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BACKGROUND: After presenting two sisters with the rare form of congenital arrhinia, this syndrome is reviewed, an explanation of the pathogenesis is offered and the therapeutic options of the functional and aesthetic reconstruction are discussed. DISCUSSION: In cases of congenital arrhinia different degrees of respiratory distress, cyanotic episodes, and impaired food intake are described. Therefore after birth respiration and food intake need to be monitored to alleviate the situation through intubation or tracheotomy. The following conclusions could be made based on the literature overview. Little is known about the pathophysiology and a great variety of therapeutic interventions and reconstruction solutions with a wide spectrum of complications are described. Due to the numerous forms of complications, which need to be compared with the reconstructive results, indications for surgical reconstruction of the airway and plastic reconstruction of the nose during childhood must be defined very stringently. CONCLUSION: One method to achieve a satisfactory plastic result is with an osseointegrated prosthesis. This facial prosthesis can be inserted without complications and can guarantee an adequate result, whereas no impairment of maxillofacial development was noted. 相似文献
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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with impairments across the lifespan. The persistence of ADHD is associated with considerable liability to neuropsychiatric co-morbidity such as depression, anxiety and substance use disorder. The substantial heritability of ADHD is well documented and recent genome-wide analyses for risk genes revealed synaptic adhesion molecules (e.g. latrophilin-3, LPHN3; fibronectin leucine-rich repeat transmembrane protein-3, FLRT3), glutamate receptors (e.g. metabotropic glutamate receptor-5, GRM5) and mediators of intracellular signalling pathways (e.g. nitric oxide synthase-1, NOS1). These genes encode principal components of the molecular machinery that connects pre- and postsynaptic neurons, facilitates glutamatergic transmission, controls synaptic plasticity and empowers intersecting neural circuits to process and refine information. Thus, identification of genetic variation affecting molecules essential for the formation, specification and function of excitatory synapses is refocusing research efforts on ADHD pathogenesis to include the long-neglected glutamate system. 相似文献
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Pinto YM Pinto-Sietsma SJ Philipp T Engler S Kossamehl P Hocher B Marquardt H Sethmann S Lauster R Merker HJ Paul M 《Hypertension》2000,36(5):747-754
Angiotensin II recruits transforming growth factor beta(1) (TGFbeta(1)) and is related to left ventricular fibrosis. However, it is unclear whether chronic in vivo reduction in left ventricular TGFbeta(1) expression blunts fibrosis and improves outcome in angiotensin II-dependent hypertension. Four-week-old male hypertensive TGR(mRen2)27 (Ren2) rats received either normal food, low-dose losartan (0.5 mg. kg(-1). d(-1)), or tranilast (a nonspecific TGFbeta inhibitor; 400 mg. kg(-1). d(-1)) (n=10 for each group) for 12 weeks and were compared with Sprague-Dawley control rats. The effect of tranilast on survival was evaluated in 34 additional untreated homozygous Ren2 rats. Tranilast or low-dose losartan did not lower blood pressure. However, the increase in left ventricular weight (Ren2 versus SD 3.1+/-0.16 versus 2.1+/- 0.06 mg/g body wt; P<0.05) was significantly (P<0.05) blunted by both tranilast (2.7+/-0.05) and losartan (2.7+/-0.07). Both drugs prevented the increase in left ventricular TGFbeta(1) mRNA and fibronectin mRNA and blunted the increase in hydroxyproline content and the increase in perivascular fibrosis. The perivascular fibrosis score correlated significantly with the level of expression of TGFbeta(1) (r=0.62; P=0.019). In situ hybridization demonstrated increases in TGFbeta(1) mRNA, predominantly in perivascular and nonmyocyte areas. Both drugs did not prevent the decrease in systolic or diastolic dP/dt, but tranilast significantly improved the survival of untreated Ren2 rats (P=0.029). In conclusion, TGFbeta(1) mRNA expression is increased predominantly in nonmyocyte regions in the hypertrophied left ventricle in this angiotensin II-dependent model of hypertension. This increase is probably due to high angiotensin II levels rather than to hypertension. This is the first study to suggest that chronic inhibition of TGFbeta(1) expression attenuates left ventricular hypertrophy and fibrosis, even without lowering blood pressure. 相似文献
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Anna Uta Rysop Lea‐Maria Schmitt Jonas Obleser Gesa Hartwigsen 《Human brain mapping》2021,42(1):110-127
When speech intelligibility is reduced, listeners exploit constraints posed by semantic context to facilitate comprehension. The left angular gyrus (AG) has been argued to drive this semantic predictability gain. Taking a network perspective, we ask how the connectivity within language‐specific and domain‐general networks flexibly adapts to the predictability and intelligibility of speech. During continuous functional magnetic resonance imaging (fMRI), participants repeated sentences, which varied in semantic predictability of the final word and in acoustic intelligibility. At the neural level, highly predictable sentences led to stronger activation of left‐hemispheric semantic regions including subregions of the AG (PGa, PGp) and posterior middle temporal gyrus when speech became more intelligible. The behavioural predictability gain of single participants mapped onto the same regions but was complemented by increased activity in frontal and medial regions. Effective connectivity from PGa to PGp increased for more intelligible sentences. In contrast, inhibitory influence from pre‐supplementary motor area to left insula was strongest when predictability and intelligibility of sentences were either lowest or highest. This interactive effect was negatively correlated with the behavioural predictability gain. Together, these results suggest that successful comprehension in noisy listening conditions relies on an interplay of semantic regions and concurrent inhibition of cognitive control regions when semantic cues are available. 相似文献
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Meyer GK Neetz A Brandes G Tsikas D Butterfield JH Just I Gerhard R 《Infection and immunity》2007,75(8):3868-3876
Clostridium difficile toxins A and B (TcdA and TcdB) are the causative agents of antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial role in the inflammatory processes underlying this disease. We studied the direct effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to degranulation, cytokine release, and the activation of proinflammatory signal pathways. TcdA and TcdB inactivate Rho GTPases, the master regulators of the actin cytoskeleton. The inactivation of Rho GTPases induced a reorganization of the actin cytoskeleton accompanied by morphological changes of cells. The TcdB-induced reorganization of the actin cytoskeleton in HMC-1 cells reduced the number of electron-dense mast cell-specific granules. Accordingly, TcdB induced the release of hexosaminidase, a marker for degranulation, in HMC-1 cells. The actin rearrangement was found to be responsible for degranulation since latrunculin B induced a comparable hexosaminidase release. In addition, TcdB as well as latrunculin B induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 and also resulted in a p38 MAPK-dependent increased formation of prostaglandins D(2) and E(2). The autocrine stimulation of HMC-1 cells by prostaglandins partially contributed to the degranulation. Interestingly, TcdB-treated HMC-1 cells, but not latrunculin B-treated HMC-1 cells, showed a strong p38 MAPK-dependent increase in interleukin-8 release. Differences in the mast cell responses to TcdB and latrunculin B are probably due to the presence of functionally inactive Rho GTPases in toxin-treated cells. Thus, the HMC-1 cell line is a promising model for studying the direct effects of C. difficile toxins on mast cells independently of the tissue context. 相似文献
10.
Gesa H. Phler Filip Klimes Andreas Voskrebenzev Lea Behrendt Christoph Czerner Marcel Gutberlet Serghei Cebotari Fabio Ius Christine Fegbeutel Christian Schoenfeld Till F. Kaireit Erik F. Hauck Karen M. Olsson Marius M. Hoeper Frank Wacker Jens Vogel‐Claussen 《Journal of magnetic resonance imaging : JMRI》2020,52(2):610-619