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Biomedical subjects

M L Shea

Publications and source records attributed to M L Shea.

11 recordsLinked to original sources

Quantitation of corneal inflammation by chemiluminescense.

Various inflammatory agents, including Pseudomonas aeruginosa, bacterial filtrates, endotoxin, and phorbol myristate acetate were found to induce significant increases in corneal chemiluminescense (CLM). Disruption of polymorphonuclear leukocytes within corneas by sonication, freeze-thawing or cryotherapy, or reduction of corneal infiltration by induction of neutropenia resulted in marked decreases of CLM. Increased corneal CLM was associated with significant increases in corneal thickness and water content. Oxygen-free radical scavengers significantly inhibited CLM of experimentally infected corneas in vitro, as did the anti-inflammatory agents prednisolone acetate, indomethacin, and salicylic acid. In vivo therapy of infected corneas with prednisolone resulted in significant reductions in corneal CLM, thickness, and water content compared with saline-treated eyes. The CLM assay is a simple technique that allows quantitation of corneal inflammation and evaluation of the effect of therapeutic agents on corneal inflammation.

Animals↗

Burnout!

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Burnout, Professional↗

A genetic defect of granulocyte oxidative metabolism in a man with disseminated aspergillosis.

A 26-year-old man presented with progressive pneumonia, and Aspergillus was grown from cultures of lung, cutaneous nodules, and urine. His PMNs had a poor CL response after exposure to phagocytic stimuli (S. aureus, latex, aggregated IgG and IgG-coated latex) (p less than 0.01 vs. controls) and soluble stimuli (PMA, sodium fluoride, and Con A) (p less than 0.05). His PMNs failed to reduce NBT, oxidize 14C-1 glucose (p less than 0.001), or iodinate proteins (p less than 0.001), normally, compared with controls, and his PMNs killed Candida albicans and Staphylococcus aureus abnormally (p less than 0.05). The patient was anergic; his plasma inhibited responsiveness of his lymphocytes to stimulation with Aspergillus and Candida antigens. His lymphocytes failed to produce the lymphokine LMIF normally. The patient's 10-month-old daughter was demonstrated to have the same defects of PMN metabolism and function. The findings in this patient were similar to those in CGd, but transmission of the defect from father to daughter and the presence of lymphocyte abnormalities make this diagnosis unlikely. Inhalation of Aspergillus by patients with defective PMN oxidative metabolism may be associated with development of significant infection.

Adult↗

Experimental bacterial keratitis: a quantitative model of leukocyte migration following transfusion.

A model for the study of polymorphonuclear leukocyte (PMN) migration after transfusion employing induction of keratitis in guinea pigs was developed. Initial studies demonstrated that compared with other agents, intracorneal injection of Pseudomonas aeruginosa following in vivo labelling of PMN by administration of 3H-thymidine produced the greatest influx of radiolabelled PMN into corneas. In subsequent studies, donor peritoneal PMN were radio-labelled by injection of donors with 3H-thymidine. Neutropenia was induced in recipients by whole body irradiation, and they were infected intracorneally with Pseudomonas prior to transfusion. Corneal radioactivity was assayed 24 h after induction of keratitis and the number of donor PMN in corneas was calculated. Half-life of transfused PMN in non-neutropenic recipients was 1.9 h. Arrival of labelled PMN at infected corneas in recipient animals ranged between 0.1-1.0% of transfused cells. Exposure of donor PMN to sonication or to 45 degrees C for 20 min reduced the proportion of PMN arriving at infected corneas (P less than 0.001). Storage of PMN for 24 h at 4 degrees C led to a greater ingress of donor PMN compared with storage at 37 degrees C (P less than 0.01). This model allows quantitation of in vivo PMN function after transfusion and should allow assessment of the effects of most aspects of PMN transfusion technique upon such function.

Animals↗

Bone CO2-titration curves in acute hypercapnia obtained with a modified titration technique.

Bone CO2-titration curves were obtained in mature rats weighing 500-600 g. Animals were exposed for one hour to 1, 3, 5, 10, or 15% CO2 in air. Measurements of bone CO2, were made using a modified titrimetric analysis on fresh and oven-dried samples of paired rat femurs. A manometric method was used for comparison. Arterial blood samples were obtained for measurements of partial pressure of CO2 in arterial blood (PaCO2). Within the range of environmental CO2 concentrations studied, a linear relationship was observed between the PaCO2 and the increment in fresh bone CO2 content. This relationship is defined by the equation: delta fresh bone CO2 (mmol/kg) = 61.8 +/- 0.68 PaCO2. The CO2 increment was confined to a heat-labile, presumably soluble pool comprising 10.5% of the total bone CO2 content. No change in the water content of the bone was observed as a result of acute CO2 exposure. The results of this study demonstrate the rapid in vivo CO2 uptake of bone in response to exposure to increased CO2 levels.

Acute Disease↗

Determination of posttransfusion granulocyte kinetics by chemiluminescence in chronic granulomatous disease.

A 14 year old boy with CGD of childhood received HLA-matched granulocyte transfusions in the therapy of an intramural abscess of the ileum. Donor granulocyte survival after transfusion was determined with the endotoxin-stimulated NBT test as well as an assay of chemiluminescence employing whole blood. The presence of circulating donor PMNs after transfusion was documented by both techniques. The half-life of donor cells in the first 5 hr following transfusion was approximately 1.4 hr with both techniques. The greatest number of transfused cells was detected by both methods in the patient's blood immediately after the completion of the transfusion. At this time 22.7% of the expected increment in donor PMN concentration was detected by the NBT test, and 13.8% of the expected increment was detected by chemiluminescence assay. Both techniques allow studies of posttransfusion granulocyte kinetics in CGD because of the basic underlying metabolic abnormality of recipient but not donor cells. The chemiluminescence assay may also be adaptable to use in neutropenic patients receiving PMN transfusions.

Adolescent↗

Effect of prolonged exposure to 0.5% CO2 on kidney calcification and ultrastructure of lungs.

Guinea pigs were exposed for up to 8 weeks to 0.5% CO2, 21% O2, and balance N2. Control groups of the same age were kept simultaneously in environmental chambers on air. A slight increase in PaCO2 and decrease in pH were observed at various periods of exposure to 0.5% CO2. After eight weeks of exposure, an increased kidney calcification, indicated by increased kidney calcium content, was found. Plasma calcium was significantly elevated at this point, apparently because of the release of calcium from bone. After 8 weeks of recovery on air that followed 8 weeks of exposure to 0.5% CO2, values had returned to control levels. No significant ultrastructural changes were found in the lungs after 4, 6, and 8 weeks of exposure to 0.5% CO2.

Animals↗