Top-down and bottom-up processes in the extrastriate cortex of cirrhotic patients: an ERP study.

OBJECTIVE: This study aims to evaluate the efficiency of top-down and bottom-up processes in the extrastriate cortex of cirrhotic patients without overt hepatic encephalopathy (HE). METHODS: Reaction times (RTs), accuracy and event-related potentials (ERPs) were recorded during the execution of a visual Simon task in 17 cirrhotic patients and 10 healthy controls. Amplitude and latency of the P1 and N1 (indexes of bottom-up processes) and of the N2pc (index of top-down processes) were measured. RESULTS: Patients were slower than controls, and patients with minimal HE (MHE) were slower than patients without MHE. The distribution analysis of RTs showed that the Simon effect decays with slower RTs in all the groups and that the shape of the distribution was different in MHE patients. No differences were found between cirrhotic patients and controls for P1 and N1 amplitude and latency. In contrast, N2pc latency was delayed in cirrhotic patients compared to controls independently of MHE. CONCLUSIONS: In the extrastriate cortex of cirrhotic patients without HE, top-down processes are altered whereas bottom-up processes are preserved. SIGNIFICANCE: The analysis of exogenous and endogenous visual components of ERPs provides a model to study the functional dissociation between top-down and bottom-up processes inside the extrastriate cortex.     

Metabolism and pharmacokinetics of p-(3,3-dimethyl-1-triazeno) benzoic acid in M5076 sarcoma-bearing mice

Summary The pharmacokinetics of the anticancer agent p-(3,3-dimethyl-1-triazeno) benzoic acid (pCOOH-DMT), a drug now in phase I clinical trial in Europe, was investigated in C57 Bl female mice with M5076 reticulum-cell sarcoma that were treated i.v. with 200 mg/kg pCOOH-DMT. The drug disappeared from plasma with a terminal half-life of about 2.5 h. Plasma clearance was approximately 6 ml/min per kg. Distribution studies showed some differences in drug levels in different tissues. The highest levels were found in the tumor, liver, kidney and lung; lower levels were found in the spleen and gut, and the lowest, in the brain. The N-desmethyl derivative of pCOOH-DMT was not detectable in plasma or tissues of mice treated with the drug. Therefore, the previous evidence of low N-demethylation of pCOOH-DMT was confirmed. pCOOH-DMT glucuronide was identified by mass spectrometry and quantified by high-performance liquid chromatography (HPLC) in plasma, tissues and urine samples. pCOOH-DMT glucuronide appears to be the major urinary metabolite of pCOOH-DMT in mice. Another metabolite identified by mass spectrometry and quantified by HPLC in some tissues and urine was pCOOH-DMT glycinate.Abbreviations DTIlC 5-(3,3-dimethyl-l-triazeno)imidazole-4-carboxamide - pCOOH-DMT p-(3,3-dimethyl-l-triazeno)benzoic acid - pCOOH-MMT p-(3-methyl-l-triazeno)benzoic acid - pCONH₂-DMT p-(3,3-dimethyl-l-triazeno)carboxamide - BSTFA N,O-bis(trimethylsilyl)trifluoroacetamide - TMCS trimethylchlorosilane - TLC thin-layer chromatography - FAB fast atom bombardment - EI electron impact - M5 M5076 reticulum-cell sarcoma - t_1/2 beta-half-life - C₀ concentration time 0 - AUC area under the concentration vs time curve - Cl total clearance - V volume of distribution     

CD1a and antitumour immune response

Primary immune response is based on the capacity of local professional antigen-presenting cells (whose prototype is represented by dendritic cells, DCs) to take up and present antigens to selected clones of T cells, but also to non-specific effector cells such as macrophages or natural killer cells. The four CD1 proteins, all of which share a limited homology to class I MHC proteins, are differently expressed in various cell types, of both mesenchymal and, as recently described, epithelial lineage. Regarding the role of CD1 molecules in the anti-tumour response, it has been reported that CD1+ dendritic cells are involved in the first steps of the primary immune response in a number of malignancies. Moreover, the presence of a high number of DCs in the tumoral or peritumoral area, as well as in the draining lymph nodes, has been shown to correlate with a better prognosis. A recent report on the presence of CD1a in metaplastic epithelial cells of Barrett esophagus introduced new questions about CD1a expression patterns. Moreover, the strong correlation between the lack of CD1a+ cells and the malignant evolution of the lesion may indicate a possible role of non-professional APCs in mediating and/or potentiating immune responses to tumours.     

Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency consists of fasting avoidance, and limiting long-chain fatty acid (LCFA) intake. This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11% as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters positively correlated with total LCFA intake and negatively correlated with MCT intake suggesting that as dietary intake of LCFA decreases and MCT intake increases, there is a corresponding decrease in plasma hydroxyacylcarnitines. There was no correlation between plasma acylcarnitines and level of carnitine supplementation. Dietary intake of fat-soluble vitamins E and K was deficient. Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic acid, were deficient. On this dietary regimen, the majority of subjects were healthy with no episodes of metabolic decompensation. Our data suggest that an LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate protein and limited LCFA intake (10% of total energy) while providing 10-20% of energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that includes all of the fat-soluble vitamins. The diet should be supplemented with vegetable oils as part of the 10% total LCFA intake to provide essential fatty acids.     

The enzyme responsible for the respiratory burst in elicited guinea pig peritoneal macrophages

The enzymatic basis of the respiratory burst induced by phorbol myristate acetate in elicited peritoneal macrophages of the guinea-pig has been studied. The following evidence suggests that a membrane-bound oxidase that preferentially uses NADPH as substrate is the main enzyme responsible for activation of the oxidative metabolism: (1) The supernatant of postnuclear fractions of resting macrophages oxidises NADH and NADPH with formation of O. The activity with both substrates is very low and does not change in the supernatant obtained from activated cells. (2) The cell-free particles of resting macrophages also oxidise both NADH and NADPH with formation of O. The activity of the cell-free particles from activated macrophages does not change when NADH is the substrate. By contrast, the activity of the cell-free particles from activated cells is markedly increased when NADPH is the substrate. (3) In cell-free particles from activated macrophages the K_m for NADPH is about one order of magnitude lower than that for NADH and the V_max with NADPH is double that with NADH. (4) The NADPH oxidase of cell-free particles is insensitive to azide, cyanide, antimycin A and rotenone and is sensitive to the sulphydryl reagent PCMB. All these drugs have the same effect on the respiratory response of intact macrophages. (5) A direct correlation is found between the degree of activation of the respiratory metabolism of intact macrophages and the extent of activation of the NADPH oxidase. A new approach designed to measure the activity of the oxidase soon after the activation of the enzyme has taken place, shows that the NADPH oxidase can account for the respiratory burst of intact macrophages.     

Signal-dependent wavelets for electromyogram classification

In the study, an efficient method to perform supervised classification of surface electromyogram (EMG) signals is proposed. The method is based on the choice of a relevant representation space and its optimisation with respect to a training set. As EMG signals are the summation of compact-support waveforms (the motor unit action potentials), a natural tool for their representation is the discrete dyadic wavelet transform. The feature space was thus built from the marginals of a discrete wavelet decomposition. The mother wavelet was designed to minimise the probability of classification error estimated on the learning set (supervised classification). As a representative example, the method was applied to simulate surface EMG signals generated by motor units with different degrees of short-term synchronisation. The proposed approach was able to distinguish surface EMG signals with degrees of synchronisation that differed by 10%, with a misclassification rate of 8%. The performance of a spectral-based classification (error rate approximately 33%) and of the classification with Daubechies wavelet (21%) was significantly poorer than with the proposed wavelet optimisation. The method can be used for a number of different application fields of surface EMG classification, as the feature space is adapted to the characteristics of the signal that discriminate between classes. An erratum to this article is available at .     

Time course of EEG background activity level before spontaneous awakening in infants

This research aimed to investigate the time course of the cortical activity level preceding spontaneous awakening as a function of age and state. Two groups of infants (1-4 and 9-14 weeks of age) were continuously monitored by polygraphic recording and behavioural observation during the night. The electroencephalographic (EEG) activity recorded by the C3-O1 lead was analysed through an automatic analysis method which provides, for each 30-s epoch, a single measure, time domain based, of the EEG synchronization. The EEG parameter values were computed in the 6 min preceding each awakening out of non-rapid eye movement (NREM) sleep and out of rapid eye movement (REM) sleep. The EEG background activity level did not change in the minutes preceding awakening out of REM sleep. Awakening out of NREM sleep was preceded by a change of EEG activity level in the direction of higher activation with different time course according to the age. Both REM and NREM sleep results suggest that a high level of EEG activity is a prerequisite for the occurrence of a spontaneous awakening.     

Epidemiological Investigation of Vaginal Saccharomyces cerevisiae Isolates by a Genotypic Method

Saccharomyces cerevisiae is a ubiquitous, ascomycetous yeast, and vaginitis caused by this organism has been reported only very rarely. The aim of the present investigation was to assess the epidemiological relatedness of a group of vaginal and commercial S. cerevisiae isolates by a previously reported genetic typing method, which divided the isolates into two broad groups with numerous subtypes. Nineteen S. cerevisiae isolates obtained from patients suffering from vaginitis and four isolates from commercial products in the same city were analyzed. The cellular DNA from each isolate was digested with the restriction endonuclease EcoRI, and restriction fragment length polymorphisms were generated by horizontal gel electrophoresis. The results showed that although vaginal isolates did not cluster in any particular genetic subtype, multiple patients were infected with indistinguishable strains (there were nine distinct strains among 23 isolates). For two of three patients, all three with two episodes of S. cerevisiae vaginitis, different strains were isolated during the recurrence of this disease. Three other patients with indistinguishable isolates were epidemiologically related in that two were practitioners in the same clinic and the third was a patient at this clinic. We also found that one commercial strain was indistinguishable from the strain isolated from three different women at the time that they were suffering from vaginitis. The findings of the present study suggest that some S. cerevisiae strains may possess properties permitting persistence in the human host. Furthermore, person-to-person contact and the proliferation of the use of S. cerevisiae as a health-food product, in home baking, and in home brewing may be a contributing factor in human colonization and infection with this organism.