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H Kosmehl

Publications and source records attributed to H Kosmehl.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Cell kinetics of oral squamous epithelial carcinomas. Determination of the proliferation index and apoptosis rate with the TUNEL method].

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.

Apoptosis↗
PubMed1998

[3-dimensional in vitro invasion model for oral squamous epithelial carcinomas. Evaluation of tumor and stromal cell properties as well as extracellular 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.

Basement Membrane↗
PubMed1998

Differential expression of laminin chains in the human major salivary gland.

Laminin represents a macromolecule family. The heterotrimeric isoforms of laminin can be determined by immunohistochemical demonstration of the single chains. The laminin chain heterogeneity of the basement membrane in adult human major salivary glands was evaluated in relation to cellular differentiation of the epithelia and the stromal compartment. Monoclonal antibodies to the laminin alpha1, alpha3 (BM165) chains and epiligrin reacted with the basement membranes of serous and mucous acini and of intercalated, striated and excretory ducts. As evidenced by a double-labelling technique, the alpha2 chain showed a spatial association with the myoepithelium of the acini, whereas the ductal basement membranes containing no myoepithelial cells were negative. Almost exclusively, beta1 chain was detected in acinar basement membrane, beta2 chain whereas in ductal basement membrane. Gamma2 chain is a unique chain belonging to the laminin-5 isoform. It was restricted to the ductal basement membrane. Alpha1, alpha2, beta1, beta2 and gamma1 chains were detected in nerves of salivary tissue and alpha1, alpha3, beta1, beta2 and gamma1 chains and epiligrin in blood vessels. Our results indicate that the acinar ductal unit contains basement membranes with different isoforms, which relate to cell differentiation and cell function.

Adult↗
PubMed1998

Cyclosporin A-induced graft-versus-host disease following autologous bone marrow and stem cell transplantation in hematological malignancies of childhood.

Cyclosporin A (CsA) can induce graft-versus-host disease (GVHD) following autologous bone marrow transplantation (ABMT) and autologous peripheral blood stem cell transplantation (APBSCT) in adults. We investigated whether GVHD can be induced following ABMT and APBSCT in childhood, and which cells are involved in the pathogenesis of this syndrome. We conducted a prospective study of 20 children and adolescents with hematological malignancies receiving CsA after ABMT and APBSCT. Skin biopsies were obtained on day 21 after transplantation or in the event of a rash. Immunophenotypic analysis of peripheral blood lymphocytes was performed on days 14, 21, 28 and 60 after transplantation. Clinical GVHD of the skin, confirmed by histological criteria, occurred in five patients. Five patients had no clinical GVHD but had acute GVHD alterations on routine skin biopsy. In all 10 patients with a positive skin biopsy for GVHD, CD4+ lymphocytes were the predominant cells in the epidermis. Immunophenotypic analysis of peripheral blood lymphocytes revealed a significantly increased CD4/CD8 ratio in patients with a positive skin biopsy (P < 0.01). Our findings indicate that it is possible to induce acute GVHD following ABMT and APBSCT in childhood. In addition, CD4+ lymphocytes play an important role in the pathogenesis of CsA-induced GVHD.

Adolescent↗
PubMed1998

Nephron sparing surgery for renal cell carcinoma 4 cm. or less in diameter: indicated or under treated?

PURPOSE: Although radical nephrectomy is the standard treatment for localized unilateral renal cell carcinoma with a normal contralateral kidney, there is ongoing interest in the use of nephron sparing surgery or partial nephrectomy in such cases. The extent of radical surgery in such cases has also been reconsidered in view of the uncertainty regarding the malignant or benign nature. MATERIALS AND METHODS: Of 14,793 autopsies in Jena from 1985 until 1995 there were 260 renal cell carcinomas. Of the 260 renal cell carcinomas the diameter was 40 mm. or less in 104. These 104 tumors were divided into group 1-20 mm. or less (33 cases), group 2-21 to 30 mm. (28) and group 3-31 to 40 mm. (43). RESULTS: Grade 1 renal cell carcinomas decreased in frequency with increasing tumor diameter, while an opposite result was noted for grade 3. Lymph node and distant metastases were well correlated with tumor size. With an increase in tumor size the frequency of venous involvement increased as well. Significantly more multifocal malignant renal cell carcinomas were seen in tumors between 21 and 40 mm. compared to those 20 mm. or less in diameter. CONCLUSIONS: The metastatic potential and biology of these small nodules are not yet known. To lower the risk of local recurrence the results of our study suggest that nephron sparing surgery might be advisable in patients with renal cell carcinoma 20 mm. or less in diameter.

Adult↗
PubMed1998

Increase of renal cell carcinoma incidence in central Europe.

OBJECTIVE: In recent years the incidence of renal cell carcinoma (RCC) diagnosis has increased about 15-20%. It remains to be established whether this increase of incidence is reality or not. The main aim of this study was to analyze the reason for the increase of incidence. METHODS: In the present study, 23, 247 autopsies performed in the years 1985-1995 in the area of Jena (Germany) (14,793 autopsies) and Hradec Králové (Czech Republic) (8,454 autopsies) were analyzed. RESULTS: In this autopsy series comprising 23,247 autopsies, the percentage of patients who died of RCC is 1.76% in Jena and 1.55% in Hradec Králové (200,000 inhabitants each). Over this time the incidence of RCC in autopsies has increased. CONCLUSION: In spite of the increased amount of incidentally found RCCs since beginning widespread use of ultrasonography, the percentage of clinically recognized RCCs in the total of all found RCCs in autopsies is nearly constant over the 11-year period in Jena and 10-year period in Hradec Králové. Thus, the increased number of radical nephrectomies is not only caused by widespread use of ultrasonography. The increasing trend of the incidence of RCC seems to be real.

Autopsy↗
PubMed1998

Increased transforming growth factor beta1 plasma level in patients with renal cell carcinoma: a tumor-specific marker?

PURPOSE: The most worrying problem with renal cell carcinoma (RCC) seems to be the prediction of metastases by means of tumor-specific markers. Therefore, much effort is committed to the development of new markers. MATERIALS AND METHODS: The level of latent transforming growth factor beta1 (TGF-beta1) was measured in plasma samples by ELISA. These samples were collected from patients with RCC before they underwent radical nephrectomy, from patients 1 h after extracorporeal lithotripsy, from patients with pyelonephritis, and from healthy controls. RESULTS: In all cases of RCC the levels of latent TGF-beta1 in plasma were much higher (n = 20, 41.0 +/- 13.9 ng/ml, range 19.3-78.1 ng/ml) than in healthy controls (n = 20, 3.8 +/- 2.9 ng/ml, range 0.6-9.9 ng/ml, p < 0.0001). The TGF-beta1 levels in plasma after extracorporeal lithotripsy (n = 20, 7.4 +/- 4. 64 ng/ml, range 2.9-21.7 ng/ml, p < 0.01) and in patients suffering from pyelonephritis (n = 20, 18.93 +/- 14.2 ng/ml, range 4.2-46.7 ng/ml, p < 0.001) were also higher than in healthy controls. CONCLUSION: We conclude that increased levels of latent TGF-beta1 are common in the plasma of RCC patients. The TGF-beta1 plasma level in RCC was found to be significantly higher than in cases of inflammation. Thus, TGF-beta1 is a possible tumor-prognostic marker in RCC.

Biomarkers, Tumor↗
PubMed1997

Cytogenetic, histopathologic, and immunologic studies of multifocal renal cell carcinoma.

BACKGROUND: Multifocal tumor areas occurred in 12-22% of patients with renal cell carcinoma. It is unknown whether these tumors have malignant potential and characterize a higher risk for metastases. The performance of nephron-sparing surgery in patients with low grade or low stage tumors is controversial. METHODS: Primary and secondary tumors were analyzed by conventional cytogenetics and fluorescence in situ hybridization. Production of interleukin (IL)-6, IL-10, IL-11, and transforming growth factor (TGF)-beta1 were determined using standard enzyme-linked immunosorbent assay and bioassays. RESULTS: In 15.2% of the renal cell carcinoma cases evaluated, multifocal tumors were detected. Cytogenetics revealed a concordance of primary and secondary tumors in 9 of 14 cases (64%). In 11 of 12 multifocal tumors (94%), the same immunologic activity status was observed in both primary and secondary tumors. CONCLUSIONS: Secondary tumors must be expected to have malignant potential similar to that of the primary tumors. This was underscored by the high concordance of cytogenetic, histopathologic, and immunologic data in this study.

Carcinoma, Renal Cell↗
PubMed1997

[Basaloid squamous epithelial carcinoma (basaloid-squamous carcinoma) of the mouth floor. Differential diagnosis and response to neoadjuvant chemotherapy].

The basaloid squamous cell carcinoma (BSCC) is a variant of squamous cell carcinoma, having histologically distinctive features and appearing in the oral cavity, upper respiratory tract and esophagus. Histological hallmarks are the presence of a basaloid component in intimate association with squamous cell carcinoma. The basaloid component is characterized by tightly packed nests of cells with scant cytoplasm and hyperchromic nuclei without visible nucleoli and an increased mitosis rate. Basaloid squamous cell carcinoma is said to have a higher malignant potential than common oral squamous cell carcinoma with an increased incidence of regional lymph-node metastases and distant metastases. Our finding of a Ki-67 index of 30% and the immunohistochemical demonstration of p53 protein speaks well for enhanced aggressive biological behavior. The differential diagnosis includes the adenoid cystic, mucoepidermoid, neuroendocrine, adenosquamous and conventional oral squamous cell carcinoma. Because of early dissemination, radical surgical treatment and additional radiation therapy are considered necessary. Our findings indicate that partial clinical and histological tumor regression occurs after systemic neoadjuvant chemotherapy.

Biomarkers, Tumor↗
PubMed1997

Quantitative evaluation of apoptosis and proliferation in renal cell carcinoma. Correlation to tumor subtype, cytological grade according to thoenes-classification and the occurrence of metastasis.

To analyse growth characteristics of human renal cell tumors, 66 renal cell carcinomas and one oncocytoma were investigated concerning the proliferative activity by immunohistochemical demonstration of the Ki-67 antigen (clone MIB1) and the apoptotic rate using the terminal deoxynucleotidyl-transferase mediated dUTP-fluorescin nick end labelling (TUNEL) method. The TUNEL method indicates DNA double strand breaks considered as a hallmark of programmed cell death (apoptosis). Apoptotic cells were observed in 57 of 67 cases. The apoptotic rate (percentage of stained tumor cells) varied from 0% to 54.1%. GI carcinomas possessed a statistically significant higher apoptotic rate than GII/GIII carcinomas. The proliferation index (percentage of Ki-67 labelled cells) ranged from 0.09% to 22.3%. The well differentiated carcinomas (GI) showed statistically lower proliferative activity than moderate and poorly differentiated carcinomas (GII/GII). The clear cell variant of renal cell carcinoma expressed a higher apoptotic rate than the chromophilic variant. A statistical correlation between apoptosis/proliferation and occurrence of metastasis could not be established. In progression from well to less differentiated renal cell carcinoma the decrease of apoptotic rate, as well as the increase of the proliferative activity, contributes to a rapid tumor growth.

Adenocarcinoma, Clear Cell↗
PubMed1997

Renal cell carcinomas produce IL-6, IL-10, IL-11, and TGF-beta 1 in primary cultures and modulate T lymphocyte blast transformation.

We investigated the immunomodulatory capacity of primary cultures of renal cell carcinomas (RCC) by assessing production of cytokines and modulation of mitogen-induced T lymphocyte blast transformation. The results clearly show that immunomodulatory capacity is a common feature of RCC and that in vitro these tumors can produce interleukin-10 (IL-10) up to 20 ng/ml, IL-6 up to 35 micrograms/ml (> 250 kU/ml in the B9 system), IL-11 up to 15 micrograms/ml, and transforming growth factor-beta 1 (TGF-beta 1) up to 22 ng/ml. Furthermore, these tumors have the capacity to modulate T cell blast transformation over two orders of magnitude in each direction. The correlations of the immunologic properties of tumor cell cultures with the conventional classification of tumors (histology, cytology, staging, grading, presence of metastases, and secondary tumors) are analyzed. The significance of these findings for modulation of local immunity by RCC as well as for patient outcome is discussed.

Adjuvants, Immunologic↗
PubMed1997

[Adrenal cortex insufficiency caused by metastatic tumors].

Clinical features and the management of adrenal insufficiency are considered with reference to etiology, diagnosis, and treatment. Specifically considered are the management of patients with Addison's disease and metastases. Adrenal insufficiency may go unrecognized in the cancer patients because features such as nausea, vomiting, anorexia as well as orthostatic hypotension are not specific and may be mistakenly attributed to advancing malignancy or side effects of therapy. Prompt recognition and treatment of adrenal insufficiency can avert potentially life-threatening situations.

Addison Disease↗
PubMed1997

Oral squamous cell carcinoma invasion is associated with a laminin-5 matrix re-organization but independent of basement membrane and hemidesmosome formation. clues from an in vitro invasion model.

The basement membrane (BM) molecule laminin-5 represents the major component of the anchoring filaments, the BM counterpart of the hemidesmosomes. Because laminin-5 is abundantly deposited adjacent to budding invasive carcinoma cells in vivo, a special invasion-promoting role is suspected. We present a 3D collagen type I gel invasion model for oral squamous cell carcinoma (OSCC) using the newly established OSCC cell lines PE/CA-PJ15, PE/CA-PJ34, and PE/CA-PJ41. The carcinoma cells on the surface of the collagen type I gel show an invasive growth exclusively in the presence of gel-inoculated (myo)fibroblasts yielded from nodular palmar fibromatosis or tumour stroma. The model is characterized by an immunohistochemical and ultrastrcutural failure of structural BM and hemidesmosome formation. In the model an invasion-associated modulation of the laminin-5 deposition (alpha3, clone BM165; gamma2, clone GB3) was demonstrated: in invasive areas a strong ribbon-like immunostaining in the tumor-gel interface. The results obtained from the invasion model suggest that the assumed invasion-promoting ability of the BM molecule laminin-5 is realized independent of a structural BM and hemidesmosome formation.

Basement Membrane↗
PubMed1996

Molecular variants of fibronectin and laminin: structure, physiological occurrence and histopathological aspects.

This review deals with biological and pathological aspects of various isoforms of the matrix molecules fibronectin and laminin. They are generated by different molecular mechanisms: ED-A+ and ED-B+ fibronectin by alternative splicing of pre mRNA, de novo-glycosylated fibronectin by alternative post-translational O-linked glycosylation of the IIICS region, and the laminin isoforms by exchange of single chains of the heterotrimeric molecule. In contrast to the "common" fibronectin, the distribution of ED-B+ and de novo-glycosylated fibronectin is restricted to embryonic tissues; they subsequently reappear in granulation tissue, in fibrosing processes and in tumour stroma. The expression of these so-called oncofetal fibronectins is stimulated by growth factors (TGF beta). The association of the ED-B+ fibronectin with proliferative activity and newly formed vessels identifies this fibronectin variant as a marker of cellular activity in the process of fibrosis and as a suitable agent for the evaluation of tumour angioneogenesis. Initial results suggest a correlation between the amount of ED-B+ and de novo-glycosylated fibronectin in tumour stroma and the behaviour of carcinomas with regard to their invasiveness and propensity for metastatic dissemination. The current nomenclature of the laminin molecule family is presented. The laminin chain constitution of basement membranes switches from embryonic or proliferatively active to adult terminally differentiated tissues [disappearance of the laminin beta 2 (s) chain] and depends on the tissue type. The discrepancy between the loss of basement membranes (multiple basement membrane defects) in carcinomas and the recently reported increased laminin chain synthesis in these tumours may be explained by abundant laminin chain deposition outside the basement membrane in the carcinoma invasion front, possibly associated with enhanced adhesion of budding tumour cells.

Animals↗
PubMed1996

The neu oncogene product in serum and tissue of patients with metastatic gastrointestinal carcinomas.

We report on our experience investigating the serum levels of the soluble domain of p185 and the neu protein expression in the corresponding tumour tissue in patients with advanced gastrointestinal carcinomas. The study included 32 patients who were treated with palliative chemotherapy. The serum levels of the neu protein were investigated by immunosorbent assay techniques. We used the alkaline phosphatase/anti-(alkaline phosphatase) method for investigating the corresponding tumour tissue immunohistochemically. Increased serum neu protein levels were found in 8 of 22 (36%) patients with colorectal carcinomas and in 2 patients with advanced abdominal adenocarcinoma of unknown primary. All other patients with advanced gastrointestinal cancers were serum-neu-protein-negative. All serum-neu-protein-positive patients with colorectal carcinomas showed also an elevated neu protein expression. The extent of serum neu protein expression corresponded to the clinical course and the tumour marker CA 19-9. The serum neu protein may be useful for monitoring patients with advanced colorectal carcinomas, particularly in cases of immunohistochemical neu-protein-positive primary tumours.

Adult↗
PubMed1996

[CD34 detection--an immunohistochemical contribution to differential diagnosis of soft tissue tumors].

CD34 is a myeloid progenitor cel antigen and present in endothelial cells and almost all vascular lesions. Additionally, CD34 has been described in numerous fibroblast-like cells and different mesenchymal tumours. The immunohistochemical evidence of CD34, however, may be of importance in the differential diagnosis of benign and malignant soft tissue lesions, if clinicopathological features and other immunohistochemical markers are regarded properly. We studied the CD34 immunopositivity of solitary fibrous tumour at different sites (11 out of 11 tumours tested stained positive), dermatofibrosarcoma protuberans (15 out of 18 stained positive), and gastrointestinal stromal tumour (15 out of 15 stained positive), and discuss the significance of these results in differential diagnosis to morphologically comparable soft tissue lesions.

Adolescent↗
PubMed1996

Reduced formamide content and hybridization temperature results in increased non-radioactive mRNA in situ hybridization signals.

To define conditions for highly sensitive non-radioactive mRNA in situ hybridization on cryostat sections the influence of decreased formamide content and hybridization temperature was studied. The examination was performed on fibromatosis nodules of palmar fibromatosis visualizing the beta actin mRNA of myofibroblasts. The results show that a decrease in formamide content and hybridization temperature is able to enhance the sensitivity of mRNA detection applicating digoxigenin labelled DNA oligodeoxynucleotide. The best hybridization signal could be obtained under formamide-free conditions. In conclusion, a simplified sensitive formamide-free mRNA in situ hybridization protocol using oligonucleotide probes on human tissue cryostat sections is presented. The negative formamide effect is seen as a result of the chemical interaction of formamide with nucleic acid strands. An omission of formamide is suggested if the target as well as the probe are single stranded.

Actins↗