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Silke Wemmert,
Vivienne Willnecker,
Christian Brunner,
Gentiana Ioana Wenzel,
Birgit Sauter,
Heike Meinelt,
Nadia Bartholmé,
Carolin Saada,
Rainer Maria Bohle,
Steffi Urbschat, Bernhard Schick
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ABSTRACT: BACKGROUND: Despite numerous studies, the tumor biology of pleomorphic adenomas, the most common salivary gland tumors, is still not completely defined. In order to identify further candidate genes important for tumor biology of pleomorphic adenomas, extended cytogenetic and molecular analysis are mandatory. METHODS: We performed a detailed molecular cytogenetic analysis using comparative genomic hybridization (CGH) followed by fluorescence in situ hybridization (FISH) with probes for chromosome X, 16p, 17, and 20 on a large cohort of pleomorphic adenomas (n = 29). RESULTS: We could confirm previously described deletions in pleomorphic adenomas affecting 16p, 17, 20q, and 22 by FISH and/or CGH analysis. Moreover, our CGH study revealed novel candidate regions on 8p23.1pter, 9p, 10q25.1q25.3, and 11q24qter in the series of analyzed pleomorphic adenomas. CONCLUSION: Our present study reveals new insights in novel candidate regions implicated in pleomorphic adenoma tumorigenesis which should be considered in further molecular studies. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
Head & Neck 09/2012; · 2.40 Impact Factor
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Annalisa Zuccotti,
Stephanie Kuhn,
Stuart L Johnson,
Christoph Franz,
Wibke Singer,
Dietmar Hecker,
Hyun-Soon Geisler,
Iris Köpschall,
Karin Rohbock,
Katja Gutsche,
Julia Dlugaiczyk, Bernhard Schick,
Walter Marcotti,
Lukas Rüttiger,
Thomas Schimmang,
Marlies Knipper
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ABSTRACT: The precision of sound information transmitted to the brain depends on the transfer characteristics of the inner hair cell (IHC) ribbon synapse and its multiple contacting auditory fibers. We found that brain derived neurotrophic factor (BDNF) differentially influences IHC characteristics in the intact and injured cochlea. Using conditional knock-out mice (BDNF(Pax2) KO) we found that resting membrane potentials, membrane capacitance and resting linear leak conductance of adult BDNF(Pax2) KO IHCs showed a normal maturation. Likewise, in BDNF(Pax2) KO membrane capacitance (ΔC(m)) as a function of inward calcium current (I(Ca)) follows the linear relationship typical for normal adult IHCs. In contrast the maximal ΔC(m), but not the maximal size of the calcium current, was significantly reduced by 45% in basal but not in apical cochlear turns in BDNF(Pax2) KO IHCs. Maximal ΔC(m) correlated with a loss of IHC ribbons in these cochlear turns and a reduced activity of the auditory nerve (auditory brainstem response wave I). Remarkably, a noise-induced loss of IHC ribbons, followed by reduced activity of the auditory nerve and reduced centrally generated wave II and III observed in control mice, was prevented in equally noise-exposed BDNF(Pax2) KO mice. Data suggest that BDNF expressed in the cochlea is essential for maintenance of adult IHC transmitter release sites and that BDNF upholds opposing afferents in high-frequency turns and scales them down following noise exposure.
Journal of Neuroscience 06/2012; 32(25):8545-53. · 7.11 Impact Factor
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ABSTRACT: Glucocorticoids (GCs) not only regulate metabolic and inflammatory mechanisms, but also are known to suppress tumor growth. Despite previous detection of glucocorticoid receptors (GRs) in juvenile angiofibromas, their distribution and function have not further been studied.
Juvenile angiofibroma tissue (n = 30), nasal mucosa specimens (n = 10), subepithelial stroma of nasal mucosa (n = 20), and primary fibroblasts from juvenile angiofibroma (n = 6) and nasal mucosa samples (n = 6) were analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence staining. The antiproliferative effect of GCs (dexamethasone, prednisolone, and hydrocortisone) in vitro was assessed using a bromdeoxyuridine (BrdU) assay.
An upregulation of GR transcripts and protein was shown in juvenile angiofibroma tissue and primary mesenchymal cells compared to nasal mucosa. Application of GCs resulted in a significantly higher antiproliferative effect on juvenile angiofibroma versus nasal mucosa fibroblasts in vitro.
Expression of GRs and antiproliferative effects of GCs on juvenile angiofibroma fibroblasts offer novel options for the treatment of this unique fibrovascular tumor. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
Head & Neck 01/2012; 34(11):1615-21. · 2.40 Impact Factor
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ABSTRACT: Juvenile angiofibroma (JA) is a unique fibrovascular tumor, which is almost exclusively found in the posterior nasal cavity of adolescent males. Although histologically classified as benign, the tumor often shows an aggressive growth pattern and has been associated with chromosomal imbalances, amplification of oncogenes and epigenetic dysregulation. We present the first genome-wide profiling of JAs (n=14) with a 100K single nucleotide polymorphism (SNP) microarray. Among the 30 novel JA-specific amplifications detected on autosomal chromosomes with this technique, the genes encoding the cancer-testis antigen BORIS (brother of the regulator of imprinted sites) and the developmental regulator protein TSHZ1 (teashirt zinc finger homeobox 1) were selected for further analysis. Gains for both BORIS (20q13.3) and TSHZ1 (18q22.3) were confirmed by quantitative genomic PCR. Furthermore, quantitative RT-PCR revealed a significant up-regulation of BORIS (p<0.001) and TSHZ1 transcripts (p<0.05) for JAs compared to nasal mucosa. Following detection of BORIS and TSHZ1 proteins in western blots of JAs, subcellular localization was determined for both proteins in immunostaining of JA cryosections. In conclusion, genomic copy number profiling using an SNP microarray has been proven to be a suitable and reliable tool for identifying novel disease-related genes in JAs and newly implicates BORIS and TSHZ1 overexpression in the pathogenesis of JAs. Detection of BORIS in JAs is described with special regard to tumor proliferation and epigenetic dysregulation, and the finding of TSHZ1 amplifications is discussed with special respect to the hypothesis of JAs as malformations of the first branchial arch artery.
International Journal of Oncology 11/2011; 39(5):1143-51. · 2.40 Impact Factor
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ABSTRACT: To study the involvement of the different semicircular canals in posttraumatic benign paroxysmal positioning vertigo (BPPV) with special reference to the anterior canal (AC).
Retrospective review.
Tertiary referral center.
Seventy-four BPPV patients.
Neurotologic assessment with video-oculography; treatment of BPPV with the canalith repositioning procedure appropriate for the affected semicircular canal.
Number of patients with AC, posterior canal (PC), horizontal canal (HC), and multiple-canal involvement in posttraumatic versus idiopathic BPPV.
85.1% of patients were classified as idiopathic BPPV, whereas 14.9% had a history of posttraumatic BPPV. The prevalence of AC BPPV was significantly higher in the posttraumatic group (27.3%) compared with that in the idiopathic group (3.2%; Fisher's exact test: p = 0.021). Multiple-canal (combined) BPPV was observed more frequently after head trauma (27.3%) compared with the idiopathic form of the disorder (1.6%; p = 0.009). In particular, the risk for combined AC/PC BPPV was greater in posttraumatic than idiopathic cases (odds ratio, 13.78; 95% confidence interval, 1.13-167.8). No significant differences were observed for the involvement of the PC and HC between the two groups. Two cases of combined AC/PC BPPV are presented with particular respect to the underlying trauma mechanism.
Head trauma is a risk factor for AC and combined BPPV, in particular AC/PC BPPV. Involvement of the AC should especially be considered in patients who experienced head trauma resulting in a nonupright position of the body.
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 09/2011; 32(8):1285-90. · 1.44 Impact Factor
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ABSTRACT: Efferent olivocochlear feedback innervation modulates the stream of auditory information from cochlea to brainstem by regulating auditory nerve activity and controlling the contribution of cochlear outer hair cells to basilar membrane motion. In our previous work, we gave a first description of glycine receptors (GlyRs) in the rat cochlea indicating a possible localization at efferent cochlear synapses. Here, we analyze the developmental regulation of GlyR transcripts and protein within the developing murine organ of Corti (postnatal days P0-P21). Using quantitative RT-PCR, GlyRα1 and α2 were identified as the predominant GlyRα subunit transcripts before the onset of hearing (<P12), whereas GlyRα3 prevailed afterwards. Compared to GlyRα subunits, high levels of GlyRβ mRNA were detected from P0-P21. Nested RT-PCR of isolated hair cells revealed a translocation of GlyRα and β transcripts from inner to outer hair cells paralleling the shift of efferent cochlear innervation from inner to outer hair cells around the onset of hearing. This observation was verified on the protein level by immunostaining of GlyRα protein on cochlear cryosections. Finally, postsynaptic clusters of α3-containing GlyRs were located to efferent synapses of the medial and lateral olivocochlear bundle in the murine organ of Corti beyond the onset of hearing. In summary, the distinct developmental regulation of GlyRs in the murine cochlea advocates a contribution of these chloride channels to efferent olivocochlear innervation.
Histochemie 08/2011; 136(4):387-98. · 2.59 Impact Factor
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Jan Weiss,
Martina Pyrski,
Eric Jacobi,
Bernd Bufe,
Vivienne Willnecker, Bernhard Schick,
Philippe Zizzari,
Samuel J Gossage,
Charles A Greer,
Trese Leinders-Zufall,
C Geoffrey Woods,
John N Wood,
Frank Zufall
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ABSTRACT: Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.
Nature 03/2011; 472(7342):186-90. · 36.28 Impact Factor
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ABSTRACT: SUMMARY: Neurogenic neoplasms account for approximately 1% of salivary gland tumors. A 45-year-old woman presented with a slowly growing unilateral parotid gland mass that was excised completely by lateral parotidectomy. No recurrence was detectable 6 months after surgery. The resection specimen contained a 1.7 × 1.2 × 1-cm whitish nodular lesion that was firm, well circumscribed, and completely surrounded by compressed normal glandular tissue. The tumor was composed of spindle cells with bipolar tapering, wavy nuclei, and palely stained cytoplasm. The tumor cells were arranged in storiform, lamellar, and whorled patterns. Nuclear atypia, necrosis, and significant mitotic activity were absent. Immunohistochemistry showed expression of epithelial membrane antigen, glucose transporter 1, claudin-1, and collagen IV. All other lineage-specific markers including protein S100 were negative in the tumor cells. To our knowledge, this case represents the first report of soft tissue perineurioma in the salivary gland. Lack of previous reports suggests underrecognition of this tumor entity at this unusual anatomical site.
Human pathology 01/2011; 42(6):904-8. · 3.03 Impact Factor
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ABSTRACT: Cochlear implantation assessment is possible using commercially available standard flat-detector computed tomography (FD-CT) protocols. Image quality is superior to multislice CT (MSCT). The radiation dose of FD-CT is lower in comparison with MSCT standard protocols and may therefore overcome the limitations of MSCT in the evaluation of cochlear implants.
FD-CT offers higher spatial resolution than MSCT. Our objective was to compare the image quality of FD-CT to conventional MSCT in the visualization of a cochlear implant electrode array with respect to radiation exposure.
An isolated temporal bone specimen was scanned using a commercially available FD-CT system and a 4 and 64 row MSCT scanner. Different scanning protocols were used. Image quality was assessed by four independent readers using a scoring system with different criteria describing delineation of the cochlea and the electrode array, image noise and spatial resolution. Radiation dose was measured using the CT dose index (CTDI) and a 16 cm acrylic phantom.
Image quality was rated superior for FD-CT for all criteria by all readers. Single electrode contacts were only visible in FD-CT and assessment of implant position was improved by FD-CT. The radiation dose of FD-CT was half that of MSCT standard protocols.
Acta oto-laryngologica 11/2009; 130(4):443-52. · 0.98 Impact Factor
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ABSTRACT: The study presented here evaluates the hearing results after the implantation of a new nickel-titanium (Nitinol) prosthesis in stapes surgery; on heating, this prosthesis crimps itself around the long process of the incus. In addition, we compare the outcome with results published in the literature. The medical records of all patients who underwent surgery for otosclerosis with implantation of a Nitinol piston during the period 2004-2006 were evaluated retrospectively. 83 patients (58 women and 25 men), with a provisional diagnosis of otosclerosis that was confirmed during surgery in all but one of the cases, were treated by primary stapes surgery (85 ears). We were able to include 53 patients (55 ears) who had audiograms with air and bone conduction preoperatively and both 2-6 weeks and about 1 year after surgery. We found a mean air-bone gap (ABG) for the frequencies 0.5, 1, 2 and 4 kHz (ABG4000) of 10.4 ± 5.5 dB after a mean postoperative follow-up period of 24.5 ± 16 days, and of 7.4 ± 3.7 dB after 462 ± 119 days. For the frequencies 0.5, 1, 2 and 3 kHz (ABG3000), the results were 9.1 ± 4.8 and 6.4 ± 3.9 dB. The differences in preoperative versus postoperative air-bone gap, referred to as ABGC, after 25 and 462 days, respectively, were 19.4 ± 8.9 and 22.3 ± 8.8 dB for AGB4000, and 19.5 ± 8.8 and 22.2 ± 8.9 for ABG3000. Very good results were achieved with a new nickel-titanium prosthesis that crimps itself around the long process of the incus, thus facilitating stapes surgery and at the same time stabilizing the high quality of the results. However, no long-term results after 10 years or more, which would allow a final judgment, are yet available.
Archives of Oto-Rhino-Laryngology 06/2009; 267(1):27-34. · 1.29 Impact Factor
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ABSTRACT: The extracellular matrix component collagen type VI demonstrates potent growth-stimulatory effects and has been associated with aggressive tumour growth. Although, juvenile angiofibromas (JAs) often exhibit an aggressive growth pattern, the collagen type VI expression of this fibrovascular tumour has not been addressed so far. RT-PCR, Western blot analysis and immunohistochemistry were used in this study to analyse collagen type VI, type VI collagen receptor subunits (integrin alpha1, alpha2, alpha10, alpha11 and beta1) and the type VI collagen receptor NG2 in JAs (N = 15) and nasal mucosa (NM, N = 8) samples. The mRNA expression of all three collagen type VI chains was found to be up-regulated significantly (P < 10(-3)-10(-5), adjusted) in JAs compared to NM tissues. The Western blot analysis proved highly prominent collagen-type VI expression in JAs. The ApoTome technique revealed strong collagen-type VI signals in tumour endothelium. NG2 (P < 10(-3), adjusted) and alpha11-integrin (P = 0.04, adjusted) showed a significantly higher mRNA expression levels in JAs than in NM samples. NG2, alpha1-, alpha2- and beta1-intergin were located to tumour vessels, and additional stromal signals were observed for NG2 and alpha1-integrin in JAs. This study demonstrates a prominent collagen-type VI expression in JAs. The collagen-type VI may exert an important growth stimulus in this tumour.
Histochemie 10/2008; 131(1):155-64. · 2.59 Impact Factor
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ABSTRACT: The cochlear efferent feedback system exerts direct impact on cochlear nerve activity and balances interaural sensitivity. So far, acetylcholine, GABA and dopamine are known to be transmitters of the inhibitory efferent system. Despite the wealth of information about glycinergic neurotransmission in the central auditory system, the inhibitory glycine receptor (GlyR) has not yet been regarded as a target molecule of efferent transmission in the cochlea. Using RT-PCR, in situ hybridization and immunohistochemistry, we show that GlyRalpha3, GlyRbeta and gephyrin are expressed in the organ of Corti and spiral ganglion neurons. Furthermore, two alternative splice variants of GlyRalpha3, corresponding to the long (alpha3_L) and short (alpha3_K) human isoforms, could be distinguished. The localization of glycine receptors below inner hair cells and in outer hair cells of the adult cochlea suggests that these inhibitory receptors may serve as target molecules of the efferent olivocochlear bundle.
Histochemie 05/2008; 129(4):513-23. · 2.59 Impact Factor
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ABSTRACT: To analyze temporal lobe gliosis and temporal lobe dysfunction after middle fossa vestibular schwannoma surgery.
Temporal lobe analysis of a series of cases.
Tertiary referral center.
Thirty-two patients after enlarged middle fossa surgery (EMFS) and 20 subjects for control (preferably husbands/wives).
Magnetic resonance evaluation of the temporal lobe and neuropsychological testing.
Magnetic resonance imaging of the temporal lobe 1 year after treatment and neuropsychological testing (Berliner Amnesia Test [BAT], Boston Naming Test [BT], Token Test, Beck Depression Inventory, Freiburger Personality Inventory).
Temporal lobe gliosis after EMFS was observed in 22 of 32 analyzed patients (degree of gliosis: 11, slight; 9, moderate; 2, severe). Neuropsychological testing of 23 of the 32 previously analyzed patients after EMFS compared with control subjects (n=20) found only in few subdomains (figural score, personality test) statistically significant worse test results, but no major disturbances of the temporal lobe function compared with the control group. Only one patient with a finding of severe temporal lobe gliosis was proven in the BAT and BT to have a temporal lobe deficit.
In a significant number of patients, temporal lobe gliosis has to be expected after EMFS; however, the gliosis is only slight or moderate in most of the patients and not associated with essential functional deficits of the temporal lobe. Nevertheless, the possibility of a severe temporal lobe gliosis with functional deficits in the BAT and BT has to be taken into consideration.
Ontology & Neurotology 02/2008; 29(1):39-45. · 1.90 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) act in diverse physiological and pathological conditions such as tumor growth and angiogenesis by cleaving extracellular matrix and nonmatrix substrates. MMPs with gelatinase/collagenase activity have not yet been studied in juvenile angiofibroma, a unique fibrovascular tumor with prominent collagen expression. Quantitative real-time polymerase chain reaction studies, Western blot analysis, immunofluorescence studies, gel zymography, and in situ zymography were used to analyze MMP-1, MMP-2, MMP-9, MMP-13, MMP-14, TIMP-1, and TIMP-2 in 9 juvenile angiofibromas and 2 inferior nasal turbinate specimens. Quantitative real-time polymerase chain reaction found significantly elevated expression of MMP-2, MMP-9, and MMP-14 (P < .05) in tumor tissue compared with the inferior nasal turbinate specimens. Western blot analysis detected more prominent MMP-1, MMP-2, and MMP-9 protein levels in juvenile angiofibromas compared with inferior nasal turbinates, but not MMP-13, MMP-14, TIMP-1, and TIMP-2. Immunofluorescent staining proved a mainly stromal localization of the analyzed MMPs. Only MMP-9 and MMP-14 were also detected in vessel walls. MMP-1, MMP-2, and MMP-13 also stained mast cells. Gel zymography indicated increased MMP-2 and MMP-9 gelatinase activity in juvenile angiofibromas compared with inferior nasal turbinates. Finally, in situ zymography detected very high stromal gelatinase/collagenase activity. This study indicates significant expression of MMPs with gelatinase/collagenase activity in juvenile angiofibromas with evidence of a disturbed balance of MMPs to TIMPs toward enhanced MMP activity. These MMPs are assumed to be involved in tumor pathology with an influence on tumor growth and angiogenesis.
Human Pathlogy 02/2008; 39(2):259-68. · 2.88 Impact Factor
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ABSTRACT: This study confirms the wide range of vascular architecture in juvenile angiofibromas. Proof of laminin alpha2 expression in tumour vessels is suggested to indicate presence of vessels of early developmental stage in juvenile angiofibromas, supporting the concept that plexus remnants of the first branchial arch artery contribute to the vascular tumour component.
Laminins, one of the major components of vascular wall basement membranes, have been implicated in tumour growth and have been shown to have developmentally regulated expression patterns. The goal of this study was to analyse the expression of laminins in juvenile angiofibromas.
A detailed analysis of the laminin isoform expression was performed by immunofluorescence staining for laminin chains alpha1, alpha2, alpha3, alpha4, alpha5, beta1, beta2, beta3, gamma1, gamma2, and gamma3 on cryosections of 10 juvenile angiofibromas and inferior nasal turbinate tissue for control.
Vascular staining of the different laminin chains revealed areas of differential vessel density in juvenile angiofibromas and irregularities in vessel size, configuration and architecture. Similar to vessels in nasal turbinates, laminins alpha4, alpha5, beta1, beta2 and gamma1 were found to be expressed in juvenile angiofibroma vessels. In contrast to vessels of nasal turbinates, staining for alpha2 and alpha3 chains was only detected in vessels of juvenile angiofibromas.
Acta Oto-Laryngologica 01/2008; 127(12):1310-5. · 1.08 Impact Factor
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Stefan Dazert, Bernhard Schick,
Rene Hartensuer,
Stefan Volkenstein,
Christoph Aletsee,
Stefan Hansen,
Wafaa E Shehata-Dieler,
Martin Eigenthaler,
Ulrich Walter,
Allen F Ryan,
Dominik Brors
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ABSTRACT: Vasodilator-stimulated phosphoprotein (VASP) has been found to be involved in intracellular signalling pathways and to play an important role in the actin associated organization and formation of the cytoskeleton. Since differential VASP expression was noted in inner ear tissues, the present study was performed to investigate the hearing development in VASP deficient mice. Hearing development in VASP-/- mice and wild type animals was investigated by auditory brain stem (ABR) measurements. In addition, inner ear tissues of wild type animals were tested for VASP expression using PCR, Western blot analysis, in situ hybridisation, and immunohistochemistry. To compare spiral ganglion (SG) neurite growth, SG explants from VASP-/- and wild type mice were analyzed under cell culture conditions. The electroacoustical results of the present study indicate that VASP deficient mice present with a later onset of hearing during postnatal development compared to wild type animals. Transient VASP expression was detected in neonatal SG of wild type mice. Tissue culture experiments with SG explants from VASP-/- animals revealed significant alterations in SG neurite extension compared to wild types. The present findings suggest a role for VASP during neonatal development of the mammalian cochlea and allow speculation on a possible delayed innervation of cochlear hair cells due to changes in SG neurite growth in VASP-deficient mice. Temporary VASP deficits in the neonatal inner ear may be compensated by related proteins like MENA leading to a delayed but complete development of hearing function in VASP-/- animals.
Brain Research 11/2007; 1178:73-82. · 2.73 Impact Factor
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ABSTRACT: Juvenile angiofibroma (JA) is regarded as a benign fibrovascular tumour of unknown aetiology. Due to its fibrovascular architecture the fibrous and vascular tumour component have been in the focus of most studies. This investigation aimed at characterizing inflammatory cells in JAs by immunohistochemical stainings and western blot analysis. Number and type of mast cells as well as T-lymphocytes were evaluated in a series of 10 JAs and 5 nasal mucosa (NM) specimens used as control tissue. A remarkable number of mast cells were found in JAs (14.6% of all cells). By using a combination of the mast cell markers tryptase and chymase three distinct mast cell populations could be identified: 12% expressed tryptase (T+) only, 3% stained for chymase (C+) only, and 85% were positive for both tryptase and chymase (TC+). Western blot analysis supported finding of remarkable expression of the mast cell markers tryptase and chymase in JAs and indicated for both proteins similar but also different molecular weights than being observed in NM. Furthermore an infiltration of the tumour by CD4- and CD8-positive T-lymphocytes (15.4% of all cells) was evident in immunofluorescent stainings. Compared to NM, a significantly higher number of TC+ (6.9% in JAs versus 2.7% in NM) and CD8-positive (9.7% in JAs versus 5.8% in NM) cells were found in the tumour tissue. Thus, mast cells and T-lymphocytes were identified as predominant cell types in JAs representing 30% of the cells in the tumour specimens analysed. Regarding these observations JAs are certainly not only built up by vascular cells and fibrous stroma cells. High rates of inflammatory cells like mast cells and T-lymphocytes have to be considered in this tumour.
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 08/2007; 264(7):769-75. · 1.29 Impact Factor
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ABSTRACT: Frequent beta-catenin mutations have been detected in juvenile angiofibromas, but the tumor pathogenesis remains unknown.
Metaphase-comparative genomic hybridization (CGH) was used to identify chromosomal aberrations in 29 tumor specimens. Two tumors were investigated using genome DNA microarrays.
Three hundred eleven chromosomal gains and losses were detected by metaphase-CGH. Frequent chromosomal gains were detected at 4q, 6, 12, and X, while frequent chromosomal losses affected regions of chromosomes 8, 16, 17, 22, and Y. Genome DNA microarray analysis in 2 tumors of the series confirmed chromosomal aberrations, detected by metaphase-CGH, and indicated genes such as AURKA (20q13.2) not being recognized by metaphase-CGH.
Metaphase-CGH results confirmed numerous chromosomal aberrations in juvenile angiofibromas. The most frequent aberrations affected sex chromosomes. Further consensus regions of chromosomal aberrations were detected at 4q, 6, 8, 12, 16, 17, and 22. AURKA and MDM2 were identified as interesting novel amplified genes in juvenile angiofibromas.
Head & Neck 06/2007; 29(5):479-87. · 2.40 Impact Factor
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ABSTRACT: Silica nanoparticles may serve as a nonviral delivery system to the sensory hair cells, spiral ganglion cells within the cochlea, and the vestibular organ, as well as the cochlear nucleus.
At present there are no targeted therapeutics for inner ear disease. A variety of viral vector systems have been tested in the inner ear with variable efficacy but they are still not regarded as safe systems for inner ear delivery. Nanoparticles are a nonviral method of delivering a variety of macromolecules that potentially can be used for delivery within the auditory system. In this study, we evaluated the distribution and safety of nanoparticles in the inner ear.
Cy3-labeled silica nanoparticles were placed on the round window membrane of adult mice. Hearing thresholds were determined after nanoparticle delivery by auditory brainstem responses (ABRs). Distribution of particles was determined by histological evaluation of the cochlea, vestibular organs, and brain stem.
Fluorescent microscopy demonstrated Cy3-labeled nanoparticles signals in the sensory hair cells and the spiral ganglion neurons of both the treated and contralateral inner ears. Additionally, the distal part of the central auditory pathway (dorsal cochlear nucleus, superior olivary complex) was found to be labeled with the Cy3-linked silica nanoparticles, indicating a retrograde axonal transport. No hearing loss or inflammation was noted in the treated cochlea.
Acta Oto-Laryngologica 06/2007; 127(5):486-90. · 1.08 Impact Factor
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Bernhard Schick MD,
Silke Wemmert,
Ulrike Bechtel,
Piero Nicolai MD,
Thiemo Hofmann MD,
Wieslaw Golabek MD,
Steffi Urbschat PhD, Bernhard Schick,
Piero Nicolai,
Thiemo Hofmann,
Wieslaw Golabek,
Steffi Urbschat
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ABSTRACT: Background.Frequent β-catenin mutations have been detected in juvenile angiofibromas, but the tumor pathogenesis remains unknown.Methods.Metaphase-comparative genomic hybridization (CGH) was used to identify chromosomal aberrations in 29 tumor specimens. Two tumors were investigated using genome DNA microarrays.Results.Three hundred eleven chromosomal gains and losses were detected by metaphase-CGH. Frequent chromosomal gains were detected at 4q, 6, 12, and X, while frequent chromosomal losses affected regions of chromosomes 8, 16, 17, 22, and Y. Genome DNA microarray analysis in 2 tumors of the series confirmed chromosomal aberrations, detected by metaphase-CGH, and indicated genes such as AURKA (20q13.2) not being recognized by metaphase-CGH.Conclusion.Metaphase-CGH results confirmed numerous chromosomal aberrations in juvenile angiofibromas. The most frequent aberrations affected sex chromosomes. Further consensus regions of chromosomal aberrations were detected at 4q, 6, 8, 12, 16, 17, and 22. AURKA and MDM2 were identified as interesting novel amplified genes in juvenile angiofibromas. © 2006 Wiley Periodicals, Inc. Head Neck, 2007
Head & Neck 04/2007; 29(5):479 - 487. · 2.40 Impact Factor
