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T Stöver

Publications and source records attributed to T Stöver.

At least 37 records · Page 2Linked to original sources
PubMed2001

Glial cell line-derived neurotrophic factor (GDNF) and its receptor complex are expressed in the auditory nerve of the mature rat cochlea.

Glial cell line-derived neurotrophic factor (GDNF) is a survival factor for many neuronal cell types which signals through a heterodimer receptor consisting of GDNF-family receptor alpha 1 (GFRalpha-1) and Ret (rearranged during transformation). GDNF expression has previously been reported in the inner hair cells of the rat cochlea, with expression of GFRalpha-1 but not Ret in the cell bodies of the auditory nerve (spiral ganglion cells), using in situ hybridization. The present study used reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry to examine GDNF, GFRalpha-1 and Ret in the adult rat auditory nerve. Semi-quantitative RT-PCR showed expression of GDNF and the two receptor components, GFRalpha-1 and Ret, in the modiolar subfraction of the cochlea containing spiral ganglion cells. A shorter mRNA splice variant for GDNF was also detected. Immunocytochemistry showed immunostaining in the modiolus for GDNF, GFRalpha-1 and Ret that was confined to spiral ganglion cells. When RT-PCR expression levels were compared to the expression in the substantia nigra, GFRalpha-1 expression levels were similar, Ret mRNA was lower in the modiolus and GDNF expression was higher in the modiolus. However, when GDNF was further assessed using Western blot, while GDNF protein was found in the modiolus it was at lower levels than in substantia nigra tissue. These results demonstrate that GDNF and both of its receptor components are found in spiral ganglion cells of the adult rat cochlea. Along with the previous report of GDNF in inner hair cells, these new results provide a basis for the role of GDNF as a survival factor for the auditory nerve, as suggested by previous studies.

Animals↗
PubMed2001

[Feasibility of inner ear gene transfer after middle ear administration of an adenovirus vector].

BACKGROUND: Several groups demonstrated in animal experiments that gene transfer is a feasible tool for inner ear intervention. Various approaches for inoculation of vectors have been successfully used for inner ear gene therapy. One possible way to reduce the risk of hearing loss following the opening of the cochlea for application of the vector into the perilymphatic space is to deliver vectors through the round window. This study was designed to determine whether middle ear application of an adenoviral vector is a feasible approach to inoculate vectors and lead to transduction of cells in the inner ear. METHODS: A unilateral middle ear application of an adenoviral vector was performed in 4 guinea pigs directly on the round window membrane (RWM) and in 4 additional animals by placing a cotton patch soaked with the vector solution on the RWM. The expression of a reporter gene (lacZ) was used to localize vector-transduced cells. RESULTS: Only one out of 8 animals showed cochlear expression of the reporter gene, whereas all 8 animals showed strong lacZ expression in the middle ear mucosa, in the RWM and in the mucosa surrounding the stapes. CONCLUSION: Our results indicate that the RWM presents a close barrier, almost completely preventing the adenovirus to diffuse into the perilymphatic space. Therefore middle ear application of an adenoviral vector cannot be used to induce inner ear gene transfer. However, middle ear application of a viral vector may be useful for developing treatment for diseases of the middle ear mucosa.

Adenoviruses, Human↗
PubMed2000

Expression of the GDNF family members and their receptors in the mature rat cochlea.

The GDNF family comprises glial cell line-derived neurotrophic factor (GDNF) and the related proteins neurturin, artemin and persephin, which form a subgroup of the TGF-beta superfamily of growth factors. All four neurotrophic factors provide neuronal cell protection and cell survival. GDNF expression was found in the cochlea, and GDNF has been shown to be effective for inner ear protection from drugs and noise-induced insults. As the other members of the GDNF family also provide protective effects on neuronal cells, they may play important roles in the inner ear. We used RT-PCR to examine the expression of GDNF, neurturin, artemin, persephin and their receptors GFRalpha-1, GFRalpha-2, GFRalpha-3 and c-ret in whole rat cochlea as well as in functionally different subfractions (modiolus and sensorineural epithelium/lateral wall) and compared the levels of neurotrophin and receptor mRNAs in the cochlea to those in substantia nigra brain region. Our results demonstrate the expression of all GDNF family members and their receptors in cochlea and substantia nigra. However, the relative levels of mRNA were different for several genes tested in subfractions of the cochlea and/or compared to expression levels in substantia nigra. The presence of mRNA for all four members of the GDNF family and their preferred receptors in the rat cochlea suggests potential functional importance of these neurotrophic factors as protection and survival factors in the inner ear.

Animals↗
PubMed2000

Upregulation of glial cell line-derived neurotrophic factor (GDNF) in the rat cochlea following noise.

There are endogenous intracellular mechanisms that provide cells with protection from stress, as well as repair from damage. These pathways often involve stress proteins and neurotrophic factors. The present study used Western blot analysis to examine changes in glial cell line-derived neurotrophic factor (GDNF) following noise overstimulation. A noise exposure was utilized which causes a temporary threshold shift and has been previously shown to upregulate heat shock protein 72 in the rat cochlea. This noise exposure also provides protection from a second noise exposure that would otherwise cause a permanent threshold shift. Experimental animals were assessed 2, 4, 8 and 12 h after cessation of noise exposure. Control animals received the same treatment except for the noise exposure and were assessed at the 8 h time point. A moderate expression of GDNF was observed in the normal cochlea. No significant change in GDNF levels was observed at 2 or 4 h following noise overstimulation. However, a significant increase was found at 8 h. At 12 h following noise overstimulation, GDNF levels were no longer significantly elevated from normal. These results suggest that GDNF is involved in the endogenous stress response in the cochlea and are consistent with the protection that exogenously applied GDNF has been shown to provide.

Animals↗
PubMed2000

Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer.

Cochlear gene transfer is a promising new approach for inner ear therapy. Previous studies have demonstrated hair cell protection with cochlear gene transfer not only in the inoculated, but also in the uninoculated ear. To characterize the kinetics of viral spread, we investigated the extent of transgene expression in the contralateral (uninoculated) cochlea after unilateral adenoviral cochlear gene transfer. We used a lacZ reporter gene vector, and demonstrated spread of the adenovirus into the cerebrospinal fluid (CSF) after cochlear inoculation of 25 microl viral vector. Direct virus application into the CSF resulted in transduction of both cochleae, whereas virus inoculation into the bloodstream did not. The cochlear aqueduct was identified as the most likely route of virus spread to the contralateral cochlea. These data enhance our understanding of the kinetics of virus-mediated transgene expression in the inner ear, and assist in the development of clinical applications for inner ear gene therapy. Our results showed a functional communication between the CSF and the perilymphatic space of the inner ear, that is not only of importance for otological gene transfer, but also for CNS gene transfer. Gene Therapy (2000) 7, 377-383.

Adenoviridae↗
PubMed2000

Mastoiditis and acute otitis media in children with cochlear implants: recommendations for medical management.

Acute otitis media (OM) or mastoiditis is a very dangerous condition for the ear after cochlear implantation. However, acute OM is very common in childhood and can occasionally occur in an implanted ear. Most cases of acute OM can be successfully treated with intravenous high-dosage antibiotics. In cases of mastoiditis and clinical signs of mastoid abscess, retroauricular drainage is necessary to prevent infection of the implant bed. In a series of 366 children given implants (1 to 14 years), acute OM occurred in 5.6% during a follow-up period of 1 to 8 years. Seven ears had to be opened by means of myringotomy. Five ears were opened by retroauricular incision with mastoid revision on the implanted side. Adenoidectomy and use of ventilation tubes before cochlear implantation, as well as careful subtotal mastoidectomy during the implantation, can reduce the incidence of acute OM in children after implantation. Early and subsequent treatment with operative mastoid drainage can prevent implant loss and should be performed at the implantation center.

Acute Disease↗
PubMed1999

Cochlear gene transfer: round window versus cochleostomy inoculation.

Two possible approaches for cochlear gene transfer have been inoculation via the round window membrane and through a cochleostomy. The aim of this study was to determine which of the two is more effective. Using both approaches, normal-hearing and deafened guinea pigs were inoculated with adenovirus carrying the reporter gene lacZ. After 5 days, the animals were killed and the cochlear tissue was stained with X-gal. The distribution and intensity of staining was estimated by a score system developed to compare gene transfer results between animals. We found that gene transfer via the cochleostomy resulted in a better distribution throughout the cochlea and in higher staining intensity, due to more efficient transfection. Auditory brainstem response (ABR) results showed that neither virus inoculation through a cochleostomy nor through the round window membrane had a significant effect on the click-ABR threshold measured on day 5 following virus injection. Gene transfer via both approaches was also found to be more effective in deafened animals than in hearing animals.

Adenoviridae↗
PubMed1999

[Sonographic diagnosis of metastatic renal cell carcinoma to the head and neck region].

In the area of the head and neck metastases from distant primary tumours are rare in comparison to the common squamous cell carcinomas of the upper respiratory and digestive tract. Thus correct preoperative diagnosis may be difficult. Two cases with distant metastases of renal cell carcinoma to the head and neck region are presented in this report. In a 60-year-old male patient, diagnostic evaluation of unilateral epistaxis revealed a radioopacity of the maxillary sinus, six months after removal of a renal cell carcinoma. In the second case a slowly progressive indolent swelling of the left neck developed in a 56-year-old man six years after resection of a renal cell carcinoma and two years after surgical treatment of a pancreatic carcinoma. Following clinical examination, modern imaging techniques with special emphasis on colour Doppler sonography with a Siemens Quantum 2000 were used for diagnostic evaluation in both patients. Sonography of metastatic renal cell carcinoma to the maxillary sinus revealed complete opacity of the antrum. The cervical mass proved to the inhomogeneous and hypoechogenic and was difficult to distinguish from the lower parotid lobe and the vessel sheath. A common feature of both tumours was a high degree of perfusion which could be confirmed by superselective angiography. The histological examination of the surgical specimen showed an isolated metastasis of a renal cell carcinoma in both cases. In patients with a history of renal cell carcinoma the possibility of distant spread to the head and neck region should be taken into account even after a long period of complete remission. Colour Doppler sonography facilitates the distinction between the normally well perfused secondary tumours and squamous cell carcinomas which usually only have a minimal blood supply. Because of the high risk of profuse bleeding a biopsy should only be performed in the operating theatre.

Carcinoma, Renal Cell↗
PubMed1999

Adenoid cystic carcinoma of the skull base.

Adenoid cystic carcinoma (ACC) is a slowly growing tumor with a particular tendency to infiltrate the surrounding tissue by perineural spread. The clinical diagnosis may prove difficult due to the submucons extension of the tumor, especially at the skull base. This article outlines the clinical characteristics, diagnostics, and treatment modalities in a series of 56 patients with an ACC in the head and neck diagnosed between 1970 and 1998 in 32 females and 24 males. The youngest patient was aged 24 years, the oldest 77 years. The average age was 54 years. In 16 patients the tumor originated in the paranasal sinuses or the nasopharynx and involved the skull base. As a rule, several months passed between the manifestation of the first symptoms such as pain, blocked nose, epistaxis, or diplopia and the initial clinical diagnosis. All patients received surgical treatment, however, complete microscopical resection could only be achieved in approximately one third of the cases. Therefore, nine patients were postoperatively treated with radiotherapy. The average survival rates of the patients with an ACC of the skull base were only 99 months as compared to 144 months in the patients without skull base involvement.

Journal Article↗