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Biomedical subjects

T Kirchner

Publications and source records attributed to T Kirchner.

At least 199 records · Page 11Linked to original sources
PubMed1990

Eleven times recurrences of a parasagittal falxmeningioma. Case report.

Although meningiomas are of benign character and generally of encapsulated growth, recurrence is a known problem in treatment. The authors present the time course of a recurrent parasagittal meningioma of the falx, which recurred eleven times. Despite modern radiological diagnostic methods, which made early diagnosis of recurrent tumour possible, and the use of modern microsurgical techniques with radical tumour extirpation and followed by radiotherapy, the fatal course of benign tumour disease could not be stopped.

Adult↗
PubMed1990

Absence of the Epstein-Barr virus genome in the normal thymus, thymic epithelial tumors, thymic lymphoid hyperplasia in a European population.

It has previously been shown that the Epstein-Barr virus (EBV) genome may be detected in some thymic tumors. We have investigated specimens of normal thymus, thymitis with lymphoid hyperplasia and a large spectrum of thymic epithelial tumors obtained from european patients for the presence of EBV genome by in situ hybridization and DNA-blotting methods. Cell lines established from seven of the thymic tumors were also tested for EBV. No EBV genome was demonstrated in any of the tumors examined, which included various types of thymoma and thymic carcinomas, nor in the non-neoplastic thymic specimens. However, unlike previous reports, no examples of lymphoepithelial-like thymic carcinoma, nor specimen from Asian patients were included in this study. We suggest that EBV is linked to a specific epithelial tumor type, namely the lymphoepithelial-like carcinoma, regardless of its site, and not to thymic tumors in general.

Adolescent↗
PubMed1990

Visualization and functional testing of acetylcholine receptor-like molecules in cochlear outer hair cells.

The efferent nerve endings at outer hair cells (OHCs) have been suggested to regulate active mechanical processes in the cochlea. The discovery of acetylcholine (ACh)-producing and -degrading enzymes in these synapses gave rise to the speculation that ACh might be one of the efferent transmitters. However, there has as yet been no identification and characterization of any corresponding receptor in OHCs which is required for further clarification of this question. In the present paper existence, location and first characterization of acetylcholine receptors (AChRs) in OHCs are reported. Using two anti-AChR monoclonal antibodies, AChR epitopes were found forming a cup at the basal end of the OHCs opposite to the efferent nerve endings. Furthermore, the studied molecules could be shown to extend through the cell membrane. In addition, the denervated OHC AChR-epitopes seem to move by lateral diffusion. Application of Carbachol and ACh to the basal pole of OHCs induced a weak, reversible cell contraction. Pharmacological controls revealed, that hte motile responses were mediated by the AChRs.

Acetylcholine↗
PubMed1990

Genomic analysis of T-cell receptor and immunoglobulin antigen receptor genes and breakpoint cluster regions in gastrointestinal lymphomas.

Sixteen cases of gastrointestinal B- and T-cell lymphoma were investigated for clonal rearrangements of immunoglobulin and T-cell receptor genes. In all cases the immunogenotype data corresponded well with the immunohistochemical findings, thus confirming the biologic heterogeneity of these lymphomas. Some cases could be distinguished by additional heterogeneity in their genotype which could not be detected by immunohistochemical methods. Moreover, the B-cell lymphomas were studied for the presence of the chromosomal translocations t(11;14) and t(14;18) using probes for bcl-1 and bcl-2 genes, respectively. While bcl-1 rearrangement was not present in these gastrointestinal lymphomas, one case of diffuse low-grade lymphoma of mucosa-associated lymphoid tissue and three cases of centroblastic lymphoma (diffuse large cell) could be shown to have detectable bcl-2 rearrangement.

Antigens, CD↗
PubMed1990

Primary liposarcoma of the jejunum.

The rare case of a primary liposarcoma of the jejunum in a 52-year-old man is described. The main tumor mass was located within the submucosa and caused chronic subileus by subtotal obstruction of the jejunum. The histology showed a mixed type liposarcoma. In the main mass features of well differentiated lipoma-like and sclerosing liposarcoma predominated. In the tumor periphery they were combined with areas of pleomorphic liposarcoma, consisting of tightly packed giant lipoblasts. After an incomplete resection well differentiated sclerosing and pleomorphic liposarcoma recurred within the intestinal wall and in the mesentery near the primary anastomosis. The unusual primary site and pattern of spread of the tumor are discussed and the literature is reviewed.

Humans↗
PubMed1990

Characterization of a protein with an acetylcholine receptor epitope from myasthenia gravis-associated thymomas.

Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis patients contain at least one protein sharing an antigenic determinant with the nicotinic acetylcholine receptor (AchR) of human muscle. We describe the characterization of this protein (p153) which has a molecular weight of 153 and an isoelectric point of 5.0. By treatment of p153 with endoglycosidases, no significant glycosylation has been detected. Immunologically, p153 crossreacts with monoclonal antibodies against the amino acid sequence 371-378 of the alpha-chain of the AchR. No cross-reactivity to the main immunogenic region of the AchR nor an alpha-bungarotoxin binding site are found. By Western blotting, p153 was generally neither detectable in normal tissues nor extrathymic tumors with the exception of paraganglioma and neuroblastoma. In conclusion, the structure of p153 is apparently unrelated to the AchR from muscle or the alpha-bungarotoxin binding proteins from thymoma. Since there is no evidence for an AchR expression in thymoma, the antigenic homology of p153 with the nicotinic AchR might be relevant for triggering an intrathymomatous autosensitization of maturing T cells and could be responsible for the high association of thymomas with myasthenia gravis.

Antibodies, Monoclonal↗
PubMed1990

[Significance of neuronal acetylcholine receptors as differentiation antigens in neuroblastomas and paragangliomas].

Using a panel of monoclonal antibodies to various epitopes of the alpha-, beta- and gamma-subunit of the muscle acetylcholine receptor (AchR), two different immunohistochemical reactivity patterns--corresponding to different neuronal AchRs--were identified in ganglia of the peripheral and central nervous system. The immunoreactivity pattern of neuroblastomas and paragangliomas was identical to the pattern found in the peripheral nervous system and has not been encountered in any other tumor type. Both the intensity of neuronal AchR immunoreactivity and the transcription of the neuronal AchR alpha-gene seem to correlated with a higher degree of neuroblastoma differentiation.

Antibodies, Monoclonal↗
PubMed1990

[Nicotinic acetylcholine receptors in tumors with rhabdomyomatous differentiation. Immunohistochemical amd molecular genetic demonstration].

The nicotinic acetylcholine receptors (AChRs) of the skeletal muscle consist of pentameric ion channels, each of which is composed of 4 kinds of subunits. During the development of the muscle a change from a fetal type (alpha beta alpha gamma delta) to an adult type (alpha beta alpha epsilon delta) of AChR is due to the replacement of the gamma-subunit with the epsilon-subunit. We investigated the expression and transcription of the AChRs in rhabdomyosarcomas (5 cases) and in nephroblastomas with rhabdomyomatous differentiation (2 cases) by immunohistochemistry using monoclonal antibodies to the alpha-, beta- and gamma-AChR-subunit, and by mRNA dot blot and in situ hybridization applying cDNA-probes of the alpha-, beta-, gamma-, delta- and epsilon-AChR-subunit. The results indicate an intratumorous coexpression of fetal and adult types of AChRs. The presence of gamma-subunits of fetal AChRs may serve as a novel selective marker of tumors with rhabdomyomatous differentiation.

Cell Differentiation↗
PubMed1990

Design, synthesis and bronchodilatory activity of a series of quinazoline-3-oxides.

A synthetic program of rational drug design was undertaken to develop a series of quinazoline-3-oxides as pulmonary-selective inhibitors of ovalbumin-induced, leukotriene-mediated bronchoconstriction. The most active and selective compounds contained a methyl group at the 4-position, a medium sized branched alkyl group at the 2-position, and a small electron donating group on the phenyl ring. Significant enhancement in selectivity was observed in comparing the pulmonary versus cardiovascular effects of these new bronchodilators with the effects of theophylline.

Animals↗
PubMed1990

[Alloplastic ligament replacement. A study of the biological fixation of 5 non-resorbable materials].

The long-term stability of alloplastic ligament prostheses depends on various parameters, on including the quality of the biologic fixation in the bone tissue. Biomechanical and histological tests were therefore performed to examine the stability obtained with five different alloplastic and non-resorbable ligament substitute materials following stress-free implantation into the distal femur and proximal tibia of Wistar rats. The materials were: a filament of the PTFE ligament prosthesis, PTFE suture material (Goretex), polyethylene terephthalate (Mersilene), polyethylene (Braun-Dexon) and polybutylene terephthalate (Miralene). The materials used were all of USP-1 quality. Extraction trials of the implants 32 weeks later did not show any differences between the PTFE materials, such as polyethylene and polyethylene terephthalate, whereas a significantly lower value was found for polybutylene terephthalate. The fixation involved connective tissue exclusively with all the materials tested except for PTFE. PTFE not only induced tight and direct bony contact externally, within the material itself extensive formation of new bone was also found. PTFE was found to be the most histocompatible material, while polyethylene terephthalate led to the most pronounced foreign-body-type reactions.

Animals↗
PubMed1989

SC-1, a functional human monoclonal antibody against autologous stomach carcinoma cells.

Human monoclonal antibodies were isolated from stomach carcinoma patients by the fusion of spleen and lymph node lymphocytes with the heteromyeloma line SPM4-0. Initial screening was carried out on autologous primary tumor cell cultures in an adhesion assay in order to select surface-reactive functional antibodies. This was followed by live cell immunoperoxidase staining assays. The human monoclonal antibody SC-1 was found to selectively react with cultured cells isolated from autologous and allogeneic stomach carcinoma patients, and with cryostat sections of the primary tumors. More extensive screening revealed that the antibody showed no reactivity with a wide range of tumor tissues and normal cells. Some reactivity was present on fetal tissues. SC-1 inhibits movement of the autologous tumor cells and identifies a protein with a molecular weight of 50,000. This study demonstrates that, with the use of selective screening assays on primary tumor material, it is possible to isolate antibodies which not only result from an immune response in the patient but also interfere with intercellular processes of tumor cells.

Antibodies, Monoclonal↗
PubMed1989

Primary cultures of human thymic epithelial tumors. Morphological and immunocytochemical characterization.

Primary cultures are introduced as a method for an immunocytochemical and functional characterization of epithelial cells (ECs) from human thymic epithelial tumors. Neoplastic ECs were obtained after enzymatic digestion of the tumor tissue with dispase. The ECs were kept in culture for up to 1.5 months. Over this period a progressive decline in their proliferation rate was observed. In all five cases studied, ECs showed a co-expression of keratin and vimentin intermediate filaments in vitro as well as strong expression of major histocompatibility complex (MHC)-class I antigens and a progressive loss of MHC-class II antigens. Acetylcholine receptor (AchR)-epitopes were detected immunohistochemically by using monoclonal antibodies (mAbs) to the cytoplasmic site of the alpha-chain if the AchR. Epitopes were found in three of five thymomas in vivo and to a varying degree in all five cases in vitro.

Antibodies, Monoclonal↗
PubMed1989

Proteins with epitopes of the acetylcholine receptor in epithelial cell cultures of thymomas in myasthenia gravis.

Thymomas from 12 patients with myasthenia gravis (MG) were investigated for the presence of epitopes of the alpha-subunit of the nicotinic acetylcholine receptor (AchR) using monoclonal antibodies (MAb) reacting against the AchR. In all but two of the tumors epitopes corresponding to antigenic determinants located on the cytoplasmic side of the AchR were identified. From eight thymomas cell lines were established that have been kept in culture for up to 6 months. The cultured cells expressed the same AchR-epitopes as did the primary tumors. During early passages the percentage of epithelial cells positive for the AchR epitopes approximately mirrored the percentage of positive cells in the original tumors. With passaging the relative number of positive cells usually declined but in some cultures an increase was observed. Three cell lines that showed extensive staining with an MAb against the AchR were radiolabeled to characterize the antigen. From protein extracts of these three cell lines proteins of 45 kd and 156 kd molecular weight (MW) were precipitated. These proteins are different from other proteins described in the context of both thymomas and MG. The negative reactivity with MAb against other epitopes of the alpha-subunit, especially against the main immunogenic region (MIR), speaks in favor of membrane-associated proteins of only limited crossreactivity to the AchR. A previous study found an almost exclusive occurrence of these AchR-epitopes in thymomas associated with MG, but not in other thymomas of similar histologic type. The expression of the proteins described here could therefore play a role in the triggering of the autoimmune process against the AchR of the motor, endplate in MG patients.

Adult↗
PubMed1989

Acetylcholine receptor epitope in proteins of myasthenia gravis-associated thymomas and non-thymic tissues.

Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis (MG) patients contain proteins which share antigenic determinants with the nicotinic acetylcholine receptor (AChR) of human muscle. Here we describe one of the proteins (p153) which (1) is not part of a compound structure, (2) has a MW of 153 kd, (3) has an isoelectric point of 5.0, and (4) is probably free of sugar residues. The protein does not bind mAb to the main immunogenic region of the AChR and has no alpha-bungarotoxin (alpha-btx) binding site. p153 was not found in both normal tissues and a variety of tumours. However, the epitope defined by mAb155 also occurs in at least two other proteins (from muscle and TE671 cells) which have MW different from 153 kd and which are unrelated to AChR. Experiments presented elsewhere [Geuder et al., this volume] show that there are no proteins in thymomas which share an extensive molecular homology with the AChR. All these findings suggest that p153 is unrelated to the AChR. As p153 is the only protein demonstrated in thymomas which is significantly correlated with MG and which shares an antigenic determinant with AChR, p153 is a candidate protein determining the AChR-specificity of the autoimmune process in MG.

Antibodies, Monoclonal↗
PubMed1989

The gene of the alpha-subunit of the acetylcholine receptor: molecular organisation and transcription in myasthenia-associated thymomas.

DNA and RNA were isolated from 5 thymomas of Myasthenia Gravis (MG) patients, from normal tissues, and from the TE671 cell line (which expresses a muscle type acetylcholine receptor, AChR). The cDNA of the alpha-subunit of the AChR, a 159 bp BglII/BstEII fragment encoding the main immunogenic region (MIR) and a 88 bp EcoRV/TaqI fragment encoding the mAb155 binding site (a cytoplasmic epitope of AChR) served as probes. Hybridizations were performed under both high and low stringent conditions. Southern blot analysis of genomic DNA, restricted with EcoRI, HindIII and BamHI/HindIII, showed a normal pattern of restriction fragments in all tissues investigated. In particular, in thymomas there was no deletion of exon 4 which encodes the MIR. Dot and Northern blot analysis of total RNA and mRNA revealed transcription of the alpha-subunit AChR gene in TE671 cells and skeletal muscle but not in other tissues including thymomas. These results confirm former reports that there are no intact AChR in thymomas of MG patients. In addition we show here that there is also no truncated, MIR-deficient AChR or a protein with extensive molecular homology with the AChR in thymomas. These investigations support our idea that an AChR-unrelated protein might play a role in the pathogenesis of thymoma-associated MG [Marx et al., this volume].

Autoimmune Diseases↗
PubMed1989

Evaluation of prognostic features in thymic epithelial tumors.

Based on the original proposals of Müller-Hermelink [3,8] and the study of 95 tumor specimens from the files of our institute we have established a new concept for the classification of thymic epithelial tumors. Thymomas are related to the structural components of normal thymus and divided in medullary, mixed, predominantly cortical and cortical types. In addition a well-differentiated thymic carcinoma with partial loss of organotypic differentiation is characterized and distinguished from other carcinoma types with total lack of specific thymic features. Prognostic evaluation showed, that medullary and mixed thymomas are always benign tumors, whereas predominantly cortical thymomas, cortical thymomas and well-differentiated thymic carcinomas are low-grade malignant tumors with increasing invasiveness and even metastatic capacity. Moreover the proliferation rate of neoplastic epithelial cells in vitro, which was studied in 12 cases, correlated to the different tumor types and their growth behaviour in vivo.

Carcinoma↗