The influence of immunomodulation on psycho-neuroimmunological functions in benign multiple sclerosis

OBJECTIVES: In multiple sclerosis (MS), several neuroimmunomodulatory effectors are known, including melatonin. They are able to influence disease-related neurophysiogical changes (disability or impaired vision) as well as neuropsychological performance (e.g. cognition and depression). In this study we assessed the relationship between immunomodulation on psycho-neuroimmunological functions in benign multiple sclerosis. METHODS: We evaluated 26 young female patients with benign MS treated with/without immunomodulating therapies with regard to their physical disabilities (Expanded Disability Status Scale, EDSS), their visually evoked potentials (VEP), their plasma melatonin concentrations as well as their performance regarding emotional and cognitive tests and compared them with healthy matched controls. RESULTS: Patients with MS showed deficits in cognitive and emotional functions compared to healthy controls, which were in accordance with their increase in EDSS over time. However, in contrast to untreated patients, patients receiving immunotherapy showed significantly increased dysfunction with respect to actual mood (p = 0.02) and a tendency to increased depression scores (p = 0.072). However, neither treatment subgroup had cognitive deficits. In untreated patients, melatonin levels correlated with reduced scores in the cognitive tests (p = 0.045) but not with depression or VEP latencies. Patients with long-standing MS (>10 years) showed a significant correlation (p = 0.01) to their increased depression scores and their melatonin levels, but no correlation with VEP or cognitive dysfunction, compared to patients with shorter disease duration (< or =10 years). CONCLUSION: These results indicate that in MS all aspects of the psycho-neuroimmunological network can be affected. Despite the potential influence of immunomodulation on depression, no connection with melatonin representing the retinohypothalamic tract/pineal gland circuits could be detected. However, visual perception as well as visuoconstructive abilities were affected in MS patients. Neuropsychological tests in MS should concentrate on cognitive variables, which reflect the clinical status more accurately and may be used to monitor disease-modifying therapies.     

Role of magical thinking in obsessive-compulsive symptoms in an undergraduate sample

Thought action fusion (TAF) is an important presenting feature of many individuals with obsessive-compulsive disorder (OCD). "Magical thinking" is a similar construct (developed within the literature on schizotypy) that may provide a more accurate depiction of difficulties encountered by individuals with OCD. This study seeks to examine relationships between components of magical thinking, TAF, and superstitiousness; establish the extent to which these constructs are independently related to OCD proneness; and establish the extent to which these biased reasoning styles are related to each of the major OCD symptom clusters (e.g., washing, checking). The Padua Inventory (PI), the Maudsley Obsessional-Compulsive Inventory (MOCI), the Magical Ideation Scale (MI), the Lucky Behaviours (Lbeh) and Lucky Beliefs (Lbel) Scales, and the Thought Action Fusion-Revised scale (TAF-R) were given to a cohort of 86 undergraduate students. Of all the measures, the MI scale was found to be the most strongly related to obsessive-compulsive symptoms. Large and significant relationships between MI scores and the two measures of OCD (i.e., MOCI and PI) were obtained even when alternative mediators (i.e., Lbeh, Lbel, TAF-R) were held constant. No other variable remained significantly related to the MOCI or PI when magical ideation scores were held constant. The findings suggest that a general magical thinking tendency may underpin previous observed links between superstitiousness, thought action fusion, and OCD severity.     

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-monthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P < 0.0001). Over the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. Although this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.     

Daytime behavior and sleep disturbance in childhood epilepsy

The purpose of this research is to further explore the relationship between sleep disturbance and daytime behavior in children with epilepsy. Parent-rating questionnaires and child symptom self-report measures were employed to evaluate daytime behavior in 30 children with epilepsy and sleep-disordered symptoms. Overnight polysomnography was used to assess for nocturnal sleep problems such as obstructive sleep apnea, nocturnal seizures, periodic leg movements, and sleep fragmentation. We hypothesized that children with epilepsy would exhibit both clinically significant behavioral and sleep problems. Results indicate that 80% of children with epilepsy exhibited sleep disruption because of either clinically significant obstructive apnea syndrome, disturbance of sleep architecture, or sleep fragmentation. These findings further suggest that daytime behavior problems encountered in children with epilepsy may be attributed to specific disruptions in sleep regulation.     

α-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer’s disease

The gene encoding α-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer’s disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that α-T-catenin is expressed in human brain, and like other α-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Aβ deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n>700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.     

The effects of paclitaxel on the three phases of restenosis: smooth muscle cell proliferation, migration, and matrix formation: an in vitro study

PURPOSE: We sought to evaluate the growth-modulating potential of paclitaxel on cultured human arterial smooth muscle cells depending on the administered dose. MATERIAL AND METHODS: For all experiments human arterial smooth muscle cells (SMCs) were used. SMCs were either cultured for 5 days or for 20 days with paclitaxel (doses: 10(-7) M, 10(-8) M, 10(-9) M). For a total period of 20 days, proliferation kinetics of the SMC were analyzed. To assess the clonogenic activity of the SMC colony-forming assays were performed. Drug- and dose-dependent cell cycle changes were analyzed by flow cytometry. The effect on cell migration was examined in a 2-chamber migration system. The effects of paclitaxel on the synthesis of tenascin were examined via immunofluorescence. RESULTS: Depending on the dose administered, paclitaxel proved to inhibit SMC proliferation effectively when administered during the total period of 20 days. When incubated for 5 days with doses of paclitaxel ranging between 10(-8) M and 10(-9) M, SMCs showed clear signs of regeneration. When being incubated with 10(-7) M of paclitaxel, however, SMCs reacted with a reduction in cell proliferation, a reduced clonogenic activity, and a drug-induced G2/M phase block. SMC migration was inhibited effectively as well as extracellular matrix formation. CONCLUSION: Paclitaxel is a potent inhibitor of SMC proliferation, SMC migration, and extracellular matrix formation in vitro, with all three phases of the restenosis process inhibited effectively.     

Distinct migratory behavior of early- and late-born neurons derived from the cortical ventricular zone

Time-lapse studies indicate that ventricular zone (VZ)-derived cells show two migratory modes in the cerebral cortex at different stages of mammalian embryogenesis: somal translocation and locomotion. We carried out a systematic analysis to examine whether the migratory behavior of cortical neurons derived from the cortical VZ is stage-dependent. We labeled VZ cells of mouse embryos with green fluorescent protein (gfp) -encoding plasmids by in utero electroporation and evaluated the labeled cells after appropriate survival periods. After electroporation at either embryonic day (E) 12.5 or E15.5, GFP+ VZ cells were initially spindle-shaped and radially oriented. After leaving the VZ, they transformed into round or horizontally oriented fusiform neurons with many short processes. They then seemed to gradually change into radially oriented bipolar cells as they moved upward. Whereas the earliest emigrants from the VZ labeled at E12.5 (early-born neurons) reached the top of the cortical plate (CP) after these changes, VZ cells labeled at E15.5 (late-born neurons) further migrated along the length of radial fibers to reach the top of the CP. A dominant negative form of the gene for cyclin-dependent kinase 5 (Cdk5DN) was then introduced into VZ cells. Transfection of E12.5 VZ with cdk5dn did not disrupt the migration of the early-born neurons. However, this caused a failure in migration of the late-born neurons, although they transformed into bipolar shapes in the intermediate zone. Thus, there appear to be at least two distinct migratory phases of cortical neurons: one common to the early- and late-born neurons, and the other specific to late-born neurons and Cdk5-dependent.     

Solitary pulmonary nodules: dynamic contrast-enhanced MR imaging--perfusion differences in malignant and benign lesions

PURPOSE: To determine whether dynamic contrast material-enhanced magnetic resonance (MR) imaging with use of kinetic and morphologic parameters reveals statistically significant differences between malignant and benign solitary pulmonary nodules. MATERIALS AND METHODS: Fifty-eight patients met the inclusion criteria of a solitary 5-40-mm pulmonary nodule without calcification or fat at computed tomography. Fifty-one patients were examined successfully; 46 received a histologic diagnosis, and five received a diagnosis by means of observation over 2 years. Dynamic MR images were acquired every 10 seconds for a total of 4 minutes. Diagnostic characteristics for differentiation were examined by using threshold values for maximum peak enhancement, slope of enhancement, and washout. Receiver operating characteristic curves were calculated to test the usefulness of these parameters. The diagnostic performance of a combination of curve profiles and morphologic contrast material distribution were tested by using a decision tree. RESULTS: Frequency of malignancy was 53% (27 of 51 nodules). Malignant nodules showed stronger enhancement with a higher maximum peak and a faster slope (P <.001). Significant washout (>0.1% increase in signal intensity per second) was found only in malignant lesions (14 of 27 lesions). Sensitivity, specificity, and accuracy were 96%, 88%, and 92%, respectively, for maximum peak; 96%, 75%, and 86% for slope; and 52%, 100%, and 75% for washout. When curve profiles and morphologic enhancement patterns were combined, sensitivity increased to 100%. CONCLUSION: Dynamic MR imaging delineates significant kinetic and morphologic differences in vascularity and perfusion between malignant and benign solitary pulmonary nodules. Washout seems to be highly specific for malignancy.