Biomedical subjects

J Forster

Publications and source records attributed to J Forster.

At least 37 records · Page 2Linked to original sources

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

Development of seasonal allergic rhinitis during the first 7 years of life.

BACKGROUND: Against the background of the controversial discussion about an increase in allergic rhinitis in recent years, intraindividual longitudinal data is lacking for IgE-mediated seasonal allergic rhinitis (SAR). Little is known about the development of SAR in terms of prevalence and incidence rates from birth to school age. OBJECTIVE: In a prospective birth cohort, we investigated the development of sensitization and symptoms of SAR. SAR should be defined with high specificity, and associated risk factors should be determined. METHODS: Annual longitudinal data about seasonal allergic symptoms and sensitization was available for 587 children from birth to their seventh birthday. The definition of SAR was based on a combination of exposure-related symptoms and sensitization. RESULTS: Up to 7 years of age, SAR developed in 15% of the children. Incidence and prevalence of symptoms and sensitization were low during early childhood (<2%) and increased steadily with age. Children in which SAR had already developed in the second year all were born in spring or early summer, resulting in at least two seasons of pollen exposure before manifestation of SAR. Risk factors assessed by multiple logistic regression analysis were male sex (odds ratio [OR] = 2.4), atopic mothers (OR = 2.6) and fathers (OR = 3.6) having allergic rhinitis themselves, first-born child (OR = 2.0), early sensitization to food (OR = 3.3), and atopic dermatitis (OR = 2.5), whereas early wheezing was not associated with SAR. CONCLUSION: The development of SAR is characterized by a marked increase in prevalence and incidence after the second year of life. Our longitudinal data further indicate that in combination with the risk of allergic predisposition, at least 2 seasons of pollen allergen exposure are needed before allergic rhinitis becomes clinically manifest.

Age Factors↗

PubMed2000

A European study on the genetics of mite sensitization.

BACKGROUND: Sensitization to mite allergens represents a prominent feature of atopy and an important predictor of bronchial asthma. OBJECTIVE: It was the intention of this study to define genetic loci linked to mite sensitization because these could represent the genetic basis of the important atopic component of asthma. METHODS: We studied a multiethnic white population of 99 families, including 224 sib pairs sensitized to Dermatophagoides pteronyssinus. A genome-wide candidate-region search was performed that covered potential asthma and atopy regions. RESULTS: As for nonparametric linkage (NPL) analysis, 14 of the candidate regions showed evidence for linkage (NPL > 2.0), and 4 of them showed prominent linkage (NPL > 3.0). However, there were substantial ethnic differences. Maximizing the LOD score analysis identified candidate regions with suspected dominant and recessive mode of inheritance. Furthermore, genetic imprinting models provided significant evidence for linkage in the 8p23 region and revealed potential maternal imprinting. The regions found are distinct to those in asthma searches that have been found to be linked to asthma, as well to other inflammatory diseases. In addition, we could not find linkage to the HLA region. By different cutoff points of the phenotype definition, the IL cluster showed evidence of being linked to the degree of sensitization rather than to sensitization per se. CONCLUSION: The results indicate that the genetic basis of the atopic component of asthma is different from that of the inflammatory component. Furthermore, it seems reasonable to assume that specific sensitizations are influenced by distinct genetic variants leading to their initiation versus those leading to their enhancement.

Allergens↗

PubMed2000

Effects of ambient ozone on lung function in children over a two-summer period.

There is a general consensus that short term exposure to ozone (O3) causes a decrease in lung function parameters such as forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). The objective of this study was to assess the reproducibility of lung function decrements after ambient O3 exposure over a two-summer period. The authors studied 797 children with a mean age of 8.2 yrs (95% confidence interval: 6.9-9.5) from the second and third grades of ten elementary schools in Austria and southwestern Germany. At the outset the various study locations were stratified into three groups with low (L), medium (M) and high (H) O3 exposure (range of mean O3 concentration in the locations April-October 1994: 24-30 (L); 33-38 (M); 44-52 (H) parts per billion (ppb)). Four lung function tests were performed on each child between March 1994 and November 1995. The increases in FVC and FEV1 recorded from one test period to the next were expressed as mL x day(-1). A significantly lower FVC and FEV1 increase was observed in children exposed to high ambient O3 concentration during the summer season. (FVC in summer 1994: 0.83 (L); 0.56 (M); 0.55 (H) mL x day(-1); p=0.004; and summer 1995: 0.80 (L); 0.63 (M); 0.56 (H) mL x day(-1); p=0.011; FEV1 in summer 1994: 0.48 (L); 0.34 (M); 0.18 (H) mL x day(-1); p=0.004 and summer 1995: 0.68 (L); 0.45 (M); 0.41 (H) mL x day(-1), p=0.006). There was no significant difference in FVC or FEV1 increase between the groups during the winter period. Adjusting for sex, age, height and passive smoke exposure, linear regression revealed a statistically significant negative association of average ambient O3 concentration with the FVC and FEV1 increase in both summers. During the winter period no association of O3 with FVC or FEV1 was observed. In conclusion, in two consecutive summer periods the authors found reproducible lung function decrements in children exposed to high levels of ambient ozone. Reoccurrence of ozone associated lung function deficits might increase the likelihood of persisting effects on the childrens' airways.

Child↗

PubMed1999

Pulmonary function in children of school age is related to the number of siblings in their family.

It has been suggested that the number of siblings in a family is a surrogate variable for exposure to early infections. Since there may be an association between early respiratory infections and impaired lung function in later life, the aim of this study was to elucidate the relationship between the number of siblings and pulmonary function. We analyzed pulmonary function data from 677 schoolchildren living in 431 nuclear families. Our results show that forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) expressed as a percentage of deviation from the predicted values (FVC%, FEV(1)%) increase significantly in line with the number of siblings in a family (FVC%: no sibling = reference, 1 sibling = +1.3%, 2 siblings = +1.9%, 3 siblings = +4.0%, 4 or more siblings = +5.1%; P-value for trend = 0.01; FEV(1)%: no sibling = reference, 1 sibling = +1.6%, 2 siblings = +2.0%, 3 siblings = +4.3%, 4 or more siblings = +6.5%; P-value for trend = 0.007). Pulmonary function values were no more strongly related to the number of older siblings than to the number of younger siblings (difference between the trend for older and younger siblings for FCV%: P = 0.7; FEV(1)%: P = 0.9). The association between pulmonary function and number of siblings can be explained neither by the child's atopic status, prevalence of asthma, or history of pneumonia, nor by former or current cigarette smoke exposure. This suggests that pulmonary function status of the child appears to be related to the number of siblings, and is unlikely to be explained solely by exposure to infections early in life. Our data therefore adds strength to the hypothesis that factors which cause the size of a sibship to influence a child's respiratory health have not yet been adequately explained.

Adolescent↗

PubMed1999

Low prevalence of the immunoglobulin-A-binding beta antigen of the C protein among Streptococcus agalactiae isolates causing neonatal sepsis.

Streptococcus agalactiae (Group B streptococcus, GBS) is the most important pathogen causing neonatal sepsis. The role of bacterial proteins contributing to pathogenicity in GBS infections has not yet been clearly determined, but the C protein complex has been suggested to be involved in both virulence and protective immunity. The aim of this study was to assess the prevalence of GBS strains bearing the gene encoding for the beta antigen of the C protein among clinical isolates from 68 neonates with sepsis, 45 newborns colonized without clinical signs of infection, and 50 isolates from pregnant women. The prevalence of the beta antigen gene in all three groups was low (24% vs. 19% vs. 22%) [corrected], and the differences between groups were not statistically significant. Clinical characteristics and cytokine plasma levels did not differ between septic patients with beta antigen-positive and -negative strains. The beta-antigen gene was not found among serotype III isolates, which accounted for roughly half of all the strains isolated. Thus, polymerase chain reaction (PCR) analysis based on the beta antigen gene seems not helpful for distinguishing invasive from colonizing GBS strains. A vaccine based on peptide antigens from the beta antigen of the C protein would most probably not provide protection against the majority of GBS isolates. When analyzing the PCR products of the C protein beta antigen gene by DNA sequencing, a genetic heterogeneity was observed, revealing small repetitive genetic elements within the amplified fragment, an observation that should be studied further.

Antigens, Bacterial↗

PubMed1999

Serum IgE levels during the first 6 years of life.

OBJECTIVE: Total serum IgE percentiles were derived for a population-based sample of 4082 white children from Germany by weighted analysis of measurements from the Multicenter Allergy Study cohort. METHODS: The children of a prospective birth cohort were selected from a complete 1-year sample of newborns in 6 obstetric departments in 1990. Total IgE was determined at 1, 2, 3, 5, and 6 years of age in 1160 newborns of the cohort. By weighting these measurements for sex, atopic family history, and elevated cord blood IgE, total serum IgE percentiles were estimated for the original population-based sample of 4082 children. RESULTS: IgE levels increased by age (P <.0001). We found statistically significant higher total IgE values in boys than in girls at each age (P <.05). Within the group of atopic children, this sex difference was not statistically significant. CONCLUSION: Our estimates of total serum IgE levels for a large population-based sample were lower than most values previously reported. We suggest that for both clinical and epidemiologic and genetic studies, IgE values should be expressed with percentiles.

Aging↗

PubMed1999

Cyanosis due to diastolic right-to-left shunting across a ventricular septal defect in a patient with repaired tetralogy of Fallot and pulmonary atresia.

Cyanosis as a result of right-to-left shunting across a ventricular septal defect is commonly encountered in patients with congenital heart disease when systolic pressure in the right ventricle exceeds that in the left ventricle. Reported is the case of a child who remained cyanosed after surgical correction of pulmonary atresia despite right ventricular systolic pressure being lower than left ventricular pressure. Colour-flow Doppler showed a residual ventricular septal defect, with right-to-left shunting in diastole alone.

Child↗

PubMed1999

Splenic peliosis: a rare complication following liver transplantation.

In this article, we report a rare case of isolated splenic peliosis in an individual who had recently undergone liver transplantation. The disorder had remained clinically and radiologically undiagnosed until he suffered a traumatic rupture of the affected organ. The relevant literature on this topic is briefly reviewed.

Biopsy↗

PubMed1999

Upper airway inflammation in children exposed to ambient ozone and potential signs of adaptation.

In order to investigate nasal inflammation and subsequent adaptation after ambient ozone exposure, nasal lavage (NL) fluid was collected from 170 schoolchildren on 11 occasions (time points) between March and October. Eosinophil cationic protein (ECP), albumin and leukocytes were quantified as markers of nasal inflammation. The highest half-hour outdoor O3 concentration for each individual on the day prior to the NL was used as a measure of exposure (O3indiv). To avoid confounding with exposure to common environmental allergens, the study population was restricted to children without sensitization to inhalant allergens. In the initial period of increased O3 levels in May (time point 4), with a median O3indiv of 135 microg x m(-3) (5th-95th percentile 100-184 microg x m(-3)), the highest medians of all 11 leukocyte and ECP measurements were observed. The highest O3indiv were observed in June at time point 7 (O3indiv 173 microg x m(-3), 5th-95th percentile 120-203 microg x m(-3)). Cross-sectional analysis of all 11 time points revealed no significant association of O3indiv on the one hand and ECP, albumin and leukocyte levels on the other. A multivariable model estimated using generalized estimating equations showed a statistically significant association of O3indiv and leukocytes and ECP as the dependent variable, when time points 1-4 were analysed (p<0.05). In the same model, this association diminished continuously when time points 5-11 were added stepwise, in spite of high O3 exposure. Not even a tendency towards an O3 effect could be recognized when time points 1-8 were considered. The results indicate: 1) acute inflammation of the nasal mucosa after the first increase in ambient ozone levels, with 2) a significant dose-dependent increase in leukocyte and eosinophil cationic protein levels, and 3) possible adaptation of the nasal mucosa in spite of constant high levels of ozone exposure in children during the summer season.

Adaptation, Physiological↗

PubMed1999

In vivo histamine release during the first minutes after deliberate sting challenges correlates with the severity of allergic symptoms.

In this study, deliberate sting challenge was investigated as a method for estimating the severity of anaphylactic reactions in bee venom-sensitized subjects. Twenty-one patients with previous anaphylactic reactions to field bee sting were subjected to a deliberate sting challenge (n = 32). To document anaphylactic reactions, plasma histamine levels were measured before, and then 1 and 2 min after, bee sting challenge. Eleven patients were re-challenged after 3-5 weeks. On 18 occasions, sting challenges caused no systemic reactions, in seven cases reactions were mild, in five moderate and in two severe. In all children showing systemic reactions, significant increases of plasma histamine were measured after 2 min. The results correlated significantly with clinical scores but not with skin prick test or with specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against bee venom. In patients developing local reactions only, no increase of plasma histamine was detected. The relative amount of released histamine correlated significantly with the severity of clinical symptoms. Significant histamine release occured during the first 2 min after sting challenge in children with subsequent systemic reactions and the severity of these subsequent anaphylactic reactions correlated with plasma histamine concentrations. The measurement of plasma histamine levels in the first minutes after challenge test may therefore be used as an objective marker of a potential systemic reaction.

Adolescent↗

PubMed1999

Association studies on beta2-adrenoceptor polymorphisms and enhanced IgE responsiveness in an atopic population.

The beta2 adrenergic receptor 2 represents a cell surface receptor responsible for the binding of endogenous catecholamines and their exogenously administered agonists and antagonists, mediating their effects to the interior of the cell. On the basis of these functions, the observed association of two of its polymorphisms, Gly16 and Gln27, with nocturnal- and steroid-dependent asthma has been discussed. It has recently been suggested that Gln27 contributes to IgE variability in families with asthma. The aim of this study was to investigate possible influences of the polymorphisms Arg16Gly and Glu27Gln on IgE levels in families recruited through an atopic index case without regard to the presence of clinical symptoms. We employed linkage analysis in affected sibpairs characterized by elevated total IgE concentrations or sensitization to common inhalant allergens. Furthermore, we tested 258 children for association of any of the polymorphisms with enhanced IgE responsiveness. We could find neither linkage at the locus 5q31 nor significant association of the polymorphisms with elevated total IgE concentrations or specific sensitization. We conclude from our data that the polymorphisms Gln27Glu and Arg16Gly of the beta2-adrenergic receptor do not play a significant role in the pathogenesis of enhanced IgE responsiveness in an atopic population in general.

Alleles↗

PubMed1999

The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction.

Interleukin-4 (IL-4) plays a major role in immunoglobulin E (IgE) production. Its signal is conferred to effector cells through binding to the alpha chain of the IL-4 receptor (IL-4Ralpha). We present further evidence for polymorphisms in the IL-4Ralpha gene having an effect on IgE regulation. For two of four common polymorphisms, S503P and Q576R, we found an association with lowered total IgE concentrations (P=0.0008 if occurring together). The polymorphism S503P has not yet been described and is located within the I4R motif of the receptor. In vitro analyses using synthetic peptides of this region showed that the tyrosine kinase Janus kinase 1 (JAK1), as well as IRS-1 and IRS-2 bind to the I4R motif irrespective of the polymorphism or a tyrosine phosphorylation. In vivo immunoassays using T cells of four different groups of individuals (S503/Q576; P503/Q576; S503/R576; P503/R576) revealed that only in case of both polymorphisms the phosphorylation of IRS-1 and IRS-2, but not JAK1 was increased. We found no binding of STAT6 to the I4R synthetic peptides; however, the phosphorylation was reduced in the presence of any of the two polymorphisms, including P503 alone. We discuss possible conformational changes of the receptor leading to the observed effects on the phosphorylation status of IRS-1, IRS-2 and STAT6, in addition to previous findings that Q576R alters STAT6 binding. We conclude that P503 and R576 influence the signal transduction pathways through the IL-4Ralpha, an effect that is magnified by the presence of both polymorphisms. This could explain the observed association effects with lowered total IgE concentrations.

Adolescent↗

PubMed1999

Characterization of the membrane-bound and a soluble form of human IL-4 receptor alpha produced by alternative splicing.

IL-4 plays a major role in IgE production. Its signal is conferred to effector cells through binding to the alpha chain of the membrane-bound human IL-4 receptor (huIL-4Ralpha). Here we present the genomic structure and organization of huIL-4Ralpha. The promotor region shows binding sites for several transcription factors involved in inflammatory processes. HuIL-4Ralpha has been shown to be organized differently to that of mouse IL-4Ralpha. A soluble form of huIL-4Ralpha is produced by alternative splicing of the huIL-4Ralpha gene (shuIL-4Ralpha/splice). Expression of the corresponding mRNA coding for the extracellular part of the receptor and an additional three amino acids is also shown. A second form of huIL-4Ralpha, i.e. shuIL-4Ralpha/prot, is produced by limited proteolysis of the receptor (shedding) and is already known. These results reveal a complex pattern for the regulation of the IL-4 pathway at the receptor level. The patterns of expression of all three receptor proteins as well as their individual meaning in the context of inflammation still have to be elucidated.

Alternative Splicing↗

PubMed1999

Q methodology, risk training and quality management.

The results of a Q methodological study of professional understandings of the notion of risk in mental health services within the UK are discussed in relation to the relevance for staff training and quality assurance. The study attempted to access the diversity of understandings of risk issues amongst a multi-professional group of staff (n = 60) attending inter-agency risk training workshops in 1998. Q methodology is presented as both an appropriate means for such inquiry and as a novel experiential technique for training purposes. A tentative argument is advanced that the qualitative accounts generated by Q research could assist in systematic reviews of quality, complementing the singularly quantitative approaches typically represented in the audit process.

Attitude of Health Personnel↗

PubMed1999

Occurrence and impact of community-acquired and nosocomial rotavirus infections--a hospital-based study over 10 y.

The need for a rotavirus vaccine in any particular country depends primarily on the number of hospitalized cases. Since only limited data are available for Germany, we undertook a retrospective hospital-based analysis in order to gather further information. From 1987 through 1996, a total of 3618 inpatients were hospitalized with a diagnosis of gastroenteritis (ICD 9). In 892 (25%) of them the causative organism was a rotavirus. During the same period, 1886 (out of 8383; 22%) stool specimens tested in the hospital laboratory were obtained from rotavirus-positive inpatients. In 49.2% the infection was community-acquired, and in the remainder of nosocomial origin. Infants under 4 months of age (n = 709: 38%) predominated among both the nosocomial and community-acquired infections. Premature neonates made up 26% of the nosocomial, but only 2% of the community-acquired cases of diarrhoea. The winter peak (January) was most pronounced in the age group 4-12 months, but in those more than 1 y old the peak came a month later. The median hospitalization time for community-acquired cases was 4 d (mean 5.9 d). The mortality was 0.1%. Rotavirus infection must therefore be regarded as a considerable burden, particularly with regard to infants and young children. Furthermore, the morbidity due to nosocomial infection with the rotavirus, analysed here in a long-term observational study, is unexpectedly high.

Child, Preschool↗

PubMed1999

The recognition pattern of sequential B cell epitopes of beta-lactoglobulin does not vary with the clinical manifestations of cow's milk allergy.

BACKGROUND: beta-Lactoglobulin (BLG) represents one of the major allergens causing cow's milk allergy (CMA) - a disease with a wide spectrum of clinical symptoms. The aim of this study was to evaluate sequential B cell epitopes of BLG by the Pin-ELISA method. Furthermore, we wanted to investigate a possible association of the IgE recognition patterns in sera of patients with BLG sensitization and the type of clinical reactions following contact with cow's milk. METHODS: Overlapping sequential decapeptides corresponding to the amino acid sequence of BLG were used in Pin-ELISAs specific for human IgE. Tested sera were from 14 individuals with CMA, 8 of them with a history of immediate systemic reactions and 6 with delayed skin reactions following contact with cow's milk. All of them showed specific IgE antibodies to BLG in the CAP-RAST. Control sera were from 5 healthy nonallergic individuals. RESULTS: All sera from BLG-sensitized individuals showed IgE binding with one region of BLG corresponding to amino acids 95-113. Furthermore, individual sera showed reactions with two further regions, 12-27 and 124-135. Inhibition of IgE binding to BLG with one soluble synthetic peptide confirmed the major epitope. No differences were found in the B cell epitope recognition pattern to BLG in the two groups of patients with CMA, characterized by acute systemic or delayed skin reactions. CONCLUSIONS: Using IgE Pin-ELISAs we were able to confirm previously described sequential B cell epitopes of BLG. However, the recognition pattern of one of the major cow's milk allergens is not predictive of the clinical type of reaction.

Amino Acid Sequence↗

PubMed1999

Linkage and association studies of atopy and the chromosome 11q13 region.

The clinical syndrome atopy is largely determined by genetic factors. In 1989, the first linkage of markers within and flanking the chromosomal region 11q13 and atopy was reported. In the following years, the gene coding for the beta chain of the high affinity IgE receptor was localised to this region and two polymorphisms in this gene have been shown to be associated with the atopic phenotype. We investigated two independent populations (population based and outpatient department) with different degrees of clinical symptoms. Using highly polymorphic markers we could find no evidence for linkage or allelic association of this particular genomic region to the atopic phenotype defined by enhanced IgE responsiveness (p>0.05). Neither did we succeed in finding either of the two polymorphisms described, nor could we identify any other polymorphisms within the gene. However, we found weak evidence for linkage in asthmatic sib pairs regarding maternal alleles (p=0.03). We conclude from our data that in our populations the gene for the beta chain of the high affinity IgE receptor is of minor importance for enhanced IgE responsiveness, and that it might influence atopy with clinical signs like asthma through maternally derived alleles.

Adolescent↗