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Biomedical subjects

D K Peters

Publications and source records attributed to D K Peters.

At least 91 records · Page 5Linked to original sources
PubMed1976

The cofactors required by C3 nephritic factor to generate a C3 convertase in vitro.

The mechanisms by which a C3 convertase is generated by C3 nephritic factor (NeF) were investigated using purified NeF, C3, C3b, factor B and factor D of the alternative pathway of complement activation. NeF could generate a C3 convertase with C3 and B in the absence of D, and without cleavage of B. At lower concentrations of NeF the addition of D was required to generate a C3 convertase, and B cleavage now occurred. The generation of both the D-independent and D-dependent C3 convertases with NeF was inhibited by preincubation of the C3 source with C3b inactivator (KAF); isolated C3b was more efficient than the C3 preparations used in generating the D-independent C3 convertase with NeF. These experiments indicate that C3b is required for the formation of both convertases, and that the reaction occurring with apparently native C3 is due to trace amounts of C3b. It is concluded that the C3 convertase generated by NeF in the absence of D is C3bB (NeF), and that generated in the presence of D is the feedback convertase C3bBb. The relevance of these experiments to reactions which may occur in vivo is discussed.

Biological Products↗
PubMed1975

Isolated glomerulonephritis with mesangial IgA deposits.

Mesangial deposits of IgA, occurring in the absence of systemic disease known to be associated with nephritis, were detected by immunofluorescence microscopy in renal biopsy specimens from 25 patients (4% of 630 specimens studied). Associated deposits of C3 were always present, usually with IgG, but IgM deposits were less common and C1q was never seen. On light microscopy most of the biopsy specimens showed mesangial of focal nuclear proliferation though some were normal. Fifteen of the 25 patients presented with macroscopic haematuria, which was usually recurrent and preceded by a sore throat, whereas the remaining, and usually older, patients presented with persistent proteinuria and were more likely to have impaired renal function. This incidence of "mesangial IgA disease" is less than that reported by French workers. There was a significantly high incidence of familial renal disease among these patients. No abnormalities of serum complement or IgA concentration were found.

Adolescent↗
PubMed1975

Recovery from Goodpasture's syndrome after immunosuppressive treatment and plasmapheresis.

A patient with Goodpasture's syndrome has recovered after treatment with immunosuppressive drugs (cyclophosphamide and prednisolone) and removal of circulating antibodies by plasma exchange. This was performed on seven occasions and seems to have hastened the decline in circulating antibody levels. Undertaken early in the course of the disease plasmapheresis could prove a useful addition to its therapy.

Adult↗
PubMed1975

Seasonal nephrotic syndrome. Description and immunological findings.

Three cases are described showing a seasonal exacerbation of their nephrotic syndrome in association with an atopic trait and grass pollen allergy. The first patient has a history of four consecutive seasonal relapses each requiring steroid therapy. Following a course of desensitization injections he has now been free of relapse for 3 consecutive years. The second patient has also had a recurrent steroid-sensitive nephrotic syndrome often associated with the pollen season and allergic rhinitis. In this patient a course of cyclophosphamide has reduced his tendency to relapse. The third patient who has been on continuous prednisone therapy shows a seasonal increase in proteinuria. Serum changes in the first two patients include: a seasonal rise in total and grass pollen specific IgE; the continued presence of grass pollen specific IgG throughout the year but with a reduction during the pollen season in association with a more pronounced fall in the total IgG level; a depression in the C3 level in association with each major relapse; a mild rise in the I-K titre and a positive result in the Clq test for circulating complexes. A renal biopsy performed on the first patient when in relapse showed minor histological changes only and IgG, IgM, IgA, IgD, IgE, C3 and fibrinogen were undetectable by immunofluorescent examination. The probable mechanism for the development of proteinuria in these patients is discussed.

Adolescent↗
PubMed1975

Guinea-pig nephrotoxic nephritis. I. The role of complement and polymorphonuclear leucocytes and the effect of antibody subclass and fragments in the heterologous phase.

In guinea-pig nephrotoxic nephritis induced by a sheep antibody there was minimal glomerular capillary deposition of C3 and accumulation of polymorphonuclear leucocytes (PMN) in the heterologous phase. The C4-deficient strain developed the same injury as normal Duncan-Hartley animals. Complement depletion with cobra venom factor, polymorph depletion with nitrogen mustard or anti-PMN serum and treatment with antihistamines provided no protection. The relationship between the dose of nephrotoxic antibody and the proteinuria was similar for gamma1 and gamma2 subclasses and the F(ab')2 fragment of gamma1 antibody. However, the F(ab') and F(ab) antibody fragments, though fixing on the glomerular basement membrane, did not cause proteinuria. It is concluded that the development of proteinuria in this system: is largely independent of the complement-polymorph system; is due to the fixation of the F(ab')2 fragment of the antibody molecule; and does not depend on an intact Fc piece.

Animals↗
PubMed1975

A quantitative evaluation of anticoagulants in experimental nephrotoxic nephritis.

The protective effects of anticoagulants in nephrotoxic nephritis in rabbits have been studied, using various doses of heparin and defibrination with ancrod. Massive doses of heparin (2000 units/kg/day) were required before significant reduction in glomerular fibrin deposition, extracepillary cell proliferation and urea retention occurred. Doses of 300 and 1000 units/kg/day were insufficient to modify fibrin deposition and cell proliferation. Defibrination with ancrod provided protection, judged by histological and functional criteria, comparable to 2000 units of heparin/kg/day; but fibrin could still be demonstrated in the glomeruli of animals treated with 2000 units of heparin/kg/day, contrasting with the virtual absence of fibrin in animals given ancrod.

Ancrod↗
PubMed1975

The effects of defibrination with ancrod in experimental allergic glomerular injury.

Quantitative studies of the effects of defibrination (with ancrod) have been undertaken in two forms of allergic glomerular damage, nephrotoxic serum nephritis and acute serum sickness in rabbits. No differences in intrarenal fixation of nephrotoxic antibody, complement activation or host antibody response were detected between defibrinated and untreated rabbits with nephrotoxic serum nephritis. Defibrination prevented intraglomerular fibrin deposition in this disease; but some glomerular damage as shown by a rise in blood urea and endothelial proliferation still occurred in defibrinated animals. No differences in immune elimination of BSA, circulating immune complex formation or intrarenal localization of immune complexes were noted in defibrinated animals with acute serum sickness. No intraglomerular fibrin deposition was detected in treated or untreated animals in this disease model. It is concluded that the protective effects of ancrod are directly related to defibrination, and not to any other modification of allergic events.

Ancrod↗
PubMed1975

The role of polymorphonuclear leucocytes in the autologous phase of nephrotoxic nephritis.

The role of polymorphonuclear leucocytes (PMN) in the autologous phase of nephrotoxic nephritis (NTN) in the rabbit has been investigated. Depletion of circulating PMN by nitrogen mustard protected renal function and immunofluorescent examination showed reduction in glomerular fibrin deposition. Depletion of circulating PMN using a highly specific goat anti-PMN serum (APS) provided similar protection of renal function, highly significant reduction in proteinuria and histological and immunofluorescent examination showed reduced glomerular PMN infiltration, extracapillary cell proliferation and virtual absence of fibrin deposition. Although protection by nitrogen mustard may have been partly due to immunosuppression, no reduction in antibody response was detected in the APS-treated rabbits. The results implicate the polymorph as the principal injurious agent in this model of NTN, responsible directly or indirectly for both proteinuria and glomerular fibrin deposition.

Animals↗
PubMed1975

Mechanisms of activation of the properdin system. Studies on properdin electrophoretic mobility in agarose activation of the alternative pathway.

The electrophoretic mobility of properdin in agarose with and without EDTA examined in sera from normal subjects and from patients with mesangiocapillary glomerulonephritis, systemic lupus erythematosus, rapidly progressive glomerulonephritis, mesangial IgG-IgA disease, minimal change glomerulonephritis and partial lipodystrophy. In 'EDTA agarose", the properdin arc of normal serum was always cathodal (gamma), whereas in non-EDTA agarose it was always (beta), indicating that agarose activated properdin with its consequent conversion from a cathodal to an anodal form. Using this change in the mobility of properdin to investigate activation of the properdin system, it was found that the lower the C3 concentration of diseased sera, the less able were they to support properdin conversion by non-EDTA agarose. This relationship we interpret as a manifestation of the requirement of an intact C3b feedback pathway for properdin activation. This view was supported experimentally by (i) decreasing ability of non-EDTA agarose to shift properdin mobility in normal serum as it was progressively depleted of components of the alternative pathway by cobra venom factor, C3 nehritic factor or Mg2+, and (ii) the inability of non-EDTA agarose to shift properdin in sera depleted of C3 or factor B, and in serum deficient in C3. The report of other workers that activated properdin causes generation of C3b, coupled with our finding that properdin activation depends on the C3b feedback, indicates that a system exists in which activation of the C3b feedback cycle allows activation of properdin, allowing in turn further amplification of the C3b feedback. That the anodal form of properdin may be a property of activated properdin was shown by our observations that properdin eluted from zymosan was anodal and activated, and that the properdin in the supernatant normal serum incubated with inulin was anodal.

Complement C3↗
PubMed1974

Glomerulonephritis associated with antibody to glomerular basement membrane.

Glomerulonephritis associated with antibody to glomerular basement membrane, shown by linear staining of the glomerular basement membrane with fluoresceinated anti-IgG antisera, was found in only 10 out of 400 (2.5%) renal biopsy specimens studied by immunofluorescence. Seven of these cases had rapidly progressive glomerulonephritis, five with lung haemorrhage (Goodpasture's syndrome) and two without, and three had less severe nephritis without lung haemorrhage. Circulating antibody to glomerular basement membrane, measured by a passive haemagglutination technique and by indirect immunofluorescence, was detected in the serum of all patients with rapidly progressive glomerulonephritis by both techniques but only by the passive haemagglutination method in two of the other three patients. Two patients died of their lung haemorrhage, one despite bilateral nephrectomy, and lung haemorrhage and circulating antibody to glomerular basement membrane persisted after bilateral nephrectomy in another patient.

Adult↗
PubMed1974

Self-induced glomerulonephritis.

A patient is described who developed renal failure due to a severe proliferative glomerulonephritis with hypocomplementaemia and cryoglobulinaemia while repeatedly injecting herself with diphtheria, pertussis, and tetanus vaccine (D.P.T. vaccine). After stopping the antigen administration there was recovery of renal function, complement values returned to normal, and cryoglobulin could no longer be recovered from the sera. The pathogenesis of the glomerulonephritis is discussed.

Adult↗
PubMed1974

Renal lesions of subacute infective endocarditis.

This paper gives an account of five patients with glomerulonephritis complicating subacute infective endocarditis. In three patients with focal (segmental) glomerulonephritis granular deposits of immunoglobulin and C3 and reduced serum complement suggested an immune-complex aetiology; but in two patients with a diffuse proliferative glomerulonephritis no Ig or C3 was detected in the diseased glomeruli and the pathogenetic mechanism remained undetermined. Four of the five patients developed renal failure needing dialysis.

Acute Kidney Injury↗
PubMed1974

Urinary fibrinogen derivative excretion and intraglomerular fibrin deposition in glomerulonephritis.

The relations between glomerular fibrin deposition, urinary excretion of fibrinogen derivatives (F.D.), and proteinuria were explored in 81 patients with glomerulonephritis. A positive correlation existed between proteinuria and F.D. excretion even when no fibrin could be detected in the glomerulus. In two patients with tubular proteinuria F.D. excretion was also raised, suggesting that tubular reabsorption or catabolism of F.D. or both normally occur.Disproportionately high titres of F.D. were observed when fibrin was deposited in an extracapillary site, but mesangial fibrin deposition was not accompanied by a higher excretion of F.D. than that observed in patients in whom intraglomerular fibrin was not detected. These observations suggest that the immunofluorescent findings on renal biopsies should be the major criteria on which a trial of anticoagulants in proliferative glomerulonephritis might be instituted and that measurement of urinary F.D. is likely to be of value in monitoring therapy in patients with extracapillary fibrin deposition.

Biopsy↗