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Biomedical subjects

L Ko

Publications and source records attributed to L Ko.

8 recordsLinked to original sources

Expression of 'Alzheimer antigens' in cultured skin fibroblasts.

When cultured skin fibroblasts were exposed to culture conditions designed to favor the expression of neuronal antigens, cells from each of 19 patients with Alzheimer's disease reacted immunocytochemically with antibodies to paired helical filaments, Alz-50, or both compared with only a small fraction of cells from 19 identically treated age-matched control cultures. Immunoblots confirmed the presence of soluble material reacting with Alz-50 antibody in the Alzheimer fibroblasts. Ultrastructurally, fascicles of 10-nm filaments were seen that occasionally twisted around each other, but no structures were seen that were identical to paired helical filaments. Thus, cultured skin fibroblasts from patients with Alzheimer's disease developed greater immunocytochemical reactivity with antibodies raised to paired helical filaments than did fibroblasts from control subjects, when cultured under the specified conditions.

Aged

Behaviour disorder in pre-school children in Hong Kong. A two-stage epidemiological study.

A representative sample of 855 Hong-Kong Chinese children aged 36-48 months were assessed using the BSQ and the PBCL. Good reliability for both instruments were found. For the BSQ and PBCL, 12.75% and 27.5% were above the cut-off points of 10+ and 12+ respectively and 5.9% were above both cut-off points. In the second stage, 234 subjects were recruited by stratified random sampling according to the results of the screening state. A clinician interviewed the parent, child and teacher before making a diagnosis. The prevalence of behaviour disorder was: nil, 53.7%; dubious, 23.1%; mild, 18.0%; moderate, 4.5%; and severe, 0.7%. There were significantly more boys in the categories mild, moderate and severe.

Adult

Pathology of Alzheimer's disease.

The fundamental pathophysiology of Alzheimer's disease remains poorly understood, but progress has been dramatic in description of the pathology at the molecular level. The characteristic Alzheimer amyloid derives, in part, by action of microglia, from a precursor protein that is well characterized at the protein and gene levels. The characteristic paired helical filaments contain phosphorylated tau proteins and perhaps other constituents. At the neurotransmitter level, Alzheimer's disease involves not only loss of cholinergic cells but of serotonergic and other neurotransmitter systems as well. Damage to mitochondria may play an important role in precipitating the cellular pathophysiology.

Alzheimer Disease

Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation.

Since previous studies have suggested that the coupling of oxidation to phosphorylation is impaired in Alzheimer brain and fibroblasts, the effects of carbonyl cyanide m-chlorophenylhydrazone, a hydrazone known to uncouple mitochondrial oxidative phosphorylation, were tested on the development of immunoreactivity with antibodies to "Alzheimer antigens" in cultured fibroblasts from cognitively intact subjects. The fibroblasts were exposed for 10 to 14 days to a medium (DMd) modeled on media that favor neuronal differentiation in fetal brain cultures. The addition of a 10-microns concentration of carbonyl cyanide m-chlorophenylhydrazone to the DMd culture medium increased by more than 10-fold the proportion of cells reacting immunocytochemically with antibodies to paired helical filaments and by 157-fold the proportion of cells reacting with the Alz-50 monoclonal antibody. These observations suggest that the oxidative abnormalities previously described in tissues from patients with Alzheimer's disease may contribute to the accumulation of abnormal cytoskeletal materials in this disorder.

Aged

Induction of epitopes associated with neurofibrillary tangles in clonal mouse neuroblastoma (S20Y) cells.

Accumulation of paired helical filaments (PHF) in neurofibrillary tangles is a key neuropathological hallmark in Alzheimer's disease (AD). To date, PHF have been found primarily in humans. Cultured murine cholinergic neuroblastoma (S20Y) cells, following exposure to a serum-free medium or a differentiation medium, developed immunoreactivity to anti-PHF antibodies, and to the Alz-50 by immunocytochemical and immunoblot analyses. Electron microscopic examination revealed abundant fascicles of 10-nm filaments coursing tortuously amongst organelles, such as mitochondria, endoplasmic reticulum and dense-core vesicles, in perikarya and in neuritic extensions. However, subcellular structures identical or similar to PHF could not be found in these non-human cells. This convenient cell culture model may prove to be useful for studying certain aspects of the mechanisms underlying the abnormal cytoskeletal alterations which are characteristic of AD and related neurodegenerative disorders.

Alzheimer Disease

Long-term neurological sequelae following vacuum extractor delivery.

Two hundred and ninety-five children delivered by vacuum extractor (VE) 10 years ago were studied to determine if they had an increased incidence of neurological abnormality; 302 children delivered spontaneously in the same hospital looked after by the same doctors in the same year matched for maternal age, gestational age and birthweight were used as controls. Fine- and gross-motor control, perceptual integration and behavioural maturity were screened by 4 tasks selected from the Quick Neurological Screening Test. Intelligence assessment was based on scholastic performance, speech ability and ability of self-care as commented by teachers and parents. Similar scorings were found between the 2 groups. Mental subnormality or severe neurological abnormality was found in 3 children delivered by VE and in 3 children delivered spontaneously and there was no evidence that it was birth-related.

Child

Purification and chemical modification of porcine bone morphogenetic protein.

Implantation of porcine bone morphogenetic protein (pBMP) in the muscle induces differentiation of mesenchymal-type cells and results in endochondral bone formation. pBMP was isolated from porcine demineralized bone matrix and purified by hydroxyapatite chromatography, Sephadex G75 gel filtration, preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), preparative isoelectric focusing (IEF), and chromatofocusing fast protein liquid chromatography (FPLC). Porcine BMP has an MW of 26 K and a range of pI from 4.65 to 4.73 determined by SDS-PAGE and IEF, respectively. Reconstitution with the citrate buffer supernatant fraction enables as little as 50 micrograms of the soluble pBMP fractions to induce osteogenesis in an in vivo assay. Chemical modification studies indicate that the osteoinductive potential of the pBMP molecule depends on tyrosine, carboxyl groups, and disulfide bonds and can be increased by modification of sulfhydryl groups. Modification of arginine and tryptophan has no effect on bioactivity. By pepsin-limited proteolysis, fragments of pBMP with an MW of 6-14 K show definite, although reduced, BMP activity.

Animals