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Biomedical subjects

R Nickel

Publications and source records attributed to R Nickel.

At least 37 records · Page 2Linked to original sources
PubMed2001

The pattern of atopic sensitization is associated with the development of asthma in childhood.

BACKGROUND: Even though atopic sensitization has been shown to be strongly associated with childhood asthma, asthma eventually develops in only one third of atopic children. OBJECTIVE: The aim of this study was to prospectively investigate the pattern of atopic sensitization typically associated with the development of asthma in childhood. METHODS: The German Multicenter Allergy Study followed 1314 children from birth to the age of 7 years. Parental questionnaires on asthma and asthmatic symptoms were completed 6 times up to the age of 2 years and from then on yearly. Determination of specific IgE to 9 food and inhalant allergens was performed yearly, and at the age of 7 years, a bronchial histamine challenge was conducted. RESULTS: Onset of atopic sensitization in atopic children with current asthma at the age of 7 years was significantly earlier than in atopic children without current asthma (39.4% before age 1 year vs 21.0%, P =.015). Early atopic sensitization without any sensitization to inhalant allergens at the age of 7 years conferred no increased risk for asthma at this age. Only those children sensitized to any allergen early in life and sensitized to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio, 10.12; 95% CI, 3.81-26.88). However, even in this group of persistently sensitized children, the risk of being asthmatic at the age of 7 years was only increased if a positive parental history of asthma or atopy was present (odds ratio, 15.56; 95% CI, 5.78-41.83), with the effect being strongest for maternal asthma. CONCLUSION: Our results indicate that an underlying factor pertaining to asthma and maternal transmission may determine both a certain pattern of sensitization and the expression of asthma.

Age Factors↗
PubMed2001

[Coping with conflict as pathogenetic link between psychosocial adversities in childhood and psychic disorders in adulthood].

OBJECTIVES: The present study explores the connection between neurotic or immature strategies for coping with conflict in the presence of specific psychosocial adversities during childhood and their cumulative effect. Here we test the hypothesis as to whether certain coping strategies can be viewed as a pathogenetic link between psychic illness in adulthood and adversities during childhood. METHODS: 407 consecutive patients referred to the outpatient unit of a psychosomatic university hospital were included in the study. The strategies for coping with conflict were assessed by means of two psychometric methods (FKBS, Hentschel et al., 1996; SBAK, Ehlers u. Peter, 1989), and the childhood adversities were assessed using the Mainz Structured Biographic Interview (Egle, 1993). RESULTS: Patients with sexual abuse and/or physical maltreatment during the first 14 years of life showed significantly higher values for immature coping mechanisms than patients without such traumatisation. Childhood adversities correlated negatively with mature coping strategies and positively with immature strategies. Significant differences also arise when patients with low risk are compared to those with a higher amount of childhood adversities. The latter group exhibits significantly higher scores for immature neurotic coping strategies, while the former exhibits mature ones. By means of a multivariate logistic regression analysis, 7 and 10% respectively of the variance of the predominant coping strategies within each group occurring in adulthood could be accounted for. CONCLUSIONS: The results suggest that in patients exposed to psychosocial stress during childhood an increased vulnerability for psychic disorders in adulthood is, in part, caused by the use of immature strategies for coping with conflict.

Adaptation, Psychological↗
PubMed2000

Two novel calcium-binding proteins from cytoplasmic granules of the protozoan parasite Entamoeba histolytica.

We report on the molecular characterisation of two novel granule proteins of the protozoon and human pathogen Entamoeba histolytica. The proteins, which were named grainin 1 and 2, show a considerable structural similarity to calcium-binding proteins, particularly within EF-hand motifs. Each grainin possesses three of these putative calcium-binding sites. Based on careful inspection of known structures of protein families containing EF-hands, a domain of grainin 1 covering two EF-hand motifs was modeled by homology. Calcium-binding activity of grainins was demonstrated by two independent methods. These granule proteins may be implicated in functions vital for the primitive phagocyte and destructive parasite such as control of endocytotic pathways and granule discharge.

Amino Acid Motifs↗
PubMed2000

Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers.

Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS'90), parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.

Child↗
PubMed2000

An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German multicenter atopy study (MAS-90).

BACKGROUND: Allergic diseases are one of the major causes of morbidity in the developed countries today, and the prevalence of these diseases is increasing steadily. Study of total serum gE level is important in understanding the genetics of allergic iseases because IgE levels are considered to be a crucial pathogenic component. IL-13 plays an important role in the induction of IgE synthesis and in the pathogenesis of allergic diseases. OBJECTIVE: We sought to examine potential variation at the IL13 gene and estimate its effect on elevated IgE level and atopic dermatitis (AD). METHODS: We conducted mutational analyses of the IL13 gene by using single-stranded conformation polymorphism and DNA sequencing. Case control studies for high-IgE phenotype and AD were performed by using subjects from the German MAS-90 cohort. RESULTS: A novel IL13 coding region variant at 4257 bp (G to A, fourth exon) was identified. Case control studies of a German sample from the MAS-90 cohort showed significant associations between the presence of the A allele and two atopic phenotypes: high IgE (odds ratio, 2.38; 95% confidence interval, 1.35-4.21; P =.0026) and AD (odds ratio, 1.77; 95% confidence interval, 1.06-2.96; P =.03). CONCLUSION: This IL13 coding region variant may be involved in the pathogenesis of AD and high total serum IgE level in a study population of white subjects.

Chromosomes, Human, Pair 5↗
PubMed1999

A genome-wide search for linkage to asthma. German Asthma Genetics Group.

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).

Asthma↗
PubMed1999

Ozone isotope enrichment: isotopomer-specific rate coefficients

Six rate coefficients of relative ozone formation contradict the role of molecular symmetry in the process that results in the enrichment of heavy ozone isotopomers. The results show that collisions between light atoms, such as 16O, and heavy molecules, such as 34O2 and 36O2, have a rate coefficient advantage of about 25 and 50 percent, respectively, over collisions involving heavy atoms and light molecules. These results suggest that the observed isotope effect for each isotopomer may be caused by the preponderance of a single reaction channel and not through molecular symmetry selection.

Journal Article↗
PubMed1999

Specific V beta T cell subsets are associated with cat and birch pollen allergy in humans.

Cognate interaction between TCRs and MHC class II molecules plays an important role in initiating the allergen-specific immune response. Therefore, we analyzed the TCR distribution of human PBLs of 56 atopic and nonatopic (NA) individuals, including 4 monozygotic twin pairs, from two extended and four nuclear families. The expression of 23 V beta and 3 V alpha elements was analyzed. The blood samples of symptomatic birch pollen-sensitized individuals that were taken < or = 6 wk after the birch pollen season (n = 8) showed a significantly higher frequency of V beta 16.1+ and V beta 20.1+ T cells compared with the blood samples of birch pollen-sensitized individuals that were obtained out of allergen season (n = 10) or from NA individuals (p < 0.0005 and p < 0.0001, respectively). Allergen-specific lymphocyte proliferation was detected in the allergic individuals, and the distribution of V beta 16.1+ and V beta 20.1+ T cells returned to normal levels after the pollen season. The frequency of these V beta-expressing T cells correlated with the levels of allergen-specific IgE Abs. In addition, cat-sensitized individuals (n = 8) showed a significantly higher frequency of V beta 17.1-expressing T cells than did NA individuals (p < 0.005). Our results indicate restricted TCR-V beta gene usage in cat and birch pollen allergies; we suggest that both genetic and environmental factors contribute to TCR-V beta gene expression and to the development of a specific T cell response.

Adolescent↗
PubMed1999

Chemokines and allergic disease.

Understanding the chemokine network has become one of the great challenges for researchers interested in inflammatory mechanisms and inflammation-based diseases. The complexity and diversity of the system provide not only a daunting task for its comprehension but also numerous opportunities for development of new, targeted therapies. It is now certain that chemokines are involved as important mediators of allergic inflammation; the fine details and scope of their roles are now under investigation. Presumably, because of distinct pressures on the immune systems of people living in different geographic regions, genetic variation of ligands, receptors, and regulatory regions in the network have emerged. Establishing the roles of these polymorphisms in determining disease susceptibility or progression among individuals and in distinct ethnic groups will provide a basis for improved understanding and treatment of allergic diseases.

Chemokines↗
PubMed1999

Dense mapping of chromosome 12q13.12-q23.3 and linkage to asthma and atopy.

BACKGROUND: Asthma is a complex disease characterized by a high prevalence of allergic diathesis and the almost ubiquitous presence of upper airway disease (eg, rhinitis). Previously, we observed linkage of asthma among Afro-Caribbean families to markers in chromosome 12q, which contains a number of genes encoding for products closely related to allergic airway inflammation and disease. OBJECTIVE: To identify susceptibility loci in chromosome 12q contributing to the genetics of upper and lower airway diseases and to expand the region to include genes encoding IFN-gamma (IFNG ) and one of the signal transducers and activators of transcription (STAT6 ), we conducted further linkage studies among 33 multiplex families. METHODS: We characterized 528 subjects from Barbados for asthma; 82% were characterized for allergic rhinitis. Two-point and multipoint linkage analysis of 22 microsatellite markers (spanning approximately 79 centimorgan) was performed. RESULTS: Affected sib-pair analysis revealed significant evidence for linkage to asthma over approximately 30 cM (P <.05 to.002), with the best evidence for linkage at a CA repeat polymorphism in the first intron of IFNG in 12q21.1 (P =.002). Evidence of linkage to allergic rhinitis was observed in the same region (D12S313, P = 0.006, and IFNGCA, P =.01, respectively). Multipoint linkage analysis also provided evidence for linkage to asthma, with the best nonparametric linkage analysis score at D12S326 (nonparametric linkage score = 3.8, P =.0008). Modest evidence for linkage to allergic rhinitis was observed next to D12S326 at D12S1052 (P =.036). CONCLUSIONS: Our findings suggest that (1) one or more loci in the chromosome 12q13. 12-q23.3 region are contributing to the expression of the clinical phenotype asthma and the strongest evidence for linkage is in a region near the gene encoding IFNG and (2) a susceptibility locus for both asthma and allergic rhinitis maps to this region.

Adult↗
PubMed1999

Pore-forming peptides of Entamoeba dispar. Similarity and divergence to amoebapores in structure, expression and activity.

Amoebapore, a 77-residue peptide with pore-forming activity from the human pathogen Entamoeba histolytica, is implicated in the killing of phagocytosed bacteria and in the cytolytic reaction of the amoeba against host cells. Previously, we structurally and functionally characterized three amoebapore isoforms in E. histolytica but recognized only one homolog in the closely related but non-pathogenic species Entamoeba dispar. Here, we identified two novel amoebapore homologs from E. dispar by molecular cloning. Despite strong resemblance of the primary structures of the homologs, molecular modeling predicts a species-specific variance between the peptide structures. Parallel isolation from trophozoite extracts of the two species revealed a lower amount of pore-forming peptides in E. dispar and substantially higher activity of the major isoform from E. histolytica towards natural membranes than that from E. dispar. Differences in abundance and activity of the lytic polypeptides may have an impact on the pathogenicity of amoebae.

Amino Acid Sequence↗
PubMed1999

Genetic markers of atopy in infancy: results from the German Multicenter Allergy Study.

Genetic studies of atopy-associated traits require unambiguous phenotypes to avoid both type 1 and 2 errors. The German Multicenter Allergy Study has provided a birth cohort with longitudinally well defined and stable phenotypes. We summarize data on candidate gene studies on chromosomes 12q, 5q, and 13q using high total IgE and atopic dermatitis (AD) as the most common atopy associated phenotypes in early childhood. We also present data on a functional RANTES promoter polymorphism that we recently identified. A significantly higher frequency of the mutant allele was seen in individuals of African descent compared to Caucasian subjects. In addition, an association of the polymorphism with AD could be demonstrated in the MAS cohort. Although the statistical approaches are limited, the MAS cohort has provided a valuable population for candidate gene studies in atopy.

Chemokine CCL5↗
PubMed1998

Molecular characterization of an exceptionally acidic lysozyme-like protein from the protozoon Entamoeba histolytica.

The protozoan parasite Entamoeba histolytica contains a second antibacterial protein with lysozyme-like properties. The newly recognized bacteriolytic protein was purified from extracts of amoebic trophozoites to allow amino-terminal sequencing. Subsequent molecular cloning revealed that it is an isoform of the amoeba lysozyme described previously but also demonstrated a substantial sequence divergence of the two forms. As lysozymes typically are basic proteins, the novel amoebic protein differs markedly in having a pI of 4.5. There is no significant similarity of both amoeba lysozymes with any bacteriolytic protein of other organisms reported so far; however, striking sequence identity is found with predicted gene products of unknown function derived from the bacteria-feeding nematode Caenorhabditis elegans.

Animals↗
PubMed1998

Early life markers of atopy and asthma.

Since early intervention could modulate the natural course of atopic disease, the availability of predictive markers is of considerable interest. As long as specific genetic markers are not available, early IgE-responses (hen's egg) together with a positive family history of atopy can be proposed as highly specific and predictive markers, which could define subgroups as potential candidates for secondary prevention.

Asthma↗
PubMed1997

Evidence for linkage of chromosome 12q15-q24.1 markers to high total serum IgE concentrations in children of the German Multicenter Allergy Study.

Linkage of asthma and high total serum IgE levels to chromosome 12q15-q24.1 has been recently described. To evaluate this region further in regard to total IgE responsiveness, we genotyped 52 unrelated German children with persistently "high" total serum IgE (selected from a noninterventional prospective multicenter cohort study) and their parents. We carefully defined a most extreme IgE phenotype and analyzed it as a dichotomous trait. We tested for linkage between high total IgE concentrations and nine polymorphic microsatellite markers on chromosome 12q15-q24.1 using the transmission/disequilibrium test. Evidence for linkage and allelic association for high total IgE was observed for four markers in this region. This study demonstrates the value of using extreme phenotypes in genetic analysis of a complex quantitative trait.

Child, Preschool↗
PubMed1997

Sensitization to hen's egg at the age of twelve months is predictive for allergic sensitization to common indoor and outdoor allergens at the age of three years.

BACKGROUND: Specific predictors for atopic sensitization in early infancy are prerequisites for preventive intervention studies. OBJECTIVE: To identify predictors of allergic sensitization to common aeroallergens in infancy, 1314 children in five German cities were followed up from birth (1990) to the age of 3 years. METHODS: Blood samples were taken from cord blood and at follow-up visits at the ages of 1, 2, and 3 years. Total serum IgE and specific IgE antibodies to common food and inhalant allergens were determined. RESULTS: Among our study population, risk factors for sensitization to indoor and/or outdoor allergens at the age of 3 years were a positive family history, the presence of hen's egg-specific IgE antibodies (> or = 0.35 kU/L), and increased log- [total IgE] levels at the age of 12 months. Elevated cord blood IgE was not associated with sensitization to inhalant allergens at the age of 3 years. Egg-specific IgE greater than 2 kU/L in combination with a positive family history of atopy was a highly specific (specificity, 99%) and predictive (positive predictive value, 78%) marker for sensitization to inhalant allergens at 3 years of age. CONCLUSIONS: Hen's egg-specific IgE at the age of 12 months is a valuable marker for subsequent allergic sensitization to allergens that cause asthma, allergic rhinitis, and atopic dermatitis.

Allergens↗
PubMed1995

Transfection and continuous expression of heterologous genes in the protozoan parasite Entamoeba histolytica.

To provide tools for functional molecular genetics of the protozoan parasite Entamoeba histolytica, we investigated the use of the prokaryotic neomycin phosphotransferase (NEO) gene as a selectable marker for the transfection of the parasite. An Escherichia coli-derived plasmid vector was constructed (pA5'A3'NEO) containing the NEO coding region flanked by untranslated 5' and 3' sequences of an Ent. histolytica actin gene. Preceding experiments had revealed that amoebae are highly sensitive to the neomycin analogue G418 and do not survive in the presence of as little as 2 micrograms/ml. Transfection of circular pA5'A3'NEO via electroporation resulted in Ent. histolytica trophozoites resistant to G418 up to 100 micrograms/ml. DNA and RNA analyses of resistant cells indicated that (i) the transfected DNA was not integrated into the amoeba genome but was segregated episomally, (ii) in the amoebae, the plasmid replicated autonomously, (iii) the copy number of the plasmid and the expression of NEO-specific RNA were proportional to the amount of G418 used for selection, and (iv) under continuous selection, the plasmid was propagated over an observation period of 6 months. Moreover, the plasmid could be recloned into E. coli and was found to be unrearranged. To investigate the use of pA5'A3'NEO to coexpress other genes in Ent. histolytica, a second marker, the prokaryotic chloramphenicol acetyltransferase (CAT) gene under control of an Ent. histolytica lectin gene promoter was introduced into the plasmid. Transfection of the amoebae with this construct also conferred G418 resistance and, in addition, allowed continuous expression of CAT activity in quantities corresponding to the amount of G418 used for selection. When selection was discontinued, transfected plasmids were lost as indicated by an exponential decline of CAT activity in trophozoite extracts.

Animals↗