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Biomedical subjects

F R Seiler

Publications and source records attributed to F R Seiler.

At least 109 records · Page 6Linked to original sources
PubMed1981

Mouse spleen cells are sensitized sheep red blood cells: an Fc-rosette-forming system allowing the detection of "activated" Fc structures.

From a variety of Fc receptor-bearing cell/sensitized red blood cell combinations, mouse spleen cells, and sensitized SRBC were selected as an Fc-specific EA rosette assay system because only this mixture combined a high percentage (about 50%) of rosette-forming cells with complete absence of spontaneous rosettes and showed no influence of complement on the rosette formation. From studies on the minimal structural requirement of IgG both for mediation and inhibition of EA rosettes using IgG and several well-defined fragments, it appeared that both the CH2 and the CH3 domain of Fc are needed for optimal interaction with the lymphocyte Fc receptor. Finally, it was demonstrated that the assay system is able to detect "activated" Fc structures (here: heat-aggregated IgG) and to differentiate between varying amounts of such structures.

Animals↗
PubMed1981

In-vivo phagocytosis: enhancement of bacterial clearance by native and enzyme-treated immunoglobulins.

The enhancement of bacterial blood clearance in mice by native and enzymatically derived fractions of rabbit anti-E. coli hyperimmune serum was tested. Native immune serum, the corresponding IgG, F(ab')2 and Facb fractions strongly augmented the phagocytosis rate of bacteria, whereas Fab/Fc, Fab, Fc fragments, corresponding preparations from normal serum, and E. coli-absorbed preparations showed no marked enhancing capacity. In one experiment opsonization by IgM was demonstrable. Mice that were injected with fatal doses of bacteria could be protected by subsequent treatment with IgG or F(ab')2 preparations of rabbit anti-E. coli serum. Conclusion is drawn that the Fc region of the IgG molecule is not predominantly responsible for opsonized clearance while the intact divalent antigen cross-linking F(ab')2 fragment - presumably by virtue of complement activation via the alternate pathway - could mediate enhanced bacterial clearance.

Animals↗
PubMed1980

BCG versus VCN: the antigenicity and the adjuvant effect of both compounds.

Enzymatically active Vibrio cholerae neuraminidase (VCN) acts as an adjuvant when it is combined with an antigen. This has been demonstrated for bacterial, viral, protein, and cellular antigens and was found for the humoral, but more pronounced for the cellular immune response. In this study, the adjuvant activity of VCN for live BCG is discussed. Live BCG itself is regarded as a rather potent immunostimulator. A total of 6.5 mU of VCN, being most effective as derived from previous adjuvant experiments, was combined with 10(6) or 10(7) live BCG and injected IV into mice. Booster injections were given on day 12. Challenge was administered in the footpad on day 17 either with 6.5 mU VCN or with 5 x 10(4) or 5 x 10(6) dead BCG. Footpad swelling was recorded 24 h after challenge. After clinical examination, mice were bled and antibodies against BCG and VCN were measured. The results show that VCN specifically enhances the cellular, not the humoral, immune reaction against BCG, while BCG is unable specifically to enhance immune reaction against VCN. However, BCG unspecifically stimulates the cellular reaction of the organism against an antigen, primarily injected, subsequent to BCG for instance, against VCN.

Adjuvants, Immunologic↗
PubMed1980

Molecular aspects of albumin functions: indications for its use in plasma substitution.

The maintenance of the circulating fluid within the vascular system is a major role of plasma albumin. Besides its role as a protein reservoir the third function of albumin is its ability to bind and transport metabolic products, regulatory mediators, nutrients and proteins and to bind and neutralize endogenous or exogenous toxins. Bilirubin binding was chosen as a method to describe functional quality of albumin preparations. Binding at the high affinity site is well preserved in all commercial albumin-containing plasma substitutes investigated with KA values in the range of 3.2 to 4.8 . 10(7) 1/mol. Presence of absence of conventional stabilizers does not influence binding characteristics since heating of products according to various pharmacopoeia levels out any difference. The importance of ligand binding properties of a plasma substitute is stressed either in intoxications, e.g. hyperbilirubinemia of neonates or in surgical situations were multiple drug applications might disturb a balanced binding situation. Though relatively mild in nature and less frequently observed in comparison with artificial plasma substitutes incidence of adverse reactions in connection with albumin was used to search for causes. Biochemical parameters like residual proteolytic activity in general or specified (prekallikrein activator), content of aggregates, anti-complementary activity and influence on granulocyte activity did not give any clear answer in this task, neither did pharmacological testing designed to detect factors leading to histamine and kinin liberation or to detect pyrogens.

Bilirubin↗
PubMed1979

A new method for fluorescence immunoassay using plane surface solid phases (FIAPS).

A method distinguished by high sensitivity, low non-specific binding, easy handling, and broad applicability with respect to various antigens is described. Films of polymethyl-methacrylate with plane surfaces were selected as solid phase for adhesive or covalent binding of different antigens (DNA, histone, human, rabbit or goat immunoglobulins). Proteins were covalently bound to the films by the azide method (Orth and Brummer, 1972). Polymethylmethacrylate films thus coated had a negligible autofluorescence and gave minimal non-specific binding of protein. Coated films were used for specificity control of FITC-labeled antibody preparations and in the double antibody and sandwich techniques for detection of antibodies or antigens in sera from man, rabbit and goat. FITC-conjugated hyperimmune antibody, in some cases purified by immunoadsorption was used as second antibody in indirect techniques. The amount of fluorescent-labeled antibody bound per unit of surface area of film was measured by incident light with a Zeiss-Axiomat fluorescence microscope equipped for fluorescence photometry and an uranyl acetate glass plate was used as a standard. The technique appears superior to present methods of quantitative immunofluorescence analysis.

Animals↗
PubMed1979

Antigen-specific detection of HBsAG-containing immune complexes in the course of hepatitis B virus infection.

In recent studies extrahepatic manifestations of viral hepatitis have been recognized as immune complex diseases. Hepatitis B surface antigen (HBsAg) has been successfully identified in immune complexes, but the pathogenic role of HBsAg-containing immune complexes (IC) remains questionable. The subject of the present study was the antigen-specific determination of IC in the course of hepatitis B virus infection using a new HBsAg-specific IC test (Pernice & Sedlacek, 1978). This test is based on the following principle: rabbit anti-HBs-coated polystyrole test tubes are incubated with the IC-containing test sample. The HBsAg-containing IC bind to the solid phase by their free antigenic determinants. There they can be quantified using a peroxidase-labelled anti-human IgG antibody. A good correlation was found between the level of HBsAg-containing immune complexes and the clinical state of six patients in a follow-up study. IC could be detected simultaneously with HBsAg and either decreased or disappeared before the occurrence of free anti-HBs. In the sera of an additional twenty-eight patient suffering from chronic active hepatitis, HBsAg-containing immune complexes were detected in 85% of cases. One patient suffering from polyarteritis nodosa was also positive. Occasionally, extremely high levels of IC were found in the course of these diseases.

Antigen-Antibody Complex↗
PubMed1979

Comparison of several in vitro assay methods for the quantitative determination of complement consumption ('binding') by gammaglobulin preparations.

Unspecifically induced activation of Complement (C) in solution can be caused either by denatured Ig molecules and by polymeric aggregates of same or more specifically by antigen-antibody complexes. As a quality criteria, e.g. for i.v.-IgG preparations, it is agreed by the majority of people concerned that the activation of C via the classical pathway might not be unspecifically initiated. Therefore, the generally used assay systems are based on quantitating the degree of consumption of C undergoing an antigen-independent, 'frustrated' activation via the classical pathway. There are principally two different types of test modifications which were investigated: a) C is being kept constant and protein is diluted or b) protein is being kept constant and C is titrated. When a group of differing IgG preparations or IgG fragments was assayed for its so-called 'anticomplementary' activity in various already described test methods, the particular test results from the individual test methods could not unequivocally be compared with each other because some of the methods had not been optimized with regard to the amount of reagents or test substance used; only a rough estimate of the data was obtained. The value of the not standardized assays remains, therefore, questionable reasonably good and reproducible results are obtained when the amount in particular of C added as well as its quality have been adequately optimized and standardized. This allows a refined differentiation of various IgG preparations by a reliable and unadjusted quantitation of C consumption. If for example, inappropriate and not optimized rations of C amboceptor (e.g. slight C excess) was used, a suppressed C consumption was found. It seems advisable to accept prophylactic testing of anticomplementary activity for quality control as one out of several other in vitro and in vivo parameters which potentially might predict safety for the patient, the physician, and also for the producer. However, it is agreed that, irrespective of in vitro tests, in vivo testing in animals and clinical proof of safety is undoubtedly needed.

Animals↗
PubMed1978

Effect of Vibrio cholerae neuraminidase on the phagocytosis of E. coli by macrophages in vivo and in vitro.

The mechanisms by which Vibrio cholerae neuraminidase VCN acts as an adjuvant is unclear. We have studied the effect of VCN on the phagocyotsis of E. coli 0111 K58 by macrophages in vivo and in vitro. (1) Using and in vivo intraperitoneal clearance test we have shown that prior injection of VCN (50 units/mouse) into the peritoneal cavity of mice enhances the clearance of the bacteria as efficiently as an optimal amount of opsonizing antiserum. We have also shown that the enhancement of intraperitoneal clearance by VCN is due to phagocytosis and intracellular killing of the organisms by macrophages. (2) VCN does not enhance the i.v. clearance of E. coli o111 K58. (3) VCN promotes the attachment of the organisms to and phagocytosis by peritoneal macrophages in vitro. Data are provided which suggest that the promotion of attachment and phagocytosis by VCN cannot be explained by a mere increase of passive absorption of the bacteria to the cell wall.

Animals↗
PubMed1977

Neuraminidase and tumor immunotherapy.

Preliminary results of first clinical studies with the enzyme neuraminidase call attention to a new kind of cancer treatment. This promising approach to tumor immunotherapy was entered into the clinical phase as a consequence of successful experimental studies in tumor-bearing mice, rats and dogs. In this review, the presently known and essential results of experimental and clinical studies on tumor immunotherapy by means of neuraminidase are presented as well as some necessary and critical considerations in this context. Moreover, out of a broad variety of results of biochemical and biological in vitro studies, it was attempted to select the more essential knowledge which could contribute to a better understanding of the still rather unclear in vivo mode of action of the enzyme neuraminidase. In a first brief paragraph (1.0), the biochemically characteristic data of the enzyme neuraminidase is presented. In the second section (2.0), the basic knowledge about the effects of neuraminidase on cell behavior is rather amply contained. Here, on the one hand, the biophysical and biochemical alterations are mentioned, the so-called ""unmasking'' effects are reconsidered and, on the other hand, the effects on the immunologically responding cell are discussed. In a third section (3.0), the diverse findings from animal experiments using neuraminidase-treated tumor cells are confronted, whereby tumor transplantation experiments and tumor therapy experiments are dealt with separately. The last section (4.0) reports about the first clinical studies with neuraminidase-treated autologous as well as homologous tumor cells, which partly brought about rather surprising and astonishing success. On the basis of recent findings by the study group of the authors, the more prior and sometimes discrepant results of various groups are critically considered. The problems of alteration of antigenicity and of other properties of cells through splitting off membrane-bound neuraminic acid, the facts of adjuvanticity of neuraminidase itself, the relation of successful therapy to dose dependency as well as the relation of undesirable methods for tumor mass reduction to the immunological responsiveness of the tumor bearer were especially looked into.

Animals↗