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Biomedical subjects

D K Peters

Publications and source records attributed to D K Peters.

At least 73 records · Page 4Linked to original sources
PubMed1978

Value of immune-complex assays in diagnosis and management.

Two complement-dependent assays for circulating immune complexes, the C1q-binding assay and the conglutinin binding, were used to study patients with suspected immune-complex disease. Complexes were detected most frequently in multisystem disease such as infective endocarditis (69%) and systemic lupus erythematosus (60%), and less frequently in isolated nephritis (26% of membrano-proliferative nephritis). Sequential estimations in 32 patients showed that concentrations of circulating immune complexes correlated with disease activity and were useful in monitoring therapy.

Adolescent↗
PubMed1978

Strong association between HLA-DRW2 and antibody-mediated Goodpasture's syndrome.

In a study of HLA types in Caucasian patients with nephritis due to antibodies to glomerular basement membrane, antigen frequencies at A, B, or CW loci were normal. However, 15 out of 17 (88%) patients to whom DRW types were definitely assigned had HLA-DRW2 compared with 32 out of 100 Caucasian blood-donors. This difference is highly significant.

Anti-Glomerular Basement Membrane Disease↗
PubMed1978

Prolonged complement activation in mice.

Because antibody responses to the alternative complement pathway activator, cobra venom factor, are T-dependent and B mice therefore do not develop resistance to its action, it was possible to examine whether renal injury occurs under circumstances of protracted third-phase alternative pathway activation. After periods of up to three months, no evidence from measurements of blood urea or proteinuria or from examinations with light microscopy immunofluorescence or electron microscopy was obtained to indicate a directly nephrotoxic effect of this type of complement activation.

Animals↗
PubMed1978

Delayed removal of renal-bound antigen in decomplemented rabbits with acute serum sickness.

We have examined the effects of complement depletion, brought about by cobra venom factor (CVF), on the clearance of radiolabelled BSA from the kidney in acute serum sickness in rabbits. The decomplemented group showed a significant decrease in the rate of clearance of renal-bound antigen with a mean half-clearance time of 19.5 days (range 9.3--60) vs 11.3 (range 8.7--15) for the control group. C3 was rapidly cleared from the glomerulus (as assessed by immunofluorescence) when further deposition was prevented by treatment with CVF. Glomerular immune complexes apparently activated the alternative pathway in vitro. These findings suggest that in immune complex nephritis, the clearance of deposited complexes from the kidney is complement-dependent.

Animals↗
PubMed1978

The immunogloblin nature of nephritic factor (NeF).

NeF was shown to be antigenically and structurally similar to IgG by the following experiments: (1) NeF activity in serum was absorbed by and, under acid conditions, could be eluted from (a) anti-myeloma IgG antibody coupled to Sepharose and (b) protein A-Sepharose. (2) Purified NeF could bind to anit-myeloma IgG-Sepharose and could be eluted with acid, and this binding was blocked by myeloma IgG. (3) An antibody to beta2, microglobulin, showing strong cross-reactivity with normal IgG, bound NeF activity before, but not after, absorption of the antiserum with IgG. (4) Sepharose-coupled antibodies to NeF could bind activity which was recovered in the acid eluate. This binding capacity was lost after absorption of the antibody with normal and myeloma IgG. (5) Structural similarity was demonstrated by pepsin and papain digestion, which resulted in NeF activity eluting with F(ab')2 and Fab fragments from protein A-Sepharose and Sephadex G-150. (6) Autoradiography of PAGE-SDS of 125I-labelled NeF eluted from EA43bBb cells showed that NeF had a larger H chain than normal IgG, suggesting that NeF might be an abnormal IgG molecule.

Chemical Phenomena↗
PubMed1977

Enhanced allergic tissue injury in Goodpasture's syndrome by intercurrent bacterial infection.

Studies of 16 relapses in seven patients receiving treatment for Goodpasture's syndrome showed that intercurrent bacterial infection seemed to be the precipitating event in 13 cases, whereas a rising antibody titre to glomerular basement membrane was responsible in only one. This association between infection and relapse in Goodpasture's syndrome has several implications for the pathogenesis of antibody-mediated tissue damage, and, clearly, more experiments are needed. Whatever the explanation, however, prevention and early diagnosis and treatment of infection in anti-GBM disease are important.

Adolescent↗
PubMed1977

Plasma-exchange and immunosuppression in the treatment of fulminating immune-complex crescentic nephritis.

Nine patients with fulminating immune-complex crescentic nephritis were treated by a regimen of intensive plasma-exchange, steroids, and cytotoxic drugs. In five patients with severe renal failure there was early and rapid improvement in renal function; in one patient an early but extensive focal necrotising glomerulitis was arrested; in two patients improvement was delayed for 3 and 7 weeks and could not confidently be attributed to therapy; one patient, anuric at presentation, did not recover renal function. Follow-up renal biopsy specimens, obtained in three patients, showed no evidence of active disease. With the Clq-deviation test, circulating immune complexes were detected in five patients before treatment and had disappeared when renal function had improved and stabilised: these patients showed the best response to therapy. In three patients temporary withdrawal of plasma-exchange was followed by the reappearance of immune complexes in the circulation and was accompanied in two patients by deterioration in renal function; reintroduction of plasma-exchange was followed by elimination of immune complexes and further improvement in renal function.

Adult↗
PubMed1977

Metabolism of the fifth component of complement, and its relation to metabolism of the third component, in patients with complement activation.

The metabolism of the fifth component of complement (C5), and its relatonship to metabolism of the third component of complement (C3), has been studied in normal subjects and patients by simultaneous administration of radioiodine labeled C5 and C3. In seven normal subjects the fractional catabolic rate of C5 ranged from 1.5 to 2.1% of the plasma pool/h and extravascular/intravascular distribution ratio from 0.22 to 0.78, these values being similar to those obtained for C3, and synthesis rate from 71 to 134 mug/kg per h, In patients with complement activation the increase in fractional catabolic rate of C5 was nearly always less than that of C3. The data also showed that there was increased extravascular distribution of C3 and C5 in most patients and considerable extravascular catabolism of both proteins in some. However, there were differences in metabolic parameters between patients with different types of complement activation. In patients with systemic lupus erythematosus, fractional catabolism and extravascular distribution of C3 and C5 were both increased, and there was marked extravascular catabolism of both proteins. There was increased fractional catabolism and extravascular distribution of C3 in patients with mesangiocapillary nephritis and (or) partial lipodystrophy, and fractional catabolism of C5 was also increased in three of six studies although distribution of C5 was always within the normal range; however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated.

Adolescent↗
PubMed1977

C3b receptors in glomerular disease.

Using two indicator systems--sheep erythrocytes or fluoresceinated S. typhi coated with C3b the presence of a receptor for C3b (but not C3d) in the normal human glomerulus is confirmed. No receptor could be detected in other species tested (mouse, rat, guinea-pig, rabbit and rhesus monkey). Binding of indicator particles was reduced or lost in diseases associated with glomerular capillary deposition of C3, but not in those with mesangial deposition alone. However in some cases the receptor was lost in the absence of detectable C3 deposition. No receptors were detected in proliferating cells in glomerular crescents.

Animals↗
PubMed1977

Guinea-pig nephrotoxic nephritis II. Autologous phase: complement activation without detectable injury.

In the autologous phase of nephrotoxic induced by sheep antibody to glomerular basement membrane (GBM) in Dunkin-Hartley and C4 deficient strain guinea-pigs, less than 50% of animals developed proteinuria at the height of the autologous antibody response despite high anti-sheep immunolglobulin tetres and fixation of guinea-pig IgG and complement in the kidney. tonly two of thirty-sdven animals (5-4%) developed progressive. In a passive model of autologous phase injury using high titres rabbit antibody to sheep IgG, proteinuria failed to occur despite fixation of up to 95 microng rabbit antibody per kidney. Repeated injection of sheep nephrotoxic antibody (NTab) caused a persisting nephrotic syndrome but not the characteristic proliferative lesion of anti GBM diseases in other species.

Animals↗
PubMed1976

Remission of myasthenia gravis following plasma-exchange.

A course of daily plasma-exchange was undertaken in 3 patients with severe myasthenia gravis (M.G.) who had failed to respond to anticholinesterases, thymectomy, and steroids. In the 2 cases with acquired M.G., exchange was associated with an unequivocal improvement in muscle weakness and fatiguability, indicating that a humoral factor in plasma is directly concerned in causing the disorder of neuromuscular transmission. The improvement began within a few days of initiating exchange and continued for several days after exchange ceased. Preliminary evidence suggests that the beneficial effect can be maintained with subsequent immunosuppressive therapy. The patient with congenital M.G. failed to improve, suggesting that its pathogenesis may differ from that of the acquired disease.

Adult↗
PubMed1976

Immunosuppression and plasma-exchange in the treatment of Goodpasture's syndrome.

Seven patients with Goodpasture's syndrome induced by anti-glomerular-basement-membrane (anti-G.B.M.) antibody were treated by a regimen of intensive plasma-exchange, cytotoxic drugs, and steroids. In the three patients retaining some renal function at presentation, this regimen led to suppression and eventual termination of antibody synthesis with improvement in renal function. In four patients, all anuric at presentation, antibody to G.B.M. persisted with variable reduction in the circulating levels. No return of renal function occurred in this group, all of whom had extensive changes on renal biopsy. Pulmonary haemorrhage, life-threatening in one patient, was rapidly controlled in all five patients in whom it was a presenting feature. In addition to its effect on antibody levels, plasma-exchange, using volume-replacement with plasma-protein fraction (P.P.F.), resulted in substantial depletion of complement and fibrinogen, mediators possibly contributing to the antibody-induced injury.

Adolescent↗
PubMed1976

The complement abnormalities of lipodystrophy.

Investigation of the serum complement system in 25 patients with various forms of lipodystrophy showed no abnormality in three patients with total lipodystrophy; a single patient with limb lipodystrophy had evidence of activation of the classical complement pathway. However, of the 21 patients with partial lipodystrophy, 17 had low serum C3, with normal C4 and C2, concentrations, accompanied in 14 by a serum C3 splitting factor indistinguishable from nephritic factor, suggesting activation of the alternative pathway. These abnormalities occurred in 10 patients without clinically overt renal disease. Seven patients had overt nephritis; renal biopsies obtained in six showed mesangiocapillary (membranoproliferative) nephritis in all. Thus, the majority of patients with partial lipodystrophy have hypocomplementemia. Although nephritis may not invariably develop, the high rate of mesangiocapillary nephritis in these patients suggests that complement activation via the alternative pathway predisposes to the development of this form of glomerular disease.

Adolescent↗
PubMed1976

Defibrination with ancrod in nephrotoxic nephritis in rabbits.

Defibrination with ancrod in nephrotoxic nephritis in rabbits. In rabbits with nephrotoxic nephritis, defibrination with ancrod provided protection when administered during the autologous phase, after extensive glomerular fibrin deposition had occurred and crescents and renal failure were developing. When further glomerular fibrin deposition was prevented by defibrination, deposited fibrin was rapidly removed, indicating that glomerular fibrin-clearing mechanisms are retained in crescentic nephritis. Defibrination had no effect on the extent of glomerular C3 deposition or on the amount of proteinuria.

Ancrod↗
PubMed1976

The role of C3 in the autologous phase of nephrotoxic nephritis.

The role of complement has been studied in the autologous phase of nephrotoxic nephritis (NTN) in rabbits. No reduction in glomerular fibrin deposition, crescent formation or protection from renal failure was observed in either the standard model of NTN when decomplementing doses of cobra venom factor (CVF) were given before the autologous phase or in a telescoped model when CVF was administered before the nephrotoxic antibody. In the latter situation glomerular fibrin deposition and crescent formation were found in the absence of detectable deposition of C3. However, substantial protection was observed when circulating polymorphonuclear leucocytes (PMN) were depleted by antipolymorph serum. These observations establish the existence of a system of allergic glomerular injury mediated by PMN but independent of C3. It is postulated that this system may account for the glomerular injury seen in patients with Goodpasture's syndrome in whom glomerular C3 deposition is not found.

Animals↗