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Biomedical subjects

F Skvaril

Publications and source records attributed to F Skvaril.

At least 55 records · Page 3Linked to original sources

Effect of spleen exposure to ultrasound on cellular and antibody-mediated immune reactions in man.

Spleen exposure to ultrasound has been reported to influence antibody response to sheep red blood cell injection in mice (decreased hemagglutination and hemolytic titers and IgM, IgG2a and IgG2b levels and elevated IgG1 levels). In a controlled clinical trial, we investigated the possible immunosuppressive side-effect of splenic exposure (2.0 mW/m2, 3.5 MHz, 5 minutes) to ultrasound on the immune response to Rubella vaccination in 41 anti-Rubella antibody-negative volunteers. The measured parameters (blood cell count, IgA, IgM, IgG including subclasses IgG1-IgG4, isoagglutinins, anti-Rubella hemagglutinin and hemolysin titers, complement C3, skin tests to mumps and tuberculin, T, B and O lymphocytes, esterase-positive and negative T-cell subsets) suggest changes dependent on the time of vaccination, but provide no evidence of an immunosuppressive effect of ultrasound in man.

Adolescent↗

Increased levels of IgG4 subclass in 5 patients with acquired respiratory disease.

5 sera from a series of more than 1,000 serum samples from hospitalized patients tested by immunoelectrophoresis were selected for further examination because of a disproportional increase in the anodic part of IgG. A marked polyclonal increase in IgG4 subclass level was detected in each of these sera. While the patients suffered from a variety of diseases (e.g. Loeffler's syndrome, leiomyosarcoma, periarteritis nodosa, chronic bronchitis, and mycosis fungoides, respectively), they all had an acquired respiratory disease as the only common clinical denominator.

Adult↗

Idiotypic and structural analysis of monoclonal human immunoglobulins with anti-streptolysin O activity.

The class, subclass and light chain distribution of eight myeloma proteins with anti-streptolysin O activity (ASO) in sera studied by our group and in cases from the literature indicates a predominance of the IgG1 kappa subclass and type of immunoglobulins. Three IgG myeloma proteins (O.I., L.F. and A.S.) were further characterized with respect to idiotypic cross-reaction and variable region subgroup. The anti-idiotypic antibodies (anti-Id) against protein O.I. and against protein L.F. both indicated idiotypic cross-reaction between O.I. and L.F. While in the case of anti-IdL.F. this cross-reaction was in the order of 5% it was much weaker when studied with anti-IdO.I.. The reaction between O.I. and anti-IdO.I. could be inhibited to 95% by the antigen streptolysin O, indicating that the idiotypic determinants are associated with the combining site. N-terminal amino acid sequence analysis showed that all three light chains fall in the V kappa III variable region subgroup. The heavy chains of proteins O.I. and L.F. with idiotypic similarities both have blocked N-termini, indicating the presence of the VHI or VHII subgroup while protein A.S. belongs to the VHIII subgroup.

Amino Acid Sequence↗

Characterization of various immunoglobulin preparations for intravenous application. I. Protein composition and antibody content.

In this comparative study we investigated 14 immunoglobulin (Ig) preparations for intravenous application; they were prepared by various manufacturers who used either placental or venous blood as the starting material. The pepsin- and plasmin-treated products and a preparation which, according to the manufacturer, was not degraded enzymatically, contained 17-86% of IgG split products. On the other hand, three chemically modified preparations, one preparation treated at pH 4, for products treated with poly(ethylene glycol) (PEG) and one preparation protected by albumin contained 90% or more of non-fragmented IgG. The IgG subclass distribution corresponded to the distribution of subclasses in normal serum only in the nonmodified and not enzymatically degraded preparations. All samples except one contained 0.1 mg/ml IgA or more, all contained only traces of IgM. No product had clinically relevant titers of irregular antibodies against erythrocyte antigens. The content of those antiviral and antibacterial antibodies that were tested for was similar in all preparations. Only the anti-HBs activity exhibited large variations. Some PEG-treated preparations showed an elevated prekallikrein activator (PKA) level, whereas all other preparations contained, if any, only traces of PKA.

ABO Blood-Group System↗

Characterization of various immunoglobulin preparations for intravenous application. II. Complement activation and binding to staphylococcus protein A.

14 immunoglobulin preparations for intravenous use were tested to assess functions of their Fc portion. Inhibition of the hemolytic activity of complement, C1q binding and the interaction of IgG subclasses with Staphylococcus protein A were investigated. Complement studies were done on both the ready-for-infusion and the heat-aggregated preparations. Three groups of products could be distinguished: (1) Enzymatically and chemically treated products were devoid of complement-activating capacity, both when tested and ready-for-infusion and as heat-aggregated preparations. The chemically treated preparations showed atypical binding properties to Staphylococcal protein A. (2) The poly-(ethylene glycol) (PEG)-treated preparations and the untreated reference activated complement before and after heat-aggregation. (3) The albumin protected and the pH 4-treated product did not spontaneously activate complement in the ready-for-infusion state but did so after heat-aggregation. These results suggest that only the albumin-protected and the pH 4-treated products can be expected both to be well tolerated when given intravenously to high-risk agammaglobulinemic patients and to exhibit normal Fc functions in vivo.

Complement Activating Enzymes↗

Humoral immune response in Epstein-Barr virus infections. I. Elevated serum concentration of the IgG1 subclass in infectious mononucleosis and nasopharyngeal carcinoma.

Using radial immunodiffusion we measured IgG subclass concentrations and studied their distribution in serum samples from patients with infectious mononucleosis (IM) and nasopharyngeal carcinoma (NPC), two Epstein-Barr virus (EBV)-associated diseases, in comparison with two control groups [completely anti-EBV negative persons and subjects carrying antibodies to the viral capsid antigen (VCA)]. Antibody titres to VCA and to the early antigen (EA) were determined by indirect immunofluorescence and revealed characteristic patterns for the respective diagnostic groups. Nephelometric assays served for quantitating total protein, albumin, total IgG, IgA and IgM in all the sera. In the IM and NPC groups the concentration of IgG1 was significantly elevated by more than 50% whereas the other three subclasses remained unchanged as compared with the controls. Correspondingly, we found a significant increase of total IgG in IM and NPC. In IM, the only disease where VCA-specific IgM antibodies have been reported to occur, IgM levels were markedly elevated. Our data suggest that the IgG1 subclass plays an important role in the humoral immune response to EBV-determined antigens and that it is possibly involved in the control of virus infection.

Animals↗

Flow-cytometric analysis of human basophil degranulation. II. Degranulation induced by anti-IgE, anti-IgG4 and the calcium ionophore A23187.

Quantification of human basophil degranulation induced by anti-IgE, anti-IgG4, and by ionophore was performed using a flow-cytometric system. It was shown that these antibodies and ionophore can degranulate basophils in a dose-dependent manner, and that there is a wide variation in the response of basophils obtained from different individuals to these stimuli. A significant correlation was observed between the degree of degranulation induced by anti-IgE and anti-IgG4, while this was not the case for anti-IgE and ionophore. It was also shown that IgG4 myeloma protein can passively sensitive basophils. In general, degranulating efficacy was in the order of ionophore greater than anti-IgE greater than anti-IgG4, both in allergic and non-allergic individuals.

Anti-Bacterial Agents↗

Clinical and immunochemical studies of 20 patients with amyloidosis and plasma cell dyscrasia.

Amyloidosis associated with plasma cell dyscrasia (AAPCD) is a relatively rare clinical entity (4% of our patients with PCD) and its early recognition and distinction from multiple myeloma (MM) may be of great therapeutic and prognostic significance. Laboratory parameters, such as concentrations of normal polyclonal Ig, Bence-Jones proteins and serum monoclonal components (MC) showed in our patients lower MC concentrations than in MM, lambda-L-chains and of gamma-H-chains predominating. Sequential skeletal X-ray studies and bone marrow morphology remain essential diagnostic procedures. Due to the lack of efficient therapeutic agents for AAPCD and the great progress achieved in recent years in the treatment of secondary amyloidosis, the immunochemical analysis of the isolated amyloid fibril as well as of the surrounding 'ground substance' should be pursued in AAPCD. Our data support previous observations, that in AAPCD the amyloid fibril subunit is an L-chain fragment predominantly derived from lambda-L-chains which originates from the same clone as the MC. The localization of an enzymatic cleavage point on the L-chain, the detection of a specific proteolytic enzyme and the identification of additional components in the amyloid substance, may further elucidate the etiopathogenesis of AAPCD.

Amyloid↗

Determination of IgG subclasses and Gm allotypes in culture supernatants of pokeweed mitogen-stimulated human blood lymphocytes.

Concentrations of the 4 IgG subclasses, of IgM, and of IgA were determined in culture supernatants of pokeweed mitogen-stimulated mononuclear cells isolated from human peripheral blood. Time-course studies showed cumulative secretion of IgM, IgA, and the subclasses IgG1, IgG2, and IgG3 but not of IgG4. In supernatants of 7-day cultures of unseparated mononuclear cells, IgG1 was predominant, followed by IgG2 and IgG3. Removal of most monocytes from the mononuclear cells resulted in an overall decrease of immunoglobulin production but had no influence on the relative IgG subclass distribution. In supernatants of T cell-enriched cultures, the synthesized IgG was deficient in IgG1. Likewise, in supernatants of B cell-enriched cultures, IgG2 exceeded IgG1 concentration. Elimination of the T gamma cells suggested some influence of this subset on IgG2 production. Gm allotypes determined in supernatants corresponded to those in serum of the blood donors.

Animals↗

[Structure and biological properties of immunoglobulins and gamma-globulin preparations. II. Properties of gamma-globulin preparations].

Various gammaglobulin preparations have been analyzed with regard to content of IgG aggregates and percentage distribution of the four IgG subclasses. Their elimination from the plasma compartment was also studied in turnover experiments. Chief attention was focused on gamma-globulin preparations for intravenous use. The various preparations clearly differed in their subclass composition and metabolic behaviour. At present these results allow no conclusions concerning the efficacy of the various preparations in severe bacterial infections, since controlled clinical trials are still lacking. They should, however, be borne in mind when selecting a gammaglobulin preparation for a planned clinical trial.

Humans↗

Kinetics of the different susceptibilities of the four human immunoglobulin G subclasses to proteolysis by human lysosomal elastase.

Human lysosomal elastase cleaves human monoclonal IgG into components that closely resemble the fragments produced by papain digestion. IgG1 produced Fab, Fc and Fab-Fc fragments; cleavage of IgG2 produced F(ab)2, Fab-Fc, Fab and Fc fragments; IgG3 gave rise to almost pure Fab and Fch (Fc covalently joined to the extended hinge region polypeptide of IgG3), and from IgG4, F(ab)2, Fab and Fc fragments were recovered. The relative susceptibilities of the four human IgG subclasses to proteolytic attack by elastase were studied kinetically and showed the following decreasing order of susceptibility: IgG3 > IgG1 > IgG2 > IgG4. The Fab fragment from papain digestion of IgG1 and the corresponding fragment from elastase digestion showed indistinguishable molecular weights and immunochemical identity.

Chromatography, Gel↗

IgG subclasses in human gamma-globulin preparations for intravenous use and their reactivity with staphylococcus protein A.

In two of four non-enzymatically treated gamma-globulin preparations C Immunoglobulin Schura, Immunoglobulin SRK), the distribution of IgG subclasses was found to be close to that of normal human serum. In two other preparations (sulphonated and beta-propiolactone-treated) IgG3 was not detectable by means of appropriate antiserum. The IgG residual portion of plasmin-treated gamma-globulin was enriched in IgG2, while IgG3 was absent. In affinity chromatography on protein A Sepharose, IgG3 in the unbound and IgG1, IgG2 and IgG4 in the bound fractions were found in Immunoglobulins Schura and SRK. In the sulphonated preparation no IgG was found in the unbound fraction, while IgG1, IgG2 and IgG4 were eluted from the bound fraction. In beta-propiolactone-treated gamma-globulin IgG1, IgG2 and IgG4 were present in both fractions. The testing of reactivity of IgG subclasses with Staphylococcus protein A can supply important information about the state of the Fc part in immunoglobulin preparations.

Chromatography, Affinity↗

In vivo behaviour of gamma globulin preparations.

Metabolic properties of standard gamma globulin (St-GG) and of several gamma globulin (GG) preparations for intravenous use were analyzed in radioactive tracer studies. The in vivo behaviour of St-GG was investigated in 16 probands and found to be comparable to that of normal IgG. The kinetics of the resorption of St-GG from intramuscular deposits, its elimination from the intravascular compartment and from the body were studied in 2 probands. Metabolic properties of GG preparations for intravenous use were compared with those of St-GG in 3-4 probands after simultaneous injection of 125I- and 131I-labelled tracer doses. Important differences in the half-times of intravascular survival, in the rates of catabolism and in the distribution in the body were noticed for most of the preparations for intravenous use except for an improved acid-treated (pH 4) GG, the in vivo behaviour of which was similar to that of St-GG.

Adult↗

[Sequential immunologic, cytochemical and autoradiographic studies on lymphoid cells in the blood of healthy adults].

Simultaneous characterization on a single slide of computer-mapped lymphoid blood cells by sequential analysis of 3 parameters (surface immunoglobulins, AET-SRBC-rosetting, unspecific acid alpha-naphthyl-acetate-esterase) served to distinguish 8 subpopulations. By previous in vitro incubation with 3HdT, the proliferative activity of the latter could also be assessed.

Autoradiography↗

Determination of IgG subgroups in cerebrospinal fluid of multiple sclerosis patients and others.

IgG subgroups (IgG1, IgG2, IgG3, IgG4) were determined by radioimmunoassay (RIA) in cerebrospinal fluid (CSF) of controls, multiple sclerosis (MS), infectious diseases (ID) and other neurological diseases (OND). The proportion of IgG1 in the total IgG subgroup concentration was significantly higher in the MS group compared to the other groups while the IgG2 proportion was significantly lower; IgG3 and IgG4 did not show any consistent change. The inverse relationship between IgG1 and IgG2 was similar in all diagnostic groups: high concentration of IgG1 was associated with low concentrations of IgG2 and vice versa. Patients with a high relative concentration of IgG1 in their CSF have a seven to eight times higher statistical risk to be suffering from MS than ID or OND. In the MS group only the IgG1 concentration correlated with the total IgG concentration determined by radial immunodiffusion, while in controls, ID and OND each IgG subgroup correlated significantly with the IgG concentration. This demonstrates that in MS a selective increase of IgG1 subgroup is mainly responsible for the increase of total IgG, while all subgroups are involved in OND and ID showing an increased total IgG concentration.

Albumins↗