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Biomedical subjects

K Fehr

Publications and source records attributed to K Fehr.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Cathepsin D agglutinators and neutral protease agglutinators in rheumatoid arthritis. II. Production of CDA and NPA by rheumatoid synovium and phagocytosis of CDA by synovial phagocytic cells.

Tissue culture methods demonstrated the production of agglutinators against the cathepsin D site in IgG (CDA) and a neutral protease site in IgG (NPA) by rheumatoid synovial tissue. Seven of 11 specimens from seropositive and 2 of 7 specimens from seronegative RA patients were positive for CDA, whereas 2 of 11 specimens from seropositive and 1 of 7 specimens from seronegative patients were positive for NPA. None of the 6 control specimens was positive for both types of agglutinators. Chromatography of two synovial tissue incubates showed that the CDA were of the IgG type. By the immunofluorescence technique, plasma cells containing CDA were demonstrated in rheumatoid synovial tissue and draining lymph nodes of rheumatoid joints. The staining for CDA in the synovium was different from the staining for pepsin agglutinators in adjacent sections. Phagolysosomes containing CDA were found in synovial exudate cells from rheumatoid patients as well as in phagocytosing lining cells and macrophages of the sublining layer of rheumatoid synovial tissue. These findings suggest that antibodies directed at hidden antigenic sites in IgG revealed by endogenous proteolysis take part in the immune reaction and in the inflammation of rheumatoid joints.

Agglutinins↗
PubMedDate not supplied

Effect of antirheumatic drugs on neutral protease from human leucocyte granules.

The inhibitory effect of 38 antirheumatic and other agents on purified neutral protease from human polymorphonuclear leucocytes has been studied by determining the decrease in enzyme activity on Z-Ala-NPH as substrate. Analgesics, salicylates, cytostatic agents and steroids, as well as D-penicillamine, colchicine, allopurinol, chlorzoxazone and chlorpromazine, either had no effect on neutral protease or inhibited it only to a very small extent. Typical antirheumatic agents like gold and pyrazolone derivatives suppressed the activity of the enzyme at a concentration of 10(-5)M. The two sulphonated polysaccharides Arteparon and pentosan polysulphate (SP 54) were the most potent inhibitors of neutral protease (inhibition down to 10(-8)M). Increasing concentrations of various inorganic salts gradually suppressed the effect of some otherwise effective drugs on neutral protease. The drugs were completely ineffective at a salt concentration of 0.5 M. At physiological concentrations, however, this effect was insignificant. Inhibition of neutral protease may be one way in which some antirheumatic drugs exert a therapeutic effect in rheumatic diseases.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Purification and some properties of collagenase proenzyme activator from rheumatoid synovial fluid.

1. An activator of leucocyte latent collagenase has been extracted from rheumatoid synovial fluid by a preparative method consisting of six steps including precipitation by ammonium sulphate and chromatography on Sephadex G-100, QAE-Sephadex and SP-Sephadex C-50. The purification factor was nearly 1000 and the activator isolated could be shown to have a high degree of homogeneity.--2. Gel chromatography indicated a molecular weight of ca. 60 000.--3. Kinetic studies of the activation and inactivation of the activator during incubation at higher temperatures demonstrated its enzymic nature.--4. Activation of latent collagenase was partially inhibited by iPr2P-F and KCN. Soybean trypsin inhibitor, iodoacetamide, TosLysCH2Cl and TosPheCH2Cl had no effect.--5. Leucocyte latent collagenase was also activated by an excess of trypsin and p-hydroxymercuribenzenesulphonic acid, but only to the extent of about 40% of its activation capacity. Purified neutral protease from human leucocyte granules had no effect on latent collagenase.--6. Several typical substrates for proteases, peptidases, esterases and glycosidases were not attacked by the activator. The possibility that the activator is a known enzyme, such as kallikrein, urokinase or cathepsin B1, could be excluded.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Systemic lupus erythematosus and the crithidia luciliae immunofluorescent test. A comparative study with an adapted Farr radioimmunoassay.

A comparative study of the Crithidia luciliae immunofluorescence (CL-IF) assay and an adapted Farr radioimmunoassay (RIA), for the measurement of antibodies to native deoxyribonucleic acid, was performed using forty-two sera from patients with systemic lupus erythematosus (SLE) and another forty-two from patients with rheumatoid arthritis. Both assays were specific for SLE. The CL-IF assay was statistically significantly more sensitive than the adapted RIA assay. This significant difference was due to greater sensitivity of the CL-IF assay in the cases of sera from patients with SLE of slight activity. Additional advantages of the CL-IF assay were its use to classify the immunoglobulin types of the antibodies (most commonly IgG or IgM) and to measure complement-fixing antibodies to native deoxyribonucleic acid; it affords a simple method of selecting and following SLE patients at risk of developing severe renal disease. These advantages plus the simplicity and inexpensiveness of the CL-IF assay make it a useful tool, especially for use in small laboratories, for the study of antibodies to native deoxyribonucleic acid in patients with SLE.

Adolescent↗
PubMedDate not supplied

The effects of gold sodium thiomalate on the binding and internalization of concanavalin A in human mononuclear phagocytes.

The effects of gold sodium thiomalate (GST) on the binding and internalization of concanavalin A (Con A) in human mononuclear phagocytes (M phi) were investigated in vitro. First, the binding and internalization of Con A were examined quantitatively using 3H-Con A. The prolonged incubation with GST induced a prominent inhibition of 3H-Con A internalization in M phi. The inhibition was increased in parallel with both increasing concentrations of GST and increasing time intervals of the incubation with GST. On the other hand, GST failed to significantly affect the binding of 3H-Con A to the M phi surface receptor. Second, the binding and internalization of Con A were examined qualitatively by fluorescein isothiocyanate-conjugated Con A (FITC-Con A). After incubation with GST for 72 h, the internalization of FITC-Con A was prominently impaired in vacuolated M phi. A significant inhibition of FITC-Con A internalization was not observed in either GST-treated nonvacuolated M phi or non-GST-treated M phi. Thus the inhibition of FITC-Con A internalization in GST-treated vacuolated M phi seemed to account for the inhibition of 3H-Con A internalization in all the GST-treated M phi populations. The binding of FITC-Con A to the cell surface receptor and the clustering of FITC-Con A receptor complexes were not detectably changed in any of the M phi populations. These results indicated that GST alters the initial step in the activation of M phi by Con A, namely the internalization of this mitogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Concanavalin A↗
PubMedDate not supplied

Temporal arteritis in polymyalgia rheumatica: immune complex deposits and the role of the leukocyte elastase in the pathogenesis.

Immunohistochemical studies were performed on the temporal artery of 34 patients with clinically established polymyalgia rheumatica (PR) or temporal arteritis, 6 patients with vasculitis, and 25 patients with various diseases. The combined immunofluorescence and peroxidase-anti-Peroxidase Methode zeigte Immunoglobulin- und C3-Ablagerunin histologically affected and to some degree also in unaffected arteries of patients with PR and in all patients with temporal arteritis. The deposits were found both inter- and intracellularly, and contained IgA and to a lesser extend IgG, IgM, and C3. Linear deposits of leukocyte elastase were found along the fragmented internal lamina, and decaying polymorphonuclear (PMN) leukocytes surrounded by elastase-containing inclusions were found in the neighborhood of zones rich in elastic material. These findings suggest that immune complex deposition is a prominent feature of temporal arteritis and that the PMN elastase is probably involved in the destruction of elastic fibers. The combined immunohistochemical investigation appears to increase the diagnostic value of temporal artery biopsy.

Aged↗