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Biomedical subjects

R C Strunk

Publications and source records attributed to R C Strunk.

At least 91 records · Page 5Linked to original sources

Inhibition of in vitro synthesis of the second (C2) and fourth (C4) components of complement in guinea pig peritoneal macrophages by a soybean oil emulsion.

Recently a soybean oil emulsion (Intralipid) (IL) has been released in the United States for use as a parenteral nutrient. The study reported here was undertaken to determine the effect of ingestion of IL on the synthesis and secretion of the second (C2) and fourth (C4) components of complement by guinea pig peritoneal macrophages in vitro. Cells exposed to IL had extensive Oil Red 0-positive granular-appearing accumulations of neutral lipid within the cytoplasm. Control cells did not stain with Oil Red 0. Incubation of the cells with concentrations of IL from 2.3--37.5 mg/100 ml resulted in a significant decrease in the production of both C2 and C4, which could not be explained by variability between plates. The decrease in total C2 or C4 production by cells incubated with IL for 4 hr was similar to the decrease in production by cells incubated with IL for 48 hr. Several lines of evidence indicated that the decrease of C2 or C4 was the result of decreased synthesis of these proteins and not interference of IL with the detection of the proteins or their secretion from the cells. Exposure of the cells to IL at all concentrations caused reduction of the number of cells having pseudopodia and a rounding-up of the cells. IL did not affect the rate of detachment of the cells from the plates through the 48-hr incubation period or the ability of the cells to exclude trypan blue. Total protein synthesis and total lysozyme production by control and IL-treated cells was similar.

Animals↗

Alternative pathway of complement activation in full term and premature infants.

Classical and alternative pathway complement levels were measured in the cord blood sera of 60 newly born infants, with weights ranging from 1200--4165 g. The impact of maternal illness and infant illness on the complement levels was also evaluated. The mean values for CH50, C3, C4, PH50, factor B, and properdin were all significantly less than normal adult levels (P less than 0.0001). All of the above determinations were significantly correlated with one another except for the relationship between properdin and factor B. CH50, PH50, C4, and properdin levels were significantly correlated with birth weight although there was much residual scatter. Neither maternal illness nor mild to moderate illness in the newborn altered the birth weight-complement relationships. Severe infant illness did significantly alter the relationship between birth weight and complement. However, the impact of this variable on the birth weight-complement relationships was not consistent among the various components. These inconsistencies and the small sample size preclude drawing any strong conclusions about severe illness and complement levels.

Adult↗

Immunofluorescence in group B streptococcal infection and idiopathic respiratory distress syndrome.

Immunofluorescence was performed on lung tissue obtained at necropsy from 18 newborn infants, including five with group B streptococcal (GBS) sepsis, seven with idiopathic respiratory distress syndrome (IRDS), and six control infants who died from other causes. Deposits of C3, IgG, and fibrin were found within hyaline membranes of infants who died with GBS sepsis or IRDS within 48 hours after birth. In some cases C4, factor B, and IgM were also observed. In five infants with IRDS who died more than five days after birth, immunofluorescent lung findings were less common and less intense. Hyaline membranes, attributed to mechanical ventilators and oxygen therapy in two infants who did not have GBS infection or IRDS, were negative for complement and immunoglobulins although fibrin was detected in one specimen. These data suggest that immunologic processes may contribute to the pathogenesis of certain types of acute lung injury, particularly in infants who die from GBS infection or IRDS during the early neonatal period.

Antigen-Antibody Complex↗

Alteration of the structure and function of guinea pig peritoneal macrophages by a soybean oil emulsion.

Studies in humans who have received Intralipid (IL) have demonstrated the presence of a fat pigment and fat droplets in reticuloendothelial phagocytic cells. Clinical data and in vitro studies suggest that these cells do not function normally. We have studied the effect of IL on the morphology and function of guinea pig peritoneal macrophages in vitro. Starch-induced macrophages were exposed to IL for up to 48 hours. Ingestion of increasing amounts of IL over the 48-hour period was confirmed by transmission electron microscopy and by oil red O stain. The uptake of the IL was associated with marked morphologic changes characterized by a decreased ability of the cells to spread and by a decrease in the number and degree of complexity of the membrane ruffles. The ingestion of IL also resulted in decreased capacity of the cells to associate with latex beads (5.7 mu in diameter) or Candida albicans and decreased capacity to adhere to and ingest sheep erythrocytes coated with IgG. After ingestion of latex beads 0.46 mu in diameter, which are similar in size to IL particles, macrophages had normal morphology and function, indicating that neither the morphologic nor functional abnormalities were due to a nonspecific effect of ingestion of small particles. Alterations of human reticuloendothelial macrophage function similar to the effects observed here could compromise host defense against infection.

Animals↗

Immune-complex-mediated glomerulonephritis and pulmonary hemorrhage simulating Goodpasture syndrome.

Two female children whose clinical presentations and renal light-microscopic findings were consistent with Goodpasture syndrome are described. Immunopathologic studies demonstrated granular deposition of immunoglobulins and complement, suggesting that the renal disease was mediated by circulating immune complexes and not by anti-glomerular basement membrane antibody. Anti-GBM antibody was absent in both patients. These patients represent the first report in children of idiopathic nephritis due to immune complexes with associated pulmonary hemorrhage. The findings raise some doubt as to the accuracy of previous reports of Goodpasture syndrome in children, and also demonstrate the diagnostic and therapeutic importance of evaluation the renal immunopathology in the child with nephritis and pulmonary hemorrhage.

Anti-Glomerular Basement Membrane Disease↗

Humoral immunity in experimental hyposplenism.

The immune response to an intravenous bolus of sheep erythrocytes, a large particulate antigen, was examined in weanling Sprague-Dawley rats after varying reduction in spleen size by splenic artery ligation (SAL) or partial amputation (pSx), and the results were compared with splenectomized (Sx) and sham-operated controls. Whereas SAL and pSx rats both produced higher 5 day (primary response) hemolysin antibody titers (P less than 0.001) than Sx rats, levels were lower (P less than 0.05) than in sham-operated rats with larger spleens (P less than 0.001). A similar heterophile pattern was seen in SAL rats at 22 days (secondary response). Within each group there was a positive correlation between splenic weight and serum hemolysin titer (r greater than 0.81) (P less than 0.001). Whereas spleen weight of sham-operated rats increased only 58%, splenic remnants in pSx rats enlarged 139% to 412%, with the greatest percentage of growth in the smallest remnants (25 mg) and the least in the largest remnants (200 mg). These data demonstrate a measurable immunologic advantage of splenic remnants (hyposplenism) over asplenism. This difference, although suboptimal as compared with that of a whole spleen (eusplenism), nonetheless may bolster body defenses to certain forms of bacterial sepsis.

Amputation, Surgical↗

Harvester ant sensitivity: in vitro and in vivo studies using whole body extracts and venom.

Harvester ant stings by Pogonomyrmex maricopa (Pm) or Pogonomyrmex rugosus (Pr) resulted in serious reactions in 8 patients, 4 with generalized reactions and 1 with large local reactions. Exposure to one species in the genus Pogonomyrmex (P) appeared to cross-sensitize ant-sensitive patients to other species in the same genus as evidenced by skin testing and leukocyte histamine release, but these patients were less sensitive to extracts from other stinging Hymenoptera, including bee, wasp, yellow jacket, hornet, and Formica ant. Pr ant venom was obtained by electrical stimulation of live ants for leukocyte histamine release studies. The venom preparation was considerably more effective in inducing histamine release than a body extract derived from gasters, the posterior abdominal segments. Rabbits immunized with an extract from one species produced precipitating antibodies against the injected extract withich cross-reacted with extracts from other species of harvester ant, but not with other stinging Hymenoptera. Humans and rabbits appear to react to certain genus-specific antigens present in Pogonomyrmex whole body extracts. Proper identification of the offending ant is crucial for proper testing and treatment of ant-sensitive patients.

Animals↗

Intrapatient variability in theophylline kinetics.

Seven asthmatic children had repeat determinations of theophylline pharmacokinetic measurements over three- to nine-month intervals. Significant intrapatient variability was found in the theophylline clearance and t1/2, which determine the dosage regimen necessary to provide given average, peak, and trough theophylline plasma levels. Repeat clearance values were, on average, 52% different from the original clearances, with a range of -57% to +142%. A single determination of theophylline kinetic measurements in any individual patient cannot be used routinely to predict future theophylline dosage regimens for that patient.

Adolescent↗

Herpes simplex virus infections in guinea pigs deficient in the fourth component of complement.

Separate groups of normal and C4-deficient guinea pigs were inoculated with herpes simplex virus by intradermal (i.d.) and intraperitoneal (i.p.) routes. Virus infection, confirmed by clinical, virological, and serological criteria, did not last longer and was not more severe in C4-deficient guinea pigs than in normal guinea pigs. Serum C component levels were measured before, during, and after herpes simplex virus infection. In normal gruinea pigs there was no evidence for C4 utilization after either i.d. or i.p. inoculation. In both normal and C4-deficient guinea pigs, C1 and C3-9 levels remained unchanged in spite of i.d. or i.p. infection. These data suggested that C4 and the classical C pathway were not important for virus clearance.

Animals↗

Serum complement depression during viral lower respiratory tract illness in cystic fibrosis.

Cystic fibrosis (CF) patients with viral lower respiratory tract illnesses (LRI) had depressed levels of the third and fourth components of complement, which returned to normal after recovery. There was no clinical evidence of immune complex disease. CF patients with LRI and no virus isolates, CF patients in stable status, and non-CF patients with LRI did not have complement depression. It is postulated that antigen-antibody complex activation of complement may occur in CF patients with viral LRI.

Adolescent↗

Complement activation and group B streptococcal infection in the newborn: similarities to endotoxin shock.

Serial measurements of CH50, C3, C4, and factor B were performed on three newborn infants with group B streptococcal sepsis. Two of the septic infants had a colonized but noninfected identical twin. All three infants with group B streptococcal sepsis had hypotension, prolonged coagulation times, neutropenia, and respiratory failure. During the course of the sepsis, factor B was depressed 30% to 35%, C3 was depressed 40% to 60%, and CH50 was depressed by 100% when compared to their cord blood levels. Two of the infants also had a 50% to 70% depression of C4. In contrast, no significant decrease in complement levels occurred in the siblings of the twins or in two additional control infants. These data are characteristic of older patients with Gram-negative sepsis and strongly suggest that the group B Streptococcus has endotoxin-like properties.

Adult↗

Complement biosynthesis in vitro by rat hepatoma cell strains.

Four separate rat hepatoma strains were examined for their capacity to synthesize complement (C). None of the strains synthesized detectable amounts of the first components (C-1), and only one strain (7800C-1) produced the fourth component (C4). However, each of the strains synthesized significant amounts of biologically active C-2 and C-3. Three of the four strains also produced C-5 and the natural inhibitor of C-1 (C1 INH). Two control rat cell strains (fibroblast and pituitary) did not synthesize any detectable C components. Production of C, studied extensively in 7800C-1 and H-4, was reversibly inhibited by cycloheximide (2 mug/ml) and [ 14-C ] amino acids were incorporated into C-2, C-3, and C-1 INH. As assessed by gel filtration, the elution positions of the C components synthesized by the cells in culture were similar to those of the corresponding proteins in normal rat serum. Hydrocortisone (10-6 to 10-7 M) stimulated the production of C-3 by H-4 but C-2 and C-5 production were not affected. These C-producing hepatoma cells may prove useful for studies of the control of C biosynthesis.

Animals↗