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Biomedical subjects

G Westphal

Publications and source records attributed to G Westphal.

At least 19 recordsLinked to original sources
PubMed2003

Cytokine gene polymorphisms in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are genetically determined inflammatory skin disorders characterized by abnormal cytokine production. From association studies there is evidence that functionally relevant cytokine gene polymorphisms contribute to the genetic basis of psoriasis. Association studies in AD have mostly been limited to polymorphisms of T-helper 2-type cytokines, which dominate in acute AD lesions. Unexpectedly, the results of recent genome scans indicate linkage of AD to psoriasis susceptibility loci. Therefore, AD may also be influenced by genes that modulate cutaneous inflammation independently from atopic mechanisms. OBJECTIVES: To investigate further the role of cytokine gene polymorphisms in AD. METHODS: Polymorphisms in the genes encoding tumour necrosis factor-alpha (TNFA-238 G/A, -308 G/A), interleukin (IL)-1beta (IL1B-511 T/C, +3953 T/C), IL-6 (IL6-174 C/G), IL-10 (IL10-1082 A/G) and the IL-1 receptor antagonist (IL1RN intron 2) were investigated in German patients with AD (n = 94) and in healthy nonatopic individuals (n = 214) by polymerase chain reaction-based methods and direct cycle sequencing. RESULTS: No association was found between AD and any of the polymorphisms analysed. This is in contrast to the recently described association between psoriasis and the TNFA-238 and IL1B-511 polymorphisms. CONCLUSIONS: Our data indicate that cytokine gene polymorphisms may act as specific markers of inflammatory skin diseases rather than contribute to a general disposition towards cutaneous inflammation.

Adolescent↗
PubMed2002

Detection and quantification of the soluble form of the human erythropoietin receptor (sEpoR) in the growth medium of tumor cell lines and in the plasma of blood samples.

The erythropoietin receptor (EpoR) belongs to the cytokine superfamily and is a type I transmembrane protein. Like other members of this family, EpoR is also synthesized as a soluble form, and is subsequently secreted by the cell. To investigate whether soluble EpoR (sEpoR) is expressed in human tumor cell lines, we developed a sensitive quantitative ELISA, using an anti-human EpoR antibody and recombinant sEpoR as standard control. With this ELISA, sEpoR could be detected in the supernatant of human tumor cell lines. Analysis of blood samples showed that sEpoR was coprecipitated during coagulation. Therefore only plasma was suitable for analysis and first measurements of plasma samples were investigated. In conclusion, an ELISA to quantify the sEpoR was established and the expression of sEpoR in human tumor cell lines was demonstrated for the first time.

Adult↗
PubMed2002

Detection of NGF-receptors TrkA and p75NTR in human tumor cell lines and effect of NGF on the growth characteristic of the UT-7/EPO cell line.

The receptors for nerve growth factor (NGF)--TrkA and p75NTR--were detected at the mRNA and the protein level in various human tumor cell lines. The NGF receptor TrkA was found on all examined tumor cell lines and is not restricted to cells belonging to the nervous system. NGF did not influence the proliferation rate of TrkA-positive cells NMB, K562, UT-7/EPO and PC-12. After NGF induction, the production level of the differentiation marker c-fos was increased in UT-7/EPO and PC- 12 cells. NGF-treatment of the UT-7/EPO cells and deprivation of erythropoietin (EPO) led to the new adherent cell line UT-7/NGF. Although UT-7/NGF showed a similar growth curve as UT-7/EPO, there were differences in the pattern of adhesion molecules and of the cytoskeleton. The effect of NGF on the cytoskeleton could not be induced in other human cell lines like NMB or KTCTL-30. TrkA inhibition with K252a--a blocker of Trk-induced receptor kinase--suggests, that the NGF signal may be transduced by the TrkA receptor in UT-7/NGF cells. This indicates that NGF is a decisive mediator of cellular adhesion.

Blotting, Western↗
PubMed2001

Response of psoriasis to interleukin-10 is associated with suppression of cutaneous type 1 inflammation, downregulation of the epidermal interleukin-8/CXCR2 pathway and normalization of keratinocyte maturation.

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from the release of cytokines by infiltrating type 1 T cells. Up- regulation of endogenous interleukin-10 controls type 1 skin responses in animal models; however, interleukin-10 production is low in psoriatic lesions. Consistent with an important role of interleukin-10 in psoriasis, we and colleagues have recently demonstrated clinical efficacy of subcutaneous administration of recombinant interleukin-10 to affected patients. Here, we studied the effects of interleukin-10 on disease-related inflammatory pathways. Patients were treated with recombinant interleukin-10 over 6 wk in an open-label phase II clinical trial. Tissue was obtained before and after therapy and examined by histology/immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcription-polymerase chain reaction. Ten of 14 patients showed a marked reduction of the clinical disease activity. The clinical response was associated with a significant decrease of cutaneous T cell infiltration and the lesional expression of type 1 cytokines interferon-gamma and tumor necrosis factor-alpha. Interleukin-10 inhibited the epidermal interleukin-8 pathway by downregulating the expression of interleukin-8, its receptor CXCR2, and its inducer interleukin-17, and partially reversed the aberrant keratinocyte maturation defining psoriatic epidermal pathology. Remarkably, there was evidence that genetic factors are involved in the response to interleukin-10 as individual variations in the downregulation of tumor necrosis factor-alpha were related to the presence of polymorphisms in the tumor necrosis factor-alpha promoter. These data suggest that excessive production of type 1 cytokines in human skin disease can be counter-regulated by the administration of recombinant interleukin-10. Genotypic analysis may help to identify patients that will preferentially respond to interleukin-10 therapy.

Cell Differentiation↗
PubMed2001

Inhibition of the human erythrocytic glutathione-S-transferase T1 (GST T1) by thimerosal.

We have investigated the interaction of thimerosal, a widely used antiseptic and preservative, with the human erythrocytic GST T1 (glutathione-S-transferase T1). This detoxifying enzyme is expressed in the erythrocytes of solely the human species and it displays a genetic polymorphism. Due to this polymorphism about 25% of the individuals of the caucasian population lack this activity ("non-conjugators"), while 75% show it ("conjugators") (Hallier, E., et al., 1993). Using our newly developed HPLC-fluorescence detection assay (Müller, M., et al., 2001) we have profiled the kinetics of enzyme inhibition in erythrocyte lysates of two individuals previously identified as "normal conjugator" (medium enzyme activity) and "super-conjugator" (very high activity). For the normal conjugator we have determined a 2.77 mM thimerosal concentration to inhibit 50% of the GST T1 activity. In the case of the super-conjugator a 2.3 mM thimerosal concentration causes a 50% inhibition of the enzyme activity. For both phenotypes a 14.8 mM thimerosal concentration results in residual enzyme activities equal to those typically detected in non-conjugator lysates. Thus, sufficiently high doses of thimerosal may be able to change the phenotypic status of an individual--at least in vitro--by inhibition of the GST T1 enzyme.

Anti-Infective Agents, Local↗
PubMed2000

Cytotoxic and mutagenic effects, particle size and concentration analysis of diesel engine emissions using biodiesel and petrol diesel as fuel.

Diesel engine exhaust particles (DEP) contribute substantially to ambient air pollution. They cause acute and chronic adverse health effects in humans. Biodiesel (rapeseed oil methyl ester. RME) is used as a "green fuel" in several countries. For a preliminary assessment of environmental and health effects of RME, the particulate-associated emissions from the DEP of RME and common fossil diesel fuel (DF) and their in vitro cytotoxic and mutagenic effects were compared. A test tractor was fuelled with RME and DF and driven in a European standard test cycle (ECE R49) on an engine dynamometer. Particle numbers and size distributions of the exhausts were determined at the load modes "idling" and "rated power". Filter-sampled particles were extracted and their cytotoxic properties tested using the neutral red assay. Mutagenicity was tested using the Salmonella typhimurium/microsome assay. Despite higher total particle emissions, solid particulate matter (soot) in the emissions from RME was lower than in the emissions from DF. While the size distributions and the numbers of emitted particles at "rated power" were nearly identical for the two fuels, at "idling" DF emitted substantially higher numbers of smaller particles than RME. The RME extracts caused fourfold stronger toxic effects on mouse fibroblasts at "idling" but not at "rated power" than DF extracts. The extracts at both load modes were significantly mutagenic in TA98 and TA100. However, extracts of DF showed a fourfold higher mutagenic effect in TA98 (and twofold in TA100) than extracts of RME. These results indicate benefits as well as disadvantages for humans and the environment from the use of RME as a fuel for tractors. The lower mutagenic potency of DEP from RME compared to DEP from DF is probably due to lower emissions of polycyclic aromatic compounds. The higher toxicity is probably caused by carbonyl compounds and unburned fuel, and reduces the benefits of the lower emissions of solid particulate matter and mutagens from RME.

Animals↗
PubMed2000

Blood cells and plasma proteins of chickens fed a diet supplemented with (1-->3),(1-->6)-beta-D-glucan and enrofloxacin.

The effects of (1-->3),(1-->6)-beta-D-glucan from Saccharomyces cerevisiae and of the fluochinolone enrofloxacin were studied on red and white blood cells and plasma proteins of growing chickens up to the 35th day of life. The prominent findings within the leukocyte population on a per cent scale are: (i) increase of leukocyte count; increase of neutrophils and decrease of lymphocytes in the control and in the antibiotic group from day 17 to day 35; (ii) a minor decrease of neutrophils and no change of lymphocytes in the glucan group; (iii) the monocytes increase from 2.5 +/- 1.8% to 6.5 +/- 7.6% in the glucan group; (iv) the basophils increase in the control group and scale down in the other groups from day 17 to day 35. The total count of leukocytes increases in the controls and in the glucan group. The total protein content of blood plasma, beta-globulin and gamma-globulin increase and the albumin-globulin-ratio and alpha-globulin decline during chickens growth. These changes are most prominent in the glucan group. The haemoglobin concentration shows in all three dietary groups a highly significant increase from day 17 to day 35 by about 17 to 27 per cent; no changes are seen in packed cell volume and number of erythrocytes per litre blood.

Animals↗
PubMed1999

Combined analysis of polymorphisms of the tumor necrosis factor-alpha and interleukin-10 promoter regions and polymorphic xenobiotic metabolizing enzymes in psoriasis.

Environmental and genetic factors are thought to interact in the manifestation of psoriasis, but knowledge about the involved genes and antigens is incomplete. This study has focused on the association between psoriasis and inherited variations in xenobiotic metabolism and cytokine production as two components that may influence cutaneous immune responses to foreign substances. Polymorphisms of N-acetyltransferase 2, glutathione S-transferases T1 and M1, and promoter polymorphisms of the genes encoding for tumor necrosis factor-alpha and interleukin-10 were investigated in 151 Caucasian patients with psoriasis (100 with type I and 51 with type II psoriasis) and in 123 healthy controls. Polymorphisms were detected by polymerase chain reaction-based methods, restriction enzyme analysis, and direct sequencing. There were no significant differences in the distribution of enzyme polymorphisms or point mutations at position -1082 of the interleukin-10 promoter between the psoriasis groups and the control group. The G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter (TNF alpha-238*A allele) was more common in type I psoriasis (27%) than in the controls [9.8%; odds ratio 3.4 (95% confidence interval 1.6-7.2); p = 0.0012; pcorr = 0.018]. Surprisingly, this overrepresentation of the tumor necrosis factor alpha-238*A allele was observed in male patients [4.1 (1.5-11.0); p = 0.0046; pcorr = 0.064] but not in female patients [1.8 (0.5-6.5); p = 0.5]. The G-->A polymorphism at position -308 of the tumor necrosis factor-alpha promoter was less frequent in type I psoriasis (23%) compared with controls (35.7%), although the negative association was weak [0.54 (0.3-0.97); p = 0.041; pcorr = not significant]. The distribution of the TNF alpha-238*A and TNF alpha-238*A alleles was similar in type II patients and controls. Our results suggest that male carriers of the G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter are at an increased risk to develop early-onset psoriasis.

Adolescent↗
PubMed1999

[Immunological reactions and health complaints in biological refuse personnel and composting by biological aerosol exposure].

Employees in waste treatment industries are exposed to high levels of airborne microorganisms. Concentrations of 10(7) cfu/m3 air were measured in composting facilities, whereas exposures of bio-waste collectors were two orders of magnitude lower with exposure peaks up to 10(6) cfu/m3 air. These exposures were compared to specific antibody levels against molds and actinomycetes, work related health complaints, and diseases of the workers. 72 bio-waste collectors and 77 compost workers were examined and interviewed for work related symptoms, current occupational exposures, smoking habits, and exposures from other sources (farming, bird breeding, gardening) by physicians specialized in occupational medicine, using a standardized protocol. Levels of specific IgG antibodies to molds and actinomycetes occurring regularly at these workplaces were determined as biomarkers of exposure. The exposure data from the workplaces indicate a higher exposure of compost workers compared to bio-waste collectors. This corresponds with significantly increased health complaints of the upper airways and the skin and higher concentrations of specific antibodies against molds and actinomycetes in the compost workers. Atopic diseases were underrepresented in the compost workers compared to bio-waste collectors and population based data, indicating a healthy worker effect in this group. Occupational diseases from airborne microorganisms eligible for insurance compensation were observed in waste treatment facilities. More detailed studies are needed for exact assessment of health risks of workers in these industries.

Actinomycetales↗
PubMed1996

The effect of human recombinant erythropoietin on the growth of a human neuroblastoma cell line.

Erythropoietin is a growth factor. Cancer can be described as disturbance of the fine balance of positive and negative growth control mechanisms. The effect of human recombinant erythropoietin (EPO) was studied on the cell growth and differentiation of a human neuroblastoma cell line (h-NMB). Cell growth curves, trypan blue staining and thymidine uptake were used to assess cell proliferation and death. To assess cell differentiation, neutral endopeptidase (cell membrane enzyme marker), creatine kinase (cytosolic enzyme marker), dopamine uptake (dopamine transporter marker) and cell morphology were determined. Specific EPO receptor mRNA, by RT-PCR technique, was demonstrated. The incubation of erythropoietin with the tumor cell line resulted in inhibition of cell proliferation as evidenced in a diminished cell growth. EPO was shown to have induced a differentiation process as seen from the two different enzymatic markers, membranal and cytosolic, and from the cells dopamine uptake studies. However, the morphological changes did not document a full differentiation effect. EPO specific antibodies blocked the effects of EPO on cell proliferation and creatine kinase activity. In this study, EPO did not produce any sign of proliferation in the nervous tumor cell line used.

Base Sequence↗
PubMed1992

[Heat-induced decomposition of disaccharide Amadori compounds in quasi-water-free reaction conditions].

The thermally induced decomposition of disaccharide Amadori compounds has been compared to those of monosaccharide ones under almost water-free conditions. The structure of the synthesized maltulosyl compound has been proved to be 4C1-alpha-D-glucopyranosyl- (1----4)-2C5-beta-D-fructopyranosylglycine by 1H- and 13C-NMR spectroscopy. The decomposition of Amadori compounds has been used to study the kinetics of the browning reaction. Compared to fructosylglycine and maltotriulosylglycine, the browning of the disaccharide is faster. Curie point pyrolysis at 300 degrees C and investigation of the pyrolysate by gas chromatography/mass spectrometry have shown that the disaccharide component influences the thermal process. Furanes and furanones have been detected as predominant degradation products, the main one being 2(5H)-furanone. For the first time, we suggest a reaction pathway for the formation of these products via the Maillard reaction which includes 1,6-anhydroglucose.

Disaccharides↗
PubMed1991

Characterisation of the gene cysH and of its product phospho-adenylylsulphate reductase from Escherichia coli.

The nucleotide sequence of the gene cysH from Escherichia coli K12 was determined. The open reading frame was 735 nucleotides in length; it was flanked by a repetitive palindromic sequence centred 36 nucleotides upstream of cysH and a terminator-like structure located 20 nucleotides downstream. CysH encoded a polypeptide of Mr 27927 consisting of 244 amino acids. The gene product was isolated as a homodimer exhibiting phospho-adenylylsulphate reductase (PAPS reductase) activity. The active enzyme was devoid of electron transferring cofactors and contained only one cysteine per subunit. Reduction of the enzyme by dithiols resulted in a shift of the apparent molecular weight from 44,000 to 62,000 without formation of an enzyme-thioredoxin complex.

Amino Acid Sequence↗
PubMed1990

PAPS-reductase of Escherichia coli. Correlating the N-terminal amino acid sequence with the DNA of gene cys H.

The DNA of the gene complementing a PAPS-reductase-deficient strain of Escherichia coli was sequenced. The N-terminal amino acid sequence of the purified PAPS-reductase confirmed that cys H is the structural gene for this enzyme. The open reading frame extends 732 bases and encodes for a peptide of Mr = 27927. The gene product is functionally active when supplemented with thioredoxin and immunologically related with the wild type enzyme.

Amino Acid Sequence↗
PubMed1989

[The Maillard reaction. 18. Radical inhibition of browning by sulfur compounds].

ESR spectroscopic investigations on the mechanism of Maillard-reactions using the model D-glucose/glycine show radical formation in some of the reaction steps. These are possibly due to competitive reactions against ionic mechanism. The formation of radicals depends on the concentration of reactants and reaches a maximum in thermically induced browning reactions. The addition of L-cysteine leads to a decrease in the radical concentration to about 60%. It can be indirectly proven that the radicals are involved in the formation of browning products. The hyperfine structures of ESR spectra are supposed to be similar to pyrazine cation radicals.

Cysteine↗
PubMed1988

[Chemistry of swine liver and products of liver processing. 1. Carbohydrate content of swine liver in relation to thermal stress].

Glucose can be extracted from the carbohydrates of pig liver by water, but glycogen only by boiling alkalies. The last one can be precipitated with ethanol. The boiling of an aqueous liver suspension causes a decrease in glucose quantity as expected. Thereby the influence of the liver proteins on carbohydrate concentration becomes apparent as well as the interaction between both substances within the reaction of non-enzymatic browning. A series of storing experiments confirmed that neither freezing nor boiling temperatures can completely stop this reaction.

Animals↗
PubMed1988

[Chemistry of swine liver and products of liver processing. 2. Interaction between water-soluble liver proteins and glucose--non-enzymatic browning reactions].

The influence of thermical treatment of pig liver on the concentration of water-soluble proteins was investigated. The latter can be partly separated by preparative thin-layer chromatography and characterized by UV-spectroscopy. The initial decrease in measurable protein content as a result of the denaturation was followed by a light increase. The latter was caused by an easier accessibility of the hydrophobe protein areas and by hydrolytical splitting of the proteins. The same assessment of quality is also valid for the model protein (bovine-serum albumin). The addition of glucose causes in both cases an intensive reaction between proteins and sugars--the result is in every case an increase in browning intensity.

Animals↗