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Biomedical subjects

J T Whicher

Publications and source records attributed to J T Whicher.

At least 19 recordsLinked to original sources

Acute phase reactants in predicting disease outcome.

From the studies which are reviewed above, it is generally apparent that in terms of the acute phase response, the initial findings in early inflammatory arthritis (particularly rheumatoid arthritis, with which the majority of such studies are concerned) have little predictive value for either the functional outcome or mortality. The wide interindividual variability in these measurements is also likely to limit their clinical usefulness as predictors of disease outcome. The trend in certain acute phase reactants may be more useful in indicating disease activity, although the number of satisfactory studies in this area is very limited.

Acute-Phase Proteins

Interleukin-6 and its relationship to C-reactive protein and fever in children with febrile neutropenia.

The assessment of febrile neutropenia is problematic. C-reactive protein (CRP) values alone do not differentiate those patients with microbiologically documented infections from those with unexplained fevers. Plasma interleukin-6 (IL-6), measured by ELISA, was correlated with different diagnostic groups in 47 episodes of febrile neutropenia in children. Samples were collected daily from admission until resolution of fever. On admission, the median IL-6 value for gram-negative infections was 1610 pg/ml (range, 896-40,000), for gram-positive infections it was 138 pg/ml (range, 66-1045), and for unexplained fevers it was 50 pg/ml (range, 24-135, with a single high value of 665 pg/ml). These medians were significantly different (P less than .005). There was no significant difference in median CRP values. IL-6 values peaked 24-48 h before CRP values. There was a positive correlation of IL-6 with the presence of fever. Plasma IL-6 may be a more sensitive marker than CRP of acute infection and should prove useful in the assessment of fevers in these patients.

Adolescent

The value of acute phase protein measurements in clinical practice.

There is clearly a role for the measurement of acute phase proteins and other indices of the acute phase reaction but it is equally clear that no one laboratory test is suitable for use in all clinical situations. The choice of acute phase protein measurement depends on the diagnostic sensitivity and specificity of the measurement in the particular clinical situation. The choice of measurement must also include a decision on time of sampling and whether single or serial sampling would be more appropriate. In most situations where acute phase measurement is useful CRP is the assay of choice with alpha 1-antichymotrypsin also being useful in inflammatory bowel disease and other situations where a wider time window is required. The ESR or plasma viscosity can be useful to screen for disease. Cytokine and enzyme-inhibitor complex measurements may be important assays in the future.

Acute-Phase Proteins

Insulin modulation of acute-phase protein production in a human hepatoma cell line.

Insulin is widely used as a growth factor in hepatocyte culture but its effect on the production of acute-phase proteins has not been studied. By measuring four positive (fibrinogen, alpha 1-antitrypsin, alpha 1-acid glycoprotein, and alpha 1-antichymotrypsin) and four negative (albumin, prealbumin, transferrin, and retinol binding protein) acute-phase proteins produced by the Hep G2 hepatoma cell line, we have shown that insulin is an important modulator of acute-phase protein production. Our data show that insulin is able to inhibit the synthesis of prealbumin, transferrin, and fibrinogen. The results also show a complex interaction between insulin, interleukin 6, and glucocorticoids because insulin is able to inhibit the dexamethasone induction of alpha 1-antichymotrypsin, and in the presence of interleukin 6, dexamethasone is able to regulate the production of fibrinogen and prealbumin. The regulatory role of insulin in fibrinogen production was confirmed by pulse chase labeling followed by immunoprecipitation and fluorography.

Acute-Phase Proteins

Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks.

Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis.

Acute Disease

Measurement of the 'fast' or complexed form of alpha 2 macroglobulin in biological fluids using a sandwich enzyme immunoassay.

A sandwich enzyme immunoassay has been developed for measuring the 'fast' or complexed form of alpha 2 macroglobulin using a complex-specific monoclonal antibody. The working range of this assay is 1.5-15 micrograms/l and is suitable for use with various biological fluids. Using this assay the normal plasma levels were found to range from 4.2 mg/l to 14.4 mg/l (0.17%-0.70% of total alpha 2 macroglobulin) with a mean value of 7.6 mg/l +/- 2.6 (0.37% +/- 0.12% of total alpha 2 macroglobulin). Elevated levels were seen in plasma samples taken on the day of admission from patients with acute pancreatitis and in some synovial fluid samples from patients with various arthritides.

Antibodies, Monoclonal

Alpha 1-microglobulin, beta 2-microglobulin and retinol binding protein in childhood febrile illness and renal disease.

Serum and urinary levels of alpha-1-microglobulin (A1M), beta-2-microglobulin (B2M) and retinol binding protein (RBP) were measured using a Mancini radial immunodiffusion technique in 52 children with renal disease, 36 with non-renal febrile illness and 29 controls. In controls the mean serum level for A1M was 25 +/- 4.6 (SD) mg/l for B2M 1.7 +/- 0.5 mg/l and for RBP 31 +/- 8 mg/l. A1M levels were not significantly altered by febrile illness while B2M was elevated and RBP markedly depressed. Serum A1M and B2M were elevated in the nephrotic syndrome, while serum B2M was also raised during infancy. Coefficients of log-transformed data with creatinine-derived glomerular filtration rate (GFR) were -0.87 for B2M, -0.71 for RBP, and -0.62 for A1M. In the urine A1M was always measurable in controls while B2M and RBP were undetectable in all but a small number. The urine levels of all three proteins increased in response to non-renal febrile illness, and rose invariably when GFR fell to below 40-50 ml/min per 1.73 m2. Of the three proteins A1M was most frequently elevated in the urine with febrile and renal illness. RBP was rarely detectable when the other two proteins were not. Urinary A1M was consistently elevated in the nephrotic syndrome in contrast to B2M, possibly as a reflection of the increased glomerular permeability. We conclude that serum B2M is superior to A1M and RBP as an index of glomerular filtration, although its levels should be interpreted with caution in febrile disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The acute phase protein response in mice does not show tolerance to recurrent sterile inflammation.

The response of acute phase proteins to repeated inflammatory stimuli was studied in BALB/c mice and Hylyne Dutch rabbits. Inflammation was produced by subcutaneous injections of turpentine/arachis oil twice weekly for three and a half weeks. Serum amyloid-P component (SAP) levels in the mice showed no significant decrease in the level of response following each injection and the pattern of response was the same in mice previously rendered tolerant to endotoxin. Haptoglobin levels in the rabbits also responded equally to repeated injections in two animals and showed a declining response in a third animal which became unwell during the experiment. The ability of experimental animals to continue to respond fully to repeated inflammatory stimuli supports the suggestion that the subnormal responses seen in certain chronic inflammatory conditions may reflect an underlying defect in the acute phase response rather than an adaptive change following chronic inflammation.

Acute-Phase Proteins

Synovial fluid concentration of five different cytokines in rheumatic diseases.

Interleukin-1 beta, interleukin-2, tumour necrosis factor alpha, and the interferons, alfa and gamma, were measured concurrently in synovial fluid samples from 68 patients with rheumatic diseases. Mean interleukin-1 beta concentrations (130.3 (SD 22) pg/ml) were higher in synovial fluids from patients with rheumatoid arthritis (RA) than in those from patients with osteoarthritis (27.8(4.5)pg/ml), while measurements in synovial fluids from patients with seronegative spondarthritis were intermediate (72.7 (32) pg/ml). Interleukin-2 and tumour necrosis factor alpha concentrations were lower in the inflammatory arthropathies (RA: 4.5 (0.6) U/ml, 0.39 (0.04) ng/ml; seronegative spondarthritis: 3.1 (0.3) U/ml, 0.33 (0.03) ng/ml respectively) than those in patients with osteoarthritis (5.2 (0.6) U/ml; 0.05 (0.04) ng/ml). Interleukin-2 and tumour necrosis factor alpha concentrations correlated in all groups (r = 0.7), as did the interferons alfa and gamma (r = 0.7). There was no relation between interleukin-1 beta and either interleukin-2 or tumour necrosis factor alpha, or between the interferons and any other cytokine. Several distinct cytokine patterns were noted. Synovial fluids from two non-arthritic subjects were also examined: interleukin-1 beta concentrations were low, but concentrations of the other cytokines were higher than those seen in most arthritic fluids.

Adult

Complement abnormalities in diffuse plane xanthomatosis with paraproteinaemia.

Paraproteinaemia may be associated with xanthomatous skin deposits and these can arise in the absence of elevated lipid levels. Two cases of benign monoclonal gammopathy with diffuse plane xanthomatosis are reported. Case 1 exhibited hypolipidaemia and a functional deficiency of C1 esterase inhibitor. Case 2 showed a normal lipoprotein profile, abnormal platelet aggregation, and a cutaneous vasculitis with evidence of complement consumption via the classical pathway. The significance of these abnormalities is discussed.

Aged

Immunogenicity of guinea-pig submandibular and coagulating gland kininogenases.

The antigenic relationship between submandibular and coagulating gland kininogenases of the guinea-pig has been examined using Ouchterlony double diffusion, crossed and rocket immunoelectrophoresis and immunofluorescent techniques. The evidence suggests a partial immunological identity between submandibular and coagulating gland kininogenases of the guinea-pig. In this respect these enzymes seem to differ from the glandular kallikreins of other species (porcine, human and rat) which apparently share a complete immunological identity.

Animals

An evaluation of the Hyland laser nephelometer PDQ system for the measurement of immunoglobulins.

The Hyland laser nephelometer PDQ system for the assay of specific proteins is described. The results of evaluating the system to measure immunoglobulins IgA, IgG, and IgM are summarised. Within-batch and between-batch precision, accuracy, reliability, and safety are discussed. This instrument represents an important development in the immunochemical assay of proteins in clinical medicine. The speed, precision, and convenience of this new generation of discrete nephelometric analysers make such systems attractive to the clinical chemist.

Autoanalysis

Method-specific variations in the calibration of a new immunoglobulin standard suitable for use in nephelometric techniques.

The putative International Federation of Clinical Chemistry immunoglobulin standard, IFCC 74/1, was calibrated against the World Health Organization (WHO) immunoglobulin standard 67/99 by three different methods: automated immunoprecipitation, Laurell rocket immunoelectrophoresis, and radial immunodiffusion. The same antisera were used in all the assays, which were performed in five expert laboratories. With the aid of linearizing transformations for the dilution curves of both materials and use of a carefully weighted statistical evaluation, values in International Units for IgG, IgA, and IgM were ascribed to IFCC 74/1. The values achieved by the three different methods were not statistically different, except in the case of IgA. IgM assays by automated immunoprecipitation were excluded owing to a high degree of imprecision.

Evaluation Studies as Topic

Two cases of alpha chain disease from Nigeria.

The first two cases of alpha chain disease from Central Africa are reported from Nigeria. Both patients show the classical features of the disease with diffuse involvement of the small bowel and malabsorption. The patients were lost to follow-up but died soon after diagnosis.

Adolescent