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In this report, we describe the implementation and application of a fully automated segmentation routine using SPM99 algorithms and MATLAB for clinical Magnetic Resonance Spectroscopic Imaging (MRSI) studies. By segmenting high-resolution 3-D image data and coregistering the results to the spatial localizer slices of a spectroscopy examination, the program offers the possibility to easily calculate segmentation maps for a large variety of MRSI experiments. The segmented data are corrected for the individual point-spread function, slice and VOI profiles for measurement sequences with selective pulses as well as for the chemical shifts of different metabolites. The new method was applied to investigate discrete hippocampal metabolite abnormalities in a small sample of schizophrenic patients in comparison to healthy controls (15 patients, 15 controls). Only after correction was the N-acetyl-aspartate (NAA) signal significantly lower in patients compared to controls. No differences were found for the corrected signals from the creatine/phosphocreatine (Cr) or choline-containing compounds (Ch). These results are in good agreement with neuropathological and previous MR spectroscopy studies of the hippocampus in schizophrenic patients. [Copyright &y& Elsevier]

The morphological changes in thin-layer tissues of Nicotiana tabacum L. cv. Samsun, cultured on Murashige and Skoog medium with 1 μM each of naphthalene acetic acid (NAA) and benzyladenine (BA), were studied during the first 8 days of culture with light and scanning electron microscopy. The first three days of culture are characterized by enlargement of all cells and cell divisions starting in the cortical parenchyma cells adjacent to the medium. Between days 3 and 6. epidermal and/or subepidermal cells start to divide, resulting in division centers, which lead to flower bud formation. The hormones NAA and BA in different concentrations affect the formation and distribution of flower buds, bud morphology and callus formation. BA influences particularly bud formation and bud morphology, while NAA affects callus formation in particular. In addition, polarity may occur in the formation of both callus and flower buds, the degree of which depends upon the hormone concentrations. [ABSTRACT FROM AUTHOR]

The in vitro development of flower buds was studied on tissue explants of epidermis and subepidermal cortex from the flower stalks of Nicotiana tabacum L. cv. Samsun. The number of flower buds formed depended mainly on cytokinin concentration. Auxin acted as a modifier in a complex way. In early development, NAA at 1 μM decreased the number of buds initiated and delayed bud emergence. At a later stage, auxin promoted bud outgrowth at the same concentration. Optimal results were obtained when explants were first incubated at low auxin concentration for 3-5 days and subsequently transferred to an elevated auxin level. Physiological processes that lead to flower bud initiation start very soon after the onset of incubation. This was inferred from experiments whereby explants were first cultured at an inductive cytokinin concentration and then transferred to a non-inductive hormone level. [ABSTRACT FROM AUTHOR]

Eph-receptors represent the largest family of receptor tyrosine kinases. Eph-receptors and their cognate ephrin-ligands are cell-surface proteins, which are able to generate bidirectional signaling. Eph/ephrin interactions are essential in a variety of processes like tumor biology and inflammation. However, the impact of Eph/ephrin-interactions in the pathophysiology of atherosclerosis is still not well understood. The aim of the present study was to investigate the involvement of the Eph/ephrin-system in the TNF-α mediated monocyte adhesion.Human umbilical vein endothelial cells (HUVEC) were treated with TNF-α and the expression of different ephrin-ligands and Eph-receptors was analyzed on mRNA and protein level. EphrinA1 was found to be highly induced by TNF-α stimulation. This induction is mediated by NFkB, as overexpression of a constitutive active IkB mutant completely abolished the ephrinA1 induction. Previous results of our group showed an involvement of ephrinA1 in the process of monocyte adhesion to endothelial cells. Therefore, the impact of TNF-α mediated ephrinA1 induction in monocyte adhesion was studied. The siRNA-mediated silencing of ephrinA1 in endothelial cells, leads to a reduction of monocyte adhesion to TNF-α stimulated endothelial cells. Using a Single-Cell-Force-Spectroscopy approach we could confirm these results. The detachment forces of monocytes from endothelial cells increase after TNF-α stimulation and more importantly were decreased in ephrinA1-silenced endothelial cells. The decrease in monocyte adhesion was accompanied by reduced cell-surface expression of VCAM-1 and ICAM-1 in TNF-α-stimulated and ephrinA1-silenced cells compared to control-transfected cells. Interestingly, the overall expression of VCAM-1 and ICAM-1 on mRNA and protein level was not influenced by ephrinA1 silencing. In contrast, the overexpression of ephrinA1 in endothelial cells shows contrary effects. Ephrin-A1 overexpression enhances the TNF-α mediated monocyte adhesion to endothelial cells as well as the detachment forces.In conclusion, these data demonstrate that endothelial ephrinA1 is induced by TNF-α in a NFkB dependent manner. This induction of ephrinA1 by TNF-α in endothelial cells represents a crucial part of the proadhesive effect of TNF-α on monocytes. Mechanistically it can be shown, that ephrinA1 regulates the trafficking of adhesion molecules and therefore the presentation on the cell surface of endothelial cells. These results might open perspectives by defining a new role of ephrinA1 in TNF-α induced inflammatory processes like monocyte adhesion in atherosclerotic plaques. [ABSTRACT FROM PUBLISHER]

Background.Previous research on impulsivity in borderline personality disorder (BPD) has revealed inconsistent findings. Impulsive behaviour is often observed during states of emotional distress and might be exaggerated by current attention deficit hyperactivity disorder (ADHD) symptoms in individuals with BPD. We aimed to investigate different components of impulsivity dependent on stress induction controlling for self-reported ADHD symptoms in BPD.Method.A total of 31 unmedicated women with BPD and 30 healthy women (healthy controls; HCs), matched for age, education and intelligence, completed self-reports and behavioural tasks measuring response inhibition (go/stop task) and feedback-driven decision making (Iowa Gambling Task) under resting conditions and after experimental stress induction. ADHD symptoms were included as a covariate in the analyses of behavioural impulsivity. Additionally, self-reported emotion-regulation capacities were assessed.Results.BPD patients reported higher impulsive traits than HCs. During stress conditions – compared with resting conditions – self-reported impulsivity was elevated in both groups. Patients with BPD reported higher state impulsivity under both conditions and a significantly stronger stress-dependent increase in state impulsivity. On the behavioural level, BPD patients showed significantly impaired performance on the go/stop task under stress conditions, even when considering ADHD symptoms as a covariate, but not under resting conditions. No group differences on the Iowa Gambling Task were observed. Correlations between impulsivity measures and emotion-regulation capacities were observed in BPD patients.Conclusions.Findings suggest a significant impact of stress on self-perceived state impulsivity and on response disinhibition (even when considering current ADHD symptoms) in females with BPD. [ABSTRACT FROM AUTHOR]

In the first three months after Transcatheter aortic valve implantation (TAVI), a remarkable number of patients have an unfavorable outcome. An inflammatory response after TAVI is suspected to have negative effects. The exact mechanisms remain unclear. We examined the influence of monocyte subpopulations on the clinical outcome, along with the degree of monocyte activation and further parameters of inflammation and platelet activation. Flow-cytometric quantification analyses of peripheral blood were done in 120 consecutive patients who underwent TAVI (one day before TAVI and on day 1 and 7 after TAVI). Monocyte-subsets were defined by their CD14 and CD16 expression, monocyte-platelet-aggregates (MPA) by CD14/CD41 co-expression. The extent of monocyte activation was determined by quantification of CD11b-expression (activation epitope). Additionally, pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, C-reactive protein were measured with the cytometric bead array method or standard laboratory tests. Elevated Mon2 (CD14++CD16+) - monocytes (38 vs. 62 cells/μl, p < 0.001) and a high expression of CD11b prior to TAVI (MFI 50.1 vs. 84.6, p < 0.05) were independently associated with death 3 months after TAVI. Mon2 showed the highest CD11b-expression and CD11b correlated with platelet activation and markers of systemic inflammation. Even CRP and IL-8 before TAVI were associated with death after TAVI. In contrast, a systemic inflammation response shortly after TAVI was not associated with early death. Elevated Mon2-monocytes and a high level of monocyte activation before TAVI are associated with early mortality after TAVI. Chronic inflammation in aging patients seems to be an important risk factor after TAVI. • An elevated content of Mon2 monocytes are associated with death after TAVI. • CD11b-expression on monocytes, as sign of enhanced cellular activity before TAVI, are associated with death after TAVI as well. • Mon2 and CD11b before TAVI may disclose a use as biomarkers and function as possible therapeutic targets in the future. • A systemic inflammatory response shortly after TAVI was not associated with worse outcome. • The kind of inflammation and the involved cells rather than the extent itself determines the survival after TAVI. [ABSTRACT FROM AUTHOR]

Objective Electroconvulsive therapy ( ECT) is a highly effective and well-tolerated therapy for severe and treatment-resistant depression. Cognitive side-effects are still feared by some patients and clinicians. Importantly, cognitive impairments are among the most disabling symptoms of depression itself. Methods Patients suffering from a severe episode of depression were treated with either ECT or treatment as usual ( TAU) in an in-patient setting. Matched healthy participants served as controls ( HC). Verbal memory was tested with the California Verbal Learning Test ( CVLT) before the specific treatment started ( ECT = 15, TAU = 16, HC = 31) and 2 months after the last ECT session or 2 months after discharge respectively. Results Before the specific treatment started, depressed patients performed substantially worse compared with HC in total, short- and long-delay recall in the CVLT, while the ECT group showed the worst performance. More severely depressed patients showed worse performances in these measures. Intriguingly, verbal memory showed a significant improvement in ECT-treated patients, but not in the other groups. No differences between the groups were found at follow-up. Conclusion Contrary to the widely feared assumption that ECT has long-term impact on memory functions, we found evidence that ECT is superior to TAU in improving verbal memory in depressed patients. [ABSTRACT FROM AUTHOR]

BackgroundImpulsivity is a core feature of borderline personality disorder (BPD) and attention deficit hyperactivity disorder (ADHD). In BPD, impulsive behavior primarily occurs under acute stress; impulse control deficits under non-stress conditions may be partly related to co-morbid ADHD. We aimed to investigate whether acute experimental stress has an impact on self-reported impulsivity, response inhibition (action withholding, action cancelation) and delay discounting in BPD compared to ADHD.MethodThirty female BPD patients, 28 female ADHD patients (excluding patients with co-morbid BPD and ADHD), and 30 female healthy controls (HC) completed self-reports and behavioral measures of impulsivity (IMT, assessing action withholding; GoStop, measuring action cancelation, Delay Discounting Task) under baseline conditions and after an experimental stress induction (Mannheim Multicomponent Stress Test).ResultsBoth patient groups reported higher impulsivity than HC, ADHD reported higher trait impulsivity than BPD. On the IMT, ADHD showed significant action-withholding deficits under both conditions, while BPD performed significantly worse than HC under stress. In BPD but not ADHD and HC, action-withholding deficits (IMT) were significantly increased under stress compared to baseline, while no group/stress effects were found for action cancelation (GoStop). Delay discounting was significantly more pronounced in BPD than in HC (no stress effect was found).ConclusionsIn BPD, behavioral deficits in action withholding (but not in action cancelation) appear to be influenced by acute experimental stress. Delay discounting seems to be a general feature of BPD, independent of co-morbid ADHD and acute stress, possibly underlying typical expressions of behavioral impulsivity in the disorder. [ABSTRACT FROM PUBLISHER]

The Eph-family, consisting of Eph-receptors and ephrin-ligands represents the largest class of receptor tyrosine-kinases. The role of Eph/ephrins in elementary physiological processes as re-endothelialisation is still not well understood. The aim of the present study was to investigate the regulation of the ligand ephrin-A1 and its potential impact on proliferation and migration of human umbilical venous (HUVEC) and arterial endothelial cells (HUAEC).Initially, it could be shown, that ephrin-A1 expression was positively correlated with the density of the endothelial cells. Thus, a significant induction of ephrin-A1 in endothelial cells was observed after contact inhibition. The impact of ephrin-A1 on endothelial proliferation and migration was studied using siRNA and adenoviral overexpression. The siRNA-mediated silencing of ephrin-A1 in HUVEC increased the proliferation. In contrast, adenoviral overexpression of ephrin-A1 decreased the proliferation, suggesting an involvement of ephrin-A1 in endothelial proliferation. To study the role of ephrin-A1 in processes associated with an endothelial defect, a wound healing assay was performed. Ephrin-A1-silenced HUVEC showed a faster gap area closure in comparison to cells transfected with a scrambled control siRNA. Interestingly, ephrin-A1-overexpressing endothelial cells showed a faster gap area closure compared to lacZ-control as well. Using live cell imaging it could be visualized that the silencing of ephrin-A1 influences the direction of the migration of HUVEC resulting in disorientation and a missing polarization of the cells. Overexpression of ephrin-A1 leads to a straight forward and faster migration compared to the controls. By using baculoviral expression of actin-GFP and talin-RFP accordingly both the silencing and the overexpression of ephrin-A1 resulted in an increased number of endothelial focal adhesions which also influenced the actin-cytoskeleton in endothelial cells. A migration assay was established to investigate endothelial response to contact with an ephrin-A1-coated surface. A temporary stop of migration was observed after surface coating with ephrin-A1-Fc. Taken together, these results show that ephrin-A1-expression depends on cell-density and is a critical determinant of endothelial proliferation. Furthermore, ephrinA1 is involved in the regulation of migration of cells, by modulating the speed of migration and more importantly the direction of migration. These results show, that ephrinA1 is highly involved in the process of wound healing which is amongst others of great importance for re-endothelialisation. [ABSTRACT FROM AUTHOR]

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-β42 (Aβ42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aβ42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aβ42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production. [ABSTRACT FROM AUTHOR]

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of alcohol induced neurotoxicity, and neuroprogenetor cell expansion during recovery from alcohol dependence. [ABSTRACT FROM AUTHOR]