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G Steiger

Publications and source records attributed to G Steiger.

34 records · Page 2Linked to original sources
PubMed1986

Complement mediated inhibition of immune precipitation and solubilization generate different concentrations of complement anaphylatoxins (C4a, C3a, C5a).

Complement prevents the formation of insoluble immune complexes (inhibition of immune precipitation (IIP], and solubilizes preformed immune aggregates (solubilization (SOL]. Since the mechanism of complement activation differs in these two reactions, it is possible that they differ also in the amount of complement fragments released, in particular the anaphylatoxins C3a, C5a and C4a. We measured C4 and C3 consumption, and the formation of complement anaphylatoxins during IIP and SOL using two different immune complex models (BSA, rabbit anti-BSA; tetanus toxoid (TT), human anti-TT). At equal immune complex concentrations in both models, SOL was more efficient than IIP at cleaving C3, and more C3a and C5a was released. Comparing the two reactions, C3a formation was followed by more C5 cleavage (C5a) during SOL. Similarly C4a formation (classical pathway activation) was followed by more C3 cleavage (C3a: classical and alternative pathway activations), during SOL. It is suggested that in vivo SOL of insoluble complexes is rapidly accompanied by a damaging phlogistic reaction, whereas IIP produces less inflammation.

Antigen-Antibody Complex↗
PubMed1985

A simple two-step procedure for the preparation of the first component of human complement (C1) in its native form.

Native human C1 was purified from fresh human serum by affinity chromatography on protein A-bound Sepharose in the presence of 4-nitrophenyl-4-guanidinobenzoate hydrochloride (NPGB) taking advantage of the successive binding of IgG to protein A followed by C1 binding to IgG. After elution the C1 preparation contained IgG as a major contaminant as shown by SDS-PAGE. C1 was further purified by gel filtration. The yield of C1 was 12% and less than 4% of this C1 was activated during purification as assessed by a C4 consumption assay.

Chromatography, Affinity↗
PubMed1985

Activation of the alternative pathway of complement by skin immune deposits.

Skin immune deposits at the basement membrane zone have been demonstrated by functional assays to activate complement. This important biologic function has not yet been explored for immune deposits present in other locations mainly because many cytoplasmic structures in the skin have the capacity to activate the complement cascade by the classical pathway. In this study the capacity of immune deposits to activate directly the alternative pathway was examined using a functional guinea pig C3 binding test. This test was devised so as to avoid complement activation by normal cutaneous structures, thus it did not examine the capacity of immune reactants to activate the classical pathway. The main findings were that alternative pathway activation could be demonstrated only when human C3 deposits were seen by direct immunofluorescence, but not all C3 deposits were found to activate the alternative pathway; such activation was restricted to vascular deposits; the phlogistic potential of the immune deposits correlated with serologic evidence of ongoing immune reactions, i.e., hypocomplementemia and circulating immune complexes. It is suggested that this test provides data on one aspect of the phlogistic potential of skin immune deposits not detectable by direct immunofluorescence.

Animals↗
PubMed1985

Formation of soluble immune complexes by complement in sera of patients with various hypocomplementemic states. Difference between inhibition of immune precipitation and solubilization.

To examine whether the ability of complement to form soluble immune complexes plays a role in preventing immune complex-mediated diseases, we analyzed the capacity of complement to inhibit immune precipitation (IIP) and to solubilize preformed immune aggregates (SOL) in 23 sera of patients with various hypocomplementemic states, and we correlated the results of these studies with the clinical syndromes found in the various patients. In sera with deficiency or depletion of early classical pathway components, IIP was profoundly altered, whereas SOL was delayed but in the normal range. In contrast, in sera with C3 depletion but intact classical pathway and in properdin-deficient serum, IIP was initially preserved, whereas SOL was abolished. Since the incidence of immune complex diseases in various hypocomplementemic states correlates with the severity of IIP defects, but not with reduced SOL, it is suggested that IIP is an essential biological function of complement that prevents the rapid formation of insoluble immune complexes in vivo.

Antigen-Antibody Complex↗
PubMed1985

The role of C1, C1-inactivator and C4 in modulating immune precipitation.

To clarify the mechanism of inhibition of immune precipitation by early components of the classical pathway of complement, aggregation of 125I-BSA-rabbit-anti-BSA antibody complexes was performed in the presence of purified C1, C1-inactivator (C1-In) and C4. C1 delayed the rate of immune precipitation in a concentration dependent manner. This phenomenon was not influenced by the presence of 0.3 mM p-nitrophenyl-p-guanidinobenzoate (NPGB) which inhibits C1 activation. The antiaggregational effect of C1 was reversed by 10 mM EDTA and by C1-In at a C1-In/C1 molar ratio of greater than or equal to 4/1. C1-In was not effective when the reaction was performed in the presence of NPGB. Thus, although the inhibitory effect of C1 on immune precipitation was not dependent upon C1 activation, the formation of C1 was required to observe the effect of C1-In. The addition of C4 to C1 did not modify the slow aggregation of complexes, even when a limiting concentration of C1 was used. C1-In and EDTA were both able to cause similar rapid precipitation of complexes prepared in the presence of C1 and C4, demonstrating that C4 did not play a significant role in delaying the precipitation reaction. However, soluble complexes prepared in the presence of C1 and C4 were specifically precipitated by the addition of excess anti-C4 antibody, attesting to the binding of C4 to immune complexes. These observations suggest that the processing of immune complexes in vivo may not be similar in different classical pathway complement deficiency states.

Animals↗
PubMed1984

The monodeiodination of triiodothyronine and reverse triiodothyronine in man: a quantitative evaluation of the pathway by the use of turnover rate techniques.

These studies were performed to evaluate the quantitative role of monodeiodination in the peripheral metabolism of T3 and rT3 in man. As a prerequisite step, the serum concentrations of two diiodothyronines (T2s), 3,5-T2 and 3',5'-T2, were established by specific RIAs. In 20 normal subjects, mean (+/- SEM) serum concentrations of 3,5-T2 and 3',5'-T2 were 0.40 +/- 0.18 and 2.07 +/- 0.13 ng/dl, respectively. The mean concentrations of both T2s were significantly increased in hyperthyroidism. In primary hypothyroidism, the mean 3,5-T2 concentration was not significantly different from normal, but 3',5'-T2 concentrations were undetectable in the majority of subjects. In the first experiments, the MCRs of rT3 and all three T2s were derived by the constant infusion method. Seven normal subjects were infused simultaneously with the three 125I-labeled T2s for 12 h, and in four of the subjects, [131I]rT3 was also administered. The MCRs (liters/day . 70 kg; mean +/- SEM) were: rT3, 130 +/- 17; 3,5-T2, 168 +/- 15; 3,3'-T2, 621 +/- 84; and 3',5'-T2, 305 +/- 45. The daily production rates (PR; micrograms per day/70 kg; mean +/- SEM) were: rT3, 29.1 +/- 1.0; 3,5-T2, 0.6 +/- 0.1; 3,3'-T2, 20.8 +/- 4.1; and 3',5'-T2, 5.7 +/- 2.1. In the four subjects who received [131I]rT3, the serum T2 concentrations and PRs were also derived by turnover rate techniques. At equilibrium, 2.0 +/- 0.7% and 6.0 +/- 1.6% of [131I] rT3 were found as [131I]3,3'-T2 and [131I]3',5'-T2, respectively. The serum T2 concentrations were derived by the product of these percentages and the serum rT3 concentrations and compared with those obtained by T2 RIA. The serum 3',5'-T2 concentration was 1.3 +/- 0.4 ng/dl (tracer), and its PR was 3.4 +/- 1.1 micrograms/day (tracer); these values were closely correlated with those obtained by RIA. Serum 3,3'-T2 concentrations were 0.4 +/- 0.2 ng/dl (tracer) and 2.7 +/- 0.4 ng/dl (RIA), and the PRs were 3.2 +/- 1.6 micrograms/day (tracer) and 20.3 +/- 5.7 micrograms/day (RIA), indicating that rT3 5'-deiodination contributes only a small proportion of serum 3,3'-T2 and its PR. An analysis of the rT3 PR and the 3,3'-T2 and 3',5'-T2 PRs derived from the turnover of rT3 revealed that 28% of the rT3 produced was degraded by monodeiodination. Of this total, 49% of the deiodination occurred at the 5' position and 51% occurred at the 5 position.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Precipitation↗
PubMed1983

Ether link cleavage is the major pathway of iodothyronine metabolism in the phagocytosing human leukocyte and also occurs in vivo in the rat.

These studies were performed to test the hypothesis that ether link cleavage (ELC) is an important pathway for the metabolism of thyroxine (T(4)) in the phagocytosing human leukocyte. When tyrosyl ring-labeled [(125)I]T(4)([Tyr(125)I]T(4)) was incubated with phagocytosing leukocytes, 50% of the degraded label was converted into [(125)I]3,5-diiodotyrosine ([(125)I]DIT). Of the remaining [Tyr(125)I]T(4) that was degraded, two-thirds was recovered as [(125)I]-nonextractable iodine ([(125)I]NEI), and one-third as [(125)I]iodide. The production of [(125)I]DIT was not observed when phenolic ring-labeled [(125)I]T(4) ([Phen(125)I]T(4)) was used, although [(125)I]NEI and [(125)I]iodide were produced. None of these iodinated compounds were formed in leukocytes that were not carrying out phagocytosis. The fraction of T(4) degraded by ELC was decreased by the addition of unlabeled T(4) and by preheating the leukocytes, findings which suggested that the process was enzymic in nature. ELC was enhanced by the catalase inhibitor aminotriazole, and was inhibited by the peroxidase inhibitor propylthiouracil, suggesting that the enzyme is a peroxidase and that hydrogen peroxide (H(2)O(2)) is a necessary cofactor in the reaction. To test this hypothesis, studies were performed in several inherited leukocytic disorders. ELC was not observed in the leukocytes of patients with chronic granulomatous disease, in which the respiratory burst that accompanies phagocytosis is absent. ELC was normal in the leukocytes of two subjects homozygous for Swiss-type acatalasemia, and aminotriazole enhanced ELC in these cells to an extent not significantly different from that observed in normal cells. ELC was normal in the leukocytes of a patient with myeloperoxidase deficiency, but could be induced by the incubation of [Tyr(125)I]T(4) with H(2)O(2) and horseradish peroxidase in the absence of leukocytes. The in vivo occurrence of ELC in the rat was confirmed by demonstrating the appearance of [(125)I]DIT in serum from parenterally injected [(125)I]3,5-diiodothyronine, but no [(125)I]DIT was produced when [(125)I]3',5'-diiodothyronine was administered. FROM THESE FINDINGS WE CONCLUDE THE FOLLOWING: (a) ELC is the major pathway for the degradation of T(4) during leukocyte phagocytosis, and accounts for 50% of the disposal of this iodothyronine; (b) the NEI and iodide formed by phagocytosing cells are derived from the degradation of the phenolic and tyrosyl rings of T(4), although ELC per se accounts for only a small fraction of these iodinated products; (c) the process by which ELC occurs is enzymic in nature, and its occurrence requires the presence of the respiratory burst that accompanies phagocytosis; (d) the enzyme responsible for ELC is likely to be a peroxidase, although a clear role for myeloperoxidase as the candidate enzyme remains to be established; (e) iodothyronines are also degraded by ELC in vivo, and the quantitative importance of this pathway in various pathophysiological states requires further investigation.

Amitrole↗
PubMed1982

Determination of chloride concentration in cheese: collaborative study.

Three samples of ground Gouda cheese containing 1-2% chloride were analyzed by 7 laboratories by 3 methods: oxidation with KMnO4 and HNO3 followed by a Volhard titration; the same but with filtering off the precipitated AgC1 before back-titration; and the general potentiometric method without ashing or oxidation. The data were analyzed by ISO statistics (ISO-R 5725) and by AOAC statistics (Youden), the major differences being the rejection of different values as outliers and in the statement of the precision parameters. The within-laboratory variability (repeatability) is comparable for all 3 methods; the between-laboratory variability (reproducibility) is comparable for the Volhard method with filtration and the potentiometric methods, but the direct Volhard method is inferior. Because of its generality and simplicity, the potentiometric method has been adopted official first action; the Volhard method with filtration has been reinstated official final action as an alternative.

Cheese↗
PubMed1978

[Application HTST-heating of the mash and its influence on the aroma composition during the production of apple brandy (author's transl)].

The influence of HTST-heating of the mash aroma composition during production of apply brandy has been investigated by means of gas chromatography and coupled gas chromatography--mass spectrometry. Starting from the apple aroma the changes in aroma components were studied quantitatively during the conventional production (without enzyme inhibition) as well as after HTST-heating (enzyme inactivation) of the mash. For this purpose 98 aroma compounds were determined in the course of mash production, fermentation and distillation. When employing HTST-heating the original aroma components of the apple particularly the fruit esters were present in appreciably higher concentrations in the mash as well as in the distillate than with the conventional production method. Simultaneously HTST-heating reduced the secondary aroma substances in mash and distillate which are formed with the conventional method by enzymatic-oxidative processes. In the unaged apple brandy obtained from HTST-treated mash lower amounts of lactates and higher concentrations of acetals were found compared with the conventionally produced distillate.

Acetates↗
PubMedDate not supplied

Determination of phosphorus in processed cheese: collaborative study.

A second interlaboratory collaborative study of the determination of phosphorus in processed cheese products by the molybdenum blue method verifies that this method is prone to producing a laboratory-induced systematic error. It would be useless to continue to make minor modifications in the details of the method, which will improve only the within-laboratory precision, until an accuracy control of the final measurement step is incorporated into the method.

Cheese↗