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Biomedical subjects

B M Iversen

Publications and source records attributed to B M Iversen.

88 records · Page 5Linked to original sources

The heterologous immune complex glomerulonephritis. A dose dependent glomerulonephritis with acute, latent and chronic phases in a long-term study.

The pathophysiology, histology and immunohistology of acute and chronic heterologous immune complex glomerulonephritis were investigated in a long-term study in male Wistar rats. The glomerulonephritis showed 3 phases: an initial nephrotic syndrome, a latent phase with stable proteinuria (40 mg/24 h), and a terminal phase with increasing proteinuria and blood pressure, and declining serum protein concentration and creatinine clearance. Antiserum doses of 1.0, 1.5 and 2.0 ml induced maximal proteinuria (112, 257 and 272 mg/24 h respectively) after 14 days whereas normal rabbit serum and 0.5 ml antiserum gave no proteinuria. After 100 days, the rats injected with 1.0 ml of antiserum did not show physiological signs of renal disease; in the rats injected with 1.5 ml of antiserum the disease run a chronic course. Equal amounts of rabbit IgG, rat IgG and rat C3 were found in 10 glomeruli from rats 100 days after injection of 0.5, 1.0 and 2.0 ml (p greater than 0.10). Intramembranous deposits and spike formation were observed in all groups. All changes increased with greater antiserum doses. Chronically diseased animals observed from 500 to 750 days showed deposits of rabbit IgG in the basement membrane, and in most animals small amounts of rat IgG and rat C3 were also observed. This is compatible with a sustained stimulus for antibody formation throughout the course of this type of glomerulonephritis.

Acute Disease↗

Indirect haemagglutination for the demonstration of antibodies to renal antigens from rats.

An indirect haemagglutination (IHA) test using tanned sheep erythrocytes was developed to detect antibodies in sera from rabbits immunized with renal tubular epithelium (RTE) or with glomerular basement membrane (GBM) from rats. The RTE antigen preparation, called Fx1A, sensitized the erythrocytes directly, whereas the GBM preparation had to be treated with collagenase. THe antisera to Fx1A gave titres up to 64,000, and the antisera to GBM up to several million. The sera were monospecific, since they gave no cross-reactions in IHA, precipitation, or absorption tests. Using the IHA test, the quantitative aspects of experimental glomerulonephritis in rats can be studied. Preliminary results obtained in transfer experiments indicate a dose-response relationship between the titres in IHA and the degree of proteinuria.

Animals↗

Localization of the C3b receptors in human renal glomeruli.

Cryostat sections of human kidney were incubated with C3b containing immune complexes. The complexes were horseradish peroxidase (HRP) and F(ab')2 fragments of rabbit IgG anti-HRP incubated in C4-deficient guinea pig serum. The peroxidase activity was revealed histochemically. The sections were studied using light and electron microscopy. The bound complexes were localized to the foot processes of the visceral epithelial cells and to the surface of the parietal epithelial cells facing Bowman's space. No receptors could be demonstrated on the endothelial or mesangial cells.

Antigen-Antibody Complex↗

Suppressed development of experimental glomerulonephritis in lactating rats.

Five of six lactating rats did not develop proteinuria after an injection of nephrotoxic serum, whereas four out of five non-lactating, non-pregnant rats showed the usual proteinuric response (P = 0.06). The amount of heterologous IgG deposits was similar in both groups, but the lactating rats had significantly less autologous IgG (P = 0.004) in the glomerular basal membrane. It is suggested that hormonal factors influence the development of experimental glomerulonephritis in lactating rats.

Animals↗

Assessment of barbiturate removal by charcoal hemoperfusion in overdose cases.

Five patients with severe barbiturate intoxication were treated with charcoal hemoperfusion. The perfusions were carried out for 3.5 hr, two of the patients requiring an additional treatment. A marked clinical improvement was observed in all of the patients. The serum concentration decreased by 17 to 42% and the amount removed corresponded to 4 to 13% of the ingested dose. The clearance decreased from the start to the end of the treatment during most of the perfusions. With phenobarbital the clearance was less reduced and the column still had the capacity to adsorb drugs after the 3.5-hr perfusion. Therefore, since the amount of drug removed was relatively small, longer lasting perfusions are recommended.

Adolescent↗

Complement receptors in pathological human renal glomeruli.

Glomerular complement receptors (GCR) were demonstrated by the adsorption of C3 coated sheep erythrocytes to cryostat sections of human kidneys. An epithelial localization of the GCR is implied by the binding pattern of the indicator cells. The GCR activity was reduced in all glomeruli where in vivo deposition of immunoglobulin and C3 along the capillary wall was observed. In fourteen out of nineteen biopsies where deposits in the mesangium were seen, reduced GCR activity was also observed, whereas GCR activity was normal in the other five. Immunofluorescence and haemadsorption tests performed on the same section showed that C3 deposits corresponded to areas showing reduced complement receptor activity. Areas outside the C3 deposits adsorbed indicator cells coated with various amounts of C3 similarly to the adsorption to glomeruli seen in normal adult and fetal kidneys. Sclerotic glomeruli showed no GCR activity. The results indicate that the complement receptors play a role for the binding of complement-containing complexes in glomeruli.

Binding Sites, Antibody↗

Membrane filtration in microscopical examination of urinary sediment.

Microscopical examination of the urinary sediment has been performed after membrane filtration and after routine centrifugation, and the results were compared. Various quantities of urine were filtered through a membrane with pore size of 3 micrometer, stained with Shorr stain and made translucent with xylol. All granular and cellular casts were counted on a trimmed membrane, 15 X 20 mm. The routine centrifugation was carried out on 10 ml urine at 1500 rpm for 3 min. Among 11 patients with glomerulonephrits and recurrent hematuria, casts were found in 9 after filtration but in only 2 after routine centrifugation. Casts were detected by the filter method in the urine after angiography of the kidneys in 8 of 12 patients, after centrifugation in only one of them. No casts were found in 6 patients with hematuria due to urological disorders and in 21 healthy persons. The diagnostic sensitivity of microscopical examination of urine was greatly increased by the filter method. This may be due to larger amount of urine examined by the filter method, but an additional cause may be that routine centrifugation destroys red cell casts.

Adolescent↗

Intestinal adaptation after jejuno-ileal bypass operation for massive obesity.

Intestinal adaptation was studied in six patients with massive obesity treated by jejuno-ileal bypass operation. Glucose absorption in the jejunum was measured by a perfusion technique. The morphometric and enzymatic measurements were carried out on biopsies from the proximal jejunum and the distal ileum. Results obtained before and six months after the operation were compared. The glucose absorption per unit length of jejunum was unchanged at a glucose concentration of 66 mmol/l in the perfusate but increased significantly at a glucose concentration of 133 mmol/l (p less 0.025). The mean sucrase activity did not change, whereas the lactase activity increased significantly in the jejunum and ileum. The mean villus height increased significantly, while the epithelial cell height and cell width were unchanged both in the jejunum and the ileum, suggesting that the operation resulted in epithelial cell hyperplasia. The glucose absorption in the jejunum was positively correlated with the villus height (r = 0.76), which suggests that the increased glucose absorption was related to an increased number of epithelial cells.

Adaptation, Physiological↗

Retroperitoneal fibrosis during treatment with methydopa.

Retroperitoneeal fibrosis (R.P.F.) and a positive direct Coombs test developed in a patient who had received 1.4 kg. of alpha-methyldopa over a period of 5 years. Immunofluorescence microscopy demonstrated deposits of IgG, IgM, and IgA on the collagen fibres of the R.P.F. Biopsy speciments of the temporal artery, the right kidney, and the R.P.F. did not show signs of general arterial disease on light, immunofluorescence, and electron microscopy. Drugs which provoke autoimmunisation and interfere with nervous transmission are known to induce deposition of collagen or R.P.F. This suggests that R.P.F. in this patient was probably caused by alpha-methydopa.

Biopsy↗

Characterization of ribosomal P autoantibodies in relation to cell destruction and autoimmune disease.

Autoantibodies against the ribosomal P proteins are related to cell death and tissue destruction and are frequently exhibited in patients with systemic lupus erythematosus (SLE). In an attempt to explore the effect of tissue destruction on the induction of anti-P autoantibodies, we searched for anti-P autoantibodies by enzyme-linked immunosorbent assay in 201 antinuclear antibody (ANA)-positive individuals, in 10 patients with treated kidney SLE and in 45 acute leukaemia patients undergoing intensive chemotherapy. The autoantibody reactivity was further characterized using one- and two-dimensional immunoblot analysis and immunofluorescence. Anti-P were detected in 5.5% (11/201) of ANA-positive individuals, but not in kidney-affected SLE patients or in patients with leukaemia. Seven of 11 anti-P-positive patients had SLE (3/11), primary Sjögrens's syndrome (1/11) and other autoimmune diseases (3/11). A relation between disease activity and anti-P was suggested by follow-up examinations in one SLE patient, supported by the absence of anti-P autoantibodies in the 10 treated kidney SLE patients. Anti-P autoantibodies were detected by immunoblot in one patient with SLE indicating anti-P2 predominance and in the patient with Sjögrens's syndrome indicating anti-P1 predominance. Diverging humoral responses in these ANA- and anti-P-positive patients were further illustrated by immunofluorescence, elucidating varying nuclear reactivity and anti-P pattern. The observation of anti-P in individuals with active autoimmune disease, but not in patients with chemotherapy-induced cell damage, suggests that anti-P antibodies are part of a specific disease process, and not elicited as a response to cell destruction per se.

Adult↗