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Biomedical subjects

R Norberg

Publications and source records attributed to R Norberg.

At least 55 records · Page 3Linked to original sources

Non-specific precipitin reactions of IgG at low ionic strength.

Precipitin reactions apparently not involving specific antibodies were obtained in immunodiffusion experiments performed at low salt concentration between IgG and the muscle proteins, actin and tropomyosin. The precipitates, which dissolved at physiologic ionic strength, may result from electrostatic interaction of molecules of different net charge and different distribution and number of charged groups.

Actins↗

Further characterization of the Ca2+-dependent F-actin-depolymerizing protein of human serum.

The F-actin-depolymerizing factor (ADF) of human serum was purified and identified as a 93000-daltons protein. The concentration of ADF was calculated to 120-150 micrograms/ml in four normal sera and about half as much in three sera from leukemia patients treated with cytostatic drugs. In the presence of Ca2+ ADF shortened actin filaments into fragments, the size of which was correlated to the actin: ADF molar ratio, as judged by electron microscopy. The severing of F-actin was not necessarily followed by an increase in the quantities of monomeric actin, as determined by a DNase I inhibition assay and a sedimentation assay. The findings indicated that ADF shortens filamentous actin by breaking bonds between adjacent actin molecules thereby forming stable ADF-actin complexes, without a monomeric net release. The effect of ADF on F-actin was rapid and was reversed upon chelation of Ca2+. ADF cross-reacted immunologically and exhibited similarity in reaction mechanism with gelsolin, the Ca2+-dependent F-actin-severing protein from macrophages. This implies that the proteins are both structurally and functionally related. The physiological role of ADF may be to handle actin released at cell destruction, probably by forming ADF-G-actin 1:1 complexes thereby preventing formation of actin filaments.

Actin Depolymerizing Factors↗

Immunologic monitoring in breast cancer patients receiving postoperative adjuvant chemotherapy.

A group of 17 patients, having undergone modified radical mastectomy for breast cancer, received 12 cycles of chemotherapy with methotrexate, 5-fluorouracil, and chlorambucil during 17 months. The number of circulating T and non T lymphocytes, as defined by E, EAC, and ME rosette formation, were reduced during treatment. The Non-T lymphocytes, however, were reduced to the highest relative extent. Relative phytohemagglutinin and mixed lymphocyte culture responses of the cells decreased, whereas purified protein derivative responses were unchanged. Serum concentrations of IgM were reduced, but IgA and IgG concentrations were unchanged or slightly increased. Antibody titres to morbilli and herpes simplex were not changed, whereas the antibody activity against cytomegalovirus (CMV) increased in several seropositive patients. None of these patients, however, developed signs of a CMV infection.

Adult↗

A radioimmunoassay for determination of anti-actin antibodies.

The reaction of spontaneously occurring human anti-human antibodies and experimentally produced rabbit anti-actin antibodies was investigated in a solid-phase radioimmunoassay (RIA). Three structurally different in vitro forms of actin monomeric G-actin filamentous F-actin and aggregated denatured actin were used as antigens. Human anti-actin antibodies reacted with F- and G-actin but not with aggregated actin, while rabbit anti-actin antibodies gave a strong reaction with all 3 forms of actin indicating differences in antibody specificities. The results of the anti-actin RIA were compared with those obtained by indirect immunofluorescence (IFL) on cryostat sections of rat stomach. The anti-actin RIA discriminated between patients' sera and control sera in most cases, although the indirect IFL test gave more conclusive results. The seemingly low sensitivity of the anti-actin RIA compared with that of indirect IFL test for detection of human anti-actin antibodies is probably due to favourable antigen distribution in tissue, not available in the solid phase. The anti-actin RIA was able to detect anti-actin antibodies in 8 out of 8 immunized rabbits although only two produced antibodies detectable by indirect IFL. The differences in reactivity between the two methods may depend on the presence of aggregated denatured actin in the antigen preparation used for immunization and exposure of the corresponding antigenic determinants of actin on the solid phase.

Actins↗

On the biochemical nature of the 'Sm' nucleoplasmic antigen.

The nucleoplasmic autoantigens RNP and Sm are of particular interest because of their associations with certain symptoms of mixed connective tissue disease and systemic lupus erythematosus. The RNP is generally thought to be a ribonucleoprotein and there is evidence that its RNA may be single-stranded. Experiments presented in this report are in support of the concept that the Sm-antigen may also be an RNA protein. Purified Sm-anti-Sm precipitates were shown to have high RNA contents and treatment of Sm-antigen with RNAase in a hypotonic medium strongly reduced in antigenicity. The latter effect indicates that the Sm-antigen may in contrast to the RNP contain double-stranded RNA, a possibility also suggested by the finding that the Sm-antigen was soluble in 2 M LiCl. The Sm-antigen was found further to differ from RNP in being selectively absorbed in BD-Sephadex, while RNP remained active in the supernatant. Cytochemical studies involving stimulation and inhibition experiments with lectins and RNA polymerase inhibitors showed that the Sm-antigen was, in distinction to RNP, sensitive to rifampicin but not to alpha-amanitine. This suggests that the RNAs of the nucleoplasmic antigens may be synthesized by different RNA polymerases.

Amanitins↗

Influence of Bestatin, a new immunomodulator, on Ig secretion by human lymphocytes in vitro and in vivo.

Bestatin, a chemically well-defined immunomodulator, was tested for its capacity to interfere with PWM-induced Ig synthesis of peripheral lymphocytes from healthy donors. It was observed that secretion of IgA, IgG and IgM was impaired when Bestatin was present in the cultures. Serum Ig concentrations and antibody activities of IgG class to cytomegalovirus, herpes simplex and morbilli virus were examined in cancer patients who were treated with 30 mg of Bestatin daily for 1-21 weeks. These values remained constant during Bestatin treatment indicating that antibody secretion in vivo was not affected.

Adult↗

Some functional properties of the RNP nucleoplasmic antigen.

The effect of nuclear stimulators and inhibitors on the nuclear contents of nucleoplasmic antigens (ENA) was studied by the indirect immunofluorescence technique. Human autoimmune sera, one reacting with RNase-A-sensitive and one with RNase-A-resistant components of ENA in the passive haemagglutination test, were used as indicators of the RNP and Sm antigens, respectively. Phytohaemagglutinin and concanavalin A both caused an accumulation of these antigens in normal blood lymphocytes. With pokeweed mitogen, staphylococcal protein A, or purified protein derivative the accumulation was apparently restricted to B cells, alpha-amanitine, 10 microgram/ml, prevented the mitogen-induced accumulation of RNP in normal human blood lymphocytes and reduced the contents of this antigen in several lymphoblastoid cell lines and in HeLa cells but did not significantly affect the contents of Sm antigen in any of these cell types. The experimental results suggest that the RNP and Sm nucleoplasmic antigens are normal rapid-phase reactants integrated in physiological nuclear mechanisms rather than inert structural constituents of the nuclear matrix or the products of a latent virus.

Antigens↗

Extremely high titers of serum antibodies against the streptococcal exoenzyme deoxyribonuclease B.

In sera from 4 of 25,000 individuals tested for antibodies against streptococci, extremely high antideoxyribonuclease B titers ( > 10(6) U/ml) were found. Two of the cases were diagnosed as monoclonal gammopathies. The M-components were shown to possess the anti-deoxyribonuclease B activity. The other two cases were diagnosed as relapsing erysipelas. The high serum titers of deoxyribonuclease B antibodies were accompanied by a very inflammatory reactivity in the patients' sera and by an oligopolyclonal pattern of immunoglobulin G. In routine diagnoses of streptococcal infections with the anti-deoxyribonuclease B test, patients with extremely high serum titers should be examined for the possible occurrence of gammopathies.

Adult↗

Polymorphonuclear function in patients with skin and joint symptoms after small-intestinal shunt operations.

Previous studies have shown that the small-bowel shunt operation for morbid obesity may be followed by signs of enhanced cell-mediated immunity and polymorphonuclear (PMN) granulocyte bactericidal capacity. In the present study seven patients, operated 4 months--4.5 years previously and exhibiting postoperative arthralgias, arthritis, and/or skin rashes, were investigated with regard to their PMN adherence and bactericidal capacity and plasma levels of complement factors 3 and 4 (C3 and C4). There patients showed a decreased PMN bactericidal capacity compared both with 10 other shunt-operated patients without skin and joint symptoms and with healthy controls, whereas PMN adherence was lower than for the non-symptomatic patients but similar to that of the controls. Two patients had C3 levels above the reference value; all had normal C4 values. Thus, a small-bowel shunt operation for obesity, complicated by skin and joint symptoms, might be associated with decreased PMN bactericidal capacity.

Adult↗

Circulating protein complexes in D-penicillamine therapy of rheumatoid arthritis. Correlation between IgG- and alpha 1-antitrypsin-IgA complexes and clinical response.

Eighteen of 24 patients with rheumatoid arthritis showed intermediate IgG-containing complexes on preparative ultracentrifugation before treatment with D-penicillamine. Serial analyses of these showed strikingly close correlation in reduction of IgG as well as alpha 1-antitrypsin-IgA complexes. Three patients did not respond to treatment clinically, and retained both types of complexes. Complexes virtually disappeared in all responders. Only small changes were found in total IgG or IgM levels and the reduction of IgA levels was moderate, except for one case who developed IgA deficiency. The importance of further analysis of non-responders is stressed.

Arthritis, Rheumatoid↗

Effects of cryoglobulins and aggregated IGG on in vitro monocyte phagocytosis.

Monocyte yeast cell phagocytosis (YCP) was low in presence of cryoglobulins(CG) from 7 of 7 patients with SLE and RA with vasculitis and from 2 of 5 patients with essential cryoglobulinaemia. IgM and C3 were detected only in CG associated with low YCP. Furthermore, low YCP was only found with CG isolated from hypocomplementaemic sera. The results also showed low YCP when heat-aggregated IgG (HAG) greater than or equal to 19S was added to the culture medium. In the presence of HAG or SLE-sera, preopsonized yeast cells could be adequately phagocytosed by monocytes whereas, in parallel cultures, the phagocytosis of untreated yeast cells was low. It is possible that CG and HAG impair YCP in the same way as SLE-sera. The nature of this presumed common mechanism has not been clarified in this limited study. The findings are, however, compatible with the possibility that immune complexes may interfere with the opsonization of the yeast cells, possibly through inactivation of complement components.

Antigen-Antibody Complex↗

F-Actin-depolymerizing activity of human serum.

Non-heated human and animal sera contain a factor which exhibited an inhibiting activity on the staining of actin-containing structures by anti-actin antibodies in indirect immunofluorescence experiments. The presence of this factor lowered the viscosity of F-actin preparations and caused, as studied by electron-microscopy, a depolymerization of F-actin filaments as well as inhibition of filament formation of G-actin. The factor was, after its reaction with F-actin, liberated seemingly unaffected, indicating an enzymatic activity. The factor tentatively termed 'F-actin depolymerizing factor' was heat-sensitive and trypsin sensitive but resisted reduction. It was Ca2+ dependent and the staining inhibiting reaction was faster at 30 degrees C and 37 degrees C than at lower temperatures. Gel filtration experiments on Sephadex G-200 suggested a molecular size of the actin depolymerizing factor slightly higher than that of albumin. The electrophoretic mobility was that of gamma 2 globulin. The physiological role of the factor might be to prevent the presence of F-actin filaments within the circulation.

Actins↗