Kindling limits the interictal neuronal temporal response properties in cat primary auditory cortex

PURPOSE: The present study examined the effect of electrical kindling on the interictal temporal response properties of single units recorded from primary auditory cortex (AI) of the adult cat. METHODS: Cats were permanently implanted with electrodes in AI, kindled twice daily for 40 sessions, and the contralateral AI was subsequently mapped. Kindling stimulation consisted of 1-s trains of biphasic square-wave pulses applied at a frequency of 60 Hz, 100 microA above the afterdischarge (AD) threshold. The EEG activity was recorded during each kindling session, and the behavioral manifestation was scored. Subsequent to kindling, multiple single-unit responses were recorded under ketamine anesthesia in response to 1-s-long periodic click trains, with click rates between 2 and 64 Hz. Neuronal responses were characterized according to their ability to respond in time-locked fashion to the clicks. RESULTS: Kindling stimulation resulted in progression of the AD characteristics and seizure behavior, with six of 10 kindled cats reaching a fully generalized state. In the fully kindled cats, the best modulation frequencies and limiting following rates for the single-unit responses were significantly lower compared with those of naive and sham controls. CONCLUSIONS: Repeated epileptiform activity interferes with temporal processing in cat auditory cortex in the interictal state. This may have implications for people with epileptic foci in auditory-related areas.     

Simultaneous 3-T fMRI and high-density recording of human auditory evoked potentials

We acquired simultaneous high-field (3 T) functional magnetic resonance imaging (fMRI) and high-density (64- and 128-channel) EEG using a sparse sampling technique to measure auditory cortical activity generated by right ear stimulus presentation. Using dipole source localization, we showed that the anatomical location of the grand mean equivalent dipole of auditory evoked potentials (AEPs) and the center of gravity of fMRI activity were in good agreement in the horizontal plane. However, the grand mean equivalent dipole was located significantly superior in the cortex compared to fMRI activity. Interhemispheric asymmetry was exhibited by fMRI, whereas neither the AEP dipole moments nor the mean global field power (MGFP) of the AEPs showed significant asymmetry. Increasing the number of recording electrodes from 64 to 128 improved the accuracy of the equivalent dipole source localization but decreased the signal-to-noise ratio (SNR) of MR images. This suggests that 64 electrodes may be optimal for use in simultaneous recording of EEG and fMRI.     

Characterization of iron deposition in endometriotic lesions induced in the nude mouse model

BACKGROUND: Pelvic endometriotic lesions are often laden with hemosiderin. In order to investigate the potential source of such iron deposits, we examined whether the seric and erythrocyte fractions of menstrual effluent might influence the occurrence of iron deposition within lesions in a murine model of endometriosis. METHODS: Endometriosis was induced in 57 nude mice by intraperitoneal injection of unfractionated human menstrual effluent, endometrial fragments plus serum, endometrial fragments plus erythrocytes or endometrial cell fraction alone. The number of implants, histologic aspect, proliferative activity and iron deposition in lesions was assessed. RESULTS: On day 5, lesions were evidenced in all 10 mice receiving menstrual effluent, in 9/13 of those injected with the cellular fraction, in 10/13 with the cellular fraction plus serum and in 10/12 with the cellular fraction plus erythrocytes. Iron conglomerates were observed at the interface between the lesion and peritoneum when menstrual effluent (47 deposits/mm(2)) and the cellular fraction with erythrocytes (20 deposits/mm(2)) were injected, but were scarce when the cellular fraction was injected without erythrocytes, either alone (4 deposits/mm(2)) or with serum (2 deposits/mm(2)) (P < 0.05). CONCLUSIONS: Iron conglomerates, typically found in the stroma of endometriotic lesions, were induced by erythrocytes present in menstrual effluent. This may be one of the factors triggering oxidative damage and chronic inflammation.     

Impaired neutralising antibody formation and high transduction efficacy after isolated hepatic perfusion with adenoviral vectors

Local adenoviral gene transfer can be performed by means of isolated hepatic perfusion (IHP). This methodology is a very effective and safe way to deliver adenoviral vectors. We studied the immune response after IHP. A decreased neutralising antibody formation was observed, offering possibilities for further research in the field of gene therapy in isolated perfusion settings.     

Involvement of endothelial monocyte activating polypeptide II in tumor necrosis factor-alpha-based anti-cancer therapy

In 1990 Clauss et al. first reported on a 44-kDa polypeptide, later called Endothelial Monocyte Activating Polypeptide II (EMAP II). This protein was discovered in the supernatant of Meth-A fibrosarcoma cells and was shown to enhance the induction of the procoagulant Tissue Factor (TF) on endothelial cells. Besides up-regulation of TF mRNA, EMAP II increases cellular receptors for TNF on endothelial cells, which is likely to enhance the predisposition of tumors to undergo thrombosis and hemorrhagic necrosis, once challenged with TNF. This feature enables EMAP II to up-regulate the TNF sensitivity of TNF-resistant tumors, an observation of importance in developing new approaches aimed at improving the efficacy of TNF as an anticancer treatment. We describe the potential additional effects of EMAP II, when used in combination with TNF, with regards to antitumor activity in the Isolated Limb Perfusion (ILP) setting. In addition, we describe our experimental data in human sarcoma, which also supports this hypothesis.     

The role of isolated limb perfusion for melanoma confined to the extremities

Isolated limb perfusion with Melphalan is the best treatment option to control symptomatic multiple small in-transit metastases. When lesions are bulky, Isolated Limb Perfusion (ILP) with Tumor Necrosis Factor (TNF) + Melphalan is superior as in soft tissue sarcoma. TNF changes the pathophysiology, greatly enhances the uptake of Melphalan and destructs selectively the vasculature of large tumors. To date, ILP is not indicated in an adjuvant setting.     

Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report

Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3 protein combined with a fixed dose of the immunological adjuvant SBAS-2, which contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.) injections at 3-week intervals. Patients whose tumour stabilised or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The vaccine was generally well tolerated. Among the 33 melanoma patients who were evaluable for tumour response, we observed 2 partial responses, 2 mixed responses and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29 months. In addition, a partial response lasting 10 months was observed in 1 of the 3 metastatic bladder cancer patients included. None of the tumour responses described above involved visceral metastases. Immunological responses to the vaccine will be reported separately.     

Bilirubin-IXbeta is a marker of meconium, like zinc coproporphyrin

BACKGROUND: Because meconium accumulates continuously in the fetal intestine, analysis of the postnatally excreted material could yield important information of intrauterine metabolism and maturation. Therefore, a study of the bilirubin pigments in meconium and in the first neonatal stools was carried out. METHODS: Meconium and stools from 37 neonates of various gestational ages were collected carefully, and stored at -20 degrees C, protected by aluminium foil. Samples were defrosted, vortex mixed with an equal amount of dimethyl sulfoxide, centrifuged, and submitted to analysis by high-pressure liquid chromatography using newly developed methods to identify and to quantitate the bilirubin-IXalpha, -IXbeta, -IXgamma, and -IXdelta isomers. In addition, samples were also submitted to diazo coupling with ethyl anthranilate. Total coproporphyrins and zinc coproporphyrin were assayed for comparison. RESULTS: Unconjugated bilirubin-IXalpha and -IXbeta were detected in meconium but not the -IXgamma or the -IXbeta isomer. Bilirubin-IXbeta was the predominant pigment and comprised 63% to 96% of the unconjugated bilirubins in the first sample of meconium excreted. Its amount decreased rapidly during the first 5 days in full-term newborns, but this occurred more slowly in preterm neonates, especially in those with a gestational age less than 30 weeks. The decrease of bilirubin-IXbeta over time correlated with that of coproporphyrin. CONCLUSIONS: Bilirubin-IXbeta is the prevailing bile pigment in the first excreted sample of meconium. It gradually decreases after birth and can be considered a biochemical marker of meconium, like zinc coproporphyrin.     

Between sound and perception: reviewing the search for a neural code

This review investigates the roles of representation, transformation and coding as part of a hierarchical process between sound and perception. This is followed by a survey of how speech sounds and elements thereof are represented in the activity patterns along the auditory pathway. Then the evidence for a place representation of texture features of sound, comprising frequency, periodicity pitch, harmonicity in vowels, and direction and speed of frequency modulation, and for a temporal and synchrony representation of sound contours, comprising onsets, offsets, voice onset time, and low rate amplitude modulation, in auditory cortex is reviewed. Contours mark changes and transitions in sound and auditory cortex appears particularly sensitive to these dynamic aspects of sound. Texture determines which neurons, both cortical and subcortical, are activated by the sound whereas the contours modulate the activity of those neurons. Because contours are temporally represented in the majority of neurons activated by the texture aspects of sound, each of these neurons is part of an ensemble formed by the combination of contour and texture sensitivity. A multiplexed coding of complex sound is proposed whereby the contours set up widespread synchrony across those neurons in all auditory cortical areas that are activated by the texture of sound.     

Adjuvant interferon-alpha for melanoma revisited: News?from?old?and?new?studies

Currently the data from 12 randomised phase III trials investigatingthe role of interferon-alpha (IFN-2a) in patients with stageII–III high-risk melanoma are available. The most prominentdifferences between these trials concern the dose of IFN-2a, theduration of IFN-2a administration, and the stage of disease. Some ofthese trials have not yet reached maturity, but despite this thepositive results from some immature trials have attracted considerableattention. When only data from mature trials is considered, one mayconclude that the use of high-dose IFN-2a does prolong disease-freesurvival (DFS) but not overall survival (OS). Combined data fromlow-dose IFN-2a trials does not suggest a benefit in either DFS or OS.A trial with intermediate-dose IFN-2a is still immature. Thereforecurrently the routine use of IFN-2a cannot be recommended outside thescope of clinical trials.