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Biomedical subjects

H Kosmehl

Publications and source records attributed to H Kosmehl.

At least 55 records · Page 3Linked to original sources
PubMed2000

The correlation of p53 protein overexpression and p53 antibodies in serum of patients with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Mutations of p53 gene were demonstrated in many solid tumors with varying frequency. We analyzed the relationship between p53 protein expression in bladder cancer tissue, p53 autoantibodies in serum and the clinical course of 32 patients with and 10 patients without transitional cell carcinoma of the urinary bladder. MATERIALS AND METHODS: In the 32 patients studied, bladder cancer was diagnosed as pTaG1-2 in 8 cases, pT1G2 in 6, pT1G3 in 7, pT2G2-3 in 7, pT3G2-3 in 3 and pT4 in 1 patient. Anti-p53 antibodies were detected by an enzyme-linked immunosorbent assay. Immunohistochemical staining was performed using a standardized alkaline phosphatase monoclonal anti-alkaline phosphatase method. To prove the statistical significance of tumor grading and staging, the Kruskal-Wallis test was applied (p < 0.01). The mean follow-up was 26 months. RESULTS: We found 12.5% p53 autoantibody-positive sera without a statistically significant correlation with tumor grade (p = 0.0569) and category (p = 0.612). Three of 4 patients who had p53 autoantibody-positive sera died within 9 months. All of these sera-positive patients had p53 protein-positive tumor tissue. Control sera were all negative for p53 autoantibodies. CONCLUSION: This study shows a strong relationship between p53 protein overexpression and the occurrence of p53 autoantibody in bladder cancer. The expression of p53 autoantibodies seems to be an event in cases of bladder cancer with an unfavorable tumor-specific outcome. Because of the small number of cases and the short follow-up time, further quantitative studies will hopefully demonstrate whether this might be of prognostic importance.

Autoantibodies↗
PubMed2000

Immunolocalization of tenascin-C, alpha9 integrin subunit, and alphavbeta6 integrin during wound healing in human oral mucosa.

Tenascin-C (TN-C) and its isoforms are multidomain extracellular matrix (ECM) proteins that are believed to be involved in the regulation of stromal-epithelial interactions. Some of the interactions between TN-C and cells are mediated by integrins. In this study we analyzed the expression of TN-C and its large molecular weight splice isoform (TN-C(L)) and the putative TN-C-binding alpha9 and alphavbeta6 integrins during human wound repair. In 3-day-old oral mucosal wounds, immunoreactivity for alpha9 integrin localized abundantly at the migrating basal wound epithelial cells. TN-C and TN-C(L) were localized in the matrix between and underneath alpha9-expressing epithelial cells. In parallel with gradual downregulation of alpha9 integrin immunoreactivity in 7-day and older wounds, the expression of alphavbeta6 integrin was temporarily induced. Integrin alphavbeta6 co-localized in the same area as TN-C and TN-C(L) immunoreactivity at the cell-cell contacts of the basal and suprabasal cell layers of the wound epithelium. During granulation tissue formation and reorganization from 7 to 28 days after wounding, TN-C and TN-C(L) were abundantly localized in the granulation tissue. The findings show that TN-C(L) is expressed under the migrating epithelial front and in the granulation tissue during matrix deposition in wound repair. Preferential localization of alpha9 integrin in migrating epithelial cells and of alphavbeta6 integrin in epithelium after wound closure suggests different functions for these integrins in wound repair.

Alternative Splicing↗
PubMed2000

Microvascular submandibular gland transfer for severe cases of keratoconjunctivitis sicca.

Free submandibular salivary gland transfer was investigated as a surgical method for the treatment of severe keratoconjunctivitis sicca. In an animal model, we examined the tolerance of warm ischemia of the submandibular gland. After temporary interruption of the blood supply (1 to 6 hours), the morphologic changes in the submandibular gland were analyzed histologically and immunohistochemically in 41 rabbits. From 1.5 hours ischemia onward, an increasing structural damage of the parenchyma with emphasis on the secretory cells was seen. Six hours of ischemia caused total necrosis of the salivary gland. Our clinical experience includes 24 highly selected patients suffering from keratoconjunctivitis sicca, in whom we transferred 31 autologous submandibular glands to the temple for permanent autologous tear substitution within the past 4 years. The glands were implanted into a pocket prepared in the temporalis muscle, and the nourishing vessels were anastomosed to the superficial temporal artery and vein. The submandibular duct was implanted into the upper lateral conjunctival fornix. The transferred glands were left denervated. In addition to the clinical examination, scintigraphy with Tc 99m pertechnetate was used to document the graft's viability after the transfer. Viable incorporation with longstanding secretory function occurred in 26 of the 30 transplanted denervated salivary glands. The resulting lubrication of the treated eyes was irregular for up to 3 months in almost even case. One year after surgery, all patients with a viable transplant developed at least occasional epiphora, which was surgically managed by reducing the size of the graft in 10 patients. No severe side effects were seen in this series. The ophthalmologic evaluation of the method included the assessment of dry eye symptoms and of the volume and quality of ocular lubrication (Schirmer test, fluorescein break-up time), the pathology of the ocular surface (rose bengal staining), and the need for pharmaceutical tear substitutes. One year after surgery, 18 of 27 cases assessed were judged as significantly improved by these tests.

Adolescent↗
PubMed1999

Synthesis and protein distribution of the unspliced large tenascin-C isoform in oral squamous cell carcinoma.

The inclusion or omission of the alternatively spliced region in the tenascin-C (Tn-C) mRNA gives rise to the large (Tn-C(L)) or small (Tn-C(S)) variant, respectively. Tn-C(L) is thought to be a typical component of provisional extracellular matrices (ECMs) and is expressed during tumour stroma remodelling. Tn-C(L) synthesis has been studied using RNA/RNA in situ hybridization, and Tn-C(L) protein distribution, using immunohistochemistry (clone BC-2), in 18 oral squamous cell carcinomas (OSCCs) of different grades of malignancy. While the Tn-C(L) protein was demonstrated within the whole stromal compartment regardless of grade of malignancy, the majority of the Tn-C(L) mRNA signal-bearing cells were carcinoma cells. Only a few stromal myofibroblasts were able to synthesize Tn-C(L), as revealed by alpha-smooth muscle actin double staining. In well-differentiated carcinomas (G1), the Tn-C(L) synthesizing carcinoma cells were localized as a single positive cell layer in the tumour stroma interface, particularly in invasive areas. A higher grade of malignancy (G2/G3) is associated with a significantly increased number of Tn-C(L) synthesizing carcinoma cells randomly distributed within the invading tumour areas. Double-staining experiments (Tn-C(L) mRNA ISH/BC-2 immunohistochemistry) indicate that these cells are capable of organizing and depositing a three-dimensional Tn-C(L) matrix. Even though an instructive and/or inductive role of the carcinoma cells in tumour stroma formation cannot be excluded, these results demonstrate that carcinoma cells can directly produce the ECM components of tumour stroma.

Basement Membrane↗
PubMed1999

[An unusual case of genital tuberculosis. A case report].

We represent and discuss etiology, diagnosis as well as differential diagnoses of tuberculous orchtitis referring to an actual case of this rare disease. In the least of all cases one can conclude from the clinical symptoms on the tuberculous origin of the disease. Other differential diagnoses will set more frequently due to rarity of this disease. Quite a lot of cases a bacterial superinfection veils the sterile leucocyturia as main characteristic of genitourinary tuberculosis. Imaging diagnostics frequently fails to give indications of tuberculous origin of the lesion. As before the evidence of Mycobacteria tuberculosis is the most important parameter to proof a tuberculosis. Despite required microbiological cultivation to make a resistogram the polymerase chain reaction is a high sensitive and comparable fast method for detection of Mycobacteria even from tissue. In such dubious cases we recommend to perform an operative denudation due to frequently difficult delimitation from malignant testicular tumours.

Antitubercular Agents↗
PubMed1999

[Increased incidence of renal cell carcinoma in central Europe. Does diagnostic increase reflect a true increase in incidence?].

In the last years the incidence of renal cell carcinoma diagnosis increased about 15-20%. The main aim of this study was to analyse the reason of the increase of incidence. In the present autopsy series comprising 23,801 autopsies the percentage of patients who died of renal cell carcinoma is 1.77% in Jena and 1.55% in Königgrätz (200,000 inhabitants each). Over this time the incidence of renal cell carcinoma in autopsies has increased. In spite of the increased amount of incidentally found renal cell carcinomas since beginning widespread use of ultrasonography the percentage of clinically recognized renal cell carcinomas on the total of all found renal cell carcinomas in autopsies is nearly constant about the 12-year period in Jena and 10-year period in Königgrätz. Thus, the increased number of radical nephrectomies is not only caused by widespread use of ultrasonography. The increasing trend of the incidence of renal cell carcinoma seems to be real.

Carcinoma, Renal Cell↗
PubMed1999

[Limits for organ-preserving surgery in renal cell carcinoma].

The indication for elective organ-preserving surgery in renal cell carcinoma is under discussion. The statements about the maximum tumor size, which could be considered for this surgical procedure, differ in the literature. In a series of 281 consecutive radical tumor nephrectomies we compared the results of preoperative ultrasound and computerized tomography regarding to tumor size and multifocality with the results of the postoperative systematically section of the removed kidneys. Further we analysed the results of 14.793 autopsies regarding to tumor size and multifocality. Serial section of the 281 nephrectomy specimens revealed a total of 64 multifocal tumors in 48 kidneys ( = 17,1 %). The correlation between tumor size and multifocality showed only in tumors up to 20 mm no additional lesions, whereas in the higher tumor categories the incidence was up to 23 %. These clinical investigations were confirmed by the results of the autopsies. In summery of the results we conclude, that the elective organ-preserving surgery of renal cell carcinoma is only indicated in tumors with a maximum diameter of 20 mm.

Carcinoma, Renal Cell↗
PubMed1999

Expression of the transmembrane protein tyrosine phosphatase RPTPalpha in human oral squamous cell carcinoma.

Little is known about the role of protein-tyrosine phosphatases (PTPs), the cellular counterparts of protein-tyrosine kinases, both for normal growth regulation and for its dysregulation in cancer. The receptor-like PTPalpha (RPTPalpha) may play a positive role in growth regulation and has been shown to be overexpressed in colon carcinoma. An RNA/RNA in situ hybridisation protocol for RPTPalpha as well as RPTPalpha immunohistochemistry was developed to evaluate RPTPalpha expression in oral squamous cell carcinomas (OSCCs) of different histological grade and to reveal the synthetically active cells and their tissue distribution. In well-differentiated OSCC (G1), RPTPalpha mRNA could be detected by in situ hybridisation exclusively in stroma cells (fibro/myofibroblasts and inflammatory cells). A higher histological grade (G2/G3) was associated with an increased number of RPTPalpha-synthesising carcinoma cells haphazardly distributed within invading tumour areas. Consistent results were obtained by immunocytochemistry. Thus, both carcinoma dedifferentiation and stroma recruitment and activation seem to be associated with an upregulation of RPTPalpha expression in OSCC. The results speak in favour of the important role of activation of stroma fibro/myofibroblasts influencing the biological behaviour of epithelial tumours and also suggest that elevated RPTPalpha expression may be a more general marker for proliferating or dedifferentiated cells.

Carcinoma, Squamous Cell↗
PubMed1999

Primary cutaneous marginal center lymphoma - complete remission induced by interferon alpha2a.

Marginal zone lymphoma (MZL) is a distinct entity among B-cell lymphomas. We report on a 53-year-old woman who developed disseminated primary cutaneous MZL with secondary lymph node involvement and perinodular spreading. The tumor cell phenotype was characterized as CD20/CD79a/kappa/lambda+/ bcl-2-positive, CD3/5/15/39/bcl-1-negative. Ki-67 was expressed by 20-35% of tumor cells. There was no evidence of systemic (including bone marrow) involvement. The diagnosis of MZL with plasmacellular differentiation (Stage IVa) was made. The patient was treated with interferon alpha2a injected s.c. at 9x10(6) U 3 days a week for 1 year. During this time the skin lesions completely disappeared. No evidence of lymph node or extracutaneous disease was found. The patient remains in complete remission. Side effects were only of grade I (WHO); the Karnovsky index was 90%. As shown for other types of primary cutaneous B-cell lymphoma, prolonged interferon alpha monotherapy may be effective in controlling the disease and/or inducing complete remission in MZL.

Adult↗
PubMed1999

Distribution of laminin and fibronectin isoforms in oral mucosa and oral squamous cell carcinoma.

The expression of laminin and fibronectin isoforms varies with cellular maturation and differentiation and these differences may well influence cellular processes such as adhesion and motility. The basement membrane (BM) of fetal oral squamous epithelium contains the laminin chains, alpha2, alpha3, alpha5, beta1, beta2, beta3, gamma1 and gamma2. The BM of adult normal oral squamous epithelium comprises the laminin chains, alpha3, alpha5, beta1, beta3, gamma1 and gamma2. A re-expression of the laminin alpha2 and beta2 chains could be shown in adult hyperproliferative, dysplastic and carcinomatous lesions. In dysplasia and oral squamous cell carcinoma (OSCC), multifocal breaks of the BM are present as indicated by laminin chain antibodies. These breaks correlate to malignancy grade in their extent. Moreover, in the invasion front the alpha3 and gamma2 chain of laminin-5 can immunohistochemically be found outside the BM within the cytoplasm of budding carcinoma cells and in the adjacent stroma. The correlation between the morphological pattern of invasive tumour clusters and a laminin-5 immunostaining in the adjacent stroma may suggest, first, that a laminin-5 deposition outside the BM is an immunohistochemical marker for invasion and second, that OSCC invasion is guided by the laminin-5 matrix. Expression of oncofetal fibronectins (IIICS de novo glycosylated fibronectin and ED-B fibronectin) could be demonstrated throughout the stromal compartment. However, the ED-B fibronectin synthesizing cells (RNA/RNA in situ hybridization) are confined to small stroma areas and to single stroma and inflammatory cells in the invasion front. A correlation of the number of ED-B fibronectin synthesizing cells to malignancy grade could not be seen. ED-B fibronectin mRNA-positive cells seem to be concentrated in areas of fibrous stroma recruitment with a linear alignment of stromal fibro-/myofibroblasts (desmoplasia). Double staining experiments (ED-B fibronectin in situ hybridization and alpha-smooth muscle actin immunohistochemistry) indicated that the stroma myofibroblasts are a preferential source of ED-B fibronectin. In conclusion, in OSCC, a fetal extracellular matrix conversion is demonstrable. Tumour cells (laminin alpha2 and beta2 chain) and recruited stromal myofibroblasts (oncofetal ED-B fibronectin) contribute to the fetal extracellular matrix milieu.

Adult↗
PubMed1999

Loss of laminin-5 in the epithelium-stroma interface: an immunohistochemical marker of malignancy in epithelial lesions of the breast.

AIMS: To demonstrate immunohistochemically the alpha3 and gamma2 chain of laminin-5 in benign epithelial and malignant lesions of the human breast. METHODS AND RESULTS: The alpha3 chain was identified by the monoclonal antibody BM165 and the gamma2 chain by GB3 in shock frozen samples using APAAP (alkaline phosphatase monoclonal anti-alkaline phosphatase) technique. The pre-existing breast epithelium, the 12 benign ductal and lobular proliferations and the three fibroadenomas showed a continuous immunostaining in the basement membrane region. In contrast to benign epithelial lesions, the 44 cases of invasive breast carcinoma showed a loss of the laminin-5 chains in more than 50% of the carcinoma stroma interface. Twenty-four out of the 44 invasive carcinomas revealed a complete loss of laminin-5 immunostaining. Focal defects of the laminin-5 immunostaining were also found in ductal carcinoma in situ in its pure form. CONCLUSIONS: As recently described, the malignant transformation of breast epithelium with expression of an invasive phenotype is associated with a decrease of hemidesmosomes. The reduced immunostaining of laminin-5 is in line with this finding because laminin-5 represents the major component of the anchoring filaments attaching hemidesmosomes to the basement membrane. We feel that immunohistochemical demonstration of laminin-5 may serve as a marker of benignity in epithelial breast lesions. While other carcinoma types exhibit an increased laminin-5 deposition, which has been suggested as an invasion promoting factor, the loss of laminin-5 in breast cancer supports the view that breast carcinomas do not utilize laminin-5 for invasion.

Breast Neoplasms↗
PubMed1999

Real indications for adrenalectomy in renal cell carcinoma.

OBJECTIVES: Adrenalectomy is a part of radical nephrectomy because of the surgical oncology principle of a 'wide margin beyond the malignancy' and due to concern over possible metastases to the ipsilateral adrenal gland, especially in upper pole tumors. But, neither the frequency, predisposing factors of the renal cell carcinoma nor mechanisms of involvement of the adrenal gland are well defined. We assessed the ipsilateral adrenal involvement in renal cell carcinoma to determine whether ipsilateral adrenalectomy during radical nephrectomy is essential. MATERIAL AND METHOD: In a series of 15,347 autopsies in Jena from 1985 through 1996, 272 renal cell carcinoma with 24 adrenal metastases were found. In the same period 9 adrenal metastases were found in 639 radical nephrectomies. Contralateral and bilateral metastases were seen in 15 cases of the autopsy series and in 2 cases of the operative series. RESULTS: The risk of adrenal metastases correlated with multifocal tumors, pleomorphic cell type, anaplastic growth pattern and tumors that were larger than 2.5 cm. Of the 24 renal cell carcinomas with adrenal metastases in the autopsy series, 23 had evidence of widespread disease and 22 had lymph node metastases. A preoperative abdominal computerized tomography was performed in all 9 patients of the operative series with renal cell carcinoma and adrenal involvement. The adrenal gland was considered abnormal in 8 of the 9 cases (88.9%). Only in 1 patient was the computerized tomography incorrectly interpreted as negative. CONCLUSION: We think adrenalectomy should only be performed if there is radiographic evidence of metastases in the adrenal gland or adrenal infiltration by a large upper-pole tumor is possible. Macroscopically normal adrenal glands should not be removed during tumor nephrectomy because the need and benefit of routine adrenalectomy are extremely limited.

Adrenal Gland Neoplasms↗
PubMed1999

Multifocality in renal cell carcinoma: A bilateral event?

OBJECTIVES: The major disadvantage of nephron-sparing surgery for renal cell carcinoma is the risk of local recurrence. This is most likely a manifestation of undetected small additional tumors in the renal remnant. To define more clearly the incidence and nature of unilateral and bilateral multifocal tumors, an autopsy study was undertaken. MATERIALS AND METHODS: In a series of 14,793 autopsies from 1985 to 1995, 260 renal cell carcinomas were found. In all cases of renal cell carcinoma a search for small renal lesions was performed in the apparently normal-appearing portion of the kidneys. Every kidney was serially and systematically cut (5 mm) to probe for intraparenchymal lesions. RESULTS: Of the 260 renal cell carcinomas 36 cases (13.85%) had multifocal malignant and/or benign nodules. The number of the additional nodules ranged from 2 to 18. 12% of the malignant multifocal carcinomas were limited to the ipsilateral kidney and 88% were bilateral. The average size of the multifocal renal lesions was 8.7 x 9.0 x 9.5 (range 3-23) mm. Renal cell carcinomas with low stage and good grading have a higher incidence of multifocal nodules. No significant difference was found with regard to metastasized and nonmetastasized renal cell carcinomas. In 38.1% of all chromophilic renal cell carcinomas additional nodules were found. CONCLUSIONS: Multifocality in renal cell carcinomas cannot be predicted reliably, although the papillary histological pattern, good grading and low staging seems to be associated with a higher incidence of multifocality. Nearly 90% of the multifocal nodules were bilateral.

Autopsy↗
PubMed1998

Evidence of ED-B+ fibronectin synthesis in human tissues by non-radioactive RNA in situ hybridization. Investigations on carcinoma (oral squamous cell and breast carcinoma), chronic inflammation (rheumatoid synovitis) and fibromatosis (Morbus Dupuytren).

The splicing variant of fibronectin containing the ED-B domain (oncofoetal fibronectin) occurs in foetal tissues, reparative processes, organ fibrosis and in tumour tissues. Consequently, a supportive effect of ED-B+ fibronectin for tissue remodelling and tumour progression is assumed. A non-radioactive RNA-RNA in situ hybridization protocol for the investigation of ED-B+ fibronectin synthesis applicable in human tissues is introduced. The ED-B+ fibronectin synthesis was investigated in human disease processes, for which the occurrence of ED-B+ fibronectin is well demonstrated by immunohistochemistry (rheumatoid arthritis, oral squamous cell carcinoma, invasive ductal carcinoma of the breast and nodular palmar fibromatosis). The ED-B+ fibronectin synthesis could be shown in lining cells and in endothelial cells of synovial villi in rheumatoid arthritis, in stromal cells of oral squamous cell carcinoma and invasive ductal carcinoma and in fibro-/myofibroblasts in the proliferative and early involutional phase of nodular palmar fibromatosis. By means of double labelling (alpha-smooth muscle actin immunostaining - ED-B+ fibronectin in situ hybridization), the ED-B+ fibronectin synthesis could be shown to be a typical feature of myofibroblasts. In contrast to the often diffuse ED-B+ fibronectin immunostaining, only a few synthetically active stromal cells were observed focally accentuated within the tumour, which were interpreted as hot spots of tumour-stroma interaction.

Arthritis, Rheumatoid↗
PubMed1998

Evaluation of microvessel density by computerised image analysis in human renal cell carcinoma. Correlation to pT category, nuclear grade, proliferative activity and occurrence of metastasis.

A high microvessel density is suspected to favour tumour progression and the occurrence of metastasis. To elucidate the significance of abundant vessels for the behaviour of human renal carcinomas, the microvessel density of 110 renal cell carcinomas was correlated to pT category, nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival interval. The microvessels were quantified using CD31 immunostaining of endothelial cells and computer-aided image analysis. The rules for reproducible microvessel counting, as defined by Weidner, were strictly observed. A statistically significant relationship between the microvessel density and nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival was found; only for tumour size could no such relation be seen. Perplexingly, there is a diminution of microvessel density in association with increasing nuclear grade, proliferative activity, relapse-free survival interval and frequency of metastasis. This finding is contradictory to the hypothesis that an increasing microvessel density indicates a worsening prognosis.

Antibodies↗