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Biomedical subjects

A Finn

Publications and source records attributed to A Finn.

At least 73 records · Page 4Linked to original sources
PubMed1998

Changes in leucocyte counts and soluble intercellular adhesion molecule-1 and E-selectin during cardiopulmonary bypass in children.

A consequence of cardiopulmonary bypass (CPB) in young children is postoperative capillary leak and associated pulmonary dysfunction. Neutrophils sequester in the lungs and may contribute to functional endothelial damage. The endothelial adhesion molecules, E-selectin and intercellular adhesion molecule-1 (ICAM-1), mediate sequential steps in adhesion by binding to leucocyte ligands. Circulating forms of these proteins have been identified. We studied changes in the plasma concentrations of soluble E-selectin and soluble ICAM-1 using fixed phase immunoassays, and associated leucocyte counts in 10 paediatric patients undergoing CPB. Concentrations of soluble L-selectin and soluble ICAM-1 consistently fell during CPB from preoperative levels of 89 +/- 17 ng/ml (mean +/- 2SEM) and 218 + 61 ng/ml, respectively, to 39 +/- 7 ng/ml and 84 +/- 24 ng/ml, respectively at the beginning of maximum hypothermia. The haemodilution that occurred during CPB largely explained this fall, but not the more marked decrease in white cell counts that also occurred over this period (6.7 +/- 1.1 to 1.7 +/- 0.5 x 10(9)/l) which may reflect increased leucocyte sequestration. By 24 h postoperatively, levels of both soluble adhesion molecules approached preoperative concentrations, as did lymphocyte counts. In marked contrast, neutrophil counts rose appreciably towards the end of CPB, and continued to rise to a maximum of 10.9 +/- 3.1 x 10(9)/l during the immediate postoperative period and remained at these elevated levels 24 h later. Major consistent changes in circulating leucocyte numbers which occur early in cardiopulmonary bypass may reflect changes in adhesion to the endothelium and consequent sequestration. Alterations in the levels of soluble adhesion proteins may influence these processes.

Cardiopulmonary Bypass↗
PubMed1998

Interleukin-8 mRNA expression in circulating leucocytes during cardiopulmonary bypass.

Interleukin-8 (IL-8) is found in patients following cardiopulmonary bypass (CPB). It may contribute to microvascular injury by activating neutrophils. We examined IL-8 mRNA expression in leucocytes in bypass. IL-8 mRNA levels were measured by Northern analysis and densitometry of isolated mononuclear leucocytes and neutrophils from blood samples taken before, during, and 2 and 48 h after CPB. Plasma IL-8 was measured at each time-point by immunoassay. A strong signal for IL-8 mRNA was detected in neutrophils in five of five and, more weakly, in mononuclear leucocytes of three of five patients studied. The signal peaked consistently during, and fell following bypass, usually to undetectable levels by 48 h. There was always a detectable signal in neutrophils preoperatively. Plasma IL-8 increased from undetectable prebypass levels and peaked later (2 h postbypass) in four of five patients. In the other patient, the cytokine remained detectable throughout. These data demonstrate that IL-8 transcription occurs in leucocytes before and during CPB, but suggest that much of the IL-8 detectable in plasma following bypass may derive, not from these leucocytes, but from other cell types. The release of some IL-8 by neutrophils could lead to local positive feedback in neutrophil recruitment and associated endothelial injury.

Aged↗
PubMed1997

Clinical spectrum of X-linked hyper-IgM syndrome.

We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.

Bone Marrow Transplantation↗
PubMed1996

Effects of inhibition of complement activation using recombinant soluble complement receptor 1 on neutrophil CD11b/CD18 and L-selectin expression and release of interleukin-8 and elastase in simulated cardiopulmonary bypass.

The inflammatory response to cardiopulmonary bypass includes activation of complement and induction of several neutrophil activation pathways. A recombinant soluble form of complement receptor 1 was used as a specific inhibitor of complement activation in simulated cardiopulmonary bypass circuits. Substantial complement activation was observed in these circuits with progressive accumulation of both plasma C3a and terminal complement complex. Soluble complement receptor 1 resulted in a significant reduction in C3a levels (p < 0.01) but did not inhibit terminal complement complex generation. A marked rise in neutrophil CD11b/CD18 expression, simultaneous loss of L-selectin expression, and a progressive accumulation of plasma elastase-alpha 1-antitrypsin occurred and were not affected by soluble complement receptor. However, generation of interleukin-8 in the circuits was inhibited (p < 0.05) by pretreatment with soluble complement receptor. These data suggest that changes in neutrophil activation seen during cardiopulmonary bypass may not be induced directly by anaphylatoxin generation.

CD11 Antigens↗
PubMed1996

CD40 ligand deficiency presenting as unresponsive neutropenia.

A male child presented with recurrent respiratory infections, otitis media, and oral ulceration and was found to be neutropenic. Investigations showed hypogammaglobulinaemia with normal serum IgM and a novel deletion in the gene for CD40 ligand on his X chromosome. Intravenous gammaglobulin did not lead to resolution of his neutropenia; G-CSF was also necessary.

Agammaglobulinemia↗
PubMed1996

Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae type b vaccines for primary immunisation.

A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody response and adverse events associated with immunisation. Adverse events, including fever, were recorded by parents in a diary for three days following each injection. Blood was taken before the first immunisation and four weeks after the third immunisation to assess antibody response. Data were compared with those from historical controls who had received DTP and PRP-T vaccines by separate injection. The combined vaccine was well tolerated. Rates of local and general reactions were similar to those reported for infants immunised by separate injection. All infants achieved protective antibody titres (> 0.01 IU/ml) for diphtheria and tetanus; 98% acquired Hib (PRP) antibody > 0.15 microgram/ml and 82.5% > 1.0 microgram/ml. Pertussis antibody titres (pertussis toxin, filamentous haemagglutinin, total agglutinins, and agglutinins 2 and 3) showed appreciable rise following immunisation. DTP and PRP-T vaccines provide similar antibody responses and adverse effects whether mixed in the same syringe or administered by separate injection. The vaccines could be combined for use in the United Kingdom primary immunisation schedule.

Antibody Formation↗
PubMed1995

Neutrophil adhesion molecules in term and premature infants: normal or enhanced leucocyte integrins but defective L-selectin expression and shedding.

The functional deficits of neonatal neutrophils are well documented and are thought to contribute to the increased susceptibility of newborn infants to infection. We measured the adhesion molecules L-selectin, CD11a/CD18 and CD11b/CD18 on neutrophils from the cord blood of term (n = 22) and premature (n = 32) infants using a whole blood method with flow cytometry and quantitative bead standards to enumerate cell surface receptors. We also assayed plasma for the shed form of L-selectin (sL-selectin). Our results suggested that L-selectin expression on term infant neutrophils is lower than that on adult neutrophils (unstimulated and stimulated, both P < 0.001), but that stimulated premature infant cell express higher L-selectin than term infants (P < 0.05); it is possible that this deficiency is caused by physiological changes occurring around the normal time of parturition. We observed reduced sL-selectin in term infants (P < 0.001) compared with adults, and even lower concentrations in premature infants (P < 0.001). The sL-selectin concentrations in plasma may be a reflection of granulopoiesis, which may be reduced in premature infants. Our results showed increased resting neonatal neutrophil expression of CD11b/CD18 compared with adults, and the absence of any neonatal deficit of the ability to up-regulate CD11b/CD18 expression on stimulation. These findings are contrary to previous reports. Further studies suggested that the isolation procedures used in previous reports reduces the capability of the cells to respond to a formyl methionine leucine phenylalanine (fMLP) stimulus. This effect is more marked in neonatal neutrophils, suggesting that the previously reported deficiency is in fact due to the isolation techniques used rather than the cells' innate ability to up-regulate CD11b/CD18 expression. The results of our study lead us to propose that the adhesive function of neonatal neutrophils may be less defective than previously thought.

Adult↗
PubMed1994

Endotoxin-induced neutrophil adherence to endothelium: relationship to CD11b/CD18 and L-selectin expression and matrix disruption.

The injury to vascular endothelium seen in severe bacterial infection may be mediated by neutrophil-derived enzymes. Neutrophil adhesion to endothelium, a prerequisite for this process, is mediated sequentially by the leukocyte adhesion molecules L-selectin and the beta 2 integrins, including CD11b/CD18. We have explored the relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury, as assessed in vitro by changes to HS and FN matrices that colocalize. Endothelial prestimulation with LPS (endotoxin) caused an increase in adherence and an inversely proportional disruption in the HS matrix; disruption of the FN matrix only occurred on the further addition of fMLP. Although maximal changes in these matrices were associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. CD11b/CD18 expression was similar in both adherent and nonadherent neutrophils, while L-selectin was shed in association with adherence in the absence of other stimuli. These changes in expression were thus independently regulated. This model may provide further insights into the interrelationship between neutrophil adhesion and activation and endothelial damage in infection with gram-negative bacteria.

Antigens, CD↗
PubMed1994

Polymorphonuclear granulocyte expression of CD11a/CD18, CD11b/CD18 and L-selectin in normal individuals.

In this study direct immunofluorescence and flow cytometry with calibration using quantitative bead standards were used to enumerate the cell surface receptors CD11a/CD18, CD11b/CD18 and L-selectin. Holding blood at room temperature and fixation of samples prior to staining induced changes in expression, while immediate staining of polymorphonuclear granulocytes (PMN) in whole blood followed by fixation produced accurate values. The ranges of PMN adhesion molecule expression in 10 normal individuals were CD11a/CD18: 14794-28725, CD11b/CD18: 5300-11939 and L-selectin: 35662-61654 receptors per cell. Differences within individuals over 4 h were also observed. Adhesion molecule expression is used as an index of the adhesive function and state of activation of the cell. The data presented here shows that there is inherent variability in the expression of the PMN adhesion molecules between and within individuals, thus direct comparisons of PMN adhesion molecule expression between patients and "normals" must be interpreted with caution.

Antigens, CD↗
PubMed1993

Changes in neutrophil CD11b/CD18 and L-selectin expression and release of interleukin 8 and elastase in paediatric cardiopulmonary bypass.

Children undergoing cardiopulmonary bypass (CPB) surgery for congenital heart defects develop an acute post-operative capillary leak which may be due to endothelial injury inflicted by adherent neutrophils (PMN). Direct immunofluorescence and flow cytometry were used to measure CD11a/CD18, CD11b/CD18 and L-selectin (L-s) expression on circulating PMN in CPB circuits containing human blood and in children undergoing CPB. In vitro, a general rise in CD11b/CD18 expression over 2 h contrasted with complete loss of L-s in a small but progressively increasing proportion of PMN. Marked but inconsistent changes in CD11b/CD18 and L-s were observed in vivo, in conjunction with fluctuations in circulating PMN count. Circulating IL-8 was detected starting at rewarming from hypothermia and reperfusion of the heart and lungs with a simultaneous, closely correlated rise in both PMN count and circulating elastase. IL-1 and TNF were not detected. These studies demonstrate changes in the pathways of PMN-endothelial interaction during and after CPB.

Antigens, CD↗
PubMed1993

Degradation of glycosaminoglycans and fibronectin on endotoxin-stimulated endothelium by adherent neutrophils: relationship to CD11b/CD18 and L-selectin expression.

Vascular endothelial injury observed in overwhelming sepsis may be caused by neutrophil-derived enzymes. Adherence to the endothelium, a prerequisite for this process, is mediated sequentially by the neutrophil adhesion molecules L-selectin and the beta 2 integrins including CD11b/CD18. The relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury was assessed by changes in heparan sulfate and fibronectin matrices. Endothelial prestimulation with lipopolysaccharide caused both an increase in adherence and a generalized reduction in heparan sulfate; disruption of the fibronectin matrix occurred only on the further addition of FMLP. Although maximal disruption of these matrices was associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. This model may provide further insights into the interrelationship between neutrophil activation and endothelial damage in gram-negative sepsis.

Antigens, CD↗