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Biomedical subjects

M B Pepys

Publications and source records attributed to M B Pepys.

At least 163 records · Page 9Linked to original sources
PubMed1986

Murine type II collagen arthritis. Association of an acute-phase response with clinical course.

The acute-phase reactant, C-reactive protein, is a good index of disease activity in patients with rheumatoid arthritis. We examined the murine acute-phase reactant, serum amyloid P, as an index of disease in type II collagen-induced arthritis in 3 mouse strains. The onset of type II collagen-induced arthritis, which is characterized by paw swelling, is associated with a significant, but transient, elevation of serum amyloid P. Anticollagen antibody titers are not temporally associated with the onset of disease. Although murine type II collagen arthritis fails to show the chronic acute-phase reactant elevation that is characteristic of arthritis in humans, the transient elevation of the acute-phase reactant is a reliable indicator of the onset of disease.

Amyloid↗
PubMed1986

Real-time measurement of serum C-reactive protein in the management of infection in the elderly.

The serum concentration of C-reactive protein (CRP), a nonspecific acute phase reactant which responds sensitively to bacterial infection, was measured by homogeneous enzyme immunoassay in all patients admitted to a general hospital geriatric unit. It was then monitored frequently in those in whom infection was suspected. Results were reported rapidly to the clinical team and particularly in the context of a patient population with complex multisystem pathology, often without pyrexia, leucocytosis or other classical signs of infection, they made a significant contribution to patient management. Very high CRP levels were most commonly due to infection (75% of those over 50 mg/l and 94% of those over 100 mg/l) and the pattern of the CRP response during antimicrobial therapy provided a sensitive, objective index of its efficacy. Failure of CRP levels to fall promptly stimulated additional diagnostic investigations, revealing resistant infection, localized pus or serious noninfective pathology, particularly malignancy, and led to appropriate management. Furthermore the CRP results on admission were of considerable prognostic significance, being significantly higher (median 70 mg/l) in those patients who did not survive than in those who did (18 mg/l).

Aged↗
PubMed1986

C-reactive protein in patients undergoing cardiac surgery.

Among 25 patients undergoing cardiac surgery with the aid of cardiopulmonary bypass, 13 who recovered uneventfully all had normal (less than 2 mg/litre) levels of serum C-reactive protein pre-operatively. In contrast, 10 of the 12 patients who suffered from various postoperative complications, including two who died, had abnormally raised levels of C-reactive protein pre-operatively. All patients showed a major acute phase response to surgery with peak C-reactive protein levels at about 46 hours but, whereas the uncomplicated cases showed a characteristic smooth biphasic pattern of declining levels thereafter, the complicated cases all exhibited significant alterations of this pattern. The occurrence during the postoperative period of a secondary rise in C-reactive protein or the failure of the level to continue falling, generally preceded clinical evidence of intercurrent infection. Pre-operative measurement of serum C-reactive protein may thus make a valuable contribution to the assessment of patients requiring elective cardiac surgery; regular postoperative monitoring can provide early warning of serious complications.

Aged↗
PubMed1986

Detection of endotoxin in mice by measurement of endotoxin-induced changes in plasma concentrations of zinc and of the acute-phase protein serum amyloid P-component.

Preparations of six bacterial endotoxins reduced plasma concentrations of zinc and increased concentrations of the acute-phase protein serum amyloid P component (SAP) in mice. The changes were sufficiently sensitive to permit use of either response in tests for endotoxin and hence for pyrogenic contamination.

Acute-Phase Proteins↗
PubMed1986

Differing acute phase responses in Crohn's disease and ulcerative colitis.

Thirty eight patients with Crohn's disease and 30 patients with ulcerative colitis have been assessed using the technique of faecal excretion of 111Indium granulocytes to quantify precisely acute inflammatory activity. At the time of each faecal granulocyte measurement the serum concentration of the acute phase protein C-reactive protein and the erythrocyte sedimentation rate were estimated. C-reactive protein concentration was significantly higher in Crohn's disease than ulcerative colitis both overall and particularly in relation to given levels of granulocyte excretion. No such distinction was observed between the erythrocyte sedimentation rates in the two diseases. The present findings show that the acute phase response differs significantly between Crohn's disease and ulcerative colitis. Patients with ulcerative colitis may be constitutionally different from those with Crohn's disease and unable to mount a major acute phase response to their own disease.

Adolescent↗
PubMed1986

Agglutination of intravenous lipid emulsion ('Intralipid') and plasma lipoproteins by C-reactive protein.

Isolated human C-reactive protein (CRP), or CRP in acute phase serum, produced in-vitro agglutination ('creaming') of the intravenously administered lipid suspension 'Intralipid'. CRP also produced similar agglutination of isolated normal very low density lipoproteins (VLDL). Agglutination in both cases was calcium-dependent and inhibitable by phosphoryl choline. These findings have important implications for patients receiving intravenous lipid suspensions and may be relevant to the pathogenesis of the fat embolism syndrome following trauma.

Acute-Phase Reaction↗
PubMed1986

Is the serum amyloid A protein in acute phase plasma high density lipoprotein the precursor of AA amyloid fibrils?

Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is generally considered to be the precursor of AA protein, which forms the fibrils in reactive systemic amyloidosis in man and animals. This view is based on amino acid sequence identity between AA and the amino-terminal portion of SAA. However, in extensive and well-controlled studies of experimentally induced murine AA amyloidosis, we were unable to demonstrate a direct precursor-product relationship between SAA, in SAA-rich HDL preparations from acute phase or amyloidotic mouse or human serum, and AA protein in the amyloid deposits. This raises the possibility that SAA in its usual form, as an apolipoprotein of HDL synthesized during the acute phase response, may not be the major precursor of AA fibrils. The amyloidogenic forms of circulating SAA molecules may not be isolated during the preparation of HDL. Alternatively, particularly in the light of recent evidence that SAA mRNA is expressed in many different tissues throughout the body of appropriately stimulated animals, amyloidogenic SAA may be derived from sources other than the liver cells in which SAA-rich HDL is synthesized.

Acute-Phase Reaction↗
PubMed1986

Secondary structure prediction of human SAA1. Presumptive identification of calcium and lipid binding sites.

Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is an acute phase protein thought to be the precursor of amyloid fibrils in reactive systemic (AA) amyloidosis. A prediction of the secondary structure of the human serum amyloid protein SAA1(alpha) is presented. The prediction was based upon one-dimensional Fourier analysis of the amino acid sequence together with sequence matching to known structural motifs. The results were compared with those from prediction algorithms based upon statistical techniques. Our findings are consistent with available experimental data. They include the putative identification of the amino-terminal 11 residues as the functionally important lipid-binding site of SAA and of a likely, neutral, calcium-binding sequence: Gly48-Pro49-Gly50-Gly51. Sequence comparisons between SAA and protein tyrosine kinases, phospholipases A2 and delta-crystallin, all of which bind both calcium and phospholipid, revealed significant homologies that support our proposals concerning structure-function relationships in SAA.

Animals↗
PubMed1986

X-ray scattering and diffraction by wet gels of AA amyloid fibrils.

Systemic amyloidosis is characterized by the extracellular accumulation of protein fibrils with typical ultrastructural morphology. The persistence in vivo of amyloid fibrils, which is responsible for their serious clinical effects, has been thought to reflect the particular, specific conformation of peptide chains constituting the fibrils. On the basis of earlier structural studies this conformation is generally considered to be almost exclusively anti-parallel beta-sheets. We have re-examined X-ray scattering by human amyloid A protein (AA) amyloid fibrils, with careful attention to the state of hydration of the preparations. We show that a stack of anti-parallel sheets is not consistent with the details of the X-ray pattern, which contains diffracted intensities that can be indexed on a 33A X 33A lattice. A structural model for the AA fibre consistent with the X-ray data is presented. The model takes account of the prediction of the secondary structure of the AA precursor SAA1(alpha) presented in our accompanying paper, and has the AA monomers arranged on a primitive lattice, with two unique molecules per unit cell.

Amyloidosis↗
PubMed1986

Circulating serum amyloid P component is the precursor of amyloid P component in tissue amyloid deposits.

Intravenous administration of 125I-labelled isolated mouse serum amyloid P component (SAP) to mice with systemic amyloidosis was followed by specific deposition of the labelled protein in amyloidotic organs. Although only a small proportion of the total injected dose became localized in this way, the amount correlated with the quantity of amyloid present in different organs and was greatest in the spleen. No such localization was detected in the organs of control, untreated mice or animals which had received inflammatory stimuli but did not have amyloidosis. The labelled SAP was found by autoradiography to be present in the same distribution within the tissues as the Congophilic amyloid deposits. These observations establish directly, for the first time, that circulating SAP is the precursor of the amyloid P component (AP) in systemic amyloidosis. They were confirmed by the further finding that intravenous injection into amyloidotic mice of human SAP, either in whole human serum or in isolated pure form, was followed by appearance of the human SAP in the mouse amyloid deposits. In addition to elucidating one aspect of the pathogenesis of amyloid deposition and strengthening the homology of functional behaviour between SAP of different species, the present results suggest a means for selective targeting of diagnostic tracers and/or effector agents to amyloid deposits in vivo.

Amyloidosis↗
PubMed1986

Isolation and characterization of guinea-pig serum amyloid P component.

A pentraxin was isolated from acute-phase guinea-pig serum by calcium-dependent affinity chromatography on agarose. It was immunochemically identical to guinea-pig amyloid P component and therefore has been called guinea-pig serum amyloid P component (SAP). Guinea-pig SAP has an apparent MW of between 265,000 and 300,000 by different techniques, and is composed of 10 noncovalently associated subunits arranged in two pentameric annular discs interacting face-to-face. It is apparently composed of two types of subunit, which run as a closely spaced doublet on reduced sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). At least one type of subunit is glycosylated. The serum concentration was 16 +/- 4 mg/l in outbred animals, rising to 25 +/- 4 mg/l in an acute-phase response. Binding to agarose correlated with the agarose pyruvate content and was completely abolished by diazomethane treatment of the agarose, which methylates the pyruvate carboxylic moiety. Binding was also inhibited in the presence of free methyl 4,6-o-(carboxyethylidine)-beta-D-galactopyranoside. No protein resembling C-reactive protein (CRP) was obtained by calcium-dependent affinity chromatography of acute-phase guinea-pig serum on phosphorylcholine (PC)-Sepharose, and it not clear whether a counterpart of CRP exists in this species.

Animals↗
PubMed1985

Human serum amyloid P component, a circulating lectin with specificity for the cyclic 4,6-pyruvate acetal of galactose. Interactions with various bacteria.

Serum amyloid P component (SAP), a normal plasma glycoprotein, has recently been shown to have Ca2+-dependent binding specificity for methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG) [Hind, Collins, Renn, Cook, Caspi, Baltz & Pepys (1984) J. Exp. Med. 159, 1058-1069]. SAP was found to bind in vitro to Klebsiella rhinoscleromatis, the cell wall of which is known to contain this particular cyclic pyruvate acetal of galactose. SAP also bound in similar amounts (approx. 6000 molecules per organism) to group A Streptococcus pyogenes, but very much less was taken up on Xanthomonas campestris, which contains the 4,6-cyclic pyruvate acetal of mannose. No SAP bound to Escherichia coli, which contains the 4,6-cyclic pyruvate acetal of glucose, or to Streptococcus pneumoniae type 4, which contains the 2,3-cyclic pyruvate acetal of alpha- rather than beta-galactopyranoside, or to other organisms (Streptococcus agalactiae, Staphylococcus aureus and Staphylococcus epidermidis), the carbohydrate structures of which are less well characterized. Binding of SAP to those organisms which it did recognize was completely inhibited or reversed by millimolar concentrations of free MO beta DG. SAP, a human plasma protein, thus behaves as a lectin and may be a useful probe for its particular specific ligand in the cell walls of bacteria and other organisms.

Amyloid↗
PubMed1985

Serum C-reactive protein in polymyalgia rheumatica. A prospective serial study.

A prospective serial study of 13 well-documented, previously untreated cases of polymyalgia rheumatica was undertaken in order to assess the behavior of the nonspecific indices of disease activity, erythrocyte sedimentation rate and serum C-reactive protein (CRP) concentration, during induction of disease remission by prednisolone therapy. The clinical manifestations of all patients responded rapidly and completely to steroids, and the serum CRP value, which was raised in all patients at presentation, fell to normal at a rate which precisely reflected the clinical improvement. The erythrocyte sedimentation rate also fell, but did so much more slowly than the CRP concentration and, in half the patients, was still not normal after 14 days. These results indicate that assay of serum CRP provides a precise means of objectively assessing the course of polymyalgia rheumatica during initial therapy with steroids, and suggest that routine measurements of CRP may make a useful contribution to the management of the disease.

Aged↗
PubMed1985

Immunohistochemical studies of C-reactive protein and apolipoprotein B in inflammatory and arterial lesions.

Interactions in vivo between C-reactive protein (CRP) and apolipoprotein B (apo-B)-containing lipoproteins were sought in inflammatory lesions and atherosclerosis. CRP was demonstrated immunohistochemically on the surface of some muscle fibres in locally induced inflammatory lesions in the rabbit, but apoB was not detected in the same distribution. CRP was not detected in catheter-induced aortic endothelial injuries in the rabbit, in arterial lesions containing apoB from cholesterol-fed rabbits, in apoB-containing human fatty streaks or in advanced human atherosclerotic lesions.

Animals↗
PubMed1985

Continuous subcutaneous insulin infusion does not induce a significant acute phase response of serum amyloid A protein.

In a study of 23 matched pairs of Type 1 (insulin-dependent) diabetic patients receiving continuous subcutaneous insulin infusion or conventional insulin injection therapy respectively, there were no significant differences in serum levels of the acute phase proteins, serum amyloid A and C-reactive protein. These results do not support the suggestion that continuous subcutaneous insulin infusion stimulates serum amyloid A production or that it carries a risk of inducing reactive systemic amyloidosis.

Adolescent↗
PubMed1985

Serum C-reactive protein response to therapeutic embolisation: possible role in management.

In a prospective study over 12 months, serum C-reactive protein concentration was measured serially in 20 consecutive patients who underwent therapeutic embolisation for various forms of malignancy and in 13 patients who had diagnostic coeliac or hepatic angiography without embolisation. All the patients who underwent successful embolisation showed a C-reactive protein response and in all cases the height of the response correlated well with the estimated size of the embolised tumour. Patients who recovered uneventfully showed a prompt fall in C-reactive protein from its peak values towards normal. In contrast, patients undergoing angiography alone showed only a minor increase in C-reactive protein concentration unless there were intercurrent complications. These results, together with the commercial availability of rapid and precise assays for C-reactive protein, indicate that serial measurement may be useful in the confirmation of tissue necrosis and assessment of its extent; also in the recognition of intercurrent complications following therapeutic embolisation.

C-Reactive Protein↗