Biomedical subjects

T Böhling

Publications and source records attributed to T Böhling.

At least 55 records · Page 3Linked to original sources

PubMed1997

Tensor fold and anterior epitympanum.

HYPOTHESIS: The aim of this study was to investigate the anatomy and pathology of the anterior epitympanum and of the tensor fold. BACKGROUND: Early studies reported data that are primarily still relevant, but contemporary reports present conflicting data, including several erroneous concepts. METHODS: Fifty-one temporal bones were dissected, and the anatomic details were photographed in 42 normal and nine infected bones. Histology was documented from seven serially sectioned bones, five normal and two infected. RESULTS: The tensor fold formed the frontal wall of the anterior epitympanum between tensor tendon and attic bony wall, the anterior insertion consisting of composite connective and fatty tissue with some bone trabeculae. The transverse crest was posterior to it and extended from the anterior tympanic spine to the facial canal. The tensor fold angle in 78% of the specimens was between 45 degrees and 80 degrees, seldom horizontal, and the size of the supratubal recess (or space) increased as the fold angle increased. In 14 ears (27%) the fold had a membrane defect connecting the two spaces. Blockade of the tympanic isthmus caused inflammatory obliteration of the anterior epitympanum when the tensor fold was intact. CONCLUSIONS: The anterior epitympanum, a closed space around the anterior half of the head of the malleus, is normally closed by an intact tensor fold, but about one fourth of ears may show membrane defects. Aeration occurs via the tympanic isthmus through a constriction formed by the head of the malleus with the medial attic wall. In surgery for ears with epitympanal pathology, incus transposition should be combined with resection of the thin portion of the tensor fold for safeguarding permanent attic aeration.

Humans↗

PubMed1996

Comparison of cytogenetics, interphase cytogenetics, and DNA flow cytometry in bone tumors.

Twenty-three samples of benign and malignant bone tumors were studied with cytogenetic analysis, interphase cytogenetics (IC) using in situ hybridization with (peri)centromeric probes for chromosomes 1, 7, and/or 8, and DNA flow cytometry (FCM). Our aim was to compare these methods in the detection of numerical chromosome aberrations (NCA) and aneuploidy. IC detected aneuploidy in 91%, FCM in 73%, and cytogenetics in 27% of the malignant tumors. In benign tumors IC detected aneuploid by in 4(33%), FCM in 2(17%), and cytogenetic analysis in 1. All of the benign tumors aneuploid by IC, two of which were also aneuploid by FCM, were histologically potentially aggressive. The clonal aberrations detected with cytogenetics usually agreed with the IC and FCM findings. All malignant tumors which had a normal karyotype were aneuploid either by IC or FCM or by both. In conclusion, IC was the most sensitive method in the detection of NCA and aneuploidy even though it was usually performed with only two (peri)centromeric probes. Aneuploidy was detected by cytogenetic analysis alone in 4 samples (17%), by cytogenetic analysis and/or FCM in 11 samples (48%), and by cytogenetic analysis, FCM, and/or IC in 16 samples (70%). Thus, the combined use of all three methods increased the sensitivity of aneuploidy detection.

Aneuploidy↗

PubMed1996

Intracranial plasmacytoma: a case report.

Multiple myeloma may have extraosseous manifestations in the cranial region. It may be a solitary intracranial tumour without any other signs of multiple myeloma, or intracranial disease may be a part of generalised disease, as in the present case. Our patient had received chemotherapy for multiple myeloma for 9 months, with good response. However, her condition suddenly deteriorated, with signs of increased intracranial pressure and a 5-cm-diameter tumour infiltrating the meninges and brain was found in the left temporal fossa. The radiological diagnosis, based on contrast-enhanced CT and angiography, was not straightforward or specific for plasmacytoma, as chemotherapy for the extracranial disease had been successful. Diseases such as meningioma, metastasis, lymphoma, chondrosarcoma or haemangioma had to be considered.

Aged↗

PubMed1996

Different expression of adhesion molecules on stromal cells and endothelial cells of capillary hemangioblastoma.

Cell-cell and cell-matrix interactions are essential for many basic functions, including differentiation and development. In pathological conditions such as inflammation and tumorigenesis adhesive events also play a major role. Cellular adhesion is mediated by specific molecules expressed by both normal and neoplastic tissues. Capillary hemangioblastoma is a tumor of controversial origin, characterized by two major components, vacuolated stromal cells and a capillary network. In order to shed light on the differentiation of the stromal cells and the interactions between the two major components of hemangioblastoma we studied the expression of several adhesion molecules by immunocytochemistry. The endothelium-associated adhesion molecules (ICAM-1, ICAM-2, VCAM-1, PECAM-1 and ELAM-1) were expressed by endothelial cells within the tumors, but not by stromal cells. In contrast, the stromal cells showed strong neuronal cell adhesion molecule (NCAM/CD56) expression, further distinguishing them from endothelial cells. In addition, the stromal cells expressed CD44, which is of interest, as this membrane protein is linked to ezrin, a cytoskeleton-associated protein also expressed by stromal cells. We conclude that the stromal cells and endothelial cells of capillary hemangioblastoma exhibit quite divergent expression patterns of adhesion molecules. The NCAM expression in stromal cells suggests neuroectodermal or mesenchymal differentiation of this tumor. In addition, the NCAM expression could contribute to the sometimes problematic differential diagnosis between capillary hemangioblastoma and metastatic renal cell carcinoma of the central nervous system.

Capillaries↗

PubMed1996

Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate implants.

In this experimental study, blocks of natural coral (calcium carbonate) and its structurally similar derivate in the form of hydroxyapatite (calcium phosphate) were implanted in rat latissimus dorsi muscle with autogenous bone marrow to compare their bone-forming capability. A block without marrow placed in the opposite latissimus muscle served as a control. The animals were killed at 3, 6 and 12 weeks and, in the hydroxyapatite group, also at 24 weeks. The sections were analysed histologically and histomorphometrically. Bone was found only in implants containing bone marrow. Bone formation was significantly (p < 0.05) higher in coral than in hydroxyapatite implants at 3 weeks (10.8% versus 4.8%) and at 12 weeks (13.7% versus 6.3%, bone/total original block area). At 12 weeks all the coral implants had lost their original structure, and the cross-sectional area of the block had diminished to 40% of the original area.

Animals↗

PubMed1996

No evidence of microsatellite instability in bone tumours.

Microsatellite instability has recently been reported in sporadic and familial colorectal tumours and can be due to defects in DNA mismatch repair genes. Such instability has subsequently been detected in several other types of sporadic tumours. We studied 29 specimens of bone tumours with different histopathological diagnoses and found no evidence of microsatellite instability. Our results suggest that mismatch repair defects are unlikely to play a significant part in the tumorigenesis of bone neoplasms. Loss of heterozygosity with at least one marker was detected in 11, i.e. in 38% of the tumour samples, most frequently with markers D2S136 at 2p (eight of 28 informative specimens, 29%) and D11S904 at 11p (four of 21 informative specimens, 19%).

Bone Neoplasms↗

PubMed1996

Expression of growth factors and growth factor receptors in capillary hemangioblastoma.

To elucidate the mechanisms underlying the regulation of growth and differentiation of capillary hemangioblastoma we studied the expression of selected growth factors and growth factor receptors by immunocytochemistry. As stromal cells of capillary hemangioblastoma express high levels of vascular endothelial growth factor (VEGF) and placental growth factor (P1GF) mRNA, we studied the distribution of the corresponding VEGF and P1GF proteins. We also studied the expression of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptors (PDGFR) because their ligands have been reported to promote angiogenesis. The stromal cells expressed abundant EGFR and, in addition, some stromal cells expressed PDGFR-alpha but not PDGFR-beta. In contrast, the endothelial cells co-expressed PDGFR-alpha and PDGFR-beta. VEGF and P1GF were expressed by scattered stromal cells; however, more intense staining was observed in the endothelial cells of the intratumoral blood vessels, possibly indicating the secreted growth factors bound to their target receptors. We conclude that capillary hemangioblastomas express a variety of growth factor receptors and ligands, potentially involved in both autocrine and paracrine loops. The uniformly high EGFR expression is unique among brain tumors and may be associated with the typical morphology of capillary hemangioblastoma. The expression of highly angiogenic growth factors and their receptors may contribute to the rich vascularity of this enigmatic tumor.

Adult↗

PubMed1996

Ezrin expression in stromal cells of capillary hemangioblastoma. An immunohistochemical survey of brain tumors.

Ezrin is a cytoskeleton-associated protein that appears to link actin filaments to the plasma membrane. Immunocytochemical studies suggest that ezrin is expressed in epithelial cells but not in mesenchymal cells. In addition, ezrin is expressed by certain epithelial tumors, such as renal cell adenocarcinomas. Ezrin serves as a tyrosine kinase substrate, and is phosphorylated in epidermal growth factor-stimulated cells. Ezrin may thus mediate regulatory signals in different cell functions. We studied the distribution of ezrin in 104 cases of primary tumors of the central nervous system (CNS) by immunocytochemistry. Special interest was focused on capillary hemangioblastoma, owing to its resemblance to renal cell adenocarcinoma, and on malignant gliomas, owing to their frequent epidermal growth factor receptor amplification. The stromal cells of hemangioblastomas were found to be strongly positive for ezrin. No expression was detected in gliomas and, except for hemangioblastomas, ezrin expression was restricted to those few CNS tumors that show epithelial differentiation, ie, choroid plexus papillomas, craniopharyngiomas, ependymomas, and cysts. The diffuse cytoplasmic expression of ezrin in the stromal cells of capillary hemangioblastoma may indicate that stromal cells overexpress ezrin or express ezrin with deficient binding properties.

Antibodies, Monoclonal↗

PubMed1996

Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas.

Capillary hemangioblastomas and hemangiopericytomas are highly vascular central nervous system tumors of controversial origin. Of interest in their pathogenesis are mechanisms regulating endothelial cell growth. The endothelial cell mitogen vascular endothelial growth factor (VEGF) stimulates angiogenesis, and together with its two receptor tyrosine kinases VEGFR-1(FLT1) and VEGFR-2(KDR), is up-regulated during the malignant progression of gliomas. We have analyzed the expression of VEGF and its receptors, the related placental growth factor (PlGF) and the endothelial receptors FLT4 and Tie by in situ hybridization in capillary hemangioblastomas and hemangiopericytomas. VEGF mRNA was up-regulated in all of the hemangiopericytomas studied and highly expressed in the stromal cells of hemangioblastomas. In addition, some hemangioblastoma tumor cells expressed high levels of PlGF. Significantly elevated levels of Tie mRNA, Tie protein, VEGFR-1, and VEGFR-2 but not FLT4 mRNAs were observed in the endothelia of both tumor types. In hemangioblastomas, however, the receptors were also highly expressed by a subpopulation of stromal cells. Consistent results were obtained for a human hemangioblastoma cell line in culture. Up-regulation of the endothelial growth factors and receptors may result in autocrine or paracrine stimulation of endothelial cells and their precursors involved in the genesis of these two vascular tumors.

Angiogenesis Inducing Agents↗

PubMed1996

Prussak's space revisited.

Thirty temporal bones were dissected under the operating microscope, and four whole temporal bone specimens were studied by light microscopy for evaluation of the lateral malleal space and Prussak's space. In all specimens Prussak's space showed a blind end toward the anterior pouch and communicated with the posterior pouch. Its roof consisted of the lateral malleal ligamental fold, which was always strongest in its anterior half and as a rule had a thin area in its posterior portion. In four ears there was a membrane defect connecting Prussak's space to the lateral malleal space. The latter did not contain additional folds and communicated freely with the upper attic. The pathways for spread of an acquired primary cholesteatoma from Prussak's space are outlined.

Culture Techniques↗

PubMed1995

Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization.

Our aim was to identify chromosomal regions that are likely to harbor previously unknown genes with an important role in the genesis of osteosarcoma. Comparative genomic hybridization was used to screen for losses and gains of DNA sequences along all chromosome arms in 11 tumors. Extensive genetic aberrations, with an average of 11 changes/tumor (range, 1-20), were found in 10 of the 11 specimens. High level amplifications of small chromosomal regions were detected in eight tumors. These involved the 12q12-q13 region (known to contain the SAS-MDM2 locus) and several previously unreported amplification sites such as 17p11-p12, 3q26, and Xq12. When all DNA sequence gains were evaluated, the gains at 8q and Xp were most common (45%). The most common losses of DNA sequences were seen at 2q, 6q, 8p, and 10p (36%). In conclusion, despite the very complex pattern of genetic changes in osteosarcomas, certain chromosomal regions appear to be affected more often than others. Most of these regions have not previously been reported to be implicated in osteosarcomas and may thus highlight locations of novel genes with an important role in the development and progression of these tumors.

Chromosome Aberrations↗

PubMed1995

Chondrosarcoma of bone. A clinical and DNA flow cytometric study.

Fifty-two patients with chondrosarcoma were treated in our hospital between 1981 and 1992. Tumours from 21 of the patients were histologically grade I, 19 were grade II, 10 were grade III and two were grade IV. Forty-seven patients were treated surgically and samples for flow cytometric DNA analysis were taken from 38 tumours with a successful measurement in 37 cases. The mean follow-up time was 40 months and during this period 17 of the patients treated surgically developed a local recurrence or metastasis. In one case, a highly anaplastic sarcoma developed after radiation treatment. Only two of the 19 diploid tumours recurred, whereas eight of the 18 aneuploid tumours showed a recurrence. These results indicate that DNA flow cytometry is of prognostic significance in chondrosarcoma and may aid in planning the treatment.

Adult↗

PubMed1994

Enhanced expression of the tie receptor tyrosine kinase mesenger RNA in the vascular endothelium of metastatic melanomas.

Angiogenesis of human melanomas has been the focus of intense interest since it was shown that the spread and prognosis of primary tumors is correlated with their vascularization (N. Weidner, J. P. Semple, W. R. Welch, and J. Folkman, N. Engl. J. Med., 324: 1-8, 1991). Basic fibroblast growth factor (bFGF) and its high-affinity receptor FGFR-1 have been implicated in melanoma growth and angiogenesis (R. Halaban, Y. Funasaka, J. Lee, J. Rubin, D. Ron, and D. Birnbaum, Fibroblast Growth Factors in Normal and Malignant Melanocytes, pp. 232-243. New York: The New York Academy of Sciences, 1991). We have studied the expression of the Tie endothelial cell receptor tyrosine kinase mRNA in skin and primary cutaneous melanomas as well as in their skin and brain metastases by in situ hybridization. The Tie probe hybridized very weakly with the vascular endothelium of capillaries of normal skin, while it was detected in larger arteries and veins as well as in capillaries around sweat glands. However, capillaries and medium-sized vessels within cutaneous and brain metastases of melanoma were strongly positive for Tie mRNA. In contrast, endothelial cells contained very little or no FGFR-1 transcripts, whereas abundant FGFR-1 mRNA was present in melanoma tumor cells and in fibrovascular stroma. In agreement with these findings, a Tie-specific amplified cDNA band was obtained by reverse transcription-polymerase chain reaction from melanoma metastases but not from normal skin. These results suggest a role for the Tie receptor in the angiogenesis associated with melanoma metastases.

Base Sequence↗

PubMed1994

In vivo evidence of the role of alpha 4 beta 1-VCAM-1 interaction in sarcoma, but not in carcinoma extravasation.

Tumor-cell invasion can occur via either lymphatics or blood vessels. When in the blood circulation, tumor cells have to adhere to endothelium lining the blood vessels before they can extravasate. Several families of adhesion molecules have been recognized: selectins and their oligosaccharide-containing ligands and integrins and their counter-receptors belonging to the immunoglobulin superfamily. Besides their essential role in leukocyte extravasation, these adhesion molecules have been proposed by vitro experiments to be involved in tumor-cell invasion by facilitating the adhesion of malignant cells to endothelium leading to extravasation and metastasis. We have previously shown that, in vitro, several sarcoma cell lines adhere strongly to cultured endothelial cells via alpha 4 beta 1-VCAM-1 interaction. Here we show that sarcoma cells, especially in the metastatic lesions, were strongly alpha 4 beta 1 positive but did not express alpha 4 beta 7, which is another receptor for VCAM-I. Furthermore, we demonstrate that the capillary endothelium within metastatic sarcoma lesions reacted strongly with anti-VCAM-I antibody and very often the alpha 4 beta 1-expressing sarcoma cells were localized in the close vicinity of VCAM-I-expressing vessels. As control material we analyzed carcinoma specimens, but could not detect any alpha 4-integrin expression on malignant cells even though the endothelial cells were often VCAM-I positive. These results suggest that carcinomas do not use alpha 4 beta 1-VCAM-I in extravasation and, taken together, provide circumstantial evidence that in vitro findings of alpha 4 beta1-VCAM-I-dependent sarcoma cell adhesion to endothelium can be extended to in vivo situations.

Adenocarcinoma↗

PubMed1994

Giant cell tumours of bone. A DNA-flow cytometric study.

The variable clinical course and locally aggressive growth of giant cell tumours of bone cause problems in planning treatment. Curettage and bone grafting is the commonest form of surgical treatment, but recurrence rates as high as 40 per cent have been reported. Thirty-four patients with a GCT were treated in our clinic between years 1982 and 1990. There were three gr 1, 24 gr II and 7 grade III tumours. Operative treatment was carried out in 31. DNA flow cytometry was performed from the sample in 28 patients. The type of treatment played an important role in tumour prognosis: there were 10 recurrences after 18 intralesional procedures, but only one recurrence after tumour resection. DNA flow cytometry was not helpful in predicting tumour behaviour.

Adolescent↗

PubMed1993

Cytogenetic study of 249 consecutive patients examined for a bone tumor.

Chromosome analysis was performed on 304 samples of 249 consecutive patients examined for a possible bone tumor. The series consisted of 86 nonneoplastic disorders, 108 benign and 78 malignant primary bone tumors, and 32 other bone malignancies. In the group of nonneoplastic disorders, one sample from an infectious lesion demonstrated a clonal chromosome aberration, i.e., additional material in the short arm of chromosome 1. Simple clonal aberrations were noted in six of 75 successfully cultured benign tumors, e.g., a chondromyxoid fibroma with an insertion type translocation from 2p21p25 to 5q13 and 2p deletion and a nonossifying fibroma with del(4)(p14). Complex clonal aberrations were evident in 21 of 54 successfully cultured malignant primary bone tumors and eight of 21 secondary bone malignancies. The complexity of clonal aberrations correlated with the grade of malignancy as the osteosarcomas and chondrosarcomas of high-grade demonstrated chaotic abnormalities. Six Ewing's sarcomas demonstrated the t(11;22)(q24;q12); in one this was the sole abnormality, and in five additional changes were evident: der(1;16)(q10;p10) in one. Homogeneously staining elongated areas interpreted as HSR were observed in three patients, all of whom had a highly malignant tumor. The most frequent nonclonal abnormality was telomeric association, which was observed mainly in giant cell tumors.

Aneuploidy↗

PubMed1993

A recurrent chondromyxoid fibroma with chromosome aberrations ins(5;2)(q13;p21p25) and 2p deletion: a case report.

We report a patient with a recurrent chondromyxoid fibroma, a rare benign tumor of the bone with clonal aberrations in chromosomes 2 and 5. Karyotyping, chromosome painting, interphase cytogenetics by in situ hybridization, and DNA flow cytometry were used. The karyotype was interpreted as 46,XX,der(2)ins(5;2)(q13;p21p25),der(2)ins(5;2)(q13;p21p25), der(5)ins(5;2) (q13;p21p25).

Adult↗

PubMed1993

Chromosome study of 249 patients examined for a bone tumor.

The authors have performed cytogenetic studies of bone tumors since 1987, and this article, based on previous work, summarizes their experiences in this field. Altogether 304 samples from 249 consecutive patients examined for a possible bone tumor at the Helsinki University Central Hospital, between October 1987 and April 1992, have been analyzed. The series consisted of 86 nonneoplastic disorders, 108 benign and 78 malignant primary bone tumors, and 32 other bone malignancies. In the group of nonneoplastic disorders, one sample from an infectious lesion demonstrated a simple clonal chromosome aberration. Simple clonal aberrations were seen in six of 75 successfully cultured benign tumors. Complex clonal aberrations occurred in 21 of 54 successfully cultured malignant primary bone tumors and in eight of 21 secondary bone malignancies. The complexity of clonal aberrations correlated with the grade of malignancy as the osteosarcomas and chondrosarcomas of high grade demonstrated chaotic abnormalities. The chaotic nature of the aberrations implicates the evolution of several different clones and thus advanced malignant transformation. Six of eight successfully cultured Ewing's sarcomas demonstrated the diagnostic t(11;22)(q24;q12); this translocation was also seen in one primitive neuroectodermal tumor. Cytogenetic study provides increasing knowledge of the biology of bone tumors and is a valuable adjunct in their evaluation.

Bone Neoplasms↗