Conduction Block in the Peripheral Nervous System in Experimental Allergic Encephalomyelitis

Experimental Allergic Encephalomyelitis (EAE) has been widely studied as a model of multiple sclerosis, a central nervous system (CNS) disease of unknown aetiology. The clinical features of both EAE and multiple sclerosis provide the only guide to the progress and severity of these diseases, and are used to assess the response to treatment. In such comparisons the clinical features of EAE are assumed to be due to lesions in the CNS, but in this disease there is also histological evidence of damage to the peripheral nervous system (1-8). However, the functional consequences of such peripheral lesions have been entirely ignored. To examine this, we have studied nerve conduction in rabbits with EAE. We report here that most of the large diameter afferent fibres are blocked in the region of the dorsal root ganglion and at the dorsal root entry zone, thus accounting for the loss of tendon jerks and also, through the severe loss of proprioceptive information, the ataxia of thse animals. We conclude that whenever clinical comparisons are made between EAE and multiple sclerosis, the pathophysiology associated with histological damage of the peripheral nervous system must be taken into account

The Pathophysiology of Acute Experimental Allergic Encephalomyelitis in the Rabbit

Clinical, histological and electrophysiological studies were performed on rabbits with acute experimental allergic encephalomyelitis (EAE). The clinical features were similar to those previously described, with the notable exception of the new findings of areflexia, respiratory slowing and hypothermia. The histological findings were also similar to those previously reported, with inflammatory demyelinating lesions both in the central and peripheral nervous system, especially the dorsal root ganglia. Electrophysiological studies performed one to nine days after the onset of neurological signs demonstrated conduction block in a high proportion of the large diameter afferents in the lumbosacral and thoracic dorsal root ganglia. Single fibre studies with spike-triggered averaging confirmed the conduction block in the dorsal root ganglia. That the conduction block was due to demyelination was indicated by slowing of conduction in large diameter fibres, normal conduction in unmyelinated fibres and the specific effects of temperature and of the potassium channel blocking agent, 4-aminopyridine. These conduction abnormalities in the peripheral nervous system, focused on the dorsal root ganglia, account for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. Such conduction block is likely to mask the expression of any lesions of the central nervous system that alone could produce similar signs. The implications of these findings for the human demyelinating diseases are discussed

Direct evidence for the magnetic ordering of Nd ions in NdFeAsO by high resolution inelastic neutron scattering

We investigated the low energy excitations in the parent compound NdFeAsO of the Fe-pnictide superconductor in the $\mu$eV range by a back scattering neutron spectrometer. The energy scans on a powder NdFeAsO sample revealed inelastic peaks at E = 1.600 $\pm 0.003 \mu$eV at T = 0.055 K on both energy gain and energy loss sides. The inelastic peaks move gradually towards lower energy with increasing temperature and finally merge with the elastic peak at about 6 K. We interpret the inelastic peaks to be due to the transition between hyperfine-split nuclear level of the $^{143}$Nd and $^{145}$Nd isotopes with spin $I = 7/2$. The hyperfine field is produced by the ordering of the electronic magnetic moment of Nd at low temperature and thus the present investigation gives direct evidence of the ordering of the Nd magnetic sublattice of NdFeAsO at low temperature

51 year-old male with dyspnea and hypoxia

AbstractWith continued advancements in medical practice, physicians are caring for more adult patients with congenital heart diseases and their sequelae. We report a 51 year-old with obstructive sleep apnea presenting with dyspnea, hypoxia and pulmonary hypertension, found to have a congenital atrial septal defect. The patient had symptomatic improvement following percutaneous closure of his ostium secundum atrial septal defect

A Role for Actin, Cdc1p, and Myo2p in the Inheritance of Late Golgi Elements in \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e

In Saccharomyces cerevisiae, Golgi elements are present in the bud very early in the cell cycle. We have analyzed this Golgi inheritance process using fluorescence microscopy and genetics. In rapidly growing cells, late Golgi elements show an actin-dependent concentration at sites of polarized growth. Late Golgi elements are apparently transported into the bud along actin cables and are also retained in the bud by a mechanism that may involve actin. A visual screen for mutants defective in the inheritance of late Golgi elements yielded multiple alleles of CDC1. Mutations in CDC1 severely depolarize the actin cytoskeleton, and these mutations prevent late Golgi elements from being retained in the bud. The efficient localization of late Golgi elements to the bud requires the type V myosin Myo2p, further suggesting that actin plays a role in Golgi inheritance. Surprisingly, early and late Golgi elements are inherited by different pathways, with early Golgi elements localizing to the bud in a Cdc1p- and Myo2p-independent manner. We propose that early Golgi elements arise from ER membranes that are present in the bud. These two pathways of Golgi inheritance in S. cerevisiae resemble Golgi inheritance pathways in vertebrate cells

Vulnerability of the Dorsal Root Ganglion in Experimental Allergic Encephalomyelitis

The dorsal (posterior) root ganglion is a relatively neglected part of the nervous system from the clinical point of view. In recent studies on the pathophysiology of experimental allergic encephalomyelitis (EAE), the main animal model of multiple sclerosis, the DRG of the rabbit was shown to be the site of extensive inflammation and demyelination and of focal conduction block in a high proportion of the large diameter afferents. The resulting severe functional peripheral deafferentation accounts for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. The vulnerability of the DRG is due to a deficient blood-nerve barrier and possibly also to a susceptibility of the branch point of the ganglion neurone to demyelination-induced conduction block. These and other studies in experimental animals suggest that in man the DRG may be a preferential (but neglected) site of focal structural and functional abnormalities in inflammatory and also other neurological diseases

Crystal structure and high-field magnetism of La2CuO4

Neutron diffraction was used to determine the crystal structure and magnetic ordering pattern of a La2CuO4 single crystal, with and without applied magnetic field. A previously unreported, subtle monoclinic distortion of the crystal structure away from the orthorhombic space group Bmab was detected. The distortion is also present in lightly Sr-doped crystals. A refinement of the crystal structure shows that the deviation from orthorhombic symmetry is predominantly determined by displacements of the apical oxygen atoms. An in-plane magnetic field is observed to drive a continuous reorientation of the copper spins from the orthorhombic b-axis to the c-axis, directly confirming predictions based on prior magnetoresistance and Raman scattering experiments. A spin-flop transition induced by a c-axis oriented field previously reported for non-stoichiometric La2CuO4 is also observed, but the transition field (11.5 T) is significantly larger than that in the previous work