To localize and identify more precisely the morphology of cells expressing the D2R mRNA, nonradioactive, digoxigenin in situ hybridization was performed. Throughout this period of development, D2R mRNA and protein were widely expressed by neostriatal cells, adjoining forebrain cells and small cellular processes. Within morphologically identifiable neurons, the expression of the D2 receptor appeared to occur after cell division ceased. D2R gene expression appeared during neuronal migration and followed the developmental pattern of neuronal settling within the neostriatum. Both D2R mRNA and protein appeared to colocalize in neostriatal cells and the labeling of both appeared to accumulate within the cells progressively with age. The structural phenotypes of neostriatal neurons bearing D2R mRNA and protein were diverse throughout postnatal development. The most frequently stained cells were a heterogeneous group of medium spiny and aspiny neurons. Large cells corresponding to aspiny neurons were less frequently stained. Both phenotypes exhibited considerable postnatal growth of their cell bodies. In addition to neurons, other cell types were also observed to express the D2R mRNA and protein over the developmental period studied. These other cells included patches of ciliated ependymal cells lining the lateral ventricles and many interfascicular oligodendroglia of forebrain fiber tracts. These results demonstrate the unexpected expression of the dopaminergic D2 receptor in non-neuronal cells within the brain. They provide a novel morphologic suggestion that the dopaminergic D2 receptor may support unrecognized, nonsynaptic functions in specific non-neuronal cell populations in the nervous system.

Animals↗

Patterns of hippocampal-cortical interaction dissociate temporal lobe memory subsystems.

A distributed network of brain regions supports memory retrieval in humans, but little is known about the functional interactions between areas within this system. During functional magnetic resonance imaging (fMRI), subjects retrieved real-world memories: autobiographical events, public events, autobiographical facts, and general knowledge. A common memory retrieval network was found to support all memory types. However, examination of the correlations (i.e., effective connectivity) between the activity of brain regions within the temporal lobe revealed significant changes dependent on the type of memory being retrieved. Medially, effective connectivity between the parahippocampal cortex and hippocampus increased for recollection of autobiographical events relative to other memory types. Laterally, effective connectivity between the middle temporal gyrus and temporal pole increased during retrieval of general knowledge and public events. The memory types that dissociate the common system into its subsystems correspond to those that typically distinguish between patients at initial phases of Alzheimer's disease or semantic dementia. This approach, therefore, opens the door to new lines of research into memory degeneration, capitalizing on the functional integration of different memory-involved regions. Indeed, the ability to examine interregional interactions may have important diagnostic and prognostic implications.

Adult↗

Activin and its receptors during gastrulation and the later phases of mesoderm development in the chick embryo.

We have cloned chick homologues of the type-II activin receptor, which we have designated cActR-IIA and -IIB. Binding assays show that the two receptors are indistinguishable in their ability to bind activin-A, with comparable kds. Injection of mRNAs encoding these receptors into Xenopus embryos causes axial duplications. Expression of both receptors can first be detected in the primitive streak by in situ hybridization. This suggests that these genes may be activated in response to mesoderm induction. In agreement with this, we find that treatment of preprimitive streak chick embryos with activin-A leads to rapid induction of the expression of cActR-IIB. At later stages, cActR-IIA transcripts become localized mainly in the notochord and myotome and cActR-IIB in the dorsal neural tube, proximal-anterior part of the limb bud, sensory placodes, and specific regions of the fore- and midbrain. To test the response of early chick embryonic tissues to activin, we designed a new in vitro assay for differentiation. We find that explants of area opaca epiblast or posterior primitive streak from various stages can respond to activin treatment by differentiating into a variety of mesodermal cell types in a dose-dependent manner. These results suggest that the importance of activin-related signaling pathways is not confined to pregastrulation stages and that these receptors may be involved in mediating the effects of inducing signals during later stages of development of the mesoderm, limbs, and nervous system.

Activin Receptors↗

Differential uptake of molecules from the circulation and CSF reveals regional and cellular specialisation in CNS detection of homeostatic signals.

The uptake of hydroxystilbamidine (OHSt, FluoroGold equivalent) and wheat germ agglutinin (WGA), into the hypothalamus, two hours after injections into either the circulation or the cerebrospinal fluid, were compared in adult rats. Following intravenous injection, OHSt was found in astrocytes of the median eminence and medial part of the arcuate nucleus whereas WGA intensely labelled the blood vessels and ependymal cells throughout the hypothalamus. In complete contrast, intracerebroventricular (icv) injection into the lateral ventricle resulted in OHSt uptake by ependymocytes and astrocytes in the area adjacent to the third ventricle, with virtually no uptake in regions taking up this dye following systematic injections, i.e., the median eminence and medial arcuate. Following icv injection WGA labelling was intense in all parts of the ependymal layer of the third ventricle, including the alpha- and beta-tanycytes. Injections into the cisterna magna gave a different pattern of uptake with OHSt being found only in astrocytes in the ventral part of the hypothalamus lateral to the arcuate nucleus whilst WGA uptake was virtually absent. This highlights the regional and cellular specialisation for uptake of molecules from the circulation and CSF. The median eminence and medial arcuate take up molecules from the circulation, with different cell types taking up different molecules. As the CSF flows through the ventricular system, different cells lining the ventricular and subarachnoid spaces take up molecules differentially. Molecules in the CSF appear to be excluded from the median eminence and medial arcuate region.

Animals↗

A method for analysis of back shape in scoliosis.

The shape of the back is an important factor in the clinical assessment of various spinal disorders, in particular scoliosis. A method of analysis of back surface shape is described which was designed to present most of the numerical parameters needed to assess the progress of the disease as it affects body shape. Measurements of back surface shape and manually marked anatomical landmarks were taken from a television/computer surface measurement system in which a plane of light was scanned over the back and from moiré topographs. The anatomical landmarks were used to define reference planes from which successive analyses were matched. Asymmetry in the transverse plane was illustrated by horizontal cross-sections and skin surface angles. The lateral deformity was shown by an estimate of the line of the vertebral bodies beneath the skin, derived by adding an extra lateral displacement to the palpated positions of the spinous processes, proportional to the rotation of the skin in the transverse plane. This model was used to estimate vertebral end-plate angles and Cobb angles. Lateral sections showed kyphosis and lordosis. Correlations of Lateral Asymmetry from the surface shape analysis with Cobb angle from X-ray measurements in three groups of patients (totalling 119 subjects) were in the range r = 0.77 to r = 0.94, p less than 0.0001. The analysis has reduced follow-up X-ray examinations at the Nuffield Orthopaedic Centre because it indicates quantitatively and with complete safety both lateral asymmetry and deformity in the transverse plane.

Adolescent↗

Medial pterygoid muscle activity during chewing and clenching.

Specific activity of the human medial pterygoid muscle in relation to jaw movements and occlusion during mastication and clenching tasks is unclear. EMG activity of the medial pterygoid, masseter, anterior, and posterior temporal muscles was recorded simultaneously with three dimensional incisor point movement of the mandible. Data were sampled and analyzed by an on-line computer system. Patterns of medial pterygoid muscle activity were consistent for ipsilateral chewing and demonstrated activity of the muscle on the chewing side that peaked near the onset of intercuspation. The muscle on the contralateral side was active at the onset of intercuspation for subjects with a chopping stroke and inactive for those with a more lateral stroke guided into intercuspation on cuspal inclines. Activity in the early part of the closing phase was associated with a marked jaw movement toward the chewing side. There was generally less activity in protrusive than intercuspal clenching when occlusion was normal but more activity if marked incisal wear was present or multiple tooth contacts could be attained on protrusion. Intercuspal clenching initiated less activity when force was directed posteriorly and more activity when directed anteriorly than vertical intercuspal clenching.

Adolescent↗

A personal computer-based spike detector and sorter: implementation and evaluation.

Many studies of neuronal activity require isolation of the extracellular wave form (spike) of a single neuron from the potentials generated by nearby cells. A variety of methods for spike sorting exists, but most are expensive and require specialized hardware and software. Moreover, there is no easy and objective way for evaluating and comparing the performance of spike sorting devices. We describe here a system for on-line spike sorting that is implemented on an IBM PC/AT computer using commercially available hardware and C-language software. Spikes are detected after crossing an amplitude threshold and are sorted or rejected by template matching. The templates are constructed in a learning phase, using a fast manual sorting of all detected spikes. Later, each detected spike is matched against all defined templates. A detected spike which does not match any template, or matches more than one, is rejected. A continuous display of the wave forms of the last 256 sorted, double-matched, and rejected spikes is used as the main tool for parameter adjustment and error detection. Also described is a new and highly versatile tool for generating appropriate wave forms for critical evaluation of sorter performance. Using the same hardware and software tools, a simulation program mimics the extra-cellular activity of several neurons by linear combination of two vectors and added random noise. The size, shape and the variability of the action potential, as well as its firing pattern, can be adjusted. Comparison of the sorter output with the known simulated activity is used to examine the sorter performance and limitations.

Action Potentials↗

Visual evoked potentials in rats selected for high or low self-stimulation.

Visual evoked potentials (VEPs) were analyzed in order to distinguish between rats from genetically high (HI) and low (LO) self-stimulation lines (LC2-HI and LC2-LO). Secondary VEP components - slow secondary negative wave (SNW) and sensory afterdischarge (SAD) - which are considered to be most sensitive indices of normal and pharmacologically-induced behavioral changes, were used for the comparison. Small, albeit statistically significant enhancement of SNW and SAD was obtained in LO rats. Unlike LO animals, HI rats gained in SNW amplitude and SAD area during repeated photic stimulation. The difference being highly significant. D,L-Amphetamine (1 mg/kg, i.p.) suppressed SAD and reduced the SNW amplitude in both HI and LO animals, although the predrug difference in their values remained practically unaltered. Apomorphine (0.25, 2.75, 5.25 mg/kg i.p.) had no measurable effect on VEP parameters even though it caused a regular picture of dose-related enhancement of locomotion and stereotypy. The effect of amphetamine can, therefore, be attributed to the activation of the norepinephrinergic system. Correspondingly, VEP variance in the two lines of rats is interpreted as related to the peculiarities of norepinephrine modulation of neocortical activity.

Amphetamine↗

Study of treatment variation in the radiotherapy of head and neck tumors using a fiber-optic on-line radiotherapy imaging system.

On-line radiotherapy imaging systems allow convenient daily acquisition of portal images for treatment verification. The information can also be used to study treatment variability. Using a prototype fiber-optic imaging system, we have measured the treatment variation of 17 head and neck patients. Daily digital portal images were acquired for the on-cord left and right lateral fields. Treatment variations were quantified using the Cumulative Verification Image Analysis (CVIA) method developed at our institute. In the CVIA method, daily portal images were aligned according to three anatomical points predefined on a digitized simulation, or prescription, image. After each image alignment, the block position was cumulated in a bit-map and superimposed on the prescription image to give a cumulative verification summary image. Iso-frequency distributions, or contours, of the block overlap were calculated and examined with respect to the prescription treatment area. The range of the treatment variation was large for the 17 patients. On average, separation of the 0% to 100% block overlap contours was about 10 mm, and the 20% to 80%, 5 mm. The block overlap contours were also used to calculate the frequency with which the prescription area as defined on the simulation film had been treated. The fraction of the prescription area treated depended on the accuracy of the treatment setup and patient repositioning, as expected. At best, approximately 95% of the prescribed area was irradiated 100% of the time during the entire course of radiotherapy. At worst, approximately 70% of the prescribed area was irradiated 100% of the time. These results demonstrate that despite immobilization, large setup variation can still occur. Presenting treatment variation data as population averages does not reflect on the large variation that may be observed in the individual patient.

Adolescent↗

Effects of chronic postnatal opioid receptor blockade by naltrexone upon proliferation capacity in the prenatally X-irradiated brain of the rat.

We recently reported that in rats prenatally X-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (NX) led to a remarkable growth spurt of the microencephalic brain. In the present study we present histological and autoradiographic results found in the subependymal layer (SEL) of the forebrain lateral ventricles. NX led to an intermittent augmentation of the mitotic index of the X-irradiated brains within a postnatal observation period of 24 weeks. The most conspicuous finding was transient hyperplasia of the SEL at 4-6 weeks of age which occurred in close proximity to an intact ependymal lining. Districts of the lateral ventricles which were denuded from ependyme and where the rest of the ependymal layer (EL) was dislocated peripherally showed upon NX treatment a long-lasting SEL hyperplasia with a tendency towards dysplasia. These results revealed that repair proliferation of embryotoxic X-irradiation is normally under strong control by the opioid system. If that system, which exerts a suppressing effect upon glial growth, is blocked by NX, prominent hyperplastic reactions occur which may be useful for repairing the lesion pattern.

Animals↗

Intrahippocampal LPS injections reduce Abeta load in APP+PS1 transgenic mice.

Multiple lines of evidence indicate that inflammatory processes are involved in the pathogenesis of Alzheimer's disease. Lipopolysaccharide (LPS) is widely used to induce inflammation in experimental systems. Consequently we injected LPS or saline intrahippocampally in 11 and 16 months old APP+PS1 transgenic mice to induce brain inflammation, then used immunocytochemistry to examine amyloid pathology 7 days later. As expected, LPS activated microglia as indicated by a significant increase in the area covered by major histocompatibility complex-II (MHC-II) immunostaining in the mice injected with LPS compared to the saline injected. Simultaneously, Abeta immunostaining showed an unexpected reduction of the Abeta load in the mice injected with LPS compared to the saline injected. This effect of LPS on the Abeta load in APP+PS1 mice strengthens the hypothesis that moderate amounts of microglial activation may be beneficial in Alzheimer's disease, by increasing the clearance of Abeta.

Amyloid beta-Peptides↗

Distribution of met-enkephalin immunoreactivity in the diencephalon and the brainstem of the dog.

The endogenous opioid system, in particular the enkephalins, has been implicated in a vast array of neurological functions. The dog could be a suitable model for the study of complex interactions between behavioral state and regulatory physiology in which the opioid system appeared to be implicated. Moreover, opiate derivatives are currently used in veterinary clinic and sometimes pharmacologically tested in the dog. However, there are no anatomical data regarding the organization of the opioid system in this species. The present work represents the first attempt to map the distribution of Met(5)-enkephalin-like-immunoreactive (Met-enk-li) cell bodies and fibers in the diencephalon and the brainstem of the dog. In the diencephalon, labeled cells were present in all the mid-line and intralaminar thalamic nuclei; the lateral posterior, pulvinar and suprageniculate nuclei; the ventral nucleus of the lateral geniculate body and the medial geniculate body. Additionally, Met-enk-li cells were seen in every hypothalamic nucleus except in the supraoptic. Variable densities of labeled fibers were also seen in all these nuclei except in the medial geniculate body and in most areas of the lateral posterior and pulvinar nuclei. In the mesencephalon, positive cells were found in the periaqueductal gray, the Edinger-Westphal and interpeduncular nuclei, delimited areas of the superior and inferior colliculi and the ventral tegmental area. In the rhombencephalon, labeled cells were seen in the majority of the nuclei in the latero-dorsal pontine tegmentum, the nuclei of the lateral lemniscus, the trapezoid, vestibular medial, vestibular inferior and cochlear nuclei, the prepositus hypoglossal, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus, the infratrigeminal nucleus and the caudal part of the spinal trigeminal nucleus and in the rhombencephalic reticular formation. The distribution of fibers included additionally the substantia nigra, all the trigeminal nerve nuclei, the facial nucleus and a restricted portion of the inferior olive. These results are discussed with regard to previous reports on the distribution of Met-enk in other species.

Animals↗

Increased number of GABAergic terminals in the nucleus accumbens is associated with alcohol preference in rats.

Ethanol is known to be anxiolytic and this effect may be mediated through GABA transmission acting on the GABAA-benzodiazepine-Cl- ionophore complex. Recent studies from our laboratory have suggested that GABA transmission and the GABAA-benzodiazepine-Cl- ionophore complex might be involved in the rewarding action of ethanol in alcohol-preferring rats. We report here immunocytochemical and morphometric studies analyzing the GABAergic terminal density in the nucleus accumbens (NA), corpus striatum, nucleus tractus solitarius, and lateral septum of the selectively bred P (alcohol-preferring) and the NP (alcohol-nonpreferring) lines of rats, as well as of the high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) lines of rats. The NA was included for analysis because this structure has been implicated as an important component of the brain reward system. An increase of GABAergic terminal density was found in the NA of the P rats, when compared with the NP rats. Similarly, there were more GABAergic terminals in the NA of HAD rats than of the LAD rats. No differences between the lines were seen in the other brain regions examined. The results suggest that alcohol preference in P and HAD rats may be related to increased GABA terminals and enhanced GABAergic inhibition within the NA.

Alcohol Drinking↗

Aeromonas flagella (polar and lateral) are enterocyte adhesins that contribute to biofilm formation on surfaces.

Aeromonas spp. (gram-negative, aquatic bacteria which include enteropathogenic strains) have two distinct flagellar systems, namely a polar flagellum for swimming in liquid and multiple lateral flagella for swarming over surfaces. Only approximately 60% of mesophilic strains can produce lateral flagella. To evaluate flagellar contributions to Aeromonas intestinal colonization, we compared polar and lateral flagellar mutant strains of a diarrheal isolate of Aeromonas caviae for the ability to adhere to the intestinal cell lines Henle 407 and Caco-2, which have the characteristic features of human intestinal enterocytes. Strains lacking polar flagella were virtually nonadherent to these cell lines, while loss of the lateral flagellum decreased adherence by approximately 60% in comparison to the wild-type level. Motility mutants (unable to swim or swarm in agar assays) had adhesion levels of approximately 50% of wild-type values, irrespective of their flagellar expression. Flagellar mutant strains were also evaluated for the ability to form biofilms in a borosilicate glass tube model which was optimized for Aeromonas spp. (broth inoculum, with a 16- to 20-h incubation at 37 degrees C). All flagellar mutants showed a decreased ability to form biofilms (at least 30% lower than the wild type). For the chemotactic motility mutant cheA, biofilm formation decreased >80% from the wild-type level. The complementation of flagellar phenotypes (polar flagellar mutants) restored biofilms to wild-type levels. We concluded that both flagellar types are enterocyte adhesins and need to be fully functional for optimal biofilm formation.

Adhesins, Bacterial↗