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Biomedical subjects

K Herrmann

Publications and source records attributed to K Herrmann.

At least 19 recordsLinked to original sources
PubMed1996

Transforming growth factor-beta controls cell-matrix interaction of microvascular dermal endothelial cells by downregulation of integrin expression.

Transforming growth factor-beta (TGF-beta) is a pleiotropic regulatory factor of tissue remodeling. Angiogenesis, a prerequisite of tissue repair and tissue expansion, is induced by TGF-beta in vivo, while proliferation and migration of cultured endothelial cells are inhibited by TGF-beta. Indirect mechanisms stimulating angiogenesis and modification of TGF-beta effects by cell-matrix interaction have been postulated to account for this paradigm. Because cellular behavior in tissue remodeling is decisively determined by cell-matrix interactions, which in turn is mediated via integrins, we investigated the effect of TGF-beta on matrix-dependent endothelial cell functions. Integrin expression of human dermal microvascular endothelial cells (HDMEC) was measured by Northern blot and fluorescence-activated cell sorter analysis after TGF-beta treatment and correlated to cell-matrix interactions, which were studied in a colorimetric cell attachment assay as well as the Boyden chamber chemotaxis assay. We found a cell-specific downregulation of integrin expression in HDMEC on the level of mRNA as well as on the cell surface. This effect correlated well with the reduction of integrin-dependent cell adhesion to several matrix proteins, in particular to fibronectin. Moreover, TGF-beta decreased fibronectin-induced chemotaxis of HDMEC. Thus, TGF-beta controls cell-matrix interaction of HDMEC by down-regulation of integrin expression. This effect of TGF-beta reflects direct and cell-specific control mechanisms on microvascular cells that may be critical for the coordinated process of angiogenesis requiring a balance of stimulatory and inhibitory factors.

Cell Adhesion↗
PubMed1995

Blockade of action potential activity alters initial arborization of thalamic axons within cortical layer 4.

In the formation of connections during the development of the nervous system, it is generally accepted that there is an early phase not requiring neural activity and a later activity-dependent phase. The initial processes of axonal pathfinding and target selection are not thought to require neural activity, whereas the later fine-tuning of connections into their final adult patterns does. We report an apparent exception to this rule in which action potential activity seems to be required very early in development for thalamic axons to form appropriate patterns of terminal arborizations with their ultimate target neurons in layer 4 of the cerebral cortex. Blockade of sodium action potentials during the 2-week fetal period when visual thalamic axons initially grow into the primary visual cortex in cats prevents the normally occurring branching of lateral geniculate nucleus axons within layer 4. This observation implies a role for action-potential activity in cerebral cortical development far earlier than previously suspected, weeks before eye-opening and the onset of the well-known process of activity-dependent reorganization of axonal terminal arbors that leads to the formation of ocular dominance columns.

Action Potentials↗
PubMed1995

Application of enzyme immunoassays for testing haemocompatibility of biomedical polymers.

In this study enzyme immunoassays are presented for the assessment of platelet adhesion/activation and fibrinogen adsorption/conformation. The estimation of platelet adhesion and activation was performed with two enzyme immunoassays (EIAs) using monoclonal antibodies directed against CD42b (GP lb) and CD 62 (GMP 140 or P-Selectin). The applicability of EIA was first demonstrated in microtitre plates coated with fibrinogen. The thrombogenic substrate showed that platelet adhesion and activation reached a plateau level within 30 min. The use of EIA for testing biomaterials was demonstrated with polymeric reference materials where a differentiation of materials with respect to adhesion and activation was achieved. To validate the EIA scanning electron microscopy was applied and confirmed the different extent of adhesion and activation of platelets on reference materials. In addition, polyurethaneureas, based on 4,4'-diphenylmethane diisocyanate and polytetramethylene glycols, with different hard segment content and composition were investigated. It was found that both adhesion and activation were not simply dependent on the hard segment content but also on the hard segment composition. To get more insight into the mechanism of this process, two EIAs for the binding of fibrinogen using polyclonal and monoclonal antibodies were developed. There it was shown that the adhesion and activation of platelets on polyurethaneureas was not simply dependent on the total amount of adsorbed fibrinogen but rather on its conformation, indicated by the binding of the monoclonal antibody directed vs the gamma-chain of fibrinogen.

Adsorption↗
PubMed1995

Immobilization of heparin on polylactide for application to degradable biomaterials in contact with blood.

The poly-(D, L-lactide) RESOMER R208 (Boehringer-Ingelheim, Germany) was modified with heparin to improve the blood contacting properties of the material. The immobilization of herapin was carried out by covalent binding with glutaraldehyde as the coupling agent. The reaction conditions, such as temperature and time, were varied to optimize the binding of heparin. The efficiency of the immobilization was monitored with respect to the total amount of coupled herapin with a toluidine blue assay and the anticoagulant activity of immobilized heparin with a factor Xa assay. The hemocompatibility of the modified polylactide was estimated after blood-material contact by the activation of platelets measured with an enzyme immuno assay for GMP140. Immobilization at ambient temperature and a reaction time of 2 h resulted in maximal heparin binding, high anticoagulant activity, and low thrombogenicity. Since the remaining unsaturated aldehyde groups of the coupling agent may cause a low hemocompatibility of the material, washing of the heparinized polylactide was carried out with ethanol. However, it was shown that washing diminished the anticoagulant activity of heparin and increased the thrombogenicity. The prolonged storage of heparinized polylactide in phosphate buffered saline for 8 days demonstrated that small quantities of heparin were released but the hemocompatibility was further improved, indicated by an increasing anticoagulant potential and a decrease in platelet activation with incubation time. A comparison of polylactide, heparinized polylactide, polypropylene, and Pellethane with respect to platelet activation by GMP140 assay and scanning electron microscopy, revealed that the heparinization of polylactide substantially improved the hemocompatibility of RESOMER R208, making the material comparable to Pellethane.

Anticoagulants↗
PubMed1995

[Reducing radiation dosage with modern DSA equipment].

PURPOSE: In angiographic and interventional procedures the often long fluoroscopy times add a great deal to the total patient dose. The new Multistar T.O.P. (Siemens) is equipped with various features for dose reduction. In this study pulsed fluoroscopy was tested versus standard continuous fluoroscopy and supervisions. MATERIALS AND METHODS: Fluoroscopy with 3, 7.5, and 15 pulses/s in the Multistar T.O.P. were compared to standard fluoroscopy and to reduced-dose supervision in a human pelvic phantom. The skin entry dose and pelvic dose were continuously registered. RESULTS: The supervision mode used 58% of the dose used in continuous fluoroscopy. Pulsed fluoroscopy with 15 pulses/s required 54%, 7.5 pulses/s 27% and 3 pulses/s. These provide adequate image quality with only 10% of the standard dose. CONCLUSIONS: It was possible to save up to 90% of the fluoroscopy dose in interventions and angiographies when using the new pulsed fluoromodes available in the Multistar T.O.P.

Angiography, Digital Subtraction↗
PubMed1994

Ultrastructural evidence for synaptic interactions between thalamocortical axons and subplate neurons.

Thalamic axons are known to accumulate in the subplate for a protracted period prior to invading the cortical plate and contacting their ultimate targets, the neurons of layer 4. We have examined the synaptic contacts made by visual and somatosensory thalamic axons during the transition period in which axons begin to leave the subplate and invade the cortical plate in the ferret. We first determined when geniculocortical axons leave the subplate and begin to grow into layer 4 of the visual cortex by injecting 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine (Dil) into the lateral geniculate nucleus (LGN). By birth most LGN axons are still confined to the subplate. Over the next 10 days LGN axons grow into layer 4, but many axons retain axonal branches within the subplate. To establish whether thalamic axons make synaptic contacts within the subplate, the anterograde tracer PHA-L was injected into thalamic nuclei of neonatal ferrets between postnatal day 3 and 12 to label thalamic axons at the electron microscope level. The analysis of the PHA-L injections confirmed the Dil data regarding the timing of ingrowth of thalamic axons into the cortical plate. At the electron microscope level, PHA-L-labelled axons were found to form synaptic contacts in the subplate. The thalamic axon terminals were presynaptic primarily to dendritic shafts and dendritic spines. Between postnatal days 12 and 20 labelled synapses were also observed within layer 4 of the cortex. The ultrastructural appearance of the synapses did not differ significantly in the subplate and cortical plate, with regard to type of postsynaptic profiles, length of postsynaptic density or presynaptic terminal size. These observations provide direct evidence that thalamocortical axons make synaptic contacts with subplate neurons, the only cell type within the subplate possessing mature dendrites and dendritic spines; they also suggest that functional interactions between thalamic axons and subplate neurons could play a role in the establishment of appropriate thalamocortical connections.

Animals↗
PubMed1994

Mg2+ and Ca2+ differentially regulate beta 1 integrin-mediated adhesion of dermal fibroblasts and keratinocytes to various extracellular matrix proteins.

The specific requirements for divalent cations in the integrin-dependent adhesion and deadhesion of human dermal fibroblasts and human epidermal keratinocytes to various extracellular matrix proteins have been studied in vitro. The adhesion of both cell types to collagen type I and to laminin was enhanced by Mg2+ in a concentration-dependent manner, while Ca2+ dose-dependently antagonized this effect, thus promoting deadhesion. The cation-dependent conversion between adhesion and deadhesion occurred already at 2 to 10 min after addition of the alternate cation and was almost completed at 20 min. Interestingly, Ca2+ could not reverse the Mg(2+)-enhanced adhesion of both cell types to fibronectin. Inhibition studies with function-blocking antibodies directed against distinct beta 1 integrins showed that the Mg(2+)-enhanced fibroblast adhesion to collagen type I was mediated by the alpha 1 beta 1 and the alpha 2 beta 1 integrins, whereas keratinocyte adhesion to collagen type I was mediated by the alpha 2 beta 1 integrin. Both cell types utilized the alpha 2 beta 1 and the alpha 6 beta 1 integrins for Mg(2+)-dependent adhesion to laminin and the alpha 5 beta 1 integrin for the adhesion to fibronectin. Integrin expression at the cell surface was not altered, indicating that divalent cation-dependent conformational changes of beta 1 integrins most likely regulate their functional activity.

Calcium↗
PubMed1994

Immunologic parameters in systemic sclerosis.

BACKGROUND: Immunologic abnormalities seem to play an important role in important role in systemic sclerosis (SSc). METHODS: We studied the following immune parameters to get more insight into SSc: autoantibodies (antinuclear antibodies (ANA), anti-Scl-70, anticentromere antibodies (ACA) subsets of lymphocyte subpopulations and markers of their activation, as well as serum levels of IL-2, the soluble IL-2 receptor (SIL-2R), IL-6 and its correlation to N-terminal procollagen-III propeptide (P III P), and finally, the IL-6 production by SSc and normal dermal fibroblasts. RESULTS: In patients with active SSc, we found a reduced number of CD2+ T-lymphocytes and an increase in the expression of T-lymphocyte activation markers such as CD25+ and CD71+, HLA-DR Ia, as well as elevated serum levels of SIL-2LR and IL-6. SSc fibroblasts did not produce more IL-6 than normal fibroblasts in monolayer cultures. CONCLUSIONS: Our data show that a wide range of immunologic parameters are altered in SSc. In general, T-helper (TH) lymphocytes are activated possibly because of reduced T-suppressor (TS) and natural killer (NK)-cell levels. TH may polyclonally stimulate B cells, which in turn produce higher amounts of autoantibodies. Our findings support the concept that TH cell-derived cytokines/growth factors stimulate matrix protein synthesis by fibroblasts, resulting in generalized fibrosis.

Adolescent↗
PubMed1993

Antibodies to retrovirus proteins in scleroderma.

In 8 out of 29 patients with scleroderma we found antibodies to HIV retroviral proteins in the Western blot analysis. The sera reacted only to one or two of the following bands: p 18, p 24, p 55, p 65 in relatively weak grades. There were no evident clinical correlations with the reactivity of certain bands, nor signs of direct HIV infection in our patients. Apart from 3 cases with positive CMV reactivity (IgM), there was no cross-reactivity to HTLV I or EBV (IgM) and to topoisomerase (Scl 70) or other autoantibodies to various nuclear antigens related to scleroderma. It is not clear whether retroviruses are involved in the pathogenesis of scleroderma or whether these antibodies are due to molecular mimicry.

Adult↗
PubMed1993

[Antibodies to retroviral proteins in progressive scleroderma].

In 8 out of 29 patients with scleroderma we found antibodies to HIV retroviral proteins in the Western blot analysis. The sera each reacted only to one or two of the p 18, p 24, p 55, and p 65 bands, and the reactions were relatively weak. There were no evident clinical correlations with the reactivity of certain bands and signs of direct HIV infection in our patients. Apart from three cases with positive CMV reactivity (IgM) there was no cross-reactivity to HTLV I or EBV (IgM) or to topoisomerase (Scl 70) or other autoantibodies to various nuclear antigens related to scleroderma. It is not clear whether retroviruses are involved into the pathogenesis of scleroderma or whether these antibodies are due to molecular mimicry.

Antibodies, Viral↗
PubMed1992

[Chemically-induced scleroderma].

Scleroderma-like diseases can be induced by a number of chemical compounds, such as plastics, solvents and drugs. Contaminated rapeseed oil was the cause of the toxic oil syndrome and L-tryptophan induces the so-called eosinophilia-myalgia-syndrome. On the other hand, paraffin and silicon can trigger so-called adjuvant disease, while long-term exposure to silica can lead to idiopathic scleroderma (associated with silicosis in some cases). In addition to the clinical features, some pathogenetic data in the literature, such as genetic factors (HLA, chromosomal anomalies, enzyme deficiencies) and the metabolism of chlorinated ethylenes via reactive epoxide intermediate products, and our own findings are reported. Silica-induced scleroderma cannot be distinguished from the idiopathic form by epidemiological, clinical or immunological studies or by parameters referring to the blood vessels or collagen metabolism. In cell culture studies it has been shown that macrophages/monocytes release IL1, IL6 and TNF after ingestion of silica, which affects fibroblasts, T-helper cells and endothelial cells. Comparative results from the silicosis literature are reported. Finally, the possibly stimulating role of ionizing irradiation (uranium mining) in favouring the development of scleroderma is discussed.

Ethylenes↗
PubMed1991

Lesions of HVc block the developmental masculinizing effects of estradiol in the female zebra finch song system.

The neural song control system of female zebra finches is permanently masculinized if the females are given estradiol within 1 month after hatching. One hypothesis is that estradiol acts on neurons in the caudal nucleus of the ventral hyperstriatum (HVc) to cause developmental changes that lead to masculinizing influences in other song control regions. To test whether lesions of HVc block the masculinizing effects of estradiol elsewhere in the song system, we gave 20-day-old females either a Silastic pellet containing estradiol or no implant, and they received either a unilateral lesion of HVc or no lesion. At 60 days of age, they were sacrificed. The volumes of brain regions and sizes of neurons were measured in four song nuclei: HVc, robust nucleus of the archistriatum (RA), lateral magnocellular nucleus of the neostriatum (IMAN), and Area X. Lesions of HVc blocked the masculinizing effects of estradiol on RA and Area X on the side of the lesion. Thus, HVc must be intact in order for estradiol to masculinize these two nuclei. This observation is compatible with the hypothesis that estradiol acts on or near HVc to masculinize several song nuclei, although other interpretations are also possible.

Animals↗
PubMed1991

Remodeling of retinal ganglion cell dendrites in the absence of action potential activity.

The dendrites of ganglion cells in the retina have an excess number of spines and branches that are normally lost during the first postnatal month of development. We investigated whether this dendritic remodeling can be prevented when the action potential activity of ganglion cells is abolished by chronic intraocular injections of tetrodotoxin (TTX) during the first 4 or 5 postnatal weeks in the cat. Dendritic tree morphologies of alpha and beta ganglion cells from TTX-treated, non-TTX-treated (contralateral eye), and normal control retinae were compared after intracellular filling with Lucifer yellow. Qualitative observations and quantitative measurements indicate that TTX treatment does not prevent the normally occurring loss of spines and dendritic branches. Indeed, the dendritic trees of both alpha and beta cells in TTX injected eyes actually have even fewer spines and branches than normal cells at equivalent ages. However, because the total dendritic lengths of these cells are also reduced after TTX blockade, spine density is indistinguishable from untreated animals at the same age. In addition, although dendritic field areas are not altered with treatment, the complexity of the dendritic trees is reduced. These observations suggest that dendritic remodeling can occur in the absence of ganglion cell action potential activity. Thus, the factors that influence the dendritic and axonal development of retinal ganglion cells must differ, because similar TTX treatment during the period of axonal remodeling does have profound effects on the final pattern of terminal arborizations.

Action Potentials↗
PubMed1991

Steady-state mRNA levels of collagens I, III, fibronectin, and collagenase in skin biopsies of systemic sclerosis patients.

Total RNA was extracted from skin biopsies of nine patients suffering from systemic sclerosis (SSc). Steady-state mRNA levels of collagen alpha 1(I) and alpha 1(III), collagenase, fibronectin, and beta-actin were studied using specific cDNA probes and compared to those of 12 sex- and age-matched healthy individuals. There was a more than three-fold elevation of collagen I mRNA levels in SSc skin compared to controls. No difference was found, however, for collagen III, collagenase, and fibronectin mRNA levels in SSc and control biopsies. The selective increase of collagen alpha 1(I) mRNA levels indicates a specific alteration of fibroblast metabolism in scleroderma. Analysis of mRNA levels in skin biopsies might not only offer a direct approach to the understanding of the pathophysiology of SSc, but also facilitate the monitoring of fibrotic activity in SSc patients during therapeutic trials.

Adult↗
PubMed1991

The development of afferent projections to the robust archistriatal nucleus in male zebra finches: a quantitative electron microscopic study.

Because the projections into the robust nucleus of the archistriatum (RA) are thought to play important roles in song learning and sexual differentiation of the zebra finch (Poephila guttata), quantitative electron microscopic techniques were used to measure the development of synaptic input to the neuropil of RA in this species. Two nuclei [hyperstriatum ventrale pars caudalis (HVc) and lateral magnocellular nucleus of the anterior neostriatum (IMAN)] that send projections to RA were lesioned at each of three different ages: 25 d after hatching, 53 d, and adulthood. In tissue from RA processed for conventional electron microscopy, lesion-induced degeneration was used to identify synapses from either HVc or IMAN. Axosomatic synapses were excluded from analysis. In control (unlesioned) animals, the density of synapses in neuropil increased slightly between days 28 and 56 and remained constant thereafter. Because of a large increase in the volume of RA, the total number of synapses in neuropil of RA tripled between days 28 and 56 and decreased significantly between day 56 and adulthood. The density and total number of synapses in neuropil originating from HVc increased significantly between days 25 and 53, but did not change significantly thereafter. In contrast, the density and total number of synapses from IMAN decreased significantly between days 25 and 53 and did not change thereafter. Presynaptic terminals from IMAN were larger than those from HVc. These data demonstrate that the most rapid phase of song learning is accompanied by a major rearrangement of synaptic contacts into RA that stem from HVc and IMAN.

Afferent Pathways↗
PubMed1990

Silica-induced scleroderma.

In a survey done in East Germany between 1981 and 1988, we found that 93 of 120 male scleroderma patients had long-term exposure to silica dust. We describe our findings in 12 patients with scleroderma and silicosis. The exposure time to silica dust was between 3 and 34 years; the interval between the beginning of exposure and the onset of scleroderma averaged 27.3 years (range 9 to 40 years). Antinuclear antibodies in titers between 80 and 10,240 with nucleolar and/or speckled patterns were found in 10 patients, antibodies against double-stranded DNA in three, Scl-70 (topoisomerase I) in three, and anticentromere antibodies in five. The following markers of collagen metabolism were increased in serum: beta-galactosidase in 12 patients, laminin peptide-P1 in 10 patients, N-terminal procollagen type III peptide in 10, and urinary sialic acid excretion in 7. We propose that crystalline particles of silica less than 5 microns may be phagocytosed by macrophages and release lymphokines and monokines, which activate fibroblasts and enhance their collagen and glycosaminoglycan synthesis. In addition, silica may act as an adjuvant to increase immune reactivity.

Biopsy↗