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  • 1
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Although several clinical studies have shown that increased serum concentrations of protein S100B predict ischaemic brain damage after cardiac surgery, S100B may also be released from the heart or other injured tissue. We therefore investigated the correlation between serum S100B levels and those of the specific cardiac marker troponin I in order to assess the cerebral vs. extracerebral origin of S100B. In 64 cardiac surgical patients, serial blood samples were drawn for the measurement of S100B and troponin I before surgery and for seven days after surgery. Neurological function was assessed before with the National Institutes of Health Stroke Scale and the Folstein Mini Mental Test. The data show that a sustained increase in serum S100B levels is associated with neurological dysfunction, as witnessed by a positive correlation between S100B values and the results of the neuropsychological tests. In contrast, the early postoperative increased levels of protein S100B derive from cardiac tissue, as shown by the positive correlation between S100B and cardiac troponin I levels.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cytokines are involved in the etiology of different disorders of the CNS. For a better understanding of their pathogenic role, we analyzed signal transduction pathways mediating the interleukin (IL)-1β-induced synthesis of IL-6 and tumor necrosis factor α (TNFα) in the human astrocytoma cell line U373 MG. Both protein kinase C and reactive oxygen intermediates (ROIs) were involved in IL-6 and TNFα gene expression by IL-1β. In contrast, protein tyrosine kinases were only necessary for expression of the IL-6 gene. Whereas activation of protein kinase A was able to induce expression of the IL-6 gene, it did not induce TNFα gene expression and was not involved in IL-1β-induced IL-6 and TNFα gene expression. Activation of the transcription factor nuclear factor-κB by IL-1β involved ROIs, whereas the IL-1β-induced activation of the transcription factor AP-1 was mediated via protein kinase C. Our findings provide the basis for the development of specific drugs for the treatment of disorders of the CNS in which cytokines play a pathogenic role.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Stimuli that evoke seizure are capable of inducing structural changes in the hippocampus. However, late-acting genes related to these changes have not been described. Administration of pentylenetetrazole (PTZ; 50 mg/kg) to rats of various ages evoked tonic-clonic seizures. Using RNA gel blot analysis we found that the level of the mRNA for microtubule-associated protein 1B (MAP1B) was robustly increased in the hippocampus of 3-month-old rats. The levels of MAP1B mRNA in hippocampus peaked at 40 h and began to decline by 72 h following PTZ treatment. Immunoblotting with anti-MAP1B antibody demonstrates the increase in content of immunoreactive proteins 40–72 h after seizure onset in the hippocampus of PTZ-treated rats. These results indicate that MAP1B is a sensitive indicator of hippocampal structural changes occurring in response to PTZ-induced seizure activity.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The molecular mechanisms underlying cell cycle control in neuronal progenitors have been investigated with adult mouse olfactory epithelium as a model system. Odorreceptive neurons of mammalian olfactory epithelium are short-lived and renewed in the adult by mitotic division of intrinsic neuronal progenitors. Ablation of the synaptic target, olfactory bulb, induces sequentially extensive apoptosis of sensory neurons and then stimulation of progenitor proliferation, peaking at 36 h and 4 days, respectively, postlesion. Known molecular effectors of G1 phase entry have been assessed on protein extracts of olfactory organs sampled at various postbulbectomy times in adult mice. The decay of βIII-tubulin and olfactory marker protein levels and the rise of proliferating cell nuclear antigen (PCNA) levels, starting 1 and 3 days, respectively, postlesion, provided the kinetic frame of neuronal dynamics. Cyclin D1, cyclin E, and cyclin-dependent kinase cdk2 levels, low in olfactory organ of intact mice, increased 3 days after bulbectomy in parallel with PCNA levels; cdk4 content was initially high and unaffected by lesioning. Western blots of the known cdk inhibitors revealed proliferation-related decreases of p18, p21, and p27 from high expression in intact organs. Immunoprecipitation of cdk2 and cdk4 fractions of protein extracts at 4 days postlesion (mitotic reaction peak) versus control, followed by cyclin D1 immunoblotting, and vice versa, revealed that levels of both cyclin D1/cdk2 and cyclin D1/cdk4 complexes, as well as their kinase activities, were dramatically increased after lesion. In vivo proliferation of olfactory neuronal lineage cells thus involves functional binding of cyclin D1 with cdk2 and cdk4, with differential activation mechanisms for cdk2 and cdk4. In addition, the RT-PCR-detected cyclin D1 mRNA level remained unaffected after bulbectomy, which indicated that the cyclin D1 rise should involve posttranscriptional mechanisms in this in vivo neuronal system. These observations are discussed, along with their relevance to cell cycle control and to olfactory neuron dynamics.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nitric oxide (NO) has been widely implicated in synaptic plasticity and memory formation. In studies of long-term potentiation (LTP), NO is thought to serve as a ‘retrograde messenger’ that contributes to presynaptic aspects of LTP expression. In this study, we examined the role of NO signaling in Pavlovian fear conditioning. We first show that neuronal nitric oxide synthase is localized in the lateral nucleus of the amygdala (LA), a critical site of plasticity in fear conditioning. We next show that NO signaling is required for LTP at thalamic inputs to the LA and for the long-term consolidation of auditory fear conditioning. Collectively, the findings suggest that NO signaling is an important component of memory formation of auditory fear conditioning, possibly as a retrograde signal that participates in presynaptic aspects of plasticity in the LA.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We wanted to know whether fast oscillations (≈ 30–80 Hz) in striate cortex of awake monkeys show sharper orientation selectivity than (i) slower components, including spike rate modulations, and (ii) broad-band signals of the same recordings. As fast oscillations are probably of cortical origin this may further clarify whether cortical network mechanisms are substantially involved in generating orientation selectivity. We recorded multi unit activity (MUA) and local field potentials (LFP, 1–140 Hz) by the same microelectrodes from upper layers of macaque striate cortex during visual stimulation with grating textures of different orientations. An orientation index (OI) was derived from the cortical responses in three frequency ranges (low, 0–11.7 Hz; medium, 11.7–31.3 Hz; and fast oscillations, 31.3–62.5 Hz) and for the broad-band LFP and MUA power. (i) Both LFP and MUA fast oscillations reveal a higher orientation index than signal components in the low and medium frequency ranges. (ii) For MUA the orientation index was significantly higher with fast oscillations than for the lower frequency ranges and the initial broad-band transient responses. (iii) LFPs show a significantly higher orientation index only for the fast oscillations during sustained activation compared with their broad-band power during the transient responses. Thus, our main result is the sharper orientation tuning of fast oscillations in spike activities of local populations compared with slower components of the same broad-band recordings. As fast oscillations occur synchronized in the awake monkey's striate cortex we assume that they have enhanced probability of activating successive stages of visual processing and hence contribute to the perception of orientation.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  The therapy of cutaneous lupus erythematosus (CLE) is often challenging, especially in patients resistant to topical treatment and established first-line systemic drugs such as antimalarials. Systemic corticosteroids are effective, but their use is limited due to well-known side-effects, especially in long-term treatment. In recent years several other immunosuppressive agents have been successfully applied in CLE. However, there are no large studies or explicit guidelines on the use of these drugs in CLE.Objectives  To perform a retrospective investigation of the efficacy of low-dose methotrexate (MTX) in the treatment of CLE.Methods  One hundred and thirty-nine patients with CLE were seen at our department between 2001 and 2003, of whom 43 patients required low-dose MTX. All had histologically confirmed CLE lesions. Clinical data including disease activity, additional treatment, laboratory parameters and side-effects were recorded carefully at the time of presentation. Statistical analyses were performed by paired nonparametric Wilcoxon test and Student's t-test using SPSS 11 software.Results  MTX led to a highly significant (P 〈 0·01) decline in disease activity. An improvement of the cutaneous lesions was recorded in nearly all patients treated with MTX (42 of 43; 98%). Severe side-effects necessitating discontinuation of MTX treatment were recorded in seven patients (16%), which quickly resolved when MTX was discontinued. Life-threatening complications were not observed. Intravenous application was tolerated better than oral administration. Interestingly, we observed a significant increase in circulating lymphocyte numbers in patients with lymphopenia (〈 1·0 × 109 cells L−1) prior to MTX treatment.Conclusions  Our study supports earlier findings reporting the efficacy of low-dose MTX in CLE lesions, particularly in recalcitrant clinical courses. MTX treatment appears to be safe if patients are carefully selected and monitored, with particular attention to side-effects and contraindications.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Background  Some patients suffering from cutaneous lupus erythematosus (CLE) develop extracutaneous manifestations during the course of the disease: up to 5% of patients with discoid LE (DLE) and up to 30% of subacute cutaneous LE (SCLE) patients show systemic involvement. Recent studies revealed some markers indicating systemic manifestations of CLE patients. However, the significance of diminished peripheral lymphocyte numbers as a marker of systemic involvement in CLE has not been investigated before. Objectives  To determine the value of lymphocytopenia (〈 1500 cells µL−1) as a marker of extracutaneous manifestations in CLE patients. Methods  The records of 72 CLE patients (44 DLE; 28 SCLE) were investigated. Systemic involvement was defined in accordance with the criteria of the European Academy of Dermatology and Venereology. Analyses of peripheral lymphocyte numbers were done by fluorescence-activated cell sorter analysis. Results  Five CLE patients developed extracutaneous manifestations during the course of disease. All these patients were lymphocytopenic. Differences between peripheral lymphocyte numbers of CLE patients with and without additional systemic involvement were highly significant (P 〈 0·01). Conclusions  Our results suggest that lymphocytopenia in patients with CLE is a high sensitive but low specific marker of systemic involvement.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Langerhans cell histiocytosis (LCH) can be a difficult therapeutic problem. We present a 40-year-old woman with a 4-year history of LCH who was successfully treated with low-dose methotrexate (20 mg weekly).
    Type of Medium: Electronic Resource
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