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Biomedical subjects

G M Johnson

Publications and source records attributed to G M Johnson.

At least 19 recordsLinked to original sources

Superoxide anion production by rat neutrophils at various stages of bleomycin-induced lung injury.

This study investigated the level of activation of neutrophils isolated from rats at various stages of bleomycin-induced lung injury. Neutrophils were collected from blood and bronchoalveolar lavage (BAL) fluid and their superoxide anion (O2-)-generating capacity measured in response to phorbol myristate acetate (PMA) and opsonized zymosan (OZ) stimulation. When stimulated with PMA, BAL neutrophils isolated from animals 3 days after bleomycin treatment had a significantly greater capacity to produce O2- than BAL neutrophils from animals 7 days after bleomycin treatment. The O2- levels of 7 day BAL neutrophils more closely resembled the resting levels obtained with circulating neutrophils from both control and bleomycin-treated animals. There were no differences observed in any of the neutrophils when stimulated with OZ. Myeloperoxidase levels were measured in plasma and BAL and found to be elevated only in plasma at 7 days after bleomycin. These data demonstrate that neutrophil activation does occur in this model and that the activation appears to be transient, in response to specific stimuli and compartmentalized between the lung and blood.

Animals

Autologous blood transfusion. Current trends, nursing implications.

Developing a quality perioperative autologous blood recovery program is a team effort. Members of transfusion committees, hospital blood bank personnel, OR staff members, and the members of the surgery committee are all possible sources of information. Your local blood center also may have literature or services that could be of assistance. Knowledge of current autologous transfusion alternatives will help nurses communicate with patients regarding transfusion therapy and will make nurses more valuable participants in the crucial decisions necessary to deliver optimal patient care in the perioperative period.

Blood Transfusion, Autologous

Suspect value of non-CSF viral cultures in the diagnosis of enteroviral CNS infection in young infants.

Laboratory criteria used for presumptive diagnosis of enteroviral meningitis were evaluated as predictors of cerebrospinal fluid (CSF) infection. Records were retrospectively analysed of infants under four months of age admitted to hospital between 1977 and 1987 with viral CSF cultures: those with enteroviruses isolated from CSF (group 1) were compared with those with enteroviruses isolated only from non-CSF sites (group 2). Predictive value computations demonstrated that no single or combined non-CSF culture accurately predicted isolation of enteroviruses from the CSF. These results suggest that CSF viral culture is imperative in establishing the diagnosis of enteroviral meningitis in young infants.

Cerebrospinal Fluid

Superoxide production by rat neutrophils in the oleic acid model of lung injury.

The purpose of this study was to investigate the superoxide anion (O2-)-generating capacity of neutrophils isolated from rats at various stages of oleic acid(OA)-induced lung injury. Neutrophils were collected from blood, bronchoalveolar lavage (BAL), and peritoneal cavity (glycogen induced) after OA administration. Control neutrophils were collected from the blood of normal animals as a representative of nonprimed cells that produce low levels of O2-. A second control was the glycogen-elicited peritoneal neutrophil of normal animals which represented primed cells that produce enhanced levels of O2-. The ability of the neutrophils to produce O2- was evaluated by using both myristate acetate and opsonized zymosan as stimulants. Neutrophils isolated from blood and BAL from OA-injured lungs produced low levels of O2- and resembled closely the circulating, nonprimed neutrophil. Myeloperoxidase levels were measured in plasma and BAL and were found to be elevated in BAL of OA-injured animals. The inability of neutrophils to produce high levels of O2- and the elevation of myeloperoxidase suggest that neutrophils present in the lung may have degranulated in response to prior activation and are therefore incapable of further superoxide production.

Animals

Septicemia in pediatric oncology patients: the significance of viridans streptococcal infections.

One hundred nine consecutive episodes of septicemia were retrospectively evaluated in 61 children with malignancy. In addition, the records of all pediatric oncology patients who received high-dose cytarabine (HDAC) chemotherapy were reviewed. Gram-positive organisms accounted for 82.6% of the septicemic episodes. In the total group, coagulase-negative staphylococci and viridans streptococci accounted for 35.8% and 28.4% of the episodes, respectively. In granulocytopenic patients, viridans streptococci were the most common pathogens (36.8%). In the subset of patients who received HDAC, 62.5% of the septicemic episodes were caused by viridans streptococci. Pulmonary complications developed in nine (29%) of the total cases of viridans streptococcal sepsis, whereas these complications occurred in only eight (10.3%) of the septic episodes caused by other organisms. In patients who had viridans septicemia, prior treatment with HDAC did not increase the incidence of pulmonary complications. In septic children with malignancy, our results demonstrate a high incidence of gram-positive organisms, including viridans streptococci, which were once regarded as culture contaminants.

Adolescent

Enhancement of neutrophil function for treatment of neonatal infections.

Newborn infants are at increased risk of morbidity and mortality from infection despite the continued development of new antibiotics. Because impairment of such host defense mechanisms as PMN function is thought to be largely responsible for this problem, correction of these defects in neonates offers a new and potentially important therapy against infection. Further studies are necessary to determine whether transfusion of either adult PMNs, antibody or fresh frozen plasma; administration of immunomodulating drugs; or some combination of these will provide maximum therapeutic benefit for the newborn infant with infection.

Humans

The erythrocyte as instigator of inflammation. Generation of amidated C3 by erythrocyte adenosine deaminase.

Myocardial ischemia is characterized by the liberation of adenosine and by complement-mediated inflammation. We have reported that amidated C3, formed when ammonia (NH3) disrupts the thiolester bond of C3, serves as an alternative pathway convertase, generates C5b-9, and stimulates phagocytic oxidative metabolism. We investigated whether the deamination of adenosine by adenosine deaminase in hematopoietic cells might liberate sufficient ammonia to form amidated C3 and thereby trigger complement-mediated inflammation at ischemic sites. In the presence of 4 mM adenosine, NH3 production per erythrocyte (RBC) was equal to that per neutrophil (PMN) (3.3 X 10(-15) mol/cell per h). Because RBC outnumber PMN in normal blood by a thousandfold, RBC are the major source of NH3 production in the presence of adenosine. NH3 production derived only from the deamination of adenosine by the enzyme adenosine deaminase and was abolished by 0.4 microM 2'-deoxycoformycin, a specific inhibitor of adenosine deaminase. When purified human C3 was incubated with 5 X 10(8) human RBC in the presence of adenosine, disruption of the C3 thiolester increased more than twofold over that measured in C3 incubated with buffer, or in C3 incubated with RBC (P less than 0.05). The formation of amidated C3 was abolished by the preincubation of RBC with 2'-deoxycoformycin (P less than 0.001). Amidated C3 elicited statistically significant release of superoxide, myeloperoxidase, and lactoferrin from PMN. Thus, the formation of amidated C3 by RBC deamination of adenosine triggers a cascade of complement-mediated inflammatory reactions.

Adenosine

Characteristics of iC3b binding to human polymorphonuclear leucocytes.

We determined in binding assays using monomeric fluid-phase iC3b and Scatchard analysis that iC3b binds to human polymorphonuclear leucocyte type 3 complement receptor (CR3), a low-density/high-affinity receptor (28,200 binding sites, affinity constant (Ka) = 2.1 +/- 0.47 X 10(6) L/M), and to the C3b receptor (CR1), a high-density/low-affinity receptor (54,700 binding sites, Ka = 1.7 +/- 2.04 X 10(5) L/M. Binding of iC3b to CR1 was confirmed by blocking experiments with polyclonal F(ab')2 antibody against CR1, and competitive binding experiments with C3b. Binding of iC3b to CR3 was demonstrated by blocking experiments with the monoclonal antibody OKM10 against the ligand binding site of CR3. Inhibition of both CR1 and CR3 did not completely reduce iC3b binding, indicating the existence of additional iC3b-binding sites on PMN. Using flow cytometric analysis of receptor expression, no positive or negative co-operativity was observed between CR1 and CR3. Expression of both receptors increased in a dose-dependent manner after incubation with f-met-leu-phe or phorbol myristate acetate; however, only CR3 expression was enhanced at very low concentrations of these stimuli. iC3b/CR3 interactions probably play a central role in host defence against microorganisms.

Complement C3b

Ligand-receptor interactions in the phagocytosis of virulent Streptococcus pneumoniae by polymorphonuclear leukocytes.

We used polyclonal and monoclonal antibodies to neutrophil complement receptors CR1 and CR3 to assess the role of these receptors in the phagocytosis of virulent Streptococcus pneumoniae serotypes 3, 6A, and 14, which bear accessible C3 ligands covalently bound to the polysaccharide capsule. When the iC3b receptor (CR3) on normal polymorphonuclear leukocytes (PMNLs) was blocked by the monoclonal antibody OKM10, phagocytosis of pneumococcal serotypes 6A and 14 (which bear exclusively iC3b) was inhibited 50%-80% in pooled human serum and completely in nonimmune serum. Blockade of the PMNL C3b receptor (CR1) failed to inhibit phagocytosis for serotypes 6A and 14. For serotype 3, which bears C3b and C3d (as well as iC3b) on the capsule, CR3-mediated phagocytosis accounted for only 20% of the uptake; again, there was no evidence for CR1-mediated phagocytosis. The iC3b ligand elicited consistently greater release of superoxide, myeloperoxidase, and lactoferrin than did C3b. The iC3b/CR3 interaction is thus the primary trigger for phagocytosis of iC3b-bearing pneumococci and for stimulation of intracellular bactericidal processes.

Complement C3b

Interference with granulocyte function by Staphylococcus epidermidis slime.

The interaction of Staphylococcus epidermidis slime with human neutrophils (PMN) was examined by using isolated slime and allowing bacteria to elaborate slime and other extracellular products in situ. S. epidermidis slime was found to contain a chemoattractant. Incubation of PMN with 50 micrograms or more of slime per ml inhibited subsequent chemotaxis of the PMN to n-formyl-methionyl-leucyl-phenylalanine by 27% and to zymosan-activated serum by 44 to 67% with increasing slime concentrations. S. epidermidis slime stimulated little degranulation of untreated PMN. After pretreatment of PMN with 5 micrograms of cytochalasin b per ml, slime predominantly induced release of specific granule contents (33.8% lactoferrin release by 250 micrograms of slime per ml versus 10% myeloperoxidase release by 250 micrograms of slime per ml). By a surface phagocytosis assay, PMN uptake of radiolabeled S. epidermidis which were incubated for 18 h on a plastic surface for slime expression was less than that for S. epidermidis adhered to the plastic for 2 h or grown in unsupplemented nutrient broth. These results suggest that S. epidermidis slime interaction with PMN may be potentially detrimental to host defense and may contribute to the ability of this organism to persist on surfaces of foreign bodies in the vascular or central nervous system.

Chemotaxis, Leukocyte

Relationships between adolescent drug use and parental drug behaviors.

The present study examined some previously reported relationships between drug use by adolescents and perceived attitudes and behaviors of their parents. An anonymous questionnaire was administered to the student body of an inner-city secondary school for difficult students. Relationships between parental use of drugs and adolescent use of the same drugs were moderate and roughly equivalent across drugs. However, parental use of marijuana was strongly related to the adolescent's use of other, harder drugs such as opiates, cocaine, amphetamines, and barbiturates. This finding is explained within the framework of Kandel's postulated stages of drug initiation. It points to a need for further study of parental influences, which may be increasingly problematic as more individuals who have grown up in our marijuana-accepting society become parents of adolescents.

Adolescent