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Biomedical subjects

A Faissner

Publications and source records attributed to A Faissner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Expression of high levels of the extracellular matrix glycoprotein, tenascin-C, in the normal adult hypothalamoneurohypophysial system.

Glia and neurons of the hypothalamoneurohypophysial system (HNS) undergo reversible morphological changes, which are concomitant with the remodelling of afferents onto the neurons, under different conditions of neurohormone secretion. Here, we show that the adult rat HNS contains high levels of tenascin-C (TN-C), which is an extracellular matrix glycoprotein whose expression is usually associated with neuronal-glial interactions in the developing and lesioned central nervous system (CNS). By using light and electron microscopic immunocytochemical procedures, we visualized TN-C immunoreactivity in the hypothalamic supraoptic (SON) and paraventricular nuclei, where somata of the neurons are localized; in the median eminence, where their axons transit; and in the neurohypophysis, where they terminate. Hypothalamic areas adjacent to the magnocellular nuclei were devoid of immunoreactivity. Electron microscopy of the neurohypophysis showed immunolabelling of perivascular spaces, glial (pituicyte) and axonal surfaces, a type of labelling that also characterized the median eminence. In the hypothalamic nuclei, there was labelling of extracellular spaces and astrocytic surfaces. In normal animals, we detected no cytoplasmic reaction in glia somata, neurons, or endothelial cells. However, in animals treated with the intracellular transport blocker colchicine, there was intracytoplasmic labelling of all HNS glial cells, indicating a glial source for TN-C. Immunoblot analysis revealed TN-C isoforms of apparent high molecular weight (225, 240, and 260 kD) in the SON and median eminence, whereas lower MW forms (190/200 kD) predominated in the neurohypophysis. By using immunocytochemistry and immunoblot analysis, we found no visible differences in TN-C expression in relation to age, sex, or differing neurohypophysial secretion, which suggests that the expression of TN-C is a permanent feature of the HNS.

Animals↗
PubMed1997

The tenascin gene family in axon growth and guidance.

Glial cells are thought to play an important role in the regulation of neural pattern formation, e.g. by guiding migrating neuroblasts and growth cones to their target regions. In addition to these supportive roles, astro- and oligodendroglia have also been attributed inhibitory functions. Thus, these lineages are believed to constrain the pathways of migrating neurons and growth cones. Recent studies have led to the current view that the inhibitory roles of the glia of the central nervous system (CNS) may be important for neural pattern formation. Furthermore, inhibitory effects of glia may play an essential role in the failure of CNS regeneration, e.g. in the astrocytic scar. Advances have been made in deciphering the molecular basis of glia-mediated inhibitory influences in the CNS. The present review focuses on the tenascin gene family of extracellular matrix glycoproteins. Of these, tenascin-C and -R are expressed in developing and lesioned neural tissue and embody both stimulatory and anti-adhesive or inhibitory properties for axon growth.

Animals↗
PubMed1997

Up-regulation of astrocyte-derived tenascin-C correlates with neurite outgrowth in the rat dentate gyrus after unilateral entorhinal cortex lesion.

The extracellular matrix protein tenascin-C has been implicated in the regulation of axonal growth. Using unilateral entorhinal cortex lesions, which induce a massive sprouting response in the denervated outer molecular layer of the rat fascia dentata, the role of tenascin-C for axonal growth was investigated in vivo. Monoclonal antibodies against the neurite outgrowth and anti-adhesive domains of the molecule were employed. Immunostaining was increased throughout the denervated outer molecular layer by day 2, reached a maximum around day 10, and was back to control levels by four weeks post lesion. Growth cone deflecting as well as neurite outgrowth promoting isoforms of tenascin-C were up-regulated after the lesion. Using electron microscopy, single intensely tenascin-C immunoreactive cells were identified as reactive astrocytes that phagocytose degenerated terminals. In situ hybridization histochemistry for tenascin-C messenger RNA revealed numerous cellular profiles in the denervated outer molecular layer of the ipsilateral and contralateral dentate gyrus two days post lesion. Tenascin-C messenger RNA-positive cells in the outer molecular layer were identified as astrocytes using double-labelling for tenascin-C messenger RNA and glial fibrillary acidic protein immunohistochemistry. Thus, a tenascin-C-rich substrate is present in the outer molecular layer during the time of sprouting and a sharp boundary is formed against the inner molecular layer. This pattern may contribute to the layer-specific sprouting response of surviving afferents after entorhinal lesion. Neurite outgrowth may be promoted within the denervated zone, whereas axons trying to grow into the denervated outer molecular layer, for example from the inner molecular layer, would be deflected by a tenascin-C-rich barrier.

Animals↗
PubMed1997

Tenascin-C synthesis and influence on axonal growth during rat cortical development.

Several putative guidance molecules are restricted to the marginal and subplate zones, the major fibre tracts in the developing cortex. It is presently unknown how their distribution is achieved and how these molecules affect neurite extension. Tenascin-C is of particular interest in this context, because it may either promote or deflect growing axons depending on its mode of presentation. Therefore, the cellular origin of tenascin-C in the developing rat cortex and its effects on the extension of cortical afferents and efferents were examined. Tenascin-C protein is first restricted to the marginal and subplate zones and spreads later into the developing grey matter, in close correlation with afferent innervation. In situ hybridization showed that tenascin-C mRNA is first confined to the ventricular zone, at some distance from the location of the protein, while at later stages tenascin-C-synthesizing cells become scattered throughout the cortical thickness, concomitant with the spread of the protein. In order to assess its function, monoclonal antibodies directed against different domains of tenascin-C were used in a quantitative axonal outgrowth assay. These perturbation experiments suggested that distinct tenascin-C fibronectin type III repeats sustain the growth of thalamic and cortical axons on cortical membrane carpets, whereas the EGF-type repeats are not involved. The combination of different antibodies revealed that separate fibronectin-type III repeats exert cooperative effects. These results suggest that ventricular zone cells regulate the establishment of thalamic and cortical axonal projections through locally restricted deposition of tenascin-C.

Animals↗
PubMed1997

Hippocampal loss of tenascin boundaries in Ammon's horn sclerosis.

Ammon's horn sclerosis (AHS) is a common finding in patients with temporal lobe epilepsy (TLE). In addition to selective neuronal cell loss and axonal reorganization, AHS is also characterized by a striking astroglial reaction. However, the functional significance of reactive astrogliosis in the pathogenesis of TLE remains to be determined. Reactive astrocytes produce a variety of cell adhesion molecules and other extracellular matrix (ECM) components with potential effects on axonal growth, axonal branching, and neosynaptogenesis in the central nervous system (CNS). In the present study we describe the distribution of the ECM glycoprotein tenascin/cytotactin (TN-C) in 44 human hippocampal specimens from patients with TLE. The distribution of TN-C immunoreactivity was evaluated with the anti-human TN-C monoclonal antibody K8 by densitometrical analysis, and TN-C protein levels were detected by immunoblotting. In the normal human hippocampus, there were distinctive boundaries between areas of high and low TN-C expression. These border zones demarcated areas with major synaptic input, i.e., the dentate gyrus molecular layer (DG-ML) and the gray matter of the Ammon's horn. TN-C and the neurite growth-associated protein GAP-43 exhibited a complementary pattern of distribution. Densitometric and protein biochemical analysis showed a significant, 4.3-fold increase of TN-C in the hippocampus of TLE patients with AHS compared with normal hippocampus obtained at autopsy. This increase in TN-C immunoreactivity was accompanied by a loss of TN-C boundaries and closely correlated with the extent of reactive gliosis, as indicated by immunoreactivity for glial fibrillary acidic protein. Furthermore, a striking colocalization between TN-C and GAP-43 was observed in the DG-ML of patients with AHS. These observations raise the intriguing possibility of pathogenetically relevant glio-neuronal interactions in human TLE.

Antibody Specificity↗
PubMed1997

Characterization of monoclonal antibodies against tenascin-C: no apparent effect on kidney development in vitro.

Tenascin-C is an extracellular matrix glycoprotein found in embryonic mesenchyme. The precise biological function of tenascin-C is unknown, but different parts of the molecule have effects on cell adhesion and other cellular activities. We studied the expression and role of tenascin-C in the embryonic mouse kidney. By Northern blots, no tenascin-C was detectable in uninduced mesenchyme from day 11 embryonic kidneys, but after 24 hours of in vitro culture both major splice variants of tenascin-C were detected. The larger variant was the predominant form. By in situ hybridization tenascin-C mRNA in 13-day old embryonic kidneys was detected in the mesenchyme surrounding newly formed epithelial structures. In 17-day old embryonic kidneys, tenascin-C mRNA was detected in mesenchyme around the forming epithelial structures in the cortex, and expression was also seen in mesenchyme surrounding the capsular epithelium of glomeruli. In newborn kidneys, expression had shifted to the medulla but was still confined to mesenchymal areas. We have characterized 6 new monoclonal antibodies against mouse tenascin-C, which all stain embryonic kidneys from different stages in a pattern consistent with earlier reports and with the mRNA data. The binding sites of the monoclonal antibodies on the tenascin-C molecule were mapped to discrete regions of tenascin-C. These six and five previously described antibodies against tenascin-C were tested in antibody perturbation experiments. Three of these have been shown by in vitro assays to perturb function of other cell types. Despite this, none of them inhibited development of mouse kidneys in organ culture, although they were tested at 1 mg/ml. It raises the possibility that tenascin-C is not crucial for kidney development. Alternatively, tenascin-C has more subtle functions which could not be identified with the assays used here.

Animals↗
PubMed1996

Tau binds to the distal axon early in development of polarity in a microtubule- and microfilament-dependent manner.

Microtubule-associated protein tau is localized to the axon in situ and has been implicated in the development of neuronal polarity. Here we report that tau is extracted differentially in cultured hippocampal neurons yielding an axon-specific localization under conditions that keep the integrity of the plasma membrane. The amount of bound tau increases toward the distal axon and is highest at the transition from the axonal shaft to the growth cone. This distribution is significantly different from the distribution of axonal microtubules that are most concentrated at the proximal axon. Distal binding of tau to one process appears early in development of polarity in culture and correlates with the onset of axon formation (day 2 in culture). Binding to the distal axon requires intact microtubules and microfilaments. Distal tau binding does not stabilize microtubules selectively against drug-induced disassembly, because colchicine-induced microtubule depolymerization is highest distally. We conclude that binding of tau to the distal axon follows a complex mechanism, is an early event in the development of polarity, and reproduces the axon-specific localization of tau in situ.

Actin Cytoskeleton↗
PubMed1996

The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum.

Grafts of embryonic ventral mesencephalic tissue placed in the striatum of 6-hydroxydopamine-lesioned rats survive, and make and receive connections to and from the host brain. The dopaminergic neurons of the graft can grow processes into the host brain, and thereby alleviate many of the behavioral deficits of this form of experimental Parkinson's disease. However, when examined some weeks after implantation, grafted substantia nigra only contains about 5% of the expected complement of dopaminergic neurons. We have examined the time course of loss of grafted neurons. We find that the majority die during the first 7 days after transplantation. However, we have shown previously that three-dimensional cultures with the same dimensions as a graft, made of identical cell suspensions, have much better dopaminergic neuronal survival. There must, therefore, be features in the environment surrounding a graft that are toxic to dopaminergic neurons. A limiting factor in the efficacy of dopaminergic grafts is the small distance over which the neurons are able to grow neurites and form connections in the host brain. We find that the growth of neurites from dopaminergic neurons into the host striatum occurs in two phases. Neurites reach their maximum length within 7 days of transplantation, and this is followed by a much slower process of branch and terminal formation. Since axon growth in the adult brain may be inhibited by a number of factors associated with reactive gliosis, we have immunostained various ages of graft for vimentin, tenascin, chondroitin sulfate proteoglycan (CS-PG) using the CS56 antibody, the DSD-1 proteoglycan, and microglia using the OX-42 antibody. We have compared this staining with that surrounding a simple stab wound. Vimentin staining was initially seen in the graft and in astrocytes immediately surrounding it. By 7 weeks staining was restricted to a ring of astrocytes surrounding the graft. Tenascin, DSD-1, and CS-PG were initially seen in and around the grafts. By 7 weeks they had disappeared from grafts, but CS-PG and tenascin persisted in small amounts around stab wounds. In general, immunostaining of these molecules persisted longer around a stab lesion than around a graft. There was also an intense local microglial reaction surrounding both grafts and stab wounds which had largely resolved by 7 weeks.

Animals↗
PubMed1996

Tenascin-C inhibits oligodendrocyte precursor cell migration by both adhesion-dependent and adhesion-independent mechanisms.

Tenascin-C is present within the developing central nervous system during oligodendrocyte precursor cell migration. Tenascin-C is antiadhesive for oligodendrocytes, suggesting a role in controlling the migration of oligodendrocyte precursors and hence the pattern of myelination. Here we show directly that tenascin-C is a repulsive (or antiadhesive) substrate for primary oligodendrocyte precursors and also inhibits their migration. The antimigratory effect of tenascin-C on oligodendroglia is mediated through two distinct mechanisms; reduced substrate adhesion and a direct inhibition of cell migration that is independent of adhesion. These two effects map to different domains of the tenascin-C molecule. The repulsive effect maps to the EGF-like repeats and the alternatively spliced FN III repeats while the direct migration-inhibiting effect maps to FN III repeats 7-8. Our results show tenascin-C to have the novel property of inhibiting migration by both adhesion-dependent and adhesion-independent mechanisms, with different regions of the same molecule responsible for the two effects.

Animals↗
PubMed1996

The proteoglycan DSD-1-PG occurs in perineuronal nets around parvalbumin-immunoreactive interneurons of the rat cerebral cortex.

Proteoglycans involved in the shaping of the developing brain are often preserved in the adult brain in more restricted locations. We have studied the fate of DSD-1-PG, a chondroitin sulfate proteoglycan containing the hybrid epitope DSD-1. DSD-1-PG exerts neurite outgrowth promoting activity and has been shown to occur in the developing brain during late brain development and into adulthood. In the adult rat brain, monoclonal and polyclonal antibodies against DSD-1-PG labelled only the circumference of a selected subpopulation of neurons. These nerve cells invariably expressed the calcium-binding protein parvalbumin. The label occupied the extracellular space in close vicinity to the cell body, surrounding axon terminals and glial end feet, but was absent from synaptic clefts. DSD-1-PG is thus shown to be an additional representative of the growing list of substances found in perineuronal locations in the adult mammalian brain.

Animals↗
PubMed1996

Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related.

The multimodular glycoprotein tenascin-C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin-C domains using antibody perturbation studies and in vitro experiments on tenascin-C fragments. In order to study potential roles of tenascin-C for glial cell biology, a library of recombinant tenascin-C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial-derived cell lines (C6, A7 and Neu7) and oligodendroglial-derived cell types (Oli-neu and G26-20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites the epidermal growth factor-like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin-C receptors which might regulate cellular responses via distinct second messenger pathways.

Animals↗
PubMed1996

Tenascin-C contains distinct adhesive, anti-adhesive, and neurite outgrowth promoting sites for neurons.

The glia-derived extracellular matrix glycoprotein tenascin-C (TN-C) is transiently expressed in the developing CNS and may mediate neuron-glia interactions. Perturbation experiments with specific monoclonal antibodies suggested that TN-C functions for neural cells are encoded by distinct sites of the glycoprotein (Faissner, A., A. Scholze, and B. Götz. 1994. Tenascin glycoproteins in developing neural tissues--only decoration? Persp. Dev. Neurobiol. 2:53-66). To characterize these further, bacterially expressed recombinant domains were generated and used for functional studies. Several short-term-binding sites for mouse CNS neurons could be assigned to the fibronectin type III (FNIII) domains. Of these, the alternatively spliced insert TNfnA1,2,4,B,D supported initial attachment for both embryonic day 18 (E18) rat and postnatal day 6 (P6) mouse neurons. Only TNfn1-3 supported binding and growth of P6 mouse cerebellar neurons after 24 h, whereas attachment to the other domains proved reversible and resulted in cell detachment or aggregation. In choice assays on patterned substrates, repulsive properties could be attributed to the EGF-type repeats TNegf, and to TNfnA1,2,4. Finally, neurite outgrowth promoting properties for E18 rat hippocampal neurons and P0 mouse DRG explants could be assigned to TNfnB,D, TNfnD,6, and TNfn6. The epitope of mAb J1/tn2 which abolishes the neurite outgrowth inducing effect of intact TN-C could be allocated to TNfnD. These observations suggest that TN-C harbors distinct cell-binding, repulsive, and neurite outgrowth promoting sites for neurons. Furthermore, the properties of isoform-specific TN-C domains suggest functional significance of the alternative splicing of TN-C glycoproteins.

Amino Acid Sequence↗
PubMed1996

Regulation of oligodendrocyte precursor migration by extracellular matrix: evidence for substrate-specific inhibition of migration by tenascin-C.

In order to analyse the role of the extracellular matrix (ECM) in the migration of oligodendrocyte precursor cells we have used a chemotaxis chamber assay in which the filter separating the wells is coated with different ECM molecules. Two molecules, fibronectin and the laminin family member merosin, promoted migration either alone or in combination with the chemotactic growth factor platelet-derived growth factor. The effects of the ECM molecules and growth factor were additive, and demonstrated that the migrating oligodendrocyte precursors respond both to haptotactic and chemotactic stimuli. A third extracellular molecule, tenascin-C, inhibited migration. This inhibition was substrate-specific; while migration on fibronectin was inhibited there was no effect on merosin-stimulated migration. This specificity confirms that tenascin-C inhibits migration by modulation of individual cell-ECM interactions rather than by a non-specific process of interference with substrate adhesion. An understanding of the role of tenascin-C in central nervous system development will therefore require characterisation of the different colocalising ECM molecules at different developmental stages.

Animals↗
PubMed1995

Cell and molecular analysis of the developing and adult mouse subventricular zone of the cerebral hemispheres.

The subventricular zone (SVZ) of the lateral ventricle remains mitotically active in the adult mammalian central nervous system (CNS). Recent studies have suggested that this region may contain neuronal precursors (neural stem cells) in adult rodents. A variety of neuronal and glial markers as well as three extracellular matrix (ECM) markers were examined with the hope of understanding factors that may affect the growth and migration of neurons from this region throughout development and in the adult. This study has characterized the subventricular zone of late embryonic, postnatal, and adult mice using several neuronal markers [TuJ1, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), neuron-specific enolase (NSE)], glial markers [RC-2, vimentin, glial fibrillary acidic protein (GFAP), galactocerebroside (Gal-C)], ECM markers [tenascin-C (TN-C), chondroitin sulfate, a chondroitin sulfate proteoglycan termed dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG)], stem-cell marker (nestin), and proliferation-specific marker [bromodeoxyuridine (BrdU)]. TuJ1+ and nestin+ cells (neurons and stem cells, respectively) persist in the region into adulthood, although the numbers of these cells become more sparse as the animal develops, and they appear to be immature compared to the cells in surrounding forebrain structures (e.g., not expressing NSE and having few, if any, processes). Likewise, NADPH-d+ cells are found in and around the SVZ during early postnatal development but become more sparse in the proliferative zone through maturity, and, by adulthood, only a few labeled cells can be found at the border between the SVZ and surrounding forebrain structures (e.g., the striatum), and even smaller numbers of positive cells can be found within the adult SVZ proper. BrdU labeling also seems to decrease significantly after the first postnatal week, but it still persists in the SVZ of adult animals. The disappearance of RC-2+ (radial) glia during postnatal development and the persistence of glial-derived ECM molecules such as tenascin and chondroitin sulfate proteoglycans (as well as other "boundary" molecules) in the adult SVZ may be associated with a persistence of immaturity, cell death, and a lack of cell emigration from the SVZ in the adult.

Aging↗
PubMed1995

An analysis of astrocytic cell lines with different abilities to promote axon growth.

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin and N-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.

Animals↗
PubMed1995

Up-regulation of a chondroitin sulphate epitope during regeneration of mouse sciatic nerve: evidence that the immunoreactive molecules are related to the chondroitin sulphate proteoglycans decorin and versican.

After transection of adult mouse sciatic nerve, the expression of a chondroitin sulphate epitope recognized by the monoclonal antibody 473-HD (mAb 473-HD) was found to be up-regulated. The epitope was localized immunocytochemically mainly in Schwann cell basal laminae and, more weakly, also in the endoneurium. In cultures of mouse dorsal root ganglion cells, Schwann cells expressed high levels but fibroblasts only low levels of the epitope. To identify the molecule(s) carrying this chondroitin sulphate epitope, human sciatic nerves were extracted with phosphate-buffered saline and shown to contain two chondroitin sulphate proteoglycans of apparent molecular weights of 130 and 900 kDa. The 900 kDa and, more weakly, the 130 kDa proteoglycan were reactive with mAb 473-HD, which was found to recognize chondroitin-6-sulphate as epitope. Following chondroitinase ABC treatment of the 130 kDa proteoglycan, a core protein of approximately 45 kDa was seen and shown to react with polyclonal antibodies against the chondroitin-dermatan sulphate proteoglycan decorin from human fibroblasts. Chondroitinase ABC treatment of the 900 kDa proteoglycan yielded a core protein with a molecular weight of approximately 400 kDa that was recognized by polyclonal antibodies against recombinantly expressed fusion proteins from human versican. After transection of adult mouse sciatic nerves, the distal nerve stumps showed up-regulation of the chondroitin-6-sulphate epitope of the 900 kDa proteoglycan, whereas the core protein of this proteoglycan did not show any detectable change in the level of expression. In contrast, the core protein of the 130 kDa proteoglycan was up-regulated in expression. These observations suggest that versican- and decorin-like molecules may contribute to successful regeneration in the peripheral nervous system of mammals.

Animals↗
PubMed1995

Significance of tenascin serum level as tumor marker in primary colorectal carcinoma.

Tenascin serum levels were evaluated in 118 patients with primary colorectal carcinoma and in a control group of 51 healthy persons in a double-sided sandwich ELISA. The data were correlated with post-operative TNM-staging. Patients with colorectal carcinomas had significantly higher serum levels of tenascin than the control group. At the 95% level of specificity, sensitivity was 25%. Tumor grading obviously had no influence on the level of tenascin in serum. With increasing pT-category, tenascin levels increased as well. In patients with distant metastatic disease, serum tenascin levels were significantly higher than in patients without distant metastases. These data suggest that, in colorectal carcinoma, the preoperative level of serum tenasin reflects the total tumor burden and correlates with metastatic disease. Our observation warrants a prospective study of the relevance of tenascin serum levels with regard to prognosis and as an indicator of relapse.

Adult↗