Biomedical subjects

R Y Lai

Publications and source records attributed to R Y Lai.

6 recordsLinked to original sources

PubMed2001

Synthesis, cyclic voltammetric studies, and electrogenerated chemiluminescence of a new donor-acceptor molecule: 3,7-[Bis[4-phenyl-2-quinolyl]]-10-methylphenothiazine.

We report here the synthesis of a novel compound that contains two electron-accepting phenylquinoline groups covalently attached to the 3,7-positions of a light-emitting electron donor, 10-methylphenothiazine. The optimized geometry as determined from semiempirical MNDO calculations shows that the phenylquinoline moieties are twisted approximately 77.5 degrees from the phenothiazine central ring. As a result, no molecular orbital overlap between these two groups exists, inhibiting any delocalization of the charge upon electrochemical oxidation or reduction. Comparison between cyclic voltammograms obtained of this compound as well as of the individual compounds, 10-methylphenothiazine and 2-phenylquinonine, did indeed show no change in the electrochemical behavior of these two groups upon the covalent attachment, confirming the results obtained from the semiempirical calculations. A shift to lower energy wavelengths of phenothiazine was observed upon the addition of the electron-deficient phenylquinoline moieties. Overall, this unique geometry allows us to electrochemically produce the stable radical ions needed to generate the light-emitting excited state of phenothiazine within a potential window not obtainable with just 10-methylphenothiazine. ECL spectrum produced by annihilation between the radical cation of phenothiazine and the radical anion of phenylquinoline shows good agreement with the fluorescence emission of 10-methylphenothiazine.

Journal Article↗

PubMed1998

Could a cycloplegic agent be replaced by a fogging or a corrective lens in the biometric measurement of the crystalline lens?

This study investigated whether a fogging or a corrective lens could be used to replace a cycloplegic agent in the ultrasonic measurement of crystalline lens thickness in myopia. A group of 28 Hong Kong Chinese adults with myopia was recruited. The crystalline lens thickness of the examined eye was measured by A-scan ultrasonography while the fixating eye was in one of three conditions: fog (+2.00 D fogging lens), full corrective lens, or cycloplegia (50 minutes after instillation of 1% cyclopentolate HCl). We found that the mean lens thickness was significantly different between the three conditions in our myopic subjects. The mean crystalline lens thickness under fogging and corrective lens conditions was significantly greater than the cycloplegic condition by 0.09 mm and 0.11 mm, respectively. The 95% limits of agreement compared to cycloplegia (fogging: -0.32 to +0.14; corrective: -0.35 to +0.13) showed marked intersubject variability, indicating that there is a risk of overestimating the lens thickness when substituting cycloplegia with either a fogging or a corrective lens.

Accommodation, Ocular↗

PubMed1996

Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines.

In Alzheimer disease (AD) the microtubule-associated protein tau is redistributed exponentially into paired helical filaments (PHFs) forming neurofibrillary tangles, which correlate with pyramidal cell destruction and dementia. Amorphous neuronal deposits and PHFs in AD are characterized by aggregation through the repeat domain and C-terminal truncation at Glu-391 by endogenous proteases. We show that a similar proteolytically stable complex can be generated in vitro following the self-aggregation of tau protein through a high-affinity binding site in the repeat domain. Once started, tau capture can be propagated by seeding the further accumulation of truncated tau in the presence of proteases. We have identified a nonneuroleptic phenothiazine previously used in man (methylene blue, MB), which reverses the proteolytic stability of protease-resistant PHFs by blocking the tau-tau binding interaction through the repeat domain. Although MB is inhibitory at a higher concentration than may be achieved clinically, the tau-tau binding assay was used to identify desmethyl derivatives of MB that have Ki values in the nanomolar range. Neuroleptic phenothiazines are inactive. Tau aggregation inhibitors do not affect the tau-tubulin interaction, which also occurs through the repeat domain. Our findings demonstrate that biologically selective pharmaceutical agents could be developed to facilitate the proteolytic degradation of tau aggregates and prevent the further propagation of tau capture in AD.

Alzheimer Disease↗

PubMed1990

Blocking cell division does not remove the requirement for Polycomb function in Drosophila embryogenesis.

The Polycomb (Pc) gene is required from the extended germ band stage onwards, to maintain spatially restricted patterns of homeotic gene expression. It has been thought to be involved in the 'stable inheritance of the determined state'. In this paper, we have tested the notion that the Pc gene is required specifically during or after DNA replication to enable the stable transmission of states of gene activity. We found that arresting cell division using the string mutation or blocking DNA replication with aphidicolin failed to prevent ectopic expression of the homeotic gene Ultrabithorax in Pc mutants. Thus, even in the absence of DNA replication, Pc is required to maintain spatially restricted patterns of homeotic gene expression. The role of the Pc gene product in the stable repression of homeotic gene transcription is discussed.

Animals↗

PubMedDate not supplied

Examination of phosphorylated tau protein as a PHF-precursor at early stage Alzheimer's disease.

Hyperphosphorylated tau protein which can be isolated on the basis of insolubility in 1% sarkosyl (A68-tau fraction) is thought to represent a precursor pool for PHF assembly, associated histologically with neuritic pathology, which feeds into a more resistant tangle-associated PHF pool via cross-linking and proteolysis. We examined these predictions at the earliest detectable stages of neurofibrillary pathology. We report that there is no evidence that neuritic pathology represents an early pathologic stage, no evidence of an association between neuritic pathology and phosphorylated tau, no evidence of selective accumulation of phosphorylated tau at early stages of pathology, and no evidence for a precursor/product relationship between phosphorylated tau and PHFs during progression of pathology. We conclude that altered phosphorylation is a secondary process affecting 5% of PHFs and does not explain PHF assembly in Alzheimer's disease.

Aged↗

PubMedDate not supplied

Quantitative analysis of tau protein in paired helical filament preparations: implications for the role of tau protein phosphorylation in PHF assembly in Alzheimer's disease.

In Alzheimer's disease, there is a major redistribution of the tau protein pool from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation in the if-II protocol developed in this laboratory. We show that 85% of tau bound in the PHF-like configuration can be recovered in the if-II PHF-fraction. Less than 1% of this material was phosphorylated at the mAb AT8 site in aged clinical controls or in cases with minimal or mild dementia. Of tau phosphorylated at the mAb AT8 site, only 12% was found to co-sediment with PHFs. These low levels could not be explained by postmortem dephosphorylation. As more than 95% of PHF-tau is not phosphorylated, even at early stages of pathology, it is misleading to use the terms "PHF-tau" and "phosphorylated tau" as though they were synonymous, particularly as this implies a pathogenetic role which phosphorylation need not have.

Alzheimer Disease↗