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Hans-Peter Rihs

Publications and source records attributed to Hans-Peter Rihs.

13 recordsLinked to original sources
PubMed2006

Concordance between the deduced acetylation status generated by high-speed: real-time PCR based NAT2 genotyping of seven single nucleotide polymorphisms and human NAT2 phenotypes determined by a caffeine assay.

BACKGROUND: The utility of typing single nucleotide polymorphisms (SNPs) for the determination of the N-acetyltransferase 2 (NAT2) acetylation status is a matter of debate. AIMS OF THE STUDY: Evaluation of the concordance between deduced genotype results of seven human NAT2 SNPs generated by Real-time PCR analysis and human NAT2 phenotypes. METHODS: NAT2 phenotypes of 38 Caucasian workers were determined using a suitable caffeine test method. Genomic DNA aliquots were used for the determination of seven human NAT2-specific SNPs (G191A, C282T, T341C, C481T, G590A, A803G, G857A). RESULTS AND CONCLUSIONS: Phenotypic results based on the molar ratio of 5-acetylamino-6-formylamino-3-methyluracil (AFMU)/(AFMU+1-methlyuric acid (1U)+1-methylxanthine (1X)) calculated from excreted caffeine metabolite levels in urine samples with 0.3 as a cut-off point between slow (<0.3) and rapid acetylators (>or=0.3). Twenty-seven samples belonged to the slow (mean 0.13; range: 0.03-0.25), 11 to the rapid (mean: 0.41; range: 0.34-0.48) acetylators. LightCycler analyses revealed 11 different NAT2 variant combinations, whereby *5B/*5B and *5B/*6A or *5A/*6C (each 21%), were the most frequent. The deduced acetylation status of the seven NAT2 SNPs matched perfectly with the 38 results determined by phenotyping. This study showed a 100% concordance between NAT2 phenotypes and the deduced NAT2 genotypes and the suitability of the high-speed NAT2-specific LightCycler analysis in a Caucasian population.

Acetylation↗
PubMed2006

Bites of the European pigeon tick (Argas reflexus): Risk of IgE-mediated sensitizations and anaphylactic reactions.

BACKGROUND: Local and systemic reactions can occur after bites of Argas reflexus (Argas), a soft tick parasitizing pigeons. OBJECTIVE: Risk assessment of IgE-mediated sensitizations and systemic reactions after Argas bites. METHODS: Case histories, skin prick tests (SPTs) with a whole-body extract of Argas containing major allergen Arg r 1, and common inhalants and specific IgE measurements were obtained from 148 subjects who had had Argas bites and 20 volunteers as a control group. RESULTS: Systemic reactions (urticaria, angioedema, dyspnea, cardiovascular dysregulation, unconsciousness) were reported in 12 of 148 (8%); 146 of 148 (99%) had local reactions. Atopy was found in 37 of 146 (25%) with local reactions and 3 of 12 (25%) with systemic reactions. SPT to Argas was positive in 24 of 148 (16%) with a high proportion of atopics 10 of 24 (42%); specific IgE to Argas was detectable in 12 of 135 (8% of 148) with moderate concordance to systemic reactions. No positive SPT or specific IgE results to Argas were obtained in the control group. Immunoblotting of 23 sera revealed an IgE-binding protein in 19 of 23 sera (82%) at 22 kd, indicating a major allergen of Argas. CONCLUSION: Severe anaphylactic reactions were infrequently (approximately 8%) found after bites of the soft tick Argas reflexus. Atopy is a risk factor for skin sensitizations to Argas, but not for systemic reactions after bites by Argas. Using a whole-body extract of Argas, diagnosis through SPT and specific IgE is hampered by false-negative and irrelevant positive results, particularly in atopy.

Adolescent↗
PubMed2006

Relevance of the recombinant lipid transfer protein of Hevea brasiliensis: IgE-binding reactivity in fruit-allergic adults.

BACKGROUND: Lipid transfer proteins (LTPs) are relevant allergens in certain plants. The role of the LTP of Hevea brasiliensis in the latex-fruit syndrome is widely unknown. OBJECTIVE: To study IgE reactivity with recombinant Hevea LTP in sera of fruit-allergic adults with and without natural rubber latex (NRL) allergy. METHODS: An LTP-specific complementary DNA of H brasiliensis leaves was amplified, subcloned into the pMAL expression system, and analyzed. The recombinant protein was coupled to ImmunoCAP, and the IgE-binding properties were studied in sera of 10 NRL-allergic patients without symptoms to fruit and 48 atopic patients with fruit allergy. Eleven of these 48 patients were also allergic to NRL, 14 displayed sensitization to NRL without symptoms on NRL exposure so far, and 23 had neither symptoms nor IgE antibodies to NRL. RESULTS: After expression in Escherichia coli, a soluble maltose-binding protein-rHev b 12 fusion protein was isolated and coupled to ImmunoCAP to determine rHev b 12 specific IgE reactivity. rHev b 12 specific IgE binding was found in 3 fruit-allergic patients with NRL sensitization (0.68, 0.88, and 0.96 kU/L) and in 3 fruit-allergic patients without NRL sensitization (1.58, 2.25, and 2.27 kU/L). The remaining 52 serum samples and all maltose-binding protein control test results were negative (< 0.35 kU/L). CONCLUSIONS: In these patients, rHev b 12 specific IgE reactivity seems to result from common cross-reactive epitopes with some of the fruit LTPs tested and underscores only an involvement in co-recognition. No clinical relevance of IgE binding to the LTP of H brasiliensis in association with NRL allergy was detected.

Adolescent↗
PubMed2006

Patterns of latex allergen recognition in children sensitized to natural rubber latex.

Single recombinant latex allergens permit the study of the pattern of sensitization to individual allergens. We aimed to quantify the IgE-response to individual latex allergens in children sensitized to latex. The study group included 31 latex-sensitized children: 26 operated at least twice, 20 of them with spina bifida; two children with one operation and three atopic non-operated children. IgE antibodies to rHev b 1, rHev b 3, rHev b 5, rHev b 6.01, rHev b 7.02 and rHev b 8, coupled to ImmunoCAPs, were measured in each serum. IgE responses to rHev b 1, rHev b 5 and rHev b 6.01 were found in 17 children each, and their mean +/- s.d. levels were 5 +/- 7.4, 16.8 +/- 14 and 10 +/- 18 kU/l, respectively. IgE responses to rHev b 3 (4 +/- 5.4 kU/l) were found in eight children. Two children had IgE to rHev b 7 (1.7 and 3.2 kU/l), and none to rHev b 8. Four sera were negative to all tested recombinant allergens. We divided the patients in three groups: sensitized only to rHev b 1, sensitized only to rHev b 5 and/or rHev b 6.01, and sensitized to both rHev b 1 and to rHev b 5 and/or rHev b 6.01. The three groups had the same profile of clinical features. Hev b 5 induces the quantitatively higher IgE responses in children with multiple surgeries sensitized to latex. Responses to Hev b 6.01 equal those of Hev b 1.

Adolescent↗
PubMed2006

Basophil Activation Test and specific IgE measurements using a panel of recombinant natural rubber latex allergens to determine the latex allergen sensitization profile in children.

There are no documented studies that describe natural rubber latex (NRL) sensitization in children with a history of surgical intervention but without any congenital malformation (urogenital anomalies, spina bifida, etc.), although some authors have studied NRL allergy in children without a history of surgical intervention. The aim of this work was to evaluate the sensitization profile to single NRL allergens in children without spina bifida and without repeated surgical interventions, by using different recombinant and natural latex allergens in two analytical techniques: specific serum immunoglobulin E (IgE) quantification and flow cytometry determination of activated basophils expressing CD63, after stimulating cells from patients with NRL allergens. A total of 23 patients and 10 healthy children were selected. Conjunctival and in-use NRL provocation tests were carried out, as well as specific IgE determination in all patients' and controls' sera with the recombinant NRL allergens: rHev b 1, rHev b 2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9 and rHev b 11 and with NRL (k82) using appropriate ImmunoCAPs. The Basophil Activation Test (BAT) was performed with whole latex extract and with the recombinant allergens rHev b 5 and rHev b 6.01, as well as with the natural allergen Hev b 6.02. The sensitivity and the specificity of NRL-specific IgE (k82) were 100%. Positive IgE responses to rHev b 5 were found in sera of 10 children, to rHev b 6.01 in 16 and for rHev b 6.02 in 15 children's sera. Specific IgE to rHev b 8 was found in four sera of the children. We only found significant differences in sensitization to rHev b 5 in children with two or more surgical interventions compared with the non-intervened group or those with only one intervention. Specific IgE in sera of children with latex-fruit syndrome recognized rHev b 6.02, but not to rHev b 11. The patients sensitized to Hev b 8, Hev b 9 and/or Hev b 11 were atopic. The four patients presenting a positive response to the NRL profilin Hev b 8 were allergic to pollen. The BAT against whole NRL extract was positive in 22 of 23 children; against rHev b 5 in 14 of the patients studied; against rHev b 6.01 in seven cases and against nHev b 6.02 in 19 children. In all the control subjects, the results using this technique were negative. If combined rHev b 5, rHev b 6.01 and nHev b 6.02 together, BAT could detect 20 of the 23 children with latex allergy. The combined use of ImmunoCAP with all the recombinant NRL allergens and BAT with rHev b 5, rHev b 6.01 and nHev b 6.02, enabled the identification of NRL allergy in 22 of 23 patients. There is a positive and significant correlation between sensitization to Hev b 5 and the number of interventions. BAT and allergen-specific IgE determination could be used as first-line in vitro diagnostic tests in patients with NRL allergy.

Adolescent↗
PubMed2006

Variation of the N-acetyltransferase 2 gene in a Romanian and a Kyrgyz population.

As part of a project on environmental disasters in minority populations, this study aimed to evaluate differences in the sequence of N-acetyltransferase 2 (NAT2) as a metabolic susceptibility gene in yet unexplored ethnicities. Eight single nucleotide polymorphisms (SNP) in the NAT2 coding region and a variant in the 3' flanking region were analyzed in 290 unrelated Kyrgyz and 140 unrelated Romanians by SNP-specific PCR analysis. The variants 341C, 481T, and 803G were less and 857A more prevalent in Kyrgyz (P < 0.0001). The variant at site 857 indicates Asian descent. 282C>T and 590G>A showed no significant variation by ethnicity. 364G>A and 411A>T turned out to be monomorphic. Database comparisons of the NAT2 minor allele frequencies support that Romanians belong to Caucasians and Kyrgyz are in between Caucasians and East Asians. The distributions of predicted haplotypes differed significantly between the two ethnicities where the Kyrgyz showed a higher genetic diversity. The haplotype without mutations was more common in Kyrgyz (40.1% in Kyrgyz, 29.3% in Romanians). Accordingly, the imputed slow acetylator phenotype was less prevalent in Kyrgyz (35.2% versus 51.4% in Romanians). We found pronounced ethnic differences in NAT2 genotypes with yet unknown effect on the health risks for environmental or occupational exposures in minority populations.

Acetylation↗
PubMed2005

Occupational exposure to polycyclic aromatic hydrocarbons in German industries: association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms.

A cross-sectional study was conducted in 170 German workers exposed to polycyclic aromatic hydrocarbons (PAH) to investigate the role of 11 polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, GSTM1, GSTT1, and GSTP1 in the association between occupational exposure to PAH and urinary PAH metabolites. Polymorphisms were genotyped with real-time PCR. Exposure to 16 PAH was measured by personal air sampling. Urinary concentrations of 1-hydroxypyrene (1-OHP) and the sum of 1-, 2+9-, 3-, and 4-hydroxyphenanthrenes (OHPhe) were determined post-shift. Urinary 1-OHP and OHPhe correlated significantly with exogenous pyrene (Spearman r=0.52, p<0.0001) and phenanthrene (Spearman r=0.72, p<0.0001), respectively. ANCOVA was applied to investigate potential predictors of the metabolite levels. Current smoking and type of industry turned out to be predictors of 1-OHP but not of OHPhe. CYP1A1 3801TC carriers showed 1.6-fold higher OHPhe levels than 3801TT carriers (p=0.03). EPHX1 113HH was associated with higher and 139RR with lower metabolite levels when compared with the corresponding reference genotypes (113YY; 139HH). In comparison to GSTP1 114AA, carriers of the V allele had 1.5-fold higher 1-OHP (p=0.03) and 2-fold higher OHPhe concentrations (p=0.001). OHPhe turned out to be also a suitable biomarker of occupational PAH exposure. The association with ambient PAH exposure and the influence of polymorphisms was more pronounced for OHPhe.

Adult↗
PubMed2005

Rapid detection of the SPINK5 polymorphism Glu420Lys by real-time PCR technology.

BACKGROUND: The SPINK5 gene, encoding the serine protease inhibitor LEKTI maps to chromosome 5q32, and has been suggested to be a locus predisposing to atopic diseases in general. The Glu420Lys variant showed significant association with atopy, asthma and atopic dermatitis in recent studies. AIMS OF THE STUDY: Development of a high throughput assay to analyse the polymorphism G1258A (Glu420Lys) in exon 14 of the SPINK5 gene followed by the validation using samples of 235 latex-allergic health care workers (HCWs) with (N=63) and without asthma (N=172), and 80 non-atopic controls. METHODS: Twenty DNA samples were first analysed by a polymerase chain restriction fragment analysis (RFLP) using Hph I to generate defined control DNAs which were used for the development of the assay suitable for the detection of the Glu420Lys variant by LightCycler technology. RESULTS AND CONCLUSIONS: 315 samples were successfully screened with this new assay. The temperatures in the melting analysis of the SPINK5 exon 14 PCR product were characteristic to the probes hybridised to the mutant (AA) at 51.5 degrees C and to the wild-type (GG) at 59.5 degrees C. The fast and reliable mutation detection in the tested samples makes this high-speed method suitable for larger epidemiological studies.

Adult↗
PubMed2004

Soybean allergy in patients allergic to birch pollen: clinical investigation and molecular characterization of allergens.

BACKGROUND: Allergic reactions to legumes are generally thought to be acquired by means of primary sensitization through the gastrointestinal tract. Recently, Gly m 4 (starvation-associated message 22), a Bet v 1-related pathogenesis-related protein 10 from soy, was suggested to be an allergen in patients with allergic reactions to a dietary product containing a soy protein isolate. OBJECTIVE: We sought to evaluate the clinical relevance of Gly m 4 in subjects allergic to birch pollen with soy allergy and to assess the risk for subjects allergic to birch pollen to acquire soy allergy. METHODS: Twenty-two patients allergic to birch pollen with soy allergy confirmed by means of positive double-blind, placebo-controlled food challenge results (n = 16) or a convincing history (n = 6) were investigated for IgE reactivity to birch pollen and soy allergens by using the Pharmacia CAP system and immunoblot analysis. Cross-reactivity was assessed by means of enzyme allergosorbent test inhibition. Ninety-four patients with birch pollen allergy were interviewed to assess soy tolerance and screened for IgE reactivity to Gly m 4 by means of immunoblotting. The Gly m 4 content in soy foods and soybean varieties was investigated by means of quantitative evaluation of immunoblots. RESULTS: During double-blind, placebo-controlled food challenge, 10 patients experienced symptoms localized to the oral cavity, and 6 patients had a more severe reaction. CAP analysis revealed Gly m 4-specific IgE in 96% (21/22) of the patients. All patients had Bet v 1-specific IgE antibodies, and 23% (5/22) had positive Bet v 2 results. In IgE immunoblotting 25% (6/22) of the patients recognized soy profilin (Gly m 3), and 64% (14/22) recognized other soy proteins. IgE binding to soy was at least 80% inhibited by birch pollen and 60% inhibited by rGly m 4 in 9 of 11 sera tested. Seventy-one percent (67/94) of highly Bet v 1-sensitized patients with birch pollen allergy were sensitized to Gly m 4, and 9 (9.6%) of those patients reported soy allergy. The Gly m 4 content in soy products ranged between 0 and 70 ppm (milligrams per kilogram). CONCLUSIONS: Our results confirm that soybean is another birch pollen-related allergenic food. Gly m 4 is the major soy allergen for patients allergic to birch pollen with soy allergy. The content of Gly m 4 in soy food products strongly depends on the degree of food processing.

Adolescent↗
PubMed2003

Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, NAT and GST genes.

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1*0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.

Arylamine N-Acetyltransferase↗
PubMed2002

HLA-DQ8 and the HLA-DQ8-DR4 haplotype are positively associated with the hevein-specific IgE immune response in health care workers with latex allergy.

BACKGROUND: Hevein is one of the most important latex allergens affecting health care workers (HCWs). OBJECTIVE: Because the genetically determined susceptibility is one important factor regulating type I allergy, the association between the hevein-specific IgE immune response and HLA class II alleles of DQB1 and DRB1, DRB3, DRB4, and DRB5 was studied. METHODS: The distribution of HLA-DQB1 and DRB1, DRB3, DRB4, and DRB5 in 269 HCWs with latex allergy, 56 latex-sensitized patients with spina bifida (SB), and 90 nonatopic control subjects under special consideration for hevein-specific IgE was examined. RESULTS: Seventy percent (189/269) of the HCWs with latex allergy and 39% (22/56) of the latex-sensitized patients with SB had increased hevein-specific IgE antibody concentrations (>0.35 kU/L). HLA data analysis revealed significantly increased phenotype frequencies for DQB1*0302 (DQ8; 91/189 [48%]) and DRB1*04 (DR4; 102/189 [54%]) in hevein-positive HCWs with latex allergy compared with the 80 hevein-negative HCWs with latex allergy (DQB1*0302: 16/80 [20%], corrected P value [P (c)] = 7.1 x 10(-4); DRB1*04: 23/80 [29%], P (c) =.01) and with control subjects (DQB1*0302: 16/89 [18%], P (c) = 1 x 10(-4); DRB1*04: 22/90 [24%], P (c) = 3.2 x 10(-4)). The DQ8-DR4 haplotype frequency was significantly elevated in HCWs with hevein-specific IgE antibodies when compared with that in HCWs without hevein-specific IgE antibodies (47% vs 18%, P (c) = 5.3 x 10(-4)) or control subjects (47% vs 18%, P (c) = 9.6 x 10(-4)). In contrast, latex-sensitized patients with SB with hevein-specific IgE antibodies showed an increased but not significant DQB1*0302 frequency (7/22 [32%] vs 2/34 [6%], P =.02, P (c) = not significant) compared with that seen in those without hevein-specific IgE antibodies. CONCLUSION: The DQB1*0302 (DQ8) alone, the DQB1*0302 (DQ8)-DRB1*04 (DR4) haplotype, or both are significantly involved in the hevein-specific IgE immune response in HCWs with latex allergy.

Adult↗