Revisiting the oddball paradigm. Non-target vs neutral stimuli and the evaluation of ERP attentional effects.

We recorded topographic mapping of auditory evoked potentials (AEPs) to homogeneous series of tones delivered in the absence of any cognitive task ("neutral condition") and compared them with responses to identical stimuli when they acted as non-targets in an oddball paradigm. With respect to the neutral condition, non-target responses showed an increase in N100 amplitude which was found to depend on two different, but partially overlapping effects. The "early effect" had similar latency and topography as exogenous N100 and may reflect changes in the overall state of alertness since its amplitude declined at the end of the test. The "late effect" affected the N100s descending slope and had features consistent with those of a processing negativity. It was frontally distributed, and topographic mapping revealed a right-sided predominance. Finally, non-target responses exhibited a central positivity (P250) which did not appear in neutral AEPs. P250 shares several features, including latency, amplitude and scalp topography, with the endogenous ERP component commonly labelled "P3a". Non-target P250 could be the result of an attentional shift towards the stimuli, and reflect some aspects of the classification process. We suggest that non-target responses in simple oddball paradigms should be routinely studied along with target responses in order to improve the diagnostic capabilities of cognitive ERPs. Notably, non-target responses may help to decide whether an abnormal target-P300 is related or not to a deficit in the mobilization of attentional resources.     

Giant axonal neuropathy: intermediate filament disease with involvement of the peripheral and central nervous system

We report a case of giant axonal neuropathy in a 14 year-old turkish boy with progressive chronic neuropathy and central involvement with mental retardation. CT showed a low density and MRI imaging multiple cavities and hypersignals of the white matter. Nerve and skin biopsies revealed an accumulation of neurofilaments in axonal swellings and an accumulation of intermediate filaments in fibroblasts, Schwann cells, endothelial cells. These findings are in accordance with the reported cases. Giant axonal neuropathy results from a generalized disorder of the intermediate filaments, but the precise biochemical defect is unknown. We would agree with Maia (1988) to name this affection "Giant Axonal Disease".     

Iridoids from Scaevola racemigera1

Five iridoids have been isolated from the aerial parts of SCAEVOLA RACEMIGERA D?niker, namely, loganin, loganic acid, sylvestroside III, cantleyoside, and scaevoloside. This latter is a novel compound whose structure 1 has been elucidated on the basis of its spectral data, mainly (1)H- and (13)C-NMR.     

Response involvement in brain stimulation reward

The hypothesis that responding contributes to the reward value of brain stimulation was tested in two novel experimental paradigms. In the first experiment rats lever-presssed for rewarding brain stimulation during 90 sec periods. After each period the lever automatically retracted and experimenter-administered stimulation (EAS) was presented at the same rate and current parameters as during the self-stimulation (SS). The rats could demonstrate a preference for SS (vs EAS) by pressing a reset lever on the opposite wall of the test chamber. This action terminated the EAS and reinstated the SS-lever for an additional 90 sec. Results showed that the rats preferred to respond for stimulation than to have that same stimulation administered by the experimenter. This was true even when a signal preceded each train of EAS or when subjects had a great deal of previous EAS experience. In the second experiment conditioned taste preferences were observed following novel taste/SS pairings but not following novel taste/EAS pairings. The data from these two experiments suggest that responding contributes to the rewarding value of brain stimulation.     

Focal expression and final activity of matrix metalloproteinases may explain irregular dysfunctional endometrial bleeding

Irregular dysfunctional bleeding of the endometrium (ie, metrorrhagia without organic lesion) is common in women, whether treated or not with ovarian hormones. Several matrix metalloproteinases (MMPs) become normally expressed and/or activated at menstruation and cause extracellular matrix breakdown. We therefore explored whether episodes of irregular dysfunctional bleeding could be associated with untimely MMP activity. By histology, foci of stromal breakdown were exclusively found in the endometrium of metrorrhagic women at bleeding. In these foci, 1) expression of estrogen receptor-alpha and progesterone receptor was altered; 2) collagenase-1 (MMP-1), stromelysin-1 (MMP-3), and gelatinase B (MMP-9) became detected in stromal cells, together with MMP-9 in neutrophils; and 3) gelatinase A (MMP-2) was more expressed and immunolocalized at the membrane of stromal cells. By biochemistry, endometrial lysates from nonbleeding metrorrhagic patients contained more latent and active MMP-2 and -9 than age-matched controls; at bleeding, collagenase activity, MMP-9, and active MMP-2 were strikingly increased whereas tissue inhibitor of metalloproteinases-1 (TIMP-1) was considerably decreased. As a functional assay, in situ gelatin zymography revealed large areas of gelatinolytic activity only in endometrium of bleeding patients. Altogether, these results strongly suggest that inappropriate focal expression and activation of several MMPs, combined with decreased inhibition, trigger irregular dysfunctional endometrial bleeding.     

High levels of Lp(a) lipoprotein in a family ith cases of severe pre-eclampsia

We report a family with two cases of severe pre-eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre-eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre-eclampsia that is genetically determined.     

Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus

A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3' to the last kringle IV structure of the gene. The "1" gene (presence of the restriction site) has a frequency of 0.316 and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1-1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.     

Implication of the C-terminal domain of nef protein in the reversion to pathogenicity of attenuated SIVmacBK28-41 in macaques

We have analyzed the nef gene sequences amplified from 12 macaques presenting various patterns of infection with SIVmacBK28-41, a clone derived from attenuated SIVmacBK28. We have observed seven mutation hot spots at positions 56, 75, 432, 588, 680, 699, and 779. The major alteration was a thymidine insertion at position 699, leading to a frameshift in the SIVmacBK28-41 nef gene and changing the last 15 amino acids of Nef into a 31-amino-acid-long C-terminal domain nearly identical to that encoded by pathogenic SIVmac239 and SIVmac251. The insertion was found at early time points in proviruses obtained from rapid progressor macaques, after 2 years postinfection in progressors, and rarely or only after 4 years postinfection in nonprogressors. Fixation of the other mutations occurred only after insertion of thymidine 699. Phylogenetic analysis demonstrated that the nef genes isolated from progressors evolved from the allele present in SIVmacBK28-41 to alleles present in SIVmac239 or SIVmac251, whereas nef sequences from nonprogressors stayed clustered with that of the inoculated molecular clone. These data stress the importance of the C-terminal extremity of the Nef protein of SIVmac239 or SIVmac251 in viral pathogenesis.     

Frequent carriage of Panton-Valentine leucocidin genes by Staphylococcus aureus isolates from surgically drained abscesses

Between 1 February and 15 April 2002, 95 patients were admitted to Gaston Bourret Territorial Hospital (New Caledonia, France) for drainage of community-acquired soft tissue abscesses. Staphylococcus aureus was detected in 68 cases (72%). Two-thirds of the patients with S. aureus infection had furuncles, which were located on the limbs in 82% of cases. The median interval between symptom onset and hospital admission was 5.7 days. Three-quarters of the patients were Melanesians living in tribes. Fifty-four S. aureus isolates were screened for toxin genes. Panton-Valentine leucocidin (PVL) genes were detected in 48 isolates (89%), the exfoliative toxin A gene was detected in 1 isolate, and no toxin genes were detected in 4 isolates. S. aureus nasal carriage was detected in 39.7% of patients with S. aureus infections. Two infecting S. aureus strains and two nasal carriage strains were resistant to methicillin. Comparative pulsed-field gel electrophoresis, performed in 16 cases, showed that five of six patients with PVL-positive nasal carriage strains were infected by the same strains. In contrast, 8 of 10 patients with PVL-negative nasal carriage strains were infected by PVL-positive strains. PVL genes thus appear to be a major virulence factor in both primary and secondary S. aureus skin infections.