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Biomedical subjects

R C Strunk

Publications and source records attributed to R C Strunk.

At least 73 records · Page 4Linked to original sources

Normal macrophage function in infants receiving Intralipid by low-dose intermittent administration.

The effect of soybean oil emulsion (Intralipid) therapy on serum complement levels was determined in infants who received Intralipid therapeutically (1 gm/kg over 12 hours, every other day). The effect of Intralipid on macrophage priming for increased superoxide anion production was studied in a mouse model. Intralipid administration did not affect either macrophage function. Serum levels of C2 and C4, complement components synthesized and secreted exclusively in macrophages, were not decreased either during the week the infants received Intralipid or in the week following administration. Macrophages from mice that had received Intralipid produced similar amounts of superoxide anion, as did macrophages from mice that had received saline solution. Our data suggest that macrophages in infants receiving Intralipid in this regimen will function normally.

Acetylmuramyl-Alanyl-Isoglutamine↗

Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide.

The third component of complement (C3) is a plasma glycoprotein with a variety of biologic functions in the initiation and maintenance of host response to infectious agents. While the hepatocyte is the primary source of plasma C3, mononuclear phagocytes contribute to the regulation of tissue availability of C3. Lipopolysaccharide (LPS), a constituent of cell walls of gram-negative bacteria, consists of a polysaccharide moiety (core polysaccharide and O antigen) covalently linked to a lipid portion (lipid A). Using metabolic labeling with [35S]methionine, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis, we examined the effects of LPS on synthesis of C3 by human mononuclear phagocytes as well as synthesis of the second component of complement (C2), factor B, lysozyme, and total protein. LPS increased C3 synthesis 5-30-fold without affecting the kinetics of secretion of C3 or the synthesis of C2, lysozyme, or total protein. Factor B synthesis was consistently increased by LPS. Experiments with lipid A-inactivated LPS (alkaline treated), LPS from a polysaccharide mutant strain, and lipid X (a lipid A precursor) indicated that the lipid A portion is the structural element required for this effect. Northern blot analysis demonstrated at least a fivefold increase in C3 mRNA in LPS-treated monolayers, which suggests that the regulation of the increase in C3 synthesis is pretranslational. C2 mRNA and factor B mRNA were increased approximately twofold. The availability of specific gene products in human mononuclear phagocytes that respond to LPS should permit understanding of the molecular regulation of more complex functions of these cells elicited by LPS in which multiple gene products are coordinately expressed.

Complement C2↗

The acute phase response of C3, C5, ceruloplasmin, and C-reactive protein induced by turpentine pleurisy in the rabbit.

Concentrations of five serum proteins, C3, C5, ceruloplasmin, C-reactive protein, and albumin, have been measured during the acute phase response in rabbits with turpentine-induced pleurisy. C-reactive protein concentrations in the circulation rose abruptly between 12 and 36 hours to a level greater than 50 times the pretreatment concentration, then returned to undetectable amounts by 96 hours. C3 and ceruloplasmin both showed some increase in concentration by 12 hours and reached their maximum concentrations of two to three times the baseline levels 48-72 hours after the turpentine treatment. Concentrations were still elevated at 120 hours, after which time they gradually returned to normal. C5 and albumin concentrations in the turpentine-treated rabbits did not differ from the baseline concentrations. The same five proteins were measured in the inflammatory exudate. C-reactive protein was not detectable at any of the time points. C3, C5, ceruloplasmin, and albumin were present in normal pleural fluid at roughly half their serum concentrations. The activities of C3, C5, and ceruloplasmin were low in the early exudate, but C3 and C5 activity rose relative to their concentrations in the later samples of pleural fluid. The specific activities of C3 and C5 were higher in the pleural fluid at 72 hours than in plasma, while that of ceruloplasmin remained less in the pleural fluid than in plasma throughout the experiment. The involvement of these proteins and their relation to the inflammatory response are discussed.

Acute-Phase Proteins↗

The late asthmatic response.

Since LARs are associated with increases in airways reactivity, their significance may go well beyond the increase in symptoms due just to the allergen exposure. This is especially true since the increase in non-specific airways reactivity can last for weeks after a single exposure to allergen. Every effort should be made to search for possible allergic triggers in patients suspected to have LARs. Careful attention to historical information and skin test reactivity are critical in this evaluation. In situations where this approach is not revealing and where serious concerns remain about potential environmental triggers, a bronchial challenge to the suspected antigen can be considered. Since the nonspecific airways reactivity in patients with LAR may possibly be due to inflammation in the airways, the potential risk of transient induction of airways inflammation must be carefully weighed against the value of information that can be obtained from this procedure. Bronchial challenge should be performed only in an inpatient setting by experienced personnel under the supervision of a physician. A full explanation of the potential risks and benefits of this type of evaluation must be given to the patient and family. Treatment is primarily directed at allergen avoidance with use of a prophylactic drug, such as cromolyn sodium, when allergen avoidance is not possible.

Allergens↗

Drug abuse and the asthmatic patient: a case report.

The case history of a 17-year-old girl with sudden onset of theophylline toxicity and a serum theophylline concentration of 63 micrograms/ml is presented. A change in theophylline elimination was not sufficient to explain this observation. Subsequently, the patient admitted to recent self-medication with several over-the-counter medications and illicit drugs. Although the etiology of theophylline toxicity in this patient could not be defined, several theories are proposed. Included is a discussion of possible interactions of illicit drugs with asthma medications and a summary of personality characteristics associated with a high potential for drug abuse.

Adolescent↗

Acute local inflammation alters synthesis, distribution, and catabolism of third component of complement (C3) in rabbits.

In order to evaluate the basis for changes in plasma concentrations of the third component of complement (C3) during inflammation, we injected purified radiolabeled C3 into normal New Zealand White rabbits and into rabbits with turpentine-induced pleurisy. In the normal animals, C3 was distributed between the intravascular compartment (75%) and the extravascular space (25%), with an exchange rate of 1.8 +/- 0.1% of the plasma pool per hour. The fractional catabolic rate (FCR) was 2.7 +/- 0.3% of the C3 plasma pool per hour, the synthesis rate was 1.0 +/- 0.2 mg C3/kg per h, and the plasma concentration was 1.23 +/- 0.3 mg C3/ml. Rabbits with turpentine-induced inflammation showed a shift of the volume of C3 distribution in favor of the extravascular compartment. In addition, the rate by which 125I-C3 was cleared from the circulation increased by 29% and was related to the appearance of 20% of the C3-bound circulating radioactivity in the affected pleural cavity at the zenith of inflammation. The FCR, calculated by measuring urinary excretion of radiolabel, increased by only 9% and was probably related to the C3 degradation that was observed in the pleural fluid during the early stages of inflammation. The plasma C3 concentration reached a peak at 230% of the baseline concentration, owing to an increase in the rate of synthesis by as much as 480%. The latter increase could be blocked by cycloheximide, an inhibitor of protein synthesis. We conclude that the increase of plasma C3 in the acute phase is due to stimulated synthesis, which is partially offset by a rise in FCR and by a shift of protein to the site of inflammation.

Acute Disease↗

Combination drug therapy in children with exercise-induced bronchospasm.

Fifty-three children with moderately severe asthma were studied to determine the capacity of drugs to block exercise-induced bronchospasm (EIB). All 53 children demonstrated EIB (as defined by a 20% fall in FEV1 or 30% fall in FEF25-75) while receiving therapeutic theophylline (serum level 10-20 micrograms/ml). EIB was completely blocked in 47 children by an inhaled metaproterenol 10 minutes prior to exercise, in addition to the theophylline. In six children, EIB was only partially blocked when either metaproterenol or cromolyn was added to the theophylline, but was completely blocked when all three drugs were used. A small group of children may benefit from combination therapy for EIB.

Adolescent↗

Failure of children with asthma to respond to daily aspirin therapy.

Adverse reactions to aspirin in asthmatic patients have been widely described in the past. In contrast to this more frequent complication, several authors have published reports suggesting that aspirin and other nonsteroidal anti-inflammatory drugs can improve asthma. We studied the effect of long-term aspirin administration in children with moderately severe asthma. Ten children who showed no immediate effect of aspirin challenge (either adverse or beneficial) were placed in a 9 wk, double-blind crossover study, receiving aspirin (10 gr twice daily) or placebo for 4 wk, then a 1 wk washout period, followed by aspirin or placebo for 4 wk. There was no difference between aspirin and placebo periods in number of wheezing episodes, frequency of additional bronchodilator or prednisone use, or daily spirometric measurements. Serum thromboxane B2 levels were significantly reduced during aspirin therapy (p less than 0.001), indicating that the patients had complied with the aspirin therapy. Thus long-term administration of aspirin to asthmatics who show no immediate beneficial or adverse response to aspirin challenge appeared not to influence the clinical course of asthma. In addition, inhibition of the platelet prostaglandin cyclooxygenase pathway in these patients did not modify the clinical course of their asthma.

Adolescent↗

Human peripheral blood monocyte-derived macrophages produce haemolytically active C3 in vitro.

The third component of complement (C3) synthesized by human monocyte-derived macrophages has been shown to have the same size and sub-unit structure as serum C3, but haemolytic activity has not been demonstrated. Human monocyte-derived macrophages were cultured from days 4 to 7 in medium without serum, and the conditioned medium was dialysed to remove inhibitors of the C3 assay and concentrated to enhance detection of low amounts of C3. Using these techniques C3 activity was detected routinely. The amount of C3 was 3.4 x 10(7) effective C3 molecules/ml of concentrated tissue culture medium (range 1.0-7.5 x 10(7)), and the number of C3 molecules synthesized by each cell was 4.4 x 10(5), assuming that each cell synthesized C3. The specific activity of the C3 synthesized by the monocytes was the same as the specific activity of C3 that had been purified from serum and then incubated with the cells and processed in the same manner as the monocyte media. Synthesis as the basis for the presence of the C3 activity in the medium was indicated by an inhibition of production of the C3 activity of 66 +/- 16% by cycloheximide, 2 micrograms/ml. Thus, human blood monocytes that migrate into areas of inflammation can mature into cells capable of producing C3 which can participate in the complement sequence and thus potentiate inflammation.

Cells, Cultured↗

Circulating immune complexes in cystic fibrosis.

The presence or absence of circulating immune complexes (CIC) was studied longitudinally over a period of 15 months in 17 patients with cystic fibrosis. (CF). Using the Raji cell assay, CIC were found in 47% of patients. Presence of immune complexes did not correlate with age at midpoint of the study severity of disease, acute pulmonary exacerbations, progression of lung disease, or nonspecific, humoral and cellular immune functions. In addition, the presence of CIC did not correlate with colonization with Pseudomonas aeruginosa, Staphylococcus aureus, Hemophilus influenzae, or streptococcus species (viridans or pneumoniae). Because CIC were present in patients without concurrent sputum colonization with Pseudomonas aeruginosa, antigens other than components of this organism may be capable of forming CIC in CF. The clinical and pathologic significant of CIC in CF remains to be determined.

Adolescent↗

Contact with specific surfaces stimulates the production of the second component of complement (C2) in human peripheral blood monocytes via a lymphocyte factor.

Whole mononuclear cells plated on surfaces coated with the polymer, poly (2-hydroxyethyl methacrylate) (poly-HEMA) produced significantly less C2 when compared to production by cells on tissue culture plastic dishes. The reduction in C2 production was dependent on the amount of poly-HEMA used to coat the dishes and was not due to nonspecific damage of the cells or effects of the poly-HEMA on the hemolytic activity of C2. T and B lymphocytes, but not monocytes, plated on tissue culture plastic produced a soluble factor that increased the production of C2 in freshly adherent monocytes. Lymphocytes plated on the poly-HEMA surface did not produce this soluble factor, which was termed surface-dependent factor (SDF). Whole mononuclear cells plated on poly-HEMA were able to respond to SDF by increasing C2 production by the same percentage as cells on the tissue culture plastic. This suggested that the primary basis for the decreased production of C2 by monocytes in the whole mononuclear cells plated on the poly-HEMA was decreased production of SDF by the lymphocytes. The effect of the poly-HEMA surface on C2 production was probably related to a generalized alteration in maturation of monocytes into macrophages, for SDF had the same type of effect on beta-glucosaminidase levels in monocytes as seen with C2, except that the magnitude of the effect was less. These studies suggest that interaction of lymphocytes with surfaces may modulate the function of the lymphocytes. In addition, interaction of lymphocytes with surfaces and the production of SDF in vivo may be responsible for enhancing maturation of monocytes in tissues.

B-Lymphocytes↗

Techniques of administration of metered-dose aerosolized drugs in asthmatic children.

The use of medications in metered-dose aerosol form in children with asthma has increased dramatically with the development of safer, inhaled beta 2-adrenergic agents and the inhaled corticosteroid, beclomethasone dipropionate. However, the most appropriate techniques of administration of these agents are presently unclear, and frequent inefficient use of these metered-dose inhalers results. We review the aerosol physiology literature to determine and recommend a most efficient inhalation technique for the use of these metered-dose aerosol devices.

Adrenergic beta-Agonists↗

Auriculotemporal syndrome in childhood.

Auriculotemporal syndrome, also known as Frey's syndrome, consists of the development of facial flushing or sweating over the distribution of the auriculotemporal nerve immediately following eating or drinking. It has been recognized in adults as a common postoperative complication of parotid-gland surgery or dorsal sympathectomy. The syndrome is uncommon in children. As its course is benign, it is important to recognize it, thus avoiding unnecessary referral and laboratory evaluation.

Female↗

Subjective psychological symptoms in outpatient asthmatic adolescents.

Outpatient adolescent asthmatics were studied using the Asthma Symptom Checklist (ASC) of Kinsman et al. The study showed that outpatient asthmatic adolescents are similar in many respects to older institutionalized asthmatics, except that in the former, psychological symptoms are more diffuse and recognition of respiratory symptoms is less severe. Further studies are needed to determine which psychological symptoms are most important in predicting prognosis in affected asthmatics or the development of "psychosomatic" asthma.

Adolescent↗

Binding of aggregated human gamma globulin by Raji cells: C1q will enhance only if it is dissociated from the C1 macromolecular complex.

The role of complement components in binding of aggregated human gamma globulin (AHG) to Raji cells was examined using the Raji cell radioimmunoassay. Incubation of AHG in normal human serum enhanced up to five-fold the binding of these complexes by Raji cells. This enhanced binding was medicated primarily by C3 receptors, however, as much as 30% of the enhanced binding was due to a heat-labile protein in serum. AHG incubated with serum-EDTA bound to Raji cells up to two-fold more than AHG incubated with unchelated serum. Since purified Clq also enhanced binding, binding of AHG after incubation with serum-EDTA was probably mediated by Clq. The enhancement effected by Clq occurred only if Clq bound first to AHG, not to the Raji cells, and if Clq bound in the absence of Clr and Cls. Speculations on a role for Clq in biological processes must consider whether the Clq in serum is available to participate. The results presented here suggest that whole serum activated by AHG contained only a small amount of Clq available for cross-linking of particles. Thus, the potential involvement of Clq in biological reactions in vivo is probably limited.

Antigen-Antibody Complex↗

Complement synthesis by guinea pig peritoneal macrophages: failure to detect chemical carcinogens.

In vitro production of the second and fourth components of complement (C2 and C4, respectively) by peritoneal macrophages from noninbred Hartley guinea pigs was tested after the animals had been inoculated with known carcinogens. The system demonstrated the capacity of N-nitrosodimethylamine to decrease C2 and C4 production. However, a similar decrease in C2 and C4 production was seen with only CCl4, 1 of the 10 chemical carcinogens studied. This system had little usefulness as a short-term screening procedure for the detection of carcinogenicity. The effect of the carcinogens on several other functions of peritoneal macrophages was also determined. The number of peritoneal exudate cells (PEC) was significantly lower in carcinogen-inoculated animals than in solvent-inoculated controls for three carcinogens: BeSO4, P < 0.005; CHCl3, P < 0.025; and CCl4, P < 0.01. However, the capacity of the PEC to adhere to plastic was decreased by only CHCl3 (P < 0.05), and adherent cells from all guinea pigs produced normal amounts of total secreted protein.

Animals↗