Selective localisation of neuro-specific T lymphocytes in the central nervous system

Using experimental autoimmune encephalomyelitis (EAE) in the rat as a model of central nervous system (CNS) inflammation, activated and quiescent T lymphocytes with different antigen specificities were labelled with the fluorescent dye Hoechst 33342 and tested by fluorescence microscopy for their ability to accumulate in different regions of the spinal cord and in other organs at varying times post inoculation. With this highly sensitive assay it was found that activated myelin basic protein (MBP)-specific T cell lines accumulated in the spinal cord (a 1000-fold increase in the lumbar/sacral region by day 4) and caused clinical signs of EAE. In contrast, interleukin-2 (IL-2)-maintained (quiescent) MBP-specific T cell lines failed to accumulate in the CNS and cause disease. Activated ovalbumin (OA)-specific and purified protein derivative of tuberculin (PPD)-specific T cell lines were also found at significantly higher levels in the spinal cord than non-activated cells although they failed to accumulate to a substantial degree when injected alone. When injected with activated MBP-specific T cells the activated OA- and PPD-specific cell lines accumulated in the spinal cord following initial accumulation of the MBP-specific cells, demonstrating that during the inflammatory process there is considerable non-specific recruitment of cells into the inflammatory site. CNS accumulation of activated MBP-specific T cell lines occurred 1-2 days later in irradiated animals than in non-irradiated recipients. This was consistent with irradiated animals also exhibiting a later onset of disease and suggests that irradiation may directly affect the endothelium in a way that makes it less adhesive. In conclusion, this study demonstrates that activated lymphocytes of any specificity enter the spinal cord, and that the neuro-antigen specific cells accumulate there and lead to the recruitment of other cells. Non-activated cells, even those with neural antigen specificity fail to enter the cord. Understanding the nature of what an 'activated' lymphocyte is may allow us to design strategies to inhibit such immune-mediated inflammation.     

Validation of esophageal pressure occlusion test after paralysis

Measurements of respiratory mechanics are frequently made in ventilated infants and children. Esophageal pressure measurements (P_es using a balloon on a catheter have been used to partition the respiratory mechanics into lung and chest wall components. Appropriate positioning of this balloon is crucial to obtain accurate estimates of pleural pressure. Traditionally, in spontaneously breathing subjects the balloon position is assessed with an occlusion test. In ventilated subjects, it is not always possible to perform an occlusion test prior to paralysis, and even if such a test is performed it may not be relevant under conditions of positive pressure ventilation. We have assessed a positive pressure occlusion test that is suitable for paralyzed subjects. By occluding the airway opening and applying gentle pressure to the abdomen or rib cage, positive swings in pressure can be measured by both P_es and airway opening pressure (P_ao). We compared traditional occlusion tests measured in 16 spontaneously breathing puppies to the positive pressure occlusion test performed after paralysis. In 2 pups we were unable to obtain a reasonable traditional occlusion test (>15% difference between P_es and P_ao) but we obtained 10 traditional occlusion tests in each of the remaining 14 pups (2.1–14 kg). In 11 of these animals Ape, was within 10% of P_ao. This compared well to positive pressure occlusion test using abdominal pressure performed after paralysis, where Apes was within 10% of ΔP_ao in 10 animals. In 9 of these pups occlusion tests were also performed by applying pressure on the rib cage, where ΔP_es was within 10% of ΔP_ao in 6 animals. These results suggest that it is possible to perform accurate occlusion tests in paralyzed subjects by abdominal or rib cage compression with the airway occluded. Pediatr Pulmonol. 1994; 17:56–62. © 1994 Wiley-Liss, Inc.     

High β-adrenoceptor density on peripheral blood mononuclear cells in progressive multiple sclerosis: a manifestation of autonomic dysfunction?

In multiple sclerosis (MS) up-regulation of β-adrenoceptors on peripheral blood mononuclear cells (PBMCs) has been attributed to either autonomic dysfunction, inflammation or a combination of the two. We have compared secondary progressive MS patients with normal subjects (NS) and two models of autonomic dysfunction; pure autonomic failure (PAF) and multiple system atrophy (MSA, Shy-Drager syndrome). There was up-regulation of β-adrenoceptors on PBMCs in MS and PAF patients but not in MSA patients. Only in PAF patients β-adrenoceptor up-regulation was correlated with low plasma levels of noradrenaline (NA) and adrenaline (Ad). In addition to studies in the basal state, measurements also were made after the centrally acting sympatholytic agent clonidine. These were combined with haemodynamic and neurohormonal measurements. After clonidine, there was a fall in blood pressure in NS and MSA patients but not in MS and PAF patients; a rise in growth hormone (GH) in NS and PAF patients but not in MS and MSA patients; and an up-regulation in PBMCs β-adrenoceptors in NS but not in MS, MSA and PAF patients. Up-regulation of β-adrenoceptors on PBMCs in MS could be attributed to autonomic dysfunction but the disparity between MS and PAF patients when considering their plasma levels of NA and Ad argue against. Although the neurohormonal responses to clonidine and the physiological assessment of autonomic function in progressive MS patients, demonstrate central autonomic dysfunction resembling that of the MSA patients, the normal basal β-adrenoceptor densities in the latter, suggests that the up-regulation of these receptors is independent of the central autonomic dysfunction in MS.     

Estimating neuron dendritic length in 3D from total vertical projections and from vertical slices

The recently developed method of total vertical projections is illustrated to estimate the total dendritic length of a human Substantia Nigra neuron. Next, the length of the different orders of dendritic branches, and the mean segment length for each order - commonly regarded as important parameters in neuron physiology - are also estimated. Finally, it is shown how to estimate the mean dendritic length in a population of neurons from vertical slices of arbitrary and unknown thickness. Being unbiased and highly efficient, the proposed methods offer interesting alternatives to current procedures used for the metric analysis of neuron arborizations.     

Human sympathetic nerve activity to glabrous skin does not increase during simulated diving

In humans, cardiovascular adjustment to simulated diving causes a marked increase in sympathetic outflow to intramuscular vessels and muscle vasoconstriction. Skin vasoconstriction in the hand also occurs during diving in humans. Skin nerve sympathetic activity (SSA), containing vasoconstrictor signals to glabrous skin, unexpectedly was reduced during diving in a previous study of SSA recorded in the peroneal nerve. SSA was recorded by microneurography in the median nerve in 13 healthy volunteers during simulated diving. Skin blood flow in the hand and one finger was monitored. The typical SSA response, irrespective of duration of diving and water temperature, was an increase during the control period immediately prior to immersion of the face and a sudden reduction of SSA when the face was immersed. The increase in SSA preceding the dive was accompanied by vasoconstriction, which continued during the dive, but re-dilation regularly occurred before the end of the dive. Inhibition of SSA was not total. Mental arithmetic during diving evoked strong bursts of SSA, similar to those seen normally during mental stress. It is concluded that the true response of SSA to simulated diving is an inhibition of the immediately preceding outflow, in agreement with observations of cutaneous blood flow in animals. The skin vasoconstriction recorded during simulated diving is a consequence of an SSA increase before the procedure, suggested to be a stress response before the forthcoming manoeuvre. The SSA response during simulated diving is the opposite to that of sympathetic outflow to muscle, which emphasizes the diversity of sympathetic regulation of different organ systems.     

Diagnostic sonography of the fetal genitourinary tract

Fetal diagnosis has vastly improved over the last decade. Ultrasound has become the imaging modality of choice. As real-time equipment has improved technologically, the ability to deduce subtle abnormalities has greatly increased. The fetal genitourinary tract may be evaluated for renal dysplasias, anomalies, or obstruction. Points of obstruction and, at times, the exact cause of obstruction may be deduced. Abnormalities of the ureter, bladder, urethra, scrotum, or reproductive system can be detected.     

The influence of muscle-conditioned media on chick embryo brainstem neurons in culture

Brainstem pieces from the trigeminal region of the metencephalic basal plate of 10-day chick embryos were dissociated and cultured in control conditions or in the presence of muscle-conditioned medium (MCM). The MCM was derived from age-matched target tissue relevant to this neuronal region (jaw musculature), from relevant target tissue of an age at which innervation would initially be taking place (4 days), and from nonrelevant target tissue also of an early stage (4-day limb bud). Neuronal survival and differentiation was assessed daily, for 7 days. Survival and differentiation were significantly enhanced by the 4-day jaw MCM compared to both the controls and the cultures grown with 10-day jaw MCM and 4-day limb MCM. These measures in the presence of 10-day jaw MCM and 4-day limb MCM did not differ, but surpassed that seen in control cultures. The results are compared to the more specific responsiveness seen in earlier (2-day) neural tube cultures, and their relationship to in vivo regenerative nerve fiber outgrowth is considered.     

Peptidergic neurons in the snail Helix pomatia: Distribution of neurons in the central and peripheral nervous systems that react with an Antibody raised to the insect neuropeptide,leucokinin I

In this study, antiserum raised against an insect myotropic peptide, leucokinin I (DPAFNSWGamide), was: used for mapping leucokinin-like immunoreactive (LK-LI) neurons in the gastropod mollusc, Helix pomatia. Immunocytochemistry performed on both whole-mounts and cryostat sections demonstrated LK-LI neurons in all ganglia of the central nervous system (CNS), except the visceral ganglion. Altogether about 700 immunolabelled neurons have been found, with nearly one-half (46%) in the cerebral ganglia. A large proportion of the LK-LI neurons have small cell bodies and are likely to be interneurons. The most prominent LK-LI cell group is represented by the entire neuron population of the mesocerebri, which is the major source of a thick fiber bundle system, encircling and innervating the whole CNS. One single LK-LI giant neuron was found, which is located in the left pedal ganglion and is termed GLPdLKC (giant left pedal leucokinin immunoreactive cell). This cell has not been identified previously. The ganglion neuropils are heavily innervated by varicose LK-LI fiber arborizations. Some integrative centers, such as the medullary neuropil of the procerebri, reveal an extreme density of LK-LI innervation. All major peripheral nerves contain a large number of LK-LI axons, and LK-LI innervation is found in the musculature of different peripheral organs (buccal mass, lip, tentacles, oviduct, intestine). Among the peripheral organs investigated, the intestine contains a rich varicose LK-LI network, composed of both intrinsic and extrinsic elements. Radioimmunoassay (RIA) demonstrates a very high content of LK-LI material in Helix ganglion extracts (about 50 pmol/CNS). This is the first report on the occurrence of a substance resembling the myotropic neuropeptide leucokinin I in a phylum outside arthropods. Based on our immunocytochemical observations, a role for leucokinin-like peptides in both central and peripheral regulatory processes in Helix is suggested. According to double-labelling experiments, only a small number of the LK-LI neurons are labelled with an antibody to the vertebrate tachykinin substance P.     

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