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Biomedical subjects

J G Raynes

Publications and source records attributed to J G Raynes.

46 records · Page 3Linked to original sources

Measurement of acute phase proteins for assessing severity of Plasmodium falciparum malaria.

Seventeen adult patients with acute Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases, were studied. Serial measurements of the serum concentration of C-reactive protein, serum amyloid A protein, and percentage parasitaemia were determined, together with initial measurement of serum electrolytes, liver function, haemoglobin, white cell and platelet counts. Initial C-reactive protein and serum amyloid A concentrations were increased (C-reactive protein mean 49.0 mg/l serum amyloid A 28 mg/l) falling towards the normal range by the seventh day of treatment. There was a significant correlation between the pretreatment parasite count and clinical and laboratory markers of inflammation. C-reactive protein and serum amyloid A concentrations correlated inversely with the serum sodium. These results indicate that measurement of acute phase reactants such as C-reactive protein and serum amyloid A may prove valuable in assessing the severity of P falciparum malaria, and in following the response to antimalarial treatment.

Acute Disease↗

Acute-phase proteins and the serological evaluation of experimental contact sensitivity in the mouse.

The evaluation of contact reactions in previously sensitized mice is assessed conventionally by measurement of increases in ear thickness following challenge. In an attempt to develop a serological method for the investigation of contact sensitization in mice, we have examined whether analysis of changes in the concentration of acute-phase proteins in response to challenge provides a reliable alternative means of evaluating elicitation reactions. Measurement of either the relative serum haptoglobin concentration, using radial immunodiffusion, or the absolute concentration of serum amyloid A, by an enzyme-linked immunosorbent assay, has been found to correlate well with induced increases in ear thickness following challenge. Changes in the concentration of acute-phase proteins proved to be of sufficient sensitivity to reflect the specificity of contact sensitization and its inhibition by antigenic competition.

Acute-Phase Proteins↗

Purification of serum amyloid A and other high density apolipoproteins by hydrophobic interaction chromatography.

A chromatographic procedure is described for the purification of apolipoprotein components of high density lipoprotein from serum. Hydrophobic interaction chromatography (HIC) using phenyl- or octyl-Sepharose was used to purify the high density lipoprotein (HDL)-associated acute phase reactant serum amyloid A (SAA). The purification of SAA is described in detail and it is shown how the main components of normal HDL, apolipoproteins AI and AII (Apo-AI, Apo-AII), can also be purified. Serum was applied at a low salt concentration and apolipoproteins were eluted with a gradient into 4 M guanidine hydrochloride, 30% ethanediol, and 10 mM NaOH. This method was also used to partially purify the low density lipoprotein component apolipoprotein B. Apolipoproteins are purified free from lipid in one rapid chromatographic procedure rather than several ultracentrifugation steps and delipidation with organic solvents. The apolipoproteins from HIC chromatography are already partially separated and can be purified to homogeneity using conventional chromatographic methods under dissociating conditions.

Apolipoprotein A-I↗

Increased collagenase activity is not detectable in cervical softening in the ewe.

Cervical tissue from ewes at various stages of pregnancy was examined for evidence that collagenase is involved in the process of cervical softening. Collagenase activity was detected in medium after 2-3 days culture of ovine cervical explants, but there was no significant difference in total enzymic activity produced by explants from non-pregnant, early pregnant or late pregnant animals when expressed as units/mg wet weight of tissue over five days in culture. Oestradiol infusion into ewes prior to parturition did not alter the enzyme activity subsequently produced in explant culture. However, the DNA concentration, and hence the number of cells per unit volume, decreased significantly with length of pregnancy, this effect being due to expansion of cervical tissue which occurs late in pregnancy. Thus, if collagenase activity is expressed relative to DNA and hence cell number, there is evidence for increased production per cell in order to keep the tissue concentration constant. However, as the concentration of collagen in cervix remains constant during pregnancy, the ratio of collagenase activity to collagen is also constant. It is therefore concluded that there is no evidence of a role for increased collagenase activity in cervical softening in the ewe.

Animals↗

Collagenase inhibitor concentration in cultured cervical tissue of sheep is increased in late pregnancy.

An inhibitor of collagenase was released from cultured cervical tissue of sheep and the amounts released were greatest from tissue in late pregnancy (145-146 days). The molecular weights of material with inhibitory activity, estimated by gel filtration of extracted inhibitor, at different stages of pregnancy were different, i.e. 20,000 from extracts of late-pregnant and post-partum samples and 29,000 from extracts of non-pregnant samples. Inhibitor from culture supernatants had a molecular weight of 42,000. We conclude that the inhibitor has binding characteristics and molecular weights similar to those of the tissue inhibitor of metalloproteinase.

Animals↗

Comparison of serum amyloid A protein and C-reactive protein concentrations in cancer and non-malignant disease.

Serum amyloid A (SAA) concentrations correlate well with C-reactive protein (CRP) concentrations. However, SAA is sometimes raised in disease when CRP is normal. This appears to occur more often in certain diseases such as rheumatoid arthritis, primary biliary cirrhosis and chronic active hepatitis. SAA concentrations did not distinguish between cancer with and without metastases as previously indicated, although mean concentrations were higher in more advanced tumours. Despite the higher sensitivity of SAA over CRP in the inflammatory response, SAA has little advantage over CRP in the assessment of malignant disease.

Aged↗

Serum concentrations of lipid bound sialic acid and acute phase proteins in patients with cancer and nonmalignant disease.

Levels of serum lipid bound sialic acid (LSA) were determined in lung cancer and the inflammatory reaction associated with pneumonia, rheumatoid arthritis and surgical wounding. The mean levels of serum LSA were raised in all these disorders and levels were closely correlated with serum alpha 1-acid glycoprotein (AGP) r = 0.9. Levels of AGP and LSA rose and fell in parallel following cholecystectomy. The major influence on the concentration of serum lipid bound sialic acid is the intensity of the response to inflammation.

Arthritis, Rheumatoid↗

Acute phase protein concentrations predict parasite clearance rate during therapy for visceral leishmaniasis.

Visceral leishmaniasis (VL) remains a major health problem in Kenya and other parts of Africa, Central America and Asia. Currently, splenic aspirate smear and culture are the standard methods of monitoring therapy and relapse. Acute phase reactant markers, C-reactive protein (CRP), serum amyloid A protein (SAA) and alpha 1-acid glycoprotein (AGP) were evaluated as less invasive techniques for monitoring therapy in 59 patients with VL before, during and after therapy. CRP, SAA and AGP were elevated in VL patients at admission and the concentrations decreased with effective therapy to reach normal levels by the end of therapy (SAA and AGP) or by 3 months follow-up (CRP). Two groups of patients were selected on the basis of rate of parasite clearance. The acute phase protein concentrations were significantly raised in those slower to clear parasites. Analysis of sensitivity and specificity of acute phase proteins as predictors of parasite clearance suggested that they might represent useful non-invasive markers for monitoring disease activity, response to therapy and relapse in VL.

Acute-Phase Proteins↗