Ex vivo model of congenital cytomegalovirus infection and new combination therapies.

Introduction: Congenital human cytomegalovirus (HCMV) infection is a major public health problem due to severe sequelae in the fetus and newborns. Currently, due to their toxicity anti-CMV treatments cannot be administered to pregnant women. We thus developed an ex vivo model of 1(st) trimester placental CMV infection to observe the route of infection across the placenta and to test the efficacy of various new drugs targeting different stages of viral cycle.

Familial 18 centromere variant resulting in difficulties in interpreting prenatal interphase FISH.

We report here on a familial case of centromeric heteromorphism of chromosome 18 detected by prenatal interphase fluorescence in situ hybridization (FISH) analysis transmitted by the mother to her fetus, and resulting in complete loss of one 18 signal. The prenatal diagnosis was performed by interphase FISH (AneuVysion probe set, and LSI DiGeorge 22q11.2 kit) because of the presence of an isolated fetal cardiac abnormality, and was first difficult to interpret: only one centromeric 18 signal was detectable on prenatal interphase nuclei, along with one signal for the Y and one for the X chromosome.

Inhibition of glycogen synthase kinase-3beta downregulates total tau proteins in cultured neurons and its reversal by the blockade of protein phosphatase-2A.

In tauopathies such as Alzheimer's disease (AD), the molecular mechanisms of tau protein aggregation into neurofibrillary tangles (NFTs) and their contribution to neurodegeneration remain not understood. It was recently demonstrated that tau, regardless of its aggregation, might represent a key mediator of neurodegeneration. Therefore, reduction of tau levels might represent a mechanism of neuroprotection.

Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection.

In tauopathies such as Alzheimer's disease (AD), the moleccular mechanisms of tau protein agregation into neurofibrillary tangles (NFTs) and their contribution to neurodegeneration are not fully understood. Recent studies indirectly demonstrated that tau, regardless of its aggregation, might represent a key mediator of neurodegeneration, especially that induced by the amyloid (Abeta) pathology. Lithium is a medication for bipolar mood disorders.

Monozygotic twins concordant for blood karyotype, but phenotypically discordant: a case of "mosaic chimerism".

We report on 23 years old discordant monozygotic (MZ) twins, one with minor anomalies and mental delay, the other one being normal. Both had 46,XX,dup(11)(p12p15)/46,XX mosaicism in blood, with a similar proportion of abnormal cells (respectively, 16% and 17%). However, interphase fluorescence in situ hybridization (FISH) analysis performed on buccal smear and urinary sediment using specific probes located at the duplicated region showed that mosaicism was only present in the abnormal twin, with 68% abnormal cells.

Linking alterations in tau phosphorylation and cleavage during neuronal apoptosis.

Neurofibrillary tangles (NFTs) are classic lesions of Alzheimer's disease. NFTs are bundles of abnormally phosphorylated tau, the paired helical filaments. The initiating mechanisms of NFTs and their role in neuronal loss are still unknown.

Two unusual chromosome aberrations ascertained by sonographic anomalies.

We describe two cases of sonographic abnormalities associated with unusual chromosomal aberrations. Case 1 presented with a cystic hygroma at 12 weeks' gestation. Cytogenetic analysis revealed an unbalanced complex chromosome rearrangement implicating chromosomes 6, 13 and 21 (karyotype: 47,XX,t(6;21;14)(q14;q21;q21)mat,+21) and corresponding to a complete trisomy 21.

"Cri-du-chat" syndrome in a patient born to a mother with a paracentric inversion of chromosome 5q.

We report the case of a female child presented at birth with hypotonia, growth retardation and respiratory distress. Chromosome study from peripheral blood showed a 46,XX,del(5)(p14pter) karyotype. Parental chromosome studies revealed that the mother carried an apparently balanced paracentric inversion of long arms of one chromosome 5, giving the karyotype 46,XX,inv(5)(q12q32), whereas paternal karyotype was normal.

Neurons overexpressing mutant presenilin-1 are more sensitive to apoptosis induced by endoplasmic reticulum-Golgi stress.

Most early-onset cases of familial Alzheimer's disease (FAD) are linked to mutations in two related genes, ps1 and ps2. FAD-linked mutant PS1 alters proteolytic processing of the amyloid precursor protein and increases vulnerability to apoptosis induced by various cell stresses. In transfected cell lines, mutations in ps1 decrease the unfolded-protein response (UPR), which is the response to the increased amounts of unfolded proteins that accumulate in the endoplamic reticulum (ER), indicating that these mutations may increase vulnerability to ER stress by altering the UPR signalling pathway.

Urethral cytology and diagnosis of the pregnancy term. About some observations on the use of this method in an hospital setting.

A retrospective study of routine urethrocytograms performed over a 10-year period in 3,478 pregnant women for the diagnosis of pregnancy term was carried out to determine the reliability of urethral cytology when two, three, or four successive urethral smears were performed at 2- or 3-day intervals, and to investigate the correlations between the cytological results and the neurological ages of newborns. Microscopical examination of the 3,478 routine smears demonstrated the existence of a before-term aspect, a near-term aspect, or an at-term aspect in 7.4%, 66.

Baicalein protects cortical neurons from beta-amyloid (25-35) induced toxicity.

Accumulation of amyloid beta peptide (Abeta) has been suggested to contribute to neurodegeneration in Alzheimer's disease (AD). Since chronic inflammation occurs in AD pathogenesis and lipoxygenases are important mediators of inflammatory processes, we evaluated the effect of lipoxygenase inhibitors on apoptosis induced by Abeta on rat cortical cells. The 12-lipoxygenase inhibitor baicalein attenuated both neuronal apoptosis and c-jun protein over-expression induced by Abeta(25- 35), whereas no protection was found with the broad spectrum lipoxygenase inhibitor nordihydroguaiaretic acid or the 5-lipoxygenase inhibitor caffeic acid.

Markers of apoptosis and models of programmed cell death in Alzheimer's disease.

Alzheimer's disease (AD) is neuropathologically marked by the presence of senile plaques composed of beta-amyloid peptide and by neurofibrillary tangles formed by abnormally phosphorylated tau protein. Many authors have also reported a neuronal loss in affected regions of the brain in AD patients. This neuronal degeneration could be linked to the triggering of intracellular pathways leading to apoptosis.

N-methyl-D-aspartate receptor blockade enhances neuronal apoptosis induced by serum deprivation.

Neuronal apoptosis a hallmark of brain development could also be involved in neurodegenerative diseases. Glutamate toxicity is widely proposed as an important factor in the pathogenesis of neurological disorders. We show here that, in rat primary cortical cultures, the blockade of N-methyl-D-aspartate (NMDA) glutamate receptors exacerbated neuronal apoptosis induced by serum deprivation.

Toxic neuronal apoptosis and modifications of tau and APP gene and protein expressions.

The causes and the mechanisms of neuronal death in Alzheimer's disease are not elucidated, although some new insights have been proposed over the past years, including free-radical toxicity, beta-amyloid toxicity, excitotoxicity, and disturbed cellular calcium metabolism. Some authors have also pointed out that apoptosis could play a role in neuronal degeneration, but it is still largely debated. Here, we review some recent data linking the induction of experimental neuronal apoptosis in vitro and the molecular pathology of the tau protein and amyloid precursor protein (APP).

The Guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates tau mRNA expression and excitotoxicity.

As in Alzheimer's disease, brains of Guam Chamorros with amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) contain intraneuronal-paired helical filaments composed of accumulated phosphorylated tau protein. Tau mRNA expression in rat neuronal cultures-normally modulated by glutamate-increases after treatment with the aglycone of cycasin, a cycad-derived toxin whose concentration in Chamorro food varies with disease incidence. Elevated Tau gene expression in vitro is coincident with increased cycasin-related DNA adducts and reduced DNA repair.

Mild kainate toxicity produces selective motoneuron death with marked activation of CA(2+)-permeable AMPA/kainate receptors.

Motoneuron death could be produced by higher sensitivity to excitoxicity during the development and pathological conditions. We report here that in ventral spinal cord cultures mild kainate exposure (12.5 microM, 20 min or 100 microM, 2.

Brefeldin A-induced apoptosis is expressed in rat neurons with dephosphorylated tau protein.

Brefeldin A (BFA) is a fungus metabolite (penicillum brefeldanum) that is known to produce the disintegration of the Golgi apparatus in exposed cells, and apoptosis in various cancer cells. This study reports that in rat primary cortical cell cultures BFA also produces apoptosis assessed by the TUNEL method and DAPI (4',6-diemidino-2-phenylindole) staining. The percentages of apoptotic neurons range from 26.

FK506 antagonizes apoptosis and c-jun protein expression in neuronal cultures.

FK506 is an immunosuppressive drug that binds to FK506 binding protein (FKBPs), a subgroup of cytosolic proteins called immunophillins. Previous works have revealed that FK506 protects neural cells from ischemia or excitotoxicity. Here we report that FK506 (10(-6) M) and not cyclosporine A (10(-6) M) blocks neuronal apoptosis induced by serum deprivation in rat neuronal cultures.

Neuronal apoptosis is associated with a decrease in tau mRNA expression.

Apoptosis is a programmed cell death that occurs during the development of the nervous system and in neurodegenerative disorders. Tau protein is a microtubule-associated protein which promotes microtubule polymerization and stabilization. Apoptosis was induced in primary neuronal cultures by glutamate exposure (200 microM, 15 min) or by serum deprivation, and tau mRNA levels were studied by quantitative in situ hybridization in apoptotic and non apoptotic neurons.