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Biomedical subjects

J Brom

Publications and source records attributed to J Brom.

At least 19 recordsLinked to original sources
PubMed2001

Influence of low molecular weight heparin (certoparin) and unfractionated heparin on the release of cytokines from human leukocytes.

We analyzed the influence of heparins (unfractionated heparin, UFH and low molecular weight heparin certoparin) on the generation of IL-1ra, IL-6, IL-10, and IL-12p40 and from leukocyte fractions in vitro. Polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from 16 different healthy donors were isolated and adjusted to 1 x 10(6) cells/ml supplemented RPMI 1640. Leukocyte fractions were differentially stimulated (PMN with 1 microg and 5 microg LPS, PBMC with 10 ng TSST- 1 or 2 microg ConA) in the presence or absence of heparins (1 U/ml, 2 U/ml, and 4 U/ml) for 24 h at 37 degrees C. Cytokine release was analyzed by ELISA. Certoparin but not UFH led to a dose-dependent increase in IL-6 from non-stimulated PBMC. In contrast, the release of IL-1ra, IL-10, and IL-12p40 was not modulated by heparins in a dose-dependent fashion. Increases in these cytokines occurred only as single incidents at intermediate heparin levels. An influence of the heparins on the apoptosis of PMN (measured as DNA-fragmentation in non-stimulated or LPS-stimulated cell-fractions) was not observed.

Cytokines↗
PubMed2001

Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the TOPAS trial. Therapy of Patients With Acute Stroke (TOPAS) Investigators.

BACKGROUND AND PURPOSE: To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]). METHODS: We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti-factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index >/=90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration. RESULTS: The proportion of patients with Barthel Index >/=90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed. CONCLUSIONS: Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.

Adolescent↗
PubMed2000

Prior cytomegalovirus, Chlamydia pneumoniae or Helicobacter pylori infection and the risk of restenosis after percutaneous transluminal coronary angioplasty.

We investigated a possible correlation between the serologic status concerning Cytomegalovirus (CMV), Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) and the occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty for symptomatic coronary artery disease. Tests for anti-CMV IgG, anti-Chlamydia pneumoniae IgG and IgA and HP IgG and IgA were performed with an enzyme-linked immunosorbent assay (ELISA). Restenosis was defined as >/=50% stenosis at follow-up angiography in a vessel with less than 50% stenosis immediately after PTCA. Of 148 patients, 112 (75.7%) were seropositive for CMV, 75 (50.7%) were seropositive for CP and 78 (52.7%) were seropositive for HP. Restenosis occured in 31.8% of patients. CMV seropositivity was established in 74.5% of patients with restenosis versus 76.2% without restenosis (P=0.82), CP seropositivity was established in 44. 7% of patients with restenosis versus 53.5% without restenosis (P=0. 32), HP seropositivity was established in 53.2% of patients with restenosis versus 52.5% without restenosis (P=0.94). In contrast to some earlier studies CMV or HP seropositivity could not be found to be associated with the risk of restenosis after coronary intervention. An association between the serological status of CP and restenosis could also not be established.

Angioplasty, Balloon, Coronary↗
PubMed1997

Effects of octreotide treatment on restenosis after coronary angioplasty: results of the VERAS study. VErringerung der Restenoserate nach Angioplastie durch ein Somatostatin-analogon.

BACKGROUND: The VERAS study (VErringerung der Restenoserate nach Angioplastie durch ein Somatostatin-analogon [Prevention of Restenosis Following Angioplasty With a Somatostatin Analogue]) was a placebo-controlled trial to evaluate the effects of octreotide for the prevention of restenosis after coronary angioplasty. Octreotide is a somatostatin analogue with antiproliferative properties on smooth muscle cell growth in vitro that limits myointimal thickening of arteries in balloon injury models. METHODS AND RESULTS: Patients received either octreotide or placebo, starting 1 hour before angioplasty and continued for 3 weeks. The minimal luminal diameters before and after angioplasty and at 6-month follow-up were analyzed with a digital quantitative algorithm. Of the initial 274 patients recruited, 217 (108 in the octreotide group and 109 in the placebo group) could be analyzed after a complete 6-month evaluation: the minimal luminal diameters were 1.67+/-0.57 mm in the octreotide-treated group and 1.66+/-0.64 mm in the placebo group (two-paired P=.70), and the relative losses were 0.16+/-0.22 and 0.13+/-0.21 (two-paired P=.27). The restenosis rates were also identical in both treatment groups: final diameter stenosis > or =50% (34.3% versus 33.9%, two-paired P=1.0), loss of > or =50% of the initial gain (34.3% versus 33.9%, two-paired P=1.0), and absolute reduction of minimal luminal diameter >0.72 mm (29.6% versus 24.8%, two-paired P=.45). Likewise, there was no difference with regard to the incidence of clinical events (death, myocardial infarction, bypass operations, reintervention). Octreotide was well tolerated, with the exception of gastrointestinal side effects, which were three times more common than in the placebo group. CONCLUSIONS: Octreotide did not reduce the angiographically determined restenosis rate or the incidence of major clinical events after coronary angioplasty.

Adult↗
PubMed1995

Expression of the adhesion molecule CD11b and polymerization of actin by polymorphonuclear granulocytes of patients endangered by sepsis.

The integrin CD11b is an important adhesion molecule mediating the transendothelial migration of circulating polymorphonuclear granulocytes into an inflammatory region. The expression of CD11b is closely related to the ability to polymerize actin, a major component of the cytoskeleton within the phagocyte. In this study we compared the CD11b expression as well as the polymerization of actin of isolated neutrophils from patients endangered by sepsis with cells from healthy donors. The patient population was subdivided into a group of patients with severe thermal injuries and a group of patients who were admitted to an intensive care unit on suspicion of sepsis. The following results were obtained: (1) cells from burn patients, but not from non-burn patients, showed a reduced basal expression of CD11b during the first week after the burn trauma; (2) stimulation with the chemotactic peptide formyl-Met-Leu-Phe (FMLP) led to a strong overexpression of CD11b on the cells from the burn patients, this effect was not observed using cells of the second subgroup; (3) the content of polymerized actin was reduced within resting and stimulated cells from burn patients during the first 2 weeks postinjury, non-burn patient cells showed an enhanced F-actin content within the first week; (4) the ability of burn and non-burn patient cells to polymerize actin after stimulation with FMLP was slightly impaired during the first week post injury/admission. The results demonstrate that cells from patients endangered by sepsis show dysfunctions on the level of adhesion molecule expression and the strongly related actin polymerization.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1993

GTP-binding proteins in polymorphonuclear granulocytes of severely burned patients.

In order to study the biochemical mechanism underlying the cellular dysfunctions of polymorphonuclear granulocytes (PMNs) from severely burned patients, we analyzed the role of GTP-binding proteins (G-proteins) in PMNs from 11 burned patients. Our data demonstrate a significant enhancement of the basal GTPase activity within unstimulated neutrophils of severely burned patients compared to cells from healthy donors. This enhancement was significant within 4 weeks after the trauma, followed by a return to control levels. The increase in GTPase activity correlated with enhanced expression of the small G-protein Ras and the regulatory Ras-GTPase activating protein (Ras-GAP) compared to that in healthy donor cells. However, expression of the Ras-related protein Rap1, which is involved in initiation of the respiratory burst, was reduced. The observed changes in G-protein activity and expression impair the signal transduction cascade as well as bacterial killing and may lead to high susceptibility toward infections and finally to septic conditions.

Adult↗
PubMed1992

Cytokine-induced (interleukins-3, -6 and -8 and tumour necrosis factor-beta) activation and deactivation of human neutrophils.

The effect of various cytokines [interleukin-3(IL-3), IL-6, IL-8, tumour necrosis factor-beta (TNF-beta)] on human neutrophils (PMN) was analysed with regard to the generation of leukotrienes and the involvement of guanosine triphosphate (GTP)-binding proteins (G proteins). Incubation of cytochalasin B-pretreated PMN with cytokines alone did not lead to a generation of leukotrienes. However, the cytokines affected the formyl-methionyl-leucyl-phenylalanine-(FMLP)-induced formation of leukotrienes in a time-dependent manner. Preincubation of the cells with the different cytokines for short periods (15 seconds at 37 degrees) enhanced the subsequent FMLP-induced leukotriene generation, whereas preincubation for prolonged times resulted in a reduced formation of leukotrienes. These results correlated with the respective G protein-associated guanosine triphosphatase (GTPase) activities within isolated membrane fractions. The present study indicates a modulation of the FMLP-induced leukotriene formation by diverse cytokines via interaction with the GTP-binding proteins.

Cells, Cultured↗
PubMed1992

Priming mechanisms and induction of heat shock proteins in human polymorphonuclear granulocytes induced by eicosanoids and cytokines.

Priming of human polymorphonuclear granulocytes (PMNs) with cytokines (IL-3, IL-6, TNF-alpha) followed by a subsequent stimulation (FMLP) led to an enhanced polymerization of actin and GTPase-activity which correlated to a loss of ras immunoreactivity and an increased expression of Rab proteins. Furthermore TNF-alpha and 12-HETE induced the heat shock proteins (hsp 70 family) in PMNs as was demonstrated by metabolic radiolabeling and Western blotting (anti-hsp 72). This activation of the stress response exerted a protective function towards a subsequent lytic attack by a bacterial cytolysin (leukocidin).

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Neomycin induces stimulatory and inhibitory effects on leukotriene generation, guanine triphosphatase activity, and actin polymerization within human neutrophils.

The effects of neomycin on human neutrophils (PMN) were studied with respect to the generation of leukotrienes, the involvement of guanine triphosphate binding proteins (G proteins) and the polymerization of actin. Incubation of neutrophils with neomycin induced the generation of low amounts of leukotrienes. Co-incubation of neutrophils with neomycin and the direct G-protein activator sodium fluoride (NaF) resulted in an enhanced leukotriene formation at 0.5 mM neomycin and an inhibition at a concentration of 10 mM. Simultaneous incubation with neomycin and formyl-methionyl-leucyl-phenylalanine (FLMP) did not affect the FMLP-induced leukotriene formation. However, pretreatment of neutrophils with 10 mM neomycin followed by the addition of NaF or FMLP resulted in an enhanced generation of leukotrienes. Crude membrane fractions of PMN incubated with neomycin at different concentrations showed an enhanced (0.5 mM) as well as a reduced (10 mM) guanine triphosphatase activity. Furthermore, incubation of neutrophils with neomycin above a concentration of 0.5 mM led to the depolymerization of actin. The presented results show inhibitory and stimulatory effects of neomycin on various cell functions, which may reflect differences in transmembrane signalling.

Actins↗
PubMed1991

Basic mechanisms of cellular priming and release of inflammatory mediators.

Simultaneous stimulation of human neutrophils (PMN) with the receptor-mediated activator formyl-met-leu-phe (FMLP) and the G protein activator sodium fluoride (NaF) resulted in the synergistic generation of leukotrienes. Activation of human platelets with thrombin and NaF showed an additive formation of 12-HETE. This enhancement in lipid mediator generation correlated with a time-dependent synergism in G protein activation after sequential stimulation of intact cells with FMLP and NaF or thrombin and NaF, respectively. In addition, polymerization of actin, an early event in cell activation, was enhanced after incubation with cytokines and FMLP.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

G protein activation and mediator release from human neutrophils and platelets after stimulation with sodium fluoride and receptor-mediated stimuli.

Human polymorphonuclear granulocytes (PMN) and platelets were pre-activated with a receptor-mediated stimulus [formyl-methionyl-leucyl-phenylalanine (FMLP) or thrombin, respectively] and subsequently incubated with sodium fluoride (NaF). We investigated various cell responses, such as chemiluminescence by PMN, platelet aggregation and the release of lipid mediators [i.e. leukotriene B4 (LTB4) and its omega-oxidation products from neutrophils and 12-hydroxy-eicosatetraenoic acid (12-HETE) from platelets]. As a marker of G protein involvement, the binding of [3H]guanylylimidodiphosphate (Gpp (NH) p) to the membrane fractions of stimulated cells was determined. PMN pre-stimulated with FMLP showed a synergistically enhanced generation of leukotrienes returning to control values with the time of preincubation. Platelets preliminary treated with thrombin followed by incubation with NaF resulted in a sub-additive and time-independent mediator generation. Neither chemiluminescence by PMN nor platelet aggregation showed a similar pattern compared to the mediator release: PMN preincubated with FMLP followed by NaF resulted in a second chemiluminescence response; the aggregation of platelets which were preincubated with thrombin was partially inhibited by the addition of NaF. Membrane fractions isolated from FMLP-pre-stimulated neutrophils showed a pattern in [3H]Gpp (NH) p-binding capacity that was comparable to the respective leukotriene release. With thrombin-prestimulated platelets, no similarities between Gpp (NH) p binding, aggregation or 12-HETE generation were observed. The sequential activation of different cell populations using the same kind of stimulation lead to different cell responses, indicating the diversity of G proteins and their control mechanisms.

Blood Platelets↗
PubMed1991

Effect of interferon-alpha on neutrophil functions.

Incubation of neutrophils with interferon-alpha (IFN-alpha) for 5 min and subsequent stimulation with the calcium ionophore A23187 enhanced the production of oxygen radicals, while a suppression was obtained with FMLP-stimulated cells. Similar data were observed for the direct G-protein activator sodium fluoride (NaF). Incubation of the cells with IFN-alpha and subsequent stimulation with FMLP (in the presence of cytochalasin b) reduced the generation of the chemotactic active leukotriene B4 (LTB4). The metabolism of LTB4 was significantly inhibited. IFN-alpha decreased the specific binding sites for LTB4 and increased the number of binding sites for FMLP. The GTPase activity as a parameter for the activation of G-proteins was enhanced by IFN-alpha. Preincubation of the cells with IFN-alpha and subsequent stimulation with NaF increased the GTPase activity synergistically, whereas co-incubation of IFN-alpha with FMLP showed additive effects. Our results clearly demonstrate the modulatory effects of IFN-alpha on granulocyte functions with regard to the receptor-mediated signal transduction.

Cells, Cultured↗
PubMed1990

Influence of ciprofloxacin on leukotriene generation from various cells in vitro.

The effect of ciprofloxacin on leukotriene generation from human polymorphonuclear leucocytes (PMN) and the respective lymphocyte, monocyte and basophil (LMB) containing cell fraction has been studied. Furthermore, the influence on the LTB4-receptor expression of PMNL, as well as on the synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) from human platelets, was analysed. The antibiotic concentrations ranged from 0.5 to 4 micrograms/10(7) cells. Analysis of the generated leukotrienes was performed by high performance liquid chromatography (HPLC). The calcium-ionophore A23187 induced leukotriene generation from PMNs and LMBs was significantly suppressed by preincubation with ciprofloxacin in a dose-dependent manner. Incubation of PMNs with the same concentrations of ciprofloxacin induced an augmentation of the LTB4-receptor expression. Preincubation of human platelets led to a suppression of the calcium-ionophore induced 12-HETE generation at high concentrations (8 and 4 micrograms/10(8) cells) and to an increased synthesis of 12-HETE at lower concentrations (0.5, 1, and 2 micrograms ciprofloxacin/1 x 10(8) platelets).

Blood Cells↗