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J Engel

Publications and source records attributed to J Engel.

At least 325 records · Page 18Linked to original sources
PubMed1992

Interictal behavioral disturbances: a search for molecular substrates.

Postictal symptoms can be disabling in themselves, but their underlying substrates may endure, giving rise to epilepsy-induced interictal behavioral disorders. Chronic temporal lobe epilepsy is reported to be associated with a variety of interictal behavioral changes which often take the form of affective disturbances. Depression, among the more common interictal psychological dysfunctions suffered by patients with temporal lobe seizures, could reflect epilepsy-induced alterations in normal opioid peptide mechanisms. In experimental animal models, certain postictal behaviors have been shown to be opioid-mediated. Furthermore, an experimental model of interictal behavioral disturbance resembles stimulation-induced defensive rage, which can be relieved by intracerebral administration of opioid peptides. Defensive rage is a species-specific behavior encountered in cats. Its correlate in humans would be difficult to predict in view of the stronger cortical control; however, it may manifest rather as insecurity, irritability, and perhaps depression. Extrapolation of animal experiments would suggest that depression and certain other common postictal and interictal affective disturbances seen in patients with temporal lobe seizures reflect mechanisms more related to opiate withdrawal, than to direct opiate actions. The activity-induced plasticity associated with recurrent temporal lobe seizures, therefore, should result in changes in opioid function that predispose to withdrawal phenomena. Limbic seizures induce enhanced enkephalin synthesis lasting for up to 2 weeks. Recurrent seizures in experimental animals, however, cause paradoxical up-regulation of mu opiate receptors. Patients with temporal lobe epilepsy demonstrate enhanced mu receptor binding in the neocortex of the epileptogenic temporal lobe on PET. The reasons for this enduring interictal effect are not clear. Nevertheless, if animals or patients become dependent on enhanced endogenous opioid activity as a result of seizures, and also have up-regulation of mu receptors, then severe withdrawal effects, such as defensive rage in cats or depression in humans, might be expected when seizures do not recur frequently. Plotting the time course of mRNAenk and enkephalin expression after seizures, and the time course of symptoms of interictal behavioral disturbances, may demonstrate a temporal relationship that supports this hypothesis. For instance, depression or other withdrawal symptoms might only occur when the interval between seizures is greater than the duration of seizure-induced enkephalin synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Binding and calcium-induced aggregation of laminin onto lipid bilayers.

Direct binding of laminin in the form of its complex with nidogen to planar lipid bilayers was demonstrated with total internal reflection fluorescence microscopy. Binding occurred equally well to zwitterionic (phosphatidylcholine) and negatively charged (phosphatidylglycerol) lipids and was enhanced by sulfatides but only at nonphysiological molar ratios higher than 30 mol %. Strong interactions with lipid bilayers were also observed for bovine serum albumin. This explains a strong inhibition of laminin binding by this protein. However, binding of laminin to sulfatide-rich bilayers was not completely inhibited. Observable by the microscopic technique was the formation of laminin clusters on the surface of the bilayer which occurred concomitantly with binding. Both processes were strongly enhanced by the presence of calcium. These results show that calcium-induced laminin self-assembly is enhanced at lipid surfaces.

Calcium↗
PubMed1991

Molecular characterization of cuticle and interstitial collagens from worms collected at deep sea hydrothermal vents.

Two different collagens were isolated and characterized from the body walls of the vestimentiferan tube worm Riftia pachyptila and the annelid Alvinella pompejana, both living around hydrothermal vents at a depth of 2600 m. The acid-soluble cuticle collagens consisted of a long triple helix (2.4 microns for Alvinella, 1.5 microns for Riftia) terminating into a globular domain. Molecular masses of 2600 and 1700 kDa, respectively, were estimated from their dimensions. The two cuticle collagens were also quite different in amino acid composition, in agreement with their different supramolecular organizations within tissues. Interstitial collagens corresponding to cross-striated fibrils underneath the epidermal cells could be solubilized by digestion with pepsin and consisted of a single alpha-chain. They were similar in molecular mass (340 kDa) and length (280 nm) but differed in composition and banding patterns of segment-long-spacing fibrils. This implicates significant sequence differences also in comparison to fibril-forming vertebrate collagens, although all form typical quarter-staggered fibrils. The thermal stability of the worm collagens was, with one exception (interstitial collagen of Riftia), in the range of mammalian and bird collagens (37 to 46 degrees C), and thus distinctly above that of shallow sea water annelids. Yet, their 4-hydroxyproline contents were not directly correlated to this stability. About 20% of Riftia collagen alpha-chain sequence was elucidated by Edman degradation and showed typical Gly-X-Y repeats but only a limited homology (45 to 58% identity) to fibril-forming vertebrate collagens. A single triplet imperfection and the variable hydroxylation of proline in the X position were additional unique features. It suggests that this collagen represents an ancestral form of fibril-forming collagens not directly corresponding to an individual fibril-forming collagen type of vertebrates.

Amino Acid Sequence↗
PubMed1991

Calcium-dependent binding of basement membrane protein BM-40 (osteonectin, SPARC) to basement membrane collagen type IV.

Basement membrane protein BM-40, prepared from the mouse Engelbreth-Holm-Swarm tumor, was used in native, denatured and proteolytically processed form for binding to various extracellular matrix proteins. BM-40 and its derivatives were also characterized by CD spectroscopy, calcium binding and epitope analysis. Of several basement membrane proteins tested only collagen IV showed a distinct and calcium-dependent binding of BM-40 in an immobilized ligand assay. This interaction was specific as shown by a low activity of other collagen types (I, III, V, VI) in direct binding and competition assays. The binding was reduced or abolished by metal-ion-chelating or chaotropic agents, high salt and reduction of disulfide bonds in BM-40. Fragment studies indicated that domains III (alpha-helix) and/or IV (EF hand) of BM-40 possess the binding site(s) for collagen IV, while the N-terminal domains I and II provide the major antigenic determinants. A major BM-40-binding site on collagen IV was dependent on a triple-helical conformation and could be localized to a pepsin fragment from the central portion of the triple-helical domain, in agreement with electron microscopic visualization of BM-40--collagen-IV complexes.

Amino Acid Sequence↗
PubMed1991

Assembly and disulfide rearrangement of recombinant surfactant protein A in vitro.

The surfactant-associated protein, protein A, produced by transgenic Chinese hamster ovary cells exhibits a heterogeneous population of structures. Electron microscopy reveals lollipop-shaped monomers consisting of a collagenous triple helix and a globular domain as well as oligomers in which two, three or more protomers are connected by their collagenous stalks. Each protomer consists of three alpha-chains (36 kDa) but under non-reducing conditions few free alpha-chains are observed by SDS/PAGE. Instead gamma-components (three chains), gamma 2 (six chains) and higher components are observed which are derived from intra- and inter-protomer disulfide cross-linking. Complete reduction at low temperature dissociates the oligomers, but preserves the intact structure of monomers as demonstrated by electron microscopy and trypsin digestion. Circular dichroism revealed an unfolding of the collagen triple helices of fully reduced protein A at 26 degrees C and of the unreduced protein A around 41.5 degrees C. Reoxidation of the fully reduced protein A re-established mainly the disulfide bonds within the triple helix but not between monomers. Very few higher assembly forms were reformed even at high protein A concentrations. Cellular in vivo systems must possess an efficient assembly mechanism which cannot be simulated by an in vitro system.

Disulfides↗
PubMed1991

Osmotic lysis of chromaffin granules treated with the ionophores nigericin and A23187 in isotonic sucrose solution at low pH.

Bovine chromaffin granules were treated with the ionophores nigericin or A23187 in sucrose solutions with the pH varying from 4.7 to 7.0. Nigericin and A23187 induced osmotic lysis of the granules in sucrose solutions at pH values below 5.8, but not at physiological pH. This effect is explained by a progressive protonation of the acidic chromogranins induced by the ionophore-promoted exchange of internal potassium- and calcium ions for external protons. The results support the view that the interactions between catecholamines and ATP with chromogranins play a significant role in osmotic pressure reduction of the granule interior.

Adenosine Triphosphate↗