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M Kokkinidis

Publications and source records attributed to M Kokkinidis.

47 records · Page 3Linked to original sources
PubMed1985

Noisy neural nets exhibiting epileptic features.

On the basis of our previous studies of noisy neural nets we propose a model for the explanation of epileptic phenomena. Our neural net model is capable of exhibiting epileptic features if the number of spontaneously firing neurons is periodically increased beyond a certain threshold. Some alternative epileptogenic mechanisms are also discussed. The epileptic behavior of the neural net is determined by a combination of certain parameters of its phase diagram. The general features of the model are consistent with several experimental observations and explain some poorly understood clinical phenomena. The differences between normal and epileptic neural nets are explained in terms of the structural properties of the model.

Epilepsy↗
PubMed1984

Noisy neural nets exhibiting memory domains.

Previous studies with probabilistic neural nets in which the neural connections are set up by means of chemical markers, revealed the existence of multiple memory domains. We generalized these studies by considering the intrinsic noise of the systems, caused by the spontaneous release of synaptic transmitter substance. A simple mathematical model is developed, which yields characteristics of multiple memory domains analogous to those occurring in noiseless nets.

Action Potentials↗
PubMed1984

A neural net model for multiple memory domains.

Previous studies with neural nets constructed of discrete populations of formal neurons have assumed that all neurons have the same probability of connection with any other neuron in the net. However, in this new study we incorporate the behavior of the neural systems in which the neural connections can be set up by means of chemical markers carried by the individual cells. With this new approach we studied the dynamics of isolated neural nets again as well as the dynamics of neural nets with sustained inputs. Results obtained with this approach show simple and multiple hysteresis phenomena. Such hysteresis loops may be considered to represent the basis for short-term memory.

Memory, Short-Term↗
PubMed1982

Structure investigations of agonists of the natural neurotransmitter acetylcholine, III. X-ray structure analysis of (2-ethoxyethyl)trimethylammonium chloride.

To elucidate the structure-activity correlations we have performed an X-ray structure analysis of the title compound (1), which is a muscarinic agonist of the natural neurotransmitter acetylcholine. 1 crystallizes in the monoclinic space group P2(1)/n with 2 molecules per asymmetric unit. Lattice parameters are: a = 10.375(6), b = 12.468(5), c = 15.274(17) A; beta = 95.32(7) degrees. The structure was solved by direct methods and refined to an R-value of 0.14 for 1828 observed reflections. Both cations in the asymmetric unit are disordered. In the crystal structure at least four conformations of the cation occur, indicating a pronounced conformational flexibility of the neurotransmitter cation. The anions are arranged stereospecifically with respect to the quaternary trimethylammonio methyl group. The geometry of triangles which are defined by a nitrogen of the quaternary ammonium group and an ether oxygen on one hand and an anion occupying a specific type of tetrahedral faces of a (CH3)3N+ CH2 group on the other hand, is characteristic for muscarinic agonists if they contain an ether or ester oxygen in the analogous position to the ester oxygen of acetylcholine.

Acetylcholine↗
PubMedDate not supplied

Novel structural features of the human histocompatibility molecules HLA-DQ as revealed by modeling based on the published structure of the related molecule HLA-DR.

Structural modeling of the HLA-DQ molecules, a group of human histocompatibility antigens linked to autoimmune diseases and immunosuppression-based on the structure of the homologous molecule DR1, has revealed an overall shape typical of the class II histocompatibility molecules, yet with several novel features. These are unique to HLA-DQ and include: (1) an antigen-binding groove with a polymorphic first pocket and anchoring in the second and/or fifth pocket, (2) a polymorphic beta 49-56 dimerization patch, and (3) in many alleles a prominent Arg-Gly-Asp loop (beta 167-169), probably involved in cell adhesion, as it exhibits an architecture similar to identical sequences involved in such function. The alpha 2 beta 2 dimerisation domain and the CD4-binding region are nearly identical to their counterparts in the structure of HLA-DR1. The significance of the few substitutions in the CD-4 binding region remains to be evaluated. The polymorphic first antigen-binding pocket and the anchoring in the second and/or fifth pocket point to differences in antigenic fragment selection compared to HLA-DR antigens, while the polymorphism in the beta 49-56 homodimerization patch implies either ease of spontaneous or T lymphocyte receptor-induced homodimerization or difficulty in the latter. As homodimerization appears to be an obligatatory intermediate in the activation of cognate DQ-restricted T lymphocytes and DQ-bearing antigen-presenting cells, the dimerization properties of DQ allels signify the respective ease or difficulty of activation of these two cell types. The RGD loop confers cell adhesion possibilities to those DQ allels that possess it, yet its putative ligand cannot be defined at present. These features are suggestive of the probable mechanisms through which some of the unique immunological properties of the HLA-DQ molecules are effected.

Amino Acid Sequence↗
PubMedDate not supplied

Structure investigations of agonists of the natural neurotransmitter acetylcholine II [1]. X-ray structure analysis of trimethyl(4-oxopentyl)ammonium-chloride.

The crystal structure of Trimethyl(4-oxopentyl)ammonium-chloride ([(CH3)3N--(CH2)3COCH3]Cl-) (1) was determined by an X-ray structure analysis. 1 crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 10.440 (3), b = 14.600 (9), c = 6.804 (9) A and with four formula units per unit cell. The structure was solved by a Patterson and a successive Fourier synthesis. The least squares refinement yielded an R-value of 0.064 for 1077 observed reflections. The cation of 1 is derived from acetylcholine by replacement of the ester oxygen with a CH2 group. It shows a potent nicotinic activity and a significant difference in conformation as compared with acetylcholine. In the crystal structure the anions are oriented stereospecifically with respect to the tetrahedron of the quaternary ammonium group. The geometry of two triangles formed by the quaternary nitrogen atom, the oxygen atom of the carbonyl group, and by either of the two anions nearest to the quaternary ammonium group is characteristic for the nicotinic activity of 1.

Acetylcholine↗
PubMedDate not supplied

The crystal structure of Z-Aib-Gly-Aib-Leu-Aib-OtBu, the synthetic, protected N-terminal pentapeptide of trichotoxin.

Z-Aib-Gly-Aib-Leu-Aib-OtBu, the alpha-aminoisobutyric acid (Aib)-containing N-terminal pentapeptide of the antibiotic trichotoxin, has been studied by x-ray crystallography. The molecule forms a right-handed helix with a reversal of the sense of the helix at the C-terminus. Torsion angles and hydrogen bonding pattern are consistent with a mixed 3(10)-/alpha-helical conformation. In the crystal, continuous columns are formed by head-to-tail arrangement of hydrogen-bonded molecules along the helix axis. The helical columns associate via hydrogen bonds forming closely packed parallel pairs.

Amino Acid Sequence↗
PubMedDate not supplied

Structure investigations of agonists of the natural neurotransmitter acetylcholine, IV. X-ray structure analyses of trimethylpentylammonium-chloride and (4-acetoxybutyl)trimethylammonium-iodide.

The crystal structures of the title compounds which display cholinergic activity at the ganglionic receptor have been determined by X-ray structure analysis. [(CH3)3N+C5H11]Cl- (1) crystallizes in the orthorhombic space group Pbnm with half a formula unit per asymmetric unit, a = 11.381(14), b = 12.871(17), c = 7.316(4) A. The intensities of 1106 independent reflections were collected with an automatic diffractometer. The structure refinement converged at R = 0.133 for the 355 observed reflections. The cation of 1 is disordered. [(CH3)3N+ (CH2)4-O-C(O)-CH3]I- (2) crystallizes in the orthorhombic space group P2(1)2(1)2(1) with four formula units per unit cell, a = 16.783(8), b = 10.276(6), c = 7.427(10) A. The intensities of 1469 independent reflections were collected. The structure refinement converged at R = 0.071 for 1383 observed reflections. In both compounds the trimethylammonio methyl groups are coordinated nearly tetrahedrally by four anions in the first coordination sphere. Anions which occupy a special face type (B) of the tetrahedron of the (CH3)3N+ -CH2-group may be treated as a "model binding site" of the receptor. In the crystal structure of 2 the anions occupying B-type faces form together with the ammonium nitrogen and the carbonyl oxygen so called "Activity triangles". The almost equal geometries of these activity triangles are correlated with the mode of pharmacological action.

Acetylcholine↗
PubMedDate not supplied

Structure investigations of agonists of the natural neurotransmitter acetylcholine, V. Structure-activity correlations for cholinergic stimulants derived from crystal structures of their halides.

General features of crystal structures of halide salts of cholinergic stimulants can be interpreted in terms of substrate-receptor interactions. The monoatomic counterions in the crystal structures are discussed as models for the binding site of the receptor with respect to the ammonium group of the cholinergic neurotransmitters. In the crystal structures the anions occupy the tetrahedral faces of the quaternary trimethylammonio methyl or related groups in a specific geometry. Crystallographic and pharmacological evidence indicates that these groups should preferentially interact with the receptor via a specific face type (B-type face). The directionality of the interaction is derived from the vectors joining N+ with the anions occupying B-type faces. So called "activity triangles", formed by the nitrogen of the ammonium group, a second polar centre of the neurotransmitter cation and a counterion occupying a B-face of the ammonium group, provide a structural criterion for the differentiation between muscarinic and nicotinic activity. It is shown that structure-activity relationships of cholinergic stimulants do not depend on the conformational details of the neurotransmitter cations, but primarily on the relative positions of the polar centres of the cations with respect to the anionic binding site of the receptor.

Acetylcholine↗
PubMedDate not supplied

Structure investigations of agonists of the natural neurotransmitter acetylcholine. VI. X-ray structure analysis of trimethyl[2-(propionyloxy)ethyl]-ammonium-iodide (O-propionylcholine-iodide).

The title compound crystallizes in the orthorhombic, noncentrosymmetric space group Pna2(1) with a = 10.241(11), b = 12.903(12), c = 9.312(9) A and with one formula unit per asymmetric unit. The stereochemically comparable torsion angles of the cation of 1 and of acetylcholine chloride are analogous. In the crystal structure the trimethylammonio methyl group is surrounded by three anions in the first coordination sphere. The geometry of a triangle formed by one of these counterions which occupies a special face of the N+C4 tetrahedron of the (CH3)3N+-CH2-R moiety, the nitrogen atom of the ammonium group and the oxygen atom of the carbonyl group is typical for nicotinic agonists.

Acetylcholine↗