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Biomedical subjects

M B Pepys

Publications and source records attributed to M B Pepys.

At least 181 records · Page 10Linked to original sources

A comparison of the erythrocyte sedimentation rate and serum C-reactive protein concentration in elderly patients.

Fifty-five consecutive admissions to an acute geriatric unit were studied prospectively. Individuals were classified according to the obvious presence or absence of an active disease process on admission and their serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured then and five days later. There was no significant difference between the ESR values in the two groups either on admission or at day 5, nor was there any significant change between admission and day 5. In contrast, CRP values were very significantly higher in the active than in the non-active group and there were marked changes over the 5-day period corresponding to changes in clinical condition. These results indicate that the serum CRP concentration is superior to the ESR as an objective, non-specific marker for disease activity in the elderly.

Aged↗

Correlation of disease activity in systemic vasculitis with serum C-reactive protein measurement. A prospective study of thirty-eight patients.

In a prospective study over 2 years, serum C-reactive protein (CRP) concentration and erythrocyte sedimentation rate were measured serially in thirty-eight patients with various types of necrotizing systemic vasculitis. The CRP concentration was always elevated in patients with active vasculitis and fell rapidly in association with clinical remission induced by immunosuppression. During periods of complete remission, in the absence of any intercurrent condition, the value remained within the normal range. In contrast the sedimentation rate responded more slowly to changes in disease activity and did not necessarily reflect the level of inflammation at a particular time. These results, together with the commercial availability of rapid and precise assays for CRP, indicate that serial measurement of the serum CRP fills the urgent need for an objective index of the activity of the systemic vasculitides and their response to therapy.

Blood Sedimentation↗

Serum C-reactive protein measurement in the detection of intercurrent infection in Oriental patients with systemic lupus erythematosus.

In a prospective study serum C-reactive protein (CRP) concentrations were measured during 28 febrile episodes in 27 Oriental patients with systemic lupus erythematosus (SLE). Although active SLE was associated with only a modest rise in serum CRP level, intercurrent infection provoked substantially higher levels. Serum CRP thus provides a sensitive objective test for this complication in SLE patients of all ethnic groups.

Adolescent↗

Circulating human leucocyte elastase in patients with inflammatory bowel disease.

The plasma concentration of human leucocyte elastase (HLE), measured by enzyme immunoassay as the complex with alpha 1-proteinase inhibitor, was determined in 94 patients with active and inactive inflammatory bowel disease. In Crohn's disease and in ulcerative colitis human leucocyte elastase levels were raised significantly above normal when the disease was active, and fell on remission. The mean human leucocyte elastase level in 31 cases of active Crohn's disease was significantly greater than the mean human leucocyte elastase level in 23 patients with active ulcerative colitis (p = 0.013). The values of human leucocyte elastase correlated significantly with Crohn's disease activity index scores (p = 0.05) and with the circulating concentration of C-reactive protein (p less than 0.05 and p less than 0.01 for ulcerative colitis and Crohn's disease respectively), but not with the erythrocyte sedimentation rate. These results indicate that the concentration of human leucocyte elastase in the plasma of patients with inflammatory bowel disease reflects the activity of their intestinal disease and suggest that serial measurements of human leucocyte elastase may be useful in the assessment and clinical management of these conditions.

Adolescent↗

Serum C-reactive protein concentration in the management of infection in patients treated by continuous ambulatory peritoneal dialysis.

In a prospective study over 21 months, serum C-reactive protein (CRP) concentration was measured serially in 39 consecutive patients undergoing continuous ambulatory peritoneal dialysis. All patients with peritonitis mounted a CRP response, and the height of the response correlated well with the severity and extent of the peritoneal damage. Patients who recovered uneventfully after antimicrobial treatment showed a prompt fall in CRP from its peak value towards normal. In contrast, each patient in whom the serum CRP value remained raised after antimicrobial treatment had a complicated course. During routine outpatient follow up the serum CRP value remained within the normal range in the absence of intercurrent complications. These results, together with the commercial availability of rapid and precise assays for CRP, indicate that serial CRP measurements may be useful in monitoring the efficacy of antimicrobial treatment during episodes of peritonitis and in the recognition of intercurrent complications in patients undergoing continuous ambulatory peritoneal dialysis.

Adult↗

Studies of the in vivo synthesis and catabolism of serum amyloid P component (SAP) in the mouse.

The production of mouse serum amyloid P component (SAP), a major acute phase protein of liver origin, was studied immunocytochemically using the peroxidase staining technique. SAP was not detectable in the cytoplasm of hepatocytes from normal, unstimulated mice, nor was it observed before 24 h after an acute phase stimulus. 125I-labelled mouse SAP was cleared from the plasma in vivo with a half-life of 7.0-8.25 h in all animals studied including: normal mice of different strains with different genetically determined plasma SAP concentrations; mice undergoing acute phase responses with greatly elevated plasma SAP levels and mice with casein-induced amyloidosis. The circulating level of SAP is thus independent of its rate of clearance and catabolism and is determined by the rate of synthesis and/or secretion of SAP.

Amyloid↗

In vivo turnover studies of C-reactive protein.

The in vivo plasma clearance rate of the acute phase reactant C-reactive protein (CRP) was studied in mice and rats. The clearance rate of 125I-human CRP in mice and 125I-rat CRP in rats showed a T1/2 of approximately 4 h. The T1/2 was independent of circulating levels of CRP and was not affected by the presence of C-polysaccharide (CPS), a ligand to which CRP binds. However, in mice receiving sufficient CPS, more radioactivity localized to the spleen compared to mice receiving 125I-CRP only. 125I-CPS was rapidly cleared at the same rate by normal mice and by mice undergoing an acute phase response while rats cleared 125I-CPS more slowly despite having high circulating CRP concentrations. These findings suggest that CRP does not provide a mechanism for extremely rapid clearance of its ligands from the circulation, although the handling and subsequent fate of these ligands may be affected.

Animals↗

Calcium-dependent aggregation of human serum amyloid P component. Inhibition by the cyclic 4,6-pyruvate acetal of galactose.

Serum amyloid P component is a normal plasma glycoprotein which is the precursor of amyloid P component, a minor but universal constituent of amyloid deposits. When isolated human P component is exposed to free ionised Ca2+ it aggregates and precipitates. This phenomenon is completely inhibited by the presence of 10(-4)-10(-2) M methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside, a recently synthesised specific ligand for amyloid P component. This observation suggests that the autoaggregation of human amyloid P component involves the Ca2+ dependent specific ligand binding property of P component, but does not distinguish between receptor-site-mediated and allosteric mechanisms.

Amyloid↗

Specific chemical dissociation of fibrillar and non-fibrillar components of amyloid deposits.

In systemic amyloidosis, a fatal disorder for which there is no effective treatment, the extracellular protein deposits are composed of amyloid fibrils together with a non-fibrillar glycoprotein, amyloid P component (AP). Methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG), a recently identified ligand for AP, was tested for its ability to produce in-vitro elution of AP which had been laid down with amyloid fibrils in vivo. Millimolar concentrations of MO beta DG completely dissociated AP from human and murine splenic amyloid deposits. Availability of this material thus provides for the first time the opportunity for specific molecular dissection of amyloid deposits. If MO beta DG or a related substance were effective in vivo it might be of therapeutic importance.

Amyloid↗

Amino acid sequence homology between rat and human C-reactive protein.

The rat serum protein that undergoes Ca2+-dependent binding to pneumococcal C-polysaccharide and to phosphocholine residues, and that is evidently a member of the pentraxin family of proteins by virtue of its appearance under the electron microscope, has been variously designated as rat C-reactive protein (CRP) [de Beer, Baltz, Munn, Feinstein, Taylor, Bruton, Clamp & Pepys (1982) Immunology 45, 55-70], 'phosphoryl choline-binding protein' [Nagpurkar & Mookerjea (1981) J. Biol. Chem. 256, 7440-7448] and rat serum amyloid P component (SAP) [Pontet, D'Asnieres, Gache, Escaig & Engler (1981) Biochim. Biophys. Acta 671, 202-210]. The partial amino acid sequence (45 residues) towards the C-terminus of this protein was determined, and it showed 71.7% identity with the known sequence of human CRP but only 54.3% identity with human SAP. Since human CRP and SAP are themselves approximately 50% homologous, the level of identity between the rat protein and human SAP is evidence only of membership of the pentraxin family. In contrast, the much greater resemblance to human CRP confirms that the rat C-polysaccharide-binding/phosphocholine-binding protein is in fact rat CRP.

Amino Acid Sequence↗

Objective monitoring of disease activity in polyarteritis by measurement of serum C reactive protein concentration.

Serial measurements of the serum concentration of C reactive protein were made in 27 patients with polyarteritis over six years. The concentration was invariably raised when the disease was active, even in patients receiving immunosuppressive treatment, and fell rapidly in association with clinical remission induced by immunosuppression. During periods of complete remission, in the absence of any intercurrent condition, the value remained within the normal range. The correlation between C reactive protein concentration and disease activity was much closer than that between erythrocyte sedimentation rate and disease activity. These results indicate that serial measurement of the serum C reactive protein concentration fills the urgent need for an objective index of the activity of polyarteritis and its response to treatment.

Adolescent↗

Binding specificity of serum amyloid P component for the pyruvate acetal of galactose.

Serum amyloid P component (SAP) is a normal plasma protein that is of interest because of its presence in amyloid deposits, its presence in normal human glomerular basement membrane, and its stable evolutionary conservation. It has calcium-dependent ligand-binding specificity for amyloid fibrils, fibronectin (Fn), C4-binding protein (C4bp), and agarose. Although the binding to agarose, a linear galactan hydrocolloid derived from some marine algae, is unlikely per se to be related to the physiological function of SAP, it does provide a model system in which to explore the precise ligand requirements of SAP. We report here that the amount of SAP from human, mouse, and plaice (Pleuronectes platessa L.) serum able to bind to agarose from different sources reflect precisely their pyruvate content. Methylation with diazomethane of the carboxyl groups in the pyruvate moiety of agarose completely abolishes SAP binding to agarose. The pyruvate in agarose exists as the 4,6-pyruvate acetal of beta-D-galactopyranose. We have therefore synthesized this galactoside, using a novel procedure, established its structure by analysis of its nuclear magnetic resonance spectra, and shown that it completely inhibits all known calcium-dependent binding reactions of SAP. The R isomer of the cyclic acetal, methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG) was effective at millimolar concentration and was more potent than its noncyclic analogue, while pyruvate, D-galactose, and methyl beta-D-galactopyranoside were without effect. The autologous protein ligands of SAP presumably, therefore express a structural determinant(s) that stereochemically resembles MO beta DG. Availability of this specific, well-characterized, low molecular weight ligand for SAP should facilitate further investigation of the function of SAP and its role in physiological and pathophysiological processes.

Amyloid↗

Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.

Animals↗