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Biomedical subjects

C E Schmidt

Publications and source records attributed to C E Schmidt.

At least 19 recordsLinked to original sources
PubMed2006

Optimizing neurotrophic factor combinations for neurite outgrowth.

Most neurotrophic factors are members of one of three families: the neurotrophins, the glial cell-line derived neurotrophic factor family ligands (GFLs) and the neuropoietic cytokines. Each family activates distinct but overlapping cellular pathways. Several studies have shown additive or synergistic interactions between neurotrophic factors from different families, though generally only a single combination has been studied. Because of possible interactions between the neurotrophic factors, the optimum concentration of a factor in a mixture may differ from the optimum when applied individually. Additionally, the effect of combinations of neurotrophic factors from each of the three families on neurite extension is unclear. This study examines the effects of several combinations of the neurotrophin nerve growth factor (NGF), the GFL glial cell-line derived neurotrophic factor (GDNF) and the neuropoietic cytokine ciliary neurotrophic factor (CNTF) on neurite outgrowth from young rat dorsal root ganglion (DRG) explants. The combination of 50 ng ml(-1) NGF and 10 ng ml(-1) of each GDNF and CNTF induced the highest level of neurite outgrowth at a 752 +/- 53% increase over untreated DRGs and increased the longest neurite length to 2031 +/- 97 microm compared to 916 +/- 64 microm for untreated DRGs. The optimum concentrations of the three factors applied in combination corresponded to the optimum concentration of each factor when applied individually. These results indicate that the efficacy of future therapies for nerve repair would be enhanced by the controlled release of a combination of neurotrophins, GFLs and neuropoietic cytokines at higher concentrations than used in previous conduit designs.

Animals↗
PubMed2005

[University clinics in the competitive hospital market].

In recent years Germany has faced a growing economization and competition among hospitals. To protect their interests hospitals have to operate similarly to other commercial businesses. Academic hospitals face difficult circumstances in this competition. They have to facilitate research and education activities which require additional financial and personnel resources but also provide maximum acute care treatment at all times. This causes additional disadvantages in terms of financial resources, compared to private hospital chains. Such examples of financial shortcomings have led to the privatization of academic research centres in Germany. An alternative strategy to privatization of academic acute care hospitals is the change of their legal status into a capital company or into a foundation, according to US experiences. Public private partnerships (PPPs) may also represent a potential alternative, as they have already produced a growing number of successful examples in the public sector in Germany. Academic acute care hospitals can also choose a strategic reorganization of their targets, similar to their privately held competitors in the market. Potential economies in scale may be achieved in areas such as medical treatment, research and personnel planning.However, it is vital that academic acute care hospitals start to act productively and also individually. This article provides a number of managerial pathways and options to maintain and strengthen operational competitiveness.

Economic Competition↗
PubMed2005

[Teamwork in the operating theatre. Effect on quality of decision-making].

German hospitals face growing economic pressure. Due to the reimbursement system with diagnosis-related groups (DRGs), revenues from capitation fees have to be earned by each clinic. This leads to minimization of resources for every single case. Cost effectiveness is also realised through shorter hospital stays, reduction of hospital beds and a steady rise in cases per year. As a consequence, all employees are confronted with an increasing workload. Compensation of these working conditions can be achieved by human engineering. Despite statements from politicians and hospital leadership in order to cope with this situation, reality is far away: overwork, shorter or missing recreation periods, pressure of time and low income of staff members have turned hospitals into a deterring workplace. If satisfaction of elementary needs such as adherence to break times, is not achieved shortly, politicians and hospital leadership will find out that without motivated and satisfied staff there will not be efficient performance. The present article addresses this issue and gives examples for increasing efficiency through motivation. Focus is on cooperation in the operation room, advantages and risks of teamwork and auxiliary measures for improvement. The aim is to underline how complex and fragile working in an operation room proceeds and how little is done to support this process. Finally, examples are described which improve teamwork, motivation, efficiency and efficacy.

Cost-Benefit Analysis↗
PubMed2001

Gelsolin overexpression enhances neurite outgrowth in PC12 cells.

The rational design of therapies for treating nerve injuries requires an understanding of the mechanisms underlying neurite extension. Neurite motility is driven by actin polymerization; however, the mechanisms are not clearly understood. One actin accessory protein, gelsolin, is involved with remodeling the cytoskeleton, although its role in cell motility is unclear. We report a two-fold upregulation of gelsolin upon differentiation with nerve growth factor. Cells that were genetically modified to overexpress gelsolin have longer neurites and a greater neurite motility rate compared to controls. These data suggest that gelsolin plays an important role in neurite outgrowth.

Animals↗
PubMed2001

Vascular graft endothelialization: comparative analysis of canine and human endothelial cell migration on natural biomaterials.

Canines are typically used as the standard preclinical model to gauge the success of vascular graft materials. However, canines spontaneously re-endothelialize vascular grafts, whereas humans do not, even after years. This raises questions of why there are differences in vascular healing between humans and other species and whether the canine is the appropriate preclinical model. In the present study we evaluated human and canine endothelial cell (EC) migration on the novel cross-linked collagen biomaterial PhotoFix(TM) pericardium. We compared in vitro migration of these cells on PhotoFix alone and on PhotoFix adsorbed with various growth factors (aFGF and bFGF) and adhesion proteins (fibronectin, collagen IV, vitronectin, and laminin). We also compared human and canine ECs in terms of their morphologies and prostacyclin production. We found that human umbilical vein ECs (HUVECs) and canine ECs (CECs) migrated well on PhotoFix, suggesting that this biomaterial may be a good vascular graft candidate. Both cell types responded similarly to different growth factors and adhesive proteins, but HUVEC migration was consistently higher than that for CECs. This suggested that human in vivo graft re-endothelialization is likely not hindered by poor endothelial migration but is hindered by other cellular or graft properties.

Animals↗
PubMed2001

Electrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterials.

Electrical charges have been shown to enhance nerve regeneration; however, the mechanisms for this effect are unclear. One hypothesis is that an electrical stimulus alters the local electrical fields of extracellular matrix molecules, changing protein adsorption. We have investigated this hypothesis--that electrical stimulation increases the adsorption of serum proteins, specifically fibronectin (FN), to the electrically conducting polymer polypyrrole (PP), thereby, increasing neurite extension. PP was used because electrical stimulation of PP has been shown to significantly enhance neurite outgrowth, and more importantly, PP can be formed into conduits to guide nerve regeneration in vivo. Here, we looked at the effects of electrical stimulation on protein adsorption when an electrical current was applied to PP (1) during protein adsorption (immediate stimulation) and (2) several hours after protein adsorption (delayed stimulation). We found that immediate stimulation of PP increases FN adsorption from purified FN and serum-containing solutions. Correspondingly, PC-12 cells grown on PP films that had been previously adsorbed with FN during immediate stimulation expressed longer neurites. However, for delayed stimulation, no significant differences in adsorption or neurite outgrowth were observed. These studies suggest that increased FN adsorption with immediate electrical stimulation may explain enhanced neurite extension on electrically stimulated PP.

Adsorption↗
PubMed2001

Genetic modification of alphaGal expression in xenogeneic endothelial cells yields a complex immunological response.

The source of cells for tissue engineering applications remains a hurdle, predominantly for procedures in which there is insufficient time to harvest a patient's own cells. Animal cells are readily available, but undergo immune rejection. Rejection of animal (i.e., xenogeneic) tissue involves practically every component of the immune system. The initial phase, hyperacute rejection (HAR), involves natural xenoreactive antibodies and the complement system, and leads to endothelial cell lysis and rapid tissue destruction. The cell-surface epitope, galactose-alpha(1,3)-galactose (alphaGal), is presumed to play a key role in HAR. The later stage of immune response (delayed xenograft rejection or DXR), is mediated by immune cells such as monocytes. Carbohydrates are likely also involved in DXR, but their role in this phase of the immune response is less clear. A better understanding of all stages of xenogeneic immune rejection may make it feasible to create cell lines that are immune tolerant. In these studies, we have genetically modified bovine endothelial cells to study the roles of carbohydrates in immune rejection. Our studies suggest that one or more epitopes other than alphaGal may influence complement-mediated lysis. Furthermore, antibodies, as instigators in the complement response, and monocytes appear to recognize different cell surface epitopes.

Animals↗
PubMed2000

Synthesis and characterization of polypyrrole-hyaluronic acid composite biomaterials for tissue engineering applications.

New tissue engineering technologies will rely on biomaterials that physically support tissue growth and stimulate specific cell functions. The goal of this study was to create a biomaterial that combines inherent biological properties which can specifically trigger desired cellular responses (e.g., angiogenesis) with electrical properties which have been shown to improve the regeneration of several tissues including bone and nerve. To this end, composites of the biologically active polysaccharide hyaluronic acid (HA) and the electrically conducting polymer polypyrrole (PP) were synthesized and characterized. Electrical conductivity of the composite biomaterial (PP/HA) was measured by a four-point probe technique, scanning electron microscopy was used to characterize surface topography, X-ray photoelectron spectroscopy and reflectance infrared spectroscopy were used to evaluate surface and bulk chemistry, and an assay with biotinylated hyaluronic acid binding protein was used to determine surface HA content. PP/HA materials were also evaluated for in vitro cell compatibility and tissue response in rats. Smooth, conductive, HA-containing PP films were produced; these films retained HA on their surfaces for several days in vitro and promoted vascularization in vivo. PP/HA composite biomaterials are promising candidates for tissue engineering and wound-healing applications that may benefit from both electrical stimulation and enhanced vascularization.

Animals↗
PubMed2000

Engineering strategies for peripheral nerve repair.

Tissue engineering in the peripheral nervous system unites efforts by physicians, engineers, and biologists to create either natural or synthetic tubular nerve guidance channels as alternatives to nerve autografts for the repair of peripheral nerve defects. Guidance channels help direct axons sprouting from the regenerating nerve end, provide a conduit for diffusion of neurotropic and neurotrophic factors secreted by the damaged nerve stumps, and minimize infiltration of fibrous tissue. In addition to efforts to control these physical characteristics of nerve guidance channels, researchers are optimizing the incorporation of biologic factors and engineering interactive biomaterial that can specifically stimulate the regeneration process. Current and future research will ultimately result in biologically active and interactive nerve guidance channels that can support and enhance peripheral nerve regeneration over longer, more clinically relevant defect lengths.

Animals↗
PubMed2000

Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering.

Various research groups around the world are actively investigating cardiovascular prostheses of biological origin. This review article discusses the need for such bioprosthetics and the potential role for natural tissues in cardiovascular applications such as cardiac valves and vascular grafts. Upon implantation, unmodified natural materials are subject to chemical and enzymatic degradation, seriously decreasing the life of the prosthesis. Therefore, methods such as glutaraldehyde and polyepoxide crosslinking treatments and dye-mediated photooxidation have been developed to stabilize the tissue while attempting to maintain its natural mechanical properties. Also, residual cellular components in a bioprosthetic material have been associated with undesired effects, such as calcification and immunological recognition, and thus have been the motivation for various decellularization processes. The effects of these stabilization and decellularization treatments on mechanical, biological and chemical properties of treated tissues have been investigated, specifically with regard to calcification, immunogenicity, and cytotoxicity concerns. Despite significant advances in the area of cardiovascular prostheses, there has yet to be developed a completely biocompatible, long-lasting implant. However, with the recent advent of tissue engineering, the possibility of applying selective cell seeding to naturally derived bioprosthetics moves us closer to a living tissue replacement.

Animals↗
PubMed2000

Assessment of airborne exposure to trihalomethanes from tap water in residential showers and baths.

This study evaluates airborne concentrations of common trihalomethane (THM) compounds in bathrooms during showering and bathing in homes supplied with chlorinated tap water. Three homes in an urban area were selected, each having three bedrooms, a full bath, and approximately 1,000 square feet of living area. THMs were concurrently measured in tap water and air in the shower/bath enclosure and the bathroom vanity area using Summa canisters. Chloroform (TCM), bromodichloromethane (BDCM), and chlorodibromomethane (CDBM) were quantified using U.S. Environmental Protection Agency (EPA) Method TO-14. Air samples were collected prior to, during, and after the water-use event for 16 shower and 7 bath events. Flow rate and temperature were measured, but not controlled. The increase in average airborne concentration (+/- standard error) during showers (expressed as microg/m3 in shower enclosure or bathroom air per microg/L in water) was 3.3+/-0.4 for TCM, 1.8+/-0.3 for BDCM, and 0.5+/-0.1 for CDBM (n = 12), and during baths was 1.2+/-0.4 for TCM, 0.59+/-0.21 for BDCM, and 0.15+/-0.05 for CDBM (n = 4). The relative contribution of each chemical to the airborne concentrations was consistent for all shower and bath events, with apparent release of TCM > BDCM > CDBM. The results are therefore consistent with their relative concentration in tap water and their vapor pressures. When the shower findings for TCM are normalized for water concentration, flow rate, shower volume, and duration, the average exposure concentrations in these urban residences are about 30% lower than those reported by other investigators using EPA analytical methods. This difference is likely attributable primarily to greater air exchange rates in residential shower/bath stalls compared to more "airtight" laboratory shower chambers. This appears to be the first field study to thoroughly evaluate THM exposures from residential showers and baths, and can be used to validate previously published models of tap water volatile chemical transfer to indoor air.

Adult↗
PubMed1999

Engineering strategies for peripheral nerve repair.

Tissue engineering in the peripheral nervous system unites efforts by physicians, engineers, and biologists toward a common goal to create either natural or synthetic tubular nerve guidance channels as alternatives to nerve autografts for the repair of peripheral nerve defects. Guidance channels help direct axons sprouting from the regenerating nerve end, provide a conduit for diffusion of neurotropic and neurotrophic factors secreted by the damaged nerve stumps, and minimize infiltration of fibrous tissue. In addition to efforts to control these physical characteristics of nerve guidance channels, researchers are optimizing the incorporation of biologic factors and engineering interactive biomaterial that can specifically stimulate the regeneration process. It is believed that current and future research will ultimately result in biologically active and interactive nerve guidance channels that can support and enhance peripheral nerve regeneration over longer, more clinically relevant defect lengths.

Animals↗
PubMed1997

Stimulation of neurite outgrowth using an electrically conducting polymer.

Damage to peripheral nerves often cannot be repaired by the juxtaposition of the severed nerve ends. Surgeons have typically used autologous nerve grafts, which have several drawbacks including the need for multiple surgical procedures and loss of function at the donor site. As an alternative, the use of nerve guidance channels to bridge the gap between severed nerve ends is being explored. In this paper, the electrically conductive polymer--oxidized polypyrrole (PP)--has been evaluated for use as a substrate to enhance nerve cell interactions in culture as a first step toward potentially using such polymers to stimulate in vivo nerve regeneration. Image analysis demonstrates that PC-12 cells and primary chicken sciatic nerve explants attached and extended neurites equally well on both PP films and tissue culture polystyrene in the absence of electrical stimulation. In contrast, PC-12 cells interacted poorly with indium tin oxide (ITO), poly(L-lactic acid) (PLA), and poly(lactic acid-co-glycolic acid) surfaces. However, PC-12 cells cultured on PP films and subjected to an electrical stimulus through the film showed a significant increase in neurite lengths compared with ones that were not subjected to electrical stimulation through the film and tissue culture polystyrene controls. The median neurite length for PC-12 cells grown on PP and subjected to an electrical stimulus was 18.14 micron (n = 5643) compared with 9.5 micron (n = 4440) for controls. Furthermore, animal implantation studies reveal that PP invokes little adverse tissue response compared with poly(lactic acid-co-glycolic acid).

Animals↗
PubMed1996

Integrin dynamics on the tail region of migrating fibroblasts.

Cell migration is a complex process that can be considered as a repeated cycle of lamellipod extension and attachment, cytoskeletal contraction, and tail detachment. While lamellipodial and cytoskeletal phenomena are currently the focus of considerable research on cell migration, under many conditions locomotion appears to be rate-limited by events at the cell rear, especially release of cell/substratum adhesions. To study the mechanism of tail detachment, we have developed a novel experimental system that permits observation of integrin dynamics on the ventral surface of migrating fibroblasts. Photoactivatable caged fluorescein is coupled to a non-adhesion-perturbing anti-avian-beta 1 integrin subunit antibody, which labels integrins on chicken fibroblasts migrating on a laminin-coated glass coverslip. Ultraviolet light is focused through a pinhole to photoactivate the caged fluorophore in a 10-micron-diameter spot at the rear of a polarized cell. The fate of integrins initially present in this spot is monitored using a cooled CCD camera to follow the movement of fluorescent intensity as a function of time over a 2 to 3 hour period. We find that a substantial fraction of the integrins is left behind on the substratum as the cell detaches and locomotes, while another fraction collects into vesicles which are transported along the cell body as the cell migrates. As aggregates rip from the cell membrane, the integrin-cytoskeletal bonds are preferentially fractured resulting in 81 +/- 15% of the integrin remaining attached to the substratum. We additionally find that adhesions sometimes disperse into integrins which can form new adhesions at other locations in the cell. Adhesions along the cell edge can release from the substrate and translocate with the cell. They either disperse in the cell membrane, rip from the cell membrane and remain attached to the substratum, or form a new aggregate. These observations indicate that the behavior of integrins at the cell rear is much more dynamic than previously appreciated, suggesting that an important locus for regulation of motility may reside in this region.

Animals↗
PubMed1995

Integrin-cytoskeletal interactions in neuronal growth cones.

Development of the nervous system requires that neuronal growth cones, in coordination with growing axons, migrate along precise paths defined by specific extracellular matrix cues until they encounter their targets. Laminin promotes growth cone migration through receptors such as the integrins, but the underlying physical mechanism is poorly understood. We have investigated the cytoskeletal associations and surface dynamics of endogenous beta 1 integrins in chick dorsal root ganglion growth cones migrating on laminin. A single-beam optical gradient trap was used to place 0.5-micron-diameter polystyrene beads conjugated with anti-beta 1 integrin monoclonal antibodies at desired locations on the growth cone surface. We found a substantial increase in the stable attachment of these beads, with subsequent slow rearward motion, on the front periphery of the growth cone compared to the base. The surface dynamics of smaller aggregates of integrin were explored by monitoring the temporal and spatial displacements of 40-nm-diameter gold particles coated with anti-beta 1 integrin antibodies. The small particles were transported preferentially to the growth cone periphery by brief directed excursions interspersed with periods of diffusion. In addition, the leading edge of the growth cone was supported to a greater extent by an actin-dependent cytoskeleton that resisted mechanical tether formation. Such a regional differentiation of the growth cone has not been documented previously and has implications for the mechanism of growth cone migration and guidance.

Animals↗
PubMed1994

Simulation of integrin-cytoskeletal interactions in migrating fibroblasts.

Cell migration is a dynamic phenomenon requiring a physical interaction between the internal cell motile machinery and the external substratum in which adhesion receptors, such as integrins, serve as the transmembrane link. To analyze quantitatively this interaction, we apply a modified Brownian dynamics algorithm to simulate cytoskeleton-mediated transport of integrin on the dorsal surfaces of migrating fibroblasts. Previously, we experimentally demonstrated that integrin is transported in an intermittent fashion, with directed excursions interspersed by diffusive periods, preferentially toward the cell edge where the integrin is likely used in the formation of nascent adhesions. Integrins containing mutations in the cytoskeleton-binding region of the cytoplasmic domain display statistically different degrees of directed transport, indicating that this phenomenon is dependent on cytoskeletal associations. In the present work, we develop a computer algorithm generating simulated integrin transport trajectories, given estimates for the rate constants defining coupling (kc) and uncoupling (ku) of integrin with cytoskeletal components. Other parameters supplied to the program, the diffusion coefficient (D) for integrin in the membrane and the instantaneous velocity (vi) of the integrin/cytoskeleton complex, have been measured independently in our experimental system. By comparing the simulated trajectories with those obtained experimentally, we are able to estimate the coupling and uncoupling rate constants for the interaction of integrin with cytoskeletal elements in vivo. We find that integrin couples with cytoskeletal elements at a rate approximately 10 times slower than its rate of uncoupling (kc = 0.3 s-1, ku = 3 s-1). Comparison of these rate constants with an equivalent rate constant for diffusion, k+ = 0.4 s-1, indicates that the coupling interaction is likely a diffusion-limited process, as is typically expected for membrane processes. We further show by calculation that directed transport is necessary for integrin to traverse the length of an extending lamellipod to its leading edge; diffusion alone is not sufficiently fast to supply adhesion receptors to points of new cell/substratum contact.

Algorithms↗
PubMed1993

Integrin-cytoskeletal interactions in migrating fibroblasts are dynamic, asymmetric, and regulated.

We have used laser optical trapping and nanometer-level motion analysis to investigate the cytoskeletal associations and surface dynamics of beta 1 integrin, a cell-substrate adhesion molecule, on the dorsal surfaces of migrating fibroblast cells. A single-beam optical gradient trap (laser tweezers) was used to restrain polystyrene beads conjugated with anti-beta 1 integrin mAbs and place them at desired locations on the cell exterior. This technique was used to demonstrate a spatial difference in integrin-cytoskeleton interactions in migrating cells. We found a distinct increase in the stable attachment of beads, and subsequent rearward flow, on the lamellipodia of locomoting cells compared with the retracting portions. Complementary to the enhanced linkage of integrin at the cell lamellipodium, the membrane was more deformable at the rear versus the front of moving cells while nonmotile cells did not exhibit this asymmetry in membrane architecture. Video microscopy and nanometer-precision tracking routines were used to study the surface dynamics of integrin on the lamellipodia of migrating cells by monitoring the displacements of colloidal gold particles coated with anti-beta 1 integrin mAbs. Small gold aggregates were rapidly transported preferentially to the leading edge of the lamellipod where they resumed diffusion restricted along the edge. This fast transport was characterized by brief periods of directed movement ("jumps") having an instantaneous velocity of 37 +/- 15 microns/min (SD), separated by periods of diffusion. In contrast, larger aggregates of gold particles and the large latex beads underwent slow, steady rearward movement (0.85 +/- 0.44 micron/min) (SD) at a rate similar to that reported for other capping events and for migration of these cells. Cell lines containing mutated beta 1 integrins were used to show that the cytoplasmic domain is essential for an asymmetry in attachment of integrin to the underlying cytoskeletal network and is also necessary for rapid, intermittent transport. However, enhanced membrane deformability at the cell rear does not require integrin-cytoskeletal interactions. We also demonstrated that posttranslational modifications of integrin could potentially play a role in these phenomena. These results suggest a scheme for the role of dynamic integrin-mediated adhesive interactions in cell migration. Integrins are transported preferentially to the cell front where they form nascent adhesions. These adhesive structures grow in size and associate with the cytoskeleton that exerts a rearward force on them. Dorsal aggregates more rearward while those on the ventral side remain fixed to the substrate allowing the cell body to move forward. Detachment of the cell rear occurs by at least two modes: (a) weakened integrin-cytoskeleton interactions, potentially mediated by local modifications of linkage proteins, which lead to weakened cell-substratum interactions and (b) ripping of integrins and the highly deformable membrane from the cell body.

3T3 Cells↗