HLA-DR4 in Felty's syndrome.
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Biomedical subjects
Publications and source records attributed to C Friman.
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Glycosaminoglycan metabolism at different developmental stages of osteoarthritis provoked by immobilization was studied in rabbits. Tissue concentrations and the specific radioactivity of glycosaminoglycans (GAG) after a long immobilization (IZ) period (12 weeks) without follow-up, and a moderate IZ time (4-7 weeks) with a long follow-up period (average 22 weeks) were compared with the results obtained after a short IZ time (17 days). In tibial weight-bearing cartilage the specific 35S-activity had increased and the galactosamine, glucosamine and uronic acid concentrations had decreased in all the IZ groups examined. In the marginal cartilage, the menisci and the collateral ligament, the specific radioactivity and GAG concentrations had decreased or were normal after a long IZ with or without follow-up, although they were markedly elevated after a short IZ time. THe depletion of GAG correlated roughly with the IZ and follow-up times, except for periodically immobilized rabbits. In long-term "chronic" disease the specific radioactivities and GAG concentrations were depressed on the contralateral, non-IZ sides. The changes in the non-IZ knee are discussed. In studies of experimental osteoarthritis it is important to determine the developmental stage of the disease to be studied.
Autogenous jugular vein was used as a mesocaval shunt in dogs with ligated portal vein. Nine out of fifteen animals survived the operation and could be used for further studies one month postoperatively. Immediately after the shunt procedure an increased portosystemic pressure gradient was observed. However, this returned to normal at one month after the operation. At this time the graft was patient in seven out of nine dogs. Histological studies of the graft showed a smooth neointima and an increased number of elastin fibers in the media. The collagen concentration of the vein wall was significantly reduced and the glucosaminoglycans were significantly increased. It was however, not possible to assess the relative role of the operative trauma and the new haemodynamic and anatomical environment.
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A study was made of glycosaminoglycan metabolism in experimental osteoarthritis caused by immobilization of the rabbit knee in extension. Samples from the medial meniscus, the medial collateral ligament of the knee and the hip joint capsule were obtained and analysed after 2, 6, 10, 17, 30 and 87 days of immobilization, samples from the mobile limb serving as controls. The tissue concentrations of glycosaminoglycans were determined from measurements of hexosamine and uronic acid after prior papain proteolysis and subsequent purification. The uptake of 35S-sulphate (DPM/microgram hexosamine) was used as an indicator of the synthesis rate of sulphated glycosaminoglycans. In both early and advanced immobilization osteoarthritis, the synthesis rate and the content of glycosaminoglycans were increased in all tissues.
A study was made of glycosaminoglycan metabolism of articular cartilage in developing experimental osteoarthrosis caused by immobilization of the rabbit knee. Cartilage samples from various sites in the knee and hip joints were analysed, samples from the mobile limb serving as controls. The concentration of glycosaminoglycans in the tissue was measured by determinations of hexosamine and uronic acid after prior papain proteolysis and subsequent purification. The uptake of 35S-sulphate was used as an indicator of the synthesis rate of sulphated glycosaminoglycans. Metabolic changes characteristic of osteoarthrosis, i.e., glycosaminoglycan depletion and increased uptake of 35S-sulphate, were found in tibial weight-bearing and femoral condylar cartilages. Net synthesis of glycosaminoglycans occurred in the tibial marginal cartilage.
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Pleural fluid glycosaminoglycans (GAG) in 64 patients with various diseases were isolated by anion-exchange chromatography after proteolysis, and characterised by spectrophotometric, electrophoretic and enzymatic techniques. GAG concentrations ranged from 7 to 1178 microng hexuronate/ml pleural fluid. The highest values (1178, 161 and 160 micron/ml) were found in patients with diffuse mesothelioma. Over 90% of the pleural fluid GAG consisted of hyaluronic acid (HA) in these patients. In other types of pleural effusion the relative HA content varied from 42 to 70% of the total GAG. Determination of pleural fluid HA consequently appears extremely valuable in the diagnosis of the form of mesothelioma producing HA. The mean GAG concentration of pleural fluid was significantly higher in tuberculous pleurisy than in hydrothorax (P less than 0.01), secondary malignant pleural effusion (P less than 0.0005) and idiopathic pleurisy (Pless than 0.03). It was impossible to demonstrate definite correlations between GAG and protein, and GAG and glucose concentrations of pleural fluid.
Plasma glycosaminoglycans (GAG) were isolated from 10 ml of plasma by a modification of the method of Calatroni et al. (3). DE-52 anion-exchange cellulose was used in the isolation of the fraction operationally defined as free GAG. Chondroitin sulphate and heparin added to plasma were quantitatively recovered in this fraction. After proteolysis with papain the fraction operationally defined as bound GAG was isolated using anion-exchange resin AG 1 X 2. GAG were measured as hexuronate with the m-hydroxydiphenyl method of Blumenkrantz and Asboe-Hansen (7) which was superior to various modifications of the carbazole/borate carbazole procedures. In 15 healthy females and in 15 healthy males the concentrations of the free GAG (mean +/- S.D., expressed as microgram per 10 ml of plasma) were: 12.2 +/- 2.8 and 16.8 +/- 3.8 (P less than 0.001); of the bound GAG 40.4 +/- 7.7, and 40.2 +/- 11.6; and of the total GAG 52.7 +/- 9.0 and 57.0 +/- 10.4, respectively. With the isolation procedures used, plasma GAG were obtained in sufficient quantity for their electrophoretic characterization. Assay of plasma GAG can be performed with satisfactory accuracy and precision within two days by the present method. In clinical chemistry its application to the study of proteoglycan and GAG metabolism in various diseases may prove valuable.
The glycosaminoglycans (GAG) directly adsorbable from undiluted plasma on DE-52 anion-exchange cellulose (free GAG) and the GAG adsorbable on AG 1 X 2 anion exchange resin after papain proteolysis (bound GAG) were determined in 35 patients suffering from active erosive rheumatoid arthritis (RA) and in 50 control subjects. Free GAG levels were significantly elevated in both female (p less than 0.001) and male (p less than 0.05) RA patients. Bound GAG levels were significantly depressed in female (p less than 0.02) but not in male RA patients. Total GAG concentrations in RA patients and in controls were fairly similar. No consistent differences in the electrophoretic patterns of the plasma GAG from RA patients and controls were discernible. The free GAG concentrations in RA plasma samples did not correlate with seropositivity or ESR.
A patient suffering from malignant mesothelioma of funicular (intra-abdominal) origin is described. The disease proved fatal after 17 years' duration, which is the longest ever described without treatment. The analysis of the pleural fluid hyaluronate concentration gave strong evidence of the malignant aetiology, while biopsies taken 17 and 8 years before the pleurisy caused marked difficulties as to interpretation. In malignant mesothelioma a markedly elevated pleural fluid hyaluronate concentration appears to be a characteristic and specific feature.
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The present study was undertaken in order to characterize further the glycosaminoglycans of normal human plasma. Coagulation factor IX concentrate prepared from undiluted plasma by DEAE-Sephadex chromatography was used as the starting material. The concentrate was subjected to proteolytic treatment with papain and pronase, deproteinised with trichloroacetic acid, dialysed and passed through an AG 1 X 2 anion-exchange column. Glycosaminoglycans were eluted stepwise from the column with NaC1. The sole glycosaminoglycan obtained was an undersulphated chondroitin-4-sulphate which was identified by chemical analyses, digestibility with testicular hyaluronidase, electrophoretic behaviour and infrared spectrum. Gel-exclusion chromatography indicated a molecular weight of 17 000 for the compound. The undersulphated chondroitin-4-sulphate was calculated to represent at least 80% of the macromolecular glycosaminoglycans present in normal human plasma and to occur in a concentration of approx. 3 mg hexuronate per 1 of plasma.
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