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Biomedical subjects

O Wegelius

Publications and source records attributed to O Wegelius.

At least 37 records · Page 2Linked to original sources

Skin response to intradermal DNA and RNA in systemic lupus erythematosus.

The local response of 18 patients with active systemic lupus erythematosus to 0.1 ml of intradermally injected 0.1% polymerized calf thymus DNA and synthetic double-stranded polyinosinic-polycytidylic acid was studied. In 14 patients positive for DNA, 61 +/- 8% of the inflammatory cells in the subepidermis at 24 hours were acid alpha-naphthyl acetate esterase-positive T lymphocytes. A leukocytoclastic vasculitis was observed in the deeper dermis. Rheumatoid arthritis patients and acne patients had negative responses. These results indicated an abnormal cellular and humoral in vivo response by patients with systemic lupus to DNA. It is suggested that the epidermal Langerhans cells were responsible for the topographic dichotomy of the local DNA response. Test results were positive for polyinosinic-polycytidylic acid in 12 patients, for DNA in 14 patients, and for both in 9 patients. In the 9 patients with positive results for both tests, comparison of responses to each test indicated that the reaction intensity was dependent on the patient and not on the type of polynucleotide acid that was injected.

DNA↗

Circulating DNA-antibodies in systemic lupus erythematosus.

Sera from 57 patients with systemic lupus erythematosus (SLE) were tested for DNA-antibodies by three different methods: a radioimmunological test using the Farr technique, the Crithidia luciliae immunofluorescence assay for anti-double-stranded (native) DNA (anti-ds-DNA), and a solid-phase immunoenzymatic assay for anti-single-stranded (denatured) DNA (anti-ss-DNA) of IgG and IgM classes. There was a positive correlation between the activity of the disease and the levels of ds-DNA-antibodies and IgG anti-ss-DNA. Patients with active nephritis had a higher amount of anti-ds-DNA and anti-ss-DNA of IgG class than patients with inactive nephritis (P less than 0.05 and 0.01, respectively). Patients with SLE nephritis had lower levels of ss-DNA-antibodies of IgM class than patients without nephritis (P less than 0.02). There was a positive correlation between the IgG-anti-ss-DNA/IgM-anti-ss-DNA ratio and the activity score of the disease. These results suggest that the anti-ss-DNA assay may be useful in the follow-up of SLE. Complement fixing anti-ds-DNA and the highest levels of anti-ds-DNA by Farr assay were usually associated with an active disease, especially nephritis and joint involvement.

Antibodies, Antinuclear↗

Purification and characterization of a nuclear SS-B antigen.

A nuclear SS-B antigen was isolated from a saline extract of acetone powder of rabbit thymus by precipitation with ammonium sulphate, affinity chromatography with Blue Sepharose CL-6B, and preparative agarose gel electrophoresis. The mol. wt of the antigen was 68,000. Its electrophoretic mobility was similar to that of pre-albumin, and the iso-electric point was around pH 4.0. The main amino acids of the antigen were glutamic acid, leucine, lysine and alanine. Both histidine and tyrosine were also found. The purified antigen precipitated with anti-SS-B sera but not with any other reference antisera. It resembled La and Ha antigens in susceptibility to proteolytic and nucleolytic enzymes and to heat. The purified SS-B antigen, however, had a higher molecular weight than did the Ha and La antigens. The molecule could not be split into subunits with mercaptoethanol or acid. Counter-electrophoresis showed antibodies to the SS-B antigen in sera from patients with rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome, but not in amy of the control sera.

Adult↗

Characteristics of the amyloid A fibril-degrading activity of human serum.

Radial diffusion in agarose gel containing amyloid A (AA) fibrils was used to study the serum enzyme capable of degrading AA fibrils in vitro. This degradative activity was unaffected by soya bean trypsin inhibitor, tosyl-lysine chloromethyl ketone, and gold thiomalate but was inhibited by bovine pancreatic trypsin inhibitor, phenylmethylsulphonylfluoride, diisopropyl fluorophosphate, alpha 1-antitrypsin, and alpha 2-macroglobulin, indicating that the enzyme involved is a serine protease. Agarose gel electrophoresis showed the enzyme to be an acidic protein with the same electrophoretic mobility as albumin. The molecular weight, measured by gel filtration, was approximately 50,000. The optimum pH of this enzyme was 7.3, and it was fairly heat-resistant. The results suggest that the AA-fibril-degrading activity in human serum is due neither to elastase nor to cathepsin G. It has many characteristics in common with the enzymes unlike elastase that are involved in the complete degradation of serum AA protein.

Adult↗

Relationship between urinary sialylated saccharides, serum amyloid A protein, and C-reactive protein in rheumatoid arthritis and systemic lupus erythematosus.

The urinary excretion of sialic-acid-containing oligosaccharides, total sialic acid, serum amyloid A protein (SAA), and C-reactive protein (CRP) has been studied in 48 patients with rheumatoid arthritis (RA) and in 17 patients with systemic lupus erythematosus (SLE). Linear regression analysis revealed a close positive correlation between serum SAA and CRP levels in both RA (r = 0.71, p less than 0.001) and SLE (r = 0.86, p less than 0.001). The urinary excretion of sialyl lactose showed a positive correlation with the serum levels of SAA and CRP in RA (r = 0.45 and r = 0.45, respectively, p less than 0.01) but not in SLE (r = 0.05 and r = 0.10 respectively). Changes in serum total sialic acid levels paralleled those in CRP and SAA in RA as well as in SLE. Patients with very active RA had higher urinary sialyl oligosaccharide excretion (p less than 0.001), higher CRP levels (p less than 0.01), and higher SAA levels ( p less than 0.05) than those with moderately active disease.

Adult↗

A family study of leprosy: subcutaneous amyloid deposits and humoral immune responses.

One group of 11 aboriginal families, consisting of 27 persons with leprosy and 43 unaffected family members, and a second group of 26 patients with leprosy were studied in the Northern Territory of Australia. Amyloid deposits were sought in fine needle aspirates of subcutaneous fat and serological investigations relevant to amyloidosis and to the humoral immune response were done. The study showed unexpectedly high frequencies of amyloid deposits, evidence of persisting hepatitis B virus (HBV) infection, and antibodies to smooth muscle, to skin basement membrane, and to extractable nuclear antigens (ENA). Compared with unaffected family members, patients with leprosy had increased serum alpha-lipoprotein (alpha-LP) and were more often hepatitis B surface antigen (HBsAg) carriers but, contrary to expectations, the presence of amyloid, the alpha-LP level, serum amyloid associated (SAA) protein, and the HBsAg carrier state all appeared unrelated to the type of leprosy.

Adult↗

Characterization of the immunocompetent cells of rheumatoid synovium from tissue sections and eluates.

T lymphocytes positively identified by alphanaphthyl acetate esterase (ANAE) (70%) were localized in perivascular "cuffs" in rheumatoid synovia. ANAE-negative lymphocytes (B lymphocytes) were primarily within the reactive lymphoid centers, whereas intracellular Ig-expressing plasma cells were outside the centers. Lysozyme of diffuse ANAE expressing mononuclear phagocytes (5-15%) were diffusely dispersed, but were seldom found in the lymphoid centers. There were few granulocytes (10%). On elution, plasma cells and lymphocytes were lost. Most granulocytes and mononuclear phagocytes in the eluate were immunoglobulin-positive. The in situ architecture is compatible with active immunologic inflammation and T-dependent immunoglobulin synthesis.

Arthritis, Rheumatoid↗

Urinary excretion of sialic acid-containing saccharides in systemic lupus erythematosus.

Urinary sialic acid-containing trisaccharides, total sialic acid, and serum sialic acid were studied in 17 patients with systemic lupus erythematosus (SLE) and in 15 healthy controls. The urinary excretion of sialyllactose, measured by a gas chromatographic method, was significantly greater in patients with SLE (37.4 +/- 21.4 mg/24 hours, SD) than in the control subjects (13.7 +/- 3.8 mg/24 hours, p less than 0.001). The mean excretion of sialyl-N-acetyllactosamine (16.6 +/- 8.5 mg/24 hours) and total sialic acid (82.5 +/- 29.4 mg/24 hours) was also greater in the SLE group than in the controls (8.7 +/- 2.8 and 58.0 +/- 16.0 mg/24 hours, respectively; p less than 0.01). Serum levels of sialic acid were correspondingly higher in the SLE patients (84.4 +/- 20.4 mg/100 ml) than in the controls (63.7 +/- 6.5 mg/100 ml, p less than 0.001). Urinary excretion of sialyl-lactose correlated positively with clinical disease activity (p less than 0.001) and with anti-DNA antibody levels (p less than 0.05). On the average, patients with moderate or severe disease excreted three times more sialyl-lactose than did those with mild or inactive disease. Our results suggest that the excretion of sialyl-oligosaccharides reflects disease activity in SLE.

Adult↗

Urinary sialyloligosaccharide excretion as an indicator of disease activity in rheumatoid arthritis.

Urinary trisaccharides containing sialic acid, urinary total sialic acid, and serum sialic acid were studied in 51 patients with rheumatoid arthritis (RA). The urinary excretion of sialyllactose and sialyl-N-acetyllactosamine was measured by quantitative gas chromatography. The output of sialyllactose was significantly greater in patients with RA (31.9 +/- 17.3 mg/24, SD) than in control subjects (15.9 +/- 5.4, P less than 0.001). The RA patients also had higher mean levels of urinary sialyl-N-acetyllactosamine (P less than 0.05), total urinary sialic acid (P less than 0.001), and serum sialic acid (P less than 0.001). Urinary excretion of sialyllactose was considerably higher in patients with active and aggressive RA and moderately higher in patients with moderate disease activity. Excretion in those with mild or almost inactive RA did not differ significantly from that in the controls. Linear regression analysis revealed a strong positive correlation between urinary sialyllactose levels and clinical disease activity (P less than 0.001), as well as between excretion of sialyllactose and sialyl-N-acetyllactosamine in RA. These results suggest that the urinary content of trisaccharides containing sialic acid is an indicator of disease activity of RA.

Adult↗

Skin lesions in Waldenström's macroglobulinaemia. Characterization of the cellular infiltrate.

A patient with Waldenström's macroglobulinaemia presenting with numerous red or brownish-red, round, papulous lesions of the skin is reported. Skin biopsy revealed a massive infiltrate of immature lymphatic cells of the dermis down to the subcutaneous fat. Approximately 80% of these cells were positive for intracellular IgM and kappa light chains as shown by the immunoperoxidase method. This finding established the skin lesions as part of Waldenström's macroglobulinaemia.

Aged↗

Fatal renal vasculitis and minimal change glomerulonephritis complicating treatment with penicillamine. Report on two cases.

Two cases with different and not previously described fatal renal complications during treatment with penicillamine are reported. A man with seronegative rheumatoid arthritis with features of systemic lupus erythematosus was treated with penicillamine for six months and developed a mild membranous glomerulonephritis and a severe renal vasculitis leading to uremia and death. A woman with primary biliary cirrhosis was treated with penicillamine for nine months and developed a nephrotic syndrome, the renal biopsy showing minimal change glomerulonephritis. The nephrotic syndrome responded to prednisone but the patient died, probably from septicemia. Penicillamine may thus cause glomerular damage without deposition of immune complexes. A restricted use of the drug is recommended.

Female↗

Resolution of renal amyloidosis secondary to rheumatoid arthritis.

A patient with seronegative rheumatoid arthritis developed a nephrotic syndrome. Histological examination of renal biopsy disclosed moderate amyloidosis. Ultrastructurally the glomerular amyloid deposits were seen to be located both within the mesangium and subepithelially in the peripheral capillaries. The patient was treated with prednisone and cyclophosphamide for two years. The nephrotic syndrome remitted and a follow-up biopsy showed almost total disappearance of Congo red positive amyloid substance. Electron microscopy showed abundant finely granular material but only small amounts of fibrillar amyloid in the mesangial regions and intramembranous lucent areas containing few amyloid fibrils but no subepithelial deposits in the peripheral capillaries. We conclude that the mesangial amyloid substance was degraded to granular material and that the subepithelial amyloid deposits were resolved by mechanisms similar to those involved in the resolution of subepithelial immune complex deposits, i.e. through slow washing out and incorporation into the basement membrane.

Amyloidosis↗

Extracorporeal irradiation of thoracic duct lymph as immunosuppressive treatment in rheumatoid arthritis.

Thoracic duct drainage and re-infusion of the irradiated lymph was carried out as immunosuppressive treatment in 2 patients with progressive, therapy-resistant rheumatoid arthritis. In both patients, a marked clinical improvement was achieved even during the first days of treatment. A reduced number of T cells in the blood was seen 3 days after onset of drainage, whereas no significant change in the number of B cells was observed. No recirculation of the infused cells could be detected, nor was the radiation removal of T cells accompanied by rapid proliferation of "new" T cells. As clinical improvement and reduction in T cells occurred simultaneously, there is probably a connection between these two events. The beneficial clinical response and the achievement of T cell suppression by thoracic duct drainage--the result of irradiation and re-infusion of irradiated lymph--encourage further clinical trials with this type of treatment in severe therapy-resistant rheumatoid arthritis.

Arthritis, Rheumatoid↗

Isolation and characterization of undersulphated chondroitin-4-sulphate from normal human plasma.

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.

Amino Acids↗