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Biomedical subjects

E Bock

Publications and source records attributed to E Bock.

At least 19 recordsLinked to original sources
PubMed1992

Biphasic changes in NCAM level after an NMDA lesion to the hippocampal formation: a quantitative dot-immunobinding assay.

With a quantitative dot-immunobinding assay, the time course changes of neuronal cell adhesion molecule (NCAM) concentrations and total tissue content were monitored in the rat hippocampus after a 40 nmol NMDA injection. A biphasic alteration was observed; a decrease occurred at day 3, an increase at day 30. The time course of changes differed from that of the glial fibrillary acidic protein (GFAP), a marker for reactive astroglial cell, but was similar to that for the markers of sprouting neurites, i.e., low (L) and high (H) molecular weight subunits of the neurofilament polypeptides. It is suggested that NCAM is implicated in the onset of neurite sprouting in the hippocampus after an excitotoxic trauma.

Animals↗
PubMed1992

NCAM as a differentiation marker of postmigratory immature neurons in the developing human nervous system.

The regional distribution and cellular localization of the neural cell adhesion molecule were investigated in the developing nervous system of human embryos and fetuses, by using immunocytochemistry with antibodies against the human neural cell adhesion molecule. Embryos and fetuses with crown-rump lengths ranging from 15 to 80 mm (corresponding approximately to 6-12 ovulation weeks) were examined. In the telencephalon, immunoreactivity was found in the primordial plexiform layer and in the early cortical plate. During later stages, immunoreactivity was present in the marginal zone, cortical plate, developing subplate zone and radiations of the internal capsule. In the mesencephalon and rhombencephalon, neuronal perikarya were outlined and strong staining was present in fiber bundles. In the spinal cord, strong immunostaining was present in fiber tracts and in dorsal and ventral roots. Immunostaining outlined perikarya of dorsal and ventral gray columns; the neuropil of the developing gray matter was also stained. Contrary to findings in some other species, precursor cells in the proliferating zones, i.e. all cells of ventricular zones and the external granular layer in the proliferation were not stained. Reactivity, however, was also observed in single mature-looking nerve cell bodies and their processes, which were localized in proliferating zones. All peripheral nervous structures including nerve fibers and peripheral nervous tissue components derived from the neural crest (i.e. sensory and autonomic ganglia) expressed the neural cell adhesion molecule. At the cellular level staining always appeared to be associated with the entire cell membrane of a given neuron including its outgrowing processes. Immunocytochemical staining for neural cell adhesion molecule is an excellent method for the identification of single nerve fibers, nerves and nerve cell bodies in situ in the developing peripheral and early central nervous system. The neural cell adhesion molecule is suggested as a marker of postmigratory immature neurons in the developing human nervous system.

Biomarkers↗
PubMed1992

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts.

Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were examined. All tumours but one expressed both cadherin and NCAM. The tumours expressed one, two or rarely three cadherin bands, and different combinations of two major isoforms of NCAM with M(r)'s of approximately 190,000 and 135,000. Polysialylation of NCAM, a feature characteristic of NCAM during embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression.

Animals↗
PubMed1992

Characterization of soluble neural cell adhesion molecule in rat brain, CSF, and plasma.

The polypeptide composition and glycosylation of soluble isoforms of neural cell adhesion molecule (NCAM) in developing rat brain, CSF, and plasma were characterized. Soluble NCAM in rat brain consisted of several glycosylated isoforms. The degree of glycosylation was developmentally regulated. After desialylation, four polypeptides of M(r) values of approximately 190,000 (s1), 135,000 (s2), 115,000 (s3), and 110,000 (s4) were observed. Polypeptides s1, s2, and s3 were also present in CSF, whereas only s3 and s4 were observed in plasma. Treatment of soluble brain NCAM with N-glycosidase F, which removes N-linked carbohydrates, produced polypeptides of M(r) values of approximately 190,000, 125,000, and 108,000-97,000. The monoclonal antibody OB11, which recognizes an epitope on the cytoplasmic part of transmembrane forms of NCAM, did not react with any of the soluble isoforms. Purified soluble NCAM, consisting mainly of s3, contained an N-terminal sequence identical to that of membrane-associated NCAM. Gel filtration of s3 indicated that it was present as a dimer under the chosen conditions. NCAM-expressing glioma cells adhered specifically to immobilized soluble NCAM. This implies that functionally significant soluble forms of NCAM are present in the extracellular fluid.

Aging↗
PubMed1992

Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas.

The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin (delta-cells), and pancreatic polypeptide (PP-cells) in a sequential order. The endocrine cells are believed to arise from a stem cell with neuronal traits. The developmental lineage from a common neuron-like progenitor is evidenced by: transient coexpression of more than one cell type-specific hormone in immature cells, expression of neuronal markers during islet cell development, and the pluripotentiality of clones of insulinoma cells to develop into cells expressing other islet cell hormones. The four mature endocrine cell types assume a particular organization within the islets of Langerhans in a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor. Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N-cadherin in brain. Insulinoma cells express E-cadherin but differ from primary islet cells by expressing a second cadherin molecule, which is similar to N-cadherin. The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype with strong neuronal traits, reflecting the early palce of glucagon-producing cells in the islet cell lineage. In contrast, insulinoma cells are more islet-like in their phenotype and show less neuronal traits.

Animals↗
PubMed1992

Glycosylation of neural cell adhesion molecules of the immunoglobulin superfamily.

Cell adhesion molecules (CAMs) are believed to play key roles during morphogenesis. In this review we focus on neural CAMs belonging to the immunoglobulin superfamily. Data concerning distribution, expression pattern, structure and function of these CAMs are accumulating these years. In general, little is known about the importance of glycosylation for the function of these CAMs. The neural cell adhesion molecule, NCAM, is probably the best described CAM, and this molecule exhibits special carbohydrate characteristics, e.g. NCAM is polysialylated. Glycosylation of NCAM seems to be regulated during development and to influence the adhesive function of the molecule. Structure, function and glycosylation of NCAM are described in detail.

Animals↗
PubMed1992

Diagnostic accuracy of 99mTc-anti-CEA immunoscintigraphy in patients with liver metastases from colorectal carcinoma.

17 patients with 43 liver metastases from colorectal carcinoma were studied by immunoscintigraphy (IS) using a 99mTc-labelled monoclonal anti-CEA antibody (BW 431/26). Sensitivity and diagnostic accuracy were 21% for all liver lesions, but 47% considering the number of patients (at least one positive finding out of multiple metastases) and 77% in patients with a single metastasis. SPECT imaging did not improve sensitivity markedly in this series. There was no correlation with CEA serum levels. Liver metastases of intermediate size with moderate tumour necrosis seem to be favourable to IS. Major reason for the low sensitivity is the poor tumour-to-background ratio caused by high unspecific uptake of 99mTc-labelled antibodies in the RES of the liver. At the moment, IS seems be only a supplementary method to conventional diagnostic procedures.

Adenocarcinoma↗
PubMed1991

Demonstration of L1-related mRNAs in rat brain using DNA oligonucleotide probes.

Only one copy of the cell adhesion molecule L1 gene is present in the mouse genome, and only one mRNA of 6 kilobases (kb) is expressed in mouse brain [1987, Neurosci. Lett. 82, 89-94]. We have constructed 5 synthetic oligonucleotide probes covering different parts of the published mouse L1 cDNA sequence. Using these probes 3 distinct mRNAs of 9.0, 7.0 and 6.0 kb in rat brain could be demonstrated. Hybridizations performed at different stringency conditions indicated that the 9.0 and 7.0 kb mRNAs were highly related to the L1 mRNA of 6.0 kb expressed in rat brain. The 7.0 kb mRNA is possibly coding for a rat homologue of chicken Nr-CAM, whereas the 9.0 kb mRNA may code for a new member of the L1 family.

Animals↗
PubMed1991

Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells.

The neural cell adhesion molecule, NCAM, plays an important role in cell-cell adhesion. Therefore, we have studied NCAM expression in the glioma cell lines BT4C and BT4Cn. We demonstrate that the 2 cell lines differ in their metastatic ability; while BT4C cells have a very low capacity for producing experimental metastases, that of BT4Cn cells is high. In BT4C cells NCAM is synthesized as 4 polypeptides with Mr's of 190,000, 140,000, 115,000 and 97,000. The 140,000, 115,000 and 97,000 polypeptides are glycosylated and for the 140,000 and 115,000 polypeptides sulfatation is observed. Conversely, no NCAM protein synthesis is observed in BT4Cn cells, even though NCAM mRNA is expressed. Thus, development of an increased metastatic capacity is accompanied by the disappearance of NCAM protein expression in this model system. The functional importance of NCAM expression was studied by a cell-substratum binding assay in which the binding of BT4C and BT4Cn cells to NCAM immobilized to glass was assessed. We found that BT4C cells adhere specifically to NCAM, and that adhesion is inhibited by anti-NCAM Fab'-fragments, while no specific binding of BT4Cn cells to NCAM was observed. The BT4C and BT4Cn cell lines thus constitute an important new model system for the study of tumor invasion and metastasis and of the role of cell adhesion molecules in these processes.

Animals↗
PubMed1991

NCAM in developing mouse gonads and ducts.

The expression of the Neural Cell Adhesion Molecule, NCAM, in mouse gonads and ducts was studied from fetal life to maturity. The methods used were immunocytochemical staining and Western blotting. The immunocytochemical studies showed that the only structures that remain NCAM-positive throughout life were the mesonephric-derived rete ovarii and rete testis. Also in the fetal gonads some somatic cell lining the groups of differentiating germ cells were stained. In the immature as well as in the mature ovary the granulosa cells and oocytes of growing and large follicles--but not of small follicles--were stained. A particularly strong staining of the cytoplasm of the oocyte, healthy as well as atretic, was seen. All cells of the testis remained negative except for weakly stained residual bodies and late spermatids. At all ages the male ducts showed only weak staining, whereas in the female Müllerian duct the epithelium became strongly positive at puberty. The stroma of the Müllerian duct was positive during a transitory period around day 16 of fetal life in both sexes. One-dimensional gel immunoblotting of total protein from gonads, rete and ducts from immature and mature mice showed that only the two largest isoforms of NCAM (NCAM-A and NCAM-B) were present. The gonads and the rete of both sexes and the adult uterus expressed only NCAM-B, whereas NCAM-A was also detected in the adult epididymis. The present findings suggest that NCAM may be involved in the normal development and formation of both the gonads and ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The cell adhesion molecule Cell-CAM 105 is an ecto-ATPase and a member of the immunoglobulin superfamily.

Cell-CAM 105 (C-CAM), a cell adhesion molecule in rat hepatocytes, was digested with trypsin, and peptides were isolated and sequenced by Edman degradation. The sequences of 4 peptides agreed with different regions of rat liver ecto-ATPase. Detailed biochemical analyses confirmed the identity between C-CAM and the ecto-ATPase. C-CAM/ecto-ATPase is a transmembrane protein having 4 immunoglobulin-like domains in the extracellular portion, demonstrating membership of the immunoglobulin superfamily. The ATPase activity suggests that ATP might influence cell adhesion, which would explain the inhibitory effect of exogenously added ATP on adhesion of several cell types.

Adenosine Triphosphatases↗
PubMed1990

Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes.

A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA oligonucleotides, that hybridize to different exons in the NCAM gene. Furthermore we have constructed three oligonucleotides, that exclusively hybridize to mRNAs lacking certain exons, by letting them consist of sequences adjacent to both sides of the splice sites. By means of these probes we have characterized the five NCAM mRNAs in rat brain.

Animals↗
PubMed1990

Characterization of N-cadherin mRNA in chicken brain and heart by means of oligonucleotide probes.

It has previously been reported, that there is only one mRNA of 4.3 kb for chicken N-cadherin in brain and heart and one gene [(1988) J. Cell Biol. 106, 873-881]. Using three synthetic oligonucleotide probes derived from the published chicken N-cadherin cDNA sequence we found hybridization to at least four mRNAs in chicken brain and heart. The measured sizes were 8.0, 4.7, 3.8, and 3.3 kb. The 8.0 kb mRNA is only seen in brain, and only when a cytoplasmic probe is employed. The 3.8 kb mRNA is only observed in heart.

Animals↗
PubMed1990

Expression of neural cell adhesion molecule-related sialoglycoprotein in small cell lung cancer and neuroblastoma cell lines H69 and CHP-212.

Monoclonal antibodies (MAbs) 123C3 and 123A8 generated against a membrane preparation of a small cell lung carcinoma (SCLC) specimen recognize not only SCLC and bronchial carcinoids but also a significant portion of non-small cell lung carcinomas (non-SCLC) of various histological types. Together with 13 other monoclonal antibodies, which show preference for SCLC, they have been ranked as SCLC cluster 1 (SC-1) Mabs. In this study we show that SC-1 MAbs are directed against a restricted number of epitopes, and that SC-1 MAbs and a polyclonal antiserum directed against the neural cell adhesion molecule (NCAM) recognize identical glycoproteins, indicating that SC-1 antigens are closely related to or identical with NCAM. Long polysialic acid units composed of alpha-(2,8)-linked N-acetylneuraminic acid units, which in mammals are found exclusively on NCAM, were present on SC-1 antigens in SCLC. This provides further evidence that SC-1 MAbs recognize NCAM. The SC-1 antigens in the SCLC cell line H69 were present in two forms, NCAM-containing alpha-(2,8)-polysialic acid units identified by antiserum 735, the NCAM-H form, and the less sialylated NCAM-L form. The NCAM-H form consisted of diffusely migrating sialoglycoproteins with a molecular weight of 200,000-250,000, which resolved after neuraminidase treatment into two proteins with molecular weights of 140,000 and 180,000. Since the NCAM-H form is expressed in the lung tumor type with a poor prognosis, our results suggest that NCAM might be implicated in the invasive behavior of these NCAM-positive lung tumors.

Antibodies, Monoclonal↗
PubMed1990

Glial fibrillary acidic protein and beta A4 protein deposits in temporal lobe of aging brain and senile dementia of the Alzheimer type: relation with the cognitive state and with quantitative studies of senile plaques and neurofibrillary tangles.

The aim of this study was to compare brain glial fibrillary acidic protein (GFAP) levels to the modifications of cognitive functions (Blessed test score [BTS]), the density of the main neuropathological lesions (senile plaques [SP] and neurofibrillary tangles [NFT]), and the density of the two main subtypes of beta A4 deposits (classic plaques and diffuse deposits) in a series of patients with normal aging and senile dementia of the Alzheimer type of various degrees of severity. GFAP levels (enzyme-linked immunosorbent assay [ELISA] technique) and the densities of changes were measured in the temporal lobe of 12 women over 75 years of age. Under these conditions, the ELISA assay could determine GFAP in brain homogenates (aqueous-Triton buffer soluble extract) in a range from 2.5 ng to 600 ng per assay. Least affected patients (with a BTS of 19 and over) all ranged below 60 micrograms/mg protein. Most affected patients (with a BTS under 6) ranged above 150 micrograms/mg protein. However, interindividual variations were wide. A significant correlation between the BTS and the amount of GFAP could be found only when using the non parametric test of Spearman. There was a significant positive correlation between the amount of GFAP and the density of 1) SP, 2) NFT both revealed by Bodian's silver stain, and 3) classic beta A4 plaques shown by immunocytochemistry. On the contrary, no correlation was observed with diffuse beta A4 deposits. One case with very large amounts of diffuse beta A4 deposits without SP or NFT showed no associated GFAP reactivity. This suggests that GFAP production is a critical event in the formation of classic SP.

Aged↗