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D K Peters

Publications and source records attributed to D K Peters.

At least 55 records · Page 3Linked to original sources
PubMed1982

Interpretation of tracer studies on plasma protein turnover: comparison of methods and optimization of techniques.

1. A comparison of several published methods for analysing plasma protein turnover data has been undertaken, with particular reference to rapidly metabolized proteins such as members of the complement series. 2. With the exception of the equilibrium time method, most methods proved adequate for the determination of overall fractional catabolic rates. A further exception is that the renal clearance method becomes invalid when the fractional catabolic rate approaches the renal iodide clearance, but this may be the method of choice for slowly metabolized proteins if accurate urine collections can be ensured. 3. For the measurement of the ratio of extra to intra-vascular protein pool size a clear preference emerged for the method of C. M. E. Matthews (1957, Physics in Medicine and Biology, 2, 36-53). For rapidly metabolized proteins the calculations must be preceded by a correction for the non-protein bound iodide retained in the intra- and extra-vascular spaces. 4. The accurate calculation of fractional catabolic rate in the extravascular pool generally requires more experimental data than are commonly collected as well as an accurate correction for non-protein bound label that remains unexcreted. Only two techniques hold promise of accurate results: Nosslin's rate equations method and a development of Vitek's deconvolution method described herein. Nosslin's integrated rate equations method is particularly affected by systematic errors in renal iodide clearance estimates and should probably not be further used for this purpose.

Blood Chemical Analysis↗
PubMed1982

Complement-mediated inhibition of immune precipitation. II. Analysis by sucrose density gradient ultracentrifugation.

The factors influencing the ultracentrifugation characteristics of immune complexes generated in the presence of fresh normal human serum have been analysed. In the absence of alternative pathway factors B, D or Properdin, the size of complexes was increased. When classical pathway function was blocked, in C1q deficient serum or in the presence of Mg EGTA, although the proportion of complexes remaining in solution were reduced their size was similar to those formed in normal human serum. In C2 deficient serum, a heterogeneous population of complexes was generated. In all instances repletion with the appropriate missing complement component reversed the abnormality. We conclude that there is normally a rapid sequential process of classical followed by alternative pathway activation leading to stable soluble complexes. In the absence of C1 activation the alternative pathway process requires precipitation of the antigen-antibody aggregates whereas in normal serum these events occur in the fluid phase. We suggest that in C2 deficient serum the C1 and/or C4 reacted complexes fail to activate the alternative pathway efficiently.

Animals↗
PubMed1982

Complement-mediated inhibition of immune precipitation. I. Role of the classical and alternative pathways.

This study has examined the mechanisms involved in complement-mediated inhibition of immune precipitation using radiolabelled BSA and rabbit anti-BSA. Purified proenzyme C1 was capable of maintaining the complexes in soluble form during the first few minutes of reaction whereas immune precipitation was immediate in the presence of purified C1q or C1 + EDTA (ethylenediamine tetra-acetate). In C1q deficient serum, initial immune aggregation was followed by partial solubilization of the formed precipitate similar to that obtained with normal human serum in the presence of Mg EGTA. In C2 deficient serum precipitation occurred at a slow rate. Repletion of the deficient component (C1q or C2 respectively) restored fully inhibition of precipitation. These experiments establish a critical role for the classical pathway, in this phenomenon. By contrast the role of the alternative pathway in maintaining complexes in solution was less important; only partial and delayed precipitation occurred in sera depleted of factor D (RD) or factor B (RB). B and D restored normal complement activity to depleted sera. No precipitation was detected in a reagent depleted of properdin (RP). The mechanisms of inhibition of precipitation are therefore distinct from those responsible for solubilization of an immune precipitate, which is largely dependent on the alternative pathway.

Animals↗
PubMed1982

Infection and immunosuppression. A study of the infective complications of 75 patients with immunologically-mediated disease.

We have studied the infective complications in a group of 75 patients with immunologically-mediated disease who required high dose immunosuppression. There were 22 patients with anti-glomerular basement membrane antibody disease, 19 patients with systemic lupus erythematosus, 18 with wegener's granulomatosis and 16 patients with other forms of systemic vasculitis. The infection rate was 3.69 infections/patient, or 0.74 infections/patient/week of immunosuppression. Bacteria were the commonest infecting organisms (76.1 per cent); serious opportunist viral and fungal infections were less frequent (10.7 per cent) but opportunist pneumonias were an important cause of death. Sixteen patients died (21 per cent) and in 10 of these (62.5 per cent) death was considered to be primarily due to infection. Analysis of six aspects of host susceptibility to infection (age, renal function, dose of prednisolone, cyclophosphamide and azathioprine, and number of plasma exchanges) revealed no single factor as predisposing to infection in the whole group, but in 23 patients who suffered severe infective complications, renal impairment and increasing doses of prednisolone were associated significantly, particularly in combination (p = 0.06). Cyclophosphamide was associated with infection only in the presence of neutropenia, which was rare (13 infections in nine patients). The duration of plasma exchange was not related to the frequency of infection. Fifty patients needed an arteriovenous shunt to provide vascular access for haemodialysis or plasma exchange, and septicaemia occurred in 13; only two episodes of septicaemia were seen in patients without a shunt.

Adolescent↗
PubMed1981

Studies on NEM-treated erythrocyte clearance in the rabbit, with special reference to the effects of circulating immune complexes.

The splenic component of mononuclear phagocytic cell function was investigated in rabbits using as a marker the clearance of N-ethylmaleimide-treated, technetium-labelled autologous erythrocytes. In 66 clearances performed in 23 normal rabbits, the clearance T1/2 was found to be between 5 and 16 min, the value for each rabbit remaining relatively constant. Clearance was proportional to incubation time or the dose of N-ethylmaleimide used. Clearance was delayed following injection of 20 to 65 mg of preformed complexes of BSA-anti-BSA made in 10-fold antigen excess. The degree and duration of this blockade was related to the dose of the complexes up to a critical value of 20 mg (antibody content after which no further decrease in clearance occurred although the duration of the blockade was longer at higher doses. Ultracentrifugation studies showed that these complexes were about 14S in size and sequential studies revealed that they were slowly cleared from the circulation. The experiments indicate that studies of splenic function may be of value in assessing immune complex disease, since circulating immune complexes of these characteristics are poorly detected by current methodology.

Animals↗
PubMed1981

Complement-mediated solubilization in patients with systemic lupus erythematosus, nephritis or vasculitis.

Solubilization of an immune precipitate by serum is a complement function mediated by the alternative pathway and enhanced by the classical pathway--it therefore provides the basis of a simple quantitative assessment of the integrity of complement function. Using a preformed radiolabelled precipitate of BSA-alpha BSA Ab, the solubilization capacity of serial sera from 75 patients with various immune complex diseases or diseases associated with hypocomplementaemia was investigated to correlate this assay of complement function prospectively with disease activity and with measurements of circulating immune complexes (CIC). Reduction in solubilization, defined by more than 25% of values in a given patient being below the normal range, was found in 11 of 12 patients with active SLE, two of 19 patients with active systemic vasculitis, three of three patients with post-streptococcal glomerulonephritis and in three of six patients with nephrotic syndrome due to other types of nephritis. In serial studies, solubilization correlated with disease activity in patients with SLE (P less than 0.005), systemic vasculitis (P less than 0.05) and post-streptococcal glomerulonephritis (P less than 0.05). CIC were found more frequently than abnormalities in solubilization; however, the solubilization assay identified a population of patients with CIC more likely to have active disease. This simple assay of complement function provides data on an aspect of immune complex disease not readily apparent from standard estimations of circulating immune complexes, and appears to be a better measure of their potential phlogistic effects.

Adult↗
PubMed1980

Relapses in Wegener's granulomatosis: the role of infection.

Out of 20 relapses that occurred in patients with Wegener's granulomatosis, nine were provoked by bacterial or viral infection. Seven of these occurred during maintenance treatment in response to infection with common pathogens, and treatment of the infection alone was insufficient to produce remission. Circulating immune complexes were seen only in relapses due to infection and rarely in infections that occurred without relapse. A possible mechanism for infection-provoked relapses is that infection-derived complexes reactivate disease; alternatively, the acute-phase or cellular response to infection may enhance quiescent disease. Infection may exacerbate Wegener's granulomatosis and other autoallergic diseases, but whether it does so by a common mechanism is not known and further study is required.

Antigen-Antibody Complex↗
PubMed1980

Complement deficiency and nephritis. A report of a family.

A family is described in which three children had homozygous deficiency of C3 and in which both parents and two other children were heterozygous for the C3 null gene. One child with heterozygous C3 deficiency was found to have membranoproliferative glomerulonephritis; proteinuria and/or microscopical haematuria was present in all three homozygous C3-deficient children. All children with homozygous or heterozygous C3 deficiency were, to a varying degree, susceptible to infection. The only child of the family with normal complement had no increased risk of infection and no renal disease. This family study provides further support for the proposal that C3 deficiency predisposes to nephritis.

Adolescent↗
PubMed1980

Inhibition of immune precipitation by complement.

Immune precipitation of bovine serum albumin (BSA) by rabbit anti-BSA antibody (Ab) was studied at 37 degrees C in the presence of normal human serum, normal rabbit serum, decomplemented serum and reagents permitting complement activation either by the classical pathway or the alternative pathway. Inhibition of precipitation occurred in the presence of complement. Antibody-excess complexes were kept soluble more easily than complexes formed at equivalence. Human serum was a better inhibitor than rabbit serum. Analysis of the phenomenon showed that during the first minutes of the reaction immune complexes were maintained in solution by the classical pathway only, but at later stages the alternative pathway was essential. Such soluble immune complexes precipitated after further incubation for 24 hr. The subsequent addition of ethylenediamine tetra-acetate (EDTA) to serum at 37 degrees C holding immune complexes in solution led to a slow aggregation of the complexes. Their size was found to be approximately 25S as assessed by sucrose density-gradient ultracentrifugation and they bore C3 and C4 fragments.

Animals↗
PubMed1979

Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange.

By studying the clearance of autologous labeled antibody-coated or heat-damaged erythrocytes, we showed that reversible blockade of the splenic component of reticuloendothelial function existed in 14 of 15 patients referred for treatment of nephritis or vasculitis. In 10 patients treated by plasma exchange--alone in three and combined with steroids and cytotoxic drugs in six--reversal of splenic blockade followed in nine, and in the three patients treated solely by plasma exchange this reversal was demonstrated to occur within 48 hours of the procedure. Only gradual reversal of splenic blockade was found in three of five patients treated by steroids with or without cytotoxic drugs; no change in splenic function was observed in two. When circulating immune complexes were detected by a C1q-binding assay, there was, in serial studies, an approximate inverse correlation between splenic function and the level of C1q-binding material, though hyposplenism was also a feature of patients in whom the C1q-binding assay was negative.

Antigen-Antibody Complex↗
PubMed1979

Complement fixation in acute serum sickness: assembly of glomerular-bound C3-convertase.

Complement (C) fixing properties of glomerular immune deposits were studied in vitro in two groups of rabbits with acute serum sickness (ASS). Deposits were studied early in decomplemented (cobra venom factor-treated) rabbits (Group I) and during the evolution of the nephritis in non-decomplemented rabbits (Group II). Following perfusion of kidneys of animals from Group I (which contained no autologous C3) with rabbit serum deficient in factor B (classical pathway) or serum pre-treated with Mg++EGTA (alternative pathway), fixation of C3 was observed in both systems. No C3 deposition was found when EDTA-rabbit serum was used. When kidney sections obtained from serial biopsies and autopsy material from Group II (which contained rabbit C3-C3rb) were incubated with purified factors B and D, followed by either purified human C3 (C3hu) or EDTA-guinea-pig serum (C3gp), fixation of C3hu or C3gp to early C3 deposits was observed. When sections were pre-incubated with heat-inactivated rabbit serum (source of C3b-inactivator), C3 fixation was substantially reduced. Little or no C3 fixation was found after incubation of sections with human or guinea-pig serum depleted of factor D (classical pathway). Thus, in ASS, glomerular complement deposition appears to be predominantly dependent on the activation of the alternative pathway (C3b-feedback) which is progressively lost during the evolution of the nephritis.

Animals↗
PubMed1979

Metabolism of human beta 1H: studies in man and experimental animals.

Metabolic studies were performed with a purified, functionally-active preparation of human beta 1H. In seven normal human subjects, the half-life ranged from 66--87 hr with fractional catabolic rates (FCR) of 1.04--1.63%/hr. Synthesis rates were 0.22--0.57 mg/kg/hr and extravascular distribution ratios were 0.34--0.67. There was evidence of extra-vascular catabolism in each subject. In sixteen patients with immunological disease four showed hypercatabolism of beta 1H. However, three patients with C3 mephritis factor (NeF) had normal beta 1H turnover despite profound reduction in C3 concentration; it is suggested that the reaction of beta 1H with the C3b. Bb convertase exposes it to a catabolic site and that in the NeF patients the NeF stabilized convertase prevents such exposure. Studies of the acute phase response were carried out in nine patients following elective surgery, with C-reactive protein (CRP) used as the control protein: six patients showed no rise in beta 1H levels and three showed a small (20%) rise whereas all exhibited a gross rise in CRP. Pre-incubation of 125I- beta 1H with NHS, with NHS in the presence of NeF and with C3b+C3b 1NA caused no change in beta 1H turnover in animals despite demonstrable total C3 conversion with the NeF.

Animals↗