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Biomedical subjects

S Yen

Publications and source records attributed to S Yen.

At least 19 recordsLinked to original sources
PubMed2000

Missense tau mutations identified in FTDP-17 have a small effect on tau-microtubule interactions.

Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) is a group of related disorders frequently characterized by the formation of tau inclusions in neurons and glial cells. To determine whether the formation of tau inclusions in FTDP-17 results from an alteration in the ability of mutant tau to maintain the microtubule (MT) system, we compared wild type four-repeat tau with three FTDP-17 mutants (P301L, V337M and R406W) for their ability to bind MT, promote MT assembly and bundling. According to in vitro binding and assembly assays, P301L is the only mutant that demonstrates a small, yet significant reduction, in its affinity for MT while both P301L and R406W have a small reduction in their ability to promote tubulin assembly. Based on studies of neuroblastoma and CHO cells transfected with GFP-tagged tau DNA constructs, both mutant and wild type tau transfectants were indistinguishable in the distribution pattern of tau in terms of co-localization with MT and generation of MT bundles. These results suggest that missense mutation of tau gene do not have an immediate impact on the integrity of MT system, and that exposure of affected neurons to additional insults or factors (e.g., aging) may be needed to initiate the formation of tau inclusions in FTDP-17.

Animals↗
PubMed2000

Evaluation of the Effect of Radiation Therapy to Nasopharyngeal Carcinoma by Positron Emission Tomography with 2-

Purpose: This investigation evaluated the effectiveness of positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose (PET-FDG) in assessing residual tumor or tumor recurrence in postradiation nasopharyngeal carcinoma (NPC) patients.Procedures: Forty-six patients with histologically proven NPC who received radiotherapy were included. PET-FDG images were analyzed by a semiquantitative method, metabolic ratio (tumor to cerebellum ratio).Results: The overall sensitivity and specificity of PET-FDG to detect residual tumors and recurrent lesions in the postradiation patients were 80% (12/15) and 87% (27/31), respectively. In patients with PET-FDG 6 months after radiation therapy, the sensitivity and specificity raised to 92% (11/12) and 100% (20/20), respectively.Conclusions: PET-FDG is effective in the evaluation of NPC treated with radiation. The optimal timing in assessing residual tumor or tumor recurrence in postradiation patients should be 6 months or later.

Journal Article↗
PubMed2000

Hostility in marital dyads: associations with depressive symptoms.

We examined the relations of hostility (of self and spouse) with self-ratings of depressive symptoms in 898 spouse pairs. Self-ratings of hostility were initially examined as predictors of depression. Next, spouse self-ratings of hostility were added to the model. Finally, the interaction of self x spouse hostility was investigated. These relations were explored for three components of hostility (Cynicism, Aggressive Responding, and Hostile Affect). Age and education were controlled in all models and effects were examined separately for women and men. Self-ratings of Hostile Affect were positively related to depressive symptoms for both women and men. Self-ratings of Cynicism were also significantly related to depression, but only for men. All three components of spouse's hostility were positively related to one's own symptoms of depression for women. For men, however, spouse's hostility was not related to symptoms of depression. These findings highlight the need to study psychosocial risk factors in social units and have potential implications for intervention.

Adult↗
PubMed2000

Sensitization of neuronal cells to oxidative stress with mutated human alpha-synuclein.

Linkage of alpha-synuclein (alpha-SN) mutations to familial Parkinson's disease (PD) and presence of alpha-SN as a major constituent of Lewy body in both sporadic and familial PD implicate alpha-SN abnormality in PD pathogenesis. Here we demonstrate that overexpression of wild-type or mutant alpha-SN does not cause any deleterious effect on the growth or continued propagation of transfected human cells, but overproduction of mutant alpha-SN heightens their sensitivity to menadione-induced oxidative injury. Such enhanced vulnerability is more pronounced in neuronal transfectants than in their nonneuronal counterparts and is associated with increased production of reactive oxygen species. The data suggest that mutated alpha-SN, especially with an alanine-to-proline substitution at residue 30, sensitizes neuronal cells to oxidative damage.

Cell Line↗
PubMed1999

FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion.

Frontal temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by splice site and missense mutations in the tau gene, and characterized by the accumulation of filamentous tau in cerebral neurons and glia. The missense mutations reduce the ability of tau to promote microtubule assembly and increase the ability of tau to form filaments. In this report we demonstrate that mutants V337M and R406W are less susceptible than mutant P301L or corresponding wild type tau to degradation by calpain I. The differences were at least in part due to changes in accessibility of a cleavage site located about 100 amino acids off the carboxy-terminus. The results suggest that the pathogenesis of some forms of FTDP-17 may involve tau accumulation due to decreased proteolytic degradation.

Calpain↗
PubMed1999

Accelerated filament formation from tau protein with specific FTDP-17 missense mutations.

Tau is the major component of the neurofibrillar tangles that are a pathological hallmark of Alzheimers' disease. The identification of missense and splicing mutations in tau associated with the inherited frontotemporal dementia and Parkinsonism linked to chromosome 17 demonstrated that tau dysfunction can cause neurodegeneration. However, the mechanism by which tau dysfunction leads to neurodegeneration remains uncertain. Here, we present evidence that frontotemporal dementia and Parkinsonism linked to chromosome 17 missense mutations, P301L, V337M and R406W, cause an accelerated aggregation of tau into filaments. These results suggest one mechanism by which these mutations can cause neurodegeneration and frontotemporal dementia and Parkinsonism linked to chromosome 17.

Alzheimer Disease↗
PubMed1995

Characterization of protein kinases involved in dentinogenesis.

Protein phosphorylation and dephosphorylation control many different cell functions as well as responses to internal and external signals. It has also been shown that highly phosphorylated acidic proteins have an important role in matrix mediated biomineralization, perhaps functioning as nucleators for crystal formation. Dentine phosphoprotein (DPP) is one of such proteins which is exclusively synthesized by the odontoblast cells and therefore a likely candidate to play a significant role in normal and abnormal dentine biomineralization. These studies are directed at characterizing the protein kinases involved in dentinogenesis and in particular the enzyme(s) responsible for DPP phosphorylation. In this report we present data which indicate that there are several different types of kinases in the odontoblast-enriched dental papilla mesenchyme (DPM), some of which can phosphorylate DPP, such as casein kinase I and II. However, a different DPP-kinase activity was identified. This enzyme(s) appears to be different from other reported kinases, and it is the only kinase that can phosphorylate both phosphorylated DPP and enzymatically dephosphorylated DPP.

Acid Phosphatase↗
PubMed1994

Short-term substance abuse prevention in jail: a cognitive behavioral approach.

This article describes a cognitive-behavioral program for substance abusers which was first implemented in the Baltimore City Jail in 1987. Similar but separate programs are provided for male and female inmates, consisting of twelve to sixteen contact hours over three to four weeks. In addition to conventional drug and alcohol information (physiologic and psychological effects, treatment options), the program emphasizes cognitive and behavioral skills which can prevent substance abuse, including training in consequential thinking, and stress and anger management. Over a two-year period, 607 males and 131 females were served, of whom 429 (59%) completed the entire program. Both males and females showed statistically significant improvement from pretest to posttest in all knowledge areas. Inmates gave high ratings to the program and group leaders reported substantial change in client attitudes toward drug and alcohol use. Knowledge scores at the end of the program were highest for those who scored higher at pretest, rated their group leader higher, and were rated by their group leader as more active participants. Client participation was the strongest predictor of program outcome.

Adult↗