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Biomedical subjects

S Maune

Publications and source records attributed to S Maune.

At least 37 records · Page 2Linked to original sources

Nitric oxide uncouples gap junctions of supporting Deiters cells from Corti's organ.

Supporting cells of Corti's organ are electrically coupled via gap junctions. They probably serve to maintain the unique cochlear environment that is required for normal sensory function. In this study we used input capacitance measurements under whole-cell voltage-clamp conditions to evaluate the effects of nitric oxide on gap junctional communication between pairs of isolated supporting Deiters cells. We show that the nitric oxide (NO) donor sodium nitroprusside causes the uncoupling of Deiters cells, and that an NO synthase inhibitor blocks the effect. The cGMP analogue 8-bromo-cGMP also uncouples Deiters cells. With either treatment, the input capacitance of pairs of Deiters cells drops to single-cell levels within minutes of application, indicative of electrical uncoupling. We surmise that the NO/cGMP pathway may serve to modulate normal cochlear homeostasis and possibly plays a role in ototoxic mechanisms.

Animals↗

[Detection of overexpression of insulin receptor gene in laryngeal carcinoma cells by using differential display method].

BACKGROUND: The insulin receptor (IR) is an essential protein localized on the surface of almost all cell types. IR belongs to the tyrosine-kinase growth factor receptor family. Insulin mediates proliferative responses in a variety of tumor cells, however, the role of the IR molecule in carcinogenesis has not yet exactly been established. METHODS: Messenger RNA from mucosal keratinocytes and laryngeal carcinoma cells were transcribed in cDNA using reverse transcriptase and amplified by PCR by means of a number of oligonucleotides. PCR products were analyzed electrophoretically. RESULTS: Comparing the electrophoretic pattern of both cell types the overexpression of a 127 bp fragment could be detected in laryngeal carcinoma cells in contrast to benign keratinocytes. Cloning and sequencing this fragment exact homologous match was found with exon-2 of the IR gene. The overexpression of the IR gene in laryngeal carcinoma cells was confirmed by Northern hybridization. CONCLUSIONS: The results show up-regulation of IR-mRNA in laryngeal carcinoma cells suggesting that the number of IR is enhanced in these cells. Hence it follows, that the overexpression of IR plays a possible role in laryngeal cancer initiation and/or progression.

Autoradiography↗

[hBD-2 gene expression in nasal mucosa].

BACKGROUND: Chronic sinusitis is one of the frequent inflammatory diseases and has a complex pathogenesis. A substantial factor seems to be recurrent bacterial infections. Pseudomonas aeruginosa (PA) frequently can be found in nasal smears of patients with persistent sinus symptoms after sinus surgery. Lately a new antimicrobial peptide of epithelial origin, human Beta-Defensin-2 (hBD-2), with a strong antibacterial effect against PA could be identified within lesional skin scales of patients suffering psoriasis. Aim of this study was to investigate hBD-2-mRNA expression in nasal cells and tissue. METHODS: Total RNA was extracted from nasal polyps and turbinates following TRIzol protocol. Epithelial cells and fibroblasts of nasal human tissue were isolated and cultivated. The cells were stimulated with PA using different time points and different concentrations. Total RNA was isolated as mentioned above, reverse transcribed and amplified in a Semi-quantitative Reverse Transcriptase PCR (SQRT-PCR) with genespecific hBD-2 primers. RESULTS: PA induces time- and dose-dependently hBD-2 gene expression in nasal epithelial cells. Unstimulated epithelial nasal cells were able to express hBD-2 mRNA constitutively, whereas nasal fibroblasts showed no hBD-2 mRNA expression. Nasal polyps showed a comparable less hBD-2 gene expression then nasal turbinates. CONCLUSIONS: hBD-2 possibly mediates a specific, early starting antimicrobial defense strategy of the nasal mucosa. This hypothesis would explain persistent infections with PA through diminished hBD-2 gene expression.

Cells, Cultured↗

[Surgery of the external auditory canal in familial bilateral auditory canal atresia].

BACKGROUND: Inherited isolated bilateral atresia of the external auditory canal is rare. Ear canal surgery procedure is difficult. METHODS: Basing on a case report of a family with inherited isolated bilateral atresia of the external auditory canal in 4 cases the way of preoperative diagnostics including human genetics and our surgical concept is described. RESULTS: Resulting clinical findings showed complete epithelialization of the ear canal and ear drum with slight conductive hearing loss. CONCLUSIONS: Canaloplasty in atresia can be easily and successfully accomplished by our modified technique.

Adolescent↗

[Differential diagnosis of sinugenic enophthalmos].

BACKGROUND: Spontaneous enophthalmos without recent trauma is a rare condition. Its origin is difficult to evaluate. METHOD: Specific properties of this symptom complex are presented based on a literature review and on case reports. Possible connections between enophthalmos and paranasal sinus diseases as well as differential diagnoses are analysed. PATIENTS: 1. 31 year old female patient with right spontaneous enophthalmos and no history of trauma. CT-imaging disclosed tissue formation in the maxillary sinus, partially destroyed medial orbital wall and floor, descended orbital contents following Caldwell-Luc procedure several years previously. After endonasal surgery of ethmoidal and maxillary sinus with removal of a large cyst good functional and cosmetical result. 2. 25 year old male patient complaining of pain in the periorbital region, presenting with left enophthalmos and superonasal deviation of the eyeball. MRI and CT revealed a tumor in the orbital floor region with total destruction of the roof of the maxillary sinus. Removal of the tumor by a combined lateral rhinotomy and subciliary approach. DIAGNOSIS: Leiomyoma. Orbital reconstruction with PDS-sheet. Postoperatively, improved globe position and motility. No recurrence during three year follow-up. CONCLUSION: When evaluating the causes of enophthalmos, chronic diseases of the paranasal sinuses or their walls must be considered. Surgical therapy is promising.

Adult↗

[Long-term outcome of frontal sinus surgery: comparison of extranasal and endonasal surgical techniques].

BACKGROUND: During the last decades rhinosurgery largely developed up to endonasal accesses. Meanwhile many of the new techniques are established, so that the outcome of traditional extranasal methods should be compared with those of endonasal accesses, in order to estimate the status and for critical consideration. METHODS: A retrospective analysis recorded the results of 236 patients, operated on primary frontal sinus disease 1985-1993. The records were consulted concerning inpatient treatment and outpatient aftercare during standardized paranasal sinus consulting hours. RESULTS: During the follow-up period (3-10 years) 8% of the patients underwent resurgery. The lowest revision rate was found after using endonasal technique (5.9%), compared with osteoclastic methods (Ritter-Jansen, Riedel: 10.6%). The domain of osteoplastic operations with a revision rate of 9.4% were fractures, osteomas and mucoceles, because of an impossible endonasal access. In decision on osteoclastic procedures, the already osteoclastically operated site was of prime importance, especially since 1990. CONCLUSION: Already during the early years endonasal techniques of paranasal sinus surgery showed better outcome than osteoclastic accesses. The analysis indicates that the change to endonasal functional paranasal sinus surgery is justified and should be kept up. The traditional methods still have their rare authorization in case of special indications, especially if an osteoclastic procedure has been carried out already.

Follow-Up Studies↗

[Analysis of the p53 gene status of lymph node metastasis in the head and neck region in occult primary cancer].

BACKGROUND: Lymph node metastasis in the head and neck region with occult primary cancer are a fairly rare tumor entity in head and neck cancer. Tumor biological parameters as well as mechanism and cause for the development of this so called "cancer of unknown primary" (CUP) are not well investigated in head and neck cancer. Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration of human malignancies and show an incidence of up to 50% in head and neck cancer. For a further tumor biological definition of CUP the p53 status was determined. METHODS: Twenty-three archival formalin fixed paraffined CUP of an occult squamous cell carcinoma of the head and neck region were examined. In all cases a primary cancer was never diagnosed. The DNA extracted from the tumor material was amplified with specific primers for exon 4-9 of the p53 gene and subsequently sequenced. RESULTS: None of the 23 CUP cases showed a mutation or polymorphism in exon 4-9 of the p53 gene. CONCLUSIONS: The total absence of p53 mutations in the so called mutational "hot spots" shows a significant difference to the frequency of primary tumors of the head and neck region. May be this tumor biological characterisation helps to further elucidate the growth behaviour of CUP in the head and neck region and the reason for their development.

Antisense Elements (Genetics)↗

Tracing human papillomavirus DNA in nasal polyps by polymerase chain reaction.

Human papillomavirus (HPV) infections are related to the genesis of various benign and malignant human neoplasias. The HPV types 16 and 18 seem to be causally related to the development of most squamous cell carcinoma of the anogenital tract and a proportion of carcinomas of the upper aerodigestive tract. The near 100% positivity of the HPV types 6 and 11 in laryngeal papillomatosis is well established. We investigated whether HPV also plays a role in non-neoplastic mucosal entities such as sinunasal polyposis, the genesis of which has been discussed as being triggered by viral infections. On DNA from 39 sinunasal polyps (33 patients), polymerase chain reaction (PCR) was performed using beta-globin primers for demonstration of amplifiable DNA in the tissue extracts. Consensus primers for the detection of several different HPV types were applied to the beta-globin-positive samples. The results were confirmed by Southern blot hybridization using consensus probes. Cycle sequencing was performed on the positive cases. All 39 samples showed positive signals for beta-globin. HPV-DNA investigations showed a slight positive signal in only 1 of the 39 investigated cases (2.6%). Further molecular investigations of this sample, including cycle sequencing, could not confirm this result. All the other tissue samples remained HPV-DNA-negative. Therefore, those HPV types readily detectable with the PCR primers and probes used are not frequently associated with sinunasal polyposis. The data confirm the hypothesis that HPV is correlated to a lesser extent to infectious mucosal lesions than to proliferative lesions. Furthermore, the results emphasize that the presence of HPV in specific lesions does not occur by chance, but represents a specific infection of the mucosa leading to proliferation and even to malignancy.

DNA, Viral↗

Acoustic rhinometry: validation by three-dimensionally reconstructed computer tomographic scans.

The aim of the present study was a validation of acoustic rhinometry (AR) by computed tomography (CT). Six healthy subjects were examined by CT and AR. The CT data were processed in a computer program (AutoCAD), and a virtual three-dimensional model of each nasal cavity was constructed. This model permitted an individual prediction of the center line of the sound wave propagation through the air volume of the nasal cavity with the cross-sectional areas oriented perpendicularly to this line. The area-distance curves derived from AR and CT were compared. Linear regression analysis revealed a reasonable agreement of AR and CT in the anterior nose below a mean of 6 cm distance from the nostrils [r = 0.839, P < 0.01, m = 1.123, b = -0.113 (AR = m x CT + b)]. The measuring accuracy using CT as gold standard revealed a mean error at the nasal valve of <0.01 cm(2) (4.52%) and at the nasal isthmus of 0.02 cm(2) (1. 87%). Beyond 6 cm, the correlation decreased (r = 0.419), and overestimation of the true area occurred (>100%). In conclusion, the measurements were reasonably accurate for diagnostic use up to the turbinate head region. Certain factors induce an overestimation of the true areas beyond this region. However, these factors are constant and reproducible in a single subject, and intraindividual comparative measurements are possible beyond the turbinate head region.

Acoustics↗

Serum p53 autoantibodies in the follow-up of head and neck cancer patients.

p53 autoantibodies (AAB) are a fairly new serological parameter in patients with malignancies. Although the actual mechanism of how they develop is still unclear, it seems that these AAB could be of prognostic relevance. Very few studies demonstrated the usefulness of p53 AAB in the follow-up of cancer patients. In this study, 109 patients with head and neck cancer were investigated using an ELISA for the presence of p53 AAB in their serum and were followed-up for at least 36 months. In 21 of the cancer patients, p53 serum AAB were detected. In 5/21 p53-seropositive AAB patients, a correlation with the clinical course was observed. Sixteen of the p53-positive patients did not show any significant AAB titer changes during the follow-up, and no significant correlation with the clinical course was seen. According to these results, the clinical value of p53 AAB in the follow-up of patients with head and neck cancer seems to be limited.

Adult↗

Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia.

Cultured lung epithelial cells release antibacterial activity upon contact with Pseudomonas aeruginosa (PA), which is impaired in cystic fibrosis (CF). In order to identify the factors responsible for killing PA by a biochemical approach, we purified antimicrobial activity from supernatants of the A549 lung epithelial cell line, previously stimulated with PA bacteria, by subsequent high performance liquid chromatography. NH(2)-terminal sequencing of a major bactericidal compound revealed it to be identical with human beta-defensin-2 (hBD-2). A mucoid phenotype of PA, but not two nonmucoid PA strains, high concentrations (> 10 microg/ml) of PA lipopolysaccharide, tumor necrosis factor alpha, and interleukin (IL)-1beta, but not IL-6, dose-dependently induced hBD-2 messenger RNA in cultured normal bronchial, tracheal, as well as normal and CF-derived nasal epithelial cells. Genomic analysis of hBD-2 revealed a promoter region containing several putative transcription factor binding sites, including nuclear factor (NF) kappaB, activator protein (AP)-1, AP-2, and NF-IL-6, known to be involved in the regulation of inflammatory responses. Thus, hBD-2 represents a major inducible antimicrobial factor released by airway epithelial cells either on contact with mucoid PA or by endogenously produced primary cytokines. Therefore, it might be important in lung infections caused by mucoid PA, including those seen in patients with CF.

Amino Acid Sequence↗

Transcriptional repression of the human galactocerebrosidase gene in squamous cell carcinomas of the larynx.

Alterations of gene expression in squamous cell carcinoma (SCC) cell lines derived from the larynx and keratinocytes derived from adjacent normal mucosa of the larynx have been studied using the mRNA differential display technique. Lane-to-lane comparison of reverse transcribed mRNA showed a strong repression of a 148 bp fragment in SCC cells. The fragment was reamplified and cloned. Sequencing revealed a 99.3% homology with a region in exon 17 of the human galactocerebrosidase (GALC) gene. Northern blot analysis confirmed the differential expression of this gene in both carcinoma cell lines and laryngeal SCC biopsies in contrast with corresponding normal mucosa. To provide further evidence for the differential expression rate, both types of cells were transiently transfected with a 152 bp (-176 to -24) high regulatory promoter element of the 5' flanking region of the GALC gene. Results of 3 independent transfection experiments indicated a 16-fold repression of the GALC gene expression in SCC cells compared with benign keratinocytes. However, neither mutation nor other alterations of the promoter sequence were detected. Expression of the GALC gene is thus greatly affected in SCCs of the larynx.

Base Sequence↗

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice.

Modulation of tumour cell growth by tumour-infiltrating leucocytes is of high importance for the biological behaviour of malignant neoplasms. In melanoma, tumour-associated macrophages (TAM) and tumour-infiltrating lymphocytes (TIL) are of particular interest as inhibitors or enhancers of cell growth. Recruitment of leucocytes from the peripheral blood into the tumour site is mediated predominantly by chemotaxins, particularly by the group of chemokines. The aim of this study was to identify peptides released by human melanoma cells with monocyte chemotactic properties. To assure the presence of biologically active mediators, biochemical purification and biological characterization of peptides was based on a detection system dependent on bioactive, monocyte chemotactic activity in vitro. Cell culture supernatants of melanoma cells were fractioned by heparin-sepharose followed by preparative reversed-phase HPLC steps to enrich monocyte chemotactic activity in one single band on a sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gel. These purified fractions were shown to react with RANTES-specific antibodies in an enzyme-linked immunosorbent assay (ELISA) as well as in Western blot analysis. Amino acid sequencing of the N-terminal protein fragment confirmed 100% homology to the RANTES protein. Further analysis showed that four out of eight melanoma cell lines constitutively expressed and secreted the beta-chemokine RANTES as detected by ELISA. The amount of RANTES protein secreted (up to 50 ng ml(-1)) was about 5-50 times higher than interleukin 8 (IL-8), determined in the same supernatant samples. Tumour necrosis factor alpha, (TNF-alpha), not, however, IL-2, interferon-gamma (IFN-gamma), or (alpha-melanocyte-stimulating hormone (alpha-MSH) was able to up-regulate RANTES and interleukin 8 secretion. Furthermore, higher levels of RANTES secretion in vitro were associated with increased tumour formation upon s.c. injection of six human melanoma cell lines in nude mice. Our data provide evidence that a subset of melanoma cells express mRNA and secrete RANTES protein which may be partly responsible for the recruitment of monocytes, T-cells and dendritic cells into the tumours. However, transplantation experiments in nude mice suggest that effects of RANTES may also benefit tumour progression. Further studies are needed to dissect the underlying mechanisms.

Animals↗

[Surgical treatment of auditory canal exostoses].

BACKGROUND: Although complications of surgical removal of external auditory canal exostoses are rare, reported surgical complications include tympanic membrane perforation, postoperative hearing loss, canal stenosis, and facial nerve injuries. PATIENTS AND METHODS: We report on our experience in exostosis surgery, consisting of 59 procedures in 48 patients. Preoperative and postoperative complaints and findings, intraoperative complications, and audiologic results are described and discussed. There has been a minimum of one year of follow-up in every case. RESULTS: Postoperative canal stenosis was seen in 2 cases of preoperative severe persistent external otitis. Temporary threshold shift was recorded in 6 patients. Persistent sensorineural hearing loss occurred in 4 patients. Six of the 10 patients with temporary or persistent hearing loss had already shown preoperative sensorineural hearing loss. Intraoperatively tympanic membrane perforation occurred in 3 cases, accidental opening of the mastoid in 1 case. CONCLUSIONS: Exostosis surgery should be reserved for uninfected ear canals. Meatal skin preservation without circular meatal flap incision is recommended to avoid postoperative canal stenosis. Especially in cases of preexisting sensorineural hearing loss, attention should be focused on the intraoperative noise reduction by tympanic membrane protection and pauses of noise exposition.

Adult↗

[Concepts for measuring quality of life in patients with chronic sinusitis].

BACKGROUND: In 1997, Benninger developed the Rhinosinusitis Disability Index (RSBI) for patients who suffered from chronic sinusitis. Its content related validity and construct related validity were established, as were its sensitivity and reliability. The aim of our study is to introduce a concept to measure quality of life in these patients according to circumstances prevalent in Germany. METHODS: The questionnaire (Rhinusitis-Beeinträchtigungs-Index, RSBI) contains 30 questions that describe the 5 aspects of quality of life. Moreover we used a standardized data sheet to acquire further information about history and diagnostic results. Using this method it is possible to specificity more precisely the patients current complaints and condition. Evaluation is possible according to complex of questions as well as simple items. The influence of treatment on quality of life can be measured as the sum of the specific scores and is expressed comprehensively in the total score. The concept of the study includes a prospective inquiry as well as before and after surgical intervention. CONCLUSION: A disadvantage of the American RSDI is that the clinical symptoms are not described in a detailed catalogue which allows the correlation of the clinical factors. Therefore we added a detailed questionnaire concerning the clinical symptoms and the individual treatment of the patient (RSBI). That permits comprehensive analysis of quality of life as it relates to different aspects of disease and different strategies in treatment.

Chronic Disease↗

Prospective randomized investigation for evaluation of postoperative changes in the microbial climate of paranasal mucosa by the use of different dissoluting techniques during postoperative care.

Endonasal dissolution by the use of NaCl-solution is a common postoperative treatment of the nasal mucosa after endonasal surgery. These procedure involve for example endonasal shower and sterilized solutions. The contamination of nasal shower in case of unprofessional cleaning after treatment was an argument against this technique in earlier discussions. The danger of such an infection should be avoided by the use of sterilized solution. Therefore the dependence of nasal microbial climate on different nasal dissoluting techniques was investigated by the use of such named endonasal shower (Siemens und Co, Bad Ems, Germany) in comparison with sterilized solution (Rhinomer, Zyma SA, Nyon, France). Microbial cultures were investigated of 80 patients after endonasal surgery (53 m, 27 f; 31 +/- 21 age). Surgery was done for the treatment of chronic polypous sinusitis. Pre-, intra- and postoperative samples were taken in 640 cases to proceed microbial cultures. Material was transferred with the use of a Port-A-Cul-transport medium and preparation of the microbial cultures was done during the first four hours. As a result 895 bacterial clones were cultivated. These consisted of 87% aerob and 13% anaerob bacteria. Staphylococcus aureus (39%) and members of the family of Enterobactericae (30%) were the most common microbes. There was neither an evidence for postoperative microbes on the nasal mucosa nor a correlation between the dissoluting technique and the postoperative outcome. The use of sterilized solutions for the postoperative care of endonasal mucosa does not cause an additional worthful effect on neither the postoperative microbial climate nor the outcome in comparison to endonasal shower.

Adolescent↗