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Biomedical subjects

A M Oliver

Publications and source records attributed to A M Oliver.

28 records · Page 2Linked to original sources

Major histocompatibility complex (MHC) class II antigen (HLA-DR, DQ, and DP) expression in human fetal endocrine organs and gut.

Monoclonal antibodies were used to analyse adrenal, pancreas, thyroid, and gut samples from human fetuses (14-19 weeks estimated gestational age; EGA) for the presence of class II major histocompatibility complex (MHC) antigens (HLA-DR, DQ, DP) by immunohistochemistry. In the adrenal definitive and fetal cortex, HLA-DR+, DP-, DQ- cells were clearly demonstrated. These DR+ cells were identified, phentotypically, as predominantly tissue macrophages and a small population of CD45R+, IgM+ lymphoid cells. Within the pancreas, numerous cells throughout the tissue were strongly DR+ but DQ-; DP+ cells were not observed until 17 weeks EGA. Using a double-labelling procedure, minor proportions of these DR+ cells were identified as macrophages or as (CD19+) B cells, while endocrine and endothelial cells were negative. Throughout the thyroid, small numbers of DR+ macrophages and small lymphoid cells were detected, although the thyroid epithelial cells were DR-, DP-, and DQ-. Large numbers of DR+, DP+, DQ- cells were observed in the stomach wall and mucosa. In the intestine, DR+, DP+, DQ+ cells positive for all MHC class II loci products were abundant throughout the lamina propria and lymphoid aggregates. The class II antigens appeared in the proportion DR greater than DP greater than DQ and expression was most prevalent in the mid-gut region. A small proportion of epithelial cells of the villi along the gut were weakly DR+ but DQ-, DP-. These results show that DR+ cells in fetal endocrine tissue are mainly 'passenger leucocytes' and that, in contrast to recent reports concerning normal adult tissue, the adrenal and pancreatic endothelial cells are DR-.

Adrenal Glands↗

The effect of clindamycin on macrophage and monocyte Fc receptors.

The effect of clindamycin on Fc receptor expression has been investigated with mouse peritoneal macrophages and human peripheral blood monocytes. When monolayers of these cells were treated with therapeutic concentrations of clindamycin for periods up to 1 hr at 37 degrees C binding of IgG2b coated sheep erythrocytes (EAG) was inhibited. No effect was observed at 4 degrees C or 22 degrees C. An independent effect of the antibiotic on the sheep erythrocytes was noted when they were pretreated with clindamycin that resulted in enhanced binding to the mouse but not the human phagocytes. These findings are discussed in relation to possible in vivo actions of the antibiotic.

Animals↗

A double-crossover study comparing conventional ventilation with high frequency ventilation in a patient with tracheoesophageal fistula.

Respiratory distress, from severe gastric aspiration pneumonitis and abdominal distention in the patient with tracheoesophageal fistula frequently requires mechanical ventilatory support. Bulk flow ventilation can lead to enlargement of the fistulous tract, elevation of gastric intraluminal pressures, raised airway pressures with hemodynamic instability, and retained secretions. We report a case of tracheoesophageal fistula, secondary to perforation of a squamous cell carcinoma of the esophagus, with temporary improvement in gas exchange on high frequency ventilation after failing on a conventional ventilator. The patient initially failed to improve on an Engstrom ventilator (Engstrom-Gambro, Inc., Barrington, IL) at 13 l/minute ventilation. Instituting high frequency jet ventilation with a VS 600 Jet Ventilator (Instrument Development Corporation, Pittsburgh, PA) at initial settings of 35 psi, rate 150, inspiratory time 40%, FiO2 0.8 and 12 cm H2O positive end expiratory pressure (PEEP), provided incremental improvement in gas exchange and oxygenation up to 26 cm H2O PEEP. However, in view of progressive multi-organ failure we terminated the jet ventilation after 48 h and returned the patient to conventional ventilation. We were unable to provide life-sustaining ventilation and oxygenation with either an Engstrom ventilator at 13 l/-minute ventilation or an MA-1 ventilator (Puritan-Bennett, Kansas City, MO) at a tidal volume of 800 cc and a ventilator rate of 30. Terminal respiratory failure occurred. Based on the period of improvement using high frequency jet ventilation, we believe this mode of ventilatory support is beneficial in the management of tracheoesophageal fistula.

Aged↗

The effect of Pseudomonas alginate on rat alveolar macrophage phagocytosis and bacterial opsonization.

Alginate obtained from a mucoid strain of Pseudomonas aeruginosa was shown to inhibit the phagocytosis of an isogenic non-mucoid revertant by rat alveolar macrophages. Phagocytosis of Staphylococcus albus, binding of sensitized sheep erythrocytes to Fc receptors and uptake of latex particles were also inhibited. These results suggest that the alginate acts as a barrier, surrounding the macrophage preventing the attachment of bacteria or other particles to the plasma membrane. This conclusion was supported by showing that alginic acid, a polysaccharide from seaweed structurally similar to alginate also inhibited the phagocytosis of non-mucoid Ps. aeruginosa. The alginate also inhibited opsonisation of the non-mucoid revertant by a non-agglutinating hyperimmune serum. It is proposed that alginate confers a selective advantage on mucoid producing forms of Ps. aeruginosa by impairing the host immune response by its action on alveolar macrophages and opsonization of bacteria.

Alginates↗

The in vitro effect of three antibiotics on alveolar macrophages.

The effects of 3 antibiotics, azlocillin, ticarcillin and tobramycin, on rat alveolar macrophage function has been examined. These antibiotics are used in the treatment of Pseudomonas aeruginosa lung infections in cystic fibrosis patients. In this study low concentrations of the antibiotics were used, similar to the low levels found in the lungs of these patients. Tobramycin, a highly active aminoglycoside, inhibited the phagocytosis of opsonized Pseudomonas aeruginosa and enhanced the binding of sheep erythrocytes sensitized with IgG2b, when pre-incubated with macrophage monolayers for 30 min. Inhibition of both phagocytosis and binding of sensitized sheep erythrocytes was observed when tobramycin was co-incubated with the macrophage monolayers and indicator cells. Azlocillin, a semi-synthetic penicillin, caused inhibition of phagocytosis of opsonized bacteria and binding of sensitized sheep erythrocytes when added with the indicator cells. However, no effect was found if the macrophages were pre-incubated with azlocillin for 30 min. Ticarcillin, a semi-synthetic penicillin which is less active in vitro as an antimicrobial agent than azlocillin, had no effect on alveolar macrophages at the concentrations used in these assays. It is postulated that if these in vitro findings with rat alveolar macrophages are reflected in the in vivo situation in humans, the effect of antibiotics on host defence may be of clinical importance.

Animals↗

Macrophage 'receptors' for bacterial cell-wall sugars and immune response genes: possible determinants of susceptibility to infection.

Recognition of bacteria, antigen presentation and regulation of the immune response by the class II antigens of the major histocompatibility complex (MHC) are among the many factors that influence a host's response to microbial infection. 'Lectin-like' receptors on the macrophage membrane recognize a variety of bacteria by interaction with their cell-wall sugars. These receptors are susceptible to environmental factors and appear to be associated with the I-A subregion of the mouse MHC. Possible effects of this recognition system on the pathogenesis of microbial infection and reactive arthritides are considered.

Animals↗

Inhibition of bacterial binding to mouse macrophages by Pseudomonas alginate.

Alginate, an acetylated polymer of D-mannuronic and L-guluronic acid obtained from a mucoid strain of Pseudomonas aeruginosa was shown to inhibit the binding of an isogenic non-mucoid revertant to mouse peritoneal and pulmonary macrophages. Inhibition of bacterial binding by the alginate was also demonstrated in tests with other non-mucoid P. aeruginosa strains and a strain of Staphylococcus albus. Since the mucoid form of P. aeruginosa eventually predominates in chronic P. aeruginosa infection in patients with cystic fibrosis, it is postulated that the alginate's inhibition of binding gives mucoid forms a selective advantage over non-mucoid forms against macrophage defence mechanisms in the lung.

Alginates↗

The effects of D-pencillamine and levamisole on leucocyte chemotaxis in the rat.

The administration of D-penicillamine (25 mg/kg) or levamisole (5 mg/kg) had no effect on leucocyte emigration into the exudates formed in inert sponges implanted in normal rats. 2 In rats, previously sensitized to Bordetella pertussis and implanted with sponges containing pertussis vaccine, an increased leucocyte migration into the exudates occurred; this was significantly enhanced by the administration of the drugs. 3 Neither drug in vitro affected the chemotaxis of rat polymorphonuclear leucocytes although random migration was significantly increased by levamisole (2 microgram to 1 mg/ml). Neither drug affected the chemotaxis of rat mononuclear cells although levamisole (25 microgram/ml) significantly increased that of human monocytes. 4 It is concluded that both drugs produce similar effects in an animal model of delayed hypersensitivity and that their clinical antirheumatic actions may have common elements.

Animals↗

Tobramycin-induced modulation of macrophage Fc-receptors.

Tobramycin is an aminoglycoside that is used therapeutically for chronic pulmonary infection that occurs in cystic fibrosis patients. The effect of this antibiotic on Fc-receptor expression was investigated using rat alveolar macrophages. When macrophage monolayers were incubated for 30 min with low concentrations of tobramycin (0.03-2.4 micrograms/ml) similar to those found in the cystic fibrosis lung, Fc-receptor expression was enhanced. This effect was dose-, temperature- and time-dependent. After 1 h pre-incubation antibody-labelled erythrocyte (EAG) binding returned to normal values and after 2 h inhibition was observed. When culture supernatants prepared from antibiotic-treated macrophages were incubated with EAG for 30 min, binding of these cells to the macrophages was decreased. This inhibition was directly proportional to the amount of supernatant added to the red cells and was greatest when the supernatant had been prepared from macrophages incubated with the antibiotic for 1 h. When macrophage monolayers were incubated for 1 h with supernatants from tobramycin-treated macrophages subsequent binding of EAG was increased. The supernatants also caused the agglutination of antibody-sensitised erythrocytes. This activity was lost after the supernatants had been absorbed against EAG. It is proposed that the supernatants contain released Fc-receptors and that tobramycin causes an increase in the shedding of Fc-receptors from the macrophage membrane. The mechanism of action of tobramycin and the in vivo relevance of these results is discussed.

Animals↗