Programmed cell death of myelin basic protein-specific T lymphocytes is reduced in patients with acute multiple sclerosis

We investigated the apoptosis of myelin basic protein (MBP)-specific T lymphocytes in multiple sclerosis (MS) patients with acute (AMS) or stable (SMS) MS by evaluating the expression of apoptosis markers on peripheral cells. Cells of healthy controls (HC) were evaluated as well. Results showed that mitogen-stimulated apoptosis was comparable among patients and controls, whereas MBP-stimulated CD4+ and CD8+ 7-AAD+ and 7-AAD+ Fas+ cell (apoptotic cells) were significantly reduced in AMS patients. A reduction of the apoptotic rate of myelin-specific CD4+ and CD8+ T lymphocytes could be involved in the immune-mediated destruction of the myelin sheath seen in AMS patients.     

Preferential expression and function of Toll-like receptor 3 in human astrocytes

In contrast to other tissues, the central nervous system (CNS) is essentially devoid of MHC expression and shielded from antibodies by the blood-brain barrier. Therefore, a rapid local innate immune response by resident brain cells is required to effectively fight infectious agents. This study analyzed the expression and function of Toll-like receptors (TLRs) in cultured human astrocytes. Quantitative PCR for TLRs 1 to 10 showed a basal expression of TLR3 that could be enhanced by IFN-gamma, IL-1beta, and IFN-beta. The other TLRs were barely detectable and not inducible by the same cytokines. IFN-gamma-activated astrocytes responded to TLR3 ligand poly (I:C) engagement with IL-6 production, while ligands of other TLRs, like LPS, lipoteichoic acid, peptidoglycan, flagellin, and CpG, had no effect. Poly (I:C) also triggered astrocyte production of TNF-alpha and the chemokines CCL2/MCP-1, CCL5/RANTES, CCL20/MIP-3alpha, and CXCL10/IP-10. The adapter molecules MyD88 (full length and short isoform), TIRAP/Mal, and TICAM-1/TRIF, which are required for TLR signaling, were all expressed by astrocytes. Thus, resting and activated human astrocytes express preferentially TLR3 and, upon TLR3 engagement, produce IL-6 and chemokines active on T cells, B cells, monocytes, and dendritic cells. These data indicate that astrocytes function as sentinels for viral infections in the CNS.     

Patterns of clinical use of antipsychotics in hospitalized psychiatric patients

The ways of using antipsychotic drugs have greatly changed over the last 10 years. The aim of this study was to evaluate such changes in psychiatric patients admitted to the Psychiatric Department of Milan's Ospedale Maggiore in 1989 (n=350), 1999 (n=718) and 2002 (n=628). The medical records of the hospitalized patients were evaluated by analyzing the anamnestic and clinical data with particular reference to age, gender, diagnosis and medication use. In 2002, atypical antipsychotics were more frequently prescribed as monotherapy upon discharge than typical antipsychotics (32.64% vs. 30.10%). Combinations of two or more antipsychotic drugs were prescribed upon discharge for 20.63% of the patients in 1989, 31.24% in 1999 and 23.09% in 2002. The combinations of one typical and one atypical drug increased from 4.04% in 1999 to 13.06% in 2002. The mean (+/-S.D.) daily antipsychotic drug dose (expressed in chlorpromazine equivalents) was significantly higher in 2002 than in 1999 and 1989. The results of this study confirm the trend to use combinations of one typical and one atypical antipsychotic, and higher doses.     

Grammatical gender in the brain: evidence from an fMRI study on Italian

The grammatical gender of a word is a lexical-syntactic property determining agreement among different sentence parts. Recent fMRI investigations identified the areas involved in the retrieval of grammatical gender near the left Broca's area providing further evidence to confirm the preeminent syntactic role of this area. However, these studies employed categorical designs based on the controversial methodology of the cognitive subtraction of neural activations related to different tasks. In the present study we identified the neural substrates of grammatical gender assignment using an fMRI parametric study. Participants decided the grammatical gender of visually presented Italian words whose gender-to-ending regularity varied. The results showed activation in left and right fronto-temporal areas suggesting an interplay of both hemispheres in the processing of grammatical gender.     

Effects of interferon beta-1b on black holes in multiple sclerosis over a 6-year period with monthly evaluations

BACKGROUND: Chronic, hypointense black holes (BHs) are recognized as a sign of permanent damage in patients with multiple sclerosis. Although the effects of interferon beta-1b in reducing the formation of new BHs are established, it is not clear whether the drug may reduce BH duration after these lesions are formed. OBJECTIVE: To analyze the effects of interferon beta-1b in reducing the duration of T1 BHs in patients with multiple sclerosis. DESIGN: Patients were clinically assessed and imaged monthly over a 36-month natural history phase and 36-month therapy phase. Numbers of contrast-enhanced lesions and newly formed BHs were counted on each scan. Each BH was counted until it was no longer seen. SETTING: Outpatient service of the Neuroimmunology Branch at the National Institutes of Health, Bethesda, Md. PATIENTS: Six patients with relapsing-remitting multiple sclerosis were included. One patient did not form any BHs during the therapy phase. Analyses were performed on the remaining 5 individuals. INTERVENTIONS: Interferon beta-1b at the dosage of 8 million international units every other day. MAIN OUTCOME MEASURES: Number and duration (in months) of newly formed BHs. RESULTS: Rate of BH accumulation decreased with treatment (P = .01), but Kaplan-Meier models revealed that the duration of BHs did not shorten (chi2(1) = 2.47, P = .12). CONCLUSIONS: Interferon beta-1b reduces the frequency of new BH formation but does not appear to decrease their duration in time. Analyses with larger patient cohorts are needed to confirm these preliminary findings.     

A latent structure analysis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Narcissistic Personality Disorder criteria

The aim of this study was to examine the latent structure of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Narcissistic Personality Disorder (NPD) criteria in a group of 641 outpatients. The consecutively admitted outpatients were administered the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, Version 2.0, and the Personality Questionnaire. Both confirmatory and exploratory factor analyses (CFA and EFA, respectively) were used to evaluate whether the NPD criteria measure a single latent trait. Latent class analysis was used to assess the diagnostic accuracy of the individual DSM-IV NPD criteria. Mean above minus below a cut (MAMBAC) and maximum covariance (MAXCOV) taxometric analyses were used to evaluate whether the latent distribution of the DSM-IV NPD features is actually discrete. Both CFA and EFA results showed that the 9 DSM-IV NPD criteria loaded on 2 correlated factors. The latent class analysis results suggested a 3-class solution for NPD criteria; relevant differences in diagnostic efficiency were observed among the NPD criteria. MAMBAC and MAXCOV analyses provided consistent evidence of taxonic (ie, discrete) latent structure for NPD. This study gave only partial support to the validity of the DSM-IV NPD construct. Taxometric analyses indicated that a typological model is appropriate for describing NPD, but CFA and EFA suggested the existence of 2 distinct-albeit correlated-clusters of narcissistic features. As a whole, the DSM-IV criteria discriminated NPD from other personality disorders, but diagnostic accuracy statistics did not replicate the rank order of diagnostic efficiency of NPD criteria proposed by the DSM-IV.     

A naturalistic study of referred children and adolescents with obsessive-compulsive disorder

OBJECTIVE: To report on clinical features, comorbidity, and response to pharmacotherapy in children and adolescents with obsessive-compulsive disorder (OCD) naturalistically followed and treated with serotonin reuptake inhibitors (SRIs). METHOD: A consecutive series of 94 patients (65 males, 29 females, age 13.6 +/- 2.8 years), referred in the period January 2001-April 2004, diagnosed with a clinical interview (Diagnostic Interview for Children and Adolescents-Revised), and followed for 10 +/- 6 months, were included in the study. RESULTS: Contamination obsessions and washing rituals were associated with less impairment than other subtypes of OCD. Aggressive sexual obsessions and checking rituals as well as symmetry obsessions and ordering-repeating rituals were more frequently comorbid with tic disorders. According to the Clinical Global Impressions-Improvement scale (score 1 or 2), 63 subjects (67%) were responders to treatment. Nonresponders were more severely impaired and had a higher number of comorbid disorders, namely, bipolar disorder and conduct disorder (p < .05). Forty-seven patients (50%) received an SRI monotherapy, whereas the other 47 (50%) needed other medications. Patients receiving SRI monotherapy were less severely impaired; had a later onset of OCD; were at a younger age at the visit, had higher rates of depression and anxiety and lower rates of bipolar disorder, attention-deficit/hyperactivity disorder, and conduct disorder (p < .05). CONCLUSIONS: Long-term naturalistic prospective studies in pediatric patients with OCD might represent an important source of information for everyday care regarding the effectiveness of a treatment over extended periods of time under routine clinical conditions.     

Development of sensitivity to texture and contour information in the human infant

Texture discrimination and bounding contour extraction are essential parts of the object segmentation and shape discrimination process. As such, successful texture and contour processing are key components underlying the development of the perception of both objects and surfaces. By recording visual-evoked potentials, we investigate whether young infants can detect orientation-defined textures and contours. We measured responses to an organized texture comprised of many Gabor patches of the same orientation, alternated with images containing the same number of patches, but all of random orientation. These responses were compared with a control condition consisting of the alternation between two independently random configurations. Significant difference potentials were found as early as 2-5 months, as were significant odd harmonics in the test conditions. Responses were also measured to Gabor patches organized either as circles (all patches tangent to an imaginary circular path) alternated with pinwheels (all patches having a fixed orientation offset from the path). Infants between 6 and 13 months also showed sensitivity to the global organization of the elements along contours. Differential responses to our texture and contour stimuli and their controls could only have been generated by mechanisms that are capable of comparing the relative orientation of 2 or more patches, as no local information at a single patch distinguished the random and organized textures or the circle and pinwheel configurations.