An in vivo murine model of rosiglitazone use in pregnancy.

Objective: To identify the effects of rosiglitazone use during murine pregnancy.

Design: The effect of rosiglitazone on blastocyst development was determined by culturing two-cell mouse embryos with rosiglitazone for 72 hours. From January to June 2005, five independent groups of ICR/CD1 female mice were treated with rosiglitazone during pregnancy, from the time of identification of seminal plugs until delivery of pups.

Structure of the SCAN domain from the tumor suppressor protein MZF1.

The SCAN domain mediates interactions between members of a subfamily of zinc-finger transcription factors and is found in more than 60 C2H2 zinc finger genes in the human genome, including the tumor suppressor gene myeloid zinc finger 1 (MZF1). Glutathione-S-transferase pull-down assays showed that the MZF1 SCAN domain self-associates, and a Kd value of 600 nM was measured by intrinsic tryptophan fluorescence polarization. The MZF1 structure determined by NMR spectroscopy revealed a domain-swapped dimer.

Variations in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) are associated with bipolar i disorder.

The vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) maps to the shared bipolar disorder (BPD)/schizophrenia (SZ) susceptibility locus on chromosome 8p21. Vesicular monoamine transporters are involved in transport of monoamine neurotransmitters which have been postulated to play a relevant role in the etiology of BPD and/or SZ. Variations in the VMAT1 gene might affect transporter function and/or expression and might be involved in the etiology of BPD and/or SZ.

Confirmatory evidence for an association of the connexin-36 gene with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a genetically determined common subtype of idiopathic generalized epilepsy. Recently, linkage of JME to the chromosomal region 15q14, as well as an allelic and genotypic association between the synonymous coding single nucleotide polymorphism c.588C>T (dbSNP: rs3743123, S196S) of the positional candidate gene connexin-36 (CX36) and JME have been reported.

Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4.

Background: Migrainous vertigo (MV) is increasingly recognized as a common cause of episodic vertigo. MV displays several clinical similarities with familial hemiplegic migraine (FHM) and episodic ataxia type 2 (EA-2), which have been linked to mutations in 3 genes, CACNA1A, encoding a neuronal calcium channel alpha subunit, ATP1A2, encoding a catalytic subunit of a Na(+)/K(+)-ATPase, and most recently the voltage-gated sodium channel SCN1A. The present study explored the hypothesis that mutations in CACNA1A, ATP1A2, SCN1A, and the calcium channel beta(4) subunit CACNB4 confer susceptibility to MV.

Rosiglitazone antagonizes vascular endothelial growth factor signaling and nuclear factor of activated T cells activation in cardiac valve endothelium.

Nuclear factor of activated T cells, Cytoplasmic 1 (NFATc1) is required for heart valve formation. Vascular endothelial growth factor (VEGF) signaling, mediated by NFATc1 activation, positively regulates growth of valvular endothelial cells. However, regulators of VEGF/NFATc1 signaling in valve endothelium are poorly understood.

Endothelium-derived microparticles inhibit human cardiac valve endothelial cell function.

Elevated numbers of endothelium-derived microparticles (EMPs) in the circulation are found in a variety of critical illnesses. EMPs have been associated with vascular dysfunction, including thrombotic complications and loss of normal vascular reactivity, common responses associated with cardiac valve injury. However, the exact mechanisms of this dysfunction and the potential impact on cardiac endothelium are unknown.

Myofibrillogenesis regulator 1 gene (MR-1) mutation in an Omani family with paroxysmal nonkinesigenic dyskinesia.

Two recurrent missense mutations (c.20C>T: A7V; c.26C>T: A9V) in the gene encoding the myofibrillogenesis regulator 1 (MR-1) have been shown to cause autosomal dominant paroxysmal nonkinesigenic dyskinesia (PNKD) in 13 families of primarily European ancestry.

Toxicity-indicating structural patterns.

We describe a toxicity alerting system for uncharacterized compounds, which is based upon comprehensive tables of substructure fragments that are indicative of toxicity risk. These tables were derived computationally by analyzing the RTECS database and the World Drug Index. We provide, free of charge, a Java applet for structure drawing and toxicity risk assessment.

Association of BRD2 polymorphisms with photoparoxysmal response.

A trait locus for electroencephalographic photoparoxysmal response (PPR) has been mapped to the chromosomal region 6p21 near a susceptibility locus for juvenile myoclonic epilepsy (JME). Linkage disequilibrium mapping revealed strong associations between JME and polymorphisms of the gene encoding the bromodomain-containing protein 2 (BRD2). The present association study tested whether genetic variation of BRD2 confers also susceptibility to PPR.

Evaluation of CACNA1H in European patients with childhood absence epilepsy.

CACNA1H was evaluated in a resource of Caucasian European patients with childhood absence epilepsy by linkage analysis and typing of sequence variants previously identified in Chinese patients. Linkage analysis of 44 pedigrees provided no evidence for a locus in the CACNA1H region and none of the Chinese variants were found in 220 unrelated patients.

Sex differences in knee joint laxity change across the female menstrual cycle.

Aim: To elucidate the hormonal influences on sex differences in knee joint behavior, normal-menstruating females were compared to males on serum hormone levels and anterior knee joint laxity (displacement at 46N, 89N and 133N) and stiffness (Linear slope of deltaForce/deltaDisplacement for 46-89N and 89-133N) across the female menstrual cycle.

Methods: Twenty-two females were tested daily across one complete menstrual cycle, and 20 males were tested once per week for 4 weeks. Five days each representing the hormonal milieu for menses, the initial estrogen rise near ovulation, and the early and late luteal phases (total of 20 days) were compared to the average value obtained from males across their 4 test days.

Absolute serum hormone levels predict the magnitude of change in anterior knee laxity across the menstrual cycle.

This study aimed to determine whether absolute sex hormone concentrations predict the magnitude of knee joint laxity changes across the menstrual cycle. Twenty-two females (18-30 years, body mass index View Article and Find Full Text PDF

Candidate gene analysis of the succinic semialdehyde dehydrogenase gene (ALDH5A1) in patients with idiopathic generalized epilepsy and photosensitivity.

Succinic semialdehyde dehydrogenase (SSADH) is involved in the degradation of the inhibitory neurotransmitter GABA and about 50% of patients with SSADH deficiency suffer from seizures. The gene encoding SSADH (gene symbol: ALDH5A1) maps in proximity to susceptibility loci for juvenile myoclonic epilepsy (JME) and photosensitivity on chromosome 6p22. The present study tested whether variation of the ALDH5A1 gene confers susceptibility to common syndromes of idiopathic generalized epilepsy (IGE) and an abnormal photoparoxysmal response (PPR).

The influence of amplifier, interface and biological noise on signal quality in high-resolution EEG recordings.

First, the intrinsic random noise sources of a biopotential measurement in general are reviewed. For the special case of an electroencephalographic (EEG) measurement we have extended the commonly used amplifier noise model by biological generated background noise. As the strongest of all noise sources involved will dominate the resulting signal to noise ratio (S/N), we have investigated under which conditions this will be the case.

Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis.

Objectives: Three recent studies revealed a haplotypic association of alcohol dependence with the gene encoding the alpha2 subunit of the gamma-aminobutyric acid type A (GABAA) receptor (GABRA2). The present study examined whether variation of the GABRA2 gene confers susceptibility to different subtypes of alcohol dependence in the German population.

Methods: A total of 257 German alcohol-dependent patients and 88 healthy population controls were genotyped for six single-nucleotide polymorphisms covering the middle part and the 3' end of GABRA2.

Age-related changes of vergence under natural viewing conditions.

Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (ages 19-73 years) to characterize the age-related effects on the dynamic parameters of vergence responses to step (transient components) and ramp or sinusoidal targets (sustained components) under natural viewing conditions. Transient vergence showed an age-related increase in latency and decreases in peak velocity and acceleration in the binocular stimulus condition but not in accommodative vergence. Sustained vergence showed no age-related effect in the binocular condition, but there was an age-related decrease in accommodative vergence steady-state velocity and an increase in latency.

Association analysis of malic enzyme 2 gene polymorphisms with idiopathic generalized epilepsy.

Purpose: Linkage disequilibrium mapping revealed allelic and haplotypic associations between single-nucleotide polymorphisms (SNPs) of the gene encoding the malic enzyme 2 (ME2) and adolescent-onset idiopathic generalized epilepsy (IGE). Homozygote carriers of the associated ME2 haplotype had a sixfold higher risk of IGE compared with any other genotype. The present population-based association study tested whether genetic variation of the ME2 gene confers susceptibility to common IGE syndromes in the German population.

Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder.

Recent studies have indicated that the brain-derived neurotrophic factor (BDNF) gene is involved in the etiology of bipolar disorder (BPD). Two family-based association studies showed that the Val allele of the functional polymorphism Val66Met in the BDNF gene is associated with BPD; however, others could not confirm the results. Here we performed a replication study in an independent sample and tested the hypothesis that the Val66 allele in the BDNF gene confers susceptibility to bipolar I disorder (BPI).

A new EF-hand containing gene EFHC2 on Xp11.4: tentative evidence for association with juvenile myoclonic epilepsy.

Genetic factors play a major role in the etiology of idiopathic generalized epilepsies (IGE). An oligogenic or polygenic predisposition is suspected in the majority of families with common IGE syndromes. It has been hypothesized that some IGE genes might increase the general level of neuronal excitability while others specify the age of onset and the seizure type.

Neonatal seizures with tonic clonic sequences and poor developmental outcome.

Seizures consisting of a tonic followed by a clonic phase have rarely been described in neonates and are not included in the current classifications of neonatal seizures. Our video archive of 105 neonates with seizures or suspected seizures revealed six neonates with such tonic clonic or tonic myoclonic sequences. Two of those neonates had pyridoxine dependent seizures.

Association analysis of the Arg220His variation of the human gene encoding the GABA delta subunit with idiopathic generalized epilepsy.

Purpose: Mutation analysis of the gene encoding the GABA delta subunit (GABRD) identified a common missense variation (c.659G>A; Arg220His) of which the His220 allele displayed decreased GABA(A) alpha(1)beta(2)delta receptor current amplitudes. The present association study tested whether the functional GABRD His220 allele confers susceptibility to common syndromes of idiopathic generalized epilepsy (IGE).

The CHRNB2 mutation I312M is associated with epilepsy and distinct memory deficits.

Mutations in nAChRs are found in a rare form of nocturnal frontal lobe epilepsy (ADNFLE). Previously, some nAChR mutations have been described that are associated with additional neurological features such as psychiatric disorders or cognitive defects. Here, we report a new CHRNB2 mutation located in transmembrane region 3 (M3), outside the known ADNFLE mutation cluster.

Genetic dissection of photosensitivity and its relation to idiopathic generalized epilepsy.

Photosensitivity or photoparoxysmal response (PPR) is a common and highly heritable electroencephalographic trait characterized by an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. PPR occurs frequently associated with idiopathic generalized epilepsies (IGEs). The present genomewide linkage scan was designed to map susceptibility loci for PPR and to explore their genetic relationship with IGE.