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Biomedical subjects

I Ott

Publications and source records attributed to I Ott.

At least 37 records · Page 2Linked to original sources

Changes in membrane glycoproteins of circulating platelets after coronary stent implantation.

OBJECTIVES: To evaluate platelet function in patients with coronary stents. DESIGN: A non-randomised control trial in 30 patients who had immediate implantation of Palmaz-Schatz coronary stents because of a suboptimal angioplasty result. All patients received a standardised anticoagulation regimen including intravenous heparin (activated partial thromboplastin time (APTT) 80 to 120 s), oral vitamin K antagonist (target international normalised ratio (INR) of 3.5), and 100 mg aspirin twice daily. Platelet surface expression of glycoprotein IIb-IIIa, activated fibrinogen receptor, and P-selectin as well as binding of von Willebrand factor and fibrinogen were determined by flow cytometry in peripheral venous blood samples collected before the intervention and then daily for 4 days after it. The results were compared with those in 30 patients undergoing elective coronary balloon angioplasty. SETTING: University hospital. RESULTS: After coronary stenting surface expression of the activated fibrinogen receptor significantly increased, peaking at day 2 (P < 0.001). Similar results were found for von Willebrand factor binding and P-selectin surface expression, with a maximum at day 2 to 4 after stenting (von Willebrand factor, P < 0.001; P-selectin, P < 0.001). The changes in platelet membrane glycoproteins coincided with a significant drop in peripheral platelet count after stent placement (P < 0.01). No significant change in fibrinogen receptor activity, von Willebrand factor binding, P-selectin surface expression, or platelet count was seen in the control group. CONCLUSIONS: The present study shows that current anticoagulation treatment is inefficient in suppressing platelet activation in patients with coronary stents and, therefore, might not be the best treatment for reducing the incidence of subacute stent thrombosis.

Adult↗

Agglutination of isolated platelet membranes.

Platelet membrane glycoproteins play a central role in platelet aggregation and thus in primary hemostasis. To investigate mechanisms of platelet-platelet interaction in the absence of cellular activation events, we studied immunological and functional aspects of isolated platelet membranes. Platelet membranes contained significant amounts of the inducible fibrinogen receptor, glycoprotein (GP) IIb-IIIa, which exposes conformation-dependent LIBS1 and PMI-1 epitopes in response to fibrinogen-mimetic peptides GRGDSP and HHLG-GAKQAGDV. In the presence of soluble fibrinogen, membrane-coated latex beads showed Ca(2+)-dependent agglutination that could be partially inhibited by GRGDSP but not by the biologically inactive peptide GRGESP. Thrombospondin enhanced agglutination of membrane-coated beads, which could be inhibited by polyvalent anti-thrombospondin Fab fragments and anti-thrombospondin monoclonal antibody MA-II. Mg2+ inhibited both GPIIb-IIIa- and thrombospondin-mediated agglutination of membranes in a dose-dependent manner. The results of the present study indicate that isolated platelet membranes are a useful tool to study regulation of GPIIb-IIIa- and thrombospondin-mediated platelet-platelet interaction.

Agglutination↗

Cardiac release of cytokines and inflammatory responses in acute myocardial infarction.

BACKGROUND: In animal models of myocardial infarction (MI), inflammatory responses compromise microcirculation during reperfusion and restrict functional recovery. To investigate cardiac inflammatory responses in patients with acute MI, we examined the cardiac release of cytokines, the expression on neutrophils of the beta 2-integrin Mac-1 (CD11b/CD18) and L-selectin (CD62L), and the cardiac release of thrombomodulin as a marker of endothelial injury. METHODS AND RESULTS: In 12 patients with acute anterior MI, blood samples were obtained from the coronary sinus and from the aorta immediately before and after recanalization of the coronary occlusion by balloon angioplasty. Twelve patients undergoing elective balloon angioplasty served as control subjects. Plasma concentrations of interleukin (IL)-1 beta, IL-6, IL-8, tumor necrosis factor-alpha, and thrombomodulin were determined by immunoassay, and surface expression of CD11b and CD62L was assessed by flow cytometry. Differences in coronary sinus and arterial blood were found in IL-6 before (median, 6.3 ng/L, P = .01) and after (13.4 ng/L, P = .002) recanalization and in IL-8 after recanalization (10.7 ng/L, P = .02). The cardiac release of both cytokines significantly (P < or = .03) increased with reperfusion. Cytokine release after reperfusion was associated with significant transcardiac gradients in surface expression on neutrophils of CD11b (10.1 mean channel of fluorescence intensity [mean fl], P = .01) and CD62L (-87 mean fl, P = .007) and with a thrombomodulin release (4.5 micrograms/L, P = .004). Transcardiac gradients in IL-1 beta and tumor necrosis factor-alpha were not found. None of the changes found in MI were detectable in the control group. CONCLUSIONS: As evidence of cardiac inflammatory responses in reperfused acute MI, the study demonstrates cardiac neutrophil activation with signs of endothelial injury and a release of the proinflammatory cytokines IL-8 and IL-6. These findings may assist in the design of pharmacological interventions aimed at reducing microvascular reperfusion injury.

Adult↗

Neutrophil hyper-reactivity after exercise-induced angina pectoris.

BACKGROUND: Previous studies have suggested an increased risk of myocardial infarction associated with physical exercise. Activated neutrophils may contribute to the triggering mechanisms. METHODS: Fifteen patients with stable angina pectoris underwent symptom-limited bicycle ergometry. In neutrophils obtained from serial blood samples, superoxide anion production (SOP) was determined by superoxide dismutase-inhibited reduction of cytochrome C and chemotactic mobility in the microchemotaxis chamber. The same ergometry was repeated after successful balloon angioplasty [percutaneous transluminal coronary angioplasty (PTCA)]. RESULTS: Rate-pressure products and systemic lactate concentrations were similar in both ergometries. Angina was induced in all exercise tests before PTCA, but in none after PTCA. Before the ergometries, systemic neutrophil counts, SOP and chemotactic mobility were essentially the same. Compared with baseline, exercise-induced angina immediately after the first ergometry was associated with an increase in neutrophil count by 0.8 +/- 0.1 nl-7 (P < 0.01), an increase in N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated SOP by 2.44 +/- 0.49 nmol/15 min/5000 cells (P < 0.01) and an increase in chemotaxis by 10.28 +/- 1.65 cells per vision field (P < 0.01). In the ergometry after PTCA this increase in SOP and in chemotaxis disappeared (0.26 +/- 0.39 nmol/15 min/5000 cells and 2.15 +/- 1.52 cells per vision field; NS), whereas the increase in neutrophil count was not significantly different from that in the ergometry before PTCA. CONCLUSION: This study reveals that neutrophil hyper-reactivity after exercise-induced angina can be attributed to myocardial ischaemia.

Aged↗

Comparison of 6 different reoviruses of various reptiles.

In the last years the number of reports on virus isolations from reptiles have increased. The relationship of reptilian viruses to mammalian and avian viruses has not been fully investigated to date. In this paper 6 reptilian reoviruses have been examined and compared with avian and mammalian reoviruses with respect to serological and physicochemical properties. Differences and similarities are described.

Animals↗

Release of chemoattractants and neutrophil activation in acute myocardial infarction immediately after successful recanalization of the infarct-related vessel by angioplasty.

The study investigated inflammatory responses in evolving myocardial infarction. Fifteen patients with acute myocardial infarction, who had undergone balloon recanalization of the infarct-related coronary artery within 4 h after onset of symptoms, were examined. Blood samples were obtained through the guiding catheter and from the pulmonary artery before and immediately after successful recanalization. After recanalization, plasma from the pulmonary artery was 47% (quartiles: 19%, 78%; P = 0.001) more chemotactic to neutrophils from normal donors than before recanalization. Furthermore, significant changes in neutrophil function were found in the pulmonary artery. Compared to the values before recanalization, the nitroblue tetrazolium score rose by 31% (quartiles: 4%, 37%; P = 0.003), FMLP-stimulated superoxide anion production by 10% (quartiles: 0%, 39%; P = 0.020), and chemotaxis by 46% (quartiles: 0%, 81%; P = 0.011), while neutrophil filterability decreased by 28% (quartiles: 15%, 47%; P = 0.010). No significant changes in neutrophil parameters were found in the arterial blood. The study indicates that chemoattractants are released in the early reperfusion period of evolving myocardial infarction. These chemoattractants may act as inflammatory mediators causing neutrophil activation.

Aged↗

Temporal organisation of action in baboons: comparisons with the temporal segmentation in chimpanzee and human behaviour.

The durations of sequences of functionally related movements, or action units, were analysed in the baboons Papio hamadryas and Papio anubis. Action units are completed within a narrow time span or temporal segment as found previously in pongids and humans. Although the temporal segmentation is generally similar in the three species, baboons show several differences from both chimpanzees and humans. Firstly, their temporal segments are shorter and less variable and the different sorts of action units, such as hand-body contact or interactions with an object, show slight but significant differences in duration. Secondly, those action units that consist of movements occurring twice last almost twice as long as action units without repetitions. In contrast, in chimpanzees and humans, repetition of a set of movements compresses the first set so that the action unit duration does not increase. This is thought to be due to a form of presyntactical motor planning. Its absence in baboons shows that presyntactical motor planning is confined to those primates with language ability and so provides further support for a relationship between motor and language systems.

Animals↗

Effects of magnesium on platelet aggregation and adhesion. Magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo.

Magnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+ (4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p < 0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p < 0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.

Bleeding Time↗

Cardiac release of chemoattractants after ischaemia induced by coronary balloon angioplasty.

OBJECTIVE: To investigate the release of chemoattractants after myocardial ischaemia during balloon angioplasty. DESIGN: Sampling of femoral arterial and coronary sinus blood before and immediately after the first balloon inflation during angioplasty. In a study group of 16 patients the balloon was kept expanded for two minutes, whereas in a control group of eight patients the first balloon inflation was brief (< 10 s). MAIN OUTCOME MEASURES: Chemotaxis of neutrophils from healthy donors towards patient plasma (Boyden chamber), superoxide anion production by normal neutrophils after incubation with patient plasma (cytochrome C reduction). RESULTS: In the study group, coronary sinus plasma after balloon deflation was more chemoattractive to normal neutrophils (median relative increase 24% (quartiles: 4%, 45%), p = 0.008) and induced a higher superoxide anion production in normal neutrophils (44% (10%, 97%), p = 0.013) than arterial plasma. Concomitantly, the degree of activation of patient neutrophils was increased in coronary sinus blood compared with arterial blood, as shown by an increased proportion of neutrophils reducing nitro-blue tetrazolium (21% (9%, 38%), p = 0.006) and a decreased neutrophil filter-ability (-16%(-3%, -40%), p = 0.003) in coronary sinus blood. In the study group before balloon inflation and in the control group before and after balloon inflation differences between arterial and coronary sinus blood were not significant. Signs of ischaemia (lactate release, ST segment changes) were only detected in the study group. CONCLUSION: After transient myocardial ischaemia during balloon angioplasty there is a local release of chemoattractants, associated with neutrophil activation.

Angioplasty, Balloon, Coronary↗

Effects of adenosine on histamine release from human lung fragments.

The actions of adenosine on histamine release of human lung fragments were investigated. Histamine release was stimulated either with the calcium ionophore A23187 or with concanavalin A. Adenosine and its analogue 5'-N-ethylcarboxamidoadenosine alone had no significant effect on basal release or on the release elicited by A 23187 or concanavalin A. However, in the presence of the adenosine receptor antagonist 8-[4-[[[[(2-aminoethyl)amino]-carbonyl]methyloxy]-phenyl]-1, 3-dipropylxanthine (XAC), which itself did not affect the release, adenosine increased the stimulated histamine release. On the other hand, in the presence of the nucleoside transport inhibitor S-(p-nitrobenzyl)-6-thioinosine (NBTI), adenosine caused a reduction in stimulated histamine release. NBTI itself caused a stimulation of release. Thus, a stimulatory effect of adenosine was seen in the presence of XAC, whereas an inhibitory effect was unmasked by NBTI. From these data it is concluded that adenosine exerts two opposing effects on histamine release in the human lung which neutralize each other: it inhibits release via a site antagonized by XAC, which presumably represents an A2 adenosine receptor, and it stimulates release via a mechanism that is blocked by NBTI, suggesting that adenosine needs to reach the interior of cells to exert this effect. The slight stimulatory effect of NBTI alone demonstrates that trapping intracellularly formed adenosine inside mast cells leads to sufficient concentrations of adenosine to stimulate histamine release. These findings suggest an important bimodal role of adenosine in regulating histamine release in the human lung.

Adenosine↗

Effect of gallopamil on neutrophil function: experimental and clinical studies.

The purpose of the study was to investigate whether gallopamil interferes with neutrophil activation. In vitro, gallopamil caused a dose-dependent reduction in phorbol myristate acetate-stimulated superoxide anion production by neutrophils as measured by the superoxide dismutase inhibited reduction of cytochrome C [concentration of 50% inhibition (IC50) = 9.5 x 10(-6) mol/L]. Furthermore, gallopamil reduced the platelet-activating factor-induced loss of neutrophil deformation, which was assessed by filtrometry (IC50 = 4.3 x 10(-6) mol/L). The effect of gallopamil was assessed in 24 patients during elective balloon angioplasty. Gallopamil (0.4 mg) or placebo (double-blind conditions) was administered by intracoronary application during the 10-min interval between the first two balloon inflations. In the placebo group, blood samples obtained simultaneously from the coronary sinus and from the femoral artery revealed an increase in the proportion of activated neutrophils in the coronary sinus blood after the second balloon inflation [nitro blue tetrazolium (NBT) score, NBT test: 15 +/- 9% relative coronary sinus and arterial blood difference, p < 0.05]; these changes in NBT score were similar to those after the first balloon inflation. In the gallopamil-treated group, however, significant arterial and coronary sinus blood differences in NBT scores were not found after the second balloon inflation. Gallopamil may, thus, attenuate the local neutrophil activation during balloon angioplasty.

Angioplasty, Balloon, Coronary↗

Selective quantitative determination of tobramycin from fermentation broth.

A derivative of Rhizobium meliloti 41 was constructed (strain GY654) which was resistant to apramycin and kanamycin but remained sensitive to tobramycin. Strain GY654 selectively measures tobramycin and 6"-O-carbamoyltobramycin in the presence of apramycin, kanamycin and 6"-O-carbamoylkanamycin B, therefore it is suitable for the rapid quantitation of 6"-O-carbamoyltobramycin and tobramycin in fermentation broths of Streptomyces tenebrarius and solvents containing antibiotic mixtures.

Biological Assay↗

Tn5 carries a streptomycin resistance determinant downstream from the kanamycin resistance gene.

In Rhizobium meliloti, Tn5 conferred resistance not only to kanamycin but to streptomycin, as well, in Escherichia coli, however only to kanamycin. Using in vitro recombinant DNA techniques, it was shown that the streptomycin resistance determinant was located downstream from the kanamycin resistance gene in the unique central region of Tn5. Expression of various cloned fragments of Tn5 suggested that both kanamycin and streptomycin resistance genes were transcribed from the same promoter. E. coli mutants allowing the expression of streptomycin resistance from Tn5 were isolated. The differential expression of the streptomycin resistance gene provides a simple selection/counterselection criterion, using only streptomycin in transfer experiments of Tn5 between E. coli and R. meliloti.

Chromosome Mapping↗