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Biomedical subjects

H Kosmehl

Publications and source records attributed to H Kosmehl.

At least 19 recordsLinked to original sources
PubMed2007

[Oral cytology: historical development, current status, and perspectives].

Oral cytology has aroused new interest caused by introduction of the cytobrush as a sampling device and the use of additional analytical methods. By brushing it is possible to reach deeper layers of the oral mucosa where squamous intraepithelial neoplasia (SIN) begins. The biological potential of the oral epithelial cells obtained can be evaluated by the following additional methods: computer-assisted image analysis (OralCDx), DNA cytometry, immunohistochemistry, monolayer cytology, and molecular biological analysis. All of those methods can increase sensitivity (up to 100%) and specificity (up to 100%) of oral brush biopsy. Nevertheless, there are reports that oral epithelial carcinomas were not identified. No comparative study exists allowing conclusions to be drawn about the value of the single methods. Immunocytochemistry with commercial antibodies against laminin-5 is generally available and methodologically easy. Oral brush biopsy as a non invasive diagnostic method can be useful for the early detection of oral mucosal lesions. Positive findings or progression of the lesion despite negative findings are indications to refer the patient to a specialized clinic where a surgical biopsy should be performed, followed by histopathological analysis. Histopathology remains the gold standard for the definitive diagnosis of oral malignant lesions.

Biomarkers, Tumor↗
PubMed2006

High-molecular tenascin-C as an indicator of atypical cells in oral brush biopsies.

Tumour-invasion like wound healing is characterised by the formation of an extracellular matrix with a high tenascin-C content. The tenascin-C molecule undergoes alternative splicing. Analysis using antibody BC2 indicates that especially the high-molecular tenascin-C (hm tn-C) variants are typically tumour-associated, while distribution in normal tissue is restrictive. This study investigated whether hm tn-C is a suitable indicator of atypical cells with invasive potential in oral brush biopsies. One hundred fifty nine consecutive oral brush biopsies with histopathological diagnoses were analysed for the identification of atypical cells. A standardised haematoxylin and eosin staining plus standardised immunocytochemistry using the monoclonal anti-hm tn-C antibody was performed. The bound hm tn-C antibodies were detected with the streptavidine/alkaline phosphatase technique in the autostainer. Conventional cytology produced four false-positives when identifying atypical cells in brush biopsies of inflammatory/benign hyperproliferative mucosa (specificity 96%), while 10 in 52 carcinomas and three of eight recurrences were not identified (sensitivity 78%). Ten of these 13 non-identified tumours could be marked when adding the hm tn-C assay (increasing specificity to 99%). Combining the two assays also reduced the false-positive outcomes from four to one (increasing sensitivity to 95%). The positive and negative predictive values were 92 and 88% for conventional cytology vs 98 and 97% for the dual assay. (1) A 95%-sensitivity proves hm tn-C assisted conventional cytology to be a suitable means of identifying atypical cells in oral brush biopsies. (2) The positive (98%) and negative (97%) predictive values obtained approximate hm tn-C assisted conventional cytology to laminin-5 (100/97%).

Biomarkers, Tumor↗
PubMed2006

[Central giant cell granuloma of the mandible. Definition and differential diagnosis].

The synopsis of radiographic examination (uni- or multilocular radiolucency), histologic findings (giant cells throughout a benign fibroblastic matrix), blood chemistry analysis (normal serum parathyroid hormone) and clinical features provides the definitive diagnosis of giant cell granuloma, allowing the clearly defined surgical management of this lesion. The case history of a 48-year-old female patient who presented with a giant cell granuloma in the right mandible is used to illustrate this controversially discussed intra-osseous lesion. The potential therapeutic change from radical operative treatment, including functional maintenance, to conservative procedures is emphasized.

Diagnosis, Differential↗
PubMed2006

[Urothelium cancer with trophoblastic differentiation. An unusual case of a 77 year old patient].

Urothelium carcinomas with beta HCG positive markers are a rarity in tumour differentiation. Syncytiotrophoblastic and, in a few cases, cytotrophoblastic giant cells are typical for this carcinoma. Such differentiation has an intensified potential for invasiveness and is accompanied by increased angiogenesis. In the present case, the mixture of trophoblastic cells indicates a common stem cell. In comparison with beta HCG negative transitional cell carcinoma, the prognosis is bad for beta HCG positive carcinoma. For this reason, a radical operation should be taken into consideration as early as possible.

Aged↗
PubMed2006

[Clinical and immunohistochemical findings of intra- and extraoral angiosarcomas].

PURPOSE: A clinico-pathologic study of typical symptoms of intra- and extraoral angiosarcomas and clinical course under therapy is presented as well as an analysis of the immunohistochemical differential diagnosis of the tumour specific formed spaces. PATIENTS AND METHODS: Four male patients aged 63-78 years suffered from angiosarcomas of the maxillary sinus, the bucca (two patients) and the alveolar ridge of the lower jaw. HISTOPATHOLOGY: For comparative analysis paraffin embedded tissue of the initial biopsies was available. The slides were stained with standardized H&E, PAS and Gömörri. For standardized immunohistochemistry following primary antibodies were applied: monoclonal antibodies to pancytoceratin clones AE1/AE3, alpha-smooth-muscle-actin clone 1A4, CD31 clone JC/70A, factor-VIII-related antigen clone F/86, Fli-1 (polyclonal, Zymed, USA), tenascin-C: BC4 (Prof. L. Zardi), oncofetal glucosylated fibronectin clone FDC6 (ACCR), laminin-5: D4B5. Detection using AP-ChemMate and Autostainer (Dako, Denmark). RESULTS: While the benign appearance of the lesions resulted primarily in wrong diagnoses the histopathologic examination of the biopsies revealed the characteristic pattern of angiosarcomas. Wide surgical excision, radiotherapy and/or antiangiogenic chemotherapy could not prevent tumour progression and death within two and a half years after primary diagnosis. All angiosarcomas reacted partially positive for factor-VIII-related antigen and CD31. The tumour associated structural defect of vascular lamina with partial loss of pericytes/vascular smooth muscle cells was identified immunohistochemically by alpha-smooth-muscle-actin and for the first time by tenascin-C. CONCLUSIONS: (1.) The variable presentation and the benign appearance of oral and perioral angiosarcomas may often delay diagnosis. Oral and perioral angiosarcomas show poor prognosis despite of multimodal therapy. (2.) Cytoceratin and laminin-5-positivity as typical epithelial antigens don't exclude angiosarcoma. Factor-VIII-related antigen, CD31 as well as Fli-1 identify angiosarcoma. (3.) alpha-smooth-muscle-actin and the loss of the tenascin-C-matrix indicate immunohistochemically the characteristic sarcomatous defect of differentiation.

Aged↗
PubMed2006

[Current classification of precursor lesions of oral squamous cell carcinoma principles of the WHO classification 2005].

The WHO classification of oral tumours summarizes the precancerous squamous cell lesions under the term epithelial precursor lesions. For the first time three classification schemas that histologically categorize oral epithelial precursor lesions are used analogously. According to the WHO suggestion of 2005 the traditional schema of grading dysplasia as mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ continues to be used. In addition the concept of intraepithelial neoplasia is introduced as squamous intraepithelial neoplasia I-III. Squamous intraepithelial neoplasia III (SIN III) combines severe dysplasia and carcinoma in situ. The Ljubljana classification of squamous intraepithelial lesions was originally established to grade laryngeal epithelial precancerous lesions. The clear and succinct nomenclature and the simple clinical utility of the Ljubljana classification have also proven to be useful for oral epithelial precursor lesions: squamous cell (simple) hyperplasia; basal/parabasal cell hyperplasia (analogous to mild dysplasia and to SIN I); atypical hyperplasia (analogous to moderate-severe dysplasia and to SIN I-III and is also called risky epithelium); carcinoma in situ (analogous to WHO carcinoma in situ and to SIN III). Atypical hyperplasia (risky epithelium) and carcinoma in situ are defined as lesions requiring either total excision or close clinical monitoring.

Carcinoma in Situ↗
PubMed2004

[Intra- and postoperative monitoring of transplanted flaps. Measurement of the partial pressure of oxygen in tissue].

BACKGROUND: According to Schmelzeisen et al. (1996), the failure rate for microvascular free flaps is 5%. While surface tissue oxygenation can be assessed clinically, if necessary by a puncture, the oxygen supply to deeper areas mostly cannot be checked. We therefore wished to find whether measurement of tissue pO(2) would prove to be an objective and practical technique that could be used for continuous and accurate intra- and postoperative evaluation of flap perfusion. MATERIAL AND METHODS: A Clark-type microcatheter was used intra- and postoperatively to monitor tissue pO(2) in 5 pedicled pectoralis major flaps and 32 free revascularized flaps (9 jejunal flaps, 5 latissimus dorsi flaps, 6 radial forearm flaps and 12 scapular flaps). RESULTS: The mean values for tissue pO(2) were significantly lower in pedicle grafts than in free revascularized flaps. Within in each flap group the pO(2) values measured did not vary significantly over an observation period of up to 77.2 h after transplantation. CONCLUSIONS: Continuous measurement of tissue pO(2) by means of a Clark-type microcatheter combined with clinical examination constitutes a reliable method of monitoring tissue oxygenation in pedicle grafts and free revascularized flaps during the intra- and postoperative phases. Analysis of small and of wide fluctuations in pO(2) values may help in the diagnosis of early arterial and venous obstructions in flaps and may in the future result in new insights into the tissue oxygenation in surgical flaps allowing some alleviation of the problems currently experienced in clinical monitoring.

Anastomosis, Surgical↗
PubMed2004

[Oral adenoid squemous carcinoma. Tumor markers and prognosis].

CASE REPORT: A 58-year-old female patient presented with an exophytic adenoid squamous cell carcinoma on the right alveolar process of the lower jaw. Histological and immunohistochemical differential diagnosis and cellular background of the unfavorable prognosis are described. The patient was treated with curative intent by radical tumor resection including partial mandibulectomy, extensive conservative/radical neck dissection, and postoperative radiation. The adenoid squamous cell carcinoma was classified as pT4, pN0, cM0, R0. During radiation, regional lymph node metastases and distant metastases developed. The patient died of distant metastases 7 months after the initial diagnosis. HISTOPATHOLOGIC FINDINGS: Tumor cells of adenoid squamous cell carcinoma express epithelial intermediate filament cytokeratin, epithelial membrane antigen (EMA), and epithelial basal membrane protein laminin-5 (Ln-5). Glandular differentiation can be excluded by the absence of epithelial mucins (Alcian blue, mucicarmine). Differentiation from angiosarcoma can be performed using endothelial differential markers CD31, CD34, and factor VIII-associated antigen (FVIII-ass. AG). Both entities are characterized by high proliferation and Ki-67 index of 20%. beta-catenin (cell-cell adhesive protein) loses its primary membrane-bound localization and can explain the histologic pattern of acantholysis. Ln-5 (guide rail of invasion) is massively expressed in adenoid squamous cell carcinoma cells and may be responsible for rapid progression. CONCLUSIONS: Pseudopapillary proliferation, cellular atypia, vascular-like cavities, expression of cytokeratin, EMA, and Ln-5 are common features of oral adenoid squamous cell carcinoma and angiosarcoma. Diagnosis is determined by the absence of endothelial differential markers CD31, CD34, and FVIII-ass. AG. Modulation of the beta-catenin pattern (transcription factor of Ln-5) and massive expression of invasion factor Ln-5 are suggested as cell biological reasons for rapid progression of adenoid squamous cell carcinoma.

Alveolar Process↗
PubMed2004

Early immunohistochemical and functional markers indicating radiation damage of the parotid gland.

In order to evaluate the correlation between functional impairment and changes in the expression pattern of immunohistochemical antibodies in the early phase of radiation-induced dysfunction of salivary glands, eight rabbits were scintigraphically examined prior to and 24 h after irradiation with 15 Gy. The parotid glands were studied using HE-staining, Ki-67, alpha-smooth muscle actin (ASMA) and tenascin-C antibodies at every scintigraphic examination. The results demonstrated a significant alteration in the 99mTc-pertechnetate uptake in all irradiated glands. HE-staining showed no relevant impairment of salivary gland tissue in this early phase. Immunohistochemically, we observed a marked re-distribution of ASMA and tenascin-C as well as a reduction of the proliferating rate of acinar cells. This immunohistochemical change correlated with the functional impairment manifested scintigraphically. This study proves the possibility to assess disorders of salivary gland function with immunohistological antibodies as early as 24 h after irradiation and yields the prerequisites to prove the effects of radioprotective agents on salivary gland tissues.

Actins↗
PubMed2004

Expression of EDA+ and EDB+ fibronectin splice variants in bone.

The extracellular matrix component fibronectin (fn) has fundamental functions in cell attachment, differentiation, proliferation, and migration. Isoforms of cellular fibronectin, named EDA+ fibronectin or embryonal EDB+ fibronectin, are generated by alternative splicing of its mRNA precursors. Little is known about the expression of EDA+ and EDB+ fibronectin splice variants in human bone. The aim of this study was to investigate the expression pattern of fibronectin splice variants in bone cell lines and in different human bone tissue samples (mature bone, early stages of fracture healing, hypotrophic nonunion, osteosarcoma). Analysis was done by immunostaining with recombinant and monoclonal antibodies, qualitative RT-PCR and LightCycler-based real-time quantitative RT-PCR assay. In osteoblast and osteosarcoma cell lines, abundant expression of EDA+ and EDB+ fibronectin was found in immunocytochemistry. High transcription levels of both splice variants mRNA were seen in quantitative RT-PCR in osteosarcoma cell lines. In mature bone, EDA+ and EDB+ were not detectable in immunohistochemistry. Transcription of mRNA in both splice variants was absent in these samples. Early stages of fracture healing and osteosarcoma cell samples exhibited extensive staining for EDA+ and EDB+ fibronectin, and high mRNA levels were found. Both osteosarcoma and bone fracture healing tissue expressed high mRNA levels of the fibronectin splice variants independent of benign or malignant behavior. Low level of EDA+ fibronectin mRNA transcription and focal immunohistochemical staining of EDA+ fibronectin was found in hypotrophic nonunions, whereas EDB+ fibronectin was not detected by immunohistochemistry and qualitative or quantitative PCR. EDA+ fibronectin was found in granulation tissue-forming processes in bone independent from bone-forming activity. EDB+ fibronectin was seen only in high-turnover new osteoid-forming processes like early stages of fracture healing and osteosarcoma and was absent in low-turnover processes like mature bone and hypotrophic nonunion. Both EDA+ and EDB+ fibronectin mark active processes in bone without differentiation between malignant or benign activity. In conclusion, EDA+ and EDB+ fibronectin splice variants are strong markers for active fibrogenetic and osteoid-forming processes in human bones.

Adolescent↗
PubMed2004

New cut-off point between T1 and T2 renal cell carcinoma - necessary for a better discriminatory power of the TNM classification.

PURPOSE: We evaluated the pathological features of tumor size, lymph node and distant metastases, cell type, growth pattern, infiltration pattern, histological grade, local invasion and venous involvement of organ-confined renal carcinomas. The aim of this study was the re-evaluation of the TNM classification and the tumor cut-off point between T1 and T2 for renal cell carcinomas from the 1987 to the 1997 versions. MATERIALS AND METHODS: (1) Patients with renal cell carcinoma who had been operated between October 1992 and August 2001 were evaluated. 437 of 691 patients showed T1 and T2 tumors. These organ-confined tumors have been divided into five groups: group 1: tumor-size of 20 mm or less (n = 16), group 2: 21-30 mm (n = 79); group 3: 31-40 mm (n = 83; group 4: 41-70 mm (n = 184), and group 5: more than 70 mm in diameter (only T2, n = 75). Follow-up ranged from 0 to 100 months (average 28.63 months). (2) Of 15,347 autopsies performed in Jena between 1985 and 1996, 272 renal cell carcinomas were revealed. In 145 of these 272 cases renal cell carcinomas were limited to the kidney. These 145 tumors were divided accordingly into 5 groups: group 1: 20 mm or less (n = 33), group 2: 21- 30 mm (n = 31); group 3: 31-40 mm (n = 29); group 4: 41-70 mm (n = 42), and group 5: T2 (n = 10). Clinicopathological criteria examined were lymph node and distant metastases, cell type, growth pattern, infiltration pattern, histological grade, local invasion and venous involvement. To identify the optimal cut-off point between T1 and T2 disease the chi2 test was used. RESULTS: (1) In the clinical series only 1.8% (n = 8) of all cases showed lymph node metastases. Distant metastases were shown in 57 cases (13.04%); within group 1: 0%, group 2: 7.59%, group 3: 1.20%, group 4: 15.76%, group 5: 28%. The tumor grading was statistically correlated with tumor size. (2) In the pathological series 94 of the evaluated 145 patients were downstaged from T2(1987) to T1(1997). Lymph node and distant metastases were well correlated with tumor size. Lymph node metastases were seen in 0, 12.9, 31, 29.3 and 40% (group 1 to group 5) and distant metastases in 12.1, 25.8, 41.4, 47.7 and 60%. There were no statistically significant differences between T2(1997) and T1(3-7 cm). The tumor grading was statistically correlated with tumor size (grade 1: in 66.7, 25.8, 17.2, 9.5 and 0%). CONCLUSION: Our data suggest that the current cut-off diameter between T1 and T2 renal cell carcinomas (7 cm) is too high. Lowering the cut-off level will result in better discriminatory power of the TNM classification. From our data, we conclude that the cut-off diameter should be lowered to 3.5 cm (p < 0.001).

Adult↗
PubMed2003

Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the synovial membranes of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: The aim of this study was to define and compare the expression of fibronectin (Fn) isoforms in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Using monoclonal antibodies specific for total Fn, extra domain (ED)-A Fn, ED-B Fn, and oncofetal glycosylated Fn, we studied the expression of the Fn isoforms in synovium. Furthermore, in situ hybridization for the detection of ED-B Fn mRNA including a double labeling technique for the detection of cell type was applied. RESULTS: Strong expression of total Fn, ED-A Fn, oncofetal glycosylated Fn and, to a lesser extent, ED-B Fn could be demonstrated in the synovial lining layer in both RA and OA. Stromal and vessel expression of Fn isoforms was more prominent in RA tissue. Pannus tissue showed strong labeling with ED-B Fn. CONCLUSION: The expression of alternatively spliced isoforms of Fn is associated with tissue remodeling and, as a partial process of this phenomenon, with neovascularization rather than underlying disease, X-ray status, or parameters of acute inflammation. In the lining layer, Fn expression correlates with hyperplasia associated with cell recruitment but not with proliferative status. Most remarkably, the expression of ED-B Fn in pannus tissue seems to be associated with the invasive phenotype described in RA tissue.

Alternative Splicing↗
PubMed2003

Acute effects of tourniquet occlusion and intraluminal shunts in beating heart surgery.

OBJECTIVE: MIDCAB and OPCAB revascularization is currently performed with temporary tourniquet occlusion of the coronary artery to achieve a bloodless surgical field. However, a trauma of the vessel wall due to snaring sometimes occurs. The use of temporary intraluminal shunts (TILS) have recently been advocated as an alternative. The aim of this experimental study was to evaluate the acute ultrastructural effects of TILS versus tourniquet occlusion on the coronary vessel wall. METHODS: Twelve pigs (40+/-3 kg) were investigated. In group A (n=6) the left anterior descending (LAD) artery was temporarily occluded with a tourniquet over 20 min. In group B (n=6) a commercially available silicone TILS (1.5-mm diameter, 12-mm length, AnastaFlo, Research Medical Inc.) was placed in the LAD. After 20 min perfusion the TILS was removed and the insertion was repaired. After 30 min reperfusion all animals were killed. Three LAD territories of each animal were examined histopathologically by scanning electron microscopy (SEM), light microscopy (LM) and transmission electron microscopy (TEM). Areas of occlusion or placement of the TILS olives were investigated. RESULTS: SEM revealed ultrastructural alterations in both groups. While marked intimal rupture appeared in all animals of group A, only two of the six animals of group B exhibited superficial endothelial abrasions. LM showed differences of intimal thickness in all groups while TEM revealed severe edema of subendothelial tissue in four of six animals in group A. CONCLUSION: The intimal lesions observed after tourniquet occlusion in our experimental off-pump surgery model confirmed other recent studies. In contrast, utilization of TILS caused only minor damage of the vessel wall. The endothelial abrasions detected in this group may be a consequence of micro-dislocations or insertion maneuvers. Chronic studies are necessary to verify as to whether the mild injury after TILS insertion will result in a reduction or even absence of de-novo stenoses compared with tourniquet occlusion.

Animals↗
PubMed2002

Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature.

Interleukin-12 (IL-12) is a heterodimeric cytokine with potent immunostimulatory activity and anti-angiogenic properties. Its clinical applications are limited, however, by severe side-effects. Here we report that an IL-12 fusion protein, consisting of IL-12 fused to a human antibody fragment specific to the oncofetal ED-B domain of fibronectin, markedly enhances the antitumor activity of this cytokine, as demonstrated in a mouse lung-metastasis model and in two models of mice bearing different aggressive murine tumors. The residual small tumor masses seen in the treated mice were infiltrated with lymphocytes, macrophages, and natural killer cells and had elevated interferon gamma (IFN-gamma). These results are of therapeutic relevance as the ED-B domain of fibronectin, a naturally occurring marker of angiogenesis identical in mouse and man, is expressed in the majority of aggressive solid tumors but is not detectable in normal vessels and tissues.

Animals↗
PubMed2002

The superficial mandibular gland of the rabbit: a new experimental model for scintigraphic evaluation of salivary glands.

The aim of this study was to provide an appropriate experimental model to study functional changes in salivary glands using scintigraphy. Although the rabbit was frequently used for laboratory experiments, there are only a few studies that describe the exact position of its different salivary glands on the sialoscintigram. Twenty rabbits were used for the study; ten of them were anatomically dissected to provide the required topographic anatomy on the different salivary and lacrimal glands. The remaining ten animals underwent a static scintigraphy after extirpation of a particular salivary gland. Changes in the pattern of tracer uptake indicated the exact position of every gland allowing its evaluation. The results show that the 99mTcO4- uptake can only be selectively evaluated in two salivary glands, the superficial mandibular gland and the parotid gland. The superficial mandibular gland was proved to be a particularly useful model to evaluate functional changes of salivary gland parenchyma due to its well defined and high enhanced structure which allows a precise detection and measurement of the tracer uptake. Additionally, the good surgical accessibility of this gland and the existence of a well defined capsule facilitate associated histological studies of its parenchyma.

Animals↗
PubMed2002

Cytokine mRNA expression in experimental porcine pneumonia.

A porcine Pasteurella multocida (P. m.) infection model was established to study the spatial distribution of cytokine mRNA-expressing cells in lung tissue during acute pneumonia. The mRNA detection was performed by non-radioactive, formamide-free in situ hybridization (ISH) using oligonucleotides against the porcine interleukins (IL): IL-1 beta, IL-2, IL-4, IL-6, IL-8, TNF alpha and TGF beta. Cytokine mRNA-expressing macrophages were demonstrated by a double staining procedure combining immunohistochemistry (IH) using the primary antibody 2G6 with IL-1 beta, IL-6 and TGF beta ISH. With the exception of some stained TNF alpha-expressing cells, no IL mRNA was detectable in the lung of unaffected animals. The experimental P. m. pneumonia was characterized by a predominant, exudative and an additional proliferative interstitial component as well as abscess formation in the lung. Many cells of the region between the abscess membrane and the affected lung area showed high IL-6, IL-1 beta, IL-4 as well as TGF beta and few cells low IL-8 mRNA expression with characteristic distribution patterns. The ISH/IH double staining procedure revealed that at least some of the IL-6 or TGF beta-producing cells belonged to the 2G6-positive macrophages.

Animals↗