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  • 1
    Keywords: brain ; Germany ; DIAGNOSIS ; IMAGES ; SYSTEM ; VOLUME ; PATIENT ; MRI ; SEQUENCE ; DISORDER ; ECHO ; AGE ; INDIVIDUALS ; ABNORMALITIES ; SECTIONS ; ADULT ; ADULTS ; CORTEX ; structure ; female ; CHILD ; ADOLESCENTS ; VOXEL-BASED MORPHOMETRY ; 3 ; RANGE ; gray matter ; white matter ; voxel based morphometry ; A ; Adolescent
    Abstract: There is evidence that adults with borderline personality disorder (BPD) are characterized by abnormalities in frontolimbic brain areas. In this study we aimed to determine whether brain volume alterations already exist in adolescents with BPD. Sixty female right-handed individuals (age range, 14-18 years), 20 with a DSM-IV diagnosis of borderline personality disorder, 20 patients with a DSM-IV defined current psychiatric disorder and 20 healthy control subjects were included. Groups were matched for age and IQ. Using a 3 T MRI scanner, we collected 1 mm axial sections using a three-dimensional sagittal isotropic Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE) sequence. Images were analyzed using voxel-based morphometry (VBM). Voxel-based analysis revealed that adolescents with BPD showed reduced gray matter in the dorsolateral cortex (DLPFC) bilaterally and in the left orbitofrontal cortex (OFC) relative to healthy control subjects. Adolescent clinical control subjects displayed significantly decreased gray matter volume in the right DLPFC in comparison with healthy control subjects. No significant gray matter differences were detected between the BPD group and the clinical control group. No group differences were found in the limbic system or in any white matter structures. The present study indicates that the early morphological changes in BPD are located in the PFC. However, these changes may not be BPD specific since similar changes were found in the clinical control group. Changes in limbic brain volumes and white matter structures might occur over the course of the illness
    Type of Publication: Journal article published
    PubMed ID: 19660555
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  • 2
    Keywords: SCHIZOPHRENIA ; PATTERNS ; AMYGDALA ; METAANALYSIS ; depression ; INTEGRITY ; MEDIAL TEMPORAL-LOBE ; CONNECTIVITY ; SPATIAL STATISTICS ; HANDEDNESS
    Abstract: BACKGROUND: The pathogenesis of borderline personality disorder (BPD) is complex and not fully understood. Using diffusion tensor imaging, recent studies suggest that white matter abnormalities may occur in adult patients with BPD. However, deeper insight into the disorder-specific developmental psychobiology (e.g., analysis of adolescents with BPD; inclusion of clinical control groups) is missing. METHODS: Twenty adolescent patients with BPD (aged 14-18 years), 20 healthy, and 20 clinical control subjects were assessed using diffusion tensor imaging. All subjects were right-handed girls, matched for age and IQ. Microstructural parameters were analyzed via tractography of the main bundles in the limbic system and using Tract-Based Spatial Statistics, an explorative, global approach. RESULTS: BPD was associated with decreased fractional anisotropy in the fornix when compared with clinical (p 〈 .001) or healthy (nonsignificant trend) control subjects. Using Tract-Based Spatial Statistics, significant disorder-specific white matter alterations were found in the long association bundles interconnecting the heteromodal association cortex and in connections between the thalamus and hippocampus. CONCLUSIONS: The study strongly supports the hypothesis that white matter alterations play a key role in the pathogenesis of BPD. These disorder-specific alterations include white matter pathways involved in emotion regulation but also affect parts of the heteromodal association cortex that are related to emotion recognition. Our findings unify previously documented deficits in emotion recognition and regulation and suggest that a large-scale network of emotion processing is disrupted in BPD. Continued research is essential to evaluate the predictive value of these early disruptions in a clinical context.
    Type of Publication: Journal article published
    PubMed ID: 23768862
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  • 3
    Keywords: INHIBITOR ; DISCOVERY ; VECTORS ; RELATE 2 SETS ; HYDROLASE ; HYDROLASE/AMINOPEPTIDASE ; ROTATION
    Abstract: The pharmacophore concept is commonly employed in virtual screening for hit identification. A pharmacophore is generally defined as the three-dimensional arrangement of the structural and physicochemical features of a compound responsible for its affinity to a pharmacological target. Given a number of active ligands binding to a particular target in the same manner, it can reasonably be assumed that they have some shared features, a common pharmacophore. We present a growing neural gas (GNG)-based approach for the extraction of the relevant features which we called PENG (pharmacophore elucidation by neural gas). Results of retrospective validation indicate an acceptable quality of the generated models. Additionally a prospective virtual screening for leukotriene A4 hydrolase (LTA4H) inhibitors was performed. LTA4H is a bifunctional zinc metalloprotease which displays both epoxide hydrolase and aminopeptidase activity. We could show that the PENG approach is able to predict the binding mode of the ligand by X-ray crystallography. Furthermore, we identified a novel chemotype of LTA4H inhibitors.
    Type of Publication: Journal article published
    PubMed ID: 25625859
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  • 4
    Keywords: GENE ; PROTEIN ; transcription ; DNA ; TRANSFORMING ACTIVITY ; CERVICAL-CARCINOMA CELLS ; INSITU HYBRIDIZATION ; FACTOR-ALPHA ; EPIDERMAL GROWTH-FACTOR ; LINKAGE MAP
    Abstract: The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cloned amplified cellular sequences from the mouse cell line Eb that cross-hybridized with the E5 ORF of HPV 18. A 2.1-kb fragment termed HC1 was sequenced. In normal murine cells, it was present as a single-copy genomic sequence located on chromosome 8. A region of 213 nucleotides corresponded to the E5 gene (HC1 E5), based on the best alignments and on the presence of direct and inverted repeats bearing a central sequence motif. These structural elements are also present in the HPV 18 E5 ORF. HC1 E5 contained an ORF that was transcribed bidirectionally. The transcription in the E5 direction was enhanced in RNA obtained from organs and tumors from carcinogen-treated animals and C127 cells. The polypeptide deduced from the sequence was related to E5 proteins from genital papillomaviruses, to the putative product of the Q300 mouse gene, and to several viral and human growth factors. The data suggest that there may be several cellular counterparts to the viral E5 proteins.
    Type of Publication: Journal article published
    PubMed ID: 1326990
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  • 5
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Instrumental neutron activation analysis has been successfully employed in three distrinct acid precipitation studies. These include the determination of ten (Al, Br, Ca, Cl, Cu, I, Mg, Mn, Na and V) elements in urban rainfall, elevated aluminum concentrations in acidified lakes and major ions (Ca, Cl, K, Mg and Na) in small-mouth bass kept in controlled pH environments. Quality control was assured by analyzing two certified standard reference materials prepared by the National Bureau of Standards (NBS 1643a) and National Research Council of Canada (hepatopancreas TORT-1 marine biological tissue).
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1741-0444
    Keywords: Biopotential recording ; Current clamping ; Impedance measurement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A simple guideline equation using the Gaussian gamma function combined with the Nernst equation is introduced for gradient calibration in FIA-ionselective potentiometry. The technique is based on the injection of a standard solution into the continuously flowing carrier stream followed by injection of the sample. Using the new expression that we have introduced, the sample concentration can be calculated on-line with a microcomputer without explicit knowledge of the Nernst factor. The beneficial features of the novel approach are discussed and demonstrated for practical problems by means of appropriate examples. Experimental conditions are given for the ionselective potentiometric determinations of iodide and cadmium. The respective advantages and restrictions over common calibration techniques are outlined.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-4919
    Keywords: ESR spin trapping ; lipid radicals ; mitochondrial uncoupling ; oxygen consumption ; myocardial reperfusion ; endothelial cell reoxygenation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The contribution of mitochondrial free radical production towards the initiation of lipid peroxidation (LPO) and functional injury in the post-ischemic heart is unclear. Using the isolated rat heart model, the effects of the uncoupler of mitochondrial oxidative phosphorylation dinitrophenol (DNP, 50 μM final) on post-ischemic lipid peroxidation-derived free radical production and functional recovery were assessed. Hearts were subjected to 30 min total global ischemia followed by 15 min of reperfusion in the presence of DNP. As expected, DNP enhanced oxygen consumption before (11.3 ± 0.9 μmol/min, p 〈 0.001) and during reperfusion (at 10 min: 7.9 ± 0.7 μumol/min), compared to the heart with control treatment (8.2 ± 0.5 and 6.7 ± 0.3, respectively). This effect was only associated with a higher incidence of ventricular tachycardia during reperfusion (80 vs. 50% for control treatment, p 〈 0.05). Electron spin resonance spectroscopy (ESR) and spin trapping with u.-phenyl-tert-butylnitrone (PBN, 3 mM final) were used to monitor free radical generation during reperfusion. The vascular concentration of PBN-radical adducts (untreated: 6.4 ±1.0 nM, at 10 min) decreased in the presence of DNP (1.7 ± 0.4 nM, p 〈 0.01). The radical concentration inversely correlated with myocardial oxygen consumption. Total liberation of free radical adducts during the initial 10 min of reperfusion was reduced by DNP (0.59 ± 0.09 nmol, p 〈 0.01) compared to the respective control treatment (1.26 ± 0.16 nmol). Similar effects, prevention of PBN adduct formation and unchanged viability in the presence of DNP, were obtained with endothelial cells during post-hypoxic reoxygenation. Since inhibition of mitochondrial phosphorylation can inhibit the formation of LPO-derived free radicals after an ischemic/hypoxic interval, mitochondria may represent an important source of free radicals capable of initiating lipid peroxidative injury during reperfusion/reoxygenation. (Mol Cell Biochem 160/161: 167–177, 1996)
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-0832
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adult black flies (Simulium decorum) that succumbed to infections caused by Erynia curvispora (= Entomophthora curvispora) were found in Ithaca, New York. Other than hyphal elements of the fungus, the only recognizable structures found within most cadavers were remnants of the tracheal system. Several female cadavers contained well developed eggs. A few males contained shrivelled testes. Germination of primary conidia produced: 1, secondary conidia similar to the primaries or; 2, rounded secondary conidia or; 3, very long germ tubes. In vitro culture of E. curvispora was achieved but its ability to sporulate and to grow vegetatively gradually disappeared. Insectary-reared S. vittatum and S. pictipes were experimentally infected by conidia from in vitro cultures in the laboratory. The incubation period of the disease under these conditions was about six days. In nature the mycosis not only decreases the life expectancy of black flies but probably limits their egg-producing capabilities as well. The mycosis probably compromises the fly's ability to vector filarial worms that cause diseases of man and other mammals.
    Type of Medium: Electronic Resource
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