Biomedical subjects

C Mittermayer

Publications and source records attributed to C Mittermayer.

At least 55 records · Page 3Linked to original sources

PubMed1998

Uremic medium increases cytokine-induced PAI-1 secretion by cultured endothelial cells.

The overall fibrinolytic activity is depressed in patients with chronic renal failure where a prothrombotic state is described, thereby enhancing the risk of vascular occlusive events. The mechanism responsible for fibrinolysis derangement has not yet been elucidated. To evaluate the effect of the uremic environment on the fibrinolytic activity of endothelial cells, we studied plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) production by human umbilical vein endothelial cells (HUVEC) in culture, exposed either to uremic or normal sera, before and after cytokine stimulation. Twenty uremics were studied: 11 were on conservative dietary treatment and nine were on maintenance hemodialysis. Eight healthy subjects served as controls. Before cytokine stimulation, no difference in the HUVEC supernatant concentration of t-PA and PAI-1 was found among the groups studied. After stimulation with interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, the HUVEC supernatant levels of PAI-1 in the uremics were higher than in the controls, whereas the supernatant levels of t-PA did not differ. Our data provide evidence that uremic serum, in concert with IL-1 or TNF-alpha, can enhance PAI-1 secretion by endothelial cells, thereby depressing the fibrinolytic system. This impaired endothelial fibrinolytic response to hypercoagulation could favor vascular events, which are the major cause of morbidity and mortality in patients with chronic uremia.

Adult↗

PubMed1998

Modulation of pro- and antifibrinolytic properties of human peritoneal mesothelial cells by transforming growth factor beta1 (TGF-beta1), tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta).

A decreased fibrinolytic activity of serosal surfaces appears to be a major factor in the development of peritoneal fibrous adhesions. Serosal fibrinolysis is regulated by mesothelial release of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2). We investigated the influence of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta1) and interleukin 1beta (IL-1beta) on pro- and antifibrinolytic properties of mesothelial cells (HOMC) using a cell/fibrin clot assay. TGF-beta1, TNF-alpha and IL-1beta induced a dose dependent 2.9, 2.3 and 1.9-fold increase of PAI-1 antigen, respectively, whereas t-PA concentrations decreased to one third of the control values. This modified PAI-1/t-PA secretion pattern leads to a significant delay of fibrinolysis. Analysis of m-RNA levels revealed increased PAI-1 m-RNA concentrations after 12 h and decreased m-RNA concentrations for t-PA after 6 h. Serosal hypofibrinolysis during peritonitis may be explained at least in part by cytokine effects which thus may favor adhesion formation.

Cell Adhesion↗

PubMed1997

[Reduction of cataract by plasma etching of intraocular lenses. An animal experiment study].

BACKGROUND: We studied if a modification of the silicon intraocular lens (IOL) by plasma etching is able to promote a bonding of the IOL surface and the capsular bag which might inhibit proliferation and migration of lens epithelial cells. METHODS: Silicon-disc lenses (90D, Adatomed), as disposable for regular cataract surgery, were used. Their haptic surface was etched via the use of a SO2 plasma, leaving the optic unmodified. The experiments were done on dwarf rabbits to allow for tight apposition of IOL and bag. Nine rabbits underwent extracapsular lensectomy using propofol anaesthesia and phaco/clear cornea surgical technique. Six eyes each received either no, a regular or a modified IOL. After 11 weeks the eyes were enucleated. Capsular bag and IOL were digitized using a flatbed scanner with transparency adapter. The data obtained were calibrated against a densitometric standard. The densities of the various specimen were analyzed quantitatively using self designed software. RESULTS: In aphacic eyes no significant posterior capsule opacification (PCO) was detectable. In the same time-span the regular IOL had developed a dense, heterogenous PCO. The plasma-treated IOL showed, especially in the central areas, a significant reduction of PCO as compared to untreated IOL. CONCLUSION: The reduction of PCO could not be explained by adhesion of the IOL surface and the capsular bag, which would impair migration of lens epithelial cells and thereby PCO. Likewise, lower PCO may be related to improved hydrophilic properties of the surface-modified IOL.

Animals↗

PubMed1997

Monocyte-biomaterial interaction inducing phenotypic dynamics of monocytes: a possible role of monocyte subsets in biocompatibility.

For the in vitro study of cell-biomaterial surface interactions, the choice of cell type is crucial. In vivo data indicate that during the healing of the implant in the tissues, the pivotal cell types are the macrophages. These cells, upon interaction with any foreign material, might initiate a spectrum of responses, which could lead to acute and chronic inflammatory changes affecting the biocompatibility of the implant. Whether the mechanisms governing the type of evolving inflammatory reaction could be attributed to the macrophages functional differentiation mirrored by monocyte subsets during the polymer interaction, is poorly described. This in vitro study, therefore, attempted to investigate whether different biomaterials influence monocyte cellular activity, determined by the myeloperoxidase level and mitochondrial XTT cleavage, and phenotype dynamics characterized by the presence of CD14, RM 3/1 and 27E10 antigens. It is shown that different polymers exert differential potential to influence monocytes, both in their cellular activity and their phenotypic pattern. Thus, these findings demonstrating material-induced monocyte activation and monocyte phenotype modulation, are suggestive of the monocyte role as reporter cells in evaluating the biocompatibility of a synthetic medical device.

Journal Article↗

PubMed1997

Screening of biomedical polymer biocompatibility in NMRI-mice peritoneal cavity: a comparison between ultra-high-molecular-weight polyethylene (UHMW-PE) and polyethyleneterephthalate (PET).

The peritoneal resident cell population is influenced by various inflammatory and immunogenic stimuli. The influence of intraperitoneal application of polyethyleneterephthalate (PET) (group A) and ultra-high-molecular-weight polyethylene (UHMW-PE) (group B) powders on peritoneal cell count and macrophage activity was investigated. Powders were tested to mimic wear particles from solid implant devices as these particles often cause chronic granulomatous inflammation. The results were compared with the inflammatory response following an abdominal midline incision (group C) and untreated animals (group D). On days 1, 7, 14 and 30 peritoneal cells were quantified and the number of active macrophages was assessed. Groups A and C mice showed a significant loss of macrophages in the peritoneal lavage at day 1 but this returned to normal values (group D) on day 7. In contrast, group B animals remained at low peritoneal cell counts but showed the highest number of active macrophages. Only in this latter group was adhesion formation and granulomatous clustering of polymer powder observed. Applying the parameters macrophage count and the number of active macrophages it can be concluded that PET elicits a weaker inflammatory reaction than UHMW-PE in mice peritoneal cavity. Thus this animal model may be used as a screening test for biomedical materials, especially their wear products.

Journal Article↗

PubMed1997

Induction of heat shock protein 70 by zinc-bis-(DL-hydrogenaspartate) reduces cytokine liberation, apoptosis, and mortality rate in a rat model of LD100 endotoxemia.

A prospective, randomized model of LD100/24 h endotoxemia was performed in male Wistar rats (n = 26; 250-300 g). The animals were divided into four groups: Group I (n = 5; saline treatment only), Group II (n = 5; Zn2+ treatment only), Group III (n = 8; saline pretreatment, lipopolysaccharide (LPS) treatment), and Group IV (n = 8; Zn2+ pretreatment, LPS treatment). Zn2+ pretreatment was carried out by intraperitoneal injection of 50 mg/kg zinc-bis-(DL-hydrogenaspartate) (10 mg/kg Zn2+). LD100/24 h endotoxemia was induced by intraperitoneal administration of 20 mg/kg LPS of the Escherichia coli strain WO111:B4. Tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 were detected by enzyme-linked immunosorbent assay (ELISA). HSP70 expression in the lungs, the liver, and the kidneys was determined by immunohistochemistry, Western blotting, and an HSP70 ELISA. Apoptosis was also detected by an in situ apoptosis detection kit (TUNEL) and a cell death detection ELISA, respectively. This rat model of endotoxemia proves the close relationship between HSP70 expression, cytokine liberation, and development of apoptosis. The data demonstrate that: 1) Zn2+ is a potent inducer of HSP70 expression; 2) the application of Zn2+ leads to slightly increased cytokine plasma levels; and 3) the manipulation of the heat shock response by Zn2+ significantly increases the survival rate after LD100 endotoxemia. Enhanced survival rate in animals pretreated with Zn2+ may be explained by increased tissue levels of HSP70, a subsequent significantly decreased liberation of the proinflammatory cytokines after LPS challenge, and a significantly decreased rate of apoptosis.

Animals↗

PubMed1996

Tumour-cell-endothelial interactions: free radicals are mediators of melanoma-induced endothelial cell damage.

Damage to vascular endothelium may play an important role during metastasis. We used a three-dimensional model of tumour cell extravasation to test the hypothesis that certain types of tumour cells are able to induce vascular endothelial cell injury. Multicellular tumour spheroids (MCTS) of 14 human cancer cell lines and spheroids from two benign cell lines were transferred onto confluent monolayers of human endothelial cells (EC). MCTS from 4 of 7 melanoma cell lines induced damage of the endothelium which was closely associated with tumour cell attachment. Endothelial cell injury became evident morphologically by loss of cell membrane integrity and sensitivity to shear stress. Similar results were obtained with EC derived from human umbilical veins, umbilical arteries and saphenous veins. Addition of the oxygen radical scavenger catalase showed a dose- and time-dependent inhibition (up to 48 h) of EC damage in the case of the melanoma cell lines ST-ML-11, ST-ML-14 and SK-MEL-28. The scavenging enzyme superoxide dismutase proved to be protective (up to 12 h) in ST-ML-12 MCTS. In contrast, allopurinol, deferoxamine mesylate, ibuprofen, nor-dihydroguaretic acid, soybean trypsin inhibitor or aprotinin had no protective effect. None of the non-melanoma cancer cell lines or benign cells induced endothelial cell damage. Endothelial injury has been shown to enhance the process of metastasis. Our results suggest that free-radical-mediated endothelial cell damage may be one of the mechanisms contributing to the devastating metastatic potential of melanoma.

Catalase↗

PubMed1996

Imaging surface spectroscopy for two- and three-dimensional characterization of materials.

Secondary ion mass spectrometry (SIMS) exhibits a unique potential for the measurement of two-and three-dimensional distributions of trace elements in advanced materials, which is demonstrated on relevant technological problems. One example is the characterization of high purity iron. With this material segregation experiments have been performed and the initial and final distribution of the trace elements have been measured. Another example is the investigation of the corrosion behaviour of high purity chromium. Samples oxidized with (16)O and (18)O have been measured to explain the growing and adhesion of the oxide layer. All imaging techniques generate a vast quantitiy of data. In order to extract the important information the assistance of chemometric tools is essential. Detection of chemical phases by classification using neural networks or de-noising of scanning-SIMS images by wavelet-filtering demonstrates the increase of the performance of analytical imaging techniques.

Journal Article↗

PubMed1996

Plasmatic parameters of coagulation activation in thrombotic microangiopathy.

Coagulation activation and fibrinolysis parameters were studied in eleven cases of thrombotic microangiopathy concerning eight adult patients. In addition to routine coagulation tests, antithrombin III, von Willebrand factor (vWF), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-dimer (DD), and plasminogen activator inhibitor type 1 (PAI-1) were measured in the plasma at the time of diagnosis and as soon as remission was achieved after therapy with plasma exchange and Iloprost. In the acute phase all patients showed normal aPTT, normal or slightly prolonged prothrombin time, normal or enhanced plasma levels of fibrinogen and antithrombin III, at variance with results in patients affected by disseminated intravascular coagulation. Mean F1+2, TAT, DD, vWF and PAI-1 were elevated in the acute phase, but decreased significantly in the early phase of remission. Our data provide evidence of increased thrombin generation rate which takes place in the acute phase of the disease and does not result in consumption coagulopathy, due to appropriate inhibition by antithrombin III; blood coagulation activation promptly decreased as soon as remission was achieved. Cross-linked fibrin deposition together with PAI-1 may consolidate the platelet plug, eventually resulting in microvascular occlusion and ischemia.

Adolescent↗

PubMed1996

Detection of minimal but significant amount of von Willebrand factor in human omentum mesothelial cell cultures.

The presence of von Willebrand factor (vWF) in human mesothelial cells is a controversial issue. The aim of this paper was to investigate the presence of vWF in human mesothelial cell cultures by means of multiple specific techniques and to compare the amount of vWF to that in endothelial cell cultures. Morphological evidence that vWF is present in the cell cytoplasm in human omentum mesothelial cells (HOMC) has been obtained by vWF staining by means of anti-vWF antibodies and immunofluorescence. The vWF concentration value (measured by ELISA) was 0.02 ng/mL in the supernatant of HOMC (160,000 ng/mL cells/mL after 12-48 hours) and between 0.08-0.12 ng/mL in the supernatant of endothelial cell cultures (160,000 cells/mL). Ethidium-bromide staining of PCR products recorded the typical vWF signal both in the endothelial and in the mesothelial cell cultures, although it was noticeably more intense in the endothelial cell culture. These data show that minimal but significant amounts of vWF are present in human mesothelial cell cultures.

Cell Culture Techniques↗

PubMed1996

Expression of tissue-type plasminogen activator, plasminogen activator inhibitor and von Willebrand factor in the supernatant of endothelial cell cultures in response to the seeding of adenocarcinoma cell line HRT-18.

Plasminogen activator inhibitor (PAI-1), tissue type plasminogen activator (tPA) and von Willebrand factor (vWF) concentrations were measured by ELISA in the supernatant of the following cultures: endothelial cells from human umbilical vein (HUVEC); human colon cancer cells (HRT-18); and co-culture cells of HUVEC + HRT-18. No measurable amount of the three substances was found in the supernatant of HRT-18 cell culture. Compared to the value in the HUVEC supernatant, in the UVEC/HRT-18 co-cultures, tPA concentration was significantly lower (P = 0.0047), PAI-1 significantly higher (P = 0.026) and vWF also significantly higher (P = 0.0048). These data indicate that HRT-18 tumor cells do not produce tPA, PAI-1 and vWF; however, these tumor cells induce endothelial cells to change the production of these substances. As a consequence, the interaction between tumor and endothelial cells in vivo may lead to depression of fibrinolysis and enhancement of platelet adhesion.

Adenocarcinoma↗

PubMed1995

Integrin expression on colorectal tumor cells growing as monolayers, as multicellular tumor spheroids, or in nude mice.

In this study we compared the expression of integrin alpha chains 2, 3, 4, 5, 6, v and the beta chains 1, 3, 4 in 2 colorectal carcinoma cell lines (HRT-18 and CX-2), growing in confluent and subconfluent monolayer cultures, as multicellular tumor spheroids and in nude mice, using the immunofluorescence technique (confocal microscopy) and flow cytometry. The fast-growing cell line HRT-18 expressed, in confluent and subconfluent monolayer cultures, alpha 2, 3 and beta 1 with a continuous membranous staining pattern, whereas alpha v, alpha 6, and beta 4 were expressed continuously membranous in the intermediate and apical part of the cell layer, and clustered at focal contacts at the base of the cells. In spheroids and tumors of nude mice the focal pattern of alpha v, 6 and beta 4 was changed into a diffuse one. Using flow cytometry, the expression of alpha 3 was found to be reduced in spheroids of HRT-18. The slowly-growing cell line CX-2 expressed, under the same conditions in monolayer culture, alpha 6, beta 1 and beta 4, and very weakly alpha 2, 3, 5 and v. Alpha 3 was expressed in spheroids of CX-2 only at the outer rim where the cells proliferate. In contrast, alpha 2 and 5 were expressed mainly in the quiescent, non-proliferating area. Alpha 6 was reduced in spheroids of CX-2. In the nude mouse tumor of CX-2, alpha 5 was expressed only focally and very weakly, alpha 2 was no longer detectable, but alpha v appeared to be enhanced in a focal pattern. These data indicate that integrin expression of tumor cells depends upon the culture system and that integrin expression in multicellular tumor spheroids is more similar to the in vivo situation in nude mouse tumors.

Animals↗

PubMed1995

Morphology of cardiac muscle in septic shock. Observations with a porcine septic shock model.

The morphology of cardiac muscle was investigated in a porcine model of septic shock, created by intermitted application of Escherichia coli-endotoxin. The earliest lesions, found after 18 h of septic shock, were endothelial cell swelling, marked leucostasis and slight ischaemic alterations of the muscle fibres. At the end point of the experiments, after 48 h, some fibrin thrombi were found associated with more pronounced ischaemic alterations of cardiac muscle cells and some necrotic fibres. Comparing these findings with the severe endothelial and muscle fibre lesions found in skeletal muscle, the endothelial cells of the heart microvasculature, are clearly more resistant to the attack of the endotoxins and mediators liberated in septic shock.

Animals↗

PubMed1995

[In vitro and in vivo studies of local disinfection and wound healing].

Wound healing represents a dynamic process of increasing scientific interest, especially with the detection of the different growth factors. Economic aspects are also of importance in the investigation of substances used for wound healing. In Germany 25% of all patients (ca. 1 million) with severe chronic venous insufficiency have crural ulcers. The influence of bacterial infection of crural ulcers is controversial. There is no doubt that the quantity of bacteria is of importance. Local antibiotic treatment is difficult, as most of the substances used are known to inhibit wound healing. In vivo and in vitro investigations showed, that chiniofon-containing antiseptic has a bacteriostatic function. Additionally it was shown, using cultures of fibroblasts, that chiniofon-containing antiseptic does not inhibit the growth of fibroblasts, whereas PVP-iodine solution, a widely used antiseptic, clearly reduces the growth of fibroblasts. The good clinical results in the treatment of acute and chronic radiation damage indicate that chiniofon-containing antiseptic may have antiflammatory activity.

Administration, Topical↗

PubMed1995

Multimedic system for telepathology and interdisciplinary councils between doctors and various hospitals.

At present, the exchange of information between clinicians and pathologists are limited to mail, telefax and telephone. The bi-directional video communication using at least two digitized phone lines (ISDN) is an additional medium for video-conference and for image exchange. The MECOM system (Medical Communication) has been set up in the department of pathology of Aixla-Chapelle Hospital (Germany) and has routinely used for two years between 4 local hospitals. Now it is mainly used for staff discussions between pathologists and practitioners involved in different oncological fields. Mecom can transmit any kind of high resolution images (x rays films, scanner images, histologic slides...) which are useful or necessary during medical staff discussions. This system requires only two phone lines to be operative. However it can turn on up to twelve parallel ISDN lines which allow to transmit 768 kbytes/sec. It manages the SG3, HVQ and H320 compression algorithms and allows the transmission of still images at a resolution varying from 256/240 to 512/480 pixels. Mecom is a modulable system which adapts to the needs. It has the following advantages. Emergency inter-disciplinary conferences. Real time images, discussion between a pathologist and an expert to confirm histo-pathological diagnosis. Abolition of distances. That is specially useful or necessary in countries with low medical population and poor transportation network.

Computer Communication Networks↗

PubMed1994

Skeletal muscle oedema and muscle fibre necrosis during septic shock. Observations with a porcine septic shock model.

In domestic pigs, intermitted application of Escherichia coli-endotoxin was used to create an animal model for a prolonged hypo- and hyperdynamic septic shock-like state and to investigate mechanisms of multiple organ failure. Here, we describe the changes in skeletal muscle after 18 h (2 animals) and 48 h (6 animals) of septic shock. Two pigs for each observation period that received physiologic saline solutions instead of endotoxin served as controls. The earliest lesions were endothelial cell damage with endomysial oedema and swelling of mitochondria in muscle fibres. With increasing degree of endothelial cell damage, pericytes showed degenerative changes with cytoplasmic fragmentation and karyolysis. After 48 h of shock, endomysial oedema was increased with fibrinogen present. Muscle fibre diameters were increased and swollen mitochondria and segmental necrosis of muscle fibres were frequently observed. However, phagocytic reaction or regenerative changes were not detected. In this respect, skeletal muscle lesions in septic shock differ from ischemic damage, which is characterized by early phagocytosis. Tumour necrosis factor alpha (TNF alpha) was increased greatly and significantly in the serum of the pigs that received endotoxin. The lesions described may be the result of both direct damage to muscle fibres by the endotoxin and/or the increased levels of TNF alpha and indirect damage because of the increased diffusion distance, due to the endomysial oedema. The loss of blood proteins into the endomysium may also play a role in generating hypoproteinemia in patients with septic shock.

Animals↗

PubMed1994

Association of different macrophage phenotypes with infiltrating and non-infiltrating areas of tumor-host interface in colorectal carcinoma.

At the tumor-host interface (interface) of well differentiated tubulary or tubulopapillary colorectal carcinomas infiltrative, poorly demarcated and non-infiltrative, well bordered areas alternate. The composition of the inflammatory infiltrate within the desmoplastic stroma of the central tumor part and the interface was analyzed, particularly emphasizing differences between infiltrative and non-infiltrative areas of the interface. Of particular interest was the distribution of the following recently identified, functionally different human macrophage phenotypes: the 27E10-positive phenotype, an inflammatory macrophage, the 25F9-positive phenotype, a mature, resident macrophage and the RM3/1-positive phenotype, associated with anti-inflammatory function. It was found that macrophages were the dominating cells in the inflammatory infiltrate of both central tumor part and interface and that the number of B-cells and NK-cells were negligible. The 27E10-positive phenotype revealed a strong association with infiltrative areas at the interface, whereas the resident macrophage together with the RM3/1 was associated with sharply bordered tumor areas dominating within the tumor stroma, particularly in carcinomas with marked desmoplastic stroma response. These findings suggest that different macrophage phenotypes, localized in different regions of the carcinoma, have different effects on tumor cells.

Adenoma↗

PubMed1994

Cytogenetic findings in squamous cell carcinoma of the oral cavity.

A case of squamous cell carcinoma (SCC) of the oral cavity is presented which, in addition to normal metaphases, cytogenetically displayed two cell clones with chromosomal aberrations: 46,XY,1+del(5)(q13),der(18)t(5;18)(q13;p11),-5 and 49,XY,+5,+7,+10 After a review of the literature of the few cytogenetically analyzed cases, the findings confirm the multiclonal origin of oral SCC and also the commonly seen aberrations of chromosome 5.

Aged↗