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Biomedical subjects

J Reinartz

Publications and source records attributed to J Reinartz.

At least 19 recordsLinked to original sources
PubMed2006

[Anesthesiological management of neuroendovascular interventions].

The endovascular treatment of diseases of intracranial and spinal vessels has become widely accepted in recent years. The patient is usually treated under general anesthesia and in choosing an appropriate anesthesia regimen and an optimized pre-interventional preparation, the anesthesiologist can influence the postinterventional result. The working environment in the angiography suite should address the requirements of a routine procedure and the necessities of complication management. Application of short-acting narcotics and relaxation of the patient if required, facilitate the intervention for both the neuroradiologist and the anesthesiologist. The patient should be supplied with everything needed before the intervention to avoid any waste of time in the case of an emergency (e.g., haemorrhage or fibrinolytic treatment). After the procedure the patient has to be monitored for at least 24 h. Peri-interventional and postinterventional complications, such as thrombo-embolism or hemorrhage, must be managed aggressively and consequently by the anesthesist to improve the postinterventional outcome. Therefore a close collaboration between the anesthesiologist and the neuroradiologist is essential.

Anesthesia↗
PubMed2006

[Endovascular occlusion of the basilar artery for the treatment of dissecting and dysplastic fusiform aneurysms].

Dissecting aneurysms of the basilar artery trunk frequently affect young adults. Fusiform shape and narrowing of the proximal parent artery are typical features. Changes in aneurysm size and geometry may be observed more rapidly than in atherosclerotic or dysplastic aneurysms. Dissecting aneurysms carry a significant risk of rupture. Thrombotic or embolic occlusion of small pontine branches may cause ischemic symptoms. Sufficiently large aneurysms compress the adjacent brainstem. The operative treatment of these aneurysms is associated with unacceptable risks. At least one posterior communicating artery with normal calibre together with the ipsilateral P1 segment needs to provide adequate collateral flow to the upper basilar artery to allow endovascular coil occlusion of the segment that is affected by the dissection and/or fusiform aneurysmal dilatation. Four illustrative cases of endovascular coil occlusion of the basilar artery for the treatment of fusiform aneurysms are presented and discussed.

Adult↗
PubMed2006

Endovascular treatment of small intracranial aneurysms: three alternatives to coil occlusion.

INTRODUCTION: Small intracranial aneurysms with a fundus diameter of 2 - 3 mm may rupture and are therefore potential targets for an endovascular approach in treatment. Currently available coil technology is less than optimal for the treatment of aneurysms within this size range. Even the smallest coils are sometimes too large. If such a minute coil can be introduced into a small aneurysm, the hemodynamic effect and the induced thrombosis are frequently inadequate to occlude the aneurysm sufficiently from the parent artery circulation. METHODS: Three technical alternatives for the endovascular treatment of small intracranial aneurysms not suitable for coil occlusion are illustrated with the following three case descriptions. RESULTS: Stent grafts are usable for the intracranial internal carotid artery and for the V4 segment. The stiffness of the stent and the high expansion pressures are the two major drawbacks. Coaxial deployment of two or more self-expanding porous stents can result in sufficient redirection of the blood flow to induce aneurysmal thrombosis. Deployment of multiple stents, however, may require several treatment sessions in order to allow for the integration of the stents into the vessel wall from session to session. A regular microcatheter can block aneurysmal inflow in aneurysms with a very narrow neck. This allows the occlusion of the aneurysm with an appropriate amount of highly concentrated, rapidly polymerizing glue. Polymer emboli may result from excessive or rapid glue injection. CONCLUSION: The available coil technology has inherent limitations in the treatment of very small intracranial aneurysms. Liquid embolic agents and stent-based extrasaccular treatment strategies may provide solutions for these challenging lesions.

Adult↗
PubMed2005

Treatment of intracranial atherosclerotic stenoses with balloon dilatation and self-expanding stent deployment (WingSpan).

The endovascular treatment of atherosclerotic intracranial arterial stenoses has previously been based on balloon dilatation or the deployment of a balloon expandable stent. Both methods have advantages (balloon: flexibility; balloon expandable stent: high radial force) and drawbacks (balloon: risk of elastic recoil and dissection; balloon expandable stent: limited flexibility, risk of injury to the vessel due to excessive straightening, overexpansion at ends of stent). A new combination of balloon dilatation, followed by the deployment of a self-expanding microstent has been applied in 15 patients with atherosclerotic arterial stenoses, symptomatic despite medical treatment. An anatomically and clinically adequate result was achieved in all patients. The initial degree of stenosis was 72% (mean). Balloon dilatation resulted in an average residual stenosis of 54% (mean), reduced further to a mean of 38% after stent deployment. Arterial dissection, occlusion of the target artery or symptomatic distal emboli was not encountered. In one patient, a side branch occlusion occurred after dilatation of a M1 stenosis, with complete neurological recovery. All patients were either stable or improved 4 weeks after the treatment. Recurrent TIA did not occur in any patient. Balloon dilatation and subsequent deployment of a self-expandable stent for the treatment of symptomatic intracranial arterial stenoses combines the advantages of both techniques and allows a rapid, clinically effective and technically safe treatment of these frequently challenging lesions.

Aged↗
PubMed2001

Molecular and functional characterization of the four-transmembrane molecule l6 in epidermal keratinocytes.

In normal human epidermal keratinocytes (NHEK) proteolytic detachment from the substrate induces a complex activation cascade including expression of new proteins, morphological alterations, and the onset of migration for epidermal regeneration. By subtractive cloning we have shown that L6, a four-transmembrane protein, is newly expressed after proteolytic keratinocyte detachment. In this study, we have generated a novel anti-L6 antibody (clone HD-pKe#104-1.1) and investigated L6 expression regulation in vitro and in vivo as well as L6 function in keratinocyte migration. Dispase-mediated detachment induced L6 expression in NHEK at the mRNA and protein level. Immunohistology of skin biopsies displayed a strong expression of L6 in follicular epidermis and epidermolytic lesions of autoimmune bullous dermatoses (bullous pemphigoid, pemphigus vulgaris), but not in normal interfollicular epidermis. In contrast to normal keratinocytes, HaCaT cells showed constitutive L6 expression, indicating a constitutively active phenotype. After artificial wounding of confluent HaCaT cultures, anti-L6 antibody strongly impaired cell migration velocity and migratory reepithelization of the defect, indicating L6 involvement in keratinocyte migration. These findings suggest that L6 is an important activation-dependent regulator of keratinocyte function and epidermal tissue regeneration.

Antibodies, Monoclonal↗
PubMed2000

Immunohistochemical and molecular characterization of cultured keratinocytes after dispase-mediated detachment from the growth substratum.

Keratinocyte activation comprises changes in protein and gene expression pattern resulting in phenotypic and functional changes necessary for re-epithelialization such as the expression of urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPA-R; CD87). As uPA and uPA-R are rapidly induced after dispase-mediated detachment of cultured normal human epidermal keratinocytes (NHEK) we hypothesized that dispase-mediated detachment may cause a similar "activation" of keratinocytes with uPA and uPA-R being only one aspect of a complex "activation reaction". To test this hypothesis we have comparatively analysed adherent versus detached keratinocyte sheets for selected indicators of keratinocyte activation by immunohistochemistry. Furthermore we have identified genes via subtraction cloning which are up-regulated upon dispase-induced detachment. The analyses provided evidence for an increased transcriptional and translational activity in detached keratinocytes, as indicated by over-expression of several ribosomal components (L3 and S10 ribosomal protein) and transcription factors (initiation factor 4A, elongation factor 1alpha). Increased proliferative activity was indicated by increased expression of the proliferation markers Ki67, keratin 6 and keratin 17. Finally, several markers of keratinocyte activation such as the integrin chain alpha(v), psoriasin, glutathion-S-transferase and heparin-binding epidermal growth factor-like growth factor were up-regulated. Furthermore mevalonate kinase, a molecule as yet unknown to be expressed in keratinocytes, was identified. The findings provide evidence that dispase-mediated detachment in cultured keratinocytes induces a reaction, which comprises the up-regulation of a complex array of proliferation- and migration-related molecules. The pattern of which resembles the activation reaction observed in the re-epithelializing keratinocytes in vivo.

Biomarkers↗
PubMed1996

Dispase-mediated basal detachment of cultured keratinocytes induces urokinase-type plasminogen activator (uPA) and its receptor (uPA-R, CD87).

Keratinocytes synthesize and secrete urokinase-type plasminogen activator (uPA), which is bound in an autocrine manner to a specific receptor (uPA-R, CD87) at their surface. Plasminogen, which is also bound to membrane binding sites, is readily activated by uPA-R-bound uPA. Thus, plasmin for proteolysis of pericullular glycoproteins is provided. While uPA-R and uPA are at low to undetectable levels in keratinocytes of the normal epidermis, both compounds are upregulated in migrating keratinocytes during reepithelialization of epidermal defects and in affected keratinocytes of various epidermal disorders, including bullous dermatoses. We have hypothesized that the disturbance of cell/matrix interactions--a common feature of these diverse pathological situations--induces uPA/uPA-R. Accordingly, we explored whether the dispase-mediated detachment of cultured keratinocytes, which have formed a multilayered epidermis-like structure in vitro, induced uPA and uPA-R. We found increases in uPA secretion, cell-associated uPA activity, and uPA- and uPA-R-antigen in keratinocytes upon dispase-mediated detachment from their growth substratum. The increase was preceded by an increase in uPA-R- and uPA-specific mRNA, which was not observed when the proteinase inhibitor phosphoramidon was added together with dispase. In conclusion, we present evidence that experimental detachment with dispase provides signals for the concomitant upregulation of uPA-R and uPA. The findings support the hypothesis that cell/matrix interactions may influence the expression of the cell surface-associated PA system in human keratinocytes.

Cell Adhesion↗
PubMed1996

Tumor necrosis factor-alpha-induced apoptosis in a human keratinocyte cell line (HaCaT) is counteracted by transforming growth factor-alpha.

The integrity of the human epidermis is guaranteed by a regulated balance of proliferation, differentiation, and physiologic cell death of its main cellular constituent, the epidermal keratinocyte. Physiologic cell death is known as apoptosis and has been recognized as an active regulatory mechanism, complementary to, but functionally opposite of, proliferation. The regulators of the delicate balance between cell death and proliferation are only partially understood in human keratinocytes. Transforming growth factor-alpha (TGF-alpha) has been identified as a positive regulator of proliferation and growth, while tumor necrosis factor-alpha (TNF-alpha) induces apoptosis. Both mediators are thought to influence epidermal keratinocytes under various physiological and pathophysiological conditions. In the current study we have begun to investigate potential regulatory interactions between these two mediators in the human keratinocyte cell line HaCaT. We have found that, when the HaCaT cells were sensitized by the translation inhibitor cycloheximide, TNF-alpha induced apoptosis, as evidenced by nuclear disintegration, DNA fragmentation ("DNA laddering"), and the appearance of soluble DNA/histone complexes. Moreover, we found that the induction of apoptosis was reduced by preincubation of the cells with TGF-alpha. The protective effect of TGF-alpha was abrogated by translation inhibition, indicating that it depended on de novo protein synthesis. Moreover, the protective effect was not accompanied by a reduced surface expression of TNF receptor molecules. We postulate that TNF-alpha-induced apoptosis in HaCaT cells is counteracted by constitutively produced suppressors of apoptosis, the synthesis of which can be downregulated by inhibition of translation and upregulated by the cytokine TGF-alpha.

Apoptosis↗
PubMed1996

Upregulation of cell-surface-associated plasminogen activation in cultured keratinocytes by interleukin-1 beta and tumor necrosis factor-alpha.

Keratinocytes synthesize and secrete urokinase-type plasminogen activator (uPA) which is bound in an autocrine manner to a specific receptor (uPA-R) at the keratinocyte surface. Plasminogen that is also bound to specific membrane binding sites is readily activated by uPA-R-bound uPA. Thus, plasmin is provided for proteolysis of pericellular glycoproteins. The expression of uPA and the uPA-R is confined to migrating keratinocytes during epidermal wound healing, rather than to keratinocytes of the normal epidermis. The regulatory factors of uPA/uPA-R expression in keratinocytes remained largely elusive. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta), are present in epidermal wounds. We have therefore tested IL-1 beta and TNF-alpha for their influence on surface-associated plasminogen activation in a human keratinocyte cell line (HaCaT) as well as in primary cultures of normal human epidermal keratinocytes. Both cytokines induced the secretion of uPA into the culture supernatants and a concomitant increase in uPA activity as well as in uPA and uPA-R antigen at the cell surface. The increase was preceded by an increase in specific mRNA. The induction was accompanied by an accelerated uPA-dependent and plasmin-mediated detachment of HaCaT cells from the culture substratum. Taken together, the proinflammatory cytokines IL-1 beta and TNF-alpha induced a coordinated increase in uPA and uPA-R as well as increased pericellular plasmin-mediated proteolysis in human epidermal keratinocytes. This function might be an element of the molecular cell biological events during epidermal wound healing.

Cell Adhesion↗
PubMed1996

Plasminogen activator inhibitor type-2 (PAI-2) in human keratinocytes regulates pericellular urokinase-type plasminogen activator.

Plasminogen activation is observed in the human epidermis during reepithelialization of epidermal defects and under certain pathological conditions. The activation reaction depends on keratinocyte-associated plasminogen activators (PAs), which convert the ubiquitous proenzyme plasminogen into the active trypsin-like serine proteinase plasmin. The PAs are controlled by PA inhibitors (PAIs), of which two major types are known: PAI-1 and PAI-2. In vitro and in vivo keratinocytes express both PAIs. In the current study, we have addressed the possible function of PAI-2 in regulating extracellular PA activity in cultured normal human epidermal keratinocytes (NHEK), the human keratinocyte cell line (HaCaT), and a Ha-ras transfected HaCaT variant (HaRas). PAI-2 was detected intracellularly in all three cell types. Whereas only the NHEK and the HaCaT cells secreted detectable levels of PAI-2 into the culture medium, all three cell types released urokinase-type PA (uPA) into the supernatants. When comparing HaCaT and HaRas cells, we found that the cell lines secreted comparable levels of uPA antigen, whereas the levels of uPA activity were low in the presence of PAI-2, indicating that PAI-2 serves to regulate uPA activity. This assumption was supported by the findings that PAI-2 formed complexes with secreted uPA and that uPA/PAI-2 complexes were present at the surface of the PAI-2-secreting HaCaT cells but not at the surface of PAI-2 nonsecreting HaRas cells. Finally, PAI-2 was found to counteract the uPA-dependent and plasmin-mediated detachment of cultured HaCaT cells. Taken together, our findings indicate that secreted PAI-2 serves to regulate the activity of extracellular uPA in keratinocytes.

Aprotinin↗
PubMed1996

Interleukin-1 beta upregulates tissue-type plasminogen activator in a keratinocyte cell line (HaCaT).

Human keratinocytes synthesize and secrete tissue-type plasminogen activator (tPA). tPA converts the inactive precursor enzyme plasminogen into the trypsin-like proteinase plasmin. tPA is not found in normal epidermis, but in lesional epidermis from patients with a variety of cutaneous diseases, including psoriasis, pemphigus and pemphigoid. The presence of tPA is probably a reaction to the disease process rather than the initiating event in these etiologically and histopathologically diverse lesions. However, the factor(s) that upregulate tPA expression and secretion in keratinocytes have remained largely elusive. We sought to determine whether the inflammatory cytokine interleukin-1 beta (IL-1 beta), which is commonly present in diverse epidermal lesions, influences tPA production. Accordingly, we studied the influence of IL-1 beta on secretion of tPA by cells of the human keratinocyte cell line HaCaT. We found that IL-1 beta increased tPA secretion in these cells. Given the observation that IL-1 beta is a common proinflammatory mediator in cutaneous diseases, our findings may explain the increase in tPA in clinically and etiologically diverse inflammatory epidermal lesions.

Cell Division↗
PubMed1995

Complement component C7 is a plasminogen-binding protein.

Ab deposition, whether by reaction with the specific Ag or by preformed immune complexes, is followed by activation and deposition of complement components. Tissue destruction is observed in the Ab- and complement-induced lesions. The proteolytic enzyme plasmin is thought to participate in the Ab- and complement-mediated organ pathology. Plasmin is generated from plasma-derived plasminogen by cell-derived plasminogen activators (PAs). Two types of PAs are known, urokinase-type PA (uPA) and tissue-type PA (tPA). We investigated whether the PA system and the complement system can interact to promote local plasmin generation. Among the terminal complement components C5b6, C7, C8, and C9, the nonenzymatic component C7 is a plasminogen-binding protein. Radioligand binding studies revealed that the isolated component, as well as C7 after its incorporation into the terminal complement complex C5b-9, can bind plasminogen. Binding was inhibited by the lysine analogues 6-aminohexanoic acid and tranexamic acid, implicating the lysine binding sites of plasminogen into the binding interaction. tPA-mediated plasminogen activation was enhanced in the presence of C7. Based on these findings, an interaction is proposed between the complement system and the plasminogen activator system; a mechanism that may focus plasmin activity to structures that have been tagged by Ab and complement deposition.

Autoradiography↗
PubMed1995

Plasmin abrogates alpha v beta 5-mediated adhesion of a human keratinocyte cell line (HaCaT) to vitronectin.

At cellular surfaces, urokinase-type plasminogen activator (uPA) is bound to a specific receptor (uPA-R). When bound to this receptor, uPA activates plasminogen, which is derived from plasma or the interstitial fluids. Thus, plasmin is provided for proteolysis of pericellular proteinaceous substrates. Here we demonstrate by immunocytology and laser scan microscopy that in the human keratinocyte cell line HaCaT uPA-R and uPA are localized together with the integrin alpha v beta 5 in focal contacts. Via the integrin alpha v beta 5, HaCaT cells adhere to vitronectin in a RGD-dependent manner. Plasmin interfered with the alpha v beta 5-mediated keratinocyte adhesion to vitronectin, most likely via cleavage of vitronectin and destruction of its cell binding function. Our findings demonstrate that plasmin, when generated by the uPA-dependent cell surface-associated pathway of plasminogen activation, can abrogate the cell-binding function of vitronectin and can thus disturb the adhesive interaction with this matrix molecule. In focal contacts molecules are assembled that are crucial for adhesion to vitronectin (i.e., the integrin alpha v beta 5), as well as for the generation of plasmin (i.e., uPA-R and uPA), which can negatively influence the binding interaction. We suggest that the plasmin-mediated abrogation of the interaction between the integrin alpha v beta 5 and vitronectin is a pathway of negative regulation; the codistribution of uPA-R/uPA and alpha v beta 5 in focal contacts may restrict this process to areas of cell/matrix contact.

Amino Acid Sequence↗
PubMed1995

tPA of human keratinocytes: contribution to cell surface-associated plasminogen activation and upregulation by retinoic acid.

We tested distinct variants of a human keratinocyte line (HaCaT) for the expression of tissue-type plasminogen activator (tPA)-specific mRNA, as well as cell surface-associated and secreted tPA. Cells of early passages (passage no. 22) only expressed urokinase plasminogen activator (uPA)- but not tPA-specific mRNA. Cells after prolonged culture (passage no. 44) expressed uPA- and tPA-specific mRNA, but did not release tPA in the extracellular space and did not display surface-associated tPA. HaCaT cells transformed with the c-Ha-ras oncogene (HaCaTras) showed both secreted and surface-associated tPA antigen. The secreted and the surface-associated plasminogen activator (PA)-activity of HaCaTras cells were in part inhibitable by anticatalytic anti-tPA antibodies, thus indicating that tPA contributes to extracellular and surface-associated plasminogen activation. Finally, we demonstrate that tPA secretion of HaCaT 44 cells can be induced by retinoic acid, most likely via interaction of retinoic acid with nuclear-associated retinoic acid-receptor(s).

Base Sequence↗
PubMed1995

Cervical vertebral strain measurements under axial and eccentric loading.

The mid to lower cervical spine is a common site for compression related injury. In the present study, we determined the patterns of localized strain distribution in the anterior aspect of the vertebral body and in the lateral masses of lower cervical three-segment units. Miniature strain gages were mounted to human cadaveric vertebrae. Each preparation was line-loaded using a knife-edge oriented in the coronal plane that was moved incrementally from anterior to posterior to induce compression-flexion or compression-extension loading. Uniform compressive loading and failure runs were also conducted. Failure tests indicated strain shifting to "restabilize" the preparation after failure of a component. Under these various compressive loading vectors, the location which resulted in the least amount of deformation for a given force application (i.e., stiffest axis) was quantified to be in the region between 0.5- 1.0 cm anterior to the posterior longitudinal ligament. The location in which line-loading produced no rotation (i.e., balance point) was in this region; it was also close to where the vertebral body strains change from compressive to tensile. Strain values from line loading in this region produced similar strains as recorded under uniform compressive loading, and this was also the region of minimum strain. The region of minimum strain was also more pronounced under higher magnitudes of loading, suggesting that as the maximum load carrying capacity is reached the stiffest axis becomes more well defined.

Aged↗
PubMed1995

Plasminogen activation by human keratinocytes: molecular pathways and cell-biological consequences.

Keratinocytes are the major cellular constituent of stratified epithelia. Defects in these epithelia are re-epithelialized by keratinocytes migrating from the edge of the defect into the wound. The cells form a monolayer with subsequent differentiation into a multilayered epithelium. It is thought that plasminogen activation by migrating keratinocytes is an important event during re-epithelialization. In the present report we summarize the studies on plasminogen activation by human keratinocytes in vitro and in vivo. Under the aspect of pericellular proteolysis the discussion is focused on the molecular mechanisms of plasminogen activation at the keratinocyte surface and on the cell-biological consequences of pericellular plasmin formation. We describe a cell surface-associated pathway of plasminogen activation which crucially depends on cell surface receptors for (pro)-uPA and plasmin(ogen). uPA bound to its receptor converts cell-bound plasminogen into the active protease plasmin. Compared to plasminogen activation in solution, activation at the keratinocyte cell surface is accelerated by a factor of approx. 7-10, and the plasmin generated and bound at the cell surface is protected against its specific inhibitor alpha 2-antiplasmin. Plasmin thus provided in the pericellular space leads to detachment of cultured keratinocytes from the growth substratum. Plasmin interferes with the adhesion of keratinocytes to fibrin, but not with the adhesion to collagen type I. By demonstrating that keratinocytes of the epithelial outgrowth in healing skin wounds express uPA and the uPA-R and that plasmin(ogen) is colocalized with uPA and/or uPA-R, indirect evidence is provided that this pathway may be operative in vivo. In view of previous findings that plasminogen activation is also observed under certain pathologic conditions in the epidermis, we conclude that plasminogen activation by keratinocytes is rather related to tissue damage and subsequent repair mechanisms than to a specific pathologic situation.

Fibrinolysin↗