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R Nolte

Publications and source records attributed to R Nolte.

At least 37 records · Page 2Linked to original sources
PubMed1985

Mechanisms of complement activation by crystalline cholesterol.

The mechanism by which cholesterol crystals activate complement in human serum has been studied. Crystals treated with serum and washed with buffer contain a fixed C3/C5 convertase. Its generation is dependent on the presence of divalent cations (and of factor B). The cholesterol-fixed convertase is subject to decay and can be regenerated by factors B and D. C2 in combination with C1 is not essential but enhances the convertase formation. These findings indicate that it is predominantly the alternative C3/C5 convertase C3bBb(P) that assembles on cholesterol during exposure to human serum. By the use of different antisera and immunofluorescence a C3 fragment, probably C3b, was demonstrated on serum-treated crystals. Its fixation is resistant to washing with urea, and with buffers of differing pH: by hydroxylaminolysis the C3 fragment dissociates from the crystals. This indicates a covalent ester bond linking the labile binding site of activated C3 to the hydroxyl group of cholesterol. Cholesterol acetate does not fix C3 nor acquire a C3-cleaving activity upon contact with serum. In addition, cholesterol crystals bind factor I (C3b inactivator) and in this way may facilitate fixation and amplification of the alternative C3/C5 convertase.

Cholesterol↗
PubMed1985

Generation of anaphylatoxin activity related to C3a, by treatment of human serum with the nitrogen nucleophile N2H4 or the chaotrope KSCN.

The present study is concerned with the proteolytic processing of complement component C3 in normal human serum treated with N2H4 or KSCN in the presence of EDTA. Upon incubation with these agents, C3 is first converted to the thiolester-cleaved form (C3i) and thereafter fragmented by factor I. In consecutive, relatively slow steps, spasmogenic and platelet-aggregating activity is released. The active principle shows characteristics of C3a. First, the pretreated sera deactivate guinea pig ileum and platelets towards the action of C3ahog, but not C5a-desArghog. Second, the activity is only stable under conditions causing inhibition of serum carboxypeptidase N, such as in the presence of EDTA or of MERGETPA (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid). Third, the molecular weight determined by gel filtration is in agreement with that of C3a. The release of C3a activity requires conversion of C3 to C3i, as well as the complement-independent generation of proteolytic activity in the pretreated sera. The enzyme releasing C3a activity is a serine esterase probably identical with Hageman factor, kallikrein, or another protease related to the contact system.

Anaphylatoxins↗
PubMed1985

Effect of different sulfonamides on the human serum complement system.

Incubation of normal human serum with different sulfonamides led to a dose-dependent inactivation of total hemolytic complement activity. A decrease of the activities of C1, C2, C3, C5 and one or several of the components C6-9 was observed after treatment of normal human serum with the sulfonamide sulfisomidine. Inactivation of complement components by sulfonamides seems to result from direct interaction with the drug as well as, to a minor extent, from activation of the alternative pathway. At relatively high concentrations, sulfonamides caused a conformational change in C3 and C4. The observed structural change is equivalent to that induced by cleavage of the internal thiolester bond in these molecules. The generation of such structurally altered C3 (C3b-like C3) as well as an antagonizing effect of sulfonamides towards the action of the regulatory protein factor I might be responsible for alternative pathway activation. The physiological relevance in vivo of the observed effects of sulfonamides remains to be assessed.

Complement C3↗
PubMed1984

[Spontaneous behavior and bioelectric activity as indicators of brain development in premature infants. A polygraphic study].

Assessment of neural integrity and developmental level of brain functions in preterm infants are essential parts of perinatal intensive care. Special techniques are needed to account for age-specific characteristics and rapid developmental changes of the preterm infant's functional repertoire during the first postnatal weeks. For the evaluation of at-risk infants with pre-, peri- and postnatal complications a well-substantiated knowledge of the developmental course in otherwise "healthy" preterms is a prerequisite. EEG--and behavioural development from 8 weeks before till 5 weeks after term, studied in a carefully selected group of 14 "low risk" preterm infants are described. Respective data from a group of "high risk" infants served to indicate possible deviations in developmental courses. EEG--and behavioural state profiles, bioelectrical age and a newly developed score of polygraphic optimality are presented as measures of brain function for clinical use. The described methods also constitute a useful complement to the neurological examination.

Brain↗
PubMed1984

Effect of metrizamide, a nonionic radiographic contrast agent, on human serum complement. Comparison with ionic contrast media.

The nonionic radiographic contrast material (RCM) metrizamide causes consumption of total complement activity in normal human serum (NHS) in vitro in the absence and to a lesser extent also in the presence of EDTA. The depression of titers of total complement is related to an inactivating effect of metrizamide on component C2. Furthermore, metrizamide induces activation of the alternative pathway as evidenced by the appearance of C3 and factor B cleavage products in NHS, dependent on the presence of divalent cations. Alternative pathway activation is probably mediated by an antagonizing effect of metrizamide on the inactivation of C3b. Unlike ionic RCM, the nonionic substance metrizamide does not lead to cleavage of the internal thiolester bond present in native C3 and C4, at concentrations that produce potent consumption of C3 activity in NHS.

Complement Activation↗
PubMed1984

Effect of different penicillin derivatives on complement components in human serum.

The effect of different penicillin derivatives on the human complement system has been studied in vitro. Four penicillins tested (benzylpenicillin, oxacillin, methicillin, azlocillin) were found to inactivate total hemolytic complement dose dependently. This effect is caused by direct inactivation of C2, C5 and one or more of the components C6-9 as well as by activation of the alternative pathway. At relatively high concentrations, penicillins induce a conformational change in C3 and C4, leading to the C3b-like or C4b-like forms of these molecules, respectively. Prominent effects on the complement system occur at penicillin concentrations exceeding those achieved in plasma under regular therapeutic use. However, a synergism of penicillins with drugs acting similarly on the complement system, such as iodinated radiographic contrast media, may be expected.

Azlocillin↗
PubMed1983

Natural antibodies against a polysaccharide (Bo) from sugar cane mediate its complement-activating effect.

The interaction of a complement activating glucan from sugar cane (Bo) with immunoglobulins was studied. Bo precipitates a small fraction of IgG from human serum. In combination with this fraction, it activates complement by the classical pathway, not in its absence. Bo is adsorbed to and can be eluted from Sepharose containing covalently coupled IgG; it is not bound when the IgG-Sepharose is lacking the Bo-reactive IgG fraction. Bo-IgG complexes activate and fix C1. The binding of C1 to aggregated IgG is not inhibited by Bo. This is in contrast to the strong inhibition of C1 fixation by the Fc-binding protein A. It is concluded that normal human serum contains natural antibodies against Bo which form complement-activating immune complexes with Bo by binding it to their F(ab) region. The antibodies do not cross-react with dextran, a glucan from barley, nor with surface constituents of E. coli.

Antibodies↗
PubMed1981

Treatment of human complement components C4 and C3 with amines or chaotropic ions. Evidence of a functional and structural change that provides uncleaved C4 and C3 with properties of their soluble activated froms, C4b and C3b.

Treatment of human components C4 and C3 with amines like hydrazine, ammonium hydroxide, and neutral ammonium salts or with chaotropic salts like KSCN and NaBr leads to complete loss of haemolytic activity. The pretreated components are, however, still active in formation of soluble C3 convertases. This activity pattern is reminiscent of the activities of C4 and C3 that have been activated by cleavage in the fluid phase. Indeed, the antigenic properties of pretreated C4 and C3 are similar to soluble C4b and C3b. The polypeptide chain structure of pretreated C4 and C3, is, however, identical to that of the untreated components when investigated by SDS gel electrophoresis. Pretreatment even reduces greatly the susceptibility of C4 to cleavage by C1s and of C3 to cleavage by classical and alternative pathway C3 convertases. Pretreated components have lost the ability to combine with EAC1 and EAC142, respectively; this fact explains their failure to exhibit haemolytic activity. In serum, pretreated C4 and C3 are cleaved in a manner similar to C4b and C3b. Amines and chaotropic ions cause the same functional and structural alterations, which are best explained by assumption of a conformational change. A similar transformation can also occur in C4 and C3 during preparation or storage.

Amines↗
PubMed1980

[Neurological complications in children with congenital cyanotic heart disease (author's transl)].

Figures of incidence and risk factors of neurological complications (NC) endangering children with cyanotic congenital heart disease (CCHD) are very different. We examined 308 children with CCHD over an 8 years' period finding 39 cases (= 12,7) of NC. There were 5 hypoxic attacks and 3 brain abscesses. In 31 patients a cerebro-vascular accident was proven or probable. 56% of NC occured during the first year of life, most frequently in children with simple TGA. Mortality was not influenced by NC. Children without NC, surviving the first year of life represent the control group for comparison of the following hematologic parameters: erythrocytes, hematocrit, MCHC, hemoglobin, O2-saturation, platelets count. Only the last two were significantly lower in patients with NC, but no parameter allows to predict NC. The hypothesis of hypochromic, microcytic anemia as essential pathogenetic factor for cerebro-vascular accidents has no base in our material.

Age Factors↗
PubMed1979

Comparison of phenytoin determinations in plasma, plasma dialysate and saliva for control of antiepileptic therapy in children.

Phenytoin was determined in plasma or serum, dialysate from plasma or serum and saliva in 45 children and 7 adults by gas chromatography. 200 microliter of plasma were necessary for dialysis. Close correlations were found between phenytoin concentrations in the different media (r greater than or equal to 0.95). Since in some cases the levels in saliva were extremely high in comparison to plasma and dialysate, precautions are advisable when using phenytoin determinations in saliva for therapeutic decisions. Clinical data from 15 children with high phenytoin levels suggest that there is no advantage in determining the unbound fraction of the drug in plasma for the control of antiepileptic therapy.

Adolescent↗
PubMed1979

Incompatibility between complement components C3 and C5 of guinea-pig and man, an indication of their interaction in C5 activation by classical and alternative C5 convertases.

The use of heterologous combinations of guinea-pig and human complement components for titration of C5 with convertases of the alternative and classical pathway has been investigated. In addition to the known unfavourable combination of C2hu with C4gp partial incompatibilities were detected between heterologous C3 and C5 as well as between CZhu and C5gp. The incompatibility between heterologous C3 and C5 is of special interest since it indicates an interaction of these two non-enzymic components. Concomitant binding studies have demonstrated that a reduced efficiency of C5 convertases correlates with decreased binding affinity of surface-fixed C3b for C5 when heterologous components are offered. Hence, the present studies give further evidence that surface-bound C3b has the function of a co-factor which binds C5; this interaction is required for C5 activation via the classical as well as the alternative pathway, i.e. by the C3/C5 convertases C42 and C3bB.

Animals↗
PubMed1978

A polygraphic study of bioelectrical brain maturation in preterm infants.

Bioelectrical brain maturation was studied in 26 low-risk preterm infants by serial polygraphic recordings. A modified method of visual EEG analysis was used, based on Parmelee's coding system, which allowed quantification. It gave the following results: (1) The main characteristics of EEG maturation in preterm infants were a progressive spatio-temporal differentiation, with an increase of rhythmic activities and a decrease of discontinuity. (2) A strong relationship was found between post-menstrual age of the infants and EEG maturity, but there were exceptions to this rule. (3) longer duration of extra-uterine life had a small accelerating influence on EEG maturation. (4) Certain basic types of EEG patterns were closely related to behavioural states, whereas EEG maturity was not state-dependent. (5) The relationship between EEG pattern types and behavioural states becomes more stable with increasing age.

Electroencephalography↗