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Aims Acute decompensated heart failure (ADHF), a live‐threatening complication of heart failure (HF), associates a further decrease of the already by HF‐impaired cardiac function with an increase in heart rate. We evaluated, using a new model of ADHF, whether heart rate reduction (HRR) opposes the acute decompensation‐related aggravation of cardiovascular dysfunction. Methods and results Cardiac output (echocardiography), cardiac tissue perfusion (magnetic resonance imaging), pulmonary wet weight, and in vitro coronary artery relaxation (Mulvany) were assessed 1 and 14 days after acute decompensation induced by salt‐loading (1.8 g/kg, PO) in rats with well‐established HF due to coronary ligation. HRR was induced by administration of the If current inhibitor S38844, 12 mg/kg PO twice daily for 2.5 days initiated 12 h or 6 days after salt‐loading (early or delayed treatment, respectively). After 24 h, salt‐loading resulted in acute decompensation, characterized by a reduction in cardiac output (HF: 130 ± 5 mL/min, ADHF: 105 ± 8 mL/min; P

Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6-thioguanine nucleotides (6-TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as follows: (a) to carry out a phenotypic study of RBC IMPDH activity in adults and children treated or not with azathioprine (AZA) for autoimmune diseases, and (b) to investigate the relationship between the activities of IMPDH, thiopurine metabolites, inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT). IMPDH activity was determined in 97 adults and 67 children treated or not with AZA. 6-Thioguanine nucleotides (6-TGN), 6-methylmercaptopurine nucleotide (6-MeMPN) levels, and ITPA as well as TPMT activities were measured in RBCs by HPLC. Using the Gaussian mixture model, distribution of IMPDH activity was evaluated. Influence of age, sex and AZA treatment on IMPDH activity was also assessed. A bimodal distribution in IMPDH activity was found with 87% of patients exhibiting normal activity and 13% of patients with high activity. No influence of age, sex and AZA therapy was found. There is no relationship between TPMT, ITPA and IMPDH activities. A negative correlation between IMPDH activity and 6-MeMPN was shown in adults and children (rs = -0.335 P = 0.014 and rs = -0.383 P = 0.012, respectively). Our results suggest that AZA-treated patients exhibiting lower IMPDH activity could have higher Me-6MPN levels with higher risk of hepatotoxicity. We demonstrated that RBC matrix could be an interesting alternative to lymphocyte matrix to monitor thiopurine metabolites and enzyme activity.

Introduction Imeglimin, a glucose‐lowering agent targeting mitochondrial bioenergetics, decreases reactive oxygen species (ROS) overproduction and improves glucose homeostasis. We investigated whether this is associated with protective effects on metabolic syndrome‐related left ventricular (LV) and vascular dysfunctions. Methods We used Zucker fa/fa rats to assess the effects on LV function, LV tissue perfusion, LV oxidative stress and vascular function induced by imeglimin administered orally for 9 or 90 days at a dose of 150 mg/kg twice daily. Results Compared to untreated animals, 9‐ and 90‐day imeglimin treatment decreased LV end‐diastolic pressure and LV end‐diastolic pressure‐volume relation, increased LV tissue perfusion and decreased LV ROS production. Simultaneously, imeglimin restored acetylcholine‐mediated coronary relaxation and mesenteric flow‐mediated dilation. One hour after imeglimin administration, when glucose plasma levels were not yet modified, imeglimin reduced LV mitochondrial ROS production and improved LV function. Ninety‐day imeglimin treatment reduced related LV and kidney fibrosis and improved kidney function. Conclusion In a rat model, mimicking Human metabolic syndrome, imeglimin immediately countered metabolic syndrome‐related cardiac diastolic and vascular dysfunction by reducing oxidative stress/increased NO bioavailability and improving myocardial perfusion and after 90‐day treatment myocardial and kidney structure, effects that are, at least in part, independent from glucose control., This study shows that imeglimin, the 1st representative of the new class of oral antidiabetic agents, glimins, immediately countered metabolic syndrome‐related cardiac diastolic and vascular dysfunction by reducing oxidative stress/increased NO bioavailability and improving myocardial perfusion, and over the long term by countering myocardial and kidney structural modifications, effects that are at least in part, independent from glucose control.

International audience; Optimal molecular diagnosis of primary dyslipidemia is challenging to confirm the diagnosis, test and identify at risk relatives. The aim of this study was to test the application of a single targeted next-generation sequencing (NGS) panel for hypercholesterolemia, hypocholesterolemia, and hypertriglyceridemia molecular diagnosis. NGS workflow based on a custom AmpliSeq panel was designed for sequencing the most prevalent dyslipidemia-causing genes (ANGPTL3, APOA5, APOC2, APOB, GPIHBP1, LDLR, LMF1, LPL, PCSK9) on the Ion PGM Sequencer. One hundred and forty patients without molecular diagnosis were studied. In silico analyses were performed using the NextGENe software and homemade tools for detection of copy number variations (CNV). All mutations were confirmed using appropriate tools. Eighty seven variations and 4 CNV were identified, allowing a molecular diagnosis for 40/116 hypercholesterolemic patients, 5/13 hypocholesterolemic patients, and 2/11, hypertriglyceridemic patients respectively. This workflow allowed the detection of CNV contrary to our previous strategy. Some variations were found in previously unexplored regions providing an added value for genotype-phenotype correlation and familial screening. In conclusion, this new NGS process is an effective mutation detection method and allows better understanding of phenotype. Consequently this assay meets the medical need for individualized diagnosis of dyslipidemia.

Background and aims This multicenter trial compared immediate‐release tacrolimus (IR‐T) vs prolonged‐release tacrolimus (PR‐T) in de novo kidney, liver, and heart transplant recipients aged

Spin-coating process of a commercially available soft thermoplastic elastomer (sTPE) is demonstrated for the realization of microfluidic prototypes. It is a reliable, wrinkling-free, and high-yield holding and transfer methodology for single and multilayered devices fabrication. Complex microfluidic systems including embedded microlenses array, dilutor-like chip for stable capillary filling, and pneumatically drive valve confirms the performances and quality of the process. The dissolved sTPE, a soft styrenic-block polymer-based material, is flexible in its raw state as poly(dimethylsiloxane) and thermoformable as classical thermoplastics. Depending on the solvent evaporation rate, two stable morphologies of the block nanodomains are revealed: either a nanocylinder or hexagonal nanospheres pattern. Both are evenly distributed over the whole surface and account for a uniform and convenient surface at a “microfluidic scale device.” Plasma hydrophilization allows a stable and hydrophilic surface (≈20° after 7 d). The biocompatibility is assessed through the cell culture proliferation assay of progenitor endothelial cells. This sTPE solution displays fast and reliable fabrication and assembly performances, it can achieve strong and stable hydrophilicity within a low level of initial equipment investment.

Rationale, aims and objectives Malnutrition screening is essential to detect and to treat patients with stunting or wasting. The aim was to evaluate the subjective perception of frequency and assessment of malnutrition by health care professionals. Research methods and procedures In a paediatric university hospital, a cross-sectional survey was conducted with a Likert scale approach to health care professionals and compared with objective measurements on a given day of frequency of malnutrition and of its screening. Results 279 health care professionals participated. The malnutrition rate, estimated versus measured, was 16.8% and 34.8%, respectively. Conversely, the estimated frequency of malnutrition screening versus measured frequency was 80.6% versus 43.1%, respectively. Furthermore, the perception of health care professionals did not differ depending on their professional category or speciality. Conclusions In conclusion, health care staff underestimates the prevalence of malnutrition in children by half and overestimates the frequency of appropriate screening practices for detection of malnutrition. This flawed/unreliable perception may disrupt both screening and the management of malnourished children. There is an urgent need to find out the reasons behind these errors caused by subjective perception in order to develop appropriate educational training to remedy the situation.

NAC proteins are plant transcription factors that are involved in tolerance to abiotic and biotic stresses, as well as in many developmental processes. Stress-responsive NAC1 (SNAC1) transcription factor is involved in drought tolerance in barley and rice, but has not been shown previously to have a role in disease resistance. Transgenic over-expression of HvSNAC1 in barley cv. Golden Promise reduced the severity of Ramularia leaf spot (RLS), caused by the fungus Ramularia collo-cygni, but had no effect on disease symptoms caused by Fusarium culmorum, Oculimacula yallundae (eyespot), Blumeria graminis f. sp. hordei (powdery mildew) or Magnaporthe oryzae (blast). The HvSNAC1 transcript was weakly induced in the RLS-susceptible cv. Golden Promise during the latter stages of R. collo-cygni symptom development when infected leaves were senescing. Potential mechanisms controlling HvSNAC1-mediated resistance to RLS were investigated. Gene expression analysis revealed no difference in the constitutive levels of antioxidant transcripts in either of the over-expression lines compared with cv. Golden Promise, nor was any difference in stomatal conductance or sensitivity to reactive oxygen species-induced cell death observed. Over-expression of HvSNAC1 delayed dark-induced leaf senescence. It is proposed that mechanisms controlled by HvSNAC1 that are involved in tolerance to abiotic stress and that inhibit senescence also confer resistance to R. collo-cygni and suppress RLS symptoms. This provides further evidence for an association between abiotic stress and senescence in barley and the development of RLS.

Objective: Recent work has focussed on schizophrenia as a ‘deficit’ state but little attention has been paid to defining illness plasticity in terms of symptomatic remission. Method: A qualitative review of a recently proposed concept of remission [N.C. Andreasen, W.T. Carpenter Jr, J.M. Kane, R.A. Lasser, S.R. Marder, D.R. Weinberger (2005) Am J Psychiatry 162: 441] is presented. Results: The proposed definition of remission is conceptually viable, and can be easily implemented in clinical trials and clinical practice. Its increasing acceptance may reset expectations of treatment to a higher level, improve documentation of clinical status and facilitate dialogue on treatment expectations. The availability of validated outcome measures based on remission will enhance the conduct and reporting of clinical investigations, and could facilitate the design and interpretation of new studies on cognition and functional outcomes. While useful as a concept, it is important to consider that remission is distinct from recovery. Conclusion: The introduction of standardized remission criteria may offer significant opportunities for clinical practice, health services research and clinical trials.

Summary. Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan–Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.

We studied brain activity during the displacement of attention in a modified visuo-spatial orienting paradigm. Using a behaviorally relevant no-shift condition as a control, we asked whether ipsi- or contralateral parietal alpha band activity is specifically related to covert shifts of attention. Cue-related event-related potentials revealed an attention directing anterior negativity (ADAN) contralateral to the shift of attention and P3 and contingent negative variation waveforms that were enhanced in both shift conditions as compared to the no-shift task. When attention was shifted away from fixation, alpha band activity over parietal regions ipsilateral to the attended hemifield was enhanced relative to the control condition, albeit with different dynamics in the upper and lower alpha subbands. Contralateral-to-attended parietal alpha band activity was indistinguishable from the no-shift task.

We report a case of long-lasting MARS therapy as a bridge to liver-kidney transplantation. A 26-month-old girl with congenital tubulointerstitial nephritis and severe liver fibrosis was placed on MARS for an acute-on-chronic liver failure due to sepsis. She underwent two sessions with good tolerance and recovered her previous neurological status. On the basis of pruritus, sleep, and vomiting improvement, repeated MARS sessions were performed to bridge her to combined liver-kidney transplantation. During eight months, 40 sessions were performed with the MARSmini kit and the MARS monitor (Gambro, Lyon, France). The treatment significantly decreased mean pruritus score from 2.2 +/- 0.9 to 0.8 +/- 0.6 night-time awakening and vomiting episodes. Body weight, height, and HC were -3.2, -3.5 and -2.2 SDS before and -1.7, -4.2, -2.0 SDS after eight months on MARS therapy, respectively. The arm circumference/HC ratio increased from 0.28 to 0.31. Mean total bilirubin serum levels were 303 +/- 72 micromol/L before and 214 +/- 42 micromol/L after MARS cycles. Long-lasting MARS dialysis is feasible in children, decreases adverse effects of severe chronic cholestasis, and may help to preserve nutritional status prior to combined liver-kidney transplantation.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, affecting 10-20% of children. Measles vaccination has been reported to have contradictory effects on incidence of AD in children. Therefore, we performed the first prospective, double-blind, placebo-controlled study to analyze the evolution of AD in infants after measles vaccination. The study included 12 infants (10-14 months old) with AD, randomly assigned to two groups: while the first group received a single dose of a standard measles vaccine ROUVAX, the second was treated with placebo (vehicle). Infants were followed-up for 6 months after administration of ROUVAX/placebo for the clinical signs associated with AD, by determination of SCORAD index. In addition, serum was taken before vaccination and 1 month later to determine the presence of seroconversion and to analyze the progression of serum levels of CCL18 (PARC) and E-selectin, known to be distinct serum markers that reflect clinical features of AD. In the vaccinated group, five of six children seroconverted 1 month after treatment and one infant showed a 50% improvement of SCORAD. Serum levels of CCL18 were significantly decreased in two treated infants (of four analyzed for this group) and E-selectin slightly decreased in one infant (of three analyzed by this test). In placebo-treated group the SCORAD improved in one patient and serum levels of CCL18 and E-selectin did not change. These data suggest that measles vaccination not only does not aggravate AD, but may also improve some of the immunological parameters of this allergic disease. Inclusion of a higher number of patients in a similar study should give a more comprehensive overview of the benefit of measles vaccination on the clinical evolution of AD patients, and potentially open new avenues to the clinical application of the anti-inflammatory effect of measles virus proteins.

A role of insulin-dependent diabetes in the onset of tardive dyskinesia has been reported and relies on weak physiopathological evidence. Objective To study the relationship between the occurrence of tardive dyskinesia and variations in glucose levels in a population of patients under typical antipsychotic treatment. Methods Sixty-nine patients with a schizophrenic disorder and who had been receiving continuous neuroleptic treatment for at least 2 years were included. Tardive dyskinesias were assessed by the Abnormal Involuntary Movements Scale (AIMS) and glucose levels by glucose oxidase method. Results No significant differences in values of fasting glucose (FG) levels, post-prandial glucose (PPG) levels and glycosylated haemoglobin between the groups with and without tardive dyskinesia were found. In the sub-group with normal FG, comparison of post-prandial delta glucose levels (difference between PPG and FG) between the two group with and without tardive dyskinesia showed a significant difference (p

Cognitive neuroscience relies on two sets of techniques to map the neural networks underlying cognition in humans: recordings of either regional metabolic changes (fMRI or PET) or fluctuations in the neural electromagnetic fields (EEG and MEG). Despite major advances in the last few years, an explicit linkage between the two is still missing and the neuroimaging community faces two complementary but unrelated sets of functional descriptions of the human brain. Such an explicit framework, linking the two approaches in potentially complex cognitive tasks and in a variety of brain regions would permit to combine them into fine spatio‐temporally‐grained human brain mapping procedures. We combined fMRI and intra‐cranial EEG recordings of the same epileptic patients during a semantic decision task and found a close spatial correspondence between regions of fMRI activations and recording sites showing EEG energy modulations in the gamma range (>40 Hz). Our findings further support previous findings that gamma band modulations co‐localize with BOLD variations and also indicate that fMRI may be used as a constraint to improve source reconstruction of gamma band EEG responses. Hum Brain Mapp, 2007. © 2007 Wiley‐Liss, Inc.

Metabolic bone disease is common in children receiving home parenteral nutrition (HPN) for intestinal failure (IF). Long-term evolution of bone mass in pediatric IF is poorly documented. The aims of this study were (1) to determine the prevalence of low bone mass (LBM) in children receiving HPN for IF, (2) to evaluate the evolution of total bone mineral content (TBMC) during HPN with dual-energy x-ray absorptiometry (DXA), and (3) to identify related factors.All children referred in our HPN center from 2004 to 2014 were eligible. Inclusion criteria were HPN dependence due to noninflammatory IF, at least 2 TBMC assessments, and HPN duration of at least 2 years at last DXA. TBMC was expressed in z score for ideal weight for height (WFH). LBM was defined by a TBMC WFH z score ≤-2 standard deviations (SD).A total of 175 DXAs for 31 children were performed, mean of 5.6 ± 2.9 assessments per child. The median time between first and last DXA recorded was 6.2 years (0.7-16.6). At the first DXA, 14 children (45%) had a LBM. TBMC increased by +0.1 ± 0.04 SD per year of HPN (P = .012). The risk of LBM decreased with an odds ratio of 0.9 per year of HPN (95% confidence interval, 0.92-0.99; P = .018). Lean mass z score and calcium parenteral intakes were related to the TBMC improvement.LBM is common in pediatric IF, but bone status could improve during HPN in these children.

Interferon-alpha (IFN) has been approved as treatment for children with chronic hepatitis B (CHB). The aims of this study were to assess the impact on children's growth of the disease itself and of IFN treatment. The growth of 142 children with CHB (70 IFN-treated, 72 untreated) was monitored for a minimum of one year. Regression analysis models were used to determine which of the variables most affected children's growth. After adjusting for racial differences, the population of 142 children with CHB had a mean baseline height for age percentile of 39 and a mean baseline weight for age percentile of 38, which were significantly different (P < 0.0001) from the 50th percentiles of their respective reference populations. The height for age Z score of untreated children was inversely correlated with serum hepatitis B virus DNA and aspartate aminotransferase levels, and the weight for age Z score was inversely correlated with serum hepatitis B virus DNA levels. While undergoing IFN therapy, children displayed a "U-shaped" growth pattern, such that height for age and weight for age Z scores at 3 or 6 months were lower than scores at baseline or 12 months. In this study the average child with CHB showed compromised growth even in the absence of IFN therapy. During IFN therapy, children's growth was temporarily disrupted.

This paper studies gamma-band responses from two implanted epileptic patients during a simple visual discrimination task. Our main aim was to ascertain, in a reliable manner, whether evoked (stimulus-locked) and induced (triggered by, but not locked to, stimuli) responses are present in intracranial recordings. For this purpose, we introduce new methods adapted to detect the presence of gamma responses at this level of recording, intermediary between EEG-scalp and unicellular responses. The analysis relies on a trial-by-trial time-frequency analysis and on the use of surrogate data for statistical testing. We report that visual stimulation reliably elicits evoked and induced responses in human intracranial recordings. Induced intracranial gamma activity is significantly present in short oscillatory bursts (a few cycles) following visual stimulation. These responses are highly variable from trial to trial, beginning after 200 ms and lasting up to 500 ms. In contrast, intracranial-evoked gamma responses concentrate around 100 ms latencies corresponding to evoked responses observed on the scalp. We discuss our results in relation to scalp gamma response in a similar protocol [Tallon-Baudry et al. (1996) J. Neurosci., 16, 4240-4249] and draw some conclusions for bridging the gap between gamma oscillations observed on the scalp surface and their possible cortical sources.

This study reports the findings of an analysis of temporal correlation between tremor of different muscles of the same and different limbs in four patients with Parkinson's disease. Spectral coherence methods were used for determining whether simultaneously occurring oscillations in the electromyograms of different muscles are statistically coupled. The incidence of significant coherence was considerably higher for muscle pairs in the same limb than for pairs in different limbs; Parkinson's disease tremor is coupled within but not between limbs. Because the characteristics of tremor are known to vary under different behavioral situations, the intralimb coupling was examined for different tasks. A mental arithmetic task resulted in an increase in the coherence between muscles of the same limb, whereas the finger-to-nose task decreased the coherence. No significant change in coherence was found for a postural task. The amplitude and regularity of tremor electromyography showed changes analogous to those in coherence. These results support the hypothesis that tremor in different limbs results from the activity of several neural circuits oscillating independently. The results also emphasize the value of these methods for rigorously characterizing tremor, in relation to disease state, behavioral conditions, and the selection of treatment strategies.

BACKGROUND: Because GB virus type C(GBV-C)/HGV (GBV-C/HGV) is blood-borne and sexually transmitted, persons at risk of infection with such viruses have a high prevalence of GBV-C/HGV markers. However, adults with no apparent risk factors, such as blood donors, frequently are positive for GBV-C/HGV markers. Mother-to-infant transmission could explain this high prevalence, but it has been studied only through small series of GBV-C/HGV-infected mothers co-infected with HCV or HIV. STUDY DESIGN AND METHODS: To determine the rate of mother-to-infant transmission of GBV-C/HGV RNA in women who are HCV- or HIV-negative, a prospective study was performed in a cohort of 288 mothers screened for viral RNA and in the infants born to GBV-C/HGV-infected mothers. RESULTS: Thirteen mothers (4.5%) were found positive for GBV-C/HGV RNA. Of the infants in whom at least one blood sample was collected between the third and the ninth months of life, 89 percent were positive for viral RNA. The majority of these newborns were negative for GBV-C/HGV RNA at birth and positive after the third month. The viral RNA titers of infants born to GBV-C/HGV-infected mothers appeared as elevated as those of their mothers. All the GBV-C/HGV-infected infants remained positive for viral RNA during the entire study period. No clinical events possibly linked to a primary GBV-C/HGV infection were reported in infants. Serum ALT level and blood count remained within normal values throughout the follow-up of all GBV-C/HGV-infected infants. CONCLUSION: The frequency of mother-to-infant GBV-C/HGV transmission is elevated and could explain the high prevalence of GBV-C/HGV markers (viral RNA and E2 antibody) in adults at low risk for blood-borne or sexually transmitted viruses, such as blood donors.

This article presents, for the first time, a practical method for the direct quantification of frequency‐specific synchronization (i.e., transient phase‐locking) between two neuroelectric signals. The motivation for its development is to be able to examine the role of neural synchronies as a putative mechanism for long‐range neural integration during cognitive tasks. The method, called phase‐locking statistics (PLS), measures the significance of the phase covariance between two signals with a reasonable time‐resolution (

Wilson disease (WD) is an autosomal recessive disorder of copper transport, manifesting as chronic liver disease and/or neurologic impairment due to accumulation of copper in several tissues, principally the liver and the brain. The WD gene encodes a copper transporting P-type ATPase that is defective in this affection. In this study, we performed DNA haplotype analysis using five polymorphic microsatellite markers (D13S295, D13S314, D13S301, D13S296, D13S316) flanking the WD locus, mutational screening on 10 exons (5, 7, 8, 9, 12, 14, 15, 17, 18, 19) by SSCP and direct sequencing in 32 WD families with hepatic and/or neurologic forms. We found nine mutations (two frameshifts, one nonsense, five missense mutations, and one in an intron), four of which were novel. The data were used to make presymptomatic diagnosis and detect carriers among siblings in the pedigrees concerned, improving genetic counselling and disease management. In addition, we tried to find a genotype-phenotype correlation in our patients. J. Trace Elem. Exp. Med. 12:321–329, 1999. © 1999 Wiley-Liss, Inc.

We report here on a first attempt to settle the methodological controversy between advocates of two alternative reconstruction approaches for temporal dynamics in brain signals: the single-channel method (using data from one recording site and reconstructing by time-lags), and the multiple-channel method (using data from a spatially distributed set of recordings sites and reconstructing by means of spatial position). For the purpose of a proper comparison of these two techniques, we computed a series of EEG-like measures on the basis of well-known dynamical systems placed inside a spherical model of the head. For each of the simulations, the correlation dimension estimates obtained by both methods were calculated and compared, when possible, with the known (or estimated) dimension of the underlying dynamical system. We show that the single-channel method fails to reliably quantify spatially extended dynamics, while the multichannel method performs better. It follows that the latter is preferable, given the known spatially distributed nature of brain processes. Hum. Brain Mapping 5:26-47, 1997. (c) 1997 Wiley-Liss, Inc.

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

Previous studies have documented a role for membrane-bound CD23 (the low affinity Fc epsilon RII) in presentation of alloantigens by B cells. The aim of the present study was to examine the involvement of cell surface CD23 in presentation of more conventional soluble protein antigens to T cells. We show that antibodies to CD23 and to its lymphocyte-associated second ligand, CD21, inhibit presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B-EBV cell lines to casein-specific HLA-DP-restricted CD4+ T cell clones obtained from patients with either reaginic or enterophatic forms of cow's milk protein intolerance. Maximal inhibition was achieved when the antibodies were added at the initiation of the culture. The absence of specific inhibition by an anti-DR alpha monoclonal antibody (mAb) argues against a steric hindrance phenomenon impeding access of the T cell receptor to major histocompatibility complex class II molecules. Rather, anti-CD23 and anti-CD21 mAb-induced inhibition of antigen presentation seems to affect at least partly, heterotypic conjugate formation through CD23/CD21 interaction. Double immunofluorescence labeling of the T cell clones and antibody inhibition of T/B conjugate formation shows that functional CD23 and CD21 molecules are induced on T cells following contact with B-EBV cell lines. Taken together, these data indicate that CD23/CD21 interactions between T and B cells are required for presentation of soluble protein antigens by B-EBV cell lines to specific CD4+ T cells. The potential implications of these findings for allergen-specific T cell activation are discussed.Previous studies have documented a role for membrane-bound CD23 (the low affinity Fc epsilon RII) in presentation of alloantigens by B cells. The aim of the present study was to examine the involvement of cell surface CD23 in presentation of more conventional soluble protein antigens to T cells. We show that antibodies to CD23 and to its lymphocyte-associated second ligand, CD21, inhibit presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B-EBV cell lines to casein-specific HLA-DP-restricted CD4+ T cell clones obtained from patients with either reaginic or enterophatic forms of cow's milk protein intolerance. Maximal inhibition was achieved when the antibodies were added at the initiation of the culture. The absence of specific inhibition by an anti-DR alpha monoclonal antibody (mAb) argues against a steric hindrance phenomenon impeding access of the T cell receptor to major histocompatibility complex class II molecules. Rather, anti-CD23 and anti-CD21 mAb-induced inhibition of antigen presentation seems to affect at least partly, heterotypic conjugate formation through CD23/CD21 interaction. Double immunofluorescence labeling of the T cell clones and antibody inhibition of T/B conjugate formation shows that functional CD23 and CD21 molecules are induced on T cells following contact with B-EBV cell lines. Taken together, these data indicate that CD23/CD21 interactions between T and B cells are required for presentation of soluble protein antigens by B-EBV cell lines to specific CD4+ T cells. The potential implications of these findings for allergen-specific T cell activation are discussed.