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F Petersen

Publications and source records attributed to F Petersen.

At least 19 recordsLinked to original sources
PubMed2002

Dosimetry inside MIR station using a silicon detector telescope (DOSTEL).

The dosimetry telescope (DOSTEL) was flown on the MIR orbital station during October 1997-January 1998. The mission average contributions to the absorbed dose rates (in water) were 126 +/- 4 microGy/d and 121 +/- 13 microGy/d for the GCR and the SAA component, respectively. The mean quality factors (ICRP60) deduced from the LET-spectra are 3.5 +/- 0.2 (GCR) and 1.3 +/- 0.1 (SAA). Separate LET spectra and temporal variations of the absorbed dose rates and of the mean quality factors are presented for these two radiation components as well as for solar energetic particles of the November 6, 1997 event.

Alpha Particles↗
PubMed2001

The utility of the VCS clip for creation of vascular access for hemodialysis: long-term results and intraoperative benefits.

UNLABELLED: The purpose of this study was to compare the effectiveness of the VCS vascular clip approximating system for the creation of hemodialysis access fistulas. 173 new vascular accesses were created, 92 prosthetic grafts and 81 autologous fistulas over a 40-month period. 50 sutured and 42 clipped fistulas comprised the prosthetic graft series, and 33 sutured and 48 clipped cases the autologous series. Risk factors associated with access patency were correlated and the primary patencies compared in the suture versus clipped group. A significant improvement in primary patency was noted for the clipped prosthetic group at all time points studied, with a positive trend also noted for clipped autologous fistulae. CONCLUSIONS: The vascular clipping system (the VCS system) provides both long-term and immediate advantages for vascular access construction. Clips have been used successfully to treat seven consecutive patients with upper extremity arterial steal syndrome without the technical difficulties associated with traditional methods of repair.

Adult↗
PubMed2000

The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages.

Unstimulated monocytes rapidly undergo physiological changes resulting in programmed cell death (apoptosis) while stimuli promoting differentiation of these cells into macrophages were shown to inhibit apoptotic processes. In the present study, we report that the platelet-derived alpha-chemokine platelet factor 4 (PF4) induces the differentiation of monocytes into macrophages, as is evident from morphological changes as well as from the up-regulation of differentiation markers (carboxypeptidase M/MAX1 and CD71). Significant alterations of the phenotype were observed after 72 hours of culture in the presence of the chemokine and required a minimal concentration of 625 nmol/L PF4. PF4-induced macrophages were characterized by a lack of HLA-DR antigen on their surface but showed a strong increase in the expression of the CD28 ligand B7-2. Furthermore, PF4 stimulation prevented monocytes from undergoing spontaneous apoptosis during 72 hours of culture as determined in an annexin-V-binding assay. Although PF4 induced the secretion of relevant amounts of TNF-alpha, neutralizing antibodies directed against TNF-alpha or granulocyte-macrophage colony-stimulating factor (GM-CSF) did not revert PF4-induced rescue from programmed cell death, suggesting that PF4 exerts its antiapoptotic effects in a TNF-alpha- or GM-CSF-independent fashion. On the basis of these results, we propose a novel role for PF4 in the control of monocyte differentiation during an inflammatory process in vivo. (Blood. 2000;95:1158-1166)

Antibodies, Monoclonal↗
PubMed2000

The beta-thromboglobulins and platelet factor 4: blood platelet-derived CXC chemokines with divergent roles in early neutrophil regulation.

The recruitment of neutrophil granulocytes to sites of tissue injury is one of the earliest events during host defense. Several chemotactic cytokines belonging to the CXC subfamily of chemokines are thought to be implicated in this kind of response. Especially those CXC chemokines that are stored in blood platelets and become immediately released upon activation are likely to dominate neutrophil-dependent host defense at the onset of inflammation. The major platelet-derived CXC chemokines are the beta-thromboglobulins and platelet factor 4 (PF-4), which are both released into the blood at micromolar concentrations. The availability as well as the functional activity of these mediators appear to be subject to tight control by diverse regulatory mechanisms. These include proteolytic processing of chemokine precursors, oligomer formation, and the differential usage of neutrophil-expressed receptors. Herein we review our work on early neutrophil regulation by PF-4, the beta-thromboglobulin neutrophil-activating peptide 2 (NAP-2) and its major precursor connective tissue-activating peptide III (CTAP-III). We moreover propose a model to assess the contribution by either of these chemokines to coordinated recruitment and activation of neutrophils in response to acute tissue injury.

Amino Acid Sequence↗
PubMed2000

Platelet-derived CXC chemokines: old players in new games.

Although platelet factor 4 (PF-4) and the beta-thromboglobulin (beta-TG) proteins represent the first chemokines to be discovered, their functional roles in host defense became clear only recently. Residing in platelets as storage proteins and becoming released into the blood at very high concentrations, these mediators appear to fulfill different and complementary tasks as first-line mediators in the recruitment and activation of leukocytes, as well in the regulation of tissue repair. Whereas both proteins are structurally closely related members of the CXC chemokine subfamily, they are subject to quite dissimilar regulatory mechanisms controlling their generation and their spectrum of biological activities. Thus, proteolytic processing of inactive precursors plays a decisive role in whether the beta-TG proteins will act as stimulatory or inhibitory agents in neutrophil activation via the G protein-coupled receptors CXCR-1 and 2. PF-4, existing as a single molecular form, is largely resistant to proteolytic modification, but its interaction with an unusual receptor(s) on leukocytes (a proteoglycan) appears to depend on its oligomeric state. There is growing evidence that both chemokines may interfere with each other at various regulatory levels to promote coordinated cell activation. Moreover, recent findings suggest novel and unexpected activities for these chemokines, which may extend our view on early host defense.

Amino Acid Sequence↗
PubMed1999

Platelet factor 4-induced neutrophil-endothelial cell interaction: involvement of mechanisms and functional consequences different from those elicited by interleukin-8.

Platelet factor 4 (PF-4), a member of the CXC-subfamily of chemokines, is secreted in high amounts by activated platelets. In previous studies, we found that PF-4 specifically binds to human polymorphonuclear granulocytes (PMN), but requires tumor necrosis factor-alpha (TNF-alpha) as a costimulus for the induction of effector functions in suspended cells. In the present study, we have examined PF-4 in comparison with interleukin-8 (IL-8) for its ability to promote interaction of PMN with cultured endothelial cells (EC). We show here for the first time that PF-4 dose-dependently induces PMN to undergo extremely firm adhesion to EC as well as to exocytose secondary granule contents in the presence of these cells. Interestingly, costimulation by TNF-alpha was not required, indicating that EC could provide a corresponding signal(s). As evident from antibody blocking experiments, PF-4-induced adhesion involved PMN-expressed L-selectin as well as leukocyte function-associated molecule-1 (LFA-1), whereas IL-8 involved MAC-1. Because blocking antibodies to LFA-1 but not to L-selectin or MAC-1 abrogated PF-4-dependent marker exocytosis from PMN, the costimulatory signal provided by EC appears to be elicited through cell-cell contact via LFA-1. IL-8, inducing the upregulation of MAC-1, did not elicit marker exocytosis in contact with EC. Our results suggest a role for PF-4 in the promotion of PMN-EC interaction that is virtually different from that exhibited by other CXC-chemokines such as IL-8.

Cell Adhesion↗
PubMed1999

Characterization of a neutrophil cell surface glycosaminoglycan that mediates binding of platelet factor 4.

Platelet factor 4 (PF-4) is a platelet-derived alpha-chemokine that binds to and activates human neutrophils to undergo specific functions like exocytosis or adhesion. PF-4 binding has been shown to be independent of interleukin-8 receptors and could be inhibited by soluble chondroitin sulfate type glycosaminoglycans or by pretreatment of cells with chondroitinase ABC. Here we present evidence that surface-expressed neutrophil glycosaminoglycans are of chondroitin sulfate type and that this species binds to the tetrameric form of PF-4. The glycosaminoglycans consist of a single type of chain with an average molecular mass of approximately 23 kDa and are composed of approximately 85-90% chondroitin 4-sulfate disaccharide units type CSA (-->4GlcAbeta1-->3GalNAc(4-O-sulfate)beta1-->) and of approximately 10-15% di-O-sulfated disaccharide units. A major part of these di-O-sulfated disaccharide units are CSE units (-->4GlcAbeta1-->3GalNAc(4,6-O-sulfate)beta1-->). Binding studies revealed that the interaction of chondroitin sulfate with PF-4 required at least 20 monosaccharide units for significant binding. The di-O-sulfated disaccharide units in neutrophil glycosaminoglycans clearly promoted the affinity to PF-4, which showed a Kd approximately 0.8 microM, as the affinities of bovine cartilage chondroitin sulfate A, porcine skin dermatan sulfate, or bovine cartilage chondroitin sulfate C, all consisting exclusively of monosulfated disaccharide units, were found to be 3-5-fold lower. Taken together, our data indicate that chondroitin sulfate chains function as physiologically relevant binding sites for PF-4 on neutrophils and that the affinity of these chains for PF-4 is controlled by their degree of sulfation.

Animals↗
PubMed1999

Production of recombinant proteins in plant root exudates.

The large-scale production of recombinant proteins in plants is limited by relatively low yields and difficulties in extraction and purification. These problems were addressed by engineering tobacco plants to continuously secrete recombinant proteins from their roots into a simple hydroponic medium. Three heterologous proteins of diverse origins (green fluorescent protein of jellyfish, human placental alkaline phosphatase [SEAP], and bacterial xylanase) were produced using the root secretion method (rhizosecretion). Protein secretion was dependent on the presence of the endoplasmic reticulum signal peptide fused to the recombinant protein sequence. All three secreted proteins retained their biological activity and, as shown for SEAP, accumulated in much higher amounts in the medium than in the root tissue.

Alkaline Phosphatase↗
PubMed1999

Pre-emptive use of aerosolized ribavirin in the treatment of asymptomatic pediatric marrow transplant patients testing positive for RSV.

Respiratory syncytial virus is a common virus which frequently causes severe lower tract disease in immunocompromised patients. The mortality rate in bone marrow transplant patients with lower tract disease varies from 31% to 100%, depending upon the treatment used, time before initiation of treatment, and whether patients are pre- or post-engraftment. Therapy with inhaled ribavirin has been used with limited success in decreasing mortality rate. Because of concern about conversion from upper respiratory tract disease to lower respiratory tract disease, we conducted a pilot study using aerosolized ribavirin in asymptomatic RSV-positive patients. Patients had NP washes performed on a weekly basis during the RSV season, for the presence of RSV. If patients were positive, but asymptomatic, and could have their transplant postponed, they were treated with ribavirin until negative. Patients who could not be postponed received aerosolized ribavirin, and began transplant conditioning. During this study, we performed 145 nasal aspirations for RSV on 25 patients; 10 aspirates were positive in seven asymptomatic patients. All positive events were successfully treated with ribavirin, which cleared the RSV for a minimum of 3 weeks. No patients became symptomatic. Thus, we conclude that ribavirin can clear asymptomatic infections in immunocompromised pediatric transplant patients.

Adolescent↗
PubMed1999

The role of cytokines in monocyte apoptosis.

Survival or apoptosis, activation and differentiation, phagocytosis and antigen presentation, migration or participation in granuloma formation are features of freshly recruited blood-borne monocytes in the local environment. In this presentation we describe that human monocytes undergo spontaneous apoptosis in vitro which involves Fas/FasL interactions, and that proinflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha), interleukin-1beta and granulocyte-monocyte-colony-stimulating factor prevent spontaneous apoptosis. In vitro infection of purified monocytes with low numbers of Mycobacterium tuberculosis H37Rv prevents spontaneous apoptosis. The apoptosis-preventing effect is correlated to the release of TNFalpha and not due to phagocytosis per se. Furthermore, the minor subset of CD64-negative monocytes is found to be less susceptible to recall antigen-activated CD4-positive T cell-mediated apoptosis than CD64-positive monocytes. Finally, recent findings of our group indicate that the chemokine platelet factor 4 protects monocytes from spontaneous apoptosis and induces the differentiation of monocytes into macrophages. From these findings we conclude that monocyte recruitment, their survival, their differentiation and their functional activity at the site of inflammation are regulated by a cytokine network which needs to be further analyzed in order to design strategies for immune intervention.

Antibodies, Bacterial↗
PubMed1998

A chondroitin sulfate proteoglycan on human neutrophils specifically binds platelet factor 4 and is involved in cell activation.

Platelet factor 4 (PF-4), a member of the alpha-chemokine subfamily of cytokines, activates human neutrophils independently of intracellular free calcium mobilization or binding to IL-8R. In the present study, we have identified and partially characterized a receptor for PF-4 on human neutrophils, which displays weak cross-reactivity with the IFN-gamma-inducible protein 10, but not with other alpha-chemokines such as IL-8, neutrophil-activating peptide 2, or melanoma growth-stimulatory activity (GRO alpha). Binding studies revealed that human neutrophils express a high number of receptors (Bmax approximately 7.6 x 10(6) sites/cell) of moderate affinity (Kd approximately 650 nM). The kinetics of PF-4-binding correlates with the proportion of PF-4 tetramers in solution and with the activation of neutrophils for exocytosis. Reduction of PF-4 binding and PF-4-induced exocytosis in the presence of various glycosaminoglycans or following treatment of cells with chondroitinase ABC (but not other glycosaminoglycan-degrading enzymes) altogether demonstrates that the PF-4 receptor is a proteoglycan of the chondroitin sulfate class. Cross-linking experiments with radiolabeled PF-4 revealed a receptor-ligand complex of approximately 250 kDa. Taken together, our data show that a distinct chondroitin sulfate proteoglycan represents specific receptors for tetrameric PF-4 on human neutrophils.

Cells, Cultured↗
PubMed1998

Maternal and neonatal outcome following prolonged labor induction.

OBJECTIVE: To examine the effect of labor induction length on maternal and neonatal outcome. METHODS: Inductions of labor were reviewed retrospectively, comparing 27 patients with infectious complications to 313 with no infections. Univariate analysis, t-test, chi2, and Fisher exact test were used for statistical analysis. Forward stepping logistic regression was used in a multivariate model to identify odds ratio (OR) and 95% confidence intervals (CI). RESULTS: There was a statistically significant increased risk of maternal infection with increasing induction time. In univariate analysis, cesarean delivery, duration of induction, duration of oxytocin administration, nulliparity, use of internal monitors, increased maternal weight gain, and low cervical dilatation at start of induction were all associated with increased maternal infection risk. Multivariate analysis showed duration of induction for each additional 2 hours (OR 1.09; 95% CI 1.01, 1.18) and nonwhite ethnicity (OR 5.95; 95% CI 1.72, 20.49) to be associated significantly with maternal infection. Maternal infection was associated with lower Apgar scores and increased neonatal intensive care unit admissions. In patients who delivered vaginally, a logistic regression model estimated infectious morbidity at 40 hours to be 10%. The cesarean rate was not increased with prolonged induction. CONCLUSION: Prolonged induction is associated with a small increased risk of infectious morbidity, with an estimated 10% incidence noted after 40 hours of induction in women who deliver vaginally.

Adult↗
PubMed1998

Intended blinders in research.

It could be argued that science is the only generally recognised cognitive authority in the world today. Science is not constrained by frontiers between countries. The art of science is influenced by more factors, how entrenched ideas govern scientific beliefs, also by talent, trends, politics, lobbying, peer-review, priority, conflict of interest etc. Therefore what might have occurred in concealment, is of common scientific interest. An actual example from Denmark is presented showing how research into patients rights and consumer protection has been employed as a technical stumbling-block by health authorities. The authorities problem was certainly a political, not intrinsically a practical medical or scientific one.

Consumer Advocacy↗
PubMed1997

The CXC-chemokine neutrophil-activating peptide-2 induces two distinct optima of neutrophil chemotaxis by differential interaction with interleukin-8 receptors CXCR-1 and CXCR-2.

The CXC-chemokines interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2), and melanoma growth-stimulatory activity (MGSA) are chemoattractants with high selectivity for neutrophils. Although IL-8 has been shown to act as an extremely potent mediator, reports on NAP-2 and MGSA are still contradictory. Here we show for the first time that NAP-2 and MGSA induce two distinct optima of neutrophil chemotaxis. A first optimum is elicited within a concentration range as low as it is characteristic for IL-8. However, a second optimum appears at more than 200-fold higher stimulus concentrations, at which IL-8 is inactive. Investigating the involvement of the two chemokine receptors CXCR-1 and CXCR-2 in NAP-2-mediated chemotaxis, we observe that the cells become desensitized to the first optimum of the chemokine after selective downregulation of CXCR-2, while both optima disappear upon simultaneous downregulation of both receptors. Blocking monoclonal antibodies (MoAbs) specific for CXCR-2 or CXCR-1 either suppress the first optimum of NAP-2-induced chemotaxis or drastically reduce the second one, respectively. These results provide evidence that both receptors are involved in NAP-2-induced neutrophil chemotaxis, with CXCR-2 rendering the cells responsive to low dosages of the chemokine, and with CXCR-1 extending their responsiveness to NAP-2 dosages higher by several orders of magnitude.

Antibodies, Monoclonal↗