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Berlin Brandenburg

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  • 1
    In: Stroke, 2014, Vol.45(9), pp.2792-2794
    Description: BACKGROUND AND PURPOSE—: This study investigated whether a short testing of neurovascular coupling during midterm pregnancy could identify women at risk for subsequent preeclampsia. METHODS—: Transcranial Doppler sonography of the posterior cerebral artery during a brief visual stimulation was analyzed in 68 women at midterm pregnancy, the primary clinical end point was preeclampsia. RESULTS—: Women with bilateral notching of the uterine arteries showed an exaggerated visually evoked blood flow increase and longer time-to-peak. Neurovascular coupling was not significantly associated with the occurrence of preeclampsia. CONCLUSIONS—: Neurovascular coupling was altered in women with impaired uteroplacentar vasoregulation but not a significant predictor of preeclampsia.
    Keywords: Medicine;
    ISSN: 0039-2499
    ISSN: 15244628
    E-ISSN: 15244628
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  • 2
    In: Developmental Medicine & Child Neurology, January 2013, Vol.55(1), pp.83-89
    Description: We aimed to investigate the induction of long‐term potentiation (LTP)‐like plasticity by paired associative stimulation (PAS) in patients with high‐functioning autism and Asperger syndrome (HFA/AS). PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS) was performed in patients with HFA/AS (=9; eight males, one female; mean age 17y 11mo, SD 4y 5mo) and in typically developing age‐matched volunteers (=9; five males, four females; mean age 22y 4mo, SD 5y 2mo). The amplitude of motor‐evoked potentials was measured before PAS, immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PAS) was performed in six additional patients with HFA/AS. Short‐interval intracortical inhibition was measured using paired‐pulse stimulation. In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor‐evoked potentials after PAS. This finding could also be demonstrated after adaptation for N20 latency. Short‐interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. Our results show a significant impairment of LTP‐like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP‐like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory‐motor integration in these patients. This article is commented on by Enticott and Oberman on pages 13–14 of this issue.
    Keywords: Medicine;
    ISSN: 0012-1622
    E-ISSN: 1469-8749
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  • 3
    Language: English
    In: Cancer Research, 04/15/2011, Vol.71(8 Supplement), pp.4724-4724
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 4
    Language: English
    In: International Journal of Cancer, 01 November 2011, Vol.129(9), pp.2297-2303
    Description: Pilocytic astrocytoma (PA) is emerging as a tumor entity with dysregulated Ras/Raf/MEK/ERK signaling. Common genetic lesions observed in PA, which are linked to aberrant ERK pathway activity, include either inactivation, or gain‐of‐function mutations. To investigate the mutation spectrum within the proto‐oncogene encoding the Ser/Thr‐kinase B‐Raf in more detail, we analyzed 64 primary tumor samples from children with PA including two patients with neurofibromatosis type 1 (NF1). The well‐known mutation was found in 6/64 (9.38%) of our samples. For the first time, we report concomitant presence of a somatic mutation in an NF1 patient indicating that more than one Ras/ERK pathway component can be affected in PA. Furthermore, 2/64 (3.13%) of our samples carried a 3‐bp insertion in resulting in the duplication of threonine 599. This conserved residue is located within the activation segment and, if phosphorylated in a Ras‐dependent manner, plays a key role in Raf activation. Here, we demonstrate that this mutant (B‐Raf) and another B‐Raf mutant, which carries two additional threonine residues at this position, display an kinase activity and cellular MEK/ERK activation potential comparable to those of B‐Raf. Notably, replacement of threonines by valine residues had similar effects on B‐Raf activity, suggesting that the distortion of the peptide backbone by additional amino acids rather than the insertion of additional, potential phosphorylation sites destabilizes the inactive conformation of the kinase domain. We also demonstrate that B‐Raf and B‐Raf, but not B‐Raf, provoke drastic morphological alterations in human astrocytes.
    Keywords: Pilocytic Astrocytoma ; Neurofibromatosis Type 1 ; B‐Raf ; Insertion Mutagenesis ; Mapk Pathway
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 5
    In: Neuropediatrics, 2018, Vol.49(03)
    In: Neuropediatrics, 2018, Vol.49(03), pp.213-216
    Description: Despite the availability of modern antibiotics, pneumococcal meningitis in both children and adults remains a severe disease—one known to frequently cause grave complications and residual disability. Although the appearance of arterial vasospasms in bacterial meningitis systematically has been investigated and reported on for adult patients, such research is lacking when it comes to infants. We report on a 4-week-old infant who, 6 days after onset of pneumococcal meningitis, suffered severe neurological deterioration with treatment-resistant seizures and coma. Generalized cortical and subcortical edema developed in conjunction with diminished cerebral blood flow, as depicted in magnetic resonance angiography and serial Doppler-sonographic examinations. The ischemia resulted in extensive cystic encephalomalacia. We propose that the degree of variation in cerebral blood flow in the acute phase was the result of an extensive arterial vasculopathy involving vasospasms. Awareness of this complication and prospective serial Doppler-sonographic examinations may improve our understanding of the connection between brain edema and vasculopathy. At present, however, no effective treatment appears available.
    Keywords: Vasospasm ; Infarct ; Vasculopathystreptococcus pneumoniae ; Infant ; Meningitis ; Brain edema
    ISSN: 0174-304X
    E-ISSN: 1439-1899
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  • 6
    Language: English
    In: Cancer Research, 04/15/2010, Vol.70(8 Supplement), pp.1178-1178
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 7
  • 8
    Language: English
    In: Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, July 2018, Vol.13, pp.171-173
    Description: Preeclampsia is a pregnancy-related hypertensive disorder with strongly impaired cerebral autoregulation in the acute stage. A history of preeclampsia is an independent cardiovascular and cerebrovascular risk factor. It is unclear whether impaired cerebral autoregulation persists after preeclampsia and thus contributes to the known increased cerebrovascular morbidity. Using transcranial Doppler, we compared cerebral hemodynamics and dynamic cerebral autoregulation of 25 women with a history of severe preeclampsia and 25 healthy mothers, on average 2–3 years postpartum. Mean arterial blood pressure (MAP) and cerebral blood flow velocities (CBFV) in the middle and posterior cerebral artery were recorded at rest, dynamic cerebral autoregulation was assessed via transfer function phase and gain between oscillations of CBFV and MAP during regular breathing at 0.1 Hz. MAP and body mass index were higher in former preeclamptic women compared with healthy mothers (p-value 〈0.001 and 0.006, respectively). CBFV in the middle cerebral artery was slightly increased in former preeclamptic women compared with healthy mothers (p-value 0.004), intima-media thickness (IMT) of the common carotid artery was higher by trend (p-value 0.065). Dynamic cerebral autoregulation was not impaired in women with a history of preeclampsia, phase even tended to be higher than in healthy mothers. Dynamic cerebral autoregulation is not persistently impaired in women after severe preeclampsia. Long-term cerebrovascular changes rather result from a higher incidence of cerebrovascular risk factors in women with a history of preeclampsia.
    Keywords: Preeclampsia ; Hellp-Syndrome ; Cerebral Autoregulation ; Cerebrovascular Risk ; Medicine
    ISSN: 2210-7789
    E-ISSN: 2210-7797
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  • 9
    Language: English
    In: Acta Neuropathologica, 2011, Vol.121(3), pp.397-405
    Description: Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 ( BRAF ) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors albeit at a low frequency. We analyzed exon 15 of BRAF spanning the V600 locus by direct sequencing in 1,320 adult and pediatric tumors of the nervous system including various types of glial, embryonal, neuronal and glioneuronal, meningeal, adenohypophyseal/sellar, and peripheral nervous system tumors. A total of 96 BRAF mutations were detected; 93 of the V600E type and 3 cases with a three base pair insertion between codons 599 and 600. The highest frequencies of BRAF V600E mutations were found in WHO grade II pleomorphic xanthoastrocytomas (42/64; 66%) and pleomorphic xanthoastrocytomas with anaplasia (15/23; 65%), as well as WHO grade I gangliogliomas (14/77; 18%), WHO grade III anaplastic gangliogliomas (3/6) and pilocytic astrocytomas (9/97; 9%). In pilocytic astrocytomas BRAF V600E mutation was strongly associated with extra-cerebellar location ( p  = 0.009) and was most frequent in diencephalic tumors (4/12; 33%). Glioblastomas and other gliomas were characterized by a low frequency or absence of mutations. No mutations were detected in non-glial tumors, including embryonal tumors, meningiomas, nerve sheath tumors and pituitary adenomas. The high mutation frequencies in pleomorphic xanthoastrocytomas, gangliogliomas and extra-cerebellar pilocytic astrocytomas implicate BRAF V600E mutation as a valuable diagnostic marker for these rare tumor entities. Future clinical trials should address whether BRAF V600E mutant brain tumor patients will benefit from BRAF V600E -directed targeted therapies.
    Keywords: BRAF ; V600E mutation ; Brain tumor ; Pleomorphic xanthoastrocytoma ; Ganglioglioma
    ISSN: 0001-6322
    E-ISSN: 1432-0533
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  • 10
    In: Stroke, 2007, Vol.38(5), pp.e17-e17
    Description: Response: Norris and Menon suspect that both patients whom we reported to have recurrent vasospasms of the internal carotid artery1 were likely to have carotid artery dissection (CAD). In fact, CAD had been the initial diagnosis in both patients. There were, however, several findings which could not be explained in the context of CAD and led us to the assumption of internal carotid artery vasospasm. We agree that MRI with MR angiography is sensitive in the diagnosis of CAD. Ultrasound detects dissection mainly by its hemodynamic sequelae than by …
    Keywords: Medicine;
    ISSN: 0039-2499
    E-ISSN: 15244628
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