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Biomedical subjects

M Westphal

Publications and source records attributed to M Westphal.

At least 127 records · Page 7Linked to original sources
PubMed1992

Treatment of tumours of the pineal region and posterior part of the third ventricle.

The evaluation of tumours located in the posterior part of the third ventricle or pineal region is achieved best by magnet resonance imaging (MRI). It shows the exact localization and extent, the involvement of neighbouring structures like thalamus or quadrigeminal plate and the displacement of the large veins, the internal cerebral veins, the vein of Galen and the veins of Rosenthal. If only CT is available, angiography should be performed prior to operation to identify the course of the veins. In children with a pineal region tumour the "tumour markers" AFP and beta-HCG should be determined before operation. We approach the rare tumours entirely located within the posterior part of the third ventricle by the posterior interhemispheric transcallosal route with the patient in prone position with the head elevated. The same approach is used for pineal region tumours extending above the internal cerebral veins. Tumours arising from the posterior thalamus extending into the thalamus and ventricle as well, are better approached by the posterior transcortical transventricular route since the lateral view is rather limited by the midline approach. The most frequent tumours in the pineal region are approached if they are located below the internal veins by the infratentorial, supracerebellar route in the sitting position. A total of 60 cases are evaluated. If AFP and/or beta-HCG are positive a highly malignant nongerminomatous germ-cell tumour must be suspected. We recommend initial chemotherapy with a combination of Vinblastine, Ifosfamide and Cis-platin without biopsy to avoid tumour seeding. After the "markers" are normalized operative removal of the residual tumour and radiotherapy should be carried out. In a series of 13 children operated on for pineal region tumours a rigid neuropsychological and endocrine evaluation was performed with encouraging results. During the last 10 years we have performed 49 open operations and 11 stereotactic biopsies. 40% of the patients were children under the age of 18. 40% of the tumours in childhood and 60% in adults were benign. In childhood 24% were germinomas and 20% non-germinomatous germ cell tumours.

Adult↗
PubMed1991

Receptors for platelet derived growth factor in human glioma cell lines and influence of suramin on cell proliferation.

A panel of 11 established human glioma cell lines was used to evaluate PDGF receptor binding using radioiodinated biosynthetic PDGF-AA and PDGF-AB as primary ligands. It was found that PDGF-receptor-binding was qualitatively heterogeneous. The affinities for PDGF-AA as well as PDGF-AB binding were within a close range of 0.13-0.33 nM and 0.16-1.1 nM, respectively. The number of binding sites per cell ranged between 56.000 and 250.000 for PDGF-AA and 72.000 to 300.000 for PDGF-AB. Two lines had only background levels of PDGF-AA binding. PDGF-AB binding was the dominant binding component in all but one cell line. In seven cell lines there were two binding components upon saturation analysis consisting of a high affinity component and a non-saturable low affinity component. PDGF and PDGF-receptors are suspected to be part of an autocrine loop in gliomas. Therefore, the effect of suramin on cell proliferation in serumfree cultures was tested in the same cell lines using doses of 25,200 or 500 micrograms/ml. It was found that the response to suramin was variable and that two cell lines still reached 2.8 fold and 4.5 fold their initial cell density even in the presence of 500 micrograms/ml whereas all other cells were completely arrested. Analyzing the response to 200 micrograms/ml it became evident, that the PDGF binding characteristics are of no reliable predictive value in respect to the efficacy of suramin.

Brain Neoplasms↗
PubMed1991

Primary spinal malignant schwannoma: clinical, histological and cytogenetic findings.

Of the 19 patients who presented between 1980 and 1990 to the Department of Neurosurgery, University of Hamburg, F. R. G. with malignant schwannoma, 5 patients suffered from primary malignant spinal schwannoma (mean age 44 years, only one patient with von Recklinghausen's disease). Here we report the clinical, histological, and cytogenetic features of the five cases with primary malignant spinal schwannoma and discuss the prognostic aspects of this rare tumor.

Adolescent↗
PubMed1990

Antigenic staining patterns of human glioma cultures: primary cultures, long-term cultures and cell lines.

The immunocytochemical staining patterns of cultured glioma cells were investigated. Fifty nine individual cases were stained at different in vitro ages for glial fibrillary acidic protein, fibronectin, galactocerebroside, HNK-1/Leu 7, A2B5, vimentin, factor VIII and A4. Histologically, the cases were composed of eight low-grade astrocytomas, 11 high-grade astrocytomas, four low-grade oligodendrogliomas, seven high-grade oligodendrogliomas and 29 glioblastomas. The 45 cases were analysed within the first 3 weeks of culture, many of them as primary cultures. In 11 cases stainings were performed repeatedly at intervals of up to 6 months. Glial fibrillary acidic protein staining was positive in most of the early cultures of astrocytomas (low and high grade) and glioblastomas; expression in more than 50% of the cells was found in 1 of 5 low-grade astrocytomas, 5 of 11 high-grade astrocytomas and 14 of 29 glioblastomas. Two of the high-grade astrocytomas were stained once more after 6 weeks in culture and were found to be only 1% positive for glial fibrillary acidic protein but strongly positive for fibronectin. The same was true for five of the glioblastoma cases. Two of these cases remained glial fibrillary acid protein positive and developed into stable permanent cell lines. Only one case started with 1% of glial fibrillary acidic protein positive cells and later developed into a 99% glial fibrillary acidic protein positive cell line. Neither HNK-1/Leu 7 expression nor A2B5 staining appeared to have a relationship to the glial fibrillary acidic protein staining. It was observed that glial fibrillary acidic protein and HNK-1/Leu 7 were both 100% in some cases but that later one of the two antigens disappeared but not the other. The amount of glial fibrillary acidic protein staining does not allow the prediction of A2B5 staining. The study shows that initiation of primary cultures on an extracellular matrix yields more glial fibrillary acidic protein positive cells in primary cultures than have been found in other studies. It is concluded that only a rigid standardization of culture conditions will ensure the validity of comparisons of in vitro data obtained in primary cultures.

Antigens, Neoplasm↗
PubMed1990

Expandable tubular stents for treatment of arterial occlusive diseases: experimental and clinical results. Work in progress.

The balloon-expandable vascular prosthesis consists of a flexible, knitted tantalum wire mesh tube. To demonstrate its pliability, this prosthesis was tested experimentally in 10 mongrel dogs by implanting it into the proximal femoral arteries. The maximum follow-up time was 1 year. On the basis of the experimental results, in which there was no relevant stenosis, occlusion, or migration of the vascular prosthesis, nine patients were treated: one with iliac artery occlusive disease and eight with superficial femoral artery (SFA) occlusive disease (four reocclusions after angioplasty and four unsatisfactory primary angioplasty results). One SFA lesion was treated with the crossover method from the contralateral side. All implants remained patent without hemodynamically significant stenoses, with the longest observation time being 6 months. Flexible, expandable vascular prostheses are promising adjuncts to angioplasty.

Aged↗
PubMed1989

A developmentally regulated gene product from Dictyostelium discoideum shows high homology to human alpha-L-fucosidase.

A cDNA library of poly(A+)-RNA has been prepared from membrane-bound polysomes of Dictyostelium discoideum and screened for clones hybridizing to mRNA species that encode developmentally regulated proteins. The clone investigated in this paper recognizes a 1.8 kb transcript that accumulates strongly between the growth phase and aggregation stage. Stimulation of cells with pulses of cAMP enhances the accumulation. The amino acid sequence derived from a complete cDNA and from a genomic clone displays extensive sequence identity to human liver alpha-L-fucosidase. The D. discoideum DNA sequence encodes a 50.5 kDa polypeptide with a hydrophobic signal peptide at the N-terminus. Antibodies against a synthetic peptide corresponding to amino acids 262-275 of the deduced protein sequence recognize a developmentally regulated 50 kDa protein in D. discoideum that is recovered in the particulate fraction.

Amino Acid Sequence↗
PubMed1989

Cyst fluids of malignant human brain tumors contain substances that stimulate the growth of cultured human gliomas of various histological type.

The contents of 14 cysts that were located within human intracranial tumors were obtained at surgery by needle aspiration. These tumor cyst fluids (TCFs) were mostly derived from glial tumors (10 cases). TCFs from one metastasis from a mammary carcinoma, one cystic meningioma, one hemangioblastoma, and a cystic acoustic neurinoma were also included. These TCFs were added to primary cultures of human gliomas, established human glioma cell lines, and normal human arachnoid cells in culture. The presence of proliferation-promoting factors in all cyst fluids could be demonstrated. On the basis of the response patterns of the cultures, it was possible to distinguish different levels of growth autonomy and growth factor sensitivity among these cultures and to speculate about varying degrees of cellular autocrine activation. The TCFs appear to contain factors that are not normally present in fetal calf serum, which is a regular constituent of most cell culture media. Some primary cultured cells as well as cell lines react in an oversensitive manner to the addition of TCFs.

Body Fluids↗
PubMed1989

Growth factor biology and oncogene activation in human gliomas and their implications for specific therapeutic concepts.

The failure of most available treatment modalities to improve the survival time and the quality of survival in patients with gliomas calls for the intense biological analysis of glial neoplasia. The untimely activation of cellular protooncogenes is often related to the process of neoplasia. Several protein growth factors as well as their cellular receptors have been identified as products of proto-oncogenes. Furthermore, these growth factors have been identified as glial mitogens in normal glial cell cultures as well as in tumors. The analysis of growth factor biology gains additional weight by the demonstration of autocrine growth factor secretion by tumor cells. The role of epidermal growth factor (EGF) and its receptor system in glial cell proliferation and differentiation is presented, with the speculation that the EGF receptor system may integrate the biological actions of many different factors, of which EGF itself may be least important. The literature on platelet-derived growth factor and insulin-like growth factors is reviewed, and the biology of fibroblast growth factor is presented in perspective with such phenomena as neovascularization and cell-matrix interactions.

Epidermal Growth Factor↗
PubMed1989

Spectrum of karyotypic aberrations in cultured human meningiomas.

Twenty-two unselected cases of meningioma were initiated in tissue culture on an extracellular matrix derived from bovine corneal endothelial cells. The cultures were available for karyotypic analysis at passages 1 to 5, representing cultivation periods of up to two months. Histologically, the meningiomas were meningiotheliomatous (16 cases), fibrous (1 case), angiotheliomatous (1 case), microcystic (2 cases), and parenchymatous (2 cases). Two of the meningotheliomatous cases had histological signs of malignancy, another case showed increased signs of proliferation, and two cases were recurrences, one after a complete course of irradiation. In five cases no structural chromosome aberrations were found. Monosomy of chromosome 22 was found in six cases and was associated with other random aberrations. Clonal or random aberrations without monosomy 22 were present in 11 cases, including one case with trisomy 7 and another case with a stable translocation marker, t(4;7). In these latter two cases, EGF-receptor binding was not elevated, compared to other meningiomas. Our results illustrate that, in addition to the frequent involvement of chromosome 22, numerous other individual clonal karyotype aberrations exist in meningioma cell populations, reflecting the heterogeneity of biological and pathological findings.

Adult↗
PubMed1988

[Percutaneously implantable balloon-inflatable vascular prostheses. Initial clinical results].

Restenosis and occlusion of atherosclerotic arteries are prevented by a newly developed arterial prosthesis consisting of a pliable and elastic wire mesh tube positioned to the balloon of an angioplasty catheter. As the balloon is inflated the prosthesis dilates and provides the arterial wall with a new mechanical support. This new device was successfully implanted in ten patients having an iliac artery stenosis and improved the therapeutic result of the preceding angioplasty. There were no complications.

Aged↗
PubMed1988

Complete cDNA sequence of a Dictyostelium ubiquitin with a carboxy-terminal tail and identification of the protein using an anti-peptide antibody.

The complete sequence of a Dictyostelium discoideum cDNA is presented that codes for monoubiquitin extended at its C-terminus by a 52 amino acid tail. The sequence of both the ubiquitin portion and the tail is highly homologous to the one of Saccharomyces cerevisiae and to a partial mouse sequence. The highly basic tail sequence contains a putative metal and nucleic acid-binding motif. The gene encoding the 0.6 kb mRNA of the C-terminally extended ubiquitin is represented only once in the haploid genome. The 0.6 kb mRNA as well as its translation product, a 15 kDa protein, is expressed in exponentially growing cells and remains present for at least 5 h of development. Using antibodies against a synthetic peptide that corresponds to the C-terminal amino acid sequence, a 15 kDa protein containing the extension a synthetic peptide that corresponds to the C-terminal amino acid sequence, a 15 kDa protein containing the extension was also detected in yeast.

Amino Acid Sequence↗
PubMed1988

Biological and karyotypic characterization of a new cell line derived from human gliosarcoma.

A cell line (NCE-G28) was established from the biopsy material of a human gliosarcoma of low histological differentiation. The initial cultures showed a mixed population of cells which in later stages became more uniform due to loss of slower growing constituents. The cells have been growing steadily for 20 months. A suspension of NCE-G28 cells injected s.c. as well as i.p. into nude mice produced solid tumors in all cases. Histologically these tumors closely resembled the original tumor. The original tumor, the nude mouse tumor, and NCE-G28 cells were immunochemically positive for glial fibrillary acidic protein as well as for neural plasma membrane antigen A2B5 expression. Two cell strains, 9B2C and 9B2E, were obtained by cloning of the initial cultures and another strain, NCE-G28T, was derived after explantation of a mouse heterotransplant. The two subclones were negative for glial fibrillary acidic protein expression but stained for cell surface fibronectin. NCE-G28T cells initially were positive for glial fibrillary acidic protein but lost this property within 8 months of cultivation. Karyotype analysis of NCE-G28 and the three strains revealed hyperdiploidy and six structurally altered marker chromosomes five of which were shared by nearly all cells. Receptors for epidermal growth factor were detected in all cell lines with the highest levels (about 300,000 receptors/cell) in the parental cell line. The epidermal growth factor receptors had an affinity of 2.5 nM (Kd) and by affinity cross-linking analysis a molecular weight of 170,000 was found. Initially, NCE-G28 cells responded to epidermal growth factor as well as fibroblast growth factor with increased rates of proliferation, while platelet derived growth factor had no effect. In higher passages the growth factor sensitivity was reduced. Using antibodies directed against synthetic protooncogene peptides the production of c-sis immunoreactive material was detected. NCE-G28 cells produce an autocrine factor which stimulated proliferation. This factor is present in conditioned medium and is active on cultured meningiomas and other glioma cell lines. NCE-G28 cells can be maintained in serum-free defined medium on plastic coated with fibronectin or an extracellular matrix from bovine corneal endothelial cells. The NCE-G28 cell line with its strains provide an in vitro model system in which the complexity of gliosarcoma cell populations and the interaction of the cloned cellular constituents can be studied.

Aged↗
PubMed1988

Glioma biology in vitro: goals and concepts.

Gliomas are heterogeneous in their cellular composition, affecting therapeutic efforts such as surgical removal, radiotherapy, chemotherapy and immunotherapy. 106 gliomas were taken into culture in our laboratory and 12 cell lines could be established there from. Experiments were carried out in as many early cultures as possible and with the constant experimental system of the cell lines. To subdivide and possibly classify the heterogeneous group of gliomas the following approaches emerged: Immunostaining of cells for glial markers such as GFAP, A4, A2B5, Leu 7 as well as fibronectin will allow one to distinguish different groups of glial cultures. Performance of growth factor sensitivity tests allows the assessment of major aspects of growth control in cultured gliomas. Cytogenetic evaluation in early cultures and correlation with the expression of oncogenes may yield useful information on mechanisms of escape from normal growth control. One of our cell lines (NCE-G28) in which cells switch from GFAP to fibronectin expression and transiently express the x-hapten may serve as a model to study crucial aspects of cellular differentiation. Using different extracellular matrices for the initiation of cultures even from very benign lesions with low proliferative potential it is possible to include these into comparative studies with glioblastomas.

Animals↗
PubMed1988

Growth factors in cultured human glioma cells: differential effects of FGF, EGF and PDGF.

Primary cell cultures were initiated from surgically obtained specimens from human gliomas. After 4-10 passages in vitro the cells from 18 individual cases were seeded onto cluster dishes and left to attach for 24 h in medium containing fetal calf serum. Thereafter the medium was changed to serumfree, defined conditions and the following growth factors were added: EGF 1.5 x 10-8 M, PDGF 35 ng/ml, FGF 80 pg/ml. The growth factors were added fresh every 2 days. After 9 or 11 days in culture, the cells on one multiwell-plate were counted. In 8 cases another set which was cultured also in a multiwell-plate but on glass cover slides was immunostained for glial fibrillary acidic protein (GFAP), fibronectin (FN), A2B5 and galactocerebroside (galC). The proliferative response pattern in consequence to the growth factor addition varied greatly between different cases. In all cases a pronounced proliferative response was accompanied by marked changes on the culture morphology. Usually the best proliferative response was obtained with PDGF (10 cases) or FGF (8 cases) whereas EGF was most effective only in one case. Two cases showed only minimal response, one of which was an oligodendroglioma D according to Ludwig and another a gliosarcoma which was re-evaluated after 1 year in culture. It could be noted, however, that FGF had a tendency to be less effective in the group of malignant astrocytomas. The staining pattern of the cultures with the afore mentioned markers was not affected by the growth factor treatment. The proliferative response usually resulted in increased staining for fibronectin and never an induction of GFAP. A2B5 staining was positive only in one case of gliosarcoma and galC staining was regularly negative.

Cell Division↗
PubMed1988

[The biology of gliomas: growth factors and oncogene expression. A current review].

In recent years several proteins with in vitro cell growth promoting activity were chemically identified and termed growth factors. Their role in normal glial development has been studied in vitro in different defined systems. In addition it has been tried to elucidate their role in the biology of gliomas. Some clues were obtained from the study of growth factor receptors and the expression of oncogenes. It has to be assumed that from the correlation and synthesis of results obtained from studies of growth factors, oncogene expression, gliogenesis and cytogenetics there will emerge useful biological concepts for specific therapeutic approaches.

Animals↗
PubMed1988

Cushing's syndrome due to bilateral adrenal macronodular hyperplasia with undetectable ACTH: cell culture of adenoma cells on extracellular matrix.

A 59-year-old man developed Cushing's syndrome with massive bilateral adrenal macronodular hyperplasia. Plasma ACTH levels were undetectable both peripherally and in the inferior petrosal sinus. Computed tomography scans of his pituitary were normal. Hypercortisolism was not suppressed by high doses of dexamethasone. His adrenal cells were successfully isolated and grown on bovine corneal extracellular matrix. The cultured cells displayed strikingly rapid growth and hypersecretion of cortisol during incubation with control serum. Addition of the patient's serum to cultured fetal adrenal cells did not accelerate their growth. This was the first experience with our in vitro system in this rare clinical condition. The techniques described here may be used for future in vitro adrenal studies. These in vivo and in vitro data indicate that this patient's bilateral adrenal hyperfunction and growth were independent of ACTH.

Adrenal Glands↗