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Biomedical subjects

D Burnett

Publications and source records attributed to D Burnett.

At least 19 recordsLinked to original sources
PubMed1992

The induction by human interleukin-6 of apoptosis in the promonocytic cell line U937 and human neutrophils.

Apoptosis of neutrophils at sites of inflammation in vivo is thought to lead to their recognition and safe elimination by macrophages. Little is known, however, about the regulation of apoptosis in myeloid cells. We report here that the human promonocytic leukemic cell line, U937, and mature human neutrophils can be induced to become apoptotic when cultured with interleukin-6. Apoptosis of U937 cells, assessed morphologically and by the presence of DNA fragmentation, was increased significantly in a dose-dependent fashion by concentrations of 0.5-100 ng/ml interleukin-6. Apoptosis of U937 cells was evident after 48 h of incubation with 20 ng/ml interleukin-6, and the effect was eliminated by adsorption of interleukin-6 with a specific monoclonal antibody. Apoptosis was not evident in the presence of the differentiating agent phorbol 12-myristate 13 acetate; the induction of apoptosis in U937 cells was not therefore a consequence of differentiation. Apoptosis of mature neutrophils was enhanced after 24 h in culture with interleukin-6. Interleukin-6 might be an important factor in the normal resolution of inflammation through the induction of apoptosis of neutrophils.

Antibodies, Monoclonal↗
PubMed1992

Use of an enzyme-linked immunosorbent assay to assess penetration of amoxicillin into lung secretions.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure total amoxicillin concentrations penetrating lung secretions, which were compared with "active" concentrations measured by conventional bioassay. An antibody was raised in rabbits to amoxicillin conjugated to bovine serum albumin and used in a competitive binding ELISA (sensitivity, 10 ng/ml; precision [coefficient of variation], 9%). The measurement of amoxicillin in lung secretions by using the ELISA method was verified by high-performance liquid chromatography. Amoxicillin concentrations were found to be similar in both whole sonicated sputum and sol-phase sputum obtained by ultracentrifugation following single oral doses of 3 g (4.6 mg/liter for sonicated and 4.7 mg/liter for sol-phase preparations) and 250 mg (0.23 mg/liter for both preparations). Eight patients with bronchiectasis received 500 mg of amoxicillin three times daily. On the second day of therapy (4 h after the morning dose), the mean concentration of amoxicillin in sputum was 0.88 mg/liter (standard error of the mean [SEM], 0.11) by ELISA and 0.40 mg/liter (SEM, 0.05) by bioassay, suggesting a significant degree of local inactivation. This difference between total and active amoxicillin levels was found to correlate significantly (r = 0.693; P less than 0.05) with beta-lactamase levels (mean, 29.5 mU/ml; SEM, 9.4). A pharmacokinetic study on day 3 revealed maximum levels in secretions 2 to 4 h after dosing (mean, 1.36 mg/liter; SEM, 0.26). At the end of successful therapy (day 14), total and active levels were lower (mean, 0.48 mg/liter; SEM, 0.11 [total]; mean, 0.21 mg/liter; SEM, 0.06 [active]); this result was associated with a reduction in lung inflammation (decreased serum-derived albumin in the lung secretions). In conclusion, antibiotic penetration is partly dependent on the degree of lung inflammation. The differences observed in total and active levels of amoxicillin and the relationship to beta-lactamase activity in sputum suggest why higher doses of antibiotic may be required to produce a therapeutic response in some patients.

Administration, Oral↗
PubMed1992

Regulation of alpha 1-antitrypsin synthesis by granulocyte macrophage colony-stimulating factor in the U937 promonocytic cell line.

Undifferentiated U937 cells possess low numbers (approximately 1,100 per cell) of receptors for granulocyte macrophage colony-stimulating factor (GMCSF). The receptors present are of at least two types with different affinities. A small number (less than 200 per cell) are of higher affinity (approximate Kd 97pM), and a larger number (approximately 900 per cell) are of lower affinity (approximate Kd 680pM). Following differentiation with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (PMA), the differentiated cells express a reduced number of receptors (approximately 680 per cell). These receptors are present as a single class with an approximate affinity of 230pM (Kd). The undifferentiated cells were responsive to GMCSF and this cytokine caused a seven-fold increase in accumulation of alpha 1-antitrypsin (alpha 1AT) compared to the control cells. This was accompanied by a similar increase in alpha 1ATmRNA, which suggests that the rate of alpha 1AT accumulation was regulated at the transcriptional level. After differentiation with PMA, alpha 1AT accumulation was not influenced by GMCSF, although the cells continued to bind the cytokine. These results imply that U937 cells do respond to GMCSF and this event involves binding of the ligand to a small number of specific cell surface receptors only present in the undifferentiated cells. Furthermore the response of these cells (in terms of alpha 1AT production) is associated with the type of GMCSF receptors expressed.

Cell Differentiation↗
PubMed1979

The metabolism of methaqualone in patients with biliary cirrhosis or secondary carcinoma of the liver.

The metabolism of methaqualone has been studied in three patients with secondary carcinoma of the liver and two with biliary cirrhosis. The urinary excretion of five C-monohydroxy metabolites and the N-oxide was studies in the 24 h period immediately after oral dosing with 250 mg methaqualone (Melsed). In both patients with biliary cirrhosis and one with primary carcinoma of the bile duct or pancreas with secondaries in the liver the pattern of metabolites was normal. In a patient with oat cell carcinoma with secondaries in the liver some metabolite patterns were disturbed and increased metabolite excretion occurred. A patient with primary carcinoma of the breast with secondaries in the liver gave a completely abnormal metabolite pattern.

Adult↗
PubMed1979

Tumour markers in breast cancer.

The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers.

Breast Neoplasms↗
PubMed1979

A study of plasma proteins in the sol phase of sputum from patients with chronic bronchitis.

We have studied the sputum/serum protein concentration ratios from 23 patients with bronchitis both in the stable clinical state and during acute chest infections. During the stable state there was a significant negative correlation (2 P less than 0.005) between the ratio and protein size. The ratios of IgG, IgA, C3, and alpha 1-antichymotrypsin were significantly displaced from this relation suggesting local production in the lung. IgM was found in all samples and alpha 2-macroglobulin in 55% of non-infected samples which may be the result of local production rather than transudation from serum, because of their larger size. During acute chest infections the albumin content of sputum rose from a mean sputum/serum ratio of 0.83 (SE +/- 0.08) X 10(-2) to 13.77 (SE +/- 3.21 X 10(-2) suggesting increased transudation from the blood. In the presence of increased transudation, local production of protein appears to be less significant.

Aged↗
PubMed1979

Alpha,-antitrypsin and leukocyte elastase in infected and noninfected sputum.

Leukocyte elastase and alpha 1-antitrypsin have been implicated in the pathogenesis of pulmonary emphysema. The relationship between these proteins has been studied in sputum both qualitatively and quantitatively in bronchitic patients with and without chest infections. Leukocyte elastase was found in 75% of the noninfected samples but was enzymatically inactive, suggesting complete inhibition. During infection, leukocyte elastase and alpha 1-antitrypsin concentrations increased, although the enzyme was only partially inactivated. The proportion of alpha 1-antitrypsin present as "complex" was smaller in the presence of infection, suggesting damage of the protein by excess enzyme.

Bronchitis↗
PubMed1978

The effect of the protein content of diluents on peak height in rocket immunoelectrophoresis.

We have investigated the effect of different diluents in the quantitation of proteins by rocket immunoelectrophoresis. alpha2-Macroglobulin produced taller peaks as the protein content of the diluent fell to zero, and the dilution was increased. A maximum increase in height of 25-30% was recorded when saline was used as the diluent compared to a sample diluted in sheep serum. Albumin and transferrin showed similar, but less significant effects. Samples and standards should therefore contain approximately equal concentrations of protein for maximum accuracy.

Humans↗
PubMed1978

An arterio-venous study of serum alpha1-antitrypsin in patients with chronic bronchitis.

The effect of passage through the lung on alpha1-antitrypsin was studied in sixteen patients with chronic obstructive airways disease. The average mixed venous value of alpha1-antitrypsin (106.2% standard serum value) was not different from the the mean arterial value (105.6%). Where individual differences were found there was a similar difference in serum albumin. However, there was a small but significant rise (p less than 0.005) in serum alpha1-antitrypsin "complex" as blood traversed the lung (mixed value = 6.3%; mixed arterial value = 6.8%). The reason is not yet clear.

Arteries↗
PubMed1978

Metabolism of methaqualone in geriatric patients.

The urinary excretion of five C-monohydroxy metabolites and the N-oxide of methaqualone has been measured in a group of eleven geriatric patients aged 71--90 years. The total excretion of the six metabolites in 24 h after the oral administration of a single dose was approximately one-half of that in a group of young healthy adults. The relative importance of the six metabolites was 4'-hydroxy greater than N-oxide greater than 2'-hydroxymethyl = 3'-hydroxy greater than 6-hydroxy = 2-hydroxymethyl which was the same order as that in young adults. The ratio of C-to N-oxidation was also the same in the two groups. There was no impairment of conjugation of the C-hydroxy metabolites with glucuronic acid in the geriatric group but there was greater interindividual variation in metabolite excretion. There was also evidence for delayed metabolism in the geriatric patients.

Aged↗
PubMed1978

Inter- and intra-individual variation in the metabolism of methaqualone in man after a single oral dose.

The urinary excretion of five C-monohydroxy metabolites and the N-oxide metabolite of methaqualone in the 24 h period immediately after oral dosing with 250 mg methaqualone (Melsed) has been measured in ninteen healthy adults (13 male, 6 female) to assess interindividual variations and in five adults (3 male, 2 female) on five separate occasions to assess intraindividual variation. The overall importance of the six metabolites was 4'-hydroxy greater than N-oxide greater than 2'-hydroxymethyl greater than 3'-hydroxy greater than 6-hydroxy = 2-hydroxymethyl. Variations in this order both within the 24 h period and within each of the three eight-hour periods constituting the 24 hours were minor and variations in the absolute amount of each metabolie excreted ranged from two to three-fold. Intraindividual variations were generally smaller than interindividual variations and for each individual the pattern of metabolism was similar on the five occasions. There is evidence that the C-oxidation of methaqualone may be more sensitive to cyclical variations in hormone levels than is N-oxidation.

Adult↗
PubMed1977

Quality control in the simultaneous assay of anticonvulsants using an automated gas chromatographic system with a nitrogen detector.

An automated gas-liquid chromatographic technique for the routine determination of phenobarbitone, primidone and phenytoin using a nitrogen-detector is described. The high selectivity of the detector for nitrogen-containing compounds allows a direct extraction procedure and the use of a phenytoin analogue as an internal standard obviates the need for accurate aliquot measurement after extraction. The anticonvulsants are chromatographed as methyl derivatives produced by on-column methylation with trimethylphenyl ammonium hydroxide following automatic liquid injection. Quality control data from an internal quality control scheme is presented and the performance of the laboratory in an inter-laboratory control scheme is reported and discussed.

Anticonvulsants↗