Scientific Publications of Eike G. Fischer

https://orcid.org/0000-0003-2033-2347

Clinical Research :

• Coronary artery bypass grafting supported with intracardiac microaxial pumps versus normothermic cardio pulmonary bypass: a prospective randomized trial.
  Meyns B, Autschbach R, Böning A, Konertz W, Matschke K, Schöndube F, Wiebe K, Fischer EG (2002)
  Europ.J.Cardio-thoracic Surgery 22,1:112-117   [Bart Meyns et al.] [PMID] [DOI]
      [Abstract]
  -Objective-: To analyze the difference in coronary artery bypass grafting (CABG) performed with normothermic cardiopulmonary bypass (CPB) and CABG supported with the intracardiac microaxial pump (ICP, Impella, Aachen, Germany). -Methods-: A prospective randomized study was conducted in seven centers. The study population consists of 199 patients undergoing isolated primary CABG (CPB group 94 patients, ICP group 105 patients). Both groups are equal in demographic variables, number of bypasses performed, and Euroscore predicted mortality. We analyzed clinical outcome, myocardial enzymes and blood parameters of hemolysis, organ function and inflammatory response. -Results-: Seventeen patients (16%), randomized in the ICP group, were switched to the CPB group. This was due to the inability to position the right side catheter adequately (n=8), to a pump failure (n=1) or to the perioperative decision that beating heart surgery is technically not possible (n=8). There was no significant difference between the two study arms regarding the pump assistance time (CPB 67.1 ± 22.9 min; ICP 67.7 ± 30.3 min; P=0.88861), the number of grafts (CPB 2.4 ± 0.7; ICP 2.3 ± 0.8) and the number of grafts to the back wall (CFX; both groups n=37). There is no significant difference in clinical outcome, evolution of myocardial enzymes, indices of organ function and hemolysis. There is a reduced inflammatory response in the ICP group as indicated in the postoperative release of granulocyte elastase (CPB 259 ± 195; ICP 150 ± 126 µg/l; P<0.00001) and complement C3 (CPB 0.73 ± 0.2; ICP 0.65 ± 0.2 g/l; P=0.008). -Conclusion-: The intracardiac pump for the right heart is difficult to introduce. As a consequence the right side pump underwent design modifications. There were no differences in clinical outcome between both groups. The inflammatory response is significantly reduced in the ICP group.
• Collection of WBC-reduced single-donor PLT concentrates with the new blood cell separator: results of a multicentre study.
  [Coleta de concentrados plaquetários de doador único com reduzido teor de leucócitos com um novo separador de células sanguíneas: resultados de um estudo multicêntrico.]
  Moog R, Zeiler T, Heuft HG, Stephan B, Fischer EG, Kretschmer V, Rödel-Spieker R, Strasser E, Zingsem J (2003)
  Transfusion 43,8:1107-1114 + Corrections: 43,10:1502  
  [PMID] [DOI]
      [Abstract]
  -BACKGROUND-: A new cell separator (COM.TEC, Fresenius) was recently developed aimed at efficient collection of WBC-reduced single-donor PLT concentrates (SDPs). -STUDY DESIGN AND METHODS-: Five German centers collected 554 WBC-reduced SDPs with help of the COM.TEC cell separator. Two multicenter cell counting studies were performed at the beginning and at the end of the study to document uniform counting results among the participating centers. -RESULTS-: A total of 441 (79.6%) PLT collections were included in the study according to the protocol. A total of 342 single-dose and 99 double-dose SDPs were collected. For single-dose SDPs, an average blood volume of 2826 ± 409 mL was processed in a donation time of 55 ± 11 minutes. Mean PLT yield of these products was 3.11 x 10¹¹ ± 0.40 x 10¹¹ and the WBC contamination was 0.11 x 10⁶ ± 0.20 x 10⁶. For double-dose SDPs (PLT count, 5.29 ± 0.93 x 10¹¹), 3943 ± 639 mL was processed. The average difference between the target and the collected PLT concentration was -2.8 ± 12.0 percent for single-dose SDPs and -1.8 ± 9.5 for double-dose SDPs, respectively. The collection efficiency was 53.7 ± 5.8 percent for single-dose SDPs and 58.2 ± 6.2 percent for double-dose SDPs. If all results of each sample from the counting study were set to unity (to the mean over all centers), most PLT determinations were very similar to the mean, for example, near or 1 if set to unity. -CONCLUSION-: The COM.TEC machine makes it possible to obtain WBC-reduced SDPs that comply with current standards.
  -
  -ANTECEDENTES-: Um novo separador de células (COM.TEC, Fresenius) foi recentemente desenvolvido com vistas à coleta eficiente de concentrados plaquetários de doador único (CPDUs).com reduzido teor de leucócitos. -DELINEAMENTO E MÉTODOS DO ESTUDO-: Cinco centros alemães coletaram 554 CPDUs com reduzido teor de leucócitos com o auxílio do separador de células COM.TEC. Dois estudos multicêntricos de contagem de células foram realizados no início e no final do estudo para documentar os resultados de contagem uniformes entre os centros participantes. -RESULTADOS-: Um total de 441 (79,6%) coletas de plaquetas foi incluído no estudo de acordo com o protocolo. Um total de 342 CPDUs de dose única e 99 de dose dupla foi coletado. Para os CPDUs de dose única, um volume de sangue médio de 2826 ± 409 ml foi processado em um tempo de doação de 55 ± 11 minutos. O rendimento médio de plaquetas desses produtos foi 3,11 x 10¹¹ ± 0,40 x 10¹¹ e a contaminação por leucócitos foi de 0,11 x 10⁶ ± 0,20 x 10⁶. Para os CPDUs de dose dupla (contagem plaquetária, 5,29 ± 0,93 x 10¹¹), 3943 ± 639 ml foram processados. A diferença media entre a concentração de plaquetas alvo e a coletada foi de –2,8 ± 12,0 % para os CPDUs de dose única e –1,8 ± 9,5 para os CPDUs de dose dupla, respectivamente. A eficiência da coleta foi de 53,7 ± 5,8 % para os CPDUs de dose única e 58,2 ± 6,2% para os CPDUs de dose dupla. Se todos os resultados de cada amostra do estudo de contagem fossem ajustados para a unidade (para a média de todos os centros) a maior parte das determinações de plaquetas seria muito similar à média, por exemplo, próximo de 1, ou 1 se ajustada para a unidade. -CONCLUSÃO-: A máquina COM.TEC torna possível obter CPDUs com reduzido teor de leucócitos que atendem aos padrões correntes.
• Evaluation of the COM.TEC cell separator in predicting the yield of harvested CD34+ cells.
  Movassaghi K, Jaque G, Schmitt-Thomssen A, Fischer EG, Paulus M, Heuft HG, Schwella N (2007)
  Transfusion 47,5:824-831 [PMID] [DOI]
      [Abstract]
  -BACKGROUND-: This multicenter study was performed with the intention to evaluate the exactness of the predicted CD34+ cell yield calculated by two leukapheresis programs of the cell separator COM.TEC upon the number of donor's circulating CD34+ cells and the blood volume processed. -STUDY DESIGN AND METHODS-: Patients and healthy donors (n = 166) received mobilization by chemotherapy and/or granulocyte colony-stimulating factor and underwent CD34+ cell harvest by the leukapheresis programs MNC or RV-PBSC (n = 203). RESULTS: CD34+ cells were collected by 112 harvests on MNC and by 91 collections on RV-PBSC. The median collection efficiency of CD34+ cells was significantly better for the program MNC than for RV-PBSC (p < 0.001): 67% (31-109) vs. 42% (19-100). The collected CD34+ cell yield was in median more exactly by MNC than by RV-PBSC (p < 0.001): 85% (31-176) vs. 59% (22-110) of the predicted value. Concentrates obtained by RV-PBSC showed in median significantly higher percentages of mononuclear cells (p < 0.001) and CD34+ cells (p < 0.001), 86% (43-99) vs. 56% (25-95) and 1.2% (0.2-14.3) vs. 0.4% (0.1-6.0), and had lower contaminations by erythrocytes (p < 0.001) and platelets (p < 0.001), 13 mL (4-48) vs. 25 mL (5-60) and 1.9 x 10¹¹ vs. 3.1 x 10¹¹, than those harvested by MNC. CONCLUSION: The significantly better collection efficiency of CD34+ cells and the more exact prediction of the harvested CD34+ cell yield make the leukapheresis program MNC a safe and efficient procedure. However, concentrates collected by RV-PBSC are of a better cellular quality with a significantly higher percentage of mononuclear and CD34+ cells and a lower contamination by erythrocytes and platelets.
• Donor safety in triple plateletpheresis: results from the German and Austrian Plateletpheresis Study Group multicenter trial.
  Heuft HG, Moog R, Fischer EG, Zingsem J; German and Austrian Plateletpheresis Study Group (2013)
  Transfusion 53,1:211-220   [Hans-Gert Heuft et al.] [PMID] [DOI]
      [Abstract]
  -BACKGROUND-: The objective was to investigate potential risks for apheresis donors associated with a triple-plateletpheresis (TP) program.
  -STUDY DESIGN AND METHODS-: Eleven hemapheresis centers randomly assigned 411 repeat donors (ratio, 1:1.2) to either double plateletpheresis (DP; 185 donors) or TP (226 donors) with a platelet (PLT) target content of at least 5.0 × 10¹¹ PLTs/DP and at least 7.5 × 10¹¹ PLTs/TP. The primary endpoint was procedure-related postapheresis PLT count of at least 150 × 10⁹ /L (probability, ≥98%). Secondary endpoints were apheresis characteristics and donor adverse reactions.
  -RESULTS-: In 6 of 1133 DPs (0.5%) in 4 of 185 donors (2.2%) and in 20 of 1020 TPs (2.0%) in 14 of 226 donors (6.2%), postapheresis PLT counts were below 150 × ⁹/L. There were marginal but significant differences in collection efficiency (DP, 69.2 ± 9.1%; TP, 70.9 ± 9.0%; p ≤ 0.0001) and collection rate (DP, 10.4 × 10⁹ ± 2.3 × 10⁹ PLTs/min; TP, 10.8 × 10⁹ ± 2.3 × 10⁹ PLTs/min; p ≤ 0.005). The PLT yields were 5.9 × 10¹¹ ± 0.8 × 10¹¹ PLTs for DP and 8.3 × 10¹¹ ± 0.9 × 10¹¹ PLT for TP (p ≤ 0.0001) at processing times of 59 ± 13 minutes (DP) versus 80 ± 16 minutes (TP; p ≤ 0.0001). Significant PLT recruitment (1.10 ± 0.14 vs. 1.20 ± 0.23; p < 0.0001) was seen for both DP and TP. DP and TP did not differ with regard to venous access problems (VAPs) without discontinuation (3.8% for both), but DP induced fewer VAPs with discontinuation (1.1% vs. 3.0%; p < 0.01). Mild citrate toxicity (1.7% vs. 3.9%; p < 0.01) and circulatory reactions (0.4% vs. 2.2%; p < 0.01) were more often noticed in TP, but caused no increase in discontinuations.
  -CONCLUSIONS-: TP results in an increase in mild donor reactions but does not significantly impair donor safety or product quality.
• Donor safety in haemapheresis: Development of an Internet-based registry for comprehensive assessment of adverse events from healthy donors.
  Heuft HG, Fischer EG, Weingand T, Burkhard T, Leitner L, Baume H, Schmidt J, Buser A, Fauchald G, Reinicke Voigt U, Mansouri-Taleghani B, for the Haemapheresis Vigilance Working Party of the German Society for Transfusion Medicine and Immunohaematology (2017)
  Transfus. Med. Hemother. 44(3):188-200   [Hans-Gert Heuft et al.] [PMID] [PMC] [DOI]
      [Abstract]
  BACKGROUND: Currently, there is an extensive but highly inconsistent body of literature regarding donor adverse events (AE) in haemapheresis. As the reports diverge with respect to types and grading of AE, to apheresis procedures and machines. the range of haemapheresis-related AE varies widely from about 0.03% to 6.6%. MATERIAL AND METHODS: The German Society for Transfusion Medicine and Immunohaematology (DGTI) formed a “Haemapheresis Vigilance Working Party” (Arbeitsgemeinschaft Hämapheresevigilanz, AGHV) to create an on-line registry for comprehensive and comparable AE assessment with all available apheresis devices in all types of preparative haemapheresis: plasmapheresis (PLS), plateletpheresis (PLT), red blood cell apheresis, all kind of leukaphereses (autologous/allogeneic blood stem cell apheresis , granulocyte apheresis, lymphocyte/monocyte apheresis) and all possible types of multicomponent apheresis. To ensure the comparability of the data, the AGHV adopted the “Standard for Surveillance of Complications Related to Blood Donation” from the International Society for Blood Transfusion in cooperation with the International Haemovigilance Network and the American Association of Blood Banks for AE acquisition and automated evaluation. The registry is embedded in a prospective observational multi-centre study including 20 study centres with a study period of 5 years. RESULTS: A preliminary evaluation encompassed the time period from January, 2012 to December, 2015. During this time the system proved to be safe ad stable. Out of approximately 345.000 haemaphereses 16.477 AE were reported (4.9%). The majority of AE occurred in PLS at 63%, followed by PLT at 34.5% and SC at 2.2%. Blood access problems (BAP) accounted for about 55% of the supplied AE, whereas citrate toxicity symptoms, vasovagal reactions and technical events (e. g. disposable leakages, software failures) rather equally affected haemaphereses at 8-15%. Out of 12.348 finalized AE, 8.759 (70.1%) were associated with a procedure-related break-off with BAP being the prevailing cause (5.463/8.759; 62.4%). An automated centre- and procedure-specific AE evaluation according to the latest IHN- and AGHV-standard is available within a few minutes. CONCLUSIONS: An on-line electronic platform for comprehensive assessment and centre-specific automated evaluation of AE in haemaphereses has been developed and proved to be stable and safe over a period of four years.
• EIT monitors valid and robust regional ventilation distribution in pathologic ventilation states in porcine study using differential DualEnergy-CT (ΔDECT)
  Reinartz SD, Imhoff M, Tolba R, Fischer F; Fischer EG, Teschner E, Koch S, Gärber Y, Isfort P, Gremse F. (2019)
  Scientific Reports 9:9796   [Sebastian Daniel Reinartz et al.] [PMID] [DOI]
      [Abstract]
  OBJECTIVES: It is crucial to precisely monitor ventilation and correctly diagnose ventilation-related pathological states for averting lung collapse and lung failure in Intensive Care Unit (ICU) patients. Although Electrical Impedance Tomography (EIT) may deliver this information continuously and non-invasively at bedside, to date there are no studies that systematically compare EIT and Dual Energy CT (DECT) during inspiration and expiration (ΔDECT) regarding varying physiological and ICU-typical pathological conditions such as atelectasis. This study aims to prove the accuracy of EIT through quantitative identification and monitoring of pathological ventilation conditions on a four-quadrant basis using ΔDECT.
  MATERIAL & METHODS: In a cohort of 13 pigs, this study investigated systematic changes in tidal volume and positive end-expiratory pressure (PEEP) under physiological ventilation conditions. Pathological ventilation conditions were established experimentally by single-lung ventilation and pulmonary saline lavage. Spirometric data were compared to voxel-based entire lung ΔDECT, and EIT intensities were compared to ΔDECT of a 12-cm slab of the lung around the EIT belt, the so called ΔDECT_Belt.
  RESULTS: To validate ΔDECT data with spirometry, a Pearson's correlation coefficient of 0.92 was found for 234 ventilation conditions. Comparing EIT intensity with ΔDECT_Belt, the correlation r = 0.84 was found. Normalized cross-correlation function (NCCF) between scaled global impedance (EIT) waveforms and global volume ventilator curves was r = 0.99 ± 0.003. The EIT technique correctly identified the ventilated lung in all cases of single-lung ventilation. In the four-quadrant based evaluation, which assesses the difference between end-expiratory lung volume (ΔEELV) and the corresponding parameter in EIT, i.e. the end-expiratory lung impedance (ΔEELI), the Pearson's correlation coefficient of 0.94 was found.
  CONCLUSIONS: The respective Pearson's correlation coefficients implies good to excellent concurrence between global and regional EIT ventilation data validated by ventilator spirometry and DECT imaging. Providing real-time identical images of the lung, EIT is a promising, clinically robust tool for bedside assessment of regional ventilation distribution and changes of end-expiratory lung volume.

Cell Pharmacology / Immunology :

• ß-Endorphin modulates immune functions - A review.
  Fischer EG, Falke NE (1984)
  Psychother.Psychosom. 42,1-4:195-204 [PMID] [DOI]
      [Abstract]
  The investigation of psychoneuroimmunological pathways represents a growing field of research . This paper reviews the current state of knowledge about a direct correlation of endogenous opioids and immunologically competent cells .
• Cell shape of polymorphonuclear leucocytes is influenced by opioids.
  Falke NE, Fischer EG (1985)
  Immunobiology 169,5:532-539 [PMID] [DOI]
      [Abstract]
  The effects of ß-endorphin(ß-End), an endogenous opioid, on shape changes in polymorphonuclear leukocyte (PMN) were tested in vitro. Cell shape changes indicate alterations of the functional status of the cells. Within 2 min ß-End, but not the opioid alkaloid levorphanol or the antagonist diprenorphine, induced a cell spreading . Subsequently ß-End and levorphanol (10⁸-8⁹ M), but not the dextrorotatory isomer, stimulated an elongation of the cells. Both effects of ß-End could be antagonized by diprenorphine in an equimolar concentration. Thus the effects were stereospecific and antagonizable. In this test system the morphological changes evoked by ß-End were equal to the effects of FMLP , a chemotactic substance, used as a reference. Our findings indicate that endogenous opioids might play a role in modulating the initial phase of the PMN's offensive behavior , presumably cell adherence and motility.
• Stereospecific opiate binding in living human polymorphonuclear leucocytes.
  Falke NE, Fischer EG, Martin R (1985)
  Cell Biol.int.Rep. 9,11:1041-1047 [PMID] [DOI]
      [Abstract]
  Living human polymorphonuclear leucocytes were incubated with various opiate agonists and antagonists in radioreceptor assays. Binding of the opiate antagonists 3H-naloxone and 3H-diprenorphine and of the benzomorphan 3H-ethylketocyclazocine was found at 4°C and at 37°C, 3H-naloxone binding was stereospecific. Binding of the opiate agonist 3H-dihydromorphine was present at 37°C but not at 4°C and had a different time course as compared to the antagonists. At both temperatures no specific binding of the proteolytic stable analogue 3H-D-Ala-D-Leu-enkephalin was found. Autoradiography showed an unspecific accumulation of 3H-naloxone inside the cells and a specific localization of grains at the cell membrane.
• Opioid effects in human granulocytes (PMN)
  Fischer EG, Falke NE (1985)
  Adv.Pharmacol.Res.Pract. Vol.2,Sect.3:243-250 (Akademiai Kiado, Budapest) [DOI]
      [Abstract]
  The interest in psychosomatic mechanisms induced us to look for connections between the opioid peptides occurring in blood and the polymorphonuclear leucocytes (PMNs). When we began these studies about four years ago it was really obscure to look for the influence of neuropeptides on the immune system. Now it is well established to do so (6). About 70% of the white blood cells are polymorpho- nuclear leucocytes (PMNs), often called granulocytes because of their vesicles. With macrophages they share a common precursor cell. Both, the PMNs and the macrophages can exert, to some extent, similar functions, such as phagocytosis, enzyme release, and migration. In addition, to these common functions, the macrophages are involved in specific immune responses. This paper will outline what is known to date about the opioid influence on granulocytes; in particular, the functional and binding studies.
• Opiate receptor mediated internalization of 125I-ß-endorphin in human polymorphonuclear leucocytes.
  Falke NE, Fischer EG (1986)
  Cell Biol.int.Rep. 10,6:429-435 [PMID] [DOI]
      [Abstract]
  The early events in the interaction of (¹²⁵I)-Tyr[27]- ß-endorphin with human polymorphonuclear leucocytes were investigated. Using ultrastructural autoradiography we found that the labeled peptide specifically bound to the plasma membrane and was internalized within two minutes of incubation at 37°C. Both processes could be inhibited by unlabeled ß-endorphin or by the opiate antagonist diprenorphine. This finding was confirmed by radioreceptorassays. With longer incubation times the specific association of the labeled ß-endorphin with the cells decreased. About 10% of the tracer was degraded within 10 min of incubation as shown by gel chromatography. The morphological changes induced by 125I-ß-endorphin in the granulocytes were investigated under the microscope. The labeled peptide had the same biological effect as unlabeled ß-endorphin.
• The influence of endogenous opioid peptides on venous granulocytes.
  Fischer EG, Falke NE (1986)
  (Plotnikoff NP et al.) Enkephalins and Endorphins: Stress and the Immune System. :263-272 (Plenum, New York) [DOI]
      [Abstract]
  Ameboid migrating phagocytes represent a phylogenetically ancient defense system. Amebocytes are found throughout the animal kingdom. All functions of the PMNs (aggregation, adherence, polarization, chemokinesis, chemotaxis, phagocytosis, pinocytosis, endocytosis, exocytosis) are primitive functions, as they occur in most of the protozoa. In mammals they appear in all embryonic cells and in some of the differentiated cells.
• Interaction of Met-enkephalin with human granulocytes.
  Fischer EG, Falke NE (1987)
  Ann.N.Y.Acad.Sci. 496:146-150 [PMID] [DOI]
      [Abstract]
  Effects of Met-enkephalin on cell shape and motility of human polymorphonuclear leucocytes (PMNs) have been found. Specific binding of tritium-labeled Met-enkephalin to the cells could not be demonstrated. There was a rapid proteolytic degradation of the peptide in the medium, followed by an uptake of the labeled tyrosine. The peptidase recognizes the N-terminal sequence of various endogenous opioid peptides. The protease inhibitors bestatin and bacitracin had only little effect on the the degradation of Met-Enk.
• Endogenous opioid peptides stimulate human phagocytes - functional and binding studies.
  Fischer EG, Falke NE (1987)
  Adv.Biosciences 66:373-379
      [Abstract]
  Endogenous opioid peptides and opioid alkaloids can modulate some functions of human phagocytes. There is good evidence for opioid receptors on these cells. Own studies will be presented in relation to the findings of other investigators in this field.
• Opioid peptides modulate immune functions. A review.
  Fischer EG (1988)
  Immunopharmacol.Immunotoxicol. 10,3: 265-326 [PMID] [DOI]
      [Abstract]
  In the past few years it has become evident that neuropeptides may be direct mediators in the modulation of the immune response and the unspecific defence by the brain. Lymphocytes have been thought to have opioid receptors and to respond to opioids with an increase in blastogenesis, cytotoxicity and factor release. Lymphocytes are said to release various neuropeptides. Furthermore, there are some unexplained effects of morphine on the immune system and of the immune system on morphine withdrawal. The purpose of this paper is to review what has been previously published in this field. The well established modulation of phagocyte functions by opioids will only be scanned.
• Endothelial cell-basement membrane interactions.
  Kirkpatrick CJ, Rixen H, Axer T, Schmitz U, Hollweg G, Klee D, Wajda R, Kampe M, Fischer EG, Mittermayer C. (1989)
  (Westerhof N, Gross DR) Vascular Dynamics and Physiological Perspectives. NATO Adv.Res.Workshop 166,Chap.10:135-148 (Plenum Publ.Corp., New York)
      [Abstract]
  One of the essential aspects of an intact blood vessel is the relationship existing between the endothelial cell layer and the underlying components of the basement membrane. These cell-matrix interactions take on particular significance in the case of damage to the endothelium, for example, in the course of inflammation or tumour cell invasion. The need to understand more about these interactions has been highlighted by the recent endeavours to 'seed' vascular prostheses with endothelial cells prior to implantation.
• In vitro studies on the expansion of endothelial cell monolayers on components of the basement membrane.
  Kirkpatrick CJ, Kampe M, Rixen H, Fischer EG, Ruchatz D, Mittermayer C (1990)
  Virchows Arch.(B) Cell Pathol. 58,3:207-213 [PMID]
      [Abstract]
  The purpose of the present study was to observe the expansion of a monolayer of endothelial cells over specific components of the basement membrane. This was performed in vitro in a monolayer expansion assay over 5 days. The control surface was uncoated glass in the form of coverslips. Test substances were coated at a concentration of 10 µg/ml. The highest expansion was obtained with a high molecular weight fragment mixture of collagen type IV (IV-F, consisting of 75, 120 and 140 KD fragments), followed by fibronectin. Collagens type I, III and IV tetramer gave similar results, less than fibronectin or collagen type IV-F, although all of the above basement membrane coatings promoted expansion significantly above that of the control (P less than 0.01). The poorest expansion was obtained with laminin, which was significantly less than the control. The pentapeptide GRGDS, related to the fibronectin cell binding region, gave expansion significantly below that of the intact fibronectin molecule, as did the intact collagen type IV molecule compared with type IV-F (P less than 0.025). This indicates that sequences of the fibronectin molecule other than the cell binding sequence may be involved in promoting endothelial cell expansion. In addition, the integrity of the collagen type IV molecule does not appear necessary for this effect. On the contrary, the higher movement on IV-F may represent an inherent repair mechanism in damaged endothelium. Autoradiographic studies show that endothelial cell proliferation at the expanding front is involved in the migration assay.
• Migration assay for endothelial cells in multiwells. Application to studies on the effect of opioids.
  Fischer EG, Stingl A, Kirkpatrick CJ (1990)
  J.Immunol.Meth. (1990) 128:235-239 [PMID] [DOI]
      [Abstract]
  An assay system is described which permits rapid and effective evaluation of endothelial cell repair, using cells growing in a monolayer. With this method it was possible to obtain highly significant results. For example, endothelial growth factor and heparin, significantly enhanced cell migration and/or proliferation, whereas beta-endorphin, an endogenous opioid, had no effect on the migration and/or proliferation of human umbilical vein endothelial cells. This model may be used to study the cell migration of a variety of cell types which under certain experimental conditions (e.g., irradiation) do not proliferate.
      click here, to read more about the assay on our website
• Opioid influence on the adherence of granulocytes to human umbilical vein endothelial cells in vitro.
  Fischer EG, Stingl A, Kirkpatrick CJ (1990)
  Cell Biol.int.Rep. 14,9:797-804 [PMID] [DOI]
      [Abstract]
  Recent studies revealed the existence of opioid receptors on human polymorphonuclear leukocytes (hPMN) and reported the effects of endogenous opioids on hPMN migration and adherence on glass or serum coated glass. Extending these studies, we investigated the influence of opioids on the adherence of hPMN to human umbilical vein endothelial cells as an in vitro model. Two different assay systems served to quantify the two basic events of adherence: attachment and spreading. hPMN in suspension were allowed to settle under the influence of ß-endorphin. After 30 and 240 sec the number of attached cells was enhanced 2.5-fold. Studying the spreading of cells, ß-endorphin increased the cell area 1.5-fold. Since adherence precedes the migration of hPMN through the endothelial cell layer towards foci of inflammation, the results suggest a modulatory role of endogenous opioids in defence mechanisms.
• Differential expansion of human endothelial monolayers on basement membrane and interstitial collagens, laminin and fibronectin in vitro.
  Kirkpatrick CJ, Kampe M, Fischer EG, Rixen H, Richter H, Mittermayer C (1990)
  Pathobiology 58,4:221-225 [PMID] [DOI]
      [Abstract]
  In this study the ability of a human endothelial cell monolayer to expand over specific components of the basement membrane and extracellular matrix was investigated over a 5-day period. The method was intended as a model to study the mechanisms of endothelial regeneration. All components were coated onto sterile coverslips at a concentration of 10 µg/ml. The highest expansion was obtained on fibronectin, laminin and collagen type III, all three being statistically significantly greater than on the uncoated control surface (0.002 greater than p greater than 0.0001). Collagens types I and IV and a high molecular weight fragment mixture of type IV (IV-F, consisting of 75, 120 and 140 kD fragments) elicited approximately similar expansion rates, significantly higher than the control (0.02 greater than p greater than 0.003), although significantly lower (approximately 15%) than collagen type III, fibronectin and laminin (p less than 0.001). The high monolayer expansion on collagen type III is surprising, as it is a relatively minor biosynthetic product of the endothelial cell. It could, however, be of significance in wound healing, in which endothelial cells come into contact with this interstitial collagen. In addition, the similar results obtained with collagens IV and IV-F indicate that expansion of the endothelial monolayer is not dependent on the integrity of the tetrameric structure of type-IV collagen.
      click here, to read more about the assay on our website
• Effect of fibrinogen fragments D and E on the adhesive properties of human granulocytes to vein endothelial cells.
  Fischer EG, Vogel P, Ziegler AS; Kirkpatrick CJ (1991)
  Haemostasis 21,3:141-146 [PMID] [DOI]
      [Abstract]
  In hyperfibrinolytic conditions, e.g. in disseminated intravascular coagulation or the adult respiratory distress syndrome, high levels of fibrinogen degradation products (FDPs) D and E are found in human plasma. This study investigates the influence of these fragments on cell attachment of human granulocytes in vitro. While leaving unaffected the adhesion of human umbilical vein endothelial cells (HUVEC) on gelatine-coated glass, both FDP fragments at 50 µg/ml inhibited granulocyte attachment to glass as well as to HUVEC monolayers. At the same concentration, the fragments diminished the superoxide release of stimulated granulocytes. These results suggest a modulatory role of pathologically elevated FDPs on the granulocyte function cascade.
• In vitro studies on PMN-independent endothelial cell damage in trauma: decrease of PMN-endothelial cell adherence by fibrinogen degradation products and disturbance of endothelial cell membrane integrity by trauma serum.
  Vogel P, v.d.Beek J, Marohl K, Fischer EG, Kirkpatrick CJ (1993)
  Eur.Surg.Res. 25,2:83-90 [PMID] [DOI]
      [Abstract]
  Trauma favors the development of adult respiratory distress syndrome (ARDS). Adherence of polymorphonuclear leukocytes (PMN) to endothelial cells (EC) with subsequent EC damage by the respiratory burst products and proteases of the PMN is thought to be one of the basic mechanisms in the pathogenesis of ARDS. Recent studies have shown that there might also be PMN-independent mechanisms of EC damage. It would speak for PMN-independent EC damage if in the state of risk for this damage factors were found which decrease PMN activity or if EC damage appeared without PMN. Because in trauma and sepsis pathologic coagulation with high levels of fibrinogen degradation products (FDP) is often diagnosed, we investigated whether FDP-D and FDP-E might influence PMN adherence to EC. We also investigated whether serum of traumatized patients might provoke EC damage in a PMN-independent system in vitro. To achieve this we evaluated the viability of EC using a fluorescence staining method. We found that both FDP-D and FDP-E decreased PMN adherence to human EC significantly (p < 0.01) at a concentration of 50 µg/ml. Furthermore we found that EC membrane integrity can be disturbed by serum of trauma patients. These results suggest that in trauma also PMN-independent mechanisms are important for EC damage.

Neurology :

• Glutamic acid diethyl ester induces catalepsy in rats. A new model for schizophrenia ?
  Kornhuber J, Fischer EG (1982)
  Neurosci.Lett. 34,3:325-329 [PMID] [DOI]
      [Abstract]
  The glutamate antagonist glutamic acid diethyl ester is found to produce catalepsy in rats, when administered into the lateral ventricle. Since the cerebrospinal fluid content of glutamate is reduced in patients with schizophrenia, the central effects of glutamate antagonists are a possible experimental model for schizophrenia.
• Failure to detect dopamine receptor IgG autoantibodies in sera of schizophrenic patients.
  v.Kirchbach A, Fischer EG, Kornhuber HH (1987)
  J.Neural.Transm. 70,1-2:175-179 [PMID] [DOI]
      [Abstract]
  Autoantibodies against dopamine receptors in schizophrenic patients have been postulated. IgG was fractionated from sera of 15 schizophrenic patients (DSM III) in an acute episode. However, 3H-spiperone binding to dopamine receptors was not inhibited by this fraction.
• T-Lymphocyte subpopulations in multiple sclerosis - Do they help to judge immunosuppressive therapy ?
  Henneberg A, Fischer EG, Kornhuber HH (1988)
  Eur.Arch.Psychiatry Neurol.Sci. 238,2:94-96 [PMID]
      [Abstract]
  T-cell subpopulations have been tested in multiple sclerosis (MS) patients before and after cyclophosphamide (n=38), corticotropin (n=37), and physiotherapeutical (n=32) treatment. There were no specific changes of subset ratios immediately after immunosuppressive treatment. However, T-cell subpopulations showed great day-to-day variations in MS patients.
• Are there antilymphocyte autoantibodies in multiple sclerosis patients ?
  Fischer EG, Ahlers F, Kornhuber HH, Henneberg A (1989)
  J.Neurol.Sci. 93,2-3:319-322 [PMID] [DOI]
      [Abstract]
  Immunoglobulins were separated from sera of 40 multiple sclerosis (MS) patients and 40 healthy controls by density and affinity chromatography. In IgM and IgG fractions of 40 MS patients and 40 controls no lymphocyte-specific binding could be detected by the help of FITC-conjugated anti-µ and anti-Fc antibodies.