Error negativity on correct trials: a reexamination of available data

The error negativity, an EEG wave observed when subjects commit an error in a choice reaction time (RT) task, is often considered as a sign of error detection. Recently, reports of Ne-like waves on correct responses did challenge this interpretation. It has been proposed, however, that these Ne-like waves result either from an artifactual contamination of response-locked activities by stimulus-locked ones, or from an implicit monitoring of the time elapsing during the RT. Our aim was to reprocess published data: (1) to compare the shape and amplitude of EMG-locked and stimulus-locked ERPs on correct trials, and (2) to compare the size of the EMG-locked Ne-like waves obtained on fast and slow trials. The results neither support the artifact hypothesis nor the RT monitoring one. Therefore, it seems that the Ne-like waves observed on correct trials do correspond to a Ne, which suggests that the Ne has a broader significance than just error detection.     

Amyloid and nonfibrillar deposits in mice transgenic for wild-type human transthyretin: a possible model for senile systemic amyloidosis

The human serum protein transthyretin (TTR) is highly fibrillogenic in vitro and is the fibril precursor in both autosomal dominant (familial amyloidotic polyneuropathy [FAP] and familial amyloidotic cardiomyopathy [FAC]) and sporadic (senile systemic amyloidosis [SSA]) forms of human cardiac amyloidosis. We have produced mouse strains transgenic for either wild-type or mutant (TTRLeu55Pro) human TTR genes. Eighty-four percent of C57BI/6xDBA/2 mice older than 18 months, transgenic for the wild-type human TTR gene, develop TTR deposits that occur primarily in heart and kidney. In most of the animals, the deposits are nonfibrillar and non-Congophilic, but 20% of animals older than 18 months that bear the transgene have human TTR cardiac amyloid deposits identical to the lesions seen in SSA. Amino terminal amino acid sequence analysis and mass spectrometry of the major component extracted from amyloid and nonamyloid deposits revealed that both were intact human TTR monomers with no evidence of proteolysis or codeposition of murine TTR. This is the first instance in which the proteins from amyloid and nonfibrillar deposits in the same or syngeneic animals have been shown to be identical by sequence analysis. It is also the first time in any form of amyloidosis that nonfibrillar deposits have been shown to systematically occur temporally before the appearance of fibrils derived from the same precursor in the same tissues. These findings suggest, but do not prove, that the nonamyloid deposits represent a precursor of the fibril. The differences in the ultrastructure and binding properties of the deposits, despite the identical sizes and amino terminal amino acid sequences of the TTR and the dissociation of deposition and fibril formation, provide evidence that in vivo factors, perhaps associated with aging, impact on both systemic precursor deposition and amyloid fibril formation.     

A novel logistic model based on clinicopathological features predicts microsatellite instability in colorectal carcinomas.

High-frequency microsatellite instability has been reported to be associated with good prognosis in colorectal adenocarcinoma. However, methods to assess microsatellite instability (MIN) are based on genetic assays and are not ideally suited to most histopathology laboratories. The aim of the present study was to develop a model for prediction of MIN status in colorectal cancer based on phenotypic characteristics. Clinicopathological features of a cohort of 204 patients with primary colon cancer were retrospectively reviewed following predetermined criteria. Genetic assessment of MIN status was performed on DNA extracted from sections of formalin-fixed, paraffin-embedded specimens by testing a panel of 11 microsatellite markers. Logistic regression analysis generated a mathematical tool capable of identifying colorectal tumors displaying MIN status with a sensitivity of 77.8% and a specificity of 96.8%. Features associated with instability included the proximal location of the lesions, occurrence of solid and/or mucinous differentiation, absence of cribriform structures, presence of peritumoral Crohn-like reaction, expansive growth pattern, high Ki67 proliferative index, and p53-negative phenotype. This approach predicts microsatellite instability in colorectal carcinoma with an overall assigned accuracy of 95.1% and a negative predictive value of 97.8%. Implementation of this tool to routine histopathological studies could improve the management of patients with colorectal cancer, especially those presenting with stage II and III of the disease. It will also assist in identifying a subset of patients likely to benefit from adjuvant chemotherapy.     

Sensitization to cross-reactive carbohydrate determinants in relation to alcohol consumption

Background Alcohol consumption is associated with increased serum IgE of unknown specificity. Objective To investigate the prevalence of specific IgE to cross‐reactive carbohydrate determinants (CCDs) in adults, and its relation to alcohol consumption. Methods Population‐based survey of 457 adults (218 abstainers, 195 light‐to‐moderate drinkers, 44 heavy drinkers). Specific IgE determinations included a CCD (MUXF³, the N‐glycan of bromelain), pollens (Lolium perenne and Olea europaea), Hymenoptera venoms (Apis mellifera and Vespula spp.), and a mite (Dermatophagoides pteronyssinus). We replicated these studies in an additional sample of alcoholics (n=138). Inhibition assays were performed in selected cases. Results In the general population, 5.6% of individuals (95% confidence interval 3.5–7.6%) showed positive (0.35 kU/L) CCD‐specific IgE. The levels of CCD‐specific IgE were particularly high in heavy drinkers, who also showed a high prevalence of positive IgE to pollens and Hymenoptera venoms, doubling (at least) the prevalence found in alcohol abstainers and light‐to‐moderate drinkers. The presence of IgE to pollens and Hymenoptera venoms was closely correlated with the presence of CCD‐specific IgE. These features were confirmed in the additional sample of alcoholics. Inhibition studies indicated a role of CCD interference in IgE positivity to pollen and Hymenoptera allergens in alcoholics. Conclusions CCD‐specific IgE is prevalent in heavy drinkers, and is associated with positive IgE to pollens and Hymenoptera venoms. Specific IgE results should be interpreted with caution in heavy drinkers.     

Familial Alzheimer disease associated with A713T mutation in APP

Mutations in APP are associated with familial early-onset Alzheimer disease (FAD). Examination of the genomic sequence in one patient with FAD revealed a change located in the axon 17 of the APP gene at position 275329G>A (GenBank accession number: D87675; GI: 2429080); cDNA sequence 2137G>A (GenBank accession number: X06989; GI: 28720). This corresponds to the mutation A713T in APP. AD stage VI of neurofibrillary degeneration and stage C of Aβ-amyloid burden was found at the post-mortem neuropathological examination. Previous studies have suggested that the mutation A713T in APP is a silent mutation or polymorphism. However, we have not found this change in APP in a control population analyzed by the amplification-refractory mutation system (ARMS). It is concluded that A713T in APP is implicated in the pathogenesis of AD. Since the immunohistochemical study indicates that A713T mutation is not likely to relate with Aβ-amyloid processing, the causative role of this rare mutation remains to be warranted.     

Identification and discrimination of Burkholderia pseudomallei, B. mallei, and B. thailandensis by real-time PCR targeting type III secretion system genes

Burkholderia pseudomallei and B. mallei are two highly pathogenic bacteria, responsible for melioidosis and glanders, respectively. The two are closely related and can also be mistaken for B. thailandensis, a nonpathogenic species. To improve their differential identification, we describe a hydrolysis probe-based real-time PCR method using the uneven distribution of type III secretion system genes among these three species.     

Pharmacological profile of nicotinic acetylcholine receptors in the rat prefrontal cortex: an electrophysiological study in a slice preparation

The specificity of nicotinic receptors in the neocortex has been questioned previously because: (i) electrophysiological responses to nicotine could not be blocked by nicotinic antagonists, and (ii) the effect of nicotine was not mimicked by acetylcholine. In the present study, the presence of functional nicotinic receptors in rat neocortex has been assessed in a slice preparation of prefrontal cortex, using evoked field potential and unit recordings. Nicotine and the nicotinic agonists, dimethylphenylpiperazinium, cytisine, acetylthiocholine, applied by iontophoresis, produced an increase in the negative wave of field potentials, reflecting an increased excitability of cortical neurons. This effect was blocked by the selective probe for neuronal nicotinic receptors Toxin F (1.4 microM in the perfusion medium) and by dihydro-beta-erythroidine (100 microM). Alpha-bungarotoxin, the blocker of skeletal muscle acetylcholine receptor had no effect. Iontophoretically applied acetylcholine, muscarine and pilocarpine, on the other hand, produced a decrease in the field potential amplitude, which was blocked by atropine and scopolamine (1-10 microM). In the presence of eserine (10 microM), the muscarinic effect of acetylcholine was dramatically altered, leading to the development of a nicotinic response sensitive to Toxin F. Thus, the physiological activation of nicotinic receptors in rat prefrontal cortex appears to require higher concentrations of acetylcholine than do muscarinic receptors. Our results show that: (i) the rat prefrontal cortex possesses functional nicotinic receptors with a pharmacological profile clearly distinct from muscle receptors, and (ii) a nicotinic effect of acetylcholine can be revealed when its degradation by acetylcholinesterase is inhibited.     

Eye and neck motor signals in periabducens reticular neurons of the alert cat

The purpose of this work was to search for neurons in the ponto-medullary reticular formation which can carry horizontal eye position signals to dorsal neck muscles of the cat. The recordings were localized in an area of the ponto-medullary reticular formation which contains reticulo-spinal neurons projecting to the neck (Peterson et al. 1980). Experiments were performed on alert, head-fixed cats. Eye movements were measured by the search-coil technique. Neuronal activity was recorded extracellularly with glass microelectrodes. Neurons were localized both by stereotaxic coordinates and by their position with respect to the antidromic field potential profile of the abducens nucleus. EMG of longissimus capitis, obliquus capitis and splenius muscles were recorded. Vestibular stimulation was produced by a turn-table. Reticular cells were found below the abducens nucleus (1 to 3.5 mm below the center of the nucleus, A.P.:5.3 to 7.2 mm;L: 1 to 1.5 mm) showing a firing rate closely related to EMG during spontaneous saccades and, to a variable degree, to the ipsilateral horizontal component of eye position. 'Tonic' and 'burst-tonic' cells were found. During vestibular stimulation, the firing rate kept the same relationship with eye position and neck EMG. It is concluded that the analyzed reticular cells are good candidates to be reticulo-spinal neurons which mediate a signal allowing a synergistic movement of head and eye during orientation in the horizontal plane.     

Acute respiratory infection by human metapneumovirus in children in southern Brazil.

BACKGROUND: Human metapneumovirus (hMPV) has been described as an etiologic agent of acute respiratory infections (ARI), mainly in pediatric patients. Viral isolation is difficult and has low sensitivity, and consequently RT-PCR assays are currently used for detection. OBJECTIVES: Detect hMPV in ARI in hospitalized children in Southern Brazil; standardize a RT-PCR for routine hMPV diagnosis; validate a positive control for molecular tests; and perform phylogenetics analyses. STUDY DESIGN: Nasopharyngeal aspirates (NPA) from 156 hospitalized children were studied. A conserved region of the nucleoprotein gene was cloned, characterized and used to standardize an RT-PCR assay. Phylogenetic analyses were performed. Clinical data were obtained from medical records. RESULTS: hMPV was detected in 6.4% of the samples. Dyspnea and wheezing were frequently reported symptoms and the most common diagnoses were bronchiolitis, acute respiratory insufficiency or laryngotracheobronchitis. Nucleotide sequence alignment revealed 97.7% identity with genotype A1 of hMPV. The detection limit of hMPV genomes by RT-PCR in clinical samples was 180 copies/microL. CONCLUSION: This is the first report of the detection and genetic characterization of hMPV infections in children with lower ARI in Southern Brazil.