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Biomedical subjects

C E McCall

Publications and source records attributed to C E McCall.

At least 109 records · Page 6Linked to original sources
PubMed1975

Enhanced bactericidal activity of phagocytes from patients with chronic granulomatous disease in the presence of sulphisoxazole.

The decrease in the frequency and severity of bacterial infections in four of five children with chronic granulomatous disease (C.G.D.) on long-term sulphonamide therapy was out of proportion to demonstrable direct antibacterial effects of the drug. In an attempt to determine the mechanism for this apparent protective effect, the killing of sulphisoxazole-resistant Escherichia coli and Staphylococcus aureus by leucocytes from five patients with C.G.D. was studied in the presence or absence of 5-50 mug. per ml. sulphisoxazole. With leucocytes from all five patients there was a modest but reproducible enhancement of bactericidal activity in the presence of the sulphonamide. Studies of phagocytosis-associated oxidative metabolism in patients' cell have not revealed a metabolic basis for improved killing.

Blood Bactericidal Activity↗
PubMed1975

The generation of superoxide anion by various types of phagocyte.

Polymorphonuclear leukocytes derived from human peripheral blood, rabbit peritoneal exudates, and guinea pig peritoneal exudates generate measurable quantities of superoxide anion when challenged with opsonized zymosan, but not when challenged with zymosan that has not been opsonized. The generation of superoxide is dependent upon the concentration of cells and closely parallels the stimulation of the hexose monophosphate shunt in the phagocytes. In contrast, no superoxide can be detected when rabbit alveolar macrophages (either normal or activated by prior vaccination of the animal with bacille Calmette-Guérin) or rabbit peritoneal macrophages are similarly treated. These data suggest that although superoxide anion may be involved in the bactericidal activity of the polymorphonuclear leukocyte, it is less likely to play a significant role in the bactericidal activity of the macrophage.

Animals↗
PubMed1975

Bactericidal activity of superoxide anion and of hydrogen peroxide: investigations employing dialuric acid, a superoxide-generating drug.

The addition of dialuric acid (a superoxide-generating drug) to a suspension of resting human neutrophils resulted in a stimulation of cellular hexose monophosphate shunt activity. Measurement of oxygen consumption demonstrated a rapid rate of oxygen uptake by the drug alone in aqueous solution. The subsequent addition of catalase (but not of superoxide dismutase) resulted in a substantial release of oxygen, indicating that H(2)O(2) was accumulating in the media. The generation of O(2) (-) by the drug was verified by measuring the rate of reduction of cytochrome c by the drug in the presence and absence of authentic superoxide dismutase. The growth of Escherichia coli B and Staphylococcus aureus was inhibited in vitro by addition of the drug to a suitable culture media; the degree of inhibition was dose dependent. This inhibition of bacterial growth could be completely reversed by the addition of as little as 5 mug of purified catalase, but was not affected by concentrations of superoxide dismutase that were 2,000-fold higher. These results suggest that the dialuric acid-induced stimulation of hexose monophosphate shunt activity in neutrophils is due to accumulated H(2)O(2). Further, the contribution of superoxide to the bactericidal activity towards E. coli and S. aureus is probably minimal compared with that of H(2)O(2).

Barbiturates↗
PubMed1975

An isotopic assay for NADPH oxidase activity and some characteristics of the enzyme from human polymorphonuclear leukocytes.

An isotopic assay for NADPH ixodase that measures the amount of NADP formed by the 6-phosphogluconate dehydrogenase reaction has been developed. Under appropriate conditions, the amount of NADP present is directly proportional to the amount of 14CO2 released from [1-14C]6-phosphogluconic acid. Because this assay employs radioisotopes, it is far more sensitive than conventional assays for the enzyme. The human granule NADPH oxidase, as measured by this assay, is active in the presence of CN minus, is stimulated by Mn-2+, and has a pth optimum of 5.5. Granules isolated from cells that have been allowed to ingest zymosan consistently exhibited more enzyme activity than did granules isolated from either resting cells or cells challenged with zymosan that was not preopsonized. This effect was observed over a wide range of substrate concentrations and could not be explained by differences in protein concentrations between the various samples. If whole homogenates are used in place of isolated granules, the enzyme activity can be observed only with a homogenate of phagocytizing cells and even then only at a high concentration of NADPH. This suggests that an inhibitor of the enzyme might be present within the cell. One patient with chronic granulomatous disease was studied. There was no difference in tnadph oxidase activity of the patients' cells when granules from resting and phagocytizing cells were compared. In contrast, the enzyme activity in granules from two control patients doubled upon phagocytosis. These results are consistent with a role for NADPH oxidase in the initiation of the respiratory burst accompanying phagocytosis by human neutrophils.

Carbon Dioxide↗
PubMed1974

Phagocytosis of live versus heat-killed bacteria by human polymorphonuclear leukocytes.

Heat-killed Pseudomonas aeruginosa are phagocytized much more slowly by human polymorphonuclear leukocytes than are the live organisms. The post-phagocytic increase in hexose monophosphate shunt activity (HMS) parallels the ingestion of the bacteria. The addition of serum to the live organisms causes a marked increase in both ingestion and cellular HMS activity; serum actually causes an inhibition of both uptake and HMS activity when added to the heat-killed organisms. Differences in postphagocytic HMS activity between live and heat-killed organisms were observed with three different species of bacteria, indicating that the phenomenon is not restricted to P. aeruginosa. These data emphasize that the influence of the particle on the phagocytic process is considerable.

Carbon Dioxide↗
PubMed1974

Reduced nicotinamide adenine dinucleotide and reduced nicotinamide adenine dinucleotide phosphate diaphorase activity in human polymorphonuclear leukocytes.

Total reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activities were examined in human neutrophils. Approximately two-thirds of each enzyme activity was located in the granule fraction with the remainder in the soluble. The activities in a 27,000 x g supernatant from a sonic extract of human polymorphonuclear leukocytes were characterized. Both NADH and NADPH diaphorase were insensitive to cyanide and azide and showed greater activity at acid pH. K(m) values for nitroblue tetrazolium were not markedly different (33 muM with NADH and 12 muM with NADPH), but there was a 40-fold difference in K(m) for the reduced pyridine nucleotides (10 muM with NADH and 400 muM for NADPH). Since the intracellular concentration of both nucleotides is estimated to be about 50 muM, it is much more likely, from a kinetic argument, that the respiratory burst of phagocytosis is intiated by the oxidation of NADH rather than of NADPH.

Azides↗
PubMed1974

Superoxide dismutase activity in leukocytes.

Superoxide dismutase activity has been identified in both human neutrophils and rabbit alveolar macrophages by two distinct assay procedures. The enzyme is insensitive to both cyanide and azide and is present in the cytosol of the cell. The identification of this enzyme in phagocytic cells is compatible with the theory that superoxide anion might be involved in the bactericidal activity of the cell. It is proposed that the enzyme functions to protect the cell against superoxide generated during the phagocytic process.

Adrenochrome↗
PubMed1974

Enhanced phagocytic capacity. The biologic basis for the elevated histochemical nitroblue tetrazolium reaction.

The biologic basis for the elevated histochemical reduction of nitroblue tetrazolium dye (NBT) in neutrophils from patients with acute bacterial infection or polycythemia vera was studied. A precipitin reaction followed mixing NBT with heparin. NBT was reduced after phagocytosis of this complex (H-NBT) by polymorphonuclear leukocytes (PMNs). Ingestion required divalent cations and was facilitated by the presence of complement. H-NBT incubated with normal but not with C2-deficient human serum converted native C3 to its inactive form. Phagocytic indices were determined in patients and controls by measuring O(2) utilization and hexose monophosphate shunt activity and by visually counting cell-associated latex particles. Significant elevations above controls were observed in phagocytes isolated from all patients with elevated histochemical NBT scores when H-NBT complex, latex, or zymosan was employed as the phagocytic particle. Increased indices were observed in the presence of fresh AB serum, heat-inactivated AB serum, or without serum. Serum from patients with elevated NBT scores did not alter phagocytosis in control phagocytes. With NADH and NADPH as substrates, total NBT diaphorase activity of sonicated leukocytes was normal in all patients. These results suggest that increased phagocytic capacity of PMNs is the primary cause of increased histochemical NBT reduction. The PMNs of patients with acute bacterial infection or polycythemia vera may have alterations in their cell membranes which lead to an enhanced rate of phagocytosis.

Animals↗
PubMed1973

Creatine phosphokinase activity in rabbit alveolar macrophages.

An enzyme is present in extracts of rabbit alveolar macrophage which can catalyze the reaction of creatine phosphate with adenosine diphosphate to form adenosine triphosphate and creatine. The enzyme is moderately activated by reduced glutathione, has a pH optimum between pH 6.5 and 7.0, and shows an absolute requirement for Mg(2+). The K(m) for creatine phosphate is approximately 3.6 mm while the K(m) for adenosine diphosphate is about 1.1 mm. The enzyme may play a role in the energy balance of the cell by creating a reserve of energy in the form of creatine phosphate.

Animals↗
PubMed1973

Effects of promethazine-hydrochloride on human polymorphonuclear leukocytes.

Promethazine hydrochloride at a concentration of 0.033 mg/ml has pronounced effects on leukocyte metabolism and function. The drug inhibits the phagocytosis-induced increases in O(2) consumption and hexose monophosphate shunt activity. Associated with these effects is an inhibition of the iodination of zymosan particles and an inhibition of bacterial killing by the cell. At least two mechanisms appear to be involved. Many of the effects can be explained by an inhibition of phagocytosis, but promethazine also inhibits the decarboxylation of amino acids and iodide fixation in a cell-free system, indicating a specific effect on metabolism. These results may partially account for the action of the drug in ameliorating the effects of erythroblastosis.

Cell Nucleus↗
PubMed1973

Inhibition of amino acid incorporation into protein of human neutrophils by phagocytosis.

The incorporation of uniformly labeled (14)C-amino acids into total protein of human polymorphonuclear leukocytes is inhibited when the cells are challenged with heat-killed Escherichia coli or latex particles. Parallel studies of amino acid incorporation and glucose oxidation indicate that the inhibition is dependent upon ingestion of the particles. It is suggested that the process of phagocytosis might inhibit the transport of amino acids into the cell either by competing for available energy or by internalizing specific transport sites.

Amino Acids↗