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Biomedical subjects

S Bartsch

Publications and source records attributed to S Bartsch.

At least 19 recordsLinked to original sources
PubMed2006

Regional and cellular distribution of the extracellular matrix protein tenascin-C in the chick forebrain and its role in neonatal learning.

The juvenile brain's pronounced synaptic plasticity in response to early experience and learning events is related to the fact that the genetically pre-programmed molecular machinery mediating neuronal development and synapse formation, is activated throughout postnatal brain development and thereby can be recruited for learning and long-term memory formation. In situ hybridization and immunocytochemistry experiments revealed that tenascin-C, one candidate molecule which we suspect to be involved in neonatal learning, is expressed in the forebrain of domestic chicks around the sensitive period during which auditory filial imprinting takes place. The involvement of tenascin-C in this juvenile learning task was tested by injections of monoclonal antibodies directed to distinct domains of the tenascin-C molecule into the avian prefrontal cortex analog, the medio-rostral nidopallium/mesopallium (formerly termed medio-rostral neostriatum/hyperstriatum ventrale), a forebrain area which has been shown to be critically involved in auditory filial imprinting. Injections of monoclonal antibody Tn 68, which is directed against a cell-binding domain of the tenascin-C molecule, strongly reduced the imprinting rate, as opposed to injections of the monoclonal antibody Tn 578, which binds to a domain involved in neurite outgrowth. Double labeling immunohistochemistry revealed that tenascin-C is associated with neurons which express the Ca(2+)-binding protein parvalbumin, and displays a staining pattern highly reminiscent of perineuronal nets of the extracellular matrix. These results indicate that a distinct domain of tenascin-C is functionally involved in the juvenile learning process of filial imprinting and further suggest a critical role of a specific neuronal subpopulation.

Age Factors↗
PubMed2004

Cadherin expression pattern in melanocytic tumors more likely depends on the melanocyte environment than on tumor cell progression.

BACKGROUND: Adhesion molecules have been assigned an important role in melanocytic tumor progression. By the loss of E-cadherin, melanocytes might escape the control of neighbouring keratinocytes. Although in vitro data support this hypothesis, there are yet no conclusive immunohistochemical results on cadherin expression in melanocytic tumors. OBJECTIVE: To gain detailed insight in the expression of cadherins and their cytoplasmic binding partners, the catenins, in various types of benign and malignant melanocytic neoplasms. METHODS: Immunohistochemical analysis of the expression of E-, P-, and N-cadherin and alpha-, beta-, and gamma-catenin in compound and dermal nevi, Spitz nevi, blue nevi, ultraviolet B (UVB)-irradiated nevi, and malignant melanomas of various tumor thickness. RESULTS: In both nevi and melanomas, E-cadherin expression in melanocytic cells decreased, following a gradient from junctional to deeper dermal localization. The pattern of E-cadherin expression was more heterogeneous in melanomas than in nevi. In some melanomas, E-cadherin was only weakly positive in the epidermal tumor cells. P-cadherin expression was similar to that of E-cadherin. N-cadherin expression in melanocytic lesions was a rare finding, however, a small percentage of melanomas showed expression in some cell nests. Some Spitz nevi exhibited strong N-cadherin immunoreactivity. Most melanocytic cells were alpha- and beta-catenin-positive and gamma-catenin-negative. UVB irradiation did not influence the expression of cadherins and catenins in melanocytic nevi in vivo. CONCLUSIONS: It is presumed that the gradual loss of E-cadherin expression represents a reaction of melanocytic cells to altered conditions in the dermal environment, e.g. lack of contact to keratinocytes, or new contact with dermal extracellular matrix molecules, respectively. Melanoma cells apparently are less dependent on these environmental factors and, therefore, show a more heterogeneous expression pattern. This might be of importance for the adaptation of the tumor cells to local requirements. However, in view of our results, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven.

Cadherins↗
PubMed2004

Haemodynamic effects of dopexamine on postprandial splanchnic hyperaemia.

BACKGROUND: The synthetic beta(2)-adrenergic and dopaminergic agonist dopexamine is supposed to prevent splanchnic hypoperfusion in critically ill patients, thus potentially interacting with haemodynamic effects of early enteral nutrition. However, precise mechanism of action and interaction with postprandial splanchnic hyperaemia of the drug are largely unknown, even in healthy subjects. MATERIALS AND METHODS: Twelve healthy volunteers received dopexamine 1 microg x kg(-1) min(-1) and dopexamine and placebo (NaCl 0.9%) 3 microg x kg(-1) min(-1) in a randomized, double-blinded order (crossover-design). Splanchnic (Doppler ultrasound) and systemic (noninvasive cardiac monitoring) haemodynamic parameters were assessed at baseline and during infusion (fasted as well as 15, 30, 45 and 60 min after a standard liquid meal). RESULTS: In fasted humans, dopexamine enhanced time-averaged maximum velocity (TAMX) in the superior mesenteric artery (1 microg + 40%; 3 microg + 82%, P < 0.05), portal vein (+ 63%; + 121%, P < 0.05) and femoral artery (+ 66%; + 87%, P < 0.05), in proportion to the increase of cardiac index (+ 33%; + 77%, both P < 0.05). In the postprandial state, TAMX rose significantly in the superior mesenteric artery (+ 139%) and portal vein (+ 68%) in the placebo group, showing the same absolute extent as dopexamine. The physiological postprandial buffer response of hepatic artery was conserved under all conditions. CONCLUSIONS: Continuous infusion of dopexamine enhances mesenterial and portal perfusion in a dose-dependent manner without affecting the extent of physiological postprandial hyperaemia. Thus, dopexamine and enteral nutrition may interact with splanchnic haemodynamics by different pathways.

Abdomen↗
PubMed2003

[Angularly stable radius plate: progress in treatment of problematic distal radius fracture?].

Fractures of the distal radius represent one of the most common fractures and have high socioeconomic relevance. Using the volar approach to avoid the soft tissue problems associated with dorsal plating, we treated a consecutive series of 49 displaced intra-articular distal radius fractures with a new fixed-angle internal fixation device. According to the AO classification, there were 21 C1, 19 C2, and nine C3 fractures. A retrospective study was carried out to obtain the functional results after open reduction and plate osteosynthesis. Loss of correction between postoperative and follow-up radiography was 1 degrees in volar tilt and radial inclination. The radial shortening was 1 mm. Wrist motion at final follow-up examination had recovered to an average of 80% of that at the normal, contralateral site. Overall outcome according to the Gartland and Werley scales showed 35% excellent, 50% good, and 15% fair results. Using the Martini score, we obtained 85% excellent and good results. The DASH score represented high subjective satisfaction.

Adult↗
PubMed2003

Lack of toxic side effects in neutrophils following hyperbaric oxygen.

Conflicting data have been reported about the impact of repeated HBO2 exposure on the production of superoxide radicals during the neutrophil respiratory burst (RB) and on phagocytosis. In this study we wanted to see if exposure to hyperoxia would affect human neutrophil RB and phagocytosis. Short- and long-term effects after single or repetitive HBO2 exposure of 2.5 atmospheres absolute over a period of 90 min were studied in 40 healthy volunteers. The RB was measured by the intracellular oxidation of dihydrorhodamine after induction by Escherichia coli (E. coli), or priming with recombinant tumour necrosis factor alpha (TNF-alpha), followed by N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation. The phagocytic activity was determined by the intake of FITC-labelled opsonized E. coli. No differences could be found between RB and phagocytic activity before and after HBO2 therapy, regardless of short- or long-term exposure. These findings indicate that exposure to hyperoxia does not impair these two important functions of the human innate host defense.

Adolescent↗
PubMed2001

The human neutrophil lipocalin supports the allosteric activation of matrix metalloproteinases.

The human neutrophil lipocalin (HNL), a member of the large family of lipocalins that exhibit various physiological functions, is coexpressed in granulocytes with progelatinase B (MMP-9). Part of it is covalently bound to the proenzyme and therefore may play a possible role in the activation process of promatrix metalloproteinases. We now report that HNL is able to accelerate the direct activation of promatrix metalloproteinases slightly. A significant enhancement of the activity could be demonstrated for the HgCl2- and the plasma kallikrein-induced activation of all three secretory forms of proMMP-9 and of proMMP-8. The same activating effects were exerted by HNL isolated from granulocytes as well as by the recombinant forms expressed by the yeast Pichia pastoris or by Escherichia coli. This demonstrates that the carbohydrate moiety is not essential for the biological activity of HNL. Activation and activity enhancement are obviously mediated by entrapping the remaining N-terminal sequence residues of the partially truncated proenzyme into the hydrophobic binding pocket of the HNL. In conclusion these results document that HNL can exert an enzyme-activating effect in the regulation of inflammatory and pathophysiological responses of granulocytes in the physiological activation of MMPs that have been subject to limited proteolytic processing.

Acute-Phase Proteins↗
PubMed2000

Severe hypomyelination of the murine CNS in the absence of myelin-associated glycoprotein and fyn tyrosine kinase.

The analysis of mice deficient in the myelin-associated glycoprotein (MAG) or Fyn, a nonreceptor-type tyrosine kinase proposed to act as a signaling molecule downstream of MAG, has revealed that both molecules are involved in the initiation of myelination. To obtain more insights into the role of the MAG-Fyn signaling pathway during initiation of myelination and formation of morphologically intact myelin sheaths, we have analyzed optic nerves of MAG-, Fyn- and MAG/Fyn-deficient mice. We observed a slight hypomyelination in optic nerves of MAG mutants that was significantly increased in Fyn mutants and massive in MAG/Fyn double mutants. The severe morphological phenotype of MAG/Fyn mutants, accompanied by behavioral deficits, substantiates the importance of both molecules for the initiation of myelination. The different severity of the phenotype of different genotypes indicates that the MAG-Fyn signaling pathway is complex and suggests the presence of compensatory mechanisms in the single mutants. However, data are also compatible with the possibility that MAG and Fyn act independently to initiate myelination. Hypomyelination of optic nerves was not related to a loss of oligodendrocytes, indicating that the phenotype results from impaired interactions between oligodendrocyte processes and axons and/or impaired morphological maturation of oligodendrocytes. Finally, we demonstrate that Fyn, unlike MAG, is not involved in the formation of ultrastructurally intact myelin sheaths.

Animals↗
PubMed2000

Long-term follow-up results of irradiation alone or combined with surgery in stage I-IV carcinoma of the uterine cervix.

OBJECTIVE: Evaluation of side effects and prognostic factors for survival in cervical carcinoma treated with radiation therapy +/- surgery. MATERIAL AND METHODS: From January 1986 to June 1995 277 female patients with cervical carcinoma were treated by irradiation in the Department of Radiation Oncology of the University of Münster. Out of them 224 patients were evaluable for clinical features. 20 of them did not undergo complete radiation series and 14 patients received irradiation for recurrent disease, therefore 190 patients (n = 103 pts. with primary irradiation, n = 87 pts. with postoperative irradiation) were analyzed for survival/therapeutic features. RESULTS: 5-year-disease-free survival rates after primary irradiation: (FIGO I number of patients too small); FIGO II (n = 33 pts.) 52%; FIGO III (n = 44 pts.) 39.5%; FIGO IV (n = 18 pts.) 26%. 5-year-survival rates after postoperative irradiation: pT1 (n = 43 pts.) 87.4%; pT2 (n = 37 pts.) 47%. As significant prognostic factors for disease specific survival after irradiation alone the hemoglobin bloodlevel at the beginning of radiation therapy, tumor stage according to FIGO, tumor size and irradiation of the paraaortic region were revealed. As significant prognostic factors for disease free survival after postoperative irradiation were seen: interval between surgery and the beginning of radiation therapy, tumor invasion of parametria, postoperative stage, involvement of lymph nodes and lymph-/hemangiosis. The documented side effects among all patients corresponded to data found in literature. CONCLUSIONS: Prognostic factors for disease free survival in our patients corresponded to the results of other studies. Acute and chronic side effects after irradiation were within the usual range. Especially in case of additional irradiation of the paraaortic region we could not find an accumulation of side effects. An elevation of disease free survival rates in patients with cervical carcinoma probably could be obtained by improving positional techniques for irradiation or changing fractionation schedules.

Adenocarcinoma↗
PubMed1999

The solution structure and dynamics of human neutrophil gelatinase-associated lipocalin.

Human neutrophil gelatinase-associated lipocalin (HNGAL) is a member of the lipocalin family of extracellular proteins that function as transporters of small, hydrophobic molecules. HNGAL, a component of human blood granulocytes, binds bacterially derived formyl peptides that act as chemotactic agents and induce leukocyte granule discharge. HNGAL also forms a complex with the proenzyme form of matrix metalloproteinase-9 (pro-MMP-9, or progelatinase B) via an intermolecular disulphide bridge. This association allows the subsequent formation of ternary and quaternary metalloproteinase/inhibitor complexes that vary greatly in their metalloproteinase activities. The structure and dynamics of apo-HNGAL have been determined by NMR spectroscopy. Simulated annealing calculations yielded a set of 20 convergent structures with an average backbone RMSD from mean coordinate positions of 0. 79(+/-0.13) A over secondary structure elements. The overall rotational correlation time (13.3 ns) derived from15N relaxation data is consistent with a monomeric protein of the size of HNGAL (179 residues) under the experimental conditions (1.4 mM protein, pH 6.0, 24.5 degrees C). The structure features an eight-stranded antiparallel beta-barrel, typical of the lipocalin family. One end of the barrel is open, providing access to the binding site within the barrel cavity, while the other is closed by a short 310-helix. The free cysteine residue required for association with pro-MMP-9 lies in an inter-strand loop at the closed end of the barrel. The structure provides a detailed model of the ligand-binding site and has led to the proposal of a site for pro-MMP-9 association. Dynamic data correlate well with structural features, which has allowed us to investigate a mechanism by which a cell-surface receptor might distinguish between apo and holo-HNGAL through conformational changes at the open end of the barrel.

Acute-Phase Proteins↗
PubMed1997

Increased number of unmyelinated axons in optic nerves of adult mice deficient in the myelin-associated glycoprotein (MAG).

We have recently demonstrated that the formation of myelin sheaths in the optic nerve of young postnatal mice deficient in the myelin-associated glycoprotein (MAG) is retarded when compared to age-matched wild-type mice. In the present study, we analyzed whether impaired myelination of retinal ganglion cell axons is detectable in adult MAG mutants. In optic nerves of 2- and 9-month-old MAG-deficient mice, we observed a significantly increased number of unmyelinated axons compared to age-matched wild-type mice. At both ages, unmyelinated axons in optic nerves of MAG mutants were of small caliber. The number of unmyelinated axons decreased significantly in 9-month-old MAG mutants when compared to 2-month-old MAG mutants, indicative of a slow and long-lasting myelination of axons in the mutant. Our observations support the view that MAG is involved in the initiation of myelination in the CNS.

Animals↗
PubMed1995

Conformational flexibility in highly sulfated beta-D-glucopyranoside derivatives.

Triggered by findings on heparin-like disaccharides, the conformation of sulfated glucopyranosides was investigated. Sodium (methyl 2,3,4-tri-O-sulfonato-beta-D-glucopyranosid)uronate tetrasodium salt is in a conformational equilibrium, to which a non-chair conformation contributes. The same is true for methyl (methyl 2,3,4-tri-O-sulfonato-beta-D-glucopyranosid)uronate trisodium salt, methyl 2,3,4,6-tetra-O-sulfonato-beta-D-glucopyranoside tetrasodium salt, and octa-O-sulfonato-beta, beta-trehalose octasodium salt, with less obvious non-chair contributions. The effect is charge related. The conformational effect, which does not occur in analogous alpha-D-glucopyranoside derivatives, is discussed in terms of the anomeric effect.

Carbohydrate Conformation↗
PubMed1995

The extracellular matrix molecule tenascin: expression in the developing chick retinotectal system and substrate properties for retinal ganglion cell neurites in vitro.

To investigate the molecular mechanisms involved in the outgrowth of retinal ganglion cell axons in the tectum, the expression of the extracellular matrix molecule tenascin was analysed in the tectum and retina of chickens by immunocytochemistry and in situ hybridization. Tissue was analysed between embryonic days 4 and 12, just before and during the period when retinal ganglion cell axons innervate their target region, the optic tectum. In the tectum, tenascin immunoreactivity becomes detectable at the anterior pole at embryonic day 4, 2 days before retinal ganglion cell axons arrive, and spreads caudally with increasing age. At early stages, tenascin is predominantly accumulated in the stratum opticum, the zone of ingrowing retinal ganglion cell axons, and along their prospective pathway. In the stratum opticum, the molecule is associated with radial glial fibres, glial endfeet and retinal ganglion cell axons located in the immediate neighbourhood of radial glial fibres. At all ages investigated, tenascin mRNA is mainly restricted to cells located in the periventricular region, suggesting that the molecule is synthesized by radial glial cells. In the retina, tenascin is expressed by amacrine, displaced amacrine and horizontal cells but not by retinal ganglion cells. To investigate whether the accumulation of tenascin in the developing and prospective pathway of retinal ganglion cell axons may affect their rate of growth we assayed the substrate properties of tenascin for retinal ganglion cell neurites in vitro. When retinal ganglion cell suspensions from 6-day-old chick embryos were maintained on homogeneous mouse or chick tenascin/polyornithine substrates, neurite length was significantly increased when compared to polyornithine substrates at coating concentrations of 10 or 20 micrograms/ml. Higher coating concentrations (35 or 70 micrograms/ml) resulted in neurite lengths comparable to control values. Together, these observations suggest that tenascin in the developing and prospective stratum opticum might serve as a performed pathway to support growth of retinal ganglion cell axons in the tectum.

Animals↗
PubMed1995

Cloning and expression of human neutrophil lipocalin cDNA derived from bone marrow and ovarian cancer cells.

Human neutrophil lipocalin (HNL) cDNA was amplified by PCR technology in combination with deoxyinosine containing oligonucleotides for cloning, sequencing and production of the recombinant protein in E. coli. The primers were targeted to the corresponding DNA backtranslate of the mature protein resulting in a PCR amplified 534 bp cDNA from different reverse transcripts of ovarian cancer cell line and bone marrow cell mRNAs. Sequence analysis revealed that two different cDNAs from ovarian cancer and bone marrow cells could be obtained. Cloning and expression of HNL cDNAs were performed in E. coli strain HMS 174 [DE3] using the pET system yielding in two recombinant proteins with a molecular weight of 21 kDa which is consistent with an 178 amino acid residues containing sequence of the mature HNL protein. N-terminal amino acid sequence analysis of the expression products showed an identical polypeptide sequence missing the E. coli processed starting methionine.

Acute-Phase Proteins↗
PubMed1995

Multiply myelinated axons in the optic nerve of mice deficient for the myelin-associated glycoprotein.

We recently reported that some retinal ganglion cell axons in mice deficient for the myelin-associated glycoprotein are concentrically surrounded by more than one myelin sheath. In the present study, we demonstrate that myelin sheaths displaced from the axon reveal a normal ultrastructure of compact myelin, with the only exception that multiple myelination of axons frequently correlates with the presence of unfused regions of major dense lines. Supernumerary sheaths terminated on other sheaths or on astrocyte cell surfaces in a pattern closely resembling the morphology of a true paranode. The thickness of compact myelin of multiply myelinated axons was significantly increased when compared with axons of similar caliber surrounded by a single myelin sheath. Our observations demonstrate that maintenance of compact myelin and paranodal regions is not dependent on direct axonal contact and that the presence of more than one concentric myelin sheath around an axon results in dysregulation of the axon-to-fiber ratio.

Animals↗
PubMed1995

Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS.

The MAG-deficient mouse was used to test whether MAG acts as a significant inhibitor of axonal regeneration in the adult mammalian CNS, as suggested by cell culture experiments. Cell spreading, neurite elongation, or growth cone collapse of different cell types in vitro was not significantly different when myelin preparations or optic nerve cryosections from either MAG-deficient or wild-type mice were used as a substrate. More importantly, the extent of axonal regrowth in lesioned optic nerve and corticospinal tract in vivo was similarly poor in MAG-deficient and wild-type mice. However, axonal regrowth increased significantly and to a similar extent in both genotypes after application of the IN-1 antibody directed against the neurite growth inhibitors NI-35 and NI-250. These observations do not support the view that MAG is a significant inhibitor of axonal regeneration in the adult CNS.

3T3 Cells↗
PubMed1994

Tenascin demarcates the boundary between the myelinated and nonmyelinated part of retinal ganglion cell axons in the developing and adult mouse.

The molecular determinants controlling the topographically restricted distribution of neural cells in the mammalian CNS are largely unknown. In the mouse, myelin-forming oligodendrocytes are differentially distributed along retinal ganglion cell axons. These axons are myelin free intraretinally and in the most proximal (i.e., retinal) part of the optic nerve, but become myelinated in the distal (i.e., chiasmal) part of the optic nerve. Tenascin protein and mRNA are detectable in increased amounts at the retinal end of the developing optic nerve before the arrival of oligodendrocyte progenitor cells and are restricted to this region in the adult optic nerve. Tenascin is a nonadhesive substrate for oligodendrocytes and their progenitor cells in vitro when offered as a substrate in choice with polyornithine. These observations suggest that tenascin is critical for the establishment and maintenance of the restricted distribution of myelin-forming oligodendrocytes along retinal ganglion cell axons of the mouse.

Animals↗
PubMed1993

Preparation of active recombinant TIMP-1 from Escherichia coli inclusion bodies and complex formation with the recombinant catalytic domain of PMNL-collagenase.

TIMP-1 is a member of the family of tissue inhibitors of metalloproteinases involved in regulating the activity of extracellular matrix degrading metalloproteinases. The TIMP-1 cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR) amplification of the corresponding mRNA from human fibroblasts. Cloning and expression of the TIMP-1 cDNA were performed in Escherichia coli. In the host vector system chosen, rTIMP-1 is stored intracellularly in its denatured, insoluble form in inclusion bodies. We report a new method for the purification and renaturation of rTIMP-1 from E. coli inclusion bodies to an active inhibitor of matrix metalloproteinases (80% yield), presumably containing the correct assignment of the six disulfide bonds. A resin with the covalently bound recombinant catalytic domain of the PMNL-collagenase as the affinity ligand provided an effective means for the separation of correctly folded, active rTIMP-1 from inactive forms with mismatched disulfides. TIMP-1 and TIMP-2, the two most extensively examined members of the family of tissue inhibitors of metalloproteinases, are known to form a complex with the activated forms of most matrix metalloproteinases and the latent forms of the 92-kDa and 72-kDa gelatinases, respectively. In this study, we report on the complex formation of the recombinant catalytic domain of the PMNL-collagenase with TIMP-1, nonglycosylated recombinant TIMP-1, and recombinant TIMP-2. The Ki values for the different inhibitors were determined in a kinetic assay using a fluorogenic substrate peptide. In this assay, rTIMP-2 had a more effective inhibitory capability against the recombinant catalytic domain of the PMNL-collagenase than TIMP-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗