PubMed Health⌕ Search

Biomedical subjects

E Koenig

Publications and source records attributed to E Koenig.

At least 55 records · Page 3Linked to original sources

Cycloheximide-sensitive [35S]methionine labeling of proteins in goldfish retinal ganglion cell axons in vitro.

Polypeptides of retinal ganglion cell axons of the goldfish, regenerating in culture, were labeled by [35S]methionine after decentralization from the explant. Microscopic samples, composed of isolated axonal fields, were analyzed by SDS ultramicroelectrophoresis and autoradiography. Of the several proteins exhibiting cycloheximide-sensitive labeling, beta-tubulin and actin were consistently and prominently labeled, although the possibility of a labeled alpha-isoform with a lower mol. wt. could not be ruled out.

Actins↗

Spinal arteriovenous malformations and fistulae: clinical, neuroradiological and neurophysiological findings.

Twenty-six patients with myelographic signs suggestive of a spinal arteriovenous malformation (AVM) were examined neurologically and neurophysiologically. By selective spinal angiography it was possible to differentiate between dural arteriovenous fistulae (dAVF 20 patients) and intradural AVMs (iAVM, 6 patients). Initial complaints were nonspecific and variable, mainly consisting of sensory disorders and muscle weakness. Later, patients suffered involvement of both the upper and lower motor neurons. There was a high percentage of lower motor neuron lesions (95%), especially in dAVF patients, which were mostly of widespread distribution and included several myotomes. Electrophysiological examination regularly revealed lower neuron involvement, frequently with pathological spontaneous activity in several myotomes, pathological sensory-evoked potentials after tibial nerve stimulation, but normal sensory conduction velocities of the sural nerve, indicating sparing of the sensory ganglion. Frequently there was a discrepancy between the localization of the dural fistula or angioma and the spinal level responsible for clinical symptoms. This suggests that it may be the inadequacy of the venous drainage system to cope with the blood volume rather than the AV-shunt that is responsible for the symptoms. An early diagnosis is essential, as removal of the shunt before there has been progression to severe neurological deficits (paraplegia) is the only way to ensure a satisfactory outcome.

Adult↗

Different affinities of alpha 2-agonists for imidazoline and alpha 2-adrenergic receptors.

It has recently been shown that imidazoline alpha 2-adrenergic agonists, such as clonidine and UK 14,304, selectively bind to both alpha 2- and imidazoline receptors in basolateral membranes from rabbit renal proximal tubule. In order to define the relative affinity of three antihypertensive alpha 2-agonists for the two classes of receptors, we performed competition studies of imidazoline alpha 2-antagonist 3H-RX 781094 and nonimidazoline antagonist 3H-rauwolscine binding to basolateral membranes from rabbit proximal tubule. The order of potency for inhibition of radioligand binding to basolateral membranes was rilmenidine greater than clonidine greater than guanfacine and clonidine greater than guanfacine greater than rilmenidine for 3H-RX 781094 and 3H-rauwolscine binding, respectively. These data show that not only clonidine, but also rilmenidine and guanfacine, drugs usually used as specific alpha 2-agonists, bind to both alpha 2- and imidazoline receptors. The higher affinity of these molecules for one or the other class of receptors could explain their different capacity to induce hypotension and side effects.

Adrenergic alpha-Agonists↗

[Selectivity of alpha 2-adrenergic agonists for the imidazoline-guanidine and alpha 2-adrenergic receptors].

Imidazolines have been proposed as highly selective drugs for alpha 2-adrenergic receptors. However, we have recently showed that the imidazoline ligand 3H-RX 781094 (idazoxan) binds to both alpha 2-receptors and imidazoline guanidinium receptive substance (IGRS) in rabbit renal proximal tubule. Binding of 3H-RX 781094 to the purified basolateral membranes (15-fold enriched in Na-KATPase activity) was rapid (t 1/2 = 5 mn.) reversible (t 1/2) = 4 mn.), saturable and of high affinity. Scatchard analysis of equilibrium binding data showed that 3H-RX 781094 labels 566 +/- 118 fmol/mg of proteins of binding sites with an apparent dissociation constant (Kd) of 1.45 +/- 0.14 nM. On the other hand, the non imidazoline ligand 3H-rauwolscine binds only to the alpha 2-adrenergic receptors with a maximal density of 155 +/- 28 fmol/mg of protein and a Kd of 11.5 +/- 1.5 nM. In order to define the relative affinity of the alpha-2-agonists, clonidine, rilmenidine and guanfacine for the two classes of receptors, we performed competition studies of the alpha 2-antagonists 3H-RX 781094 (imidazoline) and 3H-rauwolscine (non imidazoline) binding to basolateral membranes from rabbit proximal tubule. The order of potency for inhibition of the two radioligand binding was rilmenidine greater than clonidine greater than guanfacine for 3H-RX 781094 and clonidine greater than guanfacine greater than rilmenidine for 3H-rauwolscine. Therefore, rilmenidine displayed a higher affinity for IGRS than for alpha 2 adrenergic receptors; on the other hand, clonidine and guanfacine preferentially interact with alpha 2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

[Hepatic markers (Ac-HVA-IgM and AcHBc-IgM) in cases of infectious hepatitis in Dominican children].

The presence of IgM antibodies for the HVA and HBc antigens in 90 children of 15 or less years with acute hepatitis were investigated, finding that 62% (58) were positive for HVA, 8.9% (8) for HBc and 27.8% (25) did not show antibodies for HVA or HBc (non-A non-B hepatitis); comments are made on some clinical and epidemiological findings such as a higher frequency of blood transfusions in HNANB, more males in HB and HNANB, and more hepatomegaly and liver sensitivity in HNANB.

Adolescent↗

Neurophysiological characteristics of spinal arteriovenous malformations.

The aim of the study was to identify the clinical and neurophysiological pattern of deficits in spinal arteriovenous malformations (AVM) to allow an early diagnosis which is the prerequisite for effective treatment by early surgery or embolization. Among 26 patients with myelographic signs of a spinal AVM, selective spinal angiography disclosed 20 cases with a dural AV-fistula (dAVF) and 6 patients with an intradural AV-malformation (iAVM). Although the main pathogenetic factor in both disorders may be different, clinical and neurophysiological findings proved to be of limited value in differential diagnosis. Clinical symptoms presented by the patients were a variable combination of lower motor neuron lesion, sphincter disturbance, sensory transverse lesion and partly additional signs of upper motor neuron involvement. Electromyography invariably showed an increased rate of polyphasia and frequently pathological spontaneous activity usually in several myotomes. Normal sensory conduction velocity of the sural nerve contrasted with almost regularly pathological SEP's after tibial nerve stimulation. The distribution if clinical and neurophysiological findings suggests rather widespread lesions of the lower cord and/or cauda equina, frequently at a lower level than the angiographically localized shunt. This suggests a vascular myelopathy on the basis of insufficient venous drainage at least for the frequent dural AV-anomaly.

Adult↗

Interaction of clonidine and rilmenidine with imidazoline-preferring receptors.

In the present study the imidazoline radioligand 3H-RX 781094 (idazoxan) was used to characterize the alpha 2-adrenergic receptors in basolateral membranes of rabbit proximal tubule. Scatchard analysis of equilibrium binding data showed that 3H-RX 781094 labels 566 +/- 118 fmol/mg protein of binding sites with an apparent dissociation constant (Kd) of 1.45 +/- 0.14 nmol/l. However, in competition studies, only 25% of the 3H-RX 781094 binding was inhibited by catecholamines and alpha 2-adrenergic compounds; the remaining 75% of specific binding was inhibited only by molecules having an imidazoline or oxazoline ring with the following order of potency: cirazoline greater than tolazoline greater than UK 14 304 greater than rilmenidine greater than clonidine. These data suggest that imidazoline compounds bind to both alpha 2-adrenergic receptors and to a 'non-adrenergic site' which might be defined as an imidazoline-preferring receptor. Based on these results, it is possible to hypothesize that imidazoline and oxazoline drugs, such as clonidine and rilmenidine, exert their hypotensive activity partly through the stimulation of imidazoline receptors.

Animals↗

Powering of bulk transport (varicosities) and differential sensitivities of directional transport in growing axons.

Goldfish retinal ganglion cell (RGC) axons, regenerating in vitro, have varicosities, intervening phase-dense inclusions (IPDIs) and particles that are mobile. Varicosities contain an aggregate complex of cytomembranes embedded in a cytoskeletal matrix, and, when they saltate, they represent a form of bulk transport. While movement of varicosities is normally infrequent, the incidence of movement can be greatly increased by alkalinization with NH4Cl. However, alkalinization also lowers the phase density of varicosities to reveal that motile hyperdense particles appear to be responsible for powering the translocation of varicosities and IPDIs. Other effects of alkalinization include a selective arrest of all anterograde movements and approximately a 10-fold reduction in the rate of retrograde mobility of particles and IPDIs. In mildly permeabilized axons, 20 microM orthovanadate selectively arrests retrogradely directed particle movements, while 100 microM arrests both antero- and retrograde transport. In addition to demonstrating in RGC axons that antero- and retrograde mechanisms exhibit differential pharmacological and pH sensitivities, the observations indicate that a heterogenous bulk mass can be translocated in growing axons by a passive 'piggyback' mechanism.

Actomyosin↗

[Antithrombotic properties of the active metabolite of molsidomine, SIN-1].

Molsidomine and its active metabolite SIN-1 were examined in humans and animals for their fibrinolytic and antithrombotic activity. In humans six and eight hours after ingestion of molsidomine retard (8 mg) a marked shortening of euglobulin clot lysis time was observed. Neither molsidomine nor SIN-1 activated fibrinolysis in vitro. In rabbits SIN-1 decreased the size of arterial and venous thrombus. Similar results were obtained with urokinase.

Animals↗

Isolation of native Mauthner cell axoplasm and an analysis of organelle movement in non-aqueous and aqueous media.

A method for isolating Mauthner cell (M-cell) axoplasm from goldfish is described. The axon may be isolated in a fluorocarbon oil (e.g., Fluorinert), or in an aqueous bathing medium (ABM). An analysis of motile organelles in axoplasm isolated in Fluorinert or in ABM indicated that the range of particle velocities extended over an order of magnitude, and that there was a significant selective slowing of retrograde particle movement in axons isolated in ABM. No apparent correlation between particle size and velocity was noted. In addition to confirming that calcium was not required for particle transport, it was observed that adenylylimidodiphosphate produced an irreversible blockade of organelle movements, suggesting that force generating mechanisms involved in translocation are probably similar to those proposed for invertebrate axons.

Adenine Nucleotides↗

A regional analysis of alpha-spectrin in the isolated Mauthner neuron and in isolated axons of the goldfish and rabbit.

Isolated dendrites, somata, and desheathed axons of the goldfish Mauthner neuron (M-cell), in addition to other isolated myelin sheath-free axons of the goldfish spinal cord and of rabbit lumbar ventral roots, were shown by immunochemical and immunofluorescence techniques to contain alpha-spectrin (fodrin). alpha-Spectrin appeared to be organized as a randomly distributed reticular network, localized to the surface of isolated neuronal cellular structures. In addition, alpha-spectrin was also distributed nonrandomly at specialized cellular sites. These sites included synaptic junctions and morphologically differentiated nodes of Ranvier (i.e., rabbit axons, but not goldfish axons). At the latter sites, it is possible to demonstrate that alpha-spectrin is co-localized with F-actin, as indicated by a striking correspondence of fluorescent images due to double labeling, using the indirect immunofluorescence technique with alpha-spectrin antiserum, and direct binding of F-actin by rhodamine-conjugated palloidin. However, the spectrin-actin network at synaptic junctions appears to be distributed over the entire area of junctional contact and is not just restricted to postsynaptic densities. The possibility of a duality of roles of spectrin in membrane-related motile and anchorage functions is discussed.

Animals↗

Rapid mobility of motile varicosities and inclusions containing alpha-spectrin, actin, and calmodulin in regenerating axons in vitro.

Time-lapse video recording was used to investigate the bidirectional movements of motile varicosities and intervening phase-dense (IPD) inclusions associated with axons of goldfish retinal ganglion cells regenerating in vitro. In addition, analyses of fine structure and immunocytochemical distributions of alpha-spectrin (fodrin), actin, and calmodulin in axonal fields were undertaken. Varicosities and IPD inclusions undergo saltations in a random manner at mean rates of 0.218 and 3.33 micron/sec, respectively. Experiments involving calcium antagonists or depletion of internal calcium stores resulted in an arrest of all intra-axonal movement, indicating that saltations of the two mobile structures are dependent on intra-axonal calcium. The predominant structure in varicosities is a large aggregation of an anastomosing, tubular, smooth endoplasmic reticulum embedded in an amorphous matrix, suggesting a form of "packaged" cytomembranes undergoing bulk transport. IPD inclusions, presumably carrying membranes, appear to shuttle between varicosities and growth cones during axon elongation, and between growth cones and varicosities during axon retraction. alpha-Spectrin, actin, and calmodulin were shown by immunocytochemistry to be preferentially distributed to varicosities and IPD inclusions. The co-transport of spectrin, actin, and calmodulin with cytomembranes undergoing rapid saltations departs from reported results of radioactive labeling experiments insofar as spectrin, actin, and calmodulin are not normally associated with rapidly transported membrane components in the latter studies. Possible reasons for the discrepancy are discussed. Our results suggest that spectrin and actin may play a role in the packaging and axoplasmic transport of cytomembranes concerned with plasmalemma recycling.

Actins↗

Electrolysis of unipolar pacing leads.

A 90-year-old man with bradycardia and Stokes-Adams attacks had a unipolar VVI pacemaker implanted. Twice within a short period of time we registered a total loss of function: the first incident was caused by a "fracture" between lead and electrode, and the second was due to partial dissolving of the lead. Both times a new lead electrode was implanted; the second time we replaced the pulse generator as well. Pacemaker analysis showed a capacitor defect leading to a 50 microampere anodal DC leakage that caused electrolysis of the helical coil conductors. The patient had no clinical symptoms besides those due to loss of pacemaker function. The present case report and others in the literature indicate that when an electrode lead fracture is found, it is necessary to check the pacemaker for DC leakage.

Aged↗

Local protein synthesizing activity in axonal fields regenerating in vitro.

The goldfish retinal explant system of Landreth and Agranoff was used to study endogenous protein synthesizing activity of retinal ganglion cell axons regenerating in culture. Light and electron microscopic examination of axonal fields showed that axons were free of nonneural cell investment. Decentralized axons were incubated with a mixture of tritiated amino acids, and direct quantitative microanalysis of protein and tritium radioactivity was carried out on individual axonal fields. Our findings showed that radioactive amino acids were incorporated into axonal protein in a manner that inhibited significantly by cycloheximide, but not by chloramphenicol. Decentralized axons appeared to maintain their viability for at least 3-4 h. Axonal fields maintaining their central connections to the explant incorporated 3H-amino acids at an apparent rate that was similar to decentralized axonal fields. Labeled material transported into axonal fields from ganglion cell bodies appeared in significant amounts after a delay of 2-3 h. Fluorographic patterns of axonal proteins after labeling with either 3H-amino acids or [35S]methionine and separated by microelectrophoresis indicated that primarily tubulin and, to a lesser extent, actin were labeled. Our findings indicate that goldfish retinal ganglion cell axons regenerating in vitro exhibit measureable endogenous protein-synthesizing activity.

Amino Acids↗

Mauthner axon diameter and impulse conduction velocity decrease with growth of goldfish.

Conduction velocities of antidromically evoked impulses along the goldfish Mauthner axon were found to be inversely correlated with body length. To test the hypothesis that such a relation is accompanied by a reduction in axonal diameter with increasing fish size, Mauthner axon diameters were measured. A parabolic relationship with respect to body length was obtained, axonal diameter being maximal in 9.5 cm fish. To our knowledge, this is the first report of a decrease in conduction velocity and axonal size during growth of an organism were functioning of the cell is maintained.

Aging↗