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Biomedical subjects

H Renz

Publications and source records attributed to H Renz.

At least 19 recordsLinked to original sources

Unusual case presentations associated with the CD45 C77G polymorphism.

CD45, the leucocyte common antigen, is a haematopoietic cell specific tyrosine phosphatase. Human polymorphic CD45 variants are associated with autoimmune and infectious diseases and alter the phenotype and function of lymphocytes, establishing CD45 as an important regulator of immune function. Here we report four patients with diverse diseases with unusual clinical features. All four have the C77G polymorphism of CD45 exon 4, which alters the splicing and CD45RA/CD45R0 phenotype of lymphocytes. We suggest that C77G may be a contributing factor in these unusual cases.

Abscess↗

The role of Foxp3+ T cells in long-term efficacy of prophylactic and therapeutic mucosal tolerance induction in mice.

BACKGROUND: Mucosal tolerance induction is suggested as treatment strategy for allergic diseases. Using a murine model of birch pollen (BP) allergy we investigated the long-term efficacy and the underlying mechanisms of mucosal tolerance induction with two structurally different molecules in a prophylactic and in a therapeutic set-up. METHODS: The three-dimensional major BP allergen Bet v 1 or a nonconformational hypoallergenic fragment thereof was intranasally applied before (prophylaxis) or after sensitization (therapy). RESULTS: In the prophylactic application both the Bet v 1 allergen and the fragment prevented allergic sensitization, and this effect lasted for 1 year. In the therapeutic approach established allergic immune responses were also suppressed after treatment with either of the molecules. However, a long-lasting curative effect (6 months) was only achieved with the Bet v 1 allergen but not with the Bet v 1 fragment. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis of splenocytes revealed that tolerance induction with the Bet v 1 allergen was associated with enhanced expression of transforming growth factor (TGF)-beta, interleukin (IL)-10, and Foxp3 mRNA in CD4+ T cells, whereas treatment with the fragment led to the induction of either Foxp3 (prophylaxis) or IL-10 (therapy) alone. CONCLUSION: From these data we concluded (i) that the mechanisms underlying peripheral tolerance are linked to the conformation of the antigen, (ii) that mucosal tolerance is mediated by separate regulatory cell subsets, and (iii) that the long-term efficacy of immunosuppression is associated with the presence of Foxp3+ T cells.

Administration, Intranasal↗

Monitoring of plasmin and plasminogen activator activity in blood of patients under fibrinolytic treatment by reteplase.

There are no reliable data on plasmin or plasminogen activator (PA) activities in blood of patients receiving fibrinolytic treatment. This is due to continuing in vitro action of PA after blood withdrawal. These artefactual changes of PA or plasmin activities have been prevented by arginine stabilization of blood samples of myocardial infarction patients treated with plasminogen activators. Twelve patients with myocardial infarction were treated with reteplase 2 x 10,000,000 units in bolus application; one patient was treated with 100 mg t-PA in continuous infusion. Blood was immediately stabilized with EDTA and arginine. The plasma was analyzed with newly developed assays for plasmin and PA. Maximal plasmin activities in blood were obtained at 40 to 60 minutes reteplase treatment time (0.1-0.6 U/mL = approximately 0.05-0.3 micromol/L plasmin). The 50% clearance rate for plasmatic Pli was greater than 30 minutes. The plasmatic reteplase concentration peaked at approximately 2,000 U/mL after the first bolus infusion and at approximately 1,500-3,500 U/mL after the second bolus infusion. Reteplase was cleared to 50% within less than 30 minutes, also with great inter-individual variation. Arginine stabilization of blood allows reliable determinations of activities of plasmin and PA in blood of patients under fibrinolytic treatment: substantial plasmin activities occur in patients treated by reteplase. Therapeutic thrombolysis might be improved, imitating the physiologic cellular thrombolysis; i.e., polymorphonuclear phagocytes (PMN) that can be activated by singlet oxygen ((1)O(2)). PMN might be superior to PA in selective lysis of pathologic thrombi.

Arginine↗

Incremental lines in root cementum of human teeth--a reliable age marker?

In root cementum of teeth, alternating dark and light lines become visible in cross-sections under the light microscope. These lines bear an apparent resemblance to the annual rings of trees. Numerous studies have been done to correlate the number of cementum lines with the dental age by examining a great number of teeth of known age. Our study used a different approach. If lines in root cementum develop in an annual rhythm and are thus comparable to annual rings of trees, the same or at least a very similar number of these structures should be found in all areas of the root cementum of the same tooth. We counted cementum lines in the buccal, lingual, distal and mesial region of different sections, all from the middle third of the same root. This was repeated in eight teeth. To our surprise, we had immense difficulty in counting reproducible line numbers in the same cementum area at repeated counts. Nevertheless, the same tooth was found to differ markedly in the number of lines in different sections as well as in different regions of the same sections. These differences cannot be ascribed to variations caused by difficulties with reproducible line counting. Therefore, we are more than skeptical about the reliability of counting lines in root cementum as a method for determining the age of human teeth.

Adult↗

Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma.

BACKGROUND: Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found. OBJECTIVE: To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma. METHODS: Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges. RESULTS: Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected. CONCLUSION: This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.

Animals↗

Deficiency in immunoglobulin G2 antibodies against staphylococcal enterotoxin C1 defines a subgroup of patients with atopic dermatitis.

BACKGROUND AND AIM: Atopic dermatitis (AD) is a common chronic inflammatory skin disease often accompanied by cutaneous Staphylococcus aureus colonization and, in this regard, especially complicated by the presence of superantigen-producing strains. Because IgG antibodies comprise an important defence mechanism of the adaptive immune system against bacteria, it was investigated whether AD patients have an abnormal pattern or distribution of superantigen-specific IgG subclass antibodies in association with disease severity and activity. METHODS: Staphylococcal enterotoxin B (SEB) and staphylococcal enterotoxin C1 (SEC1) specific IgG antibody subclasses were assessed in n=89 adult AD patients with mild to severe disease activity as determined by the SCORAD score and in n=28 healthy age-matched controls. Results were correlated with the current status of bacterial skin colonization and severity score. RESULTS: Thirty-eight per cent of the AD patients showed a selective deficiency in IgG2 antibodies against SEC1 compared with only 14% in the control group. The absence of these antibodies was found in both currently colonized and non-colonized AD patients and was associated with a severe phenotype (SCORAD more than 40 points in two-thirds of the deficient patients). However, these patients had normal production levels of IgG2 antibodies against pneumococcal capsular polysaccharide (PCP) and SEB, but higher IgG1 and IgG4 titres against SEC1. Except for elevated total IgG1, total IgG subclass levels were normal in this AD subgroup. Yet, peripheral blood mononuclear cells (PBMCs) derived from these patients clearly produced IL-4 and IL-5 upon SEC1 re-stimulation whereas PBMCs from those providing SEC1-specific IgG2 antibodies failed in the production of these cytokines. CONCLUSION: A subgroup of AD patients suffers from a selective deficiency to produce anti-SEC1 IgG2 antibodies. This patient group is characterized by a severe AD phenotype.

Adolescent↗

Involvement of distal airways in a chronic model of experimental asthma.

BACKGROUND: Bronchial asthma is characterized by chronic airway inflammation and airway remodelling which occurs in both proximal and distal airways. These changes are associated with development of airway hyper-responsiveness and airflow limitation. OBJECTIVE: This study was aimed to analyse whether chronic inhalative allergen challenges in mice lead to morphological and physiological changes comparable with this phenotype. METHODS: For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed by aerosol allergen challenges on 2 consecutive days per week for 12 weeks. RESULTS: In chronically challenged mice, tissue inflammation in proximal as well as distal airways was observed with a predominance of lymphocytes within the cellular infiltrate. In contrast, inflammation in the airway lumen decreased over time. These changes were associated by a shift in bronchoalveolar lavage-cytokine levels from IL-4, IL-5 and TNF-alpha production (during the acute phase) towards markedly increased levels of TGF-beta during the chronic phase. Goblet cell hyperplasia and subepithelial fibrosis occurred throughout the airway tree. In terms of lung function, chronically challenged mice developed persistent bronchial hyper-responsiveness and progressive airflow limitation. Six weeks after OVA aerosol discontinuation, airway inflammation still persisted although lung function was normalized. CONCLUSION: These data indicate that our model of chronic aerosol allergen challenges leads to a phenotype of experimental asthma with participation of distal airways and persistence of inflammation thereby resembling many morphological and physiological aspects of human bronchial asthma.

Administration, Inhalation↗

Functional determination of plasmin in arginine-stabilized plasma.

Reliable data on plasmin activities in blood of patients during fibrinolytic treatment are lacking. This is due to continuing plasminogen activation by plasminogen activators after blood withdrawal. The purpose of this study was to establish a new method for stabilization of blood and to detect plasmin activity in stabilized plasma. For optimization of plasma stabilization by arginine, 50 microL pooled normal citrated plasma was incubated with 50 microL of 0 to 1500 mM arginine, pH 8.7, and 25 microL 100 IU/mL u-PA, 1250 IU/mL t-PA, 10000 U/mL reteplase, 400 U/mL plasminogen-streptokinase-activator complex, 10 microg/mL tenecteplase in 6% BSA-PBS or 25 microL 25 microg/mL plasmin in 20% glycerol. Twenty-five microliters 3 mM HD-Val-Leu-Lys-pNA were added immediately (1 step) or after 90 minutes (room temperature [RT]). The same experiment was performed with pooled normal citrated plasma supplemented with 3.2 mg/mL EDTA, preoxidized with 0 mM or 20 mM chloramine-T for 10 minutes (37 degrees C). For optimization of plasmin activity, the oxidation time of the arginine-stabilized plasma sample containing 0.5 U/mL active plasmin and the chloramine-T amount was varied. Citrated plasma is stabilized against the in vitro action of all six plasminogen activators tested if the final arginine concentration is greater than 500 mM. Neither the addition of EDTA nor the addition of chloramine-T changes this plasma-stabilizing power of arginine. The optimized functional plasmin assay consists of incubation of 10 microL arginine-stabilized plasma with 10 microL 1.5 M arginine, pH 8.7, and 10 microL 100 mM CT in PBS. After 30 minutes (37 degrees C), 75 microL 1.2 M KCl, 1.6 M Arg, 0.75 mM Val-Leu-Lys-pNA (Stop-CS Reagent), and 175 microL 6% BSA-PBS are added and the absorbance increase (DeltaA) at 405 nm is determined. With the present arginine stabilization procedure of plasma and the determination of plasmin activity in arginine-stabilized plasma as described, it is feasible to determine the activity of plasmin in blood of patients receiving fibrinolytic treatment without artefactual in vitro changes in the samples.

Arginine↗

Functional determination of plasminogen activator in arginine-stabilized plasma.

Reliable data on plasminogen activator (PA) activities in blood of patients receiving fibrinolytic treatment are lacking. This is due to the continuing in vitro action of PA after blood withdrawal. We have elaborated a new simple stabilization technique for plasma involving the addition of arginine in final concentrations greater than 500 mM. In this study, new assays for PA in stabilized plasma are developed. The assay was performed with substrate plasma, that is, pooled normal plasma, preoxidized with chloramine-T; oxidant amount and oxidation time were optimized. The chloramine consumption by plasma was assayed with a KJ-assay (absorbance increase at 405 nm by addition of 200 microL 4 M KJ to 25 microL oxidized plasma). The substrate plasma concentration in the PA assay and the PA acting time was optimized. The inhibition of PA by the cations Na(+), K(+), Mg(2+), and Ca(2+) was evaluated. The optimized PA assay consists of incubation of 10 microL arginine-stabilized plasma with 10 microL 1.5 M arginine, pH 8.7 and 10 microL 100 mM CT in PBS. After 30 minutes (37 degrees C), 175 microL 15 mM CT oxidized EDTA plasma are added. After 40 minutes (37 degrees C), 75 microL Stop-CS Reagent is added and DeltaA at 405 nm was determined, giving PA + plasmin activity in plasma. A control value (basal plasmin activity) consists of the addition of Stop-CS Reagent before 175 microL oxidized EDTA plasma. To obtain plasmatic PA activity, the control value has to be subtracted from the PA main value. The assay is matrix-independent and linear up to 1250 IU/mL t-PA, 790 U/mL reteplase, or 199 IU/mL u-PA (37 nM). With arginine stabilization of plasma and the described determination of plasminogen activator activity in arginine-stabilized plasma, it is feasible to determine the activity of plasminogen activators in blood of patients receiving fibrinolytic treatment without artefactual in vitro changes of the samples.

Arginine↗

Prenatal morphogenesis of the human incisive canal.

The literature describing the formation of the incisive canal is very bizarre. The fusion of the primary and secondary palatal processes leads to formation of a triangular seam, which erroneously has been taken for the future incisive canal. If so, the nasopalatine (incisive) nerve and its accompanying vessels were to run through the primary oronasal cavity, which is not compatible with our biological experience. This study was undertaken to shed light on this region of fusion. We focus on the formation of the incisive canal; the neighboring nasopalatine ducts, which are a transient formation, are mentioned where present. A series of seven horizontal cross-sections of human embryos and fetuses from the 7th to the 24th week of pregnancy (between 25 and 225 mm CRL, crown-rump-length) were examined histologically and partly reconstructed in 3D applying the software analySIS (Soft Imaging Systems, Münster, Germany). The incisive canal did not develop at the junction of the primary and the secondary palate, but within the primary palate rostral to that location. The nasopalatine nerve and the nasopalatine artery are structures that exist before ossification starts in the area of the future incisive canal. The neighboring nasopalatine ducts were found in regions laterally and anterolaterally of the nasopalatine nerve, and it was mostly separated from it by bone. In advanced stages of development, the nasopalatine duct only existed as single epithelial remnants and was prone to obliteration.

Body Patterning↗

A possible interdependency between the wavy path of enamel rods, distances of Retzius lines, and mitotic activity at the cervical loop in human teeth: a hypothesis.

In human enamel, the enamel rods do not run straight in most regions. Instead, they obtain an undulated path. The diameter of the enamel rods remains constant all the way, and a wavy pattern is necessary to produce the volume of the enamel mantle. It is not understood, how this undulated migration of ameloblasts is created. Considerations are presented to explain causal interdependencies between the wavy path of the enamel rods, unequal growth of the cervical loop cells and unequal distances of the striae of Retzius. To test these considerations, further research must record mitotic activity at the cervical loop during the stages of dental development. The distances of Retzius lines must be measured at different spots all over the whole enamel mantle, preferably in 3D. As a result, knowledge of the interdependency between the inner structure and the outer form of each tooth crown will lead to an understanding of tooth form and occlusion.

Ameloblasts↗

Increased airway responsiveness, allergy-type-I skin responses and systemic anaphylaxis in a humanized-severe combined immuno-deficiency mouse model.

BACKGROUND: In patients with allergic bronchial asthma, a strong relationship between elevated serum IgE antibody titres and the development of increased airway responsiveness (AR) has been demonstrated. To further elucidate the relationship between human (hu) IgE and development of increased AR, we developed an in vivo model utilizing immuno-compromised severe combined immuno-deficiency (SCID) mice. METHODS: SCID mice were either reconstituted with peripheral blood mononuclear cells (PBMC) from non-atopic, healthy or atopic individuals sensitized against house dust mite allergen (Der p), or passively sensitized with plasma from non-atopic, healthy or atopic individuals. RESULTS: In both systems, atopic hu-SCID mice developed increased AR. The following results suggest that these responses were mediated via IgE antibodies: increased AR did not occur after transfer of either PBMC or IgE-negative plasma from non-atopic individuals; increased AR occurred simultaneous with increased serotonin release detected 15 min after allergen-aerosol challenge in bronchoalveolar lavage fluid; and increased AR required at least two allergen-aerosol challenges. SCID mice reconstituted with serum containing anti-Der p IgE antibodies developed positive immediate-type skin test responses to intradermal injection of Der p as well as anti-hu-IgE antibody. In addition, IgE binding to skin mast cells was demonstrated by immunohistochemistry. Furthermore, intravenous challenge of hu anti-Der p positive SCID mice with Der p resulted in systemic anaphylaxis. CONCLUSION: These data provide evidence that passive immunization of SCID mice with hu IgE alters AR and that T cells and eosinophils were not a requirement for the development of increased AR in this model.

Animals↗

Nerve growth factor induces increased airway inflammation via a neuropeptide-dependent mechanism in a transgenic animal model of allergic airway inflammation.

BACKGROUND: Nerve growth factor (NGF) exerts an important functional impact on the pathogenesis of allergic diseases. Data obtained in animal models of allergic bronchial asthma indicate that NGF alters sensory nerve function and promotes allergic inflammation, bronchial hyper-reactivity, and airway obstruction. OBJECTIVE: To further delineate the effects of NGF on airway inflammation, we employed a transgenic (tg) animal model of allergic inflammation and asthma. METHODS: NGF-tg mice, which overexpress NGF in Clara cells of the airways, were compared with wild-type (wt) littermates regarding their ability to mount IgE-related airway inflammatory responses. Mice were sensitized intraperitoneally to ovalbumin (OVA) and locally challenged via the airways according to established protocols. RESULTS: NGF-tg mice displayed enhanced levels of OVA-specific IgE antibody titres after repeated OVA aerosol exposure. In the airways, increased numbers of eosinophils were detected. These results were confirmed to be NGF specific, because similar results were obtained following local application of NGF into the airways of wt mice. The effect of NGF was partly mediated via neuropeptides, as treatment of OVA-sensitized NGF-tg mice with the dual neurokinin (NK) receptor NK-1/NK-2 antagonist partly prevented enhanced airway inflammation. CONCLUSION: The present data indicate an important functional role of NGF in allergic airway inflammation and point to an involvement of tachykinins as mediators of NGF effects.

Animals↗

Bristle end-rounding in toothbrushes: a comparison of different evaluation techniques, bristle position and viewing angle.

OBJECTIVE: Numerous studies using various evaluation techniques have shown substantial variations in the degree of bristle end-roundness of commercially available toothbrushes. The aim of the present study was to compare the effects of the examination angle, the bristle selection and two analyzing techniques assessing bristle end-rounding measurements. METHODOLOGY: The study was conducted in two parts. Part One used five randomly selected tufts from 20 brushes that were scanned with an electron micrograph (SEM; 45x) at two viewing angles (45 degrees and 90 degrees). Those bristle tips that were visible on both viewing angles were then judged by 1) a direct comparison to a grading scale, and 2) a shape factor (SF) analysis. In Part Two of the study, SEM images of five bristles from different tufts obtained from 40 brushes were taken at a viewing angle of 45 degrees, and five bristles from different locations within a tuft were also judged by both the direct comparison to a grading scale method, and the SF analysis, to assess bristle location. RESULTS: The SF values and the direct comparison percentage of rounded bristles did not differ because of the viewing angle (45 degrees or 90 degrees; p > 0.05; Mann-Whitney test), but differed significantly at various SF thresholds (percentage of bristles above or below a certain degree of end-roundness) when bristles from Part One were compared to Part Two (p < 0.01, adjusted chi-square-test). Location of the bristles from either the edge of a tuft or those located in the inner part had no effect on the assessments (p > 0.05). The results from the subjective direct comparison grading did not differ from those found with the SF analysis (p > 0.05). CONCLUSION: SF analysis is a time-consuming method for assessing bristle end-rounding, and can be as accurately done by direct comparison to a grading scale. One viewing angle (45 degrees) of bristles from different locations within a tuft can also be used to accurately assess a brush's level of end-roundness.

Analysis of Variance↗

Significant correlation of matrix metalloproteinase and macrophage colony-stimulating factor serum concentrations in patients with head and neck cancer.

Serum matrix metalloproteinases (MMPs) and the macrophage colony-stimulating factor (M-CSF) are of potential interest as serum tumor markers in various malignancies. There is still a lack of reliable tumor markers in patients with squamous cell carcinoma of the head and neck (SCCHN). Therefore, the tumor marker potential of MMPs and M-CSF was investigated in these malignancies. Serum of 59 patients suffering from SCCHN and of 59 healthy volunteers was obtained. The concentration of MMP-3, MMP-8, MMP-9, and M-CSF was determined by sandwich enzyme immunoassays. The MMP- 3, -8, -9, as well as the M-CSF serum concentrations were significantly elevated in the patient group, compared to the healthy controls (p<0.001, p<0.05, p<0.001, p=0.002). There was significant correlation between the M-CSF and the MMP-3 serum concentration (p<0.0001), and between the M-CSF and the MMP-8 serum concentration (p=0.005). A significant correlation with the tumor stage was found only for MMP-8. MMP and M-CSF serum concentrations are of potential interest as serum tumor markers in SCCHN.

Adult↗