Quantitation of human leukocyte elastase, cathepsin G, alpha-2-macroglobulin and alpha-1-proteinase inhibitor in osteoarthrosis and rheumatoid arthritis synovial fluids.
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Aged↗
Biomedical subjects
M B Pepys
Publications and source records attributed to M B Pepys.
Plasma levels of inhibitor-bound leukocytic elastase in rheumatoid arthritis patients.
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Arthritis, Rheumatoid↗
Circulating immunoglobulins and complement in mice with Hymenolepis nana infection.
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Animals↗
Serum C-reactive protein levels in the management of infection in acute leukaemia.
C-reactive protein (CRP) was measured serially in 29 patients with acute leukaemia. Sixty-four febrile episodes (greater than or equal to 38 degrees C) occurred during 37 periods of neutropenia (less than 0.5 X 10(9)/l). In all of 41 microbiologically or clinically documented infections the maximum CRP level exceeded 30 mg/l, and in 25 it was greater than 100 mg/l. In no case in which the CRP level remained below 30 mg/l for 48 hr after the onset of fever was any clinical or microbiological evidence of infection obtained. The CRP level during documented infection began to fall 24-48 hr after appropriate treatment was begun. A CRP level above 30 mg/l in neutropenic patients was associated with early recurrence of fever if systemic antibiotics were discontinued. Graft-vs-host disease, without infection, did not result in high levels of CRP.
Acute Disease↗
Effect of ultraviolet radiation on production of epidermal cell thymocyte-activating factor/interleukin 1 in vivo and in vitro.
UV radiation was found to enhance the release by keratinocytes of epidermal cell thymocyte-activating factor (ETAF), a hormone-like molecule that is physiochemically identical to interleukin 1 (IL-1). This conclusion was supported by the following observations: (i) the keratinocyte cell line PAM 212 retained ETAF/IL-1-producing potential after exposure to UV radiation despite significant loss in cell viability; (ii) epidermal cells from normal and UV radiation-exposed mice were found to produce equivalent amounts of ETAF/IL-1 on a per cell basis with the density of epidermal cells in UV radiation-exposed skin being at least 5-fold above normal values; (iii) under the conditions used, ETAF/IL-1 could be detected in the serum of UV radiation-exposed, but not normal, animals; and (iv) many of the biologic consequences known to be mediated by elevations in ETAF/IL-1--i.e., neutrophilia, elevated levels of complement component 3, serum amyloid P, and plasma fibrinogen--were all observed in animals following a single UV radiation exposure. Animals subjected to chronic UV radiation showed an initial elevation in their levels of acute-phase reactants that returned to normal concentrations within 7 days. This correlates with observations made by others of a "desensitization" to ETAF/IL-1-mediated effects after chronic administration of known exogenous stimulators of inflammatory responses. Further, the UV radiation-induced desensitization took place in spite of demonstrable serum levels of ETAF/IL-1. These results suggest that the mechanism(s) responsible for desensitization is not an inhibition of ETAF/IL-1 synthesis but rather may result from inability of the target cells to perceive this endogenous mediator or to unavailability of serum-associated ETAF/IL-1 for the appropriate targets.
Amyloid↗
Acute phase protein response to infection in elderly patients.
The presence of infection is often difficult to diagnose in elderly patients. In view of this, laboratory markers of infection are of great clinical importance. The pattern of change in acute phase proteins has not hitherto been studied in elderly patients. In a prospective series of 114 acute elderly admissions to a Geriatric Unit there was a significant change with infection in all proteins studied, but C-reactive protein was the most sensitive marker of the presence and severity of infection and the response to antimicrobial therapy. The best pair of acute phase proteins in the prediction of infection were alpha 1-acid glycoprotein and C-reactive protein whilst albumin and alpha 1-acid glycoprotein together contributed significantly to the prediction of outcome.
Aged↗
Measurement of serum C reactive protein concentration after bone marrow transplantation for leukaemia.
C reactive protein concentration was measured serially in 19 patients with leukaemia after bone marrow transplantation. Six episodes of graft versus host disease occurred in the presence of fever but with no evidence of infection, and these were associated with C reactive protein concentrations as high as 200 mg/l. C reactive protein values were also increased in 12 febrile episodes associated with infection, in seven of which graft versus host disease was also present. C reactive protein concentrations are of no value in differentiating infection from graft versus host disease, but in both cases they may be useful as an objective index of response to appropriate treatment.
Adult↗
The acute phase response in parasite infection. Nippostrongylus brasiliensis in the mouse.
Systemic inflammatory reactions are a prominent feature of many parasitic infections and the cellular and humoral components of the acute phase reaction may have an impact on the host-parasite relationship. We examined serum changes of four acute phase reactants: alpha 1-proteinase inhibition (alpha 1Pi); complement C3; serum amyloid A protein (SAA); and serum amyloid P component (SAP), in mice undergoing a primary infection with Nippostrongylus brasiliensis. SAA and SAP showed changes within the first 2 days of infection indicating the presence of an acute phase response associated with inflammation in the lung. Alpha 1Pi and C3 serum levels were not altered. However, all four acute phase reactants were synthesized in greater amounts by primary cultures of hepatocytes taken from infected animals at this time. Subsequently, as parasite-mediated inflammatory changes occur in the gut, both serum and hepatocyte cultures demonstrate an acute inflammatory response in all four reactants. It is proposed that the early reaction between parasites and macrophage/monocyte lead to the release of a mediator of inflammation which initiates the hepatocyte response. In this infection, at least one of the APR is shown to localize to the site of inflammation influencing the host-parasite relationship.
Acute Disease↗
C-reactive protein and apoB containing lipoproteins are associated with Mycobacterium leprae in lesions of human leprosy.
Skin biopsies from patients with leprosy across the spectrum from tuberculoid (TT) to lepromatous (LL), including histoid lepromas and erythema nodosum leprosum (ENL) reactions, were stained immunohistochemically for the presence of C-reactive protein (CRP) and the apolipoprotein, apoB. Mycobacterium leprae bacillary material comprising cell walls, cytoplasmic and soluble components was present with increasing abundance towards the lepromatous end of the spectrum and always stained positively with anti-CRP. M. leprae from armadillos did not stain with anti-human CRP indicating that the staining of M. leprae in human tissues was not due to a cross-reaction between anti-CRP and the organism itself. When CRP was present in large amounts apoB was also demonstrated in the same distribution. CRP was detected on bacilli and their degradation products within the cytoplasm of macrophages even in the absence of a raised serum CRP level in some ENL patients and also in two cases of advanced resolving lepromas. These findings demonstrate remarkable persistence of CRP in association with M. leprae in vivo, and raise intriguing questions about the possible role of CRP in relation to the handling of leprosy bacilli.
Animals↗
'Amyloid degrading activity' of human serum, an in vitro clearing effect which does not involve degradation of amyloid fibrils.
Clearing of turbid amyloid A fibril containing agarose gels by human serum has been ascribed to 'amyloid degrading activity'. We report here that this optical phenomenon is not due to an enzymatic reaction, does not involve proteolysis of the fibril subunits and is not inhibited by sera of patients with AA amyloidosis. The extent of clearing correlates closely with the serum albumin concentration and, as previously reported by others, serum albumin itself causes clearing comparable to that of whole serum. Furthermore addition of albumin solutions to turbid aqueous suspensions of AA amyloid fibrils causes immediate clearing. Serum albumin is known to clarify turbid non-amyloid fibril containing gels and is used commercially to improve the optical properties of radial immunodiffusion plates. We therefore propose that this property of albumin, the mechanism of which is not yet understood, underlies the so called 'amyloid degrading activity' of human serum and the latter is not therefore likely to be of in vivo biological or clinical significance.
Amyloid↗
The failure of ascorbic acid therapy to alter the induction or remission of murine amyloidosis.
It has been claimed that ascorbic acid enhances the in vitro degradation of AA amyloid fibrils. This raises the possibility that ascorbic acid may be of benefit in systemic AA amyloidosis, a condition with serious morbidity and mortality for which there is as yet no specific treatment. The effect was therefore tested of oral or injected supplements of ascorbic acid on the induction of AA amyloidosis in mice. Amyloid was induced either by repeated injections of casein or by injection of 'amyloid enhancing factor' and silver nitrate. Mice with established amyloidosis were also treated with additional ascorbic acid. Despite the fact that plasma ascorbic acid levels were significantly higher in orally supplemented mice than in controls there was no demonstrable effect on the induction, the extent and distribution or the progression of amyloidosis.
Amyloid↗
Objective monitoring of activity in Wegener's granulomatosis by measurement of serum C-reactive protein concentration.
Serial measurements of the serum concentration of C-reactive protein were made in 38 patients with Wegener's granulomatosis during a period of 6 years. The concentration was always elevated 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 level 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 fills the urgent need for an objective index of the activity of Wegener's granulomatosis and its response to therapy.
Adolescent↗
Circulating human C-reactive protein binds very low density lipoproteins.
Native human CRP in solution formed complexes with the abnormal lipoprotein beta-VLDL in serum of patients with type III hyperlipoproteinaemia. CRP also formed complexes in sera from individuals with type IV and type V hyperlipoproteinaemia. The binding was calcium-dependent and inhibitable by free phosphoryl choline. No complexes were demonstrable in sera containing high LDL levels from cases of type IIa hyperlipoproteinaemia. Addition of isolated beta-VLDL, but not of isolated LDL, to acute phase normolipoproteinaemic serum caused the appearance of soluble CRP-lipoprotein complexes. In contrast, addition of an excess of isolated normal VLDL to acute phase serum or to isolated CRP was followed by agglutination (creaming) of the lipoprotein particles. Rabbit CRP, on the other hand, formed soluble complexes both with normal human apoB containing lipoproteins and with the abnormal beta-VLDL. Human CRP complexed with rabbit beta-VLDL but not with normal rabbit serum lipoproteins. These interactions may be important for the role of CRP in health and disease.
Animals↗
In vivo turnover studies of C-reactive protein and lipoproteins in the rabbit.
Clearance from the plasma of 125I-labelled rabbit C-reactive protein (CRP) was significantly slower in animals undergoing an acute phase response (T1/2, mean +/- s.d., 6.48 +/- 1.4 h, n = 4) than in normal rabbits (3.17 +/- 0.4 h, n = 4), P less than 0.01. In contrast there was no difference between the rates of clearance of CRP in rabbits on a normal diet and hypercholesterolaemic rabbits, the plasma of which contained high levels of beta-VLDL with which CRP is known to form circulating complexes. Furthermore the apparent rates of clearance of 125I-labelled beta-VLDL, VLDL and LDL did not differ between normal rabbits and rabbits undergoing an acute phase response. The significance of these findings is discussed.
Animals↗
Isolation and characterization of C-reactive protein from the dog.
Using calcium-dependent affinity chromatography on Sepharose-bearing, covalently-coupled pneumococcal C-polysaccharide, a protein was isolated from the serum of dogs that had undergone general anaesthesia and major surgery. This protein was confirmed as the canine analogue of C-reactive protein (CRP) in other species by virtue of its electron microscopic appearance, subunit composition and behaviour as an acute phase reactant. Dog CRP had an apparent molecular weight of approximately 100,000 and was composed of five subunits of approximately 20,000 MW each. Two of the five subunits in each molecule were glycosylated. Negatively stained preparations had the typical cyclic pentameric disc-like structure of proteins of the pentraxin family, and in some preparations had a tendency to form stacks. Serum from normal healthy dogs of various strains usually contained less than 5 mg/l of CRP but, following the stimulus of major surgery, an increase in the CRP concentration was first detected at 4 hr.
Animals↗
Demonstration of amyloid A (AA) protein and amyloid P component (AP) in deposits of systemic amyloidosis associated with renal adenocarcinoma.
The fibril protein in three cases of systemic amyloidosis associated with renal adenocarcinoma was identified as amyloid A protein (AA) using immunohistochemical staining techniques. Amyloid P component was also present in all deposits. In one case unfixed snap frozen tissues were studied directly whilst in the other two, which were investigated retrospectively, fixed paraffin sections were stained by immunofluorescence and immunoperoxidase methods after treatment with trypsin. Enzymatic digestion was necessary to restore reactivity with anti-AP but anti-AA reacted well without any such treatment. These findings establish that renal carcinoma, the carcinoma most frequently associated with systemic amyloidosis, causes the same type of secondary or reactive systemic amyloid as chronic infections and inflammatory disorders.
Adenocarcinoma↗
Serum concentrations of C-reactive protein and serum amyloid P component in plaice (Pleuronectes platessa L.) in relation to season and injected lipopolysaccharide.
1. Mean monthly serum levels of total protein, C-reactive protein (CRP) and serum amyloid P component (SAP) in plaice, showed no significant difference between the sexes. 2. Highest values for CRP and protein were found between June and September, with no significant seasonal variation in SAP. 3. There was no change in CRP concentration in plaice maintained for 7 days at a higher temperature of 18.5 degrees C. 4. Injection of lipopolysaccharide caused the highest value for CRP on day 1 and for the spleen index on day 5 after injection. 5. Phagocytic stimulation with carbon had no significant effect on the CRP response to endotoxin.
Amyloid↗
Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein.
The acute phase response among plasma proteins is a normal response to tissue injury and is therefore a fundamental aspect of many diverse disease processes. It probably usually has a beneficial net function in limiting damage and promoting repair but in some circumstances it may have pathological consequences. Sustained high levels of acute phase proteins and especially SAA are associated with the development of amyloidosis in some individuals. Increased concentrations of CRP may, by activating the complement system, contribute to inflammation and enhance tissue damage. Failure of the normal or appropriate CRP response may also possibly have deleterious effects. SAA is a polymorphic protein which is normally present only in trace amounts but which, during the acute phase response, becomes one of the major apolipoproteins associated with high-density lipoprotein particles. The function of apoSAA is not known but it must have considerable physiological significance apart from its role as the putative precursor of amyloid A protein fibrils. CRP and SAP have been very stably conserved throughout vertebrate evolution and homologous proteins are apparently present even in vertebrates. This strongly suggests that they have important functions although these have not yet been precisely delineated. The main role of CRP may be to provide for enhanced clearance of inappropriate materials from the plasma whether these are of extrinsic origin, such as microorganisms and their products, or the autologous products of cell damage and death. The interaction between aggregated CRP and plasma low-density lipoprotein may play a significant part in the normal function of CRP and may also have a role in lipoprotein metabolism, clearance, and deposition. SAP is a normal tissue protein as well as being a plasma protein. Aggregated SAP selectively binds fibronectin and this may represent an aspect of the normal function of SAP. The deposition of SAP in amyloid is evidently not a normal function but it is not known whether this deposition is involved in the pathogenesis of amyloid or whether it is merely an epiphenomenon. In any case immunohistochemical staining for SAP is useful in the diagnosis of amyloid, in investigation of glomerulonephritis, and in studying disorders of elastic tissue. Regardless of its physiological or pathophysiological functions, the assay of serum CRP is a valuable aid to clinical management in a number of different situations and in different diseases provided results are interpreted in the light of full clinical information.(ABSTRACT TRUNCATED AT 400 WORDS)
Amyloid↗