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Biomedical subjects

J Forster

Publications and source records attributed to J Forster.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1998

Detection of respiratory syncytial virus RNA in blood of neonates by polymerase chain reaction.

During the winter season of 1994/1995, nasopharyngeal aspirates and blood samples of neonates who were admitted to the Neonatal Intensive Care Unit (NICU) (group 1) and infants with respiratory tract disease (group 2) were examined prospectively for the presence of respiratory syncytial virus (RSV). Examination of nasal washes were done by antigen detection and blood samples were tested by nested reverse transcription and polymerase chain reaction (RT-PCR). The results of the 41 neonates studied were as follows: 14/41 were positive for RSV antigen in nasal washes and for RSV-RNA in blood, 5/41 were only RSV antigen positive, 13/41 neonates had negative nasal washes; 6 had positive RT-PCR results in blood. In 9/41 cases only blood samples were available. Five of these were positive by RT-PCR testing. Group 2 included 20 infants hospitalized with respiratory tract disease, e.g., pneumonia, bronchiolitis, or Upper Respiratory Tract Infection (URTI). Eleven out of twenty were positive for RSV antigen in nasal washes and 6/20 were also positive for RSV-RNA in blood. The conclusion is that viremia may be a frequent occurrence in neonates and young children.

Amino Acid Sequence↗
PubMed1998

Predisposing conditions and pathogens in bacteremia in hospitalized children.

Between 1985 and 1995, 1037 bacteremic episodes were recorded in a pediatric tertiary care center and analyzed retrospectively. Gram-positive bacteria accounted for 719 episodes (68%), gram-negative bacteria for 303 (29%), fungi for 16 (2%), and anaerobes for 12 (1%). In 526 (51%) patients, primarily neonates and oncology patients, a predisposing condition was present. In 390 (38%) episodes a clinical source of infection was documented. Mortality was highest in Pseudomonas bacteremia (45%). Since the bacterial spectrum differed widely between patient groups, the choice of empirical antimicrobial therapy should be based on any underlying condition present in the patient and the clinical source of infection. As anaerobes were rarely isolated. the routine use of anaerobic blood cultures in patients without predisposing conditions does not seem warranted.

Anti-Bacterial Agents↗
PubMed1998

[Bickerstaff encephalitis. Clinical and magnetic resonance follow-up studies].

We present a patient with Bickerstaff's brainstem encephalitis in whom MR imaging correlated with the clinical findings during the course of the disease. T2-weighted MR imaging showed increased signal intensity in the medulla oblongata, upper pons, pendunculi cerebelli and the cerebellum. In the course of the disease the lesions on MRI tended to descend more caudally. No anti-GQ1b antibody titers could be detected in the acute phase of the illness. Our findings suggest that MRI is the most valuable diagnostic tool in supporting the clinical diagnosis of Bickerstaff's brainstem encephalitis and may be helpful in the distinction between Miller Fisher syndrome and Bickerstaff's brainstem encephalitis.

Brain Stem↗
PubMed1998

High-resolution cardiac imaging using an interleaved 3D double slab technique.

A three-dimensional (3D) gradient-echo sequence with interleaved double-slab excitation was developed and optimized for the requirements in pediatric cardiac imaging. For this purpose high contrast between blood and myocardium signal should be obtained without the use of contrast agents. An acceptable measuring time for a large region examined with high spatial resolution should be achieved as well, especially with regard to the small structures of the heart and vessels of infants. The presented approach works with gradient moment nulling and a short echo time of 5.5 ms resulting in generally high signal intensity and only minor signal losses due to turbulent flow. The sequence allows simultaneous ECG-gated recording of two separately excited slabs with small thickness (10 mm) and with a distance of several centimeters between them. Thus, common effects of presaturation in 3D imaging can be avoided, although a relatively short measuring time is achievable. In order to get a 3D data set with good signal homogeneity of blood and of the other structures across a large volume of interest several double-slab measurements with suitable positions must be performed. The latter aspect is especially important for postprocessing techniques as multiple planar reconstruction and maximum intensity projection. Examples of applications of the new technique and appropriately postprocessed images are presented allowing demonstration even of subtle cardiac malformations.

Artifacts↗
PubMed1998

Linkage and allelic association of atopy and markers flanking the IL4-receptor gene.

BACKGROUND: Atopy, a clinical syndrome characterized by heightened IgE responsiveness, is largely determined by genetic factors. The disease may well be heterogeneous but the mode of inheritance is unknown. Several genes have been named which affected IgE responsiveness. However, results are conflicting reflecting heterogeneity and a complicated inheritance pattern of the atopic syndrome. In 1994 linkage of the 5q32 gene region and elevated total IgE levels were reported, leaving the IL4 gene as a prominent candidate. OBJECTIVES: We were interested in a possible involvement of the IL4-receptor gene in the development of atopy. METHODS: We employed sib-pair linkage analysis using highly polymorphic microsatellite markers within and flanking the IL4 receptor gene in atopic families, characterized for specific sensitization to inhalant allergens and elevated total serum IgE. Allele sizes were determined for all microsatellite probes to allow transmission disequilibrium analysis. RESULTS: We found significant sharing of maternal but not paternal alleles in affected sibs from two independent populations, both of which presented enhanced IgE responsiveness. Linkage and maternal inheritance could be confirmed by transmission disequilibrium analysis. CONCLUSIONS: We conclude from our findings that maternal inheritance of a gene in the chromosome 16p12 region increases the risk for enhanced IgE responsiveness. The most prominent candidate in this region is represented by the IL4 receptor gene.

Adolescent↗
PubMed1998

Cord blood-IgE as risk factor and predictor for atopic diseases.

BACKGROUND: Cord blood-IgE as risk factor or predictor for atopic diseases in infants has been discussed in a large number of papers with contradictory results. Our aim was to evaluate cord blood-IgE as risk factor and predictor for atopic dermatitis, recurrent wheezing and sensitization with emphasis on a clear-cut distinction between risk factor and predictor. METHODS: A cohort of 1314 newborns was recruited in six German obstetric departments and followed-up for 5 years. Four hundred and ninety-nine infants (38%) were considered to be at high risk with at least two atopic family members and/or a cord blood-IgE value above the threshold of 0.9 kU/L. At follow-up visits, parents filled in a questionnaire, the infants were clinically examined, and blood samples were taken. RESULTS: With regard to early onset atopic dermatitis up to 12 months we found that the odds ratios at the cord blood-IgE cut-off points of 0.70 kU/L and 1.25 kU/L with values of 0.53 and 0.32, respectively, were smaller than one (i.e. protective factors) and highly statistically significant. No significant association was found between elevated cord blood-IgE and recurrent wheezing. There was a strong positive association between elevated cord blood-IgE levels and sensitization at 12 months, but even in this case the predictive performance was rather poor: a maximum positive predictive value of 42% was attained with a cut-off point of 3.0 kU/L, but the sensitivity was only 10%. CONCLUSION: We conclude that even when elevated cord blood-IgE levels are identified as a strong risk factor for sensitization, their poor predictive performance may make them useless as a basis for preventive measures.

Child, Preschool↗