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  • 1
    Electronic Resource
    Electronic Resource
    Angewandte Informationssicherheit Ein Hacker-Praktikum an Universitäten (2000)
    Springer
    Informatik-Spektrum 23 (2000), S. 202-211 
    Details
    ISSN: 1432-122X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002870000099
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  • 2
    Electronic Resource
    Electronic Resource
    Characterization and regulation of the 3β-hydroxysteroid dehydrogenase isomerase enzyme in the rat sciatic nerve (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 84 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the peripheral nervous system, progesterone (PROG) has a stimulatory effect on myelination. It could be derived from local synthesis, as Schwann cells in culture express the 3β-hydroxysteroid dehydrogenase (3β-HSD) and convert pregnenolone (PREG) to PROG. Although 3β-HSD mRNA can be detected by RT-PCR in peripheral nerves, the activity of the enzyme has so far not been demonstrated and characterized in nerve tissue. In this study, we show that homogenates prepared from rat sciatic nerves contain a functional 3β-HSD enzyme and we have analysed its kinetic properties and its regulation by steroids. The activity of 3β-HSD in homogenates was evaluated using 3H-labelled PREG as a substrate and NAD+ as a cofactor, the levels of steroids formed were calculated either by extrapolating the relationship between tritiated peaks obtained by TLC to the initial amount of PREG, or by gas chromatography/mass spectrometry determination. A rapid increase in PROG formation was found between 0 and 50 min of incubation and no further significant changes were observed between 1 and 4 h. The calculated Km value (1.06 ± 0.19 μm) was close to the values described for the3β-HSD type-I and type-IV isoforms. Trilostane, a competitive inhibitor of the 3β-HSD caused a potent inhibition of the rate of conversion of PREG to PROG (IC50 = 4.06 ± 2.58 μm). When the effects of different steroids were tested, both oestradiol and PROG significantly inhibited the conversion of PREG to PROG.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01512.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25-Dx expression in the rat spinal cord (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 87 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Progesterone provides neuroprotection after spinal cord injury, but the molecular mechanisms involved in this effect are not completely understood. In this work, expression of two binding proteins for progesterone was studied in intact and injured rat spinal cord: the classical intracellular progesterone receptor (PR) and 25-Dx, a recently discovered progesterone membrane binding site. RT-PCR was employed to determine their relative mRNA levels, whereas cellular localization and relative protein levels were investigated by immunocytochemistry. We observed that spinal cord PR mRNA was not up-regulated by estrogen in contrast to what is observed in many brain areas and in the uterus, but was abundant as it amounted to a third of that measured in the estradiol-stimulated uterus. In male rats with complete spinal cord transection, levels of PR mRNA were significantly decreased, while those of 25-Dx mRNA remained unchanged with respect to control animals. When spinal cord-injured animals received progesterone treatment during 72 h, PR mRNA levels were not affected and remained low, whereas 25-Dx mRNA levels were significantly increased. Immunostaining of PR showed its intracellular localization in both neurons and glial cells, whereas 25-Dx immunoreactivity was localized to cell membranes of dorsal horn and central canal neurons. As the two binding proteins for progesterone differ with respect to their response to lesion, their regulation by progesterone, their cellular and subcellular localizations, their functions may differ under normal and pathological conditions. These observations point to a novel and potentially important role of the progesterone binding protein 25-Dx after injury of the nervous system and suggest that the neuroprotective effects of progesterone may not necessarily be mediated by the classical progesterone receptor but may involve distinct membrane binding sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.02055.x
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  • 4
    Electronic Resource
    Electronic Resource
    Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 86 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have previously shown that progesterone (PROG) is synthesized by Schwann cells and promotes myelin formation in the peripheral nervous system (PNS). We now report that this neurosteroid also stimulates myelination in organotypic slice cultures of 7-day-old (P7) rat and mouse cerebellum. Myelination was evaluated by immunofluorescence analysis of the myelin basic protein (MBP). After 7 days in culture (7DIV), we found that adding PROG (2–5 × 10−5 M) to the culture medium caused a fourfold increase in MBP expression when compared to control slices. The effect of PROG on MBP expression involves the classical intracellular PROG receptor (PR): the selective PR agonist R5020 significantly increased MBP expression and the PR antagonist mifepristone (RU486) completely abolished the effect of PROG on this MBP expression. Moreover, treatment of P7-cerebellar slice cultures from PR knockout (PRKO) mice with PROG had no significant effect on MBP expression. PROG was metabolized in the cerebellar slices to 5α-dihydroprogesterone (5α-DHP) and to the GABAA receptor-active metabolite 3α,5α-tetrahydroprogesterone (3α,5α-THP, allopregnanolone). The 5α-reductase inhibitor L685-273 partially inhibited the effect of PROG, and 3α,5α-THP (2–5 × 10−5 M) significantly stimulated the MBP expression, although to a lesser extent than PROG. The increase in MBP expression by 3α,5α-THP involved GABAA receptors, as it could be inhibited by the selective GABAA receptor antagonist bicuculline. These findings suggest that progestins stimulate MBP expression and consequently suggest an increase in CNS myelination via two signalling systems, the intracellular PR and membrane GABAA receptors, and they confirm a new role of GABAA receptors in myelination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01881.x
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  • 5
    Electronic Resource
    Electronic Resource
    Synthesis of progesterone in Schwann cells: regulation by sensory neurons (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 13 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In peripheral nerves, progesterone synthesized by Schwann cells has been implicated in myelination. In spite of such an important function, little is known of the regulation of progesterone biosynthesis in the nervous system. We show here that in rat Schwann cells, expression of the 3β-hydroxysteroid dehydrogenase and formation of progesterone are dependent on neuronal signal. Levels of 3β-hydroxysteroid dehydrogenase mRNA and synthesis of [3H]progesterone from [3H]pregnenolone were low in purified Schwann cells prepared from neonatal rat sciatic nerves. However, when Schwann cells were cultured in contact with sensory neurons, both expression and activity of the 3β-hydroxysteroid dehydrogenase were induced. Regulation of 3β-hydroxysteroid dehydrogenase expression by neurons was also demonstrated in vivo in the rat sciatic nerve. 3β-hydroxysteroid dehydrogenase mRNA was present in the intact nerve, but could no longer be detected 3 or 6 days after cryolesion, when axons had degenerated. After 15 days, when Schwann cells made new contact with the regenerating axons, the enzyme was re-expressed. After nerve transection, which does not allow axonal regeneration, 3β-hydroxysteroid dehydrogenase mRNA remained undetectable. The regulation of 3β-hydroxysteroid dehydrogenase mRNA after lesion was similar to the regulation of myelin protein zero (P0) and peripheral myelin protein 22 (PMP22) mRNAs, supporting an important role of locally formed progesterone in myelination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01463.x
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  • 6
    Electronic Resource
    Electronic Resource
    Expression of vanilloid receptor subtype 1 (VR1/TRPV1) in the skin – implications for neurogenic inflammation and nociceptive sensations (2004)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc
    Experimental dermatology 13 (2004), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The vanilloid receptor subtype 1 (VR1/TRPV1) is a non-selective cation channel that binds the vanilloid capsaicin and endogenous cannabinoids. In human skin, VR1 has recently been shown to be expressed by keratinocytes in vitro and in vivo. To determine a precise localization of VR1 in other cutaneous compartments in particular cutaneous nerve fibres, we investigated VR1 immunoreactivity as well as mRNA and protein expression in a series of normal and capsaicin-treated human skin. VR1 immunoreactivity could be observed in cutaneous sensory nerve fibres, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts and the secretory portion of eccrine sweat glands. Upon RT-PCR and Western blot, the expression of VR1 was confirmed in primary mast cells and keratinocytes from human skin. During capsaicin therapy, VR1-receptor distribution was unchanged, while a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed in nerve fibres. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a central role for this receptor, e.g. in nociception and inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0906-6705.2004.0212bv.x
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  • 7
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of a 1-h paclitaxel infusion (2000)
    Springer
    Cancer chemotherapy and pharmacology 45 (2000), S. 463-470 
    Details
    ISSN: 1432-0843
    Keywords: Key words Paclitaxel ; Pharmacokinetics ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To characterize the disposition of paclitaxel (PAC) after a 1-h infusion in humans and define if possible a pharmacodynamic relationship between PAC disposition and the observed toxicity. Patients and methods: PAC pharmacokinetics were studied in 43 courses of therapy in 30 patients (30 first course, 13 PK third course). PAC was administered at 150, 175, 200, 225 and 250 mg/m2 by a 1-h infusion to patients with advanced cancer (lung, breast, ovarian, cervix, and head and neck). PAC was quantified by high-performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated by noncompartmental and model-dependent methods. Results: Increases in the area under the curve and the peak plasma concentration were not proportional to increases in the dose. However, the deviation from linearity is rather moderate. The dose-limiting toxicity was central neuropathy which was not associated with pharmacokinetic deviations. Owing to the absence of grade 3 or 4 myelotoxicity, no clear correlation between this toxicity and pharmacokinetic parameters could be established. Conclusion: Within the evaluated dose range of the 1-h infusion there was only a moderate nonlinear disposition of PAC in humans and therefore a dose of 225 mg/m2 is recommended as safe. The observation of central neuropathy could not be directly related to a pharmacokinetic parameter. The complexity of the formulation which included Cremophor EL and ethanol may offer an explanation for the observed central neurotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800051020
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  • 8
    Electronic Resource
    Electronic Resource
    Supratentorial primitive neuroectodermal tumours: diffusion-weighted MRI (2000)
    Springer
    Neuroradiology 42 (2000), S. 393-398 
    Details
    ISSN: 1432-1920
    Keywords: Key words Primitive neuroectodermal tumours ; Brain, neoplasms ; Magnetic resonance imaging, diffusion weighted
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the clinical and pathological findings of supratentorial primitive neuroectodermal tumours (PNETs). These are rare, poorly differentiated, highly malignant neoplasms occurring primarily in young individuals. They frequently show dissemination to the spinal cord and sometimes also beyond neuraxis. Preoperative radiological diagnosis is difficult, due to the nonspecific CT and MRI characteristics. Our findings indicate that diffusion-weighted imaging (DWI) can be used to show the solid portion of the tumour preoperatively and to monitor postsurgical recovery. We describe the MRI findings in three patients with histologically confirmed supratentorial PNET, focussing on the role of DWI for improving the specificity of radiological diagnosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340000318
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  • 9
    Electronic Resource
    Electronic Resource
    Time-resolved projection MRA: clinical application in intracranial vascular malformations (2000)
    Springer
    Neuroradiology 42 (2000), S. 104-107 
    Details
    ISSN: 1432-1920
    Keywords: Key words Magnetic resonance angiography, time resolved ; Malformations, vascular ; Embolisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report preliminary results of imaging intracranial vascular malformations with time-resolved projection MRA after a bolus injection of contrast median before and after endovascular treatment. Projection angiograms are acquired with a slice-selective snapshot FLASH sequence with a time resolution of two images per second, 40–60 images being acquired consecutively after bolus injection of 15 ml Gd-DTPA. Postprocessing of images in 2D projection MRA by correlation analysis offers several advantages with significant improvement of signal-to-noise, leading to adequate anatomical resolution. Subsecond projection MRA is a reliable technique for imaging intracranial vessels and gives information about the haemodynamics of vascular malformations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050024
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  • 10
    Electronic Resource
    Electronic Resource
    Photoproduction of neutral pion pairs from the proton (2000)
    Springer
    The European physical journal 9 (2000), S. 5-8 
    Details
    ISSN: 1434-601X
    Keywords: PACS. 13.60.Le Meson production – 25.20.Lj Photoproduction reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: Double neutral pion photoproduction from the proton has been measured at MAMI for photon energies between threshold and 820 MeV. The reaction was identified by an invariant mass and missing mass analysis. From threshold up to 370 MeV the total cross-section does not exceed 30 nb. For higher energies it shows a smooth rise until it reaches a maximum of about 10 μb at E γ = 740 MeV. Dalitz plots of m 2(π0π0) versus m 2(p,π0) for seven bins of incident photon energy have been analysed. For E γ 〉 610 MeV, a strong contribution of a sequential decay is observed with the Δ(1232)-resonance as intermediate state. A comparison to model calculations shows that these sequential decays presumably originate from the D 13(1520) and also the P 11(1440)-resonance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100500070048
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