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101.
Wanda Kwan Ulrike Tr?ger Dimitrios Davalos Austin Chou Jill Bouchard Ralph Andre Aaron Miller Andreas Weiss Flaviano Giorgini Christine Cheah Thomas M?ller Nephi Stella Katerina Akassoglou Sarah J. Tabrizi Paul J. Muchowski 《The Journal of clinical investigation》2012,122(12):4737-4747
In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed. 相似文献
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Ulrike Klein Kai Neben Thomas Hielscher Christiane Heiß Anthony D. Ho Hartmut Goldschmidt 《Annals of hematology》2011,90(4):429-439
Over the past decade, treatment options for patients with multiple myeloma (MM) have improved substantially, resulting in
better response rates and prolonged overall survival (OS). Nevertheless, MM remains a challenging disease, especially if renal
insufficiency (RI) or extensive pre-treatment aggravates the assignment of the optimal treatment schedule. In this retrospective
study, we analyzed the outcome of lenalidomide plus dexamethasone in 167 patients with relapsed or refractory MM with focus
on RI. The baseline creatinine clearance (CLCr) was normal in 94 patients (CLCr ≥ 80 ml/min), while RI was observed in 73 patients, including 40 patients with mild RI (50 ≤ CLCr < 80 ml/min) and 33 patients with moderate or severe RI (CLCr < 50 ml/min). Response rates declined depending on the severity of RI, being 67% among patients with normal kidney function,
60% among patients with mild RI and 49% among patients with moderate or severe RI. Time to progression (TTP) was significantly
reduced in patients with severe RI and in case of >2 previous treatment lines. OS was not significantly different between
patients with normal and impaired renal function. In contrast, the number of previous treatment lines (2 vs. <2) and the use
of novel agents like bortezomib or thalidomide prior to lenalidomide plus dexamethasone therapy had a more adverse effect
on OS. In conclusion, lenalidomide plus dexamethasone is an effective regimen for relapsed or refractory patients with MM
complicated by RI with manageable toxicity. 相似文献
104.
Ulrike Weber-Stadlbauer Juliet Richetto Ramona A. J. Zwamborn Roderick C. Slieker Urs Meyer 《Neuropsychopharmacology》2021,46(2):404
Prenatal exposure to infectious and/or inflammatory insults is increasingly recognized to contribute to the etiology of psychiatric disorders with neurodevelopmental components. Recent research using animal models suggests that maternal immune activation (MIA) can induce transgenerational effects on brain and behavior, possibly through epigenetic mechanisms. Using a mouse model of MIA that is based on gestational treatment with the viral mimeticpoly(I:C) (= polyriboinosinic-polyribocytidilic acid), the present study explored whether the transgenerational effects of MIA are extendable to dopaminergic dysfunctions. We show that the direct descendants born to poly(I:C)-treated mothers display signs of hyperdopaminergia, as manifested by a potentiated sensitivity to the locomotor-stimulating effects of amphetamine (Amph) and increased expression of tyrosine hydroxylase (Th) in the adult ventral midbrain. In stark contrast, second- and third-generation offspring of MIA-exposed ancestors displayed blunted locomotor responses to Amph and reduced expression of Th. Furthermore, we found increased DNA methylation at the promoter region of the dopamine-specifying factor, nuclear receptor-related 1 protein (Nurr1), in the sperm of first-generation MIA offspring and in the ventral midbrain of second-generation offspring of MIA-exposed ancestors. The latter effect was further accompanied by reduced mRNA levels of Nurr1 in this brain region. Together, our results suggest that MIA has the potential to modify dopaminergic functions across multiple generations with opposite effects in the direct descendants and their progeny. The presence of altered DNA methylation in the sperm of MIA-exposed offspring highlights the possibility that epigenetic processes in the male germline play a role in the transgenerational effects of MIA.Subject terms: Neuroimmunology, Developmental disorders 相似文献
105.
J?rn L?tsch Carmen Walter Lisa Felden Christine Preibisch Ulrike N?th Till Martin Sandra Anti Ralf Deichmann Bruno G. Oertel 《Social cognitive and affective neuroscience》2012,7(6):698-707
Comparing pain is done in daily life and involves short-term memorizing and attention focusing. This event-related functional magnetic resonance imaging study investigated the short-term brain activations associated with the comparison of pain stimuli using a delayed discrimination paradigm. Fourteen healthy young volunteers compared two successive pain stimuli administered at a 10 s interval to the same location at the nasal mucosa. Fourteen age- and sex-matched subjects received similar pain stimuli without performing the comparison task. With the comparison task, the activations associated with the second pain stimulus were significantly greater than with the first stimulus in the anterior insular cortex and the primary somatosensory area. This was observed on the background of a generally increased stimulus-associated brain activation in the presence of the comparison task that included regions of the pain matrix (insular cortex, primary and secondary somatosensory area, midcingulate cortex, supplemental motor area) and regions associated with attention, decision making, working memory and body recognition (frontal and temporal gyri, inferior parietal lobule, precuneus, lingual cortices). This data provides a cerebral correlate for the role of pain as a biological alerting system that gains the subject''s attention and then dominates most other perceptions and activities involving pain-specific and non-pain-specific brain regions. 相似文献
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108.
Der Freie Zahnarzt - Landesverband Rheinland-Pfalz Am 18.03.2018 verstarb im Alter von 63 Jahren unser hochgeschätzter Kollege Dr. Holger Dausch. 相似文献
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110.
Mahmut Gümüş MD Chieh-I Chen MPH Cristina Ivanescu PhD Saadettin Kilickap MD Igor Bondarenko MD Mustafa Özgüroğlu MD Miranda Gogishvili MD Haci M. Turk MD Irfan Cicin MD James Harnett PharmD Vera Mastey MS Ulrike Naumann MS Matthew Reaney MS Gerasimos Konidaris MS Medha Sasane PhD Keri J. S. Brady PhD Siyu Li PhD Giuseppe Gullo MD Petra Rietschel MD Ahmet Sezer MD 《Cancer》2023,129(1):118-129