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Biomedical subjects

D Burnett

Publications and source records attributed to D Burnett.

At least 145 records · Page 8Linked to original sources
PubMed1985

4,5-Dimethylthiazole-N-oxide-S-oxide: a metabolite of chlormethiazole in man.

The metabolic fate of chlormethiazole in healthy male subjects has been investigated following the oral administration of a single dose of chlormethiazole edisylate. Five urinary C-oxidation metabolites were identified and shown to be identical with previously reported metabolites. A novel metabolite, of molecular formula C5H7NO2S, was shown by trimethylsilylation, deuterium exchange, reduction studies and by its i.r., n.m.r. and mass spectrum, to be 4,5-dimethylthiazole-N-oxide-S-oxide. This is the first reported metabolite which involves the oxidation of the two heterocyclic atoms in aromatic rings. The formation and thermal stability of the compound is ascribed to resonance stabilization.

Chemical Phenomena↗
PubMed1985

Nebulized amoxicillin in chronic purulent bronchiectasis.

Nebulized amoxicillin (500 mg twice a day) was given for four months to six patients with bronchiectasis. The patients had continually produced purulent secretions, which had failed to clear (purulent to mucoid) when amoxicillin was given orally (3 gm twice a day). All patients found the nebulization technique acceptable, and no acute effect on lung function was seen. There were significant reductions in sputum purulence (P less than 0.025) and volume (P less than 0.05) and a mean (+/- SD) increase in peak expired flow rate (P less than 0.05) from 230.5 +/- 79.2 L/min to 255 +/- 90.1 L/min. These improvements occurred despite the fact that apparently resistant bacteria were cultured. No adverse effects were noted. The response to nebulized amoxicillin after failure with the same drug given orally suggests that local concentrations of antibiotic in the lungs of these patients is important.

Adult↗
PubMed1984

Immunohistochemical demonstration of cathepsin B in the macrophages of benign and malignant lymphoid tissues.

Cathepsin B has been demonstrated by immunohistochemical means in the macrophages of palatine tonsils, reactive lymph nodes and in specimens of Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). Two cases of genuine histiocytic lymphoma showed strong staining for the enzyme in most cells. In Hodgkin's disease, many Reed-Sternberg cells and Hodgkin cells were positive. Branching and 'tingible body' macrophages (histiocytic reticulum cells, HRCs) were strongly positive in all of the specimens. In reactive lymph nodes, the sinus-lining cells and intrasinusoidal macrophages were positive for cathepsin B. True dendritic reticulum cells (DRCs) appeared to be negative. Unlike muramidase (lysozyme), cathepsin B is not seen in neutrophil polymorph leucocytes.

Cathepsin B↗
PubMed1984

Immunohistochemical demonstration of leucocyte elastase in human tissues.

A polyclonal antiserum, produced in sheep and reactive against purified human leucocyte elastase, has been applied to paraffin sections from a range of human tissues by means of the indirect immunoperoxidase method. Striking and consistent results have been obtained. Normal or inflammatory granulocytes were intensely positive, the reaction being "blocked" by pure elastase. Activity was not seen in other sites, including histiocytic reticulum and lymphoid cells, although some weaker reaction was present in gastric and ileal lining epithelium. Strong reactivity was also seen in the cells of acute and chronic myeloid leukaemia and in extramedullary haemopoiesis. The advantages of this technique are compared with those for muramidase (lysozyme), alpha 1-antitrypsin, and naphthol-AS-D-chloroacetate esterase.

Granulocytes↗
PubMed1984

Evidence that alveolar macrophages can synthesize and secrete alpha 1-antichymotrypsin.

Alpha 1-antichymotrypsin (alpha 1-AC) is a protein that inhibits chymotrypsinlike proteinases, such as leukocyte cathepsin G. It also inhibits cytotoxic "killer" cell activity in vitro and may therefore be important for the control of immunologic and inflammatory processes in the lung. Alpha 1-AC is present in lung secretions at high concentrations, suggesting local production within the lung. We investigated the possibility that alveolar macrophages may be capable of synthesizing and secreting alpha 1-AC. Human alveolar macrophages were cultured in the presence of L-75Se selenomethionine, and the culture supernatants were examined by immunoelectrophoresis followed by autoradiography. The results showed that the radio-amino acid was incorporated into alpha 1-AC, suggesting de novo synthesis of the protein. Cycloheximide inhibited incorporation of the label. Immunohistochemical staining of human lung tissue for alpha 1-AC showed the protein to be present within alveolar macrophages.

Autoradiography↗
PubMed1983

Serum secretory component: a potential marker of biliary obstruction.

Secretory Component (SC) was measured in serum samples from patients with a variety of disorders using enzyme-linked immunosorbent assay (ELISA). The overall precision of the method at high and low concentrations of SC was 11% (CV). Serum concentrations of SC were significantly higher in patients with several forms of liver disease (means = 82.37 mg/l +/- SD 56.9) compared with normals (means = 6.0 +/- SD 4.2), patients with diseases of mucosal surfaces (means = 7.4 mg/l +/- SD 4.2) and patients with elevated alkaline phosphatase due to causes other than overt liver disease (means = 16.4 mg/l +/- SD 7.6). Serum SC levels correlated strongly with serum alkaline phosphatase activity (rs = 0.648) in the presence of liver disease. Raised serum SC in liver disease probably reflects reflumeans of biliary SC and secretory IgA into blood due to cholestasis. Estimation of serum SC could be clinically useful as an index of biliary obstruction, especially to distinguish a raised serum alkaline phosphatase activity of liver or bone origin.

Alkaline Phosphatase↗
PubMed1983

Evidence for a single-chain structure of native human ceruloplasmin using sodium dodecyl sulfate-polyacrylamide-crossed immunoelectrophoresis.

A simple method is described for the analysis of proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with crossed immunoelectrophoresis. The technique allows the identification of specific proteins and estimation of their molecular weights after the electrophoresis of complex mixtures such as blood plasma. Human ceruloplasmin was estimated to have a molecular weight of 128,000 using this method. Reduction of plasma with 2-mercaptoethanol in the presence of protease inhibitors did not result in dissociation of ceruloplasmin into detectable smaller subunits, suggesting that native ceruloplasmin is composed of a single polypeptide chain.

Ceruloplasmin↗
PubMed1983

Synthesis of cathepsin B by cells derived from the HL60 promyelocytic leukaemia cell line.

Cells of the human promyelocytic HL60 line were induced to differentiate into granulocyte-like cells with dimethylsulphoxide (DMSO) or macrophage-like cells with 12-0-tetradecanoylphorbol-13-acetate (TPA). The synthesis of Cathepsin B by these cells was studied by immunoperoxidase staining and assay of cell lysates using the fluorimetric substrate benzoyloxycarbonyl-phenylanalyl-arginine-4-methyl-7-coumarylamide. Only 2-5% of the uninduced HL60 cells and DMSO-induced cells were immunohistochemically positive for Cathepsin B, compared with over 80% of the TPA-induced cells. Cathepsin B activity was lowest in the lysates of uninduced HL60s. DMSO-induced cells contained 1.5-2-fold the enzyme activity of HL60s and TPA-induced cell lysates demonstrated 5-14-fold the activity of uninduced HL60s. Induction of Cathepsin B synthesis was therefore associated with differentiation of the promyelocytes into cells of the monocyte/macrophage type, but not granulocyte-like cells. Cathepsin B was located immunohistochemically in human palatine tonsils. The enzyme was only demonstrated within macrophages in these tissues. Cathepsin B may therefore be a useful immunohistochemical marker for malignant and nonmalignant cells of the monocyte/macrophage lineage.

Cathepsin B↗
PubMed1983

Cathepsin B-like cysteine proteinase activity in sputum and immunohistologic identification of cathepsin B in alveolar macrophages.

Cathepsin B-like cysteine proteinase activity was measured, using a fluorimetric assay, in sputum samples from 27 subjects with chronic obstructive airways disease. Thirteen of the subjects had a current acute respiratory infection. Enzyme activity was detected in 11 of the 13 infected and 12 of the 14 noninfected samples. The mean cathepsin B activity observed in the infected samples was significantly greater than that of the noninfected samples. Most of the cathepsin B-like activity in sputum represented enzyme in free solution but a small proportion appeared to be complexed with alpha 2-macroglobulin. Immunohistochemical localization of cathepsin B in human lung tissue sections detected the enzyme only within macrophages.

Cathepsin B↗
PubMed1983

High-dose cytoreductive therapy with autologous bone marrow transplantation in advanced malignancies.

Twenty-one patients with advanced malignancies received high-dose chemotherapy and/or radiotherapy followed by autologous bone marrow infusion. Eighteen patients (85.7%) had fever greater than or equal to 100 degrees F for a median of 6 days; 14 of these patients required broad-spectrum antibiotics for a median of 13 days. Nineteen patients (90.5%) had a granulocyte count less than 500/mm3 for a median of 11 days. Thrombocytopenia (platelet count less than 50,000/mm3) was observed in 18 patients (85.7%) for a median of 14 days. Mucositis and diarrhea were not common, occurring in six (28.6%) and seven (33.3%) patients, respectively. Of the 21 patients studied, 16 were evaluable for tumor response; there were four complete responses and four partial responses, and two patients who showed no change for variable times. Two patients have unmaintained remissions for greater than 2 years. Our response rate (complete plus partial) is 50%. Our study shows that high-dose cytoreductive therapy can be given with moderate toxicity when combined with autologous bone marrow infusion. Because responses in this group of patients are generally of short duration, we believe that patients with advanced malignancies who have had less exposure to therapy or who have a high likelihood of disease recurrence should be considered for high-dose cytoreductive therapy with autologous transplantation.

Adult↗
PubMed1983

Dual role of the liver in regulating circulating polymeric IgA in man: studies on patients with liver disease.

The human liver probably removes circulating polymeric IgA by two routes: (1) secretory component-mediated endocytic transport of polymeric IgA from portal tract blood vessels into bile across biliary epithelial cells and (2) uptake with possible catabolism by hepatocytes and/or sinusoidal phagocytic cells by uncharacterized receptor(s). Failure of either clearance mechanism due to liver disease results in elevated serum polymeric IgA levels. In patients with cholestasis, the raised serum polymeric IgA concentration is due to reflux of biliary secretory immunoglobulin into the blood.

Alkaline Phosphatase↗
PubMed1982

Metabolic oxidation of methaqualone in extensive and poor metabolisers of debrisoquine.

The metabolism of methaqualone to the glucuronides of 5 C-monohydroxy metabolites and to the N-oxide has been studied in 2 groups of healthy young adults phenotyped as extensive and poor metabolisers of debrisoquine. No significant interphenotype differences were observed with respect to the excretion of any of the 6 metabolites. It is probable that the genetic regulation of the pathways leading to these metabolites is at a locus other than that which is responsible for the regulation of the oxidation of debrisoquine, guanoxan, phenacetin, phenytoin and sparteine.

Adult↗
PubMed1982

The influence of the menstrual cycle on the metabolism and clearance of methaqualone.

1 The rate of methaqualone metabolism in women was shown to be significantly increased at the time of ovulation. 2 The apparent first order rate constants for the formation of five C-monohydroxy metabolites of methaqualone on day 15 of the menstrual cycle were approximately double that on day 1. 3 The N-oxidation of methaqualone showed considerable inter-individual variation in its sensitivity to the menstrual cycle, and in a group of ten women the difference in N-oxide excretion between days 1 and 15 was not statistically significant. 4 The serum clearance of methaqualone on day 15 was higher (mean value 94.6 ml min-1 on day 1, 176.0 ml min-1 on day 15), serum half-life shorter (mean t1/2 beta 16.3 h on day 1, 11.6 h on day 15) and the AUC alpha smaller (mean value 44.0 micrograms ml-1 h on day 1, 24.4 micrograms ml-1 h on day 15) than on day 1. 5 The relative importance of the five hydroxy metabolites was unchanged during the menstrual cycle but the C/N oxidation ratio was greater on day 15 than on day 1. 6 The data for methaqualone metabolism in a control group of men was similar to than in women on day 1 of a menstrual cycle.

Adult↗
PubMed1982

The influence of oral contraceptives on the metabolism of methaqualone in man.

1 Oral contraceptives were shown to suppress the mid-cycle increase in methaqualone metabolism observed in premenopausal women not receiving oral contraceptive therapy. No women were identified in whom this suppression was not observed. 2 Combined oestrogen-progestogen contraceptives produced the effect in all nine women studied. The effect was also observed in one woman who was receiving progestogen-only contraceptives. 3 The effect of the combined contraceptives was observed within one month of the commencement of the contraceptive therapy. 4 The results emphasise the need to monitor the effect of the menstrual cycle in women not receiving oral contraceptive therapy when the effects of such therapy is studied. 5 These effects are more likely to be the consequence of an inhibition of hormonal control of hepatic metabolic activity by the synthetic steroids than they are to simple inhibition of hepatic metabolism.

Adult↗