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Biomedical subjects

F Skvaril

Publications and source records attributed to F Skvaril.

At least 19 recordsLinked to original sources

[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

Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis.

We determined immunoglobulin G (IgG) subclass concentrations and studied their distributions in the cerebrospinal fluids of patients suffering from multiple sclerosis, other inflammatory neurological diseases, and non-inflammatory diseases of the nervous system in comparison with a control group. In addition, the four subclass concentrations were measured in serum specimens of the multiple sclerosis and control groups. These data were correlated with the extent of local IgG synthesis in the subarachnoid spaces of the patients belonging to the different groups. We found a selective elevation of the IgG1 subclass in the cerebrospinal fluids of multiple sclerosis patients, and there was only a very small overlap of the IgG1 ranges of the multiple sclerosis and control groups. No major differences were detected between the IgG subclass distributions in different courses of multiple sclerosis nor between multiple sclerosis and control sera. The group with non-inflammatory diseases showed a uniform elevation of all four subclasses and a greater overlap with the normal range. This latter feature was combined with an elevated IgG1 concentration in the group with other inflammatory diseases. It is concluded that locally synthesized IgG in the cerebrospinal fluids of multiple sclerosis patients consists mainly of IgG1.

Humans

Fluorometric determinations of the relative immunoglobulin content of plasma cells of patients with monoclonal gammopathy.

The relative cytoplasmic immunoglobulin content of fixed plasma cells taken from the bone marrow of five patients with myeloma and five patients with benign monoclonal gammopathy was determined with a microscope fluorometer. In eight of the ten piasma cell populations studied, the distribution of the fluorescence intensities was close to normal. In three of these eight populations a significant difference in the variances of the heavy and light chain fluorescence intensities was found. Variances of heavy and light chain fluorescence intensities were smaller in patients with an immunoglobulin A-type gammopathy than in those with an immunoglobulin G-type gammopathy. No difference was found if normalized relative frequency distribution patterns of heavy or light chain fluorescence intensities of patients with myeloma were compared with those of patients with benign monoclonal gammopathies.

Bence Jones Protein

Immunological abnormalities and HLA antigen frequencies in IgA deficient patients with epilepsy.

Twenty-three epileptics with constitutional factors for seizures and low IgA serum concentrations were studied. Imbalance of the IgG subclasses was often observed, the IgG4 being undetectable in 13 (65%) patients. The percentage of circulating lymphocytes positive for surface immunoglobulins was normal except for slightly increased values for IgA in six (28.5%) patients. Of the epileptics, 48% showed subnormal proportions of lymphocytes forming spontaneous rosettes. There was a distinct trend for HLA-A2 antigen in the patients tested.

Adolescent

Differentiation between benign and malignant monoclonal gammopathies by discriminant analysis on serum and bone marrow parameters.

Bone marrow samples of 28 individuals with clinically benign and of 41 patients with malignant monoclonal gammopathy were analyzed for the total number of lymphoplasmocellular elements containing cytoplasmic immunoglobulins and for the monoclonal fraction of these cells. Monoclonal immunoglobulin components were determined in sera. A discriminant analysis was performed on the data: the variables were transformed and in a stepwise procedure used for the construction of a discriminant function which by adividing point allowed a good distinction between the two groups of patients. By use of this discriminant function, 91% of the patients in the sample were correctly classified.

Adult

Cytoplasmic immunoglobulins in bone marrow cells of polyclonal and of monoclonal origin.

Cytoplasmic immunoglobulins in human bone marrow plasma cells and lymphoid cells were characterized by direct immunofluorescence with fluorochrome-labelled reagents specific for immunoglobulin heavy and light chains. The percentage distribution of cells containing IgA, IgG or IgM and kappa- or lambda-immunoglobulins was determined in bone marrow samples from 168 immunologically normal individuals, in 11 patients with polyclonal increase of bone marrow plasma cells and in 80 patients with benign or malignant monoclonal gammopathies. A clear differentiation between monoclonal and polyclonal cell populations could be obtained in all cases.

Adult

Anticomplementary properties of plasmin-treated human G immunoglobulin and its components.

Plasmin-treated human gamma-globulin, isolated plasmin residual portion (PRG), Fab and Fc fragments were tested for anticomplementary properties. The plasmin digest had very low anticomplementary activity while some of its components were anticomplementary, the latter probably due to alterations resulting from the isolation procedures employed. The highest activity was found in the isolated Fc fragment, no activity being detected in the isolated Fab fragment. Various mixtures of the isolated components were also tested, the results indicating that the increase in anticomplementary activity of the PRG and the Fc fragment was markedly lower when the Fab fragment was present.

Chromatography

[Distinction between benign and malignant monoclonal gammopathies on the basis of bone marrow and serum studies].

Studies were performed on bone marrow and serum from 28 patients with clinically benign gammopathy and 41 patients with the malignant monoclonal form. In the bone marrow samples, the total number of plasma cells and the monoclonal fraction of these cells were determined by immunofluorescence. Serum samples were analyzed for monoclonal immunoglobulin components and for the total serum protein content. The data could be used for discriminant analysis. The variables had to be transformed and were included in the discriminant function in a stepwise procedure. The resulting function made possible a clear distinction between benign and malignant monoclonal gammopathies.

Blood Proteins

Differentiation of plasma and myeloma cells of man. Combined planimetric and cytophotometric studies.

Plasmacytoid cells in the bone marrow of 3 patients with myeloma and plasma cells in the bone marrow of a 6-year-old boy with an infectious disease were assessed cytophotometrically, first after Giemsaand second after Feulgen staining. The cell and nuclear surface and the nuclear/cytoplasmic ratio were determined from the number of measuring points. The nuclear DNA content of individual cells was registered and the distribution of DNA within the nucleus was assessed by the distributional error. Both the mean nuclear/cytoplasmic ratio and the distributional error of myeloma cells varied from patient to patient but could not be used to differentiate between normal plasma cells and myeloma cells. It was not possible either to differentiate these cell types by multiplying the mean nuclear/cytoplasmic ratio with the mean distributional error of the nuclear DNA. A strong correlation between cell and cytoplasmic surface area was observed both in normal plasma cells and in myeloma cells.

Bone Marrow

Distribution of IgG subclasses in commercial and some experimental gamma-globulin preparations.

The IgG subclass distribution was determined in six commercial and in four experimental human gamma-globulin preparations. The concentrations of IgG subclasses were measured in a modified radiommunoassay using subclass-specific antisera. In commercial gamma-globulins, the distribution of the subclasses corresponded roughly to the distribution in normal human serum. A considerable enrichment of the IgG 4 was found in experimental lots prepared either from the ethanol fraction III or from the rivanol-precipitable IgG.

Blood Specimen Collection

Monoclonal IgG3-kappa and IgG1-lambda proteins with different idiotypic determinants present in a single patient.

Two monoclonal proteins belonging to IgG3-kappa and IgG1-lambda subclasses were detected in a single patient. Immunochemical analysis revealed that the idiotypic determinants of the two proteins were different. Examination of bone marrow by an immunofluorescence technique indicated that these two proteins were produced in different cells, although both kappa and lambda chains were present in a minute proportion of the cells. J chain was present in all cells that produced IgG.

Bone Marrow

Uncommon Gm phenotypes in sera from neuroblastoma patients.

Gm phenotypes and IgG subclass levels were determined in the sera of 68 patients with neuroblastoma. The frequency of the uncommon phenotypes Gm(a+,f+,g-,b+) and Gm(a+,f+,g+,b-) was found to be significantly higher in the neuroblastoma group than in normal blood donors (p less than 0.001). IgG subclass concentrations in the nine sera with uncommon Gm phenotypes and in the sera of neuroblastoma patients were inconspicuous.

Adolescent

[Prophylaxis and therapy with gamma globulin. General characterization and clinical use of gamma globulin preparations].

For accurate evaluation of the usefulness of gamma-globulin treatment, the clinical indications for passive immune prophylaxis and immunotherapy and the specific characteristics of commercially available gamma-globulin preparations have to be considered. Detailed investigations of currently used gamma-globulin preparations have shown that as yet no ideal product is available. Classical standard gamma-globulin and, in particular, enzymatically treated (Gamma-Venin, Veinoglobuline) or chemically modified preparations (Gamma-Globulin i.v. SRK, Intraglobin) for intravenous use have some deficiencies and involve potential risks for the patient. Nor is the infusion of "fresh frozen plasma" a safe and generally applicable alternative to the use of gamma-globulin concentrates. Thus from the outset the preconditions for effective treatment with gamma-globulin are not optimal. Standard and hyperimmune preparations, given once intramuscularly, are suitable for the prophylaxis of viral and bacteriotoxic diseases. In patients apt to react abnormally it is important to distinguish clearly between the few accepted indications and those that are more doubtful. Anti-D immunoglobulin is essential for the prevention of Rhesus sensitization after the delivery of a Rhesus-positive child. In general, gamma-globulin is recommended for substitution therapy and for the prophylaxis of recurrent acute bacterial infections in patients suffering from transient, congenital and acquired antibody-deficiency states. In such cases, high doses of an intravenously administrable preparation with a relatively long biologic half-life are recommended. The evidence for the effectiveness of gamma-globulin treatment of bacterial infections in patients without manifest disturbance of humoral immunity is equivocal. This is true, for example, of the oft-recommended combined use of antibiotics and high doses of intravenous gamma-globulin which is said to provide optimum antibacterial and antitoxic protection. There is even less chance of obtaining beneficial effects if gamma-globulin is given as an "ultimo ratio" in severe generalized bacterial infections resistant to antibiotic treatment. Localized and predominantly chronic infections are barely influenced by gamma-globulin. It is still too early to make a final assessment regarding the place and value of immunoglobulin concentrates for prophylactic and therapeutic purposes. This will only be possible if a preparation becomes available which contains all immunoglobulins in a biologically optimum state and concentration, is well tolerated and can be given in adequate doses both intramuscularly and intravenously.

Complement System Proteins

[Changes of kappa/lambda ratio of human serum immunoglobulins in the course of development].

In sera of normal individuals of different age groups the kappa- and lambda-type immunoglobulins were measured and the kappa/lambda ratio was calculated. The relative concentration of lambda-immunoglobulins in sera of newborns and young children was found to be significantly higher than in the adult sera. The well-known asynchronous maturation of immunoglobulin classes and IgG subclasses in the early childhood is evidently accompagnied by a asynchronous maturation of immunoglobulin types.

Adult