The composite N1 component to gaps in noise.

OBJECTIVE: To indicate whether the double peaked N(1) to gaps in continuous white noise is a composite of onset and offset responses to transients or whether it reflects higher processing such as change or mismatch detection and to assess the role of attention in this process. METHODS: Evoked potentials were recorded to two binaural stimulus types: (1) gaps of different durations randomly distributed in continuous white noise; and (2) click pairs at intervals identical to those between gap onsets and offsets in the continuous noise stimulus. Potentials to these stimuli were recorded while subjects read a text and while detecting gaps in noise or click pairs. RESULTS: Potentials were detected to all click pairs and to gaps of 5 ms or longer, corresponding to the subjects' psychoacoustic gap detection threshold. With long gap durations of 200-800 ms, distinct potentials to gap onset and gap offset were observed. The waveforms to all click pairs and to offsets of long gaps were similar and single-peaked, while potentials to gaps of 10 ms and longer, and potentials to onsets of long gaps were double-peaked, consisting of two N(1) negativities, 60 ms apart, irrespective of gap duration. The first (N(1a)), was more frontal in its distribution and similar to that of clicks. The second (N(1b)) peak's distribution was more central/temporal and its source locations and time course of activity were distinct. No effects of attention on any of the varieties and constituents of N(1) were observed. CONCLUSIONS: Comparing potentials to gap onsets, to click pairs and to gap offsets, suggests that potentials to gap onsets involve not only sound onset/offset responses (N(1), N(1a)) but also the subsequent pre-attentive perception of the cessation of an ongoing sound (N(1b)). We propose that N(1b) is distinct from change or mismatch detection and is associated with termination of an ongoing continuous stimulus. We propose to call it the N(egation)-process. SIGNIFICANCE: A constituent of the N(1) complex is shown to be associated with the pre-attentive perception of termination of an ongoing stimulus and to have distinct scalp distribution and intracranial sources.     

Positive clinical impressions: II. Participants' evaluations

Nine months after the residential stage of Koach, participants were asked to evaluate the program's effectiveness. Most of the veterans reported improvement in the areas queried, and especially in social relations, and nearly all of them stated that they would recommend the program to other veterans. The commander-therapists became the major source of help for these veterans following the Koach project, and about half reported that they participated regularly in self-help groups. Most of the participants acquired coping techniques that continued to serve them 9 months after the end of the residential stage of Koach. One of the more important measures of Koach was thought to be the veterans' own evaluations of the project, their assessment of the project's success in achieving its aims, and their satisfaction with it. In this article we will present the subjects' evaluations of treatment effectiveness as expressed in behavioral and emotional changes that they attributed to the treatment.     

Evidence for Na+/Ca2+ exchange in the rectal gland of Squalus acanthias

Previously we have shown that stimulation of in vitro perfused rectal gland tubules (RGT) of the dog-fish Squalus acanthias by adenosine 3',5'-cyclic monophosphate (cAMP), (as a cocktail comprising 0.1 mmol/l dibutyryl-cAMP, 10 micromol/l forskolin and 0.1 mmol/l adenosine, hereafter termed STIM) leads to an increase in cytosolic Ca2+ ([Ca2+]i) and that this assists Cl- secretion by enhancing basolateral K+ conductance. In the present study we examined the mechanism of the cAMP-induced increase in [Ca2+]i. [Ca2+]i was measured using the fura-2 technique in isolated in vitro perfused RGT. As before, STIM enhanced [Ca2+]i. This elevation of [Ca2+]i was prevented completely when STIM was added in the presence of the Na+2Cl-K+ cotransport inhibitor furosemide (0.5 mmol/l). This suggests that the increase in [Ca2+]i induced by STIM is caused by a concomitant increase in cytosolic Na+ ([Na+]i) and not by the activation of second messenger cascades. Furosemide prevents this increase in [Na+]i and hence the elevation of [Ca2+]i. Moreover, the plateau phase of the [Ca2+]i transient produced by carbachol (CCH, 0.1 mmol/l) was augmented strongly when bath Na+ was reduced to 5 mmol/l. These data suggest that the level of [Ca2+]i is determined by Na(+)-dependent Ca2+ export, most likely via a Na+/Ca2+ exchanger. The increase in [Na+]i accompanying stimulation of Cl- secretion reduces the rate of Ca2+ export leading to an elevation of [Ca2+]i, as does a reduction in bath Na+ which augments the [Ca2+]i plateau produced by CCH.     

Malignancy may adversely influence the quality and behaviour of oocytes

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age- matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.      

Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

Background  

The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.     

KCNE1 reverses the response of the human K+ channel KCNQ1 to cytosolic pH changes and alters its pharmacology and sensitivity to temperature

Previous studies have shown that heteromultimeric KCNQ1/KCNE1 (KvLQT1/minK) channels and homomultimeric KCNQ1 (KvLQT1) channels exhibit different current properties, e.g. distinct kinetics and different sensitivities to drugs. In this study we report on the divergent responses to internal pH changes and further characterize some of the current properties of the human isoforms of KCNQ1 and KCNE1 expressed in Chinese hamster ovary (CHO) cells or Xenopus laevis oocytes. Decreasing the bath temperature from 37 degrees C to 20 degrees C increased the half-activation time by a factor of 5 for KCNQ1/KCNE1 currents (IKs) but by only twofold (not significant) for KCNQ1 currents (IK) in CHO cells. Acidification of cytosolic pH (pHi) increased IKs but decreased 1K whereas intracellular alkalinization decreased I(Ks) but increased IK. pHi-induced changes in intracellular Ca2+ activity ([Ca2+]i) did not correlate with the current responses. At 20 degrees C mefenamic acid (0.1 mM) significantly augmented IKs but slightly decreased IK. It changed the slow activation kinetics of I(Ks) to an instantaneous onset. The form of the current/voltage (I/V) curve changed from sigmoidal to almost linear. In contrast, at 37 degrees C, mefenamic acid also increased I(Ks) but slowed the activation kinetics and shifted the voltage activation to more hyperpolarized values without markedly affecting the sigmoidal shape of the I/V curve. The potassium channel blockers clotrimazole and tetrapentylammonium (TPeA) inhibited I(Ks) with a lower potency than I(K). These results show that coexpression of KCNE1 reversed pH regulation of KCNQ1 from inhibition to activation by acidic pHi. In addition, KCNE1 altered the pharmacological properties and sensitivity to temperature of KCNQ1. The pH-dependence of I(Ks) might be of clinical and pathophysiological relevance in the pathogenesis of ischaemic cardiac arrhythmias.     

Orofaciodigital syndrome--a new variant? Psychiatric, neurologic and neuroradiological findings

Oral-facial-digital (OFD) syndromes are a heterogeneous group of inherited syndromes that have in common anomalies of the face (median cleft lip), the tongue (bifid or lobulated tongue with harmartomas), and the digits (brachydactyly, polydactyly, syndactyly). Due to more or less subtle clinical features, at least seven causally different entities can be identified: 1) OFDS I; 2) OFDS II (Mohr syndrome); 3) OFDS III; 4) OFDS with tibial anomalies (OFDS IV); 5) OFDS V (Thurston syndrome); 6) OFDS VI (Váradi syndrome); and 7) OFDS VII (Whelan syndrome). The neuro-psychiatric clinical observations and MRI findings of a 40 year old woman with a OFD syndrome are described. The observed findings (leukoaraiosis, epilepsy, major depression) in combination with a proven OFD syndrome possibly reflect a new type of OFD syndrome.