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Biomedical subjects

D Katenkamp

Publications and source records attributed to D Katenkamp.

At least 73 records · Page 4Linked to original sources
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

Immunomodulation of rat antigen-induced arthritis by leflunomide alone and in combination with cyclosporin A.

The effects of the new immunomodulating isoxazol derivative leflunomide, in comparison with cyclosporin A, on established antigen-induced arthritis in rats as well as serum antibody levels were determined. When treatment with leflunomide, at concentrations from 2.5 to 10 mg/kg/d, was started on day 3 of arthritis, the acute and chronic phases of arthritis were effectively inhibited. This was demonstrated by decreased joint swelling and reduced histopathological arthritis score at the end of experiment (day 26). Furthermore, the treatment resulted in a significantly reduced level of serum antibodies to the matrix components collagen type I, type II and proteoglycans. Neither leflunomide nor cyclosporin A, at doses of 1 mg/kg/d, had an effect on the severity of arthritis and antibody levels. However, when both drugs were used together, at these non-effective doses, the histopathological score of chronic arthritis was significantly reduced. The results of our experiments demonstrate that leflunomide has a strong suppressive effect on both acute and chronic phases of antigen-induced arthritis and formation of autoantibodies in rats. Furthermore, orally administered doses of leflunomide were as effective as doses of cyclosporin A given intraperitoneally. The combination of sub-effective doses of leflunomide and cyclosporin A resulted in significant inhibition of chronic arthritis.

Animals↗
PubMed1996

[Low malignancy myxofibrosarcoma versus low malignancy fibromyxoid sarcoma. Distinct entities with similar names but different clinical course].

Low-grade myxofibrosarcoma (MFS) and low-grade fibromyxoid sarcoma (FMS) are two distinct entities in the spectrum of myxoid mesenchymal sarcomas with fibroblastic differentiation. Low-grade MFS is seen often in the extremities of elderly patients, subcutaneously more frequent than in deep soft tissues, whereas the majority of cases of low-grade FMS occur in young to middle-aged adults, commonly in deep soft tissues of the shoulder region, the extremities and the trunk. Histologically, low-grade MFS shows a multinodular growth pattern and is composed of round or polygonal tumour cells mixed with elongated, curvilinear, thin-walled blood vessels in a myxoid matrix. The tumour cell nuclei in low-grade MFS display at least moderate nuclear pleomorphism and hyperchromasia. Low-grade FMS, however, is composed of bland fusiform tumour cells arranged in a whorled or swirling pattern, or occasionally more linear, and set characteristically in an alternating fibrous and myxoid stroma. Low-grade MFS recurs frequently but has a very low metastatic potential, whereas low-grade FMS is characterised by an indolent but ultimately malignant clinical course with metastases in more than half of the cases, which underlines the importance of distinguishing between the two entities.

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

[Infantile rhabdomyofibrosarcoma. An aggressive tumor in the spectrum of spindle cell tumors in childhood].

We report a case of an intrathoracic, extrapleural, infantile rhabdomyofibrosarcoma in a 4-year-old boy. Histologically, the primary lesion showed extensive hyalinization and stroma sclerosis and was composed of relatively uniform spindle-shaped, at least focally rather polygonal tumour cells with scattered intracytoplasmatic globoid inclusions. Although chemo- and radiotherapy was given postoperatively, local recurrences and metastases in the lung and thymus have developed; the patient died of tumour disease 3 years later. Recurrences and metastases showed features of tumour progression with higher cellularity and increased mitotic activity. Immunohistochemically, the tumour cells stained strongly positive for vimentin, desmin, and muscle-specific actin, and at least focally for MyoD1; the tumour did not stain for alpha-smooth muscle actin, neural and epithelial markers, or CD34 and CD31. The differential diagnosis of these aggressive tumours in the spectrum of spindle-cell lesions in early childhood is discussed.

Biomarkers, Tumor↗
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↗
PubMed1996

Matrix remodelling in dilated cardiomyopathy entails the occurrence of oncofetal fibronectin molecular variants.

OBJECTIVES: To investigate whether disturbance of the cellular homoeostasis and integrity of cardiomyocytes in dilated cardiomyopathy (DCM) is accompanied by alterations in cell-matrix relations as indicated by changes in the deposition of fibronectin (FN) isoforms. DESIGN: Tissue from a case series of patients with DCM was investigated by immunohistochemistry with antibodies against FN (all variants, clone IST4), ED-A+ FN (clone IST9), ED-B+ FN (clone BC1), and oncofetal glycosylated FN (clone 5C10). The sites of de novo synthesis of FN were demonstrated by means of non-radioactive RNA in situ hybridisation (ISH) with biotinylated FN cDNA fragments as the probe. SETTING: University hospital. PATIENTS: Samples from 10 patients with clinical criteria and histological diagnosis of DCM and from 3 individuals with normal hearts. INTERVENTIONS: Samples were obtained by right ventricular endomyocardial biopsy. MAIN OUTCOME MEASURE: Distribution of oncofetal FN variants in DCM hearts. RESULTS: Immunostaining of FN (IST4, all variants) showed a coarse interstitial network in normal and diseased myocardium. ED-A+ FN was deposited as fine interstitial spots in normal myocardium and in DCM samples. Immunostaining for oncofetal glycosylated FN and ED-B+ FN was not seen in normal adult myocardium, whereas myocardium from DCM patients showed focal and delicate staining in the interstitium. RNA ISH showed that these deposits resulted from local FN synthesis. CONCLUSION: The results accord with de novo expression of oncofetal FN variants in hearts from patients with DCM. The oncofetal FN variants may serve as disease markers in myocardium affected by DCM.

Adult↗
PubMed1996

Adoptive transfer of susceptibility to antigen-induced arthritis into severe combined immunodeficient (SCID) mice: role of CD4+ and CD8+ T cells.

Antigen-induced arthritis (AIA) in mice occurs after immunization and a subsequent intra-articular injection with methylated bovine serum albumin (mBSA). The role of T lymphocytes in the adoptive transfer of susceptibility to AIA into SCID mice was investigated. Pooled spleen and lymph node cells from immunized syngeneic or allogeneic donor mice, isolated either before or after the induction of arthritis, could transfer the capacity both to develop arthritis and to produce antibodies to mBSA, collagen type II and cartilage proteoglycans into SCID mice. The intra-articular injection of mBSA in responder animals, immediately after the cell transfer, resulted in a chronic arthritis in the induced joint. The histologic examination revealed synovial hyperplasia, mononuclear infiltration of the synovial membrane, exudation of polymorphonuclear leucocytes into the joint space, and chondrocyte death. The depletion of CD4+ T cells before transfer prevented the manifestation of arthritis in SCID mice, with a concomitant decrease in antibody levels to mBSA, collagen type II and cartilage proteoglycans. In contrast, removal of CD8+ T cells did not significantly affect the transfer of arthritis into SCID mice. The results demonstrate an essential role of CD4+ T cells in the pathogenesis of AIA, whereas CD8+ T cells do not seem to be required for the induction and perpetuation of this disease.

Adoptive Transfer↗
PubMed1996

[Cyto- and molecular genetic studies of renal cell carcinoma with special reference to multifocal carcinoma lesions].

In 86 consecutive radical nephrectomies we found in 12 kidneys (13.8%) a total of 17 multicentric foci of carcinoma. Beside the usual histopathological investigations we performed in seven secondary tumors further cyto-and molecular genetic analyses. The structural and/or numerical chromosome aberrations in the small secondary tumors were similar to the changes in the main tumors. We conclude that these foci have malignant potential. In eight of these results and the multicentricity that was found, we continue to recommend elective radical nephrectomy in renal cell carcinoma.

Aged↗
PubMed1995

[Ectopic hamartomatous thymoma. Case report with special reference to differential diagnosis].

We report the case of an ectopic hamartomatous thymoma in a 56-year-old male patient. The lesion arose subcutaneously in the supraclavicular region. Histologically, the well-circumscribed but unencapsulated tumour was composed of uniform fusiform tumour cells. In addition, mature fatty tissue, scattered T-lymphocytes, and an epithelial and a myoepithelial tumour cell component were found. The epithelial differentiation of the spindle cell tumour component was confirmed immunohistochemically and by electron microscopy. Ectopic hamartomatous thymoma has to be distinguished from ectopic cervical thymoma, thymolipoma, ectopic salivary tissue, teratoma, peripheral nerve sheath tumours, malignant epithelial tumours with thymus-like differentiation, biphasic synovial sarcoma, and skin adnexal tumours.

Biomarkers, Tumor↗
PubMed1995

Differential expression of fibronectin splice variants, oncofetal glycosylated fibronectin and laminin isoforms in nodular palmar fibromatosis.

The tissue formation process in nodular palmar fibromatosis (Morbus Dupuytren) was investigated by the demonstration of fibronectin splice variants (ED-A and ED-B fibronectin), de novo glycosylated fibronectin and laminin isoforms (A, M, B1, B2, s chains) in association to the proliferative activity (Ki-67 antigen) and the occurrence of myofibroblast phenotype (alpha-smooth muscle actin, desmin). The proliferative noduli of the fibromatosis were characterized by a diffuse immunostaining for alpha-smooth muscle actin, and single cells positive for desmin and the Ki-67 antigen. In contrast to the surrounding aponeurosis as extracellular matrix, components of the whole proliferative noduli were defined: ED-A, ED-B and de novo glycosylated fibronectin, B1 and B2 laminin chain, tenascin and collagen type IV. The demonstration of the A and M laminin chain was restricted to a few cells of the proliferative noduli. S laminin could be visualized in the majority of palmar aponeurotic fibroblasts. As revealed by mRNA, in situ hybridization a de novo synthesis of fibronectin could only be detected within proliferative noduli. There is a positive correlation between the myofibroblast phenotype formation, cellular proliferation and the occurrence of ED-A and ED-B containing fibronectin, as well as de novo glycosylated fibronectin in Dupuytren's disease. The ultrastructural irregularities of myofibroblastic basal lamina and the heterogeneity of the myofibroblast phenotype are equivalent to the variability of laminin isoform immunostaining.

Alternative Splicing↗
PubMed1995

Integrin receptors and their relationship to cellular proliferation and differentiation of oral squamous cell carcinoma. A quantitative immunohistochemical study.

The expression of extracellular matrix (ECM) proteins (fibronectin, laminin, collagen IV) and ECM receptors of integrin type (alpha 2 beta 1, collagen receptor; alpha 6 chain of the fibronectin receptor; alpha 6 chain of the laminin receptor) were examined in normal oral squamous epithelium and in invasive areas of squamous cell carcinomas with various differentiation and proliferation activities (Ki-67 antigen labelling), evaluating the presence, quantity (using an image analysis system) and distribution of the integrin subunits. In the mucosa, there was uniform immunostaining for alpha 2 beta 1 and alpha 6 concentrated at the cell membrane in the basal/supra basal cell zone, whereas, alpha 5 showed a discontinuous staining of the basal cell-basement membrane interface. alpha 2 and alpha 6 could be visualized in all carcinomas. alpha 5 showed low expression preferentially in less differentiated carcinomas. In contrast to normal mucosa, there was an increase in alpha 6 staining in well-differentiated carcinomas. Dedifferentiation of oral carcinomas was accompanied by an increase in cellular proliferation and with a decrease in alpha 2 beta 1 and alpha 6 staining. This reduction of alpha 6 staining was shown to be statistically significant, suggesting that this integrin may be a valuable grading parameter for oral squamous cell carcinoma.

Basement Membrane↗
PubMed1995

TGF beta and bFGF synthesis and localization in Dupuytren's disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin.

Nodular palmar fibromatosis is a self-limited proliferation of fibro-/myofibroblasts associated with growth factor synthesis and abundant fibronectin extracellular matrix deposition. bFGF and TGF beta are potent modulators of fibro-/myofibroblast proliferation and differentiation. Moreover, in vitro investigations evidenced a TGF beta 1-dependent regulation of alternative splicing of fibronectin mRNA. To investigate a possible implication of these growth factors in the tissue formation process of palmar fibromatosis, TGF beta 1/2 and bFGF synthesis, as well as TGF beta 1/3 and bFGF tissue distribution, is demonstrated by RNA in situ hybridization and/or immunohistochemistry in relation to myofibroblast phenotype development (alpha-smooth muscle actin, desmin immunohistochemistry), expression of different fibronectin isoforms (ED-A+, ED-B+ and oncofetal glycosylated fibronectin immunohistochemistry, fibronectin RNA in situ hybridization) and cellular activity (cyclin RNA in situ hybridization, Ki-67 immunolabelling). The myofibroblast phenotype (alpha-smooth muscle actin, desmin), the growth factor synthesis (TGF beta 1 and 2, bFGF), fibronectin matrix synthesis (RNA in situ hybridization with cDNA) and ED-A+, ED-B+ and oncofetal glycosylated fibronectin immunostaining are exclusively localized in the active proliferative nodules (Ki-67 immunolabelling and cyclin mRNA demonstration). Whereas the growth factor synthesis is restricted to the proliferative areas of the fibromatosis only, TGF beta 1, TGF beta 3 and bFGF proteins can also be detected immunohistochemically with a lower intensity in the surrounding aponeurotic tissue. The spatial correlation of myofibroblast phenotype, TGF beta and bFGF synthesis and the occurrence of the oncofetal molecular fibronectin variants (ED-B+ and oncofetal glycosylated fibronectin) in the active proliferative fibromatosis nodules suggests a pathogentic role of these growth factors and matrix components in the tumorous tissue formation process. The presence of the bFGF and TGF beta 1/3 proteins in fibroblasts neighbouring the proliferative nodules may point to a recruitment of quiescent aponeurotic fibroblasts in the fibromatous tissue formation process.

DNA, Complementary↗
PubMed1994

Appearance of the myofibroblastic phenotype in Dupuytren's disease is associated with a fibronectin, laminin, collagen type IV and tenascin extracellular matrix.

The proliferative nodules of Dupuytren's disease are electron microscopically characterized by the occurrence of myofibroblasts with a basal lamina-like material. As reported in the literature, immunohistochemical investigations showed a fibronectin matrix but failed to demonstrate laminin. This discrepancy between electron microscopic features and immunohistochemical findings prompted us to examine the composition of extracellular matrix (fibronectin, laminin, collagen type IV and tenascin) in relation to the myofibroblast phenotype in proliferative nodules from 13 native surgical specimens of nodular palmar fibromatosis (Dupuytren's disease). The immunohistochemical staining for fibronectin was positive within the whole palmar aponeurosis and was particularly intense in the proliferative areas, whereas laminin, collagen type IV and tenascin labelling was restricted to the alpha-smooth muscle actin-positive proliferative nodules. To exclude definitively an unspecific laminin labelling, SDS-PAGE and immunoblot were performed. The electrophoretic pattern of Dupuytren's disease tissue revealed laminin and was in congruence with human placental tissue used as positive control. The results substantiate an extracellular matrix formation by myofibroblasts with fibronectin, laminin, collagen type IV and tenascin as constituents. Therefore, laminin expression can no longer be considered to be a distinguishing feature between myofibroblasts and smooth muscle cells.

Cell Adhesion Molecules, Neuronal↗