A F Strachan

C reactive protein concentrations during long distance running.

Long distance runners competing in events ranging from 15 to 88 km showed a distance related acute phase response as indicated by significantly raised serum C reactive protein concentrations. In trained athletes only a small rise in C reactive protein concentrations was seen after races of less than 21 km. After an 88 km ultramarathon concentrations comparable to those found in patients with small myocardial infarctions were detected. Indomethacin did not affect the increases in C reactive protein after the ultramarathon. This study has established serial C reactive protein concentrations for given race distances. These data may help in diagnosing myocardial infarction during long distance running. The acute phase response should be measured in untrained people running shorter distances to provide comparative data for the physically untrained population.

Standardisation of the quantitation of serum amyloid A protein (SAA) in human serum

An adequate method for standardising the quantitation of serum amyloid A protein (SAA) in human serum was developed. Acute phase high density lipoprotein3 (HDL3) was used as a standard. The concentration of the SAA in the standard was determined by the use of purified SAA. After protein determination, various concentrations of purified SAA were run on SDS-polyacrylamide gel together with the HDL3 standard containing an unknown amount of SAA amongst the apolipoproteins. From the standard curve obtained by pyridine extraction (Coomassie blue colour yield at A605 nm) the concentration of SAA in the HDL3 standard was determined. An established immunoradiometric assay (IRMA) for SAA was standardised with the HDL3. SAA concentrations in normal and acute phase sera were determined.

C‐reactive protein and serum amyloid A protein in pregnancy and labour

Summary. Serum levels of C‐reactive protein (CRP) and amyloid A protein (SAA) were measured prospectively using immunoradiometric assays in normal pregnant women, newborn infants and women with prelabour rupture of membranes (PROM), focusing on the peripartum period. CRP levels in 50 healthy women at 38 weeks gestation did not differ significantly from previously established normal values. CRP levels in 67 healthy women sampled serially in labour from admission to 96 h postpartum confirm the physiological occurrence of a major acute phase response. The serial CRP levels of 16 women with PROM did not differ significantly from the wide range of CRP levels found in the normal postpartum period. This complicates the use of CRP as an early predictor of clinical chorio‐amnionitis. Serial SAA levels in 17 women at 38 weeks gestation, immediately postpartum and 24 h postpartum showed a parallel rise to CRP in the peripartum period. Significant differences between maternal and neonatal CRP and SAA levels were demonstrated, implying a lack of transplacental transfer during labour.

Serum amyloid A protein and C-reactive protein levels in pulmonary tuberculosis: relationship to amyloidosis.

C-reactive protein and serum amyloid A protein levels were measured in 54 patients with pulmonary tuberculosis. The primary tuberculous complex was associated with an insignificant acute phase response, while post-primary tuberculosis without evidence of lung destruction caused modest increases in C-reactive protein and serum amyloid A protein. In most patients with post-primary pulmonary tuberculosis with significant pulmonary destruction there was a major acute phase response, with very high serum amyloid A protein and C-reactive protein levels. The response in these patients is most likely to be due to secondary bacterial infection in addition to infection by Mycobacterium tuberculosis. Patients with miliary tuberculosis showed a major acute phase response. Serum amyloid A protein and C-reactive protein levels decreased rapidly after initiation of treatment in the patients with post-primary tuberculosis without significant pulmonary destruction.

Value of C reactive protein measurement in tuberculous, bacterial, and viral meningitis.

The value of C reactive protein measurement in the differential diagnosis of meningitis was assessed in a population where tuberculous meningitis is prevalent. C reactive protein was measured serially with a sensitive radioimmunoassay in sera from 31 children with bacterial meningitis, 15 with tuberculous meningitis (6 with miliary tuberculosis), and 28 with viral meningitis. Concentrations of C reactive protein in patients with tuberculous meningitis lay between those of patients with bacterial and viral meningitis--a finding which detracts from the virtually absolute discrimination C reactive protein measurement allows between bacterial and viral meningitis. In all but two of the patients with tuberculous meningitis, C reactive protein concentrations fell rapidly after treatment began and became normal after 10 days. This fall did not, however, exclude the development of hydrocephalus as a complication. Measurement of C reactive protein remains a useful additional parameter in the diagnosis and management of the various types of meningitis.

Acute Phase Response in Bronchiectasis and Bronchus Carcinoma

Measurement of the acute phase response in patients suffering from bronchiectasis, emphysema, bronchus carcinoma and various benign space occupying lesions was undertaken, using sensitive immunoradiometric assays for C-reactive protein and serum amyloid-A protein. In some patients with bronchiectasis, clinically judged to be in remission, the results show a major ongoing acute phase response. Such a response could predispose these patients to the development of reactive secondary amyloidosis. In bronchus carcinoma, the application of these measurements to judge the extent of tumour growth is limited as infection complicating obstruction is a more potent initiator of the acute phase response than the neoplastic process per se.

The N-Terminus is the Lipid-Binding Site of SAA: Supporting Evidence by MoAbs

SAA is a major acute-phase protein comprising of 104 amino acids ciruclating in the plasma, assembled to subfraction of high density lipoproteins (HDL3). Two amyloid A proteins, NORl and NOR2, corresponding to residues 2–82 and 2–45, respectively, were extracted from an amyloidotic goiter of an FMF patient’s NOR. Three MoAbs against NOR2 were raised in mice. Two MoAbs recognize AA and SAA in addition to NOR2 and the third one recognizes NOR2 only. The binding of these MoAbs to NOR2 was inhibited by SAA-related peptides 2–82, 2–45, 2–15, 1–6. Almost no inhibition was observed with peptide 29–41. Two MoAbs recognize purified SAA dissolved in normal human sera. These MoAbs could not detect SAA in various acute-phase sera. Nevertheless, subjecting acute-phase HDL to denaturing conditions (SDS, urea) enables recognition of six SAA isoforms by these MoAbs. Supposing that denatured SAA is detached from HDL, these findings support the theory that the N-terminus of SAA functions as an anchor to the lipid layer of HDL.

Structure, Metabolism and Function of Acute Phase High Density Lipoprotein

The acute phase response is a multi-system adaptation induced by autologous cell death or by products of exogenous invasion (Kushner 1982). These influence macrophages to secrete various monokines that, among other functions, affect hepatic gene expression for many proteins (Ramadori et al. 1985). This response consists of a variety of biochemical, cellular, hormonal and metabolic changes with characteristic increases in many plasma proteins. Serum amyloid A protein (apo-SAA) is particularly notable in that it is normally present in trace amounts in human serum, but the concentration increases up to 100-fold within 48 hours of initiation of the acute phase. (Eriksen and Benditt 1984; McAdam et al. 1978; de Beer et al. 1982). Segrest et al. (1976) first noted that a 45-residue fragment of the apo-SAA cleavage product, amyloid A protein (AA), formed stable complexes with phospholipid. This finding preceded the discovery, by Benditt and Eriksen (1977), that apo-SAA is transported in human plasma mainly with high density lipoproteins (HDL) and is thus classified as an apolipoprotein. Although HDL (expressed as HDL cholesterol) is a significant negative acute phase reactant, it can play a role in inflammation. HDL has been reported to function as a vehicle to transfer damaged cellular constituents to the liver and to bind bacterial lipopolysaccharides (Ulevitch et al. 1981) and neutrophil elastase (Jacob et al. 1981). The function of apo-SAA rich HDL in response to injury is, however, unknown. The phylogenetic conservation of the association of apo-SAA with HDL suggests that it plays an important role.