The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease

We determined apolipoprotein E (ApoE) genotypes in 122 autopsied demented patients. The frequency of the ApoE epsilon 4 allele was 39.6% in Alzheimer's disease (AD), 29.0% in the Lewy body variant of AD (LBV), and 6.25% in diffuse Lewy body disease. For AD and LBV patients, the epsilon 4 frequency was significantly higher than that reported in nondemented controls (10 to 15%). Therefore, LBV and AD share ApoE epsilon 4 as a genetic risk factor, providing further evidence that these conditions overlap.     

Analysis of the Design-Build Delivery Method in Air Force Construction Projects

The design-build (DB) method for construction project delivery continues to grow in both the private and public sector; additionally, research has shown that the DB method outperforms the design-bid-build (DBB) method. The Air Force has applied the results of these previous research efforts to its military construction (MILCON) program without performing empirical studies to validate the approach. Therefore, the objective of this study was to compare the performance of the DB delivery method with the traditional DBB approach for the Air Force MILCON program. Data related to 835 (278 DB and 557 DBB) MILCON projects for fiscal years 1996–2006 were subsequently analyzed. The DB method had better performance in three of six metrics with the performance being significantly better for cost growth and the number of modifications per million dollars. The traditional DBB method performed significantly better in terms of total project time. Furthermore, the DB method was best suited for various facility types. This study provides empirical evidence of how the DB method provides an advantage over the traditional DBB method for Air Force MILCON projects.     

Integrating language and gesture in infancy.

Whether language/gesture correlations in early language development can be explained by parallelism or comprehension mediation was examined. Study 1, parental report data for 95 1-year olds, suggested that word comprehension and production are dissociated in this age range and that the comprehension and production factors map onto distinct aspects of gesture. Study 2 tested 41 13–15-month-olds in a task in which the modeled gesture was accompanied by supportive, contradictory, or neutral narratives. Results showed that infants can use adult speech as an aid in reproduction of modeled gestures (comprehension mediation). However, there is still additional variance in gestural production that correlates with expressive vocabulary when comprehension-related variance is moved. Thus, comprehension mediation and parallelism both appear to be operating. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic evidence that the Lewy body variant is indeed a phenotypic variant of Alzheimer''s disease

To investigate the role of cyclic adenosine monophosphate (cAMP) in penile erection in relation to the effect of prostaglandin E1 (PGE1) male adult New Zealand white rabbits were utilized as a model to study intracavernous pressure (ICP) in vivo. After intracavernous injection of PGE1 (0.2-1.6 micrograms/kg) and 8-bromocyclic adenosine monophosphate (8-Br-cAMP, 0.5-1.5 mg/kg), both drugs raised the ICP in a dose-dependent manner. The increased ICPs induced by PGE1 and 8-Br-cAMP were 33.4 +/- 8.12 and 24.1 +/- 4.9 mm Hg, respectively (p < 0.05, paired Student's t test). Administrations of cyclic adenosine monophosphothioate, Rp-isomer (cAMP antagonist, 0.02-0.08 mumol/kg) prior to PGE1 injections inhibited the effect of PGE1 in vivo in a dose-dependent manner. The systemic blood pressures and heart rates in rabbits were unchanged during all the intracavernous injections. The corpus cavernosal tissues isolated from rabbits were studied for the cAMP contents after incubation of different doses of PGE1 in vitro. The cAMP contents were also elevated in a manner parallel with the increases in PGE1 concentrations (3-9 microM). We conclude: (1) the feasibility of intracavernous injection of vasoactive drugs is similar to that in man, thus the rabbit can be used as a suitable alternative for the studies of penile erection, and (2) cAMP is mediated in PGE1-induced relaxation of the rabbit corpus cavernosum, and the cAMP system only participates partially in penile erection.     

A 25-week placebo-controlled study of eptastigmine in patients with Alzheimer disease

Studies of Pneumocystis carinii have been limited by our inability to propagate it in continuous culture. In this context, studies of P. carinii antigens have provided significant insight into the biology of this organism. The mannose-rich surface major surface glycoprotein of P. carinii termed glycoprotein A (gpA) is the best studied of these P. carinii antigens. Significant genetic and immunologic diversity exists between the gpA molecules expressed by P. carinii derived from different mammalian sources. The molecular and biochemical nature of gpA and other P. carinii antigens including p55 are reviewed. In addition, available information concerning the role of P. carinii gpA and other antigens in host-organism interactions are also discussed.     

Correlation of nicotinic binding with neurochemical markers in Alzheimer's disease

The loss of neocortical synapses that occurs in Alzheimer's disease (AD) has been shown to correlate with cognitive decline. In addition, marked losses in the cholinergic system in AD, specifically choline acetyltransferase (ChAT) activity and high affinity presynaptic neuronal nicotinic cholinergic receptors (nAChRs), have also been described. We hypothesized that in AD, the loss of [3H]-ligand binding to nAChRs, which are largely presynaptic, would correlate with changes in two other presynaptic markers: synaptophysin (Syn), a measure of synaptic density, and ChAT activity. The midfrontal (MF) cortex of 36 autopsy confirmed (NIA and CERAD criteria) AD patients (mean death age +/- SD 80.1 +/- 8.4 years) who met NINDS-ADRDA criteria for a clinical diagnosis of probable or possible AD, and 11 nondemented controls (mean death age +/- SD 77.9 +/- 8.0) were examined. Synapse counts were quantified by a dotimmunobinding assay for Syn. ChAT activity was assessed by standard biochemical assays. Nicotinic cholinergic receptor binding was assayed using the high affinity nicotinic agonist [3H]-(+/-)-epibatidine ([3H]-EPI). The mean +/- SD Syn in AD (83.4 +/- 31.9 arbitrary units (AU)/mg protein) was significantly lower than controls (126.1 +/- 19.9, p = 0.0003; t-test). The mean ChAT activity in AD (139.0 +/- 75.6 nmol ACh/hr/100 mg protein) was significantly lower than controls (219.6 +/- 70.8, p = 0.004). The mean [3H]-EPI total binding in AD (6.2 +/- 2.8 fmol/mg protein) was significantly lower than controls (14.8 +/- 3.2; p < 0.0001). Syn correlated with [3H]-EPI binding in AD (r = 0.48, p = 0.006; Pearson) but ChAT did not (r = -0.20, p = 0.34). We conclude that loss of high affinity nAChR binding correlates with loss of synapses in AD. The lack of correlation between [3H]-EPI binding and ChAT activity suggests that the targeted receptor populations may not be located exclusively on cholinergic neurons.     

Fibre optic bronchoscopy in children (author''s transl)]

Alterations in the activity of rat liver monoxygenases were studied in dynamics of cholestasis development after ligation of biliary duct and the effects observed were compared to the latter after addition of cholesterol hydroxylated derivatives in vitro. Sodium deoxycholate at concentration 0.06-0.07% was shown to stimulate the alterations in the microsomal monooxygenases activity within fourth day and at concentration 0.09-0.12%--within seventh day of cholestasis.     

Lack of long-term effects after beta-amyloid protein injections in rat brain

Rat beta(1-42) peptide (beta/A4) or phosphate buffered saline (PBS) was bilaterally injected into the hippocampus (HIP) or the lateral ventricle (ICV) of 3-month-old Fischer-344 rats. Fifteen months later, the animal's ability to learn a spatial memory task was tested using the Morris water maze. Acquisition of the task was impaired by the bilateral injection of either peptide or PBS into the hippocampus. Hippocampal-injected animals showed an increased average latency to find the platform by approximately 6 s (p < 0.05). However, injection of rat beta-peptide into the hippocampus or lateral ventricles failed to induce behavioral impairment when compared to vehicle injected controls. Retention of this task was not significantly impaired in any group. The spatial acuity test, a trial without the platform, revealed that both groups of animals that received hippocampal injections were impaired, spending 23% less time in the target quadrant compared to ICV-injected animals (p < 0.005). Hippocampal ChAT activity was decreased in beta/A4-injected animals but not significantly (p < 0.06). beta/A4-immunoreactivity was detected at the bottom of the needle track and the adjacent parenchyma of beta/A4 hippocampal-injected animals after 16 months. However, long-term in vivo deposition of beta/A4 in both regions did not result in an upregulation of hippocampal amyloid precursor protein (APP) expression and there was no qualitative neuronal loss in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effect of RU24722 on tyrosine hydroxylase in the rat locus coeruleus: differential effects of two enantiomeric forms

RU24722, as a racemic mixture, has been found to act on neuronal activity and the long-term regulation of tyrosine hydroxylase in the locus coeruleus of the rat. In this study, the effects of two enantiomeric derivatives of RU24722 (3 alpha and 16 alpha forms), as compared to the racemic form itself, are studied. The short-term effect was estimated 20 min after treatment by measuring variations in 3,4-dihydroxyphenylacetic acid content in the locus coeruleus. The long-term effect was determined by evaluating tyrosine hydroxylase protein concentration in the locus coeruleus 3 days after a single injection. Comparison of actions of both enantiomers showed that the 16 alpha form was 3-fold more potent in eliciting tyrosine hydroxylase protein elevations at three days, whereas the 3 alpha isomer increased 3,4-dihydroxyphenylacetic acid content 2-fold more in the short-term. These results seem to show that the 16 alpha configuration is crucial for the long term regulation of tyrosine hydroxylase protein elicited by RU24722 within the locus coeruleus.