Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

OBJECTIVES: Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. MATERIAL AND METHODS: An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. RESULTS: Labelling indices were significantly lower for Msx-1 (P < 0.03) and RANKL (P < 0.003) and significantly higher (P < 0.02) for BMP-2 in ONJ compared with healthy bone. Expression was sevenfold lower (P < 0.03) for Msx-1, 22-fold lower (P < 0.001) for RANKL and eightfold higher (P < 0.02) for BMP-2 in ONJ bone. CONCLUSIONS: Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future.

Vertical distraction of fibula transplant in a case of mandibular defect caused by shotgun injury.

This case demonstrates the successful aesthetic and functional reconstruction of a complex facial gun-shot injury with extended bone defects and soft tissue destructions using a 3-step procedure. Initially, a reconstruction plate was inserted, later a fibula transplant enabled the basic reconstruction and finally was distructed in a 3rd session. The rationale behind the sequencing of surgical sessions was the extended bony defect and soft-tissue destruction. The main problem in this type of wound is hypoxia or anoxia of the receptor bed for the transplant. A microvascular anastomosized bone transplant is necessary for sufficient oxygen tension in the recipient site. The anatomical dimensional disproportion of the transplanted free fibula graft and the shape of the mandible were corrected prior to the insertion of dental implants by means of vertical distraction.

A comparative quantitative analysis of laminin-5 in the basement membrane of normal, hyperplastic, and malignant oral mucosa by confocal immunofluorescence imaging.

Laminin-5 (Ln-5) is a heterotrimeric basement membrane (BM) molecule (alpha3beta3gamma2). It is a principal protein constituent of the anchoring filaments, which connect the BM with the hemidesmosomes of the basal keratinocytes and possess a crucial function in keratinocyte adhesion. Confocal immunofluorescence imaging is introduced for a quantitative evaluation of the Ln-5 content in the BM of oral squamous epithelium. The BM of normal oral mucosa was used as a reference (100%) for comparative analysis and showed a nearly uniform Ln-5 immunofluorescence intensity (99-100%). In all hyperplastic lesions of oral mucosa, the Ln-5 immunofluorescence intensity was increased (107-141%). The increased Ln-5 content in the BM of hyperplastic lesions suggests an increased keratinocyte-BM adhesion, possibly resulting in a higher stability of the oral mucosa. In contrast, in the oral squamous cell carcinoma (OSCC) invasive front, the remaining BM segments were characterized by a decrease in Ln-5 immunofluorescence intensity (35-74%). A stronger decrease of Ln-5-linked kerationocyte-BM adhesion correlates with a higher tumor grade. Because in central areas of carcinoma BM segments with a normal Ln-5 content could be demonstrated, the fundamental Ln-5 diminution in BM segments of the invasive front should be considered as an invasion-associated phenomenon.

Fibrillary co-deposition of laminin-5 and large unspliced tenascin-C in the invasive front of oral squamous cell carcinoma in vivo and in vitro.

PURPOSE: Invasion of oral squamous cell carcinoma (OSCC) is associated with laminin-5 (Ln-5) synthesis, focal Ln-5 loss from the basement membrane (BM), and Ln-5 depositions in the stroma beneath invading carcinoma cell complexes. METHODS: The study is focused on the laminin-5 matrix reorganisation within the stroma of the OSCC invasive front outside the basement membrane region as well as in OSCC-fibroblast co-culture in relation to unspliced tenascin-C (Tn-CL) and ED-B+ fibronectin (ED-B+ fn) using confocal laser scanning microscopy. RESULTS: In vivo, Ln-5 was demonstrated as fibrillary deposition in the invasive front. It was co-localised to Tn-CL. In pure OSCC cultures, Ln-5 was synthesised and deposited as a spot-like matrix. Fibrillary structures were not found. In contrast, in the OSCC-fibroblast co-culture, a fibrillary Ln-5 matrix organisation was revealed within the interface of OSCC cell-fibroblast complexes exclusively in co-distribution with Tn-CL and ED-B+ fn. CONCLUSION: At least in vitro, a carcinoma cell-stroma fibroblast interaction is indispensable for fibrillary Ln-5/Tn-CL matrix organisation. Behind the parallels to the initial basement membrane formation in organotypic cultures, the fibrillary multiprotein complexes at the OSCC cell-fibroblast interface are suggested as provisional basement membrane fragments with a possible supportive role for invasive tumour behaviour.

Establishment and cidofovir sensitivity of a cell line from a heart transplant recipient with multiple cutaneous tumors.

A new cell line, designated as Tuwei00, is described. It originated from an Epstein-Barr virus-positive skin tumor biopsy of a heart transplant recipient, whose numerous cutaneous neoplasms were treated with the antiviral drug cidofovir what caused at least transient remissions. The cell line was established in vitro and maintained for more than 70 passages. Cells of early passages were characterized by a slower growth, the inability to form colonies and a higher sensitivity to cidofovir. After overcoming a crisis, the cells grew faster, to a higher density and were able to form adherent colonies from single cells as well as colonies in soft agar. Chromosome analysis showed diploidy/hyperdiploidy at the earlier and hypodiploidy at the later passages. Sensitivity to cidofovir was distinctly higher in early passages of Tuwei00 cells than in later passages and was characterized by distinct decline of cell survival after long term cidofovir exposure. Established normal human keratinocytes, HaCaT cells, which were checked for comparison, showed a low cidofovir sensitivity similar to late passage Tuwei00 cells.

Multifocal oncocytic adenomatous hyperplasia of the parotid gland. A case report.

A case report of a multifocal oncocytic adenomatous hyperplasia occurring in a parotid gland is presented. The differential diagnosis of (multicystic) Warthin's tumor is discussed.

Computertomographische Aspekte der Schädelentwicklung eines Kindes mit Cherubismus.

The clinical picture of cherubism is similar to that of fibrous dysplasia. The initial clinical appearance involves the deformation of the maxillo-facial area with orthodontic disorder. Usually it is found in the mandible, giving the child a chubby-faced appearance, and it often occurs together with symmetric submandibular lymph node enlargement. This appearance reminds one of the cherubs seen in art. Only histological evidence for cherubism is inconclusive. The presence of multi-nucleated giant cells resembles fibrous dysplasia. A combination of clinical, radiographical, and histological findings eventually leads to the correct diagnosis.An example is given of a patient displaying the typical disease process. Over a period of 12 years, we observed the progression of the disease from its initial appearance in a young child, through the full and characteristic display of a cherubic youth, and finally its regression.In conclusion, we advise restraint in planning surgical intervention. The disease's etiology is not entirely clear. The latest research points to genetic defects that lead to failure in the expression of matrix proteins.

Method of Converse for correction of prominent ears: comparison of results.

We compared the objective and subjective evaluations of the results after correction of the earposition by the method of Converse with the results by the method of Reichert and Mustarde. The mean values obtained by the method of Converse correspond to the mean normal values. The patients are very satisfied with their results. A comparison of the results of these three methods do not show any aggravating differences.

[Soft tissue injuries, burns and scars]. / Weichteilverletzungen, Verbrennungen und Narben.

The principles of diagnosis and therapy of soft tissue injuries, burns and scars that have been established in the course of many years' experience of facial and plastic surgery are expounded. The goal of early definitive management cannot always be achieved, particularly in the case of burns. Possible consequences are outlined. Recommendations are given, based on analysis of the authors' own case material and taking recent developments into account.

[Interdisciplinary cooperation of internists and maxillomandibular surgeons in the treatment of hemophiliacs (author's transl)]. / Interdisziplinäre Zusammenarbeit von Internisten und Kieferchirurgen bei der Betreuung von Hämophilie-Patienten.

The treatment of hemophiliacs at the Jena Center of Hemophilia is described from a stomatological point of view, the emphasis being on the advantage involved in treatment on an outpatient basis by close cooperation between stomatologists and internists. The clinical results obtained show quite clearly that this particular method of treatment has proved useful. Finally, the method of using GRF type adhesives is discussed critically, and substitution therapy, which is prerequisite to surgical operations performed on hemophiliacs, is recommended to be continued to be used.

[Results of McKissock reduction mammoplasty]. / Ergebnisse der Mammareduktionsplastik nach McKissock.

Reducing mammoplasty is medically justified a surgical intervention to handle certain indications. Results obtained from this approach are discussed in comparison to other methods, primarily the Strömbeck technique, with reference being made to 217 patients of whom the majority had undergone McKissock operations. Ninety per cent of these patients were absolutely satisfied, and only eight per cent had restrictions. However, broadened or hypertrophic scars were recorded from 21 per cent in objective assessments by follow-up examiners. The method according to McKissock can be recommended for cases of mammary ptosis and macromastia. A two-stage approach, according to Joseph, should be taken to cases in which more than 1,400 g of tissue are removed from one side. No increased incidence of mammary tumours was recordable in the wake of reducing mammoplasty.

[Late results of breast augmentation]. / Spätergebnisse der Mammaaugmentation.

Late results of augmentation mammaplasty with dermis fat transplants and implants are presented and discussed separately. With correct handling and strict indication a mammary implant heals in without complications and with good results. The problem of capsular fibrosis is discussed. Prerequisites for augmentation mammoplasty are detailed information about and strict selection of candidates.

[Unilateral hyperplasia of the TMJ condyle]. / Die unilaterale Hyperplasie des Kiefergelenkkopfes.

Based on 8 case reports, the clinical features, etiology and therapy of unilateral condylo-mandibular hyperplasia are discussed. It is assumed that the underlying cause of this clinical picture is traumatic damage to the articular cartilage. According to our findings a distinction can be made between condylar hyperplasia and condylo-mandibular hyperplasia depending on the type of trauma and whether this damage occurs prior to or after completion of mandibular growth. Resection of the affected condyle is the treatment of choice. Immediate reconstruction of the joint using autogenous material (costal cartilage, iliac crest grafts) is recommended. In those cases of condylo-mandibular hyperplasia where esthetic impairment is only slight and the occlusion is left intact, the indication for surgery must be carefully discussed with the patient.

[Partial loss of the auricle: multiphase reconstruction and complete preservation of the helix]. / Partieller Ohrmuschelverlust. Mehrphasige Rekonstruktion unter vollständigem Erhalt der Helix.

The loss of the auricle is a dramatic event in terms of aesthetics of the face. Secondary reconstruction of the ear is difficult and complicated. Therefore, a replantation of the amputated part should be tried. Proper securing and transport of the amputate is essential, in addition to the patient being sent to a specialized clinic. An anatomically correct form of the auricle is necessary for successful reconstruction of the ear. The amputated auricular cartilage is denuded of the skin except for the helical portion and is inserted into a retroauricular pocket. The helix is treated as a composite graft. After 1 to 2 months, the replanted auricular cartilage is elevated, adapted to the remaining ear stump and covered with a skin graft retroauricularly. By means of a representative case, a replantation method is demonstrated which allows complete reconstruction of the helix. In consequence, the replanted ear does not show any deficits compared with the original state.

[Computed tomographic aspects of skull development in a child with cherubism]. / Computertomographische Aspekte der Schädelentwicklung eines Kindes mit Cherubismus.

The clinical picture of cherubism is similar to that of fibrous dysplasia. The initial clinical appearance involves the deformation of the maxillofacial area with orthodontic disorder. Usually it is found in the mandible giving the child a chubby-faced appearance, and it often occurs together with symmetric submandibular lymph node enlargement. This appearance reminds one of the cherubs seen in art. Only histological evidence for cherubism is inconclusive. The presence of multi-nucleated giant cells resembles fibrous dysplasia. A combination of clinical, radiographical and histological findings eventually leads to the correct diagnosis. An example is given of a patient displaying the typical disease process. Over a period of 12 years, we observed the progression of the disease from its initial appearance in a young child, through the full and characteristic display of a cherubic youth, and finally its regression. In conclusion, we advise restraint in planning surgical intervention. The diseases etiology is not entirely dear. The latest research points to genetic defects that lead to failure in the expression of matrix proteins.

[Qualitative and quantitative studies of the inflammatory reaction in the tumor boundary zone of intraoral squamous cell carcinomas]. / Qualitative und quantitative Untersuchungen zur entzündlichen Reaktion im Bereich der Tumorgrenzzone intraoraler Plattenepithelkarzinome.

The inflammatory cellular infiltration in the tumor boundary zone was analyzed in 10 primary tumors, completely histologically worked up and not pretreated, using a metric and reproducible evaluation system at a line of 10 cm per case. The part of the tumor boundary zone free of inflammation varied between 2% and 79%, where as only 3 of the examined 10 tumor cases showed actions free of inflammation under 10%. In the differential cell picture of the inflammation the lymphocytes dominate (74, 12% +/- 6.79) while the part of plasmacytes varied between 1.8% and 29.2%. In spite of the exclusion of bacterially infected and necrotic tumor sections an average percentage of granulocytes (10.25% +/- 5.30) was ascertained in the inflammatory cell infiltrate.

[Cell kinetics of oral squamous epithelial carcinomas. Determination of the proliferation index and apoptosis rate with the TUNEL method]. / Zellkinetik oraler Plattenepithelkarzinome. Bestimmung des Proliferationsindex und der Apoptoserate mittels der TUNEL-Methode.

Tumour growth is directly related to the multiplication of tumour cell numbers which can be caused, firstly, by increased proliferation and, secondly, by prolongation of the life span of tumour cells. The aim was the quantification of the increase and decrease (apoptosis) in cell numbers in relation to the cytological grading of oral squamous epithelial cell carcinoma. Proof of apoptosis-specific fragmentation of DNA (double-strand breaks) by the TUNEL method (TdT-mediated dUTP nick end labelling) and of proliferative activity by the monoclonal antibody MIB 1 was found in 41 oral squamous epithelial carcinomas of different grading. With progression of the cytological grading, an increase of proliferative activity and a decrease of apoptotic activity occurs. The apoptosis rates were 13.5% for G1 carcinomas, 8.5% for G2 carcinomas and 6.1% for G3 carcinomas. The results confirm that during progression to higher malignant cellular phenotypes of oral squamous carcinoma, increased proliferative activity as well as reduced apoptosis rates contribute substantially to the multiplication of tumour cell numbers and show that during progression a loss of control of programmed cell death (apoptosis) occurs. However, the high standard deviations of apoptosis rates within the different grades disprove an individual prognostic significance.

[3-dimensional in vitro invasion model for oral squamous epithelial carcinomas. Evaluation of tumor and stromal cell properties as well as extracellular matrix]. / Dreidimensionales In-vitro-Invasionsmodell für orale Plattenepithelkarzinome. Evaluation von Tumor- und Stromazelleigenschaften sowie der extrazellulären Matrix.

UNLABELLED: Because tumour cell invasion is a three-dimensional process involving tumour cells as well as stromal cells, tumour invasion models should include equivalents of both compartments in a spatially defined organisation. AIMS: Evaluation of differentiation and invasive potential in relation to basement membrane (BM) formation of new human oral squamous cell carcinoma (OSCC) cell lines under the influence of fibromatosis fibroblasts in a 3D co-culture system (collagen type I/fibroblast-containing matrix). MATERIAL AND METHODS: OSCC cell lines were established and cultured on collagen type I matrix with and without the inclusion of fibro-/myofibroblasts derived from nodular palmar fibromatosis). Evaluation of invasion was done by conventional H & E staining after paraffin embedding; immunohistochemistry was performed for cytokeratins (MNF 116), involucrin (Sy5), vimentin (V9), collagen type IV (CIV22), laminin (alpha 1-chain, 4C7), and Ki-67 (MIB1); and electron microscopy followed. RESULTS: The OSCC cell lines PE/CA-PJ15, PE/CA-PJ34, PE/CA-PJ41 were invasive exclusively on gels containing fibroblasts with stratification of the multilayerd OSCC cell coat and polarised expression of cytokeratin and involucrin. There was no evidence for BM, either by immunohistochemistry or by electron microscopy, although OSCC are immunohistochemically positive for collagen type IV and laminin in the 2D cell culture. There were no differences in proliferative activity of the gels with and without fibroblasts. CONCLUSIONS: Carcinoma cell invasion depends on the presence of fibroblasts in the gel indicating the important role of tumor stromal fibro-/myofibroblasts during carcinomic invasion. The absence of a BM does not, per se, imply an invasive tumour growth. Moreover, stratification and terminal differentiation of epithelial tumour cells occur independently of a structural BM.

[Tumors of the face in organ transplant patients]. / Tumoren des Gesichts bei organtransplantierten Patienten.

BACKGROUND: The greatly enhanced risk of developing pre-cancerous lesions, basal cell carcinomas, and squamous cell carcinomas in organ transplant recipients is demonstrated on the basis of three of our own cases. DISCUSSION: Immunosuppression is discussed as the primary reason for enhanced tumour incidence and the occurrence of multiple synchronic and metachronic tumours after organ transplantation. UV exposition and oncogenic viruses must be taken into account as further factors for tumour disposition. More aggressive tumour behaviour has to be expected. In consequence, a focused clinical monitoring and a stringent therapy of the skin tumours is absolutely necessary.