Two cellular systems have been used to investigate the modulation of tau hyperphosphorylation. In the first system, the effects of the excitatory amino acid glutamate, the microtubule destabilising agent colchicine, and beta 25-35-amyloid peptide on tau phosphorylation were studied in rat cortical neurones in primary culture. Using immunocytochemistry and western blot analysis, we demonstrated that tau in these cultures is normally highly phosphorylated, but a proportion becomes rapidly dephosphorylated following treatment of the cultures with glutamate or colchicine. These changes in tau phosphorylation occurred prior to cell death. In the second system, the ability of p42 MAP and p44 MAP kinases, glycogen synthase kinases 3 alpha and 3 beta (GSK-3 alpha and GSK-3 beta) to phosphorylate tau in transfected COS cells was investigated. Both GSK-3 alpha and GSK-3 beta phosphorylated tau to produce a PHF-like state of phosphorylation but the MAP kinases failed to induce such a transformation in tau. These results suggest that aberrant regulation of GSK-3 alpha/beta may be a pathogenic mechanism in Alzheimer's disease.

Amyloid beta-Peptides↗

PubMedDate not supplied

Neurodegenerative changes including altered tau phosphorylation and neurofilament immunoreactivity in mice transgenic for the serine/threonine kinase Mos.

Transgenic mice expressing the oncogenic protein-serine/threonine kinase Mos at high levels in the brain display progressive neuronal degeneration and gliosis. Gliosis developed in parallel with the onset of postnatal transgene expression and led to a dramatic increase in the number of astrocytes positive for GFAP, vimentin, and possibly tau. Interestingly, vimentin is normally expressed only in immature or neoplastic astrocytes, but appears to be induced to high levels in Mos-transgenic, mature astrocytes. Mos can activate mitogen activated protein kinase (MAPK) and MAPK has been implicated in Alzheimer-type tau phosphorylation. In the Mos-transgenic brain we found increased levels of phosphorylation at one epitope on tau containing serines 199 and 202 (numbering according to human tau), a pattern similar but not identical to that found in Alzheimer's disease. In addition, Mos-transgenic mice express a novel neurofilament-related protein that might be a proteolytic neurofilament heavy chain degradation product. These results suggest that activation of protein phosphorylation in neurons can result in changes in cytoskeletal proteins that might contribute to neuronal degeneration.

Animals↗

PubMedDate not supplied

Mercury excretion and intravenous ascorbic acid.

We tested the hypothesis that intravenous ascorbic acid increases urinary excretion of mercury in subjects with low mercury levels from dental amalgam, food, and other sources. From 89 adult volunteers we selected 28 subjects with the highest mercury excretions (2 to 14 micrograms/24 h). We administered intravenous infusions of 500 ml lactated Ringer's solution with and without addition of 750 mg of ascorbic acid/kg body weight, up to 60 g ascorbic acid. Average mercury excretion during the 24 h after infusion of ascorbic acid was 4.0 +/- 0.5 micrograms (mean +/- SEM), which was not significantly more than after infusion of Ringer's solution alone (3.7 +/- 0.5 micrograms). Lead excretion was similarly unaffected. If ascorbic acid administered intravenously benefits some persons with suspected adverse reactions to mercury, the benefit in subjects similar to ours appears unrelated to short-term enhanced excretion of mercury or lead.

Adolescent↗

PubMedDate not supplied

Gender differences in social and psychological problems of substance abusers: a comparison to nonsubstance abusers.

This study examines gender differences in 16 social and psychological problems among substance abusers and nonsubstance abusers in a community population to determine whether such differences are simply a reflection of differences between men and women in the general population. Data were gathered from 119 respondents using the Addiction Severity Index. Loglinear analysis suggests that problems typically attributed to "being a female substance abuser" may be due to the effect of gender or substance abuse alone. Only two problems significantly distinguish female substance abusers from the other comparison groups: psychiatric hospitalizations and relatives with substance abuse. However, women in the overall sample were more troubled by family problems, had more parents with psychiatric problems, and received more outpatient psychiatric treatment. Problems associated with substance abuse, not gender, include divorce, problems controlling violence, and parents with substance abuse problems. These findings suggest that substance-abusing women experience a "double whammy" because they incur both the problems of women and the problems of substance abusers. Disaggregating gender and substance abuse effects has implications for treatment-matching and relapse prevention, specifically for suggesting strategies that address the special vulnerabilities of substance-abusing women.

Adult↗

PubMedDate not supplied

Nucleoside modifications affect the structure and stability of the anticodon of tRNA(Lys,3).

NMR spectroscopy was used to determine the solution structures of RNA oligonucleotides comprising the anticodon domain of tRNA(Lys,3). The structural effects of the pseudouridine modification at position 39 were investigated and are well correlated with changes in thermodynamic parameters. The loop conformation differs from that seen in tRNA(Phe) and provides an explanation of the critical role of modification in this tRNA.

Anticodon↗

PubMedDate not supplied

Ring volume/ring liner ratio and effective setting expansion.

Effective radial setting expansion of wax patterns in a gypsum-bonded investment is influenced by many factors, especially by the diameter of the cylindrical casting ring. The hypothesis tested was that the ratio of the volume of the casting rings to the volume of the ring liner is a primary determinant of radial setting expansion. Mesio-occlusodistal inlay wax patterns were invested individually in plastic casting rings of different lengths and diameters and imaged using xeroradiography. Effective setting expansion was determined in 34-mm-long, 28-mm-diameter rings and used as a predictor of expansion in rings of different sizes. Experimental setting expansion results did not differ significantly from the predicted values.

Dental Casting Investment↗