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Biomedical subjects

J Wieslander

Publications and source records attributed to J Wieslander.

At least 127 records · Page 7Linked to original sources
PubMed1985

Separation and characterization of two populations of aggregating proteoglycans from cartilage.

Intermediary gel immunoelectrophoresis was used to show that purified aggregating cartilage proteoglycans from 2-year-old steers contain two distinct populations of molecules and that only one of these is immunologically related to non-aggregating cartilage proteoglycans. The two types of aggregating proteoglycans were purified by density-gradient centrifugation in 3.5M-CsCl/4M-guanidinium chloride and separated by zonal rate centrifugation in sucrose gradients. The higher-buoyant-density faster-sedimenting proteoglycan represented 43% of the proteoglycans in the extract. It had a weight-average Mr of 3.5 X 10(6), did not contain a well-defined keratan sulphate-rich region, had a quantitatively dominant chondroitin sulphate-rich region and contained 5.9% protein and 23% hexosamine. The lower-buoyant-density, more slowly sedimenting, proteoglycan represented 15% of the proteoglycans in the extract. It had a weight-average Mr of 1.3 X 10(6), contained both the keratan sulphate-rich and the chondroitin sulphate-rich regions and contained 7.3% protein and 23% hexosamine. Each of the proteoglycan preparations showed only one band on agarose/polyacrylamide-gel electrophoresis. The larger proteoglycan had a lower mobility than the smaller. The distribution of chondroitin sulphate chains along the chondroitin sulphate-rich region was similar for the two types of proteoglycans. The somewhat larger chondroitin sulphate chains of the larger proteoglycan could not alone account for the larger size of the proteoglycan. Peptide patterns after trypsin digestion of the proteoglycans showed great similarities, although the presence of a few peptides not shared by both populations indicates that the core proteins are partially different.

Amino Acids↗
PubMed1985

A method for the quantification of cartilage proteoglycan structures liberated to the synovial fluid during developing degenerative joint disease.

An enzyme linked immunosorbent assay for the quantification of proteoglycans or proteoglycan fragments in biological fluids is presented. The assay has been used to determine concentrations of articular cartilage proteoglycans and/or fragments thereof in synovial fluid in early stages of osteoarthrosis. Osteoarthrosis was induced in one knee joint of nine German wire haired pointers by transection of the anterior cruciate ligament. All dogs developed osteoarthrosis in terms of macroscopic as well as microscopic criteria. Attempts were made to aspirate synovial fluid, prior to surgery and at various times in the postoperative period, from the joint operated on as well as from the contralateral joint. Concentrations of proteoglycans (fragments) of one type of aggregating proteoglycan were significantly higher in the synovial fluid samples from the joint operated on compared to the contralateral joint (p less than 0.001), while the difference observed when the other type of aggregating proteoglycan was used as the test antigen was less significant (p less than 0.05). The concentration of proteoglycans (fragments) in synovial fluid samples from joints operated on was significantly higher after the operation when compared with the preoperative concentration (p less than 0.001). No correction has been made for the increased dilution due to hydrops of the joints operated on.

Animals↗
PubMed1985

The involvement of type IV collagen in Goodpasture's syndrome.

Goodpasture's syndrome, involving lung and kidney, is considered to be caused by autoantibodies to basement membranes. This paper has described the isolation and identification of the antigen, which is isolated from collagenase digests of glomerular basement membrane, as a monomer protein of 26,000 daltons and two dimers of about 50,000 daltons. Further analyses indicated that the antigenic protein is derived from the globular domain of type IV collagen corresponding to the NCl peptide. All 22 patients with Goodpasture's syndrome studied had circulating antibodies to this antigen, a few had additional antibodies to laminin, and only one also had antibodies to the 7S collagen domain. No other patient with glomerulonephritis had circulating antibodies to the antigen. The isolated protein can therefore be used in an assay specific for Goodpasture's syndrome. Interestingly the protein antigen could be identified in glomerular, lung, and placenta basement membranes, although the components reacting with the antibodies represented different proportions of the preparations.

Amino Acids↗
PubMed1984

Goodpasture antigen of the glomerular basement membrane: localization to noncollagenous regions of type IV collagen.

The glomerular basement membrane antigen in Goodpasture syndrome is a collagenase-resistant molecule with a monomer molecular weight of about 26,000. Type IV collagen isolated from glomerular basement membrane contains collagenase-resistant sequences within its structure. Polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay, and chemical analysis were used to demonstrate that the collagenase-resistant sequences of type IV collagen contain Goodpasture antigen.

Anti-Glomerular Basement Membrane Disease↗
PubMed1984

Isolation of the specific glomerular basement membrane antigen involved in Goodpasture syndrome.

The antigen involved in the glomerulonephritis associated with antibodies to glomerular basement membrane (GBM) was purified from human GBM digested with highly purified clostridial collagenase. The purified nonreduced sample contained two components with closely similar mobilities on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. After reduction they moved as one, nonantigenic, component, corresponding to a molecular weight of 26,000. Immunologically identical aggregates of higher molecular weight (i.e., 48,000) were also identified in the crude digest. Reduction of such aggregates after purification released some protein with a molecular weight of 26,000, but a large proportion was insensitive to reduction. Seven patients with Goodpasture syndrome all had circulating anti-GBM antibodies directed only against the purified antigen.

Amino Acids↗
PubMed1983

Antiglomerular basement membrane antibody: antibody specificity in different forms of glomerulonephritis.

Components were solubilized from human glomerular basement membrane by digestion with collagenase and pepsin or by extraction with guanidine-HCl either directly or after previous digestion with the enzyme. The diverse preparations were used as antigens in the enzyme-linked immunosorbent assay (ELISA) of antibody titers in sera from patients with Goodpasture syndrome and patients with other forms of glomerulonephritis, that is, systemic lupus erythematosus, periarteritis nodosa, and IgA-related nephropathy. Patients with Goodpasture syndrome had high titers of IgG antibodies reacting most strongly with collagenase digests. The antigen(s) was only partly solubilized by guanidine-HCl extraction, was destroyed by pepsin digestion as well as reduction, and partly destroyed by trypsin digestion. The antigen(s) is most likely noncollagenous protein. Antibodies from patients with other forms of nephritis were directed primarily against antigens in guanidine-HCl extracts, while the antigen(s) was not solubilized by collagenase digestion. Pepsin digestion destroyed the antigen(s). The antibodies were of a different class, that is, the patients with systemic lupus erythematosus had IgG and IgA as well as IgM antibodies; the patients with periarteritis nodosa had IgM or IgG and IgA antibodies, while the patients with IgA-related nephritis had the highest recorded titers of IgA but also had IgG as well as IgM antibodies. None of the patients had antibodies directed against triple helical collagen. The antibody response in anti-GBM antibody-related nephritis, then, is different both with respect to antigen and antibody class and depends on the underlying disease syndrome.

Anti-Glomerular Basement Membrane Disease↗
PubMed1982

Urinary excretion of beta-hexosaminidase in patients with vesico-ureteric reflux.

Urinary excretion of beta-hexosaminidase was studied in 50 patients with vesico-ureteric reflux (VUR) in order to obtain information on the renal injury in this disease. There was no correlation between urinary enzyme excretion and the degree of VUR. Patients without pyelonephritis changes and with normal serum creatinine values showed normal excretion of beta-hexosaminidase. Patients with pyelonephritic changes but normal serum creatinine had enzyme activity towards the upper limit of the normal range whilst patients with pyelonephritic changes and decreased renal function (high serum creatinine) showed increased excretion of urinary beta-hexosaminidase. Some of the patients with VUR and asymptomatic bacteriuria exhibited increased excretion of urinary beta-hexosaminidase and six with acute pyelonephritis had very high levels. These findings indicate that the infective process plays an essential role, besides VUR, in the development of kidney damage.

Adolescent↗
PubMed1982

Clinical experience of long-term treatment with minoxidil in severe arterial hypertension.

Minoxidil was used in 25 patients with severe hypertension whose blood pressure (BP) could not be controlled with conventional treatment or who suffered from intolerable side effects during treatment with other drugs. In 6 patients minoxidil was withdrawn after a short time owing to side effects or because hypertension could be controlled by regular dialysis treatment. The remaining 19 patients were treated with minoxidil for 0.5-4.5 years. The hypotensive effect of minoxidil in combination with beta-blockers and diuretics was good or acceptable in all patients. Neither orthostatic hypotension nor development of resistance was observed. Minoxidil was well tolerated in one patient with porphyria and in two patients who have had the hydralazine syndrome. Eighteen patients had kidney failure with elevated serum creatinine. With one exception the uraemia progressed if the serum creatinine level was above 300 mumol/litre at the start of the treatment. All patients tended to develop oedema, but this was controlled by concomitant diuretic therapy. Eighteen patients developed hypertrichosis. No other significant side effects were observed. One patient died and two patients developed pericarditis in the highly uraemic phase in connection with the start of dialysis. Neither the death nor the cases of pericarditis can be attributed to minoxidil. Minoxidil was found to be effective in severe hypertension in connection with advanced renal disease and can be considered as a valuable addition to the established therapeutic arsenal for treatment of severe hypertension.

Adult↗
PubMed1981

Immunochemical analysis of cartilage proteoglycans. Cross-reactivity of molecules isolated from different species.

Antibodies directed against whole bovine nasal-cartilage proteoglycan and against the hyaluronic acid-binding region and chondroitin sulphate peptides from the same molecule were used in immunodiffusion and immunoelectromigration experiments. Proteoglycans from bovine nasal and tracheal cartilage showed immunological identity, with all three antisera. Proteoglycans from pig hip articular cartilage, dog hip articular cartilage, human tarsal articular cartilage and rat chondrosarcoma reacted with all the antisera and showed immunological identity with the corresponding structures isolated from bovine nasal-cartilage proteoglycans. In contrast, proteoglycans from rabbit articular cartilage, rabbit nasal cartilage and cultured chick limb buds did not react with the antibodies directed against the hyaluronic acid-binding region, though reacting with antibodies raised against whole proteoglycan monomer and against chondroitin sulphate peptides. All the proteoglycans gave two precipitation lines with the anti-(chondroitin sulphate peptide) antibodies. Similarly, the proteoglycans reacting with the anti-(hyaluronic acid-binding region) antibodies gave two precipitation lines. The results indicate the presence of at least two populations of aggregating proteoglycan monomers in cartilage. The relative affinity of the antibodies for cartilage proteoglycans and proteoglycan substructures from various species was determined by radioimmunoassay. The affinity of the anti-(hyaluronic acid-binding region) antibodies for the proteoglycans decreased in the order bovine, dog, human and pig cartilage. Rat sternal-cartilage and rabbit articular-cartilage proteoglycans reacted weakly, whereas chick limb-bud and chick sternal-cartilage proteoglycans did not react. In contrast, the affinity of antibodies to chondroitin sulphate peptides for proteoglycans increased in the order bovine cartilage, chick limb bud and chick sternal cartilage, dog cartilage, rat chondrosarcoma, human cartilage, pig cartilage, rat sternal cartilage and rabbit cartilage.

Animals↗
PubMed1981

Antibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults.

Forty-seven adults with urinary tract infection (UTI), 9 with recent acute pyelonephritis and 38 with previous renal infection, were investigated for the presence of autoantibodies to Tamm-Horsfall protein (THP). All patients except 6 had or had had vesicoureteric reflux (VUR). In patients with recent acute pyelonephritis, only IgA antibodies were significantly elevated. Among the patients with previous UTI, more than 6 months before the time of testing, a graded response was found for IgG and IgM specific antibodies, with the lowest value in those with renal damage and elevated serum creatinine and the highest in those with a normal X-ray. A negative correlation was found between IgG antibodies to THP and elevated serum creatinine (r = -0.76, P less than 0.02). No significant correlation was found between VUR itself and antibodies to THP. A low IgG antibody level to THP in patients with a history of previous UTI seems to be a useful indicator of renal scarring. Possible immunologic mechanisms behind the low antibody level and the renal damage are discussed.

Adolescent↗
PubMed1980

Immunochemical analysis of cartilage proteoglycans. Radioimmunoassay of the molecules and the substructures.

Antibodies specifically reacting with the link proteins, the hyaluronic acid-binding region and chondroitin sulphate-peptides were used to design specific radioimmunoassay procedures. The sensitivity of the method used for the link protein was about 20 ng/ml, and the other two components could be determined at concentrations of about 2 ng/ml. The radioimmunoassay procedures were tested by using proteoglycan subfractions or fragments thereof. The procedures used to quantify link protein and hyaluronic acid-binding region showed no cross-interference. Fragments of trypsin-digested proteoglycan monomers still reacted in the radioimmunoassay for hyaluronic acid-binding region. Subfractions of proteoglycan monomers separated according to size had a gradually higher relative content of the hyaluronic acid-binding region compared with both chondroitin sulphate-peptides and uronic acid, when the molecules were smaller. The proteoglycans therefore may contain a variably large chondroitin sulphate-rich region, which has a constant substitution with polysaccharide side chains.

Animals↗
PubMed1980

Different antibody response in experimental and spontaneous glomerulonephritis.

The immune nephritis antibody response against the collagen and glycoprotein portions of the glomerular basement membrane (GBM) has been monitored by using either type IV collagen prepared from pepsin digests or a collagenase digest of GBM. Sheep immunized with GBM, according to Steblay, respond by developing antibodies directed against the collagen and the glycoprotein portions, respectively. Circulating antibodies directed against sheep GBM structures were not demonstrated until overt clinical disease with high serum creatinine values and proteinuria. Such antibodies could, however, be eluted from the kidneys, where they adsorbed in a linear fashion as demonstrated by immunofluorescence microscopy. In spontaneous human nephritis in Goodpasture's syndrome, circulating antibodies were present at the time of diagnosis. These antibodies reacted only with the glycoprotein portion of the basement membrane, and not with the type IV collagen.

Animals↗
PubMed1979

Human glomerular basement membrane. Heterogeneity of antigenic determinants.

Human glomerular basement membrane was solubilized by digestion with proteolytic enzymes and immunoreactive components were quantitated and characterized by using rabbit antibodies raised against the particulate membrane. A number of antigens were demonstrated but they did not separate on gel filtration. However, two antigenic components in a collagenase digest of the membrane could be separated and isolated by Sepharose 6B chromatography. Chemical characterization suggests that both fragments are noncollagenous glycopeptides (molecular weights approx. 1,000,000 and 60,000--200,000, respectively).

Amino Acids↗
PubMed1979

Human glomerular basement membrane. Antigenic determinants in human urine.

Antisera against particulate human glomerular basement membrane prepared from cadaver kidneys were raised in rabbits. It was shown that both normal individuals and patients with glomerular and tubular diseases excrete in their urine several antigens reactive with these antibodies. One antigen crossreacted immunologically with an antigen from human glomerular basement membrane while several others did not. One of the urinary antigens and the antigen crossreacting with the basement membrane were separated from the others by ion exchange chromatography and gel filtration, respectively. The pattern of anttigen excretion differed depending on the underlying renal disease but the multitude of different antigens detected complicates the interpretation of the patterns of excretion in different diseases.

Antigens↗
PubMed1979

Immunochemical analysis of cartilage proteoglycans. Antigenic determinants of substructures.

Antibodies were raised in rabbits by injection of cartilage proteoglycan monomers, isolated hyaluronic acid-binding region, polysaccharide-peptides prepared by trypsin digestion of proteoglycans and link-protein. The rabbits injected with the proteoglycan monomers made antibodies reacting with the intact proteoglycan. The antiserum contained antibodies specific for, and also reacting with, the isolated hyaluronic acid-binding region and the keratan sulphate-rich region. In addition there were probably antibodies reacting with other structures of the proteoglycan monomer. When isolated hyaluronic acid-binding region was used for immunization the antibodies obtained reacted specifically with the hyaluronic acid-binding region. The antibodies obtained from rabbits immunized with the polysaccharide-peptides reacted with the proteoglycan monomers and showed a reaction identical with that of the chondroitin sulphate-peptides isolated after trypsin digestion of proteoglycans. The antibodies prepared with the link-protein as the antigen reacted only with the link-protein and not with any preparation from the proteoglycan monomer. Neither did any of the antisera raised against the proteoglycan monomer or its substructures react with the link-protein. Separately it was shown that the peptide 'maps' prepared from trypsin digests of the link-protein and the hyaluronic acid-binding region were different. Therefore it appears that the link-protein is not structurally related to the proteoglycan or the hyaluronic acid-binding region. Digestion of proteoglycan monomers or isolated hyaluronic acid-binding region with trypsin did not destroy the antigenic sites of the hyaluronic acid-binding region. In contrast trypsin digests of previously reduced and alkylated preparations did not react with the anti-(hyaluronic acid-binding region). The trypsin digests, however, reacted with both the antibodies directed against the chondroitin sulphate-peptides and those against the keratan sulphate-peptides. Trypsin digestion of the link-proteins destroyed the antigenic site and the reactivity with the antibodies. By combining immunoassay of proteoglycan preparations before and after trypsin digestion it is feasible to quantitatively determine its substructures by using the antisera described above.

Animals↗
PubMed1979

Renal transplantation in insulin-treated diabetics.

In our view, renal transplantation in the uremic diabetic patient is justified. Recipients should be selected with caution. Patients with both loss of vision and heart disease will only rarely benefit from renal transplantation. Living related donor should be preferred if possible.

Adult↗
PubMed1977

Determination of the Tamm and Horsfall glycoprotein in human urine.

A method for the routine determination of the Tamm and Horsfall glycoprotein in human urine is presented. The method is based on quantitative electroimmunoassay. It was demonstrated that the solubility of the Tamm and Horsfall glycoprotein was dependent on urinary ionic strength and pH. To minimize these variables all urines were buffered to pH 5.5 and then preincubated at 37 degrees C in 0.3% sodium dodecyl sulphate. This procedure solubilized and maintained the Tamm and Horsfall glycoprotein in solution. Excess sodium dodecyl sulphate was removed by gel filtration before the quantities of the Tamm and Horsfall glycoprotein were determined by electroimmunoassay. The method is simple, reproducible, has high precision and compares favourably with earlier published methods for the determinations of the Tamm and Horsfall glycoprotein.

Amino Acids↗