Biomedical subjects

F R Seiler

Publications and source records attributed to F R Seiler.

At least 73 records · Page 4Linked to original sources

PubMed1987

Tumor therapy of neoplastic diseases with tumor cells and neuraminidase: experimental studies on chessboard vaccination in transplantation tumors.

The therapeutic effect of intradermal (i.d.) injection of tumor cells mixed with VCN on growth of spontaneous metastases in transplantable tumors in mice (3-Lewis lung adenocarcinoma; B16-melanoma) and rats (R-3230 mammary adenocarcinoma) was investigated. Intradermal injection was done in a chessboard-like manner; increasing numbers (10(5), 10(6) and 10(7)) of Mitomycin-treated tumor cells (M-TC) were each mixed with increasing amounts (10, 50 and 100 mU) of Vibrio cholerae Neuraminidase (VCN). These different mixtures were injected i.d. at different sites one day after resection of the primary tumor graft to mice and rats, suffering from minimal residual disease. The therapeutic effect of this so-called chessboard vaccination on minimal residual disease was compared to that of the subcutaneous or i.d. injection of VCN-treated M-TC (10(5), 10(6), 10(7) or 10(8) cells) or of single mixtures of M-TC and VCN. The results show that compared to VCN-treated M-TC or single mixtures of M-TC and VCN, chessboard vaccination is the only procedure that is therapeutically effective on metastasation of Lewis lung adenocarcinoma. The therapeutic effect could be abrogated by heat-inactivation of VCN. Incomplete chessboard vaccinations (10(5), 10(6), 10(7) tumor cells, each mixed with 5 mU VCN only) were likewise ineffective. However, treatment with incomplete chessboard vaccinations in combination with a low dose of cyclophosphamide (which is not immunosuppressive, but partly inhibits tumor growth) had a synergistic therapeutic effect on minimal residual disease of Lewis lung adenocarcinoma. In contrast, growth of metastases of B16-melanoma and R-3230 adenocarcinoma could not significantly be influenced by any of those treatments. The DTH response of tumor bearing animals against i.d. applied tumor cells was neither significantly enhanced by the admixture of enzymatically active VCN nor did the DTH response seem to be predictive for a tumor-therapeutic effect. Thomsen-Friedenreich antigens could serologically be detected on untreated cells of Lewis lung adenocarcinoma, B16-melanoma and R-3230 adenocarcinoma. Exposure of Thomsen-Friedenreich antigens after treatment with VCN was enhanced on cells of all tumors except Lewis lung adenocarcinoma. As chessboard vaccination only proved to be successful in Lewis lung adenocarcinoma, but not in the other tumors, it can be concluded that the exposure of Thomsen-Friedenreich antigen plays no decisive role in tumor therapy with tumor cells and VCN. Chessboard vaccination was tolerated without any side effects. Tumor enhancement was not observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

PubMed1987

Quality criteria for i.v. immunoglobulins: importance of tests and product properties.

Quality criteria for i.v. immunoglobulins (i.v. Igs) are critically discussed laying emphasis on spontaneous anticomplementary activity (aca) and size-dependent composition. Considering the percentage of fractions obtained by gel filtration (Ultrogel AcA 34), however, the monomeric IgG containing fraction contributed the major part of aca under the experimental conditions chosen. Subclass IgG3 seems to contribute considerably to aca. No correlation was found between aca and the percentage of fractions containing components larger in size than IgG dimers in various commercially available Igs. Moreover, the subclass distribution in different batches of individual products showed considerable variations. The amount of IgG4 is correlated with that of IgA in chemically unmodified products relatively poor in IgA (approx. less than or equal to 10 mg/5 g Ig), indicating that attempts to reduce IgA consequently result in removal of IgG4.

Germany, West↗

PubMed1986

Tumor therapy of neoplastic diseases with tumor cells and neuraminidase. Further experimental studies on chessboard vaccination in canine mammary tumors.

The therapeutic effect of i.d. injection of tumor cells mixed with Vibrio cholerae neuraminidase (VCN) on tumor progression in dogs with spontaneous mammary tumors was investigated. The i.d. injections were performed in a chessboard-like manner: different numbers (10(5), 10(6), 10(7), and 10(8) of mitomycin-treated autologous tumor cells (M-TC) were each mixed with different amounts (10, 50, and 100 mU) of VCN. These different mixtures were injected i.d. at different sites in dogs on the day of resection of a part of multiple tumors.

Adjuvants, Immunologic↗

PubMed1986

The functional inhibition of activated C1 inhibitor in normal human serum causes spontaneous consumption of the complement components C2, C3, C4, and factor B.

The human complement components C1r, C1s, C4, C3, factor B, and/or activated C1INH were functionally blocked in normal human serum (NHS) and EGTA- or EDTA-treated NHS by polyclonal monospecific Fab'-fragments to the individual components. The results of inhibition experiments are compatible with the formation of a classical pathway fluid-phase C3 convertase (C4b2a) spontaneously generated by the inhibition of activated C1INH. This process in both NHS and EGTA-NHS was accompanied by the consumption of C2, C4, C3, and factor B but only by poor enhancement of C5 conversion. Blocking subcomponent C1r, completely inhibited spontaneous activation of the complement components, indicating that the control of C1r hydrolysis is the essential role of activated C1INH as a regulator of C1 activation in NHS. Non-complement serum proteases were inactive during the initiation of the activation process. The presence of blood cells during functional inhibition of activated C1INH in NHS slightly decreased the consumption of C3 but not of C2 and C4.

Angioedema↗

PubMed1986

Quality criteria for i.v.-immunoglobulins: importance of tests and product properties.

Quality criteria for i.v.-immunoglobulins (i.v.- Igs) are critically discussed laying emphasis on spontaneous anticomplementary activity (aca) and size-dependent composition. Considering the percentage of fractions obtained by gel filtration (Ultrogel AcA 34), however, the monomeric IgG containing fraction contributed the major part of aca under the experimental conditions chosen. Subclass IgG3 seems to contribute considerably to aca. No correlation was found between aca and the percentage of fractions containing components larger in size than IgG dimers in various commercially available Igs. Moreover, the subclass distribution in different batches of individual products showed considerable variations. The amount of IgG4 is correlated with that of IgA in chemically unmodified products relatively poor in IgA (approx. less than or or equal to 10 mg/5 g Ig), indicating that attempts to reduce IgA consequently result in removal of IgG4.

Complement C3↗

PubMed1986

Distinction of two CD3-monoclonal antibodies in respect to the effectivity to modulate the induction of IgM- and gamma-interferon synthesis.

Monoclonal antibodies which specifically bind to epitopes within the T3-antigen complex (CD3 mAb) are excellent tools to analyse mechanisms of T-cell activation and of the interactions between T-cells, B-cells, accessory cells and intermediating immunefactors. In the present study we could show, that the CD-3 mAbs BMA 030 and BMA 031 are highly effective in modulating immunereactions, similar to antibodies directed to the T4-antigen (CD4-mAb) or the T8-antigen (CD8-mAbs) respectively. The data substantiate that depending on the experimental system BMA 030 and BMA 031 are clearly distinctive in their efficacy to modulate immunereactions. For therapeutical use of CD-3-monoclonal antibodies in organ transplantation those clone-specific differences of mAbs with identical binding specificity might cause for crucial differences in clinical applicability.

Antibodies, Monoclonal↗

PubMed1986

Effect of recombinant human interferon gamma and interleukin 2 on CFU-GM.

Human bone marrow CFU-GM were cultured with rHu-GM-CSF and varying concentrations of rHu-gamma-IFN. Concentration-dependent suppression of CFU-GM precursors by gamma-IFN was demonstrated. This suppression was, in part, reversible by addition of rHu-IL-2. Reversal was also concentration-dependent. Both immune-regulatory T-cell mediators seem to act on a more primitive stage of committed progenitor cell development.

Bone Marrow Cells↗

PubMed1986

Toxicity of "hydrophobic groupings" and the role of carbohydrates in Plasmodium falciparum infection.

We have tested various carbohydrate structures and neoglycoproteins (carbohydrate haptens attached to BSA) as inhibitors of the invasion of human red blood cells by Plasmodium falciparum merozoites (strain FCB) in synchronous in vitro cultures, using 3H-hypoxanthine incorporation into intraerythrocytic parasites as analytical tool, and have got the following results: The inhibition rate of N-acetyl-D-glucosamine glycosides is increased with increasing lipophilicity of the aglycon or spacer: CH3 less than (CH2)2NHCO(CH2)2COOCH3 less than (CH2)8COOCH3; p-Nitrophenyl glycosides proved to exhibit a toxic effect; The inhibition rate of synthetic disaccharide glycosides increased in the order beta DGal(1----4) beta DGlcNAcOCH3 less than beta DGlcNAc(1----4) beta DGlcNAcOCH3 less than beta DGlcNAc(1----4) alpha DManOCH3 less than beta DGlcNAc(1----4) beta DManO(CH2)8COOCH3; The O-linked tetrasaccharide alpha NeuAc(2----3) beta DGal(1----3) [alpha NeuAc(2----6)] alpha DGalNAcol, isolated from glycophorin A, was the best carbohydrate inhibitor tested so far; The inhibition rate of carbohydrates attached to BSA by an aliphatic spacer [-(CH2)8COOCH3] was not enhanced compared to the haptens; [DNP]33-BSA proved to be an extraordinary inhibitor of invasion which, however, most likely has to be attributed to a toxic effect; Observed toxicities appear to be attributable to hydrophobic interactions between the inhibitors and the RBC and merozoite membranes, which hampers both, intraerythrocytic growth of the parasite and its capability of RBC invasion.

Animals↗

PubMed1985

Immunohistochemical localization and molecular characteristics of three monoclonal antibody-defined epitopes detectable on carcinoembryonic antigen (CEA).

Three murine monoclonal antibodies (MAbs) reactive to different epitopes on CEA were selected according to their ability to bind to various human tissue sections. The most selective MAb, BW 431/31, bound to the majority of colon carcinomas but only faintly to normal colon mucosa. In addition to the tissues stained by MAb BW 431/31, MAb BW 250/183 reacted with granulocytes, colon mucosa and faintly with pancreatic ducts. The third MAb, BW 374/14, reacted with granulocytes, colon mucosa, strongly with pancreatic ducts and with alveolar and bronchial epithelium. The antigenic determinants recognized by the 3 MAbs in human tissue sections were resistant to formaldehyde fixation and paraffin embedding as well as to periodic acid oxidation and neuraminidase treatment. The last two treatments suggest that the epitopes are protein in nature. Using MAb affinity chromatography, 3 antigen preparations were isolated from a human colon carcinoma xenograft with an approximate molecular weight of 180 kd. These preparations were shown to bear the epitopes from each of the MAbs and from a polyclonal antiserum specific for purified CEA. Furthermore, the ability of MAb BW 431/31 to localize its antigenic determinant in vivo on a human colon carcinoma xenograft is evaluated and its possible application in the patient is suggested.

Animals↗

PubMed1985

The modulation of immune complex aggregation by classical pathway-mediated reactions.

Classical pathway (CP)-triggered reactions of complement-modulated immune complex (IC) aggregation (tetanus toxoid/human anti-tetanus toxoid-IgG; ICs of equivalence) were investigated turbidimetrically during the early stages of reaction. Monospecific Fab'- or Fab-fragments (rabbit) directed against certain complement components were used to block the complement function in normal human serum (NHS). Additionally, parts of the reactions were studied using purified complement components. C1q in serum generated by the addition of EDTA as well as purified C1q were found to increase the IC aggregation. In contrast to C1q, macromolecular C1 is able to inhibit IC aggregation, whereas additional participation of C-1 INH reversed this process. The cooperation of the remaining CP proteins (C4, C2, C4bp, and I) reconstituted the inhibition capacity of the complement. Whereas C3 supported significantly inhibition, a significant influence of other effector pathway (EP) components (C5-C9) was not detectable turbidimetrically.

Antigen-Antibody Complex↗

PubMed1985

Influence of different immunoglobulin G preparations on phagocytosis of Pseudomonas aeruginosa by polymorphonuclear granulocytes.

Commercially available immunoglobulin products suitable for intravenous application in humans are made by enzymatic or chemical modification of the IgG molecule. In order to examine, to which extent in vitro biologic functions of the IgG molecule are preserved in such preparations, specific antipseudomonal IgG from the rabbit was modified according to some of these procedures. The opsonizing activity of the different IgG preparations was evaluated in an in vitro system measuring the phagocytosis of Pseudomonas aeruginosa by rabbit granulocytes. The results demonstrated that the product Fab/Fc, which is made by papain or plasmin degradation of the IgG molecule, was still able to enhance phagocytosis but not to activate complement. The smaller papain- or plasmin-derived fragments Fab and Fc had no opsonizing activity. The pepsin-derived product F(ab')2 which possesses a divalent antigen binding site but lacks the Fc part, only enhanced phagocytosis when complement concentrations of more than 20% were present in the phagocytic system. Since the F(ab')2 fragment is not able to interact with Fc receptors or to activate complement via the classical pathway, the phagocytosis-enhancing activity of this molecule must be attributed to alternative complement pathway activation. In contrast to the enzymatically derived IgG preparations, a newly developed S-sulphonated IgG product was as efficient as unmodified IgG both in Fc- and complement-mediated opsonization.

Animals↗

PubMed1985

In vitro and in vivo activities of different immunoglobulin G preparations from the rabbit against Enterobacteriaceae.

Specific rabbit IgG, prepared against three enterobacterial strains, was modified according to procedures used for the production of human IgG preparations suitable for intravenous infusion. The resulting products were examined for their in vitro opsonic and in vivo protective activity against the respective bacterial strains. A sulfonated IgG preparation (S-sIgG) and the enzymatically derived fragments F(ab')2 and Fab/Fc were opsonic in vitro and provided in vivo protection against lethal enterobacterial infection in mice. Protection by Fab fragments varied in the different in vivo models.

Animals↗

PubMed1985

Tumor growth and metastasis increases the serum concentration of basement membrane proteins.

Serum concentrations of two basement membrane proteins, laminin and collagen type IV, were studied in three spontaneously metastasising experimental tumors: 3LL Lewis Lung and B16 melanoma of the mouse and R3230 adenocarcinoma of the rat. In the Lewis Lung tumor the mass of the primary tumor or the degree of metastasis correlated well with the concentration of serum laminin. In B16 melanoma the level of serum laminin was only significantly raised when the tumor had metastasised to the lung. No correlation between tumor mass and serum laminin was found in the R3230 adenocarcinoma. The serum concentrations of collagen IV, however, were raised to a certain extent during primary tumor growth and metastasis. Immunofluorescent staining for laminin in the Lewis Lung tumor demonstrated positive reactions in the primary tumor and in metastases of the lung. The data indicate the possibility of using similar tests for clinical tumor diagnosis.

Adenocarcinoma↗

PubMed1985

Jackfruit (Artocarpus integrifolia) and the Agaricus mushroom lectin fit also to the so-called peanut receptor.

The lectin from jackfruit (Artocarpus integrifolia) reacts with the peanut-specific lectin receptor represented by the T-disaccharide, which is also part of the Thomsen (= T)-Friedenreich antigen, namely O-beta-D-galactosyl-(1----3)-N-acetyl-D-galactosamine. The difference between the jackfruit lectin and peanut lectin has been shown to be mainly due to the further linkage of the T-disaccharide: Whereas the peanut lectin reacts with both anomeric forms, jackfruit lectin and the closely - with respect to its specificity - related Agaricus bisporus mushroom lectin react predominantly with the alpha-linked T-disaccharide, so that they cannot detect the lipid-linked T-disaccharide, as the peanut lectin does.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1984

The influence of Aclacinomycin A on the immune response and on experimental immune disorders.

The anti-cancer drug Aclacinomycin A (ACM) was able to inhibit the humoral immune response of mice against sheep red blood cells. This could be demonstrated in the formation of antibody secreting cells (PFC) and serum antibody titers, when ACM was administered either together with the antigen or three days after antigen application. Cellular immunity was not affected by the drug. In two murine Graft-vs-Host (GvH) disease models leading to two different B cell dependent auto-immune diseases (immune complex glomerulonephritis and immune hemolytic anemia) a protective effect of ACM was observed when it was administered at the time of the graft. The application of ACM in the induction phase mitigated the development of glomerulonephritis and prevented animals from dying due to hemolytic anemia. Only a slight therapeutical effect was observed when ACM was given after the appearance of clinical symptoms. In a T cell induced auto-immune disease (experimental allergic encephalomyelitis (EAE], ACM had no discernible effect on the course of the disease. It seems that the therapeutic effects of ACM on GvH-diseases are mediated via suppression of B-lymphocytes.

Aclarubicin↗

PubMed1984

Immunosuppression as a desired pharmacological effect.

The immunosuppressive efficacy of the antineoplastic antibiotic Aclacinomycin A (ACM) was assayed in several test models for humoral and cellular immune response. Humoral immune response, measured as splenic plaque forming cells (PFC) in vitro and in vivo was markedly inhibited by ACM. Suppression of PFC in vivo could be observed when ACM was administered together with the antigen, or three days later. Concomitantly a decrease of circulating antibodies to SRBC was obtained. No effect on T-cell mediated immune response - DTH reaction and allogeneic cytotoxic lymphocytes - or on skin transplantation or a T-cell mediated autoimmune disease, EAE, was observed. ACM beneficially influenced the course of the disease in two GvH-models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B-cell mediated autoimmune disease with fatal outcome. It was concluded that the therapeutic effect of ACM on GvH-disease is mediated via its suppression of the B-cell response.

Aclarubicin↗

PubMed1984

The interaction of IgG with Fc gamma receptors on human neutrophils.

The interaction of IgG with Fc gamma receptors on human PMN was studied by investigating the capacity of IgG and some of its fragments to mediate and inhibit, respectively, binding of immune complexes to these receptors and the subsequent activation of the cells. Fragments included Fab/Fc which is monovalent but contains the complete Fc region, Facb (divalent, C gamma 3 domains removed), Fc, pFc' (a C gamma 3 dimer) and a peptide corresponding to the greater part of one C gamma 2 domain (amino acids 278 through 333) including the carbohydrate side chains. F(ab')2 and Fab served as controls. The results indicate that human IgG interacts with human PMN Fc receptors predominantly through its C gamma 2 domains, while binding of rabbit IgG involves additional sites in C gamma 3. The C gamma 2 binding site on human IgG appears to be located between those for C1 and protein A and to contain lysine residues. For its correct exposure the C gamma 2 domains must be kept in the native conformation, in which both the hinge disulfide bridges and the carbohydrate moieties are involved. A role of the sugars in the actual binding, on the other hand, can be excluded.

Antigen-Antibody Complex↗

PubMed1984

Phagocytosis of immune complexes by human neutrophils and monocytes: relative importance of Fc and C3b receptors.

Human neutrophils and peripheral blood monocytes were studied for their Fc- and C3b-receptors after incubation of the cells with two types of immune complexes (IgG or F(ab')2. Immune complexes can bind to and activate phagocytes via Fc- and C3b-receptors. On mononuclear phagocytes an additional receptor is found that is able to interact directly with F(ab')2-complexes. C3b- and Fc-receptors can mediate ingestion of appropriately opsonized particles, C3b-receptors being at least as efficient as Fc-receptors. The extents of cell activation and phagocytosis in vitro depend on a number of variables, like complex size, ligand (antibody, C3b) density on the surface of opsonized particles, receptor number etc., which are not controlled in most studies and thus may explain the discrepant results reported in the literature. With the in vitro results obtained here, we cannot fully explain in vivo data obtained by various groups, where F(ab')2 antibodies yielded full protection against different types of infections. Therefore, great caution must be applied in all attempts to extrapolate in vitro data to the actual situation in vivo.

Animals↗