Dataset Information

Apraxia of lid opening.

ABSTRACT: We describe eyelid movement abnormalities in an 80-year-old man with apraxia of lid opening (ALO), resulting from involuntary levator palpebrae inhibition (ILPI) and pretarsal orbicularis oculi (OO) contraction. He was unable to open his lids at will following closure. Attempted eye opening resulted in forceful contraction of the frontalis muscle, backward thrusting of the head and lengthened lid closure. The inability to reopen the lids was not evident during spontaneous reflex blinking and he had no difficulty in keeping the lids open once they had been manually lifted up. There were no episodes of involuntary drooping of the eyelids or spasmodic contraction of the OO causing involuntary eyelid closure. Pursuit eye movements were not restricted, the vestibulo-ocular reflex was preserved and both horizontal and vertical saccades were normal. Despite the clinically visible persistence of pretarsal OO activity, treatment with botulinum toxin injections in the pretarsal and preseptal portions of the muscle did not reduce his difficulty in initiating lid elevation but he found some benefit using lid crutches. ALO is thought to be due to an abnormality in the supranuclear control of eyelid movement. ILPI can present either isolated or combined with blepharospasm. The excitatory levator palpebrae response necessary to lift the lids up is likely to be in very close connection with the OO antagonistic inhibitory response. Alterations in one or another pre-motor structure may result in inability to raise the lids due to inhibition of the levator palpebrae as well as persistence of the pretarsal OO.

SUBMITTER: Ugarte M

PROVIDER: S-EPMC1955626 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Apraxia of lid opening.

Ugarte Marta M Teimory Masoud M

The British journal of ophthalmology 20070701 7

We describe eyelid movement abnormalities in an 80-year-old man with apraxia of lid opening (ALO), resulting from involuntary levator palpebrae inhibition (ILPI) and pretarsal orbicularis oculi (OO) contraction. He was unable to open his lids at will following closure. Attempted eye opening resulted in forceful contraction of the frontalis muscle, backward thrusting of the head and lengthened lid closure. The inability to reopen the lids was not evident during spontaneous reflex blinking and he ...[more]

PMID: 17576707

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Project description:The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD) of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol) and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA) for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent systems, which could lead to weaknesses in the catalytic H-bond network and most likely a drop in catalytic activity. The conformational variation of the lid domain caused by the solvent molecules influenced its gradual opening. Formation of additional hydrogen bonds and hydrophobic interactions indicates that the contribution of the cooperative network of interactions could retain the stability of the protein in some solvent systems. Time-correlated atomic motions were used to characterize the correlations between the motions of the atoms from atomic coordinates. The resulting cross-correlation map revealed that the organic solvent mixtures performed functional, concerted, correlated motions in regions of residues of the lid domain to other residues. These observations suggest that varying lengths of polar organic solvents play a significant role in introducing dynamic conformational diversity in proteins in a decreasing order of polarity.

Project description:The Group IVA (GIVA) phospholipase A(2) associates with natural membranes in response to an increase in intracellular Ca(2+) along with increases in certain lipid mediators. This enzyme associates with the membrane surface as well as binding a single phospholipid molecule in the active site for catalysis. Employing deuterium exchange mass spectrometry, we have identified the regions of the protein binding the lipid surface and conformational changes upon a single phospholipid binding in the absence of a lipid surface. Experiments were carried out using natural palmitoyl arachidonyl phosphatidylcholine vesicles with the intact GIVA enzyme as well as the isolated C2 and catalytic domains. Lipid binding produced changes in deuterium exchange in eight different regions of the protein. The regions with decreased exchange included Ca(2+) binding loop one, which has been proposed to penetrate the membrane surface, and a charged patch of residues, which may be important in interacting with the polar head groups of phospholipids. The regions with an increase in exchange are all located either in the hydrophobic core underneath the lid region or near the lid and hinge regions from 403 to 457. Using the GIVA phospholipase A(2) irreversible inhibitor methyl-arachidonyl fluorophosphonate, we were able to isolate structural changes caused only by pseudo-substrate binding. This produced results that were very similar to natural lipid binding in the presence of a lipid interface with the exception of the C2 domain and region 466-470. This implies that most of the changes seen in the catalytic domain are due to a substrate-mediated, not interface-mediated, lid opening, which exposes the active site to water. Finally experiments carried out with inhibitor plus phospholipid vesicles showed decreases at the C2 domain as well as charged residues on the putative membrane binding surface of the catalytic domain revealing the binding sites of the enzyme to the lipid surface.

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Apraxia of lid opening.

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Apraxia of lid opening.

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