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H Renz

Publications and source records attributed to H Renz.

At least 37 records · Page 2Linked to original sources
PubMed2003

In vitro simulation of therapeutic plasmatic fibrinolysis.

One type of therapy for thromboembolism is plasmatic thrombolysis. Several plasminogen activators (PA) are clinically available, including urokinase (u-PA), tissue plasminogen activator (t-PA), streptokinase (SK), plasminogen-streptokinase-activator-complex (PSAC), or mutants of t-PA such as reteplase (RP) or tenecteplase (TP). Therapeutic plasmatic fibrinolysis was simulated, using the PA at relevant plasma concentrations, and plasmin (Pli) and PA activities were determined. Normal citrated plasma was supplemented with 31 to 1,000 IU/mL u-PA, 0.31 to 20 microg/mL t-PA, 125 to 4,000 IU/mL SK, 12.5 to 400 U/mL PSAC, 125 to 4,000 U/mL RP, or 0.31 to 10 microg/mL TP. Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (CT), to destroy plasmatic PAI-1 and alpha2-antiplasmin. After 0 to 80 minutes (37 degrees C), 50-microL samples were withdrawn and added to 100 microL 1.5 M arginine, pH 8.7, and oxidized with 50 microL of 20 mM CT. For determination of plasmin activity, 10 microL thereof was incubated with 150 microL 1.5 M arginine, pH 8.7, and 100 microL 20 mM CT preoxidized (15 minutes 37 degrees C) pooled normal citrate buffered EDTA-plasma for 30 minutes (37 degrees C). For determination of [PA+Pli]-activity, arginine was added after this incubation. 25-microL 6 mM Val-Leu-Lys-pNA were added and deltaA/h at room temperature (RT) was monitored, using a microtiterplate reader. [PA+Pli]-Pli = PA. The PA concentration required to induce 25% [ED25] of the maximally inducible Pli-activity in plasma (= 1 U/mL = 45 mg/L = 0.53 micromol/L active Pli; deltaA = 363 +/- 8 mA/h RT) after 10 minutes (37 degrees C) were 320 IU/mL u-PA, 8 microg/mL t-PA, 140 U/mL PSAC, 6,000 IU/mL SK, 720 U/mL RP, and approximately 150 microg/mL TP. The approximate activity half-lives of the PA in plasma were 30 minutes for u-PA, 30 minutes for t-PA, greater than 80 minutes for SK, greater than 80 minutes for PSAC, 50 minutes for RP, and 80 minutes for TP. The present study shows--for the first time--a combined kinetic in vitro simulation of the plasmatic activity of six different PAs. At clinically used concentrations, RP induces the highest plasmatic Pli activity. Due to unselective generation of plasmin in plasma, all PA are of some danger in inducing severe hemorrhagias. Clinical thrombolysis might be improved by usage of more physiologic activators of thrombolysis, such as activators of polymorphonuclear neutrophils.

Fibrinolysin↗
PubMed2003

Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions.

Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data and animal studies indicate that the T-helper (Th) type-2 cell cytokine, interleukin (IL)-5, plays an important role in eosinophil maturation, differentiation, recruitment, and survival. The objective of this study was to determine whether intravenous treatment with monoclonal anti-IL-5 would affect the number of peripheral blood eosinophils, their activation status, T-cell activation or the pattern of Th1 and Th2 cytokine production. Over a period of 6 months, 19 asthmatics were investigated in a double-blind, placebo-controlled, multicentre study with mepolizumab (SB 240563) anti-IL-5 antibody administered three times. Before each infusion and 12 weeks after the last infusion, peripheral blood leukocytes were examined, qualitative and quantitative distribution of eosinophils and lymphocyte subpopulations, frequencies of IL-2, -3, -4, -5, -10, -13, interferon-gamma-producing CD4 T-cells and serum eosinophil cationic protein (ECP) levels were determined. Treatment with mepolizumab resulted in a marked, rapid and sustained decrease of eosinophil numbers (median values from 300 to 45 per microL) paralleled by decreased levels of serum ECP (median values from 15 to 5 microg x L(-1)). Distribution of T-cell subsets and T-cell cytokine production were not altered during antibody treatment. In conclusion, administration of mepolizumab to asthmatic patients markedly reduces peripheral blood eosinophils without altering the distribution and activation status of lymphocytes.

Adult↗
PubMed2002

The bidirectional capacity of bacterial antigens to modulate allergy and asthma.

In recent decades, the prevalence of allergic diseases including bronchial asthma, hay fever and atopic dermatitis, has risen steadily in high-income countries. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and lifestyle conditions are thought to play an important role. Epidemiological and clinical studies have provided indirect evidence that infections may prevent the development of atopy and atopic disease. This is referred to as the "hygiene hypothesis". According to the hygiene hypothesis, viral and/or bacterial infections could inhibit the T-helper (Th)-2 immune response associated with atopic reactions by stimulating a Th-1 response involved in defence of bacterial infections and delayed-type hypersensitivity reactions. In particular, the prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand, several studies suggested that infections exacerbate established allergic diseases, e.g. bronchial asthma, airway hyperresponsiveness and atopic dermatitis. Therefore, viral and/or microbial infections and/or their products may have bidirectional effects on the development of allergy and asthma. This review will focus on recent findings related to the interaction between allergic disorders and infectious diseases, with the main emphasis on bacterial infections.

Animals↗
PubMed2001

Singlet oxygen (1O(2)) disrupts platelet aggregates.

INTRODUCTION: Important mediators of activated polymorphonuclear leukocytes (PMN) are the oxidants HOCl and chloramine, which generate the nonradical photon-emitting oxidant singlet oxygen (1O(2)). Since 1O(2) inhibits platelet aggregation, we became interested in a possible oxidant mediated reversibility of platelet aggregation. METHODS: Chloramine T (CT) is a stable 1O(2) generator that mimics the natural chloramine N-chloro-taurine. Platelet-rich plasma (PRP) was incubated with CT 0-8 min after addition of the aggregation agonist (10 microM adenosine-5'-diphosphate, ADP, or 5 microg/ml collagen) and the aggregation was monitored. Platelet function was also analyzed by the platelet function analyzer, PFA-100. Fifty microliters of 200 micromol/l ADP was added to 400 microl PRP. After 1 min at 37 degrees C, 50 microl of 0 or 30 mmol/l CT was added, and after an incubation for 3 min at 37 degrees C, 50 microl of 25% glutaraldehyde was added. The samples were analyzed in a transmission microscope at x3000 and x7000 magnification. RESULTS: Chloramines inhibit platelet function in PRP: about 1 mM CT suppresses 50% of the aggregatory capacity of thrombocytes in normal PRP (effective dose 50%, ED(50)=1 mM chloramine), which is identical to the ED(50) for CT in whole blood. The ADP- or collagen-induced platelet aggregation can be reversed by addition of CT: up to 2 min after the addition of ADP as the aggregation inducer, the aggregation is reversible to more than 70% by addition of a 1O(2) release-inducer (3 mM CT). In contrast, addition of CT 8 min after the addition of ADP results only in about 50% reversal of platelet aggregation. The electron microscopic images of platelets before ADP, after incubation for 4 min at 20 micromol/l ADP, after incubation for 1 min at 20 micromol/l ADP, and a further incubation for 3 min at 3 mmol/l CT demonstrate an ADP-dependent formation of platelet aggregates, which are disrupted by 1O(2) into the single platelets; a phenomenon comparable to the decomposition of a puzzle or the continental drift of the major earth plates. The morphology of oxidized and unoxidized platelets is similar. CONCLUSION: This study demonstrates that 1O(2) inhibits and reverses platelet aggregation. The physiologic signal action and the direct anticoagulant action of 1O(2) might be a new principle for pharmacologic intervention in atherothrombosis.

Blood Platelets↗
PubMed2001

Arginine inhibits hemostasis activation.

BACKGROUND: The diagnosis and the therapy of in vivo hemostasis activation is of great clinical importance. Artefactual changes of the hemostasis (i.e., coagulation or fibrinolysis) in vitro have to be prevented. Usual in vitro anticoagulation by sodium citrate does not fully inhibit coagulation--or fibrinolysis--activation. Therefore, there is need for a simple physiologic inhibitor of hemostasis activation both in diagnosis and therapy of hemostasis activation. METHODS: Whole blood clotting time (WBCT), prothrombin time (PT), activated partial thromboplastin time (APTT), in vitro bleeding test closure time (IVBT-CT), and whole blood aggregometry (WBA) were determined in normal human blood or plasma, supplemented with increasing concentrations of L-arginine or guanidine. RESULTS: Arginine in concentrations of 5-100 mM inhibited the WBCT, PT, APTT, IVBT-CT, and WBA. Arginine (50 mM) resulted in a two-fold prolongation of WBCT, PT, or IVBT-CT (the anti-epinephrine action is superior to the anti-ADP action), a four-fold prolongation of APTT or a 60% inhibition of WBA. CONCLUSION: L-Arginine (or guanidine) inhibited the activation of hemostasis. Arginine might be used as hemostasis stabilizer both in the diagnosis and therapy of hemostasis activation. The usage of arginine as an in vitro hemostasis inhibitor might be indicated in the diagnosis of hemostasis activation, as occurring in pharmacological thrombolysis or disseminated intravascular coagulation (DIC). The storage of blood or blood products might be improved by arginine stabilization. The amino acid (and nitric oxide precursor) L-arginine could be an interesting new pharmacologic agent to inhibit a pathologic hemostasis activation.

Arginine↗
PubMed2001

The role of neurotrophins in bronchial asthma.

Allergic bronchial asthma is characterized by chronic inflammation of the airways, development of airway hyperreactivity and recurrent reversible airway obstruction. Target and effector cells responsible for airway hyperresponsiveness and airway obstruction include sensory and motor neurons as well as epithelial and smooth muscle cells. Although it is well established that the inflammatory process is controlled by T-helper (Th) 2 cells and the Th2-derived cytokines interleukin-4, airway hyperresponsiveness-5 and interleukin-13, the mechanisms by which immune cells interact with neurons, epithelial cells or smooth muscle cells still remain uncertain. Since there is growing evidence for extensive communication between neurons and immune cells, the mechanisms of this neuro-immune crosstalk in lung and airways of asthmatic patients are recently becoming the focus of asthma research. Neurotrophins represent candidate molecules regulating and controlling this crosstalk between the immune and peripheral nervous system. They are constitutively expressed by resident lung cells and produced in increasing concentrations by immune cells invading the airways under pathological conditions. They modify the functional activity of sensory and motor neurons, leading to enhanced and altered neuropeptide and tachykinin production. These effects are defined as "neuronal plasticity". The consequences are the development of "neurogenic inflammation" due to neuropeptide and tachykinin activities.

Animals↗
PubMed2001

Neurotrophins in bronchial asthma.

Allergic bronchial asthma (BA) is characterized by chronic airway inflammation, development of airway hyperreactivity and recurrent reversible airway obstruction. T-helper 2 cells and their products have been shown to play an important role in this process. In contrast, the mechanisms by which immune cells interact with the cells residing in lung and airways, such as neurons, epithelial or smooth muscle cells, still remains uncertain. Sensory and motor neurons innervating the lung exhibit a great degree of functional plasticity in BA defined as "neuronal plasticity". These neurons control development of airway hyperresponsiveness and acute inflammatory responses, resulting in the concept of "neurogenic inflammation". Such quantitative and/or qualitative changes in neuronal functions are mediated to a great extent by a family of cytokines, the neurotrophins, which in turn are produced by activated immune cells, among others in BA. We have therefore developed the concept that neurotrophins such as nerve growth factor and brain-derived neurotrophic factor link pathogenic events in BA to dysfunctions of the immune and nervous system.

Animals↗
PubMed2001

Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression.

Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma. We could suppress GATA-3 expression in interleukin (IL)-4-producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3, whereas nonsense control oligonucleotides were virtually inactive. In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in lung cells associated with a reduction of intracellular GATA-3 expression. Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of eosinophils and Th2 cytokine production. Furthermore, treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice, as assessed by both enhanced pause (PenH) responses and pulmonary resistance determined by body plethysmography. These data indicate a critical role for GATA-3 in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of airway hyperresponsiveness such as in asthma. This approach has the potential advantage of suppressing the expression of various proinflammatory Th2 cytokines simultaneously rather than suppressing the activity of a single cytokine.

Animals↗
PubMed2001

Thrombin converts singlet oxygen (1O2)-oxidized fibrinogen into a soluble t-PA cofactor. A new method for preparing a stimulator for functional t-PA assays.

Activated phagocytes, particularly polymorphonuclear leukocytes (neutrophils), by means of oxidative photonic burst, i.e., the combined activation of NADPH-oxidase and myeloperoxidase, generate large amounts of oxidants of the hypochlorite/chloramine type that are an important physiologic source for the nonradical, photon-emitting oxidant singlet oxygen (1O2), which (in the dark blood stream) is both a signal and an agent of defense against bacteria or fibrin. 1O2-oxidized fibrinogen or oxidized fibrin monomer has previously been shown to be unpolymerizable, and methionine to methionine sulfoxide-oxidized fibrinogen occurs in circulating blood. The present study demonstrates that thrombin converts oxidized fibrinogen into a soluble stimulator of tissue-type plasminogen activator (t-PA). After addition of 0.1 IU thrombin to 25 microl oxidized normal human plasma and an incubation time of 10 min (room temperature), t-PA activity increases about 20-fold when compared with oxidized plasma without the addition of thrombin. Thus, since oxidized fibrin monomer is a t-PA cofactor, thrombin-degraded oxidized fibrinogen can be used as a stimulator in functional t-PA assays.

Electrophoresis, Polyacrylamide Gel↗
PubMed2001

Selection of B-cell chronic lymphocytic leukemia cell variants by therapy with anti-CD20 monoclonal antibody rituximab.

OBJECTIVE: Anti-CD20 chimeric monoclonal antibody rituximab (Mabthera; IDEC-C2B8) is currently tested in several clinical trials for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). In the present study, we investigated whether rituximab therapy may select for CD20(-) subclones. MATERIALS AND METHODS: Leukemic B-CLL cells were isolated from patients with B-CLL and sensitivity to rituximab-induced cell death was examined. Levels of CD20 protein and mRNA were determined using flow cytometry and real-time PCR, respectively. Clonality analyses of leukemic cells throughout rituximab therapy were performed by GeneScan analysis of patient clone specific rearrangements of the complementarity determining region III of the heavy chain immunoglobulin. RESULTS: Cytotoxicity of rituximab in vitro did not depend on the protein levels of CD20. During therapy with rituximab CD20(+) B-CLL cells were depleted and CD20(-) leukemic cells emerged. After treatment, the initial CD20(+) B-CLL cell clone reexpanded. CD20(-) B-CLL cells retained their capacity to synthesize the CD20 molecule. CONCLUSIONS: These data support the concept that in B-CLL rituximab treatment may not lead to the emergence of CD20(-) leukemic variants. Our findings support clinical studies investigating the benefit of prolonged period of rituximab therapy in B-CLL disease.

Antibodies, Monoclonal↗
PubMed2001

Prenatal development of the muscles in the floor of the mouth in human embryos and fetuses from 6.9 to 76 mm CRL.

The development of the muscles in the floor of the mouth is described in 10 human embryos and fetuses ranging from 6.9 to 76 mm CRL by means of computer-aided graphical 3D-reconstructions. All primordia of the muscles in the floor of the mouth could be identified from the 15.6 mm CRL stage on. The proportions and insertion lines of the early muscles were found to be different from adult anatomy. Each muscle first inserted in the medial surface of Meckels cartilage, but during the developmental period between 19 and 68 mm CRL the insertion lines were gradually transposed to the bony ridges of the mandible which progrediently embraced Meckels cartilage. The fibers of the mylohyoid muscles left the anterior region near the symphysis mentalis free during all stages of this study. The digastric muscle revealed only one belly with a constriction of its continuous fibers where it passed the hyoid bone primordium. There was no attachment of digastric muscle fibers to the hyoid; only geniohyoid and mylohyoid fibers. Geniohyoid and genioglossus muscles basically correspond to their definite arrangement, but they underwent proportional changes. Individual specimens embodied irregularities such as accessory geniohyoid and hyoid portions and muscle fibers separate from the mylohyoide muscle.

Cartilage↗
PubMed2001

Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: clinical and immunological effects.

Cyclosporin A (CsA) is an effective and well-tolerated treatment for severe childhood atopic dermatitis (AD). By starting at a low dose, the therapeutic safety should be further increased. The aim of this study was to evaluate low-dose CsA in childhood AD with respect to clinical outcome and modulation of T-cell dysregulation. In an open prospective study, 10 children (age: 22-106 months) with severe AD (mean objective SCORAD score > 40 on two baseline measurements at a minimum interval of 2 weeks) were treated with CsA solution for 8 weeks. All patients received a starting dose of 2.5 mg/kg/day, which was increased stepwise in non-responders to a maximum of dose of 5 mg/kg/day. Disease activity was monitored using the SCORAD index. The frequency of cytokine-producing peripheral blood T lymphocytes was analyzed by intracellular cytokine staining, and T-cell numbers were measured by fluorescence-activated cell sorter (FACS) analysis. Twenty healthy age-matched children were included as controls for the immunological data. Nine of the 10 patients had a SCORAD reduction of at least 35%. In seven patients this was achieved with low-dose CsA at 2.5 mg/kg/day (n = 4) and 3.5 mg kg/day (n = 3). Seven of the nine responders experienced no relapse within the 4-week follow-up period. At baseline the percentage of interleukin-4 (IL-4), IL-13, and human leucocyte antigen (HLA)-DR-positive CD3(+) cells was higher in the patient group than in the controls. After CsA treatment there was a significant reduction in interferon-gamma (IFN-gamma), IL-2, IL-4, IL-13, and HLA-DR-positive CD3(+) cells. Hence, in severe pediatric AD, CsA microemulsion, when started at a low dose (2.5 mg/kg/day), improves clinical measures of disease, reduces T-lymphocyte cytokine production, and regulates T-cell activation.

Adolescent↗
PubMed2001

Outline and arrangement of enamel rods in human deciduous and permanent enamel. 3D-reconstructions obtained from CLSM and SEM images based on serial ground sections.

Human enamel rods were made visible continuously from the dentino-enamel junction (DEJ) up to the enamel surface. From 12 teeth (1st and 2nd dentition) enamel blocks from the cervical third were prepared with perpendicular planes, embedded in resin, and ground down in steps of 15 microm parallel to the enamel surface. Enamel rods were made visible by acid etching (35% H3PO4, 45 s), sputtered and examined in the scanning electron microscope (SEM). Prior to this, the enamel blocks were viewed under the CLSM and optical sections at distances of 2 microm were obtained, starting in the same plane as the grinding surface. The outlines of the rods were digitized and reconstructed three dimensionally. For the first time, the path of single and grouped enamel rods on their way through the entire enamel layer was depicted. 3D images obtained from confocal laser scanning microscopy (CLSM) data were similar to those gained from SEM images. Single rods did not maintain their same outline throughout their path; arcade outlines predominated close to the DEJ, while keyhole outlines prevailed at the enamel surface. Within a group of rods, neighborhood relations changed, and neighbor rods influenced their outlines mutually, including the variable extent of the tail. The interdependence between the plasticity of the rods and the ameloblasts' forms should be topics of further research.

Dental Enamel↗
PubMed2001

[Allergen immunotherapy - a position paper of the German society for allergology and clinical immunology].

Mechanisms of allergen immunotherapy (AIT) are complex inducing numerous immunological effects. Successful AIT is most likely based on a functional switch of and tolerance induction in specific T cells downregulating allergic hypersensitivity and inflammation. Subcutaneous AIT for allergic rhinoconjunctivitis and allergic asthma has been successfully assessed in controlled studies with several clinically important allergens (i. e. birch-, grass- and mugwortpollen, dust mites, animal dander) and has shown convincing clinical efficacy. Considered as the only causal treatment besides allergen avoidance at present, AIT can alter the natural course of allergic diseases. Hymenopteravenom hypersensitivity (to bee- and wasp venom) treated with AIT gives the best results compared to AIT with other allergens. AIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens, which do not or hardly permit allergen avoidance and which are available as suitable extracts. Decisions about indication and allergen selection should only be made by a physician with certified training or qualified knowledge and skills in allergology. AIT is administered by physicians experienced in this therapy. After addressing tolerability and present status of health the recommended or individually adjusted does is injected and precisely documented, followed by a mandatory waiting period of 30 minutes. Indication for and application of AIT in children are quite similar compared to the treatment of adults. Children tolerate AIT very well and benefit especially from its immunomodulatory effects. Risk factors for and results of unwanted systemic effects can effectively be minimized by training of the staff members involved, adhering to safety standards and immediate emergency treatment. Modified allergens, recombinant proteins and immunomodulatory adjuvants created by basic research are promises for an improved efficacy of AIT with reduced unwanted effects in the future.

Allergens↗
PubMed2001

Procalcitonin versus interleukin-6 levels in bronchoalveolar lavage fluids of trauma victims with severe lung contusion.

OBJECTIVE: To examine whether measurement of procalcitonin (PCT) in comparison with interleukin-6 is a reliable marker to score the extent of lung contusion in bronchoalveolar lavage (BAL) fluids in polytrauma patients. DESIGN: Prospective, nonrandomized, observational study. SETTING: Twelve-bed intensive care unit in a 1,100-bed primary care university hospital. PATIENTS: Fourteen trauma victims presenting with severe lung contusion and acute lung injury or acute respiratory distress syndrome were enrolled in the study. INTERVENTIONS: Bronchoscopy with collection of lavage fluid and serum blood samples. Samples were obtained on days 1 and 2 after severe chest trauma, and lung contusion was assessed by computed tomography scan. MEASUREMENTS AND MAIN RESULTS: PCT was detectable in BAL fluids of all 14 patients. A significant correlation for PCT serum and BAL levels was found on day 2 (p =.0063). For PCT, no significant correlations (Spearman rank) were found to the lung injury score (p =.93), the abbreviated injury scale-lung (p =.33), or the sepsis-related organ failure assessment score-lung (p =.38). Also, for interleukin-6 there was no significant correlation to the lung injury score (p =.62), abbreviated injury scale-lung (p =.45), or the sepsis-related organ failure assessment score-lung (p =.54). CONCLUSIONS: PCT and interleukin-6 BAL levels cannot be considered as reliable parameters to assess the extent of lung contusion.

Adult↗