Search Results - (Author, Cooperation:H. Jepsen)

2011-08-06

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

0038-1098

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Physics

Electronic Resource

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

ZnCl2 exerted a dose-dependent inhibition of citrate-phosphate dextrose (CPD) plasma-induced release of 125I-labelled BSA-anti-BSA immune complexes (IC) bound to complement receptor lype I (CRl. CD35) in human whole blood. Maximal inhibition was observed at 10mM of ZnCl2.Furthermore, the release of IC bound to erythrocyte (E)-CRI by purified factor I. factor Ideficient serum plus purified factor I. or normal human. Serum was reduced by approximately 90%, 64%, and 52%, respectively, in the presence of 10 mM ZnCl2.The effect of ZnCl2 on factor 1-mediated degradation of cell-bound C3b/C4b was also investigated employing CPD blood or E from a factor I-deficient donor. These cells expressed covalently bound C3b and C4b as demonstrated by a simple agglutination technique. Upon incubation of CPD whole blood with purified factor I. or of E wilh purified factor I or normal CPD plasma, the C-fragments were cleaved and the cells were no longer agglutinated by antibodies to C3c and C4c. The presence of ZnCl2 prevented Ihis factor 1-mediaied degradation of C3b and C4b, as evidenced by the unaffected agglutination of the cells by the antibodies.We conclude that ZnCl2 inhibited factor I aclivity since: (1) release of complementpreopsonized IC from E-CR 1 by purified factor I was markedly inhibited (90%) in the presence of ZnCl2, (2) preincubation of the cells with ZnCl2 caused only a moderate inhibition (32 38%) of the IC release, and (3) degradation by purified factor I of covalently cell-bound C3 band C4b was abrogated in the presence of 10 mM ZnCl2.

Electronic Resource

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Erythrocytes (E) from three factor I-deficient patients were investigated for surface-bound complement factors and CR1 (CD 35) expression and function. The E were coated with C4b,C3b, and factor H. Following plasma infusion of in vitro incubation of the patients’ E with normal human serum (NHS) or purified factor I, cell-bound C4b and C3b could no longer be detected. The E now expressed C3d, and factor H was unaffected, indicating that factor H was hound to the C3d part of the C3b molecules, providing the co-factor for effective cleavage of E-bound C3b when purified factor 1 was added. The binding of monoclonal anti-CR1 antibodies (M710) to the patients’ E was markedly reduced compared with control E, and was not normalized by treatment with NHS, probably because covalently bound C3d/factor H interfered with the binding of M710. By contrast, the reduced ability of the patients’ E-CR1 to bind complement-opsonized immune complexes (IC) was normalized after plasma infusion. This shows that the impaired CR1 function was acquired and emphasizes the importance of performing functional CR1 assays. Complement opsonization of IC for binding to normal E was severely compromised in the patients’ sera due to consumption of factor B and C3. After plasma infusion the opsonization capacity of the patients’ sera was restored. Thus, two mechanisms of importance for normal clearance of IC were compromised in factor I-deficient patients: (1) the opsonization of IC for binding to E-CRI, and (2) the capacity of E-CRI to bind opsonized complexes. Both dysfunctions were temporarily corrected by plasma infusion.

Electronic Resource

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The binding of 125I-labelled bovine serum albumin (BSA)-anti-BSA immune complexes (IC) to Raji cells and polymorphonuclear(PMN)cells in vitro was studied. The IC were reacted for 1 h at 37°C with normal human serum (NHS) diluted 1:2 in the presence or absence of human erythrocytes (E) before presentation for Raji cells or PMN cells. The IC showed a two to three fold increased binding to C3d, g receptors (CR2) on Raji cells, when E-CR1 had been present during the reaction with NHS, compared to IC similarly reacted with NHS only. Blocking of the E-CR1 by a polyclonal anti-CR1 antibody reduced the subsequent binding of IC to Raji cells to the same level as that obtained with IC reacted with serum only. Binding to PMN granulocytes of IC reacted with NHS in the presence of E-CR1 showed a 60% reduction compared to the binding of IC reacted with NHS only. It is concluded that interaction of complement-reacted IC with CR1 on erythrocytes leads to a more efficient generation of CR2-binding C3d, g-containing IC with reduced reactivity to PMN cells.

Electronic Resource

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The binding of complement (C)-solubilized 125I bovine serum albumin (BSA) anti-BSA immune complexes (IC) to CR1 receptors on human red blond cells (RBC-CR1) was studied. The binding of IC to CRI was strongly dependent on the molar antigen lo antibody ratio, and IC formed in moderate antigen excess showed no binding. IC solubilized, in 50% human serum in the presence of autologous RBC bound rapidly lo RBC-CRI, with maximal binding within less than 1 min at 37°C. Release of CRI-hound IC under these conditions occurred slowly, requiring more than.30 min. Only binding of ‘partially’ solubilized, e.g., anti C3c (C4c) and conglutinin-reactive 1C occurred, whereas fully solubilized complexes (IC-C3dg. C4d) showed virtually no binding. Solubilization of IC in the presence of Mg-EGTA or in C2-deficient serum resulted in a markedly delayed binding of IC ti RBC, indicating the importance of an intact classical pathway in preparing the IC for binding to RBC-CR1. C-solobilized IC could be absorbed to solid-phase conglutinin or antibody to C3c abd C4c, and tgese kugabds were able to inhibit the binding of solubilized IC to RBC. Heparin also exerted a marked, dose-dependent inhibitory effect on the binding of presolubilized IC to RBC-CR1, whereas the binding was unaffected by the addition of monosaccharides or by the concentration of Ca2− or Mg2− ions.

Electronic Resource

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The release of 125I-bovine serum albumin (BSA)-anti-BSA immune complexes (IC) hound to human erythrocyte complement receptors (E-CR1) was studied. IC were complement-solubilized in normal human serum (NHS), and reacted with human erythrocytes at conditions optimal for binding of the IC to E-CRI. E-CRI-bound IC could he released by the addition of NHS or purified factor I. Factor I-deficient or I-depleted serum mediated no release, and addition of purified factor 1 restored the release. Factor H was not required for the release of IC. The kinetics of IC release was influenced by the NHS concentration, the presence of EDTA, and the time of prior storage of the erythrocytes at 4°C. NHS (1:5 to 1:10) in the presence of EDTA caused nearly maximal release within 10–20 min at 37°C. In the absence of EDTA the NHS-induced IC release was markedly slower. IC released within she first 30 min showed significant rebinding to new E. The release of IC was not associated with loss of the IC binding activity of E-CRI. The NHS-mediated release of IC could be inhibited by rabbit anti-CRI and by a mixture of protease inhibitors. Release induced by purified factor 1 was also inhibited by protease inhibitors. The affinity of IC binding to E-CRI was reduced alter cleavage of CRI-bound C3b-IC to iC3h-IC by factor I.

Electronic Resource

0340-1855

Schlüsselwörter Iloprost ; Prostacyclin ; progressive ; systemische Sklerodermie ; Raynaud-Syndrom ; Lungenfunktion ; Key words Iloprost ; prostacyclin ; systemic sclerosis ; lung function ; Raynaud‘s syndrome

Springer Online Journal Archives 1860-2000

Medicine

Summary A 57-years old female patient with systemic sclerosis underwent a prolonged intravenous therapy during 21 consecutive days with iloprost, a stable analogue of prostacyclin. Beginning with 0,5 ng/kg/minute the dose was increased every 2 days up to 2 ng/kg/minute. At the end of follow up, Iloprost was shown to enhance the perfusion of the finger and to improve pulmonary-function tests including the diffusion-capacity. Furthermore, the Erythrocyte Sedimentation Rate and the C-reactive protein decreased. The case report shows the necessity of a controlled study of prolonged iloprost therapy.

Zusammenfassung Bei einer 57-jährigen Patientin mit einer progressiven systemischen Sklerodermie wurde eine prolongierte Therapie mit Iloprost über 21 Tage durchgeführt. Die Dosierung betrug über eine Einschleichphase von 6 Tagen 2 ng/kgKG×min. Die Therapie führte zu einer Verbesserung der Entzündungsparameter, der Lungenfunktion, insbesodere der Diffusionskapazität und der ausgeprägten akralen Durchblutungsstörung. Die Kasuistik unterstreicht die Notwendigkeit einer kontrollierten Studie, die den Effekt einer Verlängerung der Therapie mit Iloprost im Vergleich zu bisher durchgeführten Studien, die in der Regel über drei bis fünf Tage erfolgten, auf Symptome der Sklerodermie untersucht.

Electronic Resource