Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF.

Objective: Comparative study of CSF levels of tau and AD7C-neuronal thread protein (NTP) in patients with AD and control subjects.

Background: AD is characterized by neurofibrillary tangles composed of the abnormally hyperphosphorylated microtubule-associated protein tau. AD7C-NTP is a proposed AD marker expressed at early stages of neurofibrillary degeneration.

Erythrocytes stored in CPD SAG-mannitol: evaluation of their deformability.

The erythrocytes deformability of three blood samples coming from healthy donors has been evaluated by Laser-assisted Optical Rotational Cell Analyzer (LORCA). Blood samples were stored in CPD SAG-mannitol. The study of progressive reduction in the Elongation Index (EI) during the preservation may be used as way of evaluation of erythrocyte vitality in stored blood samples.

Isolated bilateral submandibular abscesses in a preterm infant: a case report.

Isolated submandibular suppurative sialadenitis in the newborn is a rare entity. Only six cases have been reported in the literature. A rare case of isolated bilateral submandibular abscesses in a premature infant is presented.

Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human.

The Ets transcription factors of the PEA3 group--E1AF/PEA3, ETV1/ER81 and ERM--are almost identical in the ETS DNA-binding and the transcriptional acidic domains. To accelerate our understanding of the molecular basis of putative diseases linked to ETV1 such as Ewing's sarcoma we characterized the human ETV1 and the mouse ER81 genes. We showed that these genes are both encoded by 13 exons in more than 90 kbp genomic DNA, and that the classical acceptor and donor splicing sites are present in each junction except for the 5' donor site of intron 9 where GT is replaced by TT.

Genomic organization of the human e1af gene,a member of Ets transcription factors.

The E1AF protein belongs to the family of Ets transcription factors and is involved in the regulation of metastasis gene expression. It has recently been reported in an undifferentiated child sarcoma that part of this gene could be fused by translocation to the ews gene. We show here that the human e1af gene, which is located in the q21 region of chromosome 17, is organized in 13 exons distributed along 19kb of genomic DNA.

7-Nitroindazole prevents 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced ATP loss in the mouse striatum.

The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is dependent upon the MAO-B (monoamine oxidase type B)-catalyzed production of 1-methyl-4-phenylpyridinium ion (MPP(+)) and is likely to involve a perturbation of energy metabolism. Protection against MPTP neurotoxicity has been shown by treating mice with 7-nitroindazole (7-NI), a reversible inhibitor of both MAO-B and neuronal nitric oxide synthase (nNOS) activity. The objective of the present study was to evaluate (i) the relationship between the neuroprotective effect of 7-NI and MPTP-induced energy deficiency, and (ii) the role of nitric oxide production as a potential mechanism for energy perturbation after MPTP exposure.

Impaired glutamate clearance as a consequence of energy failure caused by MPP(+) in astrocytic cultures.

Astrocytes are the site of bioactivation of the parkinsonism-inducing agent 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) into its toxic 1-methyl-4-phenylpyridinium (MPP(+)) metabolite. The mechanism by which MPP(+) is capable of decreasing astrocytic glutamate uptake was evaluated in this study using primary cultures of astrocytes. Addition of glutamate to these cultures was followed by its efficient clearance from the extracellular space.

Novel alpha-synuclein-immunoreactive proteins in brain samples from the Contursi kindred, Parkinson's, and Alzheimer's disease.

A specific mutation (A53T) in the encoding region for alpha-synuclein has been identified in a large multigenerational family with an autosomal dominant parkinsonism known as the Contursi kindred. In this study, we used a monoclonal antibody directed against alpha-synuclein in order to identify novel proteins in the brain of an affected member of this kindred who had come to autopsy. Homogenates from the frontal cortex and caudate nucleus were examined using Western blot techniques and compared to matched autopsy specimens from control subjects and patients with various forms of parkinsonism.

Absence of mutations in the coding region of the alpha-synuclein gene in pathologically proven Parkinson's disease.

A missense mutation of the alpha-synuclein gene has been associated with parkinsonism in a large Italian kindred. Recently, alpha-synuclein was also identified in Lewy bodies. Using reverse transcribed-polymerase chain reaction (RT-PCR) technique, we sequenced the entire coding region of the alpha-synuclein gene using brain tissue from 24 pathologically proven Parkinson's disease cases.

Regulation of the human P450scc gene by steroidogenic factor 1 is mediated by CBP/p300.

Regulation of the human CYP11A gene encoding cytochrome P450scc, which catalyzes the first step of steroid synthesis, is regulated by many trans-acting transcription factors including steroidogenic factor 1 (SF-1). Transfection experiments in human adrenal NCI-H295 cells demonstrate regulation of the P450scc gene promoter region that contains several putative SF-1 binding sites. Cotransfection of SF-1 with a luciferase reporter construct containing the P450scc gene 5'-flanking region from nucleotides -1676 to +49 increased promoter activity, and deletion of the nucleotide sequence from position -1676 to -1620, which removes a putative cAMP response element (CRE), did not affect the stimulatory response to SF-1.

Inhibition of monoamine oxidase contributes to the protective effect of 7-nitroindazole against MPTP neurotoxicity.

The ability of 7-nitroindazole (7-NI) to protect against MPTP-induced neurotoxicity has been attributed to its inhibition of neuronal nitric oxide synthase. In the present study, 7-NI was found to counteract almost completely striatal dopamine depletion caused by a single subcutaneus injection of 20 mg/kg MPTP in mice. This effect, however, was accompanied by a significant reduction in the striatal levels of MPP+, the toxic metabolite generated via monoamine oxidase B-catalyzed MPTP oxidation.

Structure-function relationships of the PEA3 group of Ets-related transcription factors.

The PEA3 group of transcription factors belongs to the Ets family and is composed of PEA3, ERM, and ER81, which are more than 95% identical within the DNA-binding domain--the ETS domain--and which demonstrate 50% aa identity overall. We present here a review of the current knowledge of these transcription factors, which possess functional domains responsible for DNA-binding, DNA-binding inhibition, and transactivation. Recent data suggest that these factors are targets for signaling cascades, such as the Ras-dependent ones, and thus may contribute first to the nuclear response to cell stimulation and second to Ras-induced cell transformation.

Expression of the PEA3 group of ETS-related transcription factors in human breast-cancer cells.

The PEA3 group of transcription factors belongs to the ets family and is composed of 3 known members, PEA3, ERM and ER81, which are more than 95% identical within the DNA-binding ETS domain and exhibit 50% aa identity overall. Recently, transgenic mice bearing the c-erbB-2/neu oncogene have been shown to over-express PEA3 mRNA in mammary adenocarcinomas, suggesting a role for this gene family in mammary tumorigenesis. In the present work we characterized the mRNA expression levels of PEA3-group genes in a series of human epithelial breast cell lines.

Nigrostriatal monoamine oxidase A and B in aging squirrel monkeys and C57BL/6 mice.

In this study we assessed the two forms of monoamine oxidase (MAO) in the caudate, putamen, and substantia nigra of young (4-year-old), intermediate-aged (11-year-old), and aged (20-year-old) squirrel monkeys and in the striata of young (2-month-old) and older (10-month-old) C57Bl/6 mice. MAO A and B activities were determined by measuring the rate of oxidation of the specific substrates phenethylamine and serotonin. In squirrel monkey, the vast majority of MAO activity was MAO B with activity of this isoform 10 times greater than of MAO A, while in mice the activity of the two forms was approximately equivalent.

p53 protein expression in benign lesions of the upper respiratory tract.

Objective: p53 is a tumor suppressor gene that is lost or mutated in most forms of human malignancy. There are, however, very few studies evaluating p53 expression in normal epithelium or benign lesions.

Design: We screened for p53 protein expression in a variety of benign epithelial lesions of upper respiratory tract using monoclonal antibody DO-1 on paraffin-embedded material.

(+)MK-801 does not prevent MPTP-induced loss of nigral neurons in mice.

The present study was designed to evaluate the effects of 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)MK-801] on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal damage in the mouse, with the goal of clearly defining what protective effects, if any, this noncompetitive N-methyl-phenyl-1,2,3,6-tetrahydropyridine receptor antagonist may have against MPTP neurotoxicity. Animals were treated with MPTP (40 mg/kg s.c.

Role of nitric oxide in methamphetamine neurotoxicity: protection by 7-nitroindazole, an inhibitor of neuronal nitric oxide synthase.

The role of nitric oxide (NO.) in the neurotoxic effects of methamphetamine (METH) was evaluated using 7-nitroindazole (7-NI), a potent inhibitor of neuronal nitric oxide synthase. Treatment of mice with 7-NI (50 mg/kg) almost completely counteracted the loss of dopamine, 3,4-dihydroxyphenylacetic acid, and tyrosine hydroxylase immunoreactivity observed 5 days after four injections of 10 or 7.

Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of L-DOPA-treated monkeys.

The effects of monoamine oxidase (MAO) inhibitors on the metabolism of dopamine synthesized from exogenous L-DOPA were investigated in the striatum and substantia nigra of squirrel monkeys. Administration of a single dose of L-DOPA (methyl ester, 40 mg/kg, i.p.

The ETS-related transcription factor ERM is a nuclear target of signaling cascades involving MAPK and PKA.

Recent studies support a model for signal transduction from activated receptor tyrosine kinases to Ras which, in turn, activates the pathway of the mitogen-activated protein kinase (MAPK). Although some members of the Ets transcription factor family have been shown to be activated by this signaling pathway, no data are available on the activation of the PEA3 group of Ets proteins. This group is composed of three members -- PEA3, ER81 and ERM -- which are very similar in the DNA-binding domain, the ETS domain, in the 32 residue amino-terminal acidic domain and in the 61 residue carboxy-terminal domain.

Astrocytes as the site for bioactivation of neurotoxins.

Evidence obtained from studies on the mechanisms of action of dopaminergic neurotoxins suggests that glial cells may play an important role in neurodegenerative processes. A possible link between the function of glial cells and nerve cell damage could relate to the ability of astrocytes to convert innocuous compounds into toxic metabolites. Indeed, a mechanism of metabolic activation has been demonstrated in the MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine) model of dopaminergic toxicity.

CYP2D6 allelic frequencies in young-onset Parkinson's disease.

Parkinson's disease (PD) is thought to develop as a result of interactions between genetic susceptibility factors and environmental exposures. One candidate gene is CYP2D6, which codes for the debrisoquine 4-hydroxylase cytochrome P450. Impairment of debrisoquine 4-hydroxylase activity has been associated with an increased risk of PD in patients with younger age at disease onset.

Genomic organization of the human ERM (ETV5) gene, a PEA3 group member of ETS transcription factors.

The ERM protein belongs to the family of Ets transcription factors. We show here that the human ERM gene is organized into 14 exons distributed along 65 kb of genomic DNA on chromosome 3. The two main functional domains of ERM, the acidic domain and the DNA-binding ETS domain, are overlapped by three different exons each.

Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV.

Reactions of oestrogens and androgens at position C-17 are catalysed by 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs). Cloning of the cDNA of a novel human 17 beta-HSD IV and expression of its mRNA are described. A probe derived from the recently discovered porcine 17 beta-oestradiol dehydrogenase (17 beta-EDH) was used to isolate a 2.

Iron-mediated bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in glial cultures.

Primary cultures of mouse astrocytes were treated with both the monoamine oxidase (MAO) A inhibitor, clorgyline, and the MAO B inhibitor, deprenyl, prior to the addition of the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Production of the 1-methyl-4-phenylpyridinium (MPP+) toxic metabolite was reduced to 11%, but not completely blocked, by MAO inhibition. This residual MPP+ production appeared to be iron-dependent since it was decreased (30 to 50%) by iron chelators, i.