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H Jacobi

Publications and source records attributed to H Jacobi.

At least 19 recordsLinked to original sources

Inhibition of rBet v 1-induced basophil histamine release with specific immunotherapy -induced serum immunoglobulin G: no evidence that FcgammaRIIB signalling is important.

BACKGROUND: Human basophils and mast cells express the low-affinity immunoglobulin (Ig)G receptor FcgammaRIIB. It has previously been shown in artificial model systems that cross-linking of the high-affinity IgE receptor FcepsilonRI and FcgammaRIIB leads to inhibition of FcepsilonRI signalling. OBJECTIVE: The aim of the present study was to investigate whether cross-linking of FcepsilonRI and FcgammaRIIB contributes to IgG-mediated inhibition of histamine release in human basophils in a system using the sera from specific immunotherapy (SIT) patients and the major allergen from birch pollen, Bet v 1. As IgG4 furthermore has been proposed to have special blocking properties, we investigated the significance of IgG subclass specificity for this inhibition. METHODS: Binding of recombinant Bet v 1-IgG complexes to FcgammaRII and IgG-binding activities in the sera from 25 birch pollen-allergic patients treated with SIT were measured using (125)I-rBet v 1. Inhibition of basophil histamine release was assessed by incubating washed leucocytes with complexes of rBet v 1-IgG with or without blocking of FcgammaRII. RESULTS: We observed low binding of rBet v 1-IgG complexes to FcgammaRII, which was negatively correlated with the relative IgG4-binding activities. Blocking of FcgammaRII did not reverse the SIT-IgG-induced inhibition of basophil histamine release. However, IgG-binding activities correlated significantly with the ability of the SIT sera to inhibit basophil histamine release. CONCLUSION: We suggest that at least in birch pollen SIT, the contribution of FcgammaRIIB-mediated inhibitory signalling to SIT-IgG-induced inhibition of human basophil histamine release is of minor importance. The main contributor to the inhibitory effect of SIT-induced IgG seems to be blocking of the allergen-IgE interaction.

Allergens↗

Mode of action of intranasal corticosteroids.

The mode of action of intranasal corticosteroids (INCS) is complex. It is not known whether INCS penetrate the nasal mucosa or act on target cells; however, their low systemic activity supports the concept of local action on nasal mucosa. This local effect can nonetheless influence a variety of inflammatory cells and their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent release of histamine is a possible but unproven mode of action. Epithelial cells are an important target for corticosteroids, and INCS concentration is high at the epithelial surface. INCS may combine with the corticosteroid receptors in epithelial cells, which are then expelled into the airway lumen together with the dead epithelial cells or migrating inflammatory cells. A reduced influx of mediator cells may explain some of the effects of INCS on rhinitis symptoms, but it cannot explain all of the effects because INCS also reduce the early-phase sneezing and rhinorrhea after an allergen challenge outside the pollen season. In this situation, the number of surface mast cells/basophils is very low, as it is in the absence of allergic rhinitis. The mechanism by which INCS treatment of allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic symptoms of an early-phase response involving mast cell release of histamine, remains to be determined. Studies should be conducted to characterize the broad range of mechanisms by which INCS produce their therapeutic effects in allergic rhinitis.

Administration, Intranasal↗

Synergistic DNA damaging effects of 4-nitroquinoline-1-oxide and non-effective concentrations of methyl methanesulfonate in human fibroblasts.

DNA damage and DNA repair in human fibroblasts induced by the combination mixture of the genotoxic agents methyl methanesulfonate (MMS) and 4-nitroquinoline-1-oxide (4-NQO) were studied using the comet assay and the unscheduled DNA synthesis (UDS), respectively. Cells were simultaneously treated for 1h with the no observed effect concentration (noec) of MMS and increasing concentrations of 4-NQO or vice versa. Different results were obtained with the two types of mixtures. When the noec of 4-NQO was combined with increasing concentrations of MMS, no combination effects were observed. However, in experiments with increasing concentrations of 4-NQO and the noec of MMS, an increase in DNA damage and repair (and an enhancement of cytotoxicity) was demonstrated. Quantitative analysis of the effects by the isobologram method confirmed synergistic responses in both tests. We are proposing interactive actions between 4-NQO and MMS, whereby 4-NQO facilitates the attack of MMS on the DNA bases.

4-Nitroquinoline-1-oxide↗

Induction of lipid peroxidation in human fibroblasts by the antioxidant propyl gallate in combination with copper(II).

The antioxidant propyl gallate (PG) induced lipid peroxidation in combination with non-toxic Cu(II) concentrations in human fibroblasts. This was measured by the thiobarbituric acid assay (TBA assay) and by detection of accumulating fluorescent products after a 1-h treatment of cells with CuCl2/PG at concentrations higher than 0.125 mM. PG alone led to a significant reduction of thiobarbituric acid-reactive substances (TBARS) demonstrating its antioxidative properties. Time course studies of lipid peroxidation by PG/Cu(II) showed that formation of TBARS was preceded by a lag phase of 60 min. Thereafter, the TBARS value increased rapidly for 1 h and then reached a constant maximum or slightly decreased. The induction of lipid peroxidation by PG/Cu(II) is probably due to the formation of reactive species like reactive oxygen species (ROS), Cu(I) and semiquinone radicals which are able to participate in initiation and propagation of lipid peroxidation. Combination effects of PG/Cu(II) were demonstrated also on inhibition of membrane-bound succinate dehydrogenase. Cytosolic esterases were affected only slightly. The greater susceptibility of membrane-bound enzymes is in accordance with the lipid peroxidation-inducing effects of PG/Cu(II).

Antioxidants↗

Cytotoxicity and mutagenicity of a 2,4,6-trinitrotoluene (TNT) and hexogen contaminated soil in S. typhimurium and mammalian cells.

The toxicity and mutagenicity of aqueous and organic extracts of soil contaminated with TNT, TNT metabolites and hexogen was determined in mammalian cell lines and in prokaryotic cells. The prokaryotic toxicity was determined via the colony forming ability of Salmonella typhimurium (strains TA 98 and TA 100). The same strains were used to test mutagenicity in the Ames test. The mammalian toxicity was analyzed in human fibroblasts by the inhibition of cell growth and cell viability (MTT assay). The mammalian mutagenicity was tested with the HPRT test in V79 cells (hamster lung). The aqueous soil extract did not reveal toxicity or mutagenicity in any of the tests performed. The DMSO/ethanol extract showed toxicity and mutagenicity in S. typhimurium. Thereby strain TA 98 was more sensitive than strain TA 100. In human fibroblasts cell growth was strongly inhibited, whereas no reduction of cell viability was found in the MTT test. Mutagenicity of the DMSO/ethanol extract of the soil was demonstrated in V79 cells.

Animals↗

Synergistic DNA damaging effects of malondialdehyde/Cu(II) in PM2 DNA and in human fibroblasts.

Malondialdehyde (MDA) is a product of lipid peroxidation (LPO). In combination with CuCl2 MDA induced single strand breaks in PM2 DNA whereas MDA or CuCl2 alone had no effect. Cu(II) oxidized MDA by a radical mechanism under formation of Cu(I). DNA strand break induction was inhibited by catalase (98%), neocuproine (76%) and DMSO (61%). The synergistic damaging effect of MDA and Cu(II) was also demonstrated in human fibroblasts measured by alkaline elution. The combination MDA/CuCl2 caused extensive DNA breakage while neither MDA nor CuCl2 alone induced DNA damage within the cell. Synergistic cytotoxic effects were observed 18 h after a simultaneous treatment of the cells with MDA and CuCl2 for 1 h.

Administration, Topical↗

DNA strand break induction and enhanced cytotoxicity of propyl gallate in the presence of copper(II).

The antioxidant propyl gallate (PG) induced single strand breaks in PM2 DNA at concentrations higher than 0.25 microM when it was combined with copper concentrations at 5 microM and above. In combination with 100 microM CuCl2, extensive double strand breakage was also observed. Neither PG alone nor CuCl2 showed any strand breaking properties. DNA strand breakage was inhibited by addition of catalase or the Cu(I) chelator neocuproine, indicating the involvement of H2O2 and a Cu(II)/Cu(I) redox cycle in the DNA damage. DNA damage of PG/Cu(II) was also observed in human fibroblasts. Using the alkaline elution technique concentrations of 0.15-0.5 mM PG induced DNA strand breaks in combination with 2.5 mM CuCl2, while the single substances did not show any effect. At these concentrations cell viability measured by the MTT assay was not reduced by more than 10%; however, cell growth was inhibited by PG in combination with Cu(II). This growth inhibition was apparently due to the DNA damage incurred by PG/Cu(II). The synergistic interaction between PG and Cu(II) is probably caused by a redox reaction between both compounds, whereby reactive species such as ROS are formed, which are responsible for the observed genotoxic and cytotoxic effects. Our results demonstrate that the antioxidative and cytoprotective properties of propyl gallate may change to prooxidative, cytotoxic and genotoxic properties in the presence of Cu(II).

Catalase↗

[Pseudoxanthoma elasticum. Skin changes as a marker of systemic illness].

Angioid streaks were diagnosed in a 42-year-old woman. Since age 20 she had developed circumscribed atrophic yellow-grey lesions on her neck, axillae and other flexural sites. In spite of highly characteristic skin changes, the diagnosis of pseudoxanthoma elasticum was first confirmed by a biopsy from lesional skin 22 years after the disease onset. Based on the present case and an analysis of the recent literature, the findings characteristic for pseudoxanthoma elasticum in the skin, eyes and cardiovascular system are delineated, the differential diagnosis of the skin lesions, as well as the pathogenesis and the prognosis are discussed, and the new classification of pseudoxanthoma elasticum, based on major and minor criteria, is described.

Adult↗

[Congenital familial plaque-shaped glomus tumors. An unusual variant of multiple regional glomus tumors].

Plaque-like glomus tumours are an unusual and very rare clinical form of multiple regional glomus tumours. We report on a 16-year-old girl with this variety of glomus tumours. The irregular angiomatous plaques localized on her back and right hip were present from birth and enlarged with body growth. In addition, there were some bluish nodules scattered on the right mamma, the abdomen and the left shoulder. The family history showed hereditary influences. The proper diagnosis was based on histological and immunohistochemical findings. In the present case report, the clinical, histopathological and immunohistochemical features and the differential diagnosis of multiple plaque-like glomus tumours are discussed.

Adolescent↗

Correlation of the lipophilicity of xenobiotics with their synergistic effects on DNA synthesis in human fibroblasts.

The binary combination effects of DNA synthesis of human fibroblasts were investigated using 2,4-D with 15 xenobiotics of different chemical substance classes. Results were compared with previous investigations on cell growth. Each of the 15 chemicals tested at their no effect concentrations (NOEC's) increased the effects of 2,4-D on DNA synthesis. Thereby, the EC20 value of 2,4-D was reduced by approximately 40% in the combinations. The NOEC's of the xenobiotics used in the combinations varied by a factor of 1,600 and depended strongly on the lipophilicity of the agents combined with 2,4-D. A significant statistical correlation of r = 0.90 was found between the NOEC's of the 15 combined xenobiotics and their lipophilicity. The combination effects on DNA synthesis were similar to those on cell growth. The regression lines of the relationship between the NOEC's and lipophilicity in both assays showed only slight differences in the slopes. This is an additional confirmation of our hypothesis on a facilitated uptake of 2,4-D in the binary combinations.

2,4-Dichlorophenoxyacetic Acid↗

Suitability of different cytotoxicity assays for screening combination effects of environmental chemicals in human fibroblasts.

Cytotoxicity screening assays measuring survival, growth, colony forming ability, DNA and protein synthesis in human fibroblasts were tested for their suitability to determine combination effects. Thereby, the dose-response curves of a hydrophilic substance A alone and after pretreatment with a membrane damaging substance B were compared. Substances B were applied at concentrations which did not induce toxic effects in the assays (noec). Synergistic combination effects were demonstrated by reduction of the EC20 value of substances A in the combination in comparison to substances A alone. The following substance pairs (substance B/substance A = membrane damaging/hydrophilic) were tested: n-dodecylbenzenesulfonic acid/2,4-dichlorophenoxyacetic acid, 2,4,6-trichlorophenol/2,4-dichlorophenoxyacetic acid, 1,1,2,2-tetrachloroethane/4-chloroaniline, pentachlorophenol/CrCl3. While survival, growth, and DNA synthesis assays were suitable methods for detecting synergistic combination effects, the growth assay was the most sensitive. Here, all four substance pairs showed synergistic combination effects.

Cell Division↗

Correlation of synergistic cytotoxic effects of environmental chemicals in human fibroblasts with their lipophilicity.

The cytotoxic combination effects of 2,4-D with 12 xenobiotics having different lipophilicity were investigated in human fibroblasts at their no effect concentrations (NOEC). Each of the chemicals tested in binary combinations enhanced the toxicity of 2,4-D. These synergistic combination effects were independent of the chemical structure of the test compounds. However, the NOEC's of the xenobiotics used in the combinations varied by a factor of 10,000. For strongly lipophilic compounds the lowest NOEC's were needed to induce synergistic cytotoxicity. A linear regression analysis of the concentrations (NOEC's) of the 12 combined xenobiotics against their lipophilicity revealed a correlation with r = 0.96 for 11 agents. This close correlation may be explained by the membrane damaging properties of lipophilic compounds which enhance the uptake of hydrophilic agents.

2,4-Dichlorophenoxyacetic Acid↗

Indicators for microbiologically induced corrosion of copper pipes in a cold-water plumbing system.

Corrosion damage in the copper cold-water plumbing system of a large building was investigated. An unusual combination of corrosion patterns was found on the inner copper pipe surfaces that were in contact with water. Damage was in the form of shallow cavities, a surface cover or pinprick-like pits. The corrosion system was influenced by thermal treatment and also by cefoxitin dosing. The latter fact in particular is a clear indication of microbiological involvement in this corrosive action. Different parameters, to be measured in standing water (24-h stagnation), are considered typical for this type of corrosion: the detection of Sphingomonas spec. and other species in whose cell wall regions copper can accumulate, a copper content of more than 2 mg/l, oxygen consumption of more than 4 mg/l and an increase in pH. With the help of these indicators, it is possible to recognize microbiologically induced corrosion in copper plumbing systems before pipe perforation occur.

Bacteria↗

Successful outcome of cryosurgery in patients with granuloma annulare.

Several therapeutic methods have been employed in the management of localized granuloma annulare (GA), with varying degrees of success. We performed a prospective trial to evaluate the efficacy, cosmetic results, and safety of cryosurgical treatment in GA. Thirty-one patients with localized GA were treated by cryosurgery, using the contact method. Nitrous oxide (-86 degrees C) or liquid nitrogen (-196 degrees C) were used as refrigerants, and were applied with closed probes; each lesion was treated with one freeze-thaw cycle of 10-60 s per session. If necessary, treatment was repeated after 20-30 days. Resolution of the lesions was obtained in all patients, and in 25 of 31 patients (80.6%) they resolved after a single freeze-thaw cycle. Relapse occurred in only one of 11 patients who were followed for more than 2 years, and this occurred 16 months after treatment. Excellent cosmetic results were obtained in 14 of 28 patients who were eligible for evaluation (50%), and good results in 11 (39.3%). The cosmetic result obtained by cryosurgery with nitrous oxide was independent of the size of the lesion, whereas in the group of patients treated with liquid nitrogen a better cosmetic result was obtained with smaller lesions (comparison of lesions < or = 2.40 cm2 with those > 2.40 cm2; P = 0.04). The duration of the lesion, its location, previous treatment with another method, and the number of treatment sessions, did not have any influence on the cosmetic result. The treatment was generally well tolerated. Blister formation occurred in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Synergistic effects of Cu(II) and dimethylammonium 2,4-dichlorophenoxyacetate (U46 D fluid) on PM2 DNA and mechanism of DNA damage.

Dimethylammonium 2,4-dichlorophenoxyacetate (2,4-D . DMA) induced strand breaks in PM2 DNA when incubated with CuCl2, whereas 2,4-D . DMA alone or CuCl2 alone did not show any or only a negligible effect. The formation of single strand breaks increased linearly with time and concentration of 2,4-D . DMA. Neocuproine, a specific Cu(I) chelator totally prevented strand break formation. So did catalase (up to 100 mM 2,4-D . DMA), but DMSO had only a small protective effect. 2,4-Dichlorophenol, CO2 and formaldehyde were detected as reaction products of 2,4-D and CuCl2. From these results a redox reaction of Cu(II) and 2,4-D is proposed, which could explain the DNA damaging properties of CuCl2/2,4-D . DMA.

2,4-Dichlorophenoxyacetic Acid↗

Synergistic effects of U46 D fluid (dimethylammonium salt of 2,4-D) and CuCl2 on cytotoxicity and DNA repair in human fibroblasts.

The cytotoxicity of U46 D Fluid was tested in human fibroblasts after pretreatment with non-toxic or slightly toxic concentrations of CuCl2. While cell survival, colony-forming ability and protein synthesis were not affected by pretreatment with CuCl2, the inhibition of cell growth was enhanced as was inhibition of DNA synthesis. Synergistic effects of CuCl2 and U46 D Fluid were also detected on the induction of DNA repair measured by unscheduled DNA synthesis. While neither U46 D Fluid nor CuCl2 alone induced DNA repair, preincubation with CuCl2 followed by treatment with U46 D Fluid strongly provoked DNA repair.

2,4-Dichlorophenoxyacetic Acid↗

[Photoallergic contact eczema caused by 4-isopropyldibenzoylmethane].

Dibenzoylmethanes are widely used in UVA absorbing sunscreens but also in cosmetics protecting against skin aging. We report on a 25 years old female with photoallergic contact dermatitis caused by 4-Isopropyl-dibenzoylmethane (Eusolex 8020, Merck), who had taken Contralum Ultra Creme because of a polymorphic light eruption.

Adult↗