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G Hänsch

Publications and source records attributed to G Hänsch.

18 recordsLinked to original sources
PubMed2000

[Vasculitis 1998: new aspects in diagnosis and therapy].

The Chapel Hill conference established the most actual classification of systemic vasculitides. Disease activity and organ damage were standardized by means of a new scoring system (BVAS; VDI). Bacterial infection is frequent during the active phase of vasculitis. The measurement of serum procalcitonin helps to differentiate between disease activity and infection. In a recent study the European vasculitis group (EC-BCR project) found that the presence of C-ANCA/PR 3-ANCA or P-ANCA/MPO-ANCA is as reliable as histological proof of vasculitis. In rare cases ANCA is positive in diseases other than vasculitis, which has to be kept in mind for diagnosis and therapy. The association between ANCA and IgA nephropathy is exciting. The occurrence of IgA-GN in patients with Wegener's granulomatosis is usually a secondary event whereas in patients with rapidly progressive IgA-GN microscopic polyangiitis follows. Many observations support the view that ANCA-positive vasculitides are T-cell mediated diseases. Our investigations demonstrate that neutrophils express class II antigens during active disease and are able to trigger T-cell activation via infectious stimuli. With regard to therapy of ANCA-positive vasculitides several strategies are currently being examined in different European countries (EUVAS) with the aim to limit cyclophosphamide to the active stage of the disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

L-fucose residues on cellulose-based dialysis membranes: quantification of membrane-associated L-fucose and analysis of specific lectin binding.

Contact of mononuclear human leukocytes with cellulose dialysis membranes may result in complement-independent cell activation, i.e. enhanced synthesis of cytokines, prostaglandins and an increase in beta 2-micro-globulin synthesis. Cellular contact activation is specifically inhibited by the monosaccharide L-fucose suggesting that dialysis membrane associated L-fucose residues are involved in leukocyte activation. In this study we have detected and quantitated L-fucose on commercially-available cellulose dialysis membranes using two approaches. A sensitive enzymatic fluorescence assay detected L-fucose after acid hydrolysis of flat sheet membranes. Values ranged from 79.3 +/- 3.6 to 90.2 +/- 5.0 pmol cm-2 for Hemophan or Cuprophan respectively. Enzymatic cleavage of terminal alpha-L-fucopyranoses with alpha-L-fucosidase yielded 7.7 +/- 3.3 pmol L-fucose per cm2 for Cuprophan. Enzymatic hydrolysis of the synthetic polymer membranes AN-69 and PC-PE did not yield detectable amounts of L-fucose. In a second approach, binding of the fucose specific lectins of Lotus tetragonolobus and Ulex europaeus (UEAI) demonstrated the presence of biologically accessible L-fucose on the surface of cellulose membranes. Specific binding was observed with Cuprophan, and up to 2.6 +/- 0.3 pmol L-fucose per cm2 was calculated to be present from Langmuir-type adsorption isotherms. The data presented are in line with the hypothesis that surface-associated L-fucose residues on cellulose dialysis membranes participate in leukocyte contact activation.

Acrylic Resins↗
PubMed1994

Atherogenesis and cardiac death: are they related to dialysis procedure and biocompatibility?

Cardiac events are a major cause of death in dialysed patients. This is due, at least in part, to the high prevalence of atherosclerotic coronary heart disease. To a large extent, however, coronary lesions are acquired in the predialytic phase of chronic renal failure. The susceptibility of the heart to ischaemia is modulated by a number of factors, e.g. microvascular abnormalities, increased cardiac pulsatile workload, disturbed cardiac glucose metabolism, imbalanced autonomic innervation. The paradoxical result of there being no relationship of cardiac death in dialysis patients to blood pressure may be explained by confounding factors. Intradialytic hypotension appears to be an independent risk factor. The dialysis patient is exposed to hypertension and dyslipidaemia, two potent risk factors of atherosclerosis. Although no definite information is available, it is conceivable that factors related to dialysis procedures may also influence early or late events in atherogenesis. Such potential factors include oxidative modification of lipids, modulation of insulin resistance or glucose metabolism by non-insulin-dependent pathways, expression of adhesion molecules and activation of potential effector cells in atherogenesis, particularly monocytes and platelets, changes of synthesis and/or response to endothelin and nitroxide (EDRF), and possibly also accelerated formation of advanced plaques by hyperphosphataemia and/or hyperparathyroidism. Such proatherogenic mechanisms must be balanced against factors potentially protecting against atherogenesis; these comprise altered arachidonic acid metabolism (increased prostacyclin and decreased thromboxane synthesis), impaired platelet aggregation, antiatherosclerotic effects of heparin, and diminished concentrations of 1,25(OH)2D3, i.e. of a proatherogenic compound.

Arteriosclerosis↗
PubMed1993

Genetic basis of human complement C8 beta deficiency.

The eighth component of human complement (C8) is a serum protein consisting of three chains (alpha, beta, and gamma) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the beta subunit is non-covalently bound to the disulfide-linked alpha-gamma subunit. Patients with C8 beta deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizes was observed in a C8 beta-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8 beta-deficient individuals was carried out. As a cause for C8 beta deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8 beta-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8 beta deficiency in the Caucasian population. In addition, two C8 beta-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined.

Base Sequence↗
PubMed1992

Biocompatibility of synthetic oxygen carriers and fluorosurfactants.

A system for testing the biocompatibility of synthetic oxygen carriers is described including tests of hemolysis, complement activation and proliferation of cell lines or lymphocytes. Of 17 surfactants tested in this system, 6 were compatible in all tests while the other compounds showed individually differing patterns of incompatibility. We conclude that, in order to conduct a meaningful screening, a series of different assays has to be applied. In addition to our system, further assays, covering cytokine induction and phagocytosis should be attempted.

Blood Substitutes↗
PubMed1986

Membrane factors responsible for homologous species restriction of complement-mediated lysis: evidence for a factor other than DAF operating at the stage of C8 and C9.

Species-restricted lysis of complement refers to the relative inefficiency of complement to lyse cells from the homologous species. Restriction occurs at least at the steps involving C3/C5 convertase formation and the C9 insertion phase of the complement cascade, and is presumed to be mediated by inhibitory factors in the target cell membrane. In this study, we have examined whether decay accelerating factor (DAF), a membrane protein known to modulate C3/C5 convertase activities on cell surfaces, acts as a regulatory protein in species-restricted lysis of human erythrocyte (E). The role of DAF was assessed in homologous lysis by the classic pathway, in reactive lysis, and in lytic steps requiring C8 and C9. The results indicated that DAF participated in regulating C3/C5 deposition on the surface of homologous E, but had no effect on homologous restriction in reactive lysis and in the reaction of C8 and C9 with antibody-sensitized E C1-7. Treatment of E with pronase or with dithiothreitol (DTT) abolished the restricting effect of homologous C8/C9, indicating that species-restricted lysis by C5b-9 involves membrane factor(s) sensitive to pronase and DTT.

Animals↗
PubMed1985

The role of complement in inflammation.

The inflammatory process may be initiated by a great variety of stimuli. Amongst the diverse pathogenic pathways that lead from the primary stimulus to the tissue response, the serum complement system (C) seems the most important and, certainly, it is the best analyzed of the mediator systems.

Complement Pathway, Alternative↗
PubMed1983

Lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by acid-activated serum.

Erythrocytes from paroxysmal nocturnal hemoglobinuria patients (PNH-E) are much more susceptible to lysis by acid-activated human serum than normal human erythrocytes. Acidification of normal human serum to pH 6.4 in the absence of erythrocytes generates this lytic activity independently of the alternative pathway of complement activation. A shift of pH of a mixture of purified human C5 and C6 to 6.4 at 0 degrees C generates a similar activity C(56)a that lyses PNH-E together with C7-C9 much more efficiently than normal erythrocytes. Since acid-activation of normal human serum occurs in the absence of C3, the acid-activated C56 appears to be the lytic principle in acidified human serum.

Animals↗
PubMed1983

Activation of the fifth and sixth components of the human complement system: C6-dependent cleavage of C5 in acid and the formation of a bimolecular lytic complex, C5b,6a.

Acidification of C5 and C6 or serum to pH 6.4 at 0 degrees C, followed by neutralization, generates a factor-designated C(56)a that causes lysis of nonsensitized erythrocytes in the presence of C7, C8, and C9. C(56)a is functionally similar to alternative pathway-generated C5b,6 in respect to the formation of C5b,6,7 sites on cells, the potentiation of lytic activity by membrane-bound C3b or the membrane-active agent A2C, and the required species compatibilities between target membranes and terminal components for optimal activity. The formation of C(56)a complex from purified components C5 and C6 proceeds independently of the classical or alternative pathway C5 convertases and requires the simultaneous H+ ion treatment of the components. The generation of C(56)a from C5 and C6 and the physicochemical properties of the complex were studied in detail and compared with those of C5b,6. Acid generation of C(56)a is dose-dependent on C5 and C6 and its efficiency is similar to that of the conventional convertase in the production of lytic activity. Sucrose gradient ultracentrifugation of C(56)a containing activated 125I-C5 demonstrated a shift in sedimentation from that of native C5 to 11S, which is consistent with C5,6 complex formation. C(56)a sedimentation was identical to C5b,6, and both migrated coincident with lytic complex activity. These complexes, however, are not identical because unlike C5b,6, C(56)a is unstable at 37 degrees C, demonstrating a nonlinear decay curve. In the presence of C7, both complexes exhibit similar first order decay with a T1/2 of 3 min at 37 degrees C. SDS-PAGE autoradiographic analysis of the C5-subunit structure of 125I-C5 in C(56)a and the Zx-activated C5b,6 complex prepared from purified components showed similar alpha-chain cleavage to several fragments of 109,000, 100,000, and 58,000 daltons. Conversion to lower m.w. peptides by acid treatment was more extensive. Comparison of the 125I-C5 polypeptide chains in the membrane attack complex extracted from guinea pig erythrocyte membranes, prepared by acid activation or classical pathway lysis with whole serum, demonstrated similar C5 alpha-chain cleavage to a predominant subunit of 102,000 daltons. Acid activation also produced a 109,000 dalton C5 alpha'-fragment barely detectable with classical pathway activation. Low pH treatment of C5 alone did not inactivate C5 function, form a lytic complex on the subsequent addition of C6, or cleave the C5 alpha-chain. Thus, it is postulated that local high H+ ion concentration during simultaneous acidification of C5 and C6 allows complex formation with the concomitant C6-dependent cleavage of the C5 alpha-chain and the generation of lytic capacity.

Centrifugation, Density Gradient↗
PubMed1981

Effect of agents that produce membrane disorder on lysis of erythrocytes by complement.

To evaluate the effect of membrane lipid acyl-chain packing on the efficiency of cell lysis by complement, we have studied membrane modulation by 2-(2-methoxy)-ethoxyethyl-8-(cis-2-n-octylcyclopropyl)-octanoate (A2C) and by myristoleyl alcohol, the cis isomer of a C14:1 aliphatic alcohol. These substances are known to increase the membrane lipid disorder by virtue of the bend in their acyl chains, which is believed to loosen the phospholipid acyl-chain packing. We have found that both of these compounds markedly enhance the lysis of erythrocytes by the terminal complement proteins C5b-9. The enhancing effect by A2C is operative in the formation of erythrocytes carrying complement components C5b, C6, and C7, as well as in the subsequent reactions with complement components C8 and C9. We have also found that A2C-treated erythrocytes bind C5b6 to a measurable extent, whereas untreated erythrocytes do not. We attribute this to a shift in the partition equilibrium of C5b6 toward membrane association, which would improve lytic efficiency. The increase of membrane lipid disorder by these agents would also be expected to increase insertion of hydrophobic peptides from C7, C8, and C9, with consequent gain in lytic efficiency. Treatment of erythrocytes with sublytic doses of NaDodSO4, or Triton X-100 did not enhance lysis by C5b-9 appreciably, suggesting that enhancement of lysis by C5b-9 is not a general property of amphiphiles.

Complement C5↗
PubMed1979

Isolation of late complement components by affinity chromatography: I. Purification of the human complement component C9 and production of a C9-defective human serum.

A new procedure for the isolation of the human complement component C9 is described. This procedure offers the possibility to prepare functionally pure C9 in a one-step procedure with a high recovery of 10-22% of the biological activity. The 125iodinated C9 had a molecular weight of 78,000 daltons and was only contaminated in traces with other proteins. Further purification by absorption with an "anti-impurity" column lead to a C9 preparation which behaved as a homogenous single polypeptide chain in SDS polyacrylamide gel electrophoresis after reduction with mercaptoethanol. It formed a single bell-shaped precipitate in crossed immunoelectrophoresis with antibodies against human serum in the gel of the second dimension. The recovery of the biological activity after the second purification step was in the order of 6-10%. Both preparative steps could be performed within a few hours 450 microgram C9 protein were isolated from 135 ml human serum. A human serum completely defective in C9 was prepared by the extensive absorption of a smaller volume of human serum proteins with the anti-C9 column.

Complement C9↗
PubMed1979

Isolation of late complement components by affinity chromatography. II. Purification of the human complement component C6.

We developed a new procedure for the rapid and gentle isolation of the human complement component C6 comparable to that described previously for C9. The procedure is based on affinity chromatography. As a first step, C6 is immunoabsorbed on insolubilized anti-C6 antibodies. These antibodies were derived from C6-defective rabbits (Freiburg strain). C6 was eluted with 3 M thiocyanate, pH 7.2, with a recovery of 15--23% of its hemolytic activity and a more than 270--fold purification. Impurities were removed in a second step by an "anti-impurity" column. The final product yielded a 12% recovery of the hemolytic activity and the purification factor was higher than 1300. The final product was homogeneous in SDS polyacrylamide and immunoelectrophoresis.

Animals↗
PubMed1978

Deviated lysis: lysis of unsensitized cells by complement. V. Generation of the activity of low pH or low ionic strength.

In serum exposed to acid pH (6.4), a serum activity was generated which lyzed unsensitized erythrocytes in the presence of EDTA. It was similar to the d.l. activity found following serum activation by inulin (2). In contrast to the d.l. generation by the classical or by the alternative pathway of C activation, the generation of d.l. by acid pH did not require C4 plus C2 or C3 plus factor B resp. It was, thus, not dependent on any hitherto known pathway of C activation. A similar activity appeared when NHS was centrifuged in a sucrose gradient at low ionic strength. Physicochemical alterations of the component proteins which influence their affinity for each other are seen as the basis for the activation of the attack phase of C.

Animals↗
PubMed1977

Deviated lysis: transfer of complement lytic activity to unsensitized cells. IV. Parital isolation of the activity.

Deviated lysis (d.l.) was previously characterized as the lysis of non-sensitized erythrocytes by activated complement (C) in the presence of EDTA (1, 2, 3). The lytic activity was present in serum fractions of a m.w. in the proximity of 220,000. All the C factors C5 through C9 were found in these fractions and they were all needed for lysis. It is proposed that in d.l. small aggregates of the C components C5 through C9 coexist in the reaction mixture without further interaction. Only when appropriate receptors such as present on target cells surfaces are available, the factors react in a sequential order eventually to result in lysis of the target cell.

Animals↗
PubMed1976

Deviated lysis: Transfer of complement lytic activity to unsensitized cells II. Generation of the activity by inulin and by antigen antibody complexes.

Deviated lysis (d.l.) activity, i.e. lysis of unsensitized cells by lytic C activity, was generated via the classical pathway of Cactivation (ag ab complexes) and via the alternative pathway (inulin). The activity was observed on the surface of the activating particles and in the fluid phase. The activity was relatively stable at 32 degrees C. Its generation involved the C components C6 through C9 and possibly also C5.

Animals↗