Peer-based differences among boys with ADHD.

Examined the peer interactions and peer acceptance of three groups of boys ages 8 to 11 1/2 years: attention deficit hyperactivity disorder (ADHD), predominantly inattentive type; ADHD, combined type; and nonclinical controls (N = 45). Peer nominations were obtained from each boy's classroom. Newly acquainted peers consisting of boys from each of the 3 groups were observed for 3 play sessions, after which peer nominations were obtained.

Verbs, events and spatial representations.

Are concepts expressed in language also represented spatially? To pursue this question we investigated the structure of events. Events are defined as actions with spatial trajectories that can be perceived by our senses and described in language. Events are expressed linguistically in sentences containing verbs which determine the thematic roles of the arguments (e.

Modulation of the in situ activity of tissue transglutaminase by calcium and GTP.

Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes the posttranslational modification of proteins by transamidation of specific polypeptide-bound glutamine residues. Previous in vitro studies have demonstrated that the transamidating activity of tTG requires calcium and is inhibited by GTP. To investigate the endogenous regulation of tTG, a quantitative in situ transglutaminase (TG) activity assay was developed.

Lithium attenuates nerve growth factor-induced activation of AP-1 DNA binding activity in PC12 cells.

This investigation tested if lithium, the primary therapeutic agent for bipolar mood disorder, modulated activation of the AP-1 transcription factor in PC12 cells treated with nerve growth factor (NGF), which induces robust responses in these cells. NGF induced large, time-dependent increases in AP-1 DNA binding activity. Pretreatment with 5 mmol/L lithium for 24 h reduced AP-1 induction by NGF by 42%; shorter treatments and lower concentrations of lithium had smaller inhibitory effects on AP-1.

Dexamethasone attenuates NF-kappa B DNA binding activity without inducing I kappa B levels in rat brain in vivo.

This investigation tested if glucocorticoid hormones modulate activation of the NF-kappa B transcription factor in rat brain in vivo. Dexamethasone (2 mg/kg) administration decreased NF-kappa B DNA binding in cerebral cortex and hippocampus nuclear extracts, maximally at 3-6 h after dexamethasone, followed by recovery at 24 h. Dexamethasone did not inhibit NF-kappa B by increasing the level of the inhibitory protein I kappa B alpha, as occurs in some peripheral cells, but instead lowered I kappa B alpha levels.

Handicap-related problems in mothers of children with physical impairments.

An inventory was developed for the measurement of handicap-related problems experienced by mothers of children with chronic physical conditions and an initial evaluation of its psychometric properties was completed in a sample of 119 mothers of children with physical or sensory impairments. Principal component analysis of the Handicap-related Problems for Parents Inventory (HPPI) yielded three subscales, which accounted for 54% of the total variance. The HPPI demonstrated excellent internal consistency for each scale and total score.

Cholinergic activation of phosphoinositide signaling is impaired in Alzheimer's disease brain.

The function of the phosphoinositide signal transduction system was compared in membranes from Alzheimer's disease (AD) and control postmortem brain. [3H]Phosphatidylinositol hydrolysis was concentration-dependently stimulated by GTP[S] and this was 40% lower than controls in AD prefrontal cortical membranes. Carbachol induced a response greater than that of GTP[S] alone, and this response was impaired in AD by 45%.

Phosphoinositide signaling in human brain.

The phosphoinositide signal transduction system constitutes one of the primary means for intercellular communication in the central nervous system, but only recently has this system been studied in human brain. Although some investigations have studied phosphoinositide signaling in slices from biopsied human brain, due to the limited access to such material a greater number of studies have utilized membranes prepared from postmortem human brain. With membranes exposed to exogenous labeled phosphoinositides, activation of phospholipase C with calcium, with G-proteins stimulated by GTP gamma S or NaF, or with several receptor agonists, have demonstrated that all of the components of the phosphoinositide system are retained in human brain membranes and are responsive to appropriate stimuli.

Cholinergic stimulation of AP-1 and NF kappa B transcription factors is differentially sensitive to oxidative stress in SH-SY5Y neuroblastoma: relationship to phosphoinositide hydrolysis.

Oxidative stress appears to contribute to neuronal dysfunction in a number of neurodegenerative conditions, notably including Alzheimer's disease, in which cholinergic receptor-linked signal transduction activity is severely impaired. To test whether oxidative stress could contribute to deficits in cholinergic signaling, responses to carbachol were measured in human neuroblastoma SH-SY5Y cells exposed to H2O2. DNA binding activities of two transcription factors that are respondent to oxidative conditions, AP-1 and NF kappa B, were measured in nuclear extracts.

Inhibitory effects of cocaine on NGF-induced neuronal differentiation: incomplete reversibility after a critical time period.

We extend our findings showing dose-dependent cocaine inhibition of differentiation in NGF-stimulated PC-12 cells without affecting cell viability by demonstrating that neurite extension is severely limited after 24 h, maximal effect is reached at 36 h and recovery is only partial. Cocaine metabolites lack these effects. A similar process may occur following human prenatal exposure, perhaps through cocaine-induced changes in gene expression or other intracellular signalling events.

Development and evaluation of a measure of concerns related to raising a child with a physical disability.

Developed a measure of perceived disability-related stress, the Parents of Children with Disabilities Inventory (PCDI). A content analysis of concerns expressed by mothers identified four primary domains: Medical and Legal Concerns, Concerns for the Child, Concerns for the Family, and Concerns for the Self. Item analysis performed on an initial item pool administered to 48 mothers recruited from area spina bifida and cerebral palsy clinics identified 40 items for further investigation.

Tau protein is phosphorylated by cyclic AMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II within its microtubule-binding domains at Ser-262 and Ser-356.

Phosphorylation of tau protein at Ser-262 has been shown to diminish its ability to bind to taxol-stabilized microtubules. The paired helical filaments (PHFs) found in Alzheimer's disease brain are composed of PHF-tau, which is hyperphosphorylated at multiple sites including Ser-262. However, protein kinase(s) able to phosphorylate this site are still under investigation.

The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain.

The function of the phosphoinositide second messenger system was assessed in occipital, temporal, and frontal cortex obtained postmortem from subjects with bipolar affective disorder and matched controls by measuring the hydrolysis of [3H]phosphatidylinositol ([3H]PI) incubated with membrane preparations and several different stimulatory agents. Phospholipase C activity, measured in the presence of 0.1 mM Ca2+ to stimulate the enzyme, was not different in bipolar and control samples.

Altered brain sodium channel transcript levels in human epilepsy.

Normal, and perhaps pathological, characteristics of neuronal excitability are related to the distribution and density of voltage-gated ion channels such as the sodium channel. We studied normal and epileptic human brain using the ligase detection reaction to measure the relative quantities of mRNAs encoding sodium channel subtypes 1 and 2. Normal brains exhibited characteristic 1:2 ratios which varied by brain region, but the ratios were invariate among individuals.

Postnatal changes in serine/threonine protein phosphatases and their association with the microtubules.

The activities and protein levels of three serine/threonine protein phosphatases were determined in homogenates and microtubule preparations from rat brain at various ages from postnatal day 1 (P1) through adulthood. The activities and levels of the calcium/calmodulin-dependent protein phosphatase, phosphatase 2B increased significantly from P1 to P21 in brain homogenates and remained elevated in the adult. The association of phosphatase 2B with microtubules was also found to be increased in the adult compared to the neonate (P3).

Circadian variation in rat brain AP-1 DNA binding activity after cholinergic stimulation: modulation by lithium.

The potential influence of a circadian rhythm and its modulation by lithium on the stimulation of AP-1 DNA binding activity by the cholinergic agonist pilocarpine was investigated in rat cerebral cortex. Stimulation of AP-1 binding after pilocarpine (30 mg/kg) was evident within 1 h and was maximally stimulated by 200% at 2 h. Pilocarpine-stimulated AP-1 binding exhibited a circadian rhythm in AP-1 binding measured at 0800, 1200, and 1600 hours, 2 h after pilocarpine.

Selective inhibition of the expression of signal transduction proteins by lithium in nerve growth factor-differentiated PC12 cells.

This investigation examined if lithium, the primary therapeutic treatment for bipolar affective disorder, modulated the levels of selected signal transduction proteins in PC12 cells. Nerve growth factor (NGF) induced differentiation of PC12 cells, and after 12 days of NGF treatment there were large increases in the levels of the heterotrimeric G protein subunits alpha o1, alpha i1, beta, and alpha s, small increases in those of alpha i2 and alpha q, and a slight decrease in that of alpha o2. Lithium (1 mM, equivalent to the therapeutic concentration) selectively reduced NGF-induced increases in levels of G protein subunits, generally having the greatest inhibition on those that were increased the most by NGF.

Transglutaminase cross-linking of the tau protein.

Tissue transglutaminase (EC 2.3.2.

Perceived role restriction and adjustment of mothers of children with chronic physical disability.

Examined the relationship between maternal perceived role restriction, the extent to which a mother feels unable to pursue her own interests due to responsibilities with raising a child with a chronic physical condition, and psychosocial adjustment in 50 mothers with children 6-11 years old who had a chronic physical disability. Perceived role restriction accounted for a significant increment in the variation in adjustment beyond that contributed by objective indices of the child's disability. Neither these objective parameters of the child's disability nor his or her level of problem behaviors predicted perceptions of role restriction.

Phosphorylation of tau in situ: inhibition of calcium-dependent proteolysis.

In this study, the in situ phosphorylation and subsequent calcium-activated proteolysis of tau protein were examined in human neuroblastoma (LA-N-5) cells, which were differentiated into a neuronal phenotype. The phosphorylation of tau was increased by treating the cells with forskolin and rolipram, which elevate cyclic AMP levels, by treating with the phosphatase inhibitor okadaic acid, or by treating with a combination of both treatments. Phosphorylated tau migrated slightly slower on sodium dodecyl sulfate-polyacrylamide gels than tau from untreated cells.

Modulation by inositol of cholinergic- and serotonergic-induced seizures in lithium-treated rats.

Hippocampal and cortical EEG recordings in rats were used to monitor the in vivo modulation by lithium of responses to agonists for 5HT2/5HT1c serotonergic (DOI) and cholinergic (pilocarpine) receptors and the influence of inositol administration. Administration of DOI (8 mg/kg) or pilocarpine (30 mg/kg) to rats pretreated with lithium acutely (3 mmol/kg) or chronically (dietary, 4 weeks) resulted in seizures, whereas these doses did not cause seizures without lithium pretreatment. This indicated that lithium most likely affects a signal transduction process common to both systems, which is the phosphoinositide second messenger system.