Biomedical subjects

J A McLaurin

Publications and source records attributed to J A McLaurin.

5 recordsLinked to original sources

PubMed2001

Cellular membrane composition defines A beta-lipid interactions.

Alzheimer's disease pathology has demonstrated amyloid plaque formation associated with plasma membranes and the presence of intracellular amyloid-beta (A beta) accumulation in specific vesicular compartments. This suggests that lipid composition in different compartments may play a role in A beta aggregation. To test this hypothesis, we have isolated cellular membranes from human brain to evaluate A beta 40/42-lipid interactions. Plasma, endosomal, lysosomal, and Golgi membranes were isolated using sucrose gradients. Electron microscopy demonstrated that A beta fibrillogenesis is accelerated in the presence of plasma and endosomal and lysosomal membranes with plasma membranes inducing an enhanced surface organization. Alternatively, interaction of A beta with Golgi membranes fails to progress to fibril formation, suggesting that A beta-Golgi head group interaction stabilizes A beta. Fluorescence spectroscopy using the environment-sensitive probes 1,6-diphenyl-1,3,5-hexatriene, laurdan, N-epsilon-dansyl-L-lysine, and merocyanine 540 demonstrated variations in the inherent lipid properties at the level of the fatty acyl chains, glycerol backbone, and head groups, respectively. Addition of A beta 40/42 to the plasma and endosomal and lysosomal membranes decreases the fluidity not only of the fatty acyl chains but also the head group space, consistent with A beta insertion into the bilayer. In contrast, the Golgi bilayer fluidity is increased by A beta 40/42 binding which appears to result from lipid head group interactions and the production of interfacial packing defects.

Aged↗

PubMed2000

Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.

In Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro.

Amyloid beta-Peptides↗

PubMed1995

Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter.

T-cell reactivity to human myelin basic protein (MBP) has been extensively studied using T-cell lines and clones generated from both peripheral blood and cerebrospinal fluid, from normal controls and multiple sclerosis (MS) patients. These studies have largely utilized myelin basic protein isolated from control human adult white matter. In our study, we used MBP reactive T-cell lines as a probe to investigate antigenic differences in a series of MBP preparations isolated from either control human white matter or white matter from the central nervous system (CNS) of MS patients. Autologous peripheral blood derived mononuclear cells were used as antigen presenting cells (APC). Although the majority of T-cells were found to react equally well with all preparations of MBP isolated from both control and MS white matter, we were also able to identify T-cell lines which reacted well with all preparations of MBP isolated from controls but failed to react with MBP isolated from MS white matter. These differences were unlikely to reflect differences in degradation products or excess peptides present in the MS brain since SDS-PAGE and HPLC did not show any difference in the MS samples compared to the controls, and the concentration response curves for a human T-cell clone specific for the 84-102 region of MBP were similar for all the MBP preparations. We did not detect differences in amino acid content amongst MBP preparations although single amino acid substitutions cannot be ruled out. These results raise the possibility that MBP isolated from MS brain may differ in charge microheterogeneity which would affect antigenic determinants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Opportunities for older children and adolescents with disabilities through the Supplemental Security Income Program.

The revitalization of the Supplemental Security Income Program for low-income children with disabilities has important implications for state Title V programs for children with special health care needs. Historically, this program has focused primarily on recipients under the age of 7. The files of children between the ages of 7 and 16 referred to Children's Special Health Services, North Carolina's Title V children with special health care needs program from July to August 1991 were analyzed to determine whether there was documentation that children in this age group were receiving recommended services. Reports in the files indicated that most (n = 214, 77%) of the children's needs for specific services were being met. The utility of information that currently exists on older children and adolescents eligible for SSI for assisting Title V children with special health care needs programs in coordinating care is discussed.

Adolescent↗

PubMed1995

Oligodendrocytes and myelin.

Although it was initially thought to be a passive structure, the oligodendrocyte and myelin unit is now considered highly dynamic with many important functions beyond its role in myelination. Inhibitors of neurite growth can be localized to oligodendrocyte and myelin, highlighting the importance of oligodendrocytes in general CNS maintenance and in neuronal regeneration following many types of CNS insults. Understanding of the genesis of oligodendrocytes and myelin is increasing and will surely lead to better strategies to treat demyelinating diseases including MS.

Humans↗