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Biomedical subjects

V Stephan

Publications and source records attributed to V Stephan.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of respiratory syncytial virus detection by rapid antigen tests in childhood.

BACKGROUND: Rapid and reliable diagnosis is crucial for clinical management of respiratory syncytial virus infection in childhood. We assessed the performance characteristics of respiratory syncytial virus antigen immunoassays in children hospitalized for respiratory infection. METHOD: A total of 1600 children up to three years of age hospitalized for diseases potentially caused by RSV were included in the study. Nasopharyngeal secretions were obtained in a standardized manner in the first 24 hours after hospital admission and tested in parallel by PCR and rapid antigen tests for RSV. The following parameters were recorded: recruitment center, gender, age, presence of fever, rhinitis, stridor, barking cough, cough, wheezing, vomiting, disturbed eating or sleep, tachypnea, tachycardia, increased body temperature, decreased oxygen saturation, C-reactive protein, erythrocyte sedimentation rate and chest X-ray results. RESULTS: Considering PCR testing as gold standard, rapid antigen testing had a specificity of 89.9% and a sensitivity of 66.2% for all samples tested. Logistic regression analysis revealed age and recruitment center as the only parameters influencing sensitivity whereas no such influence on specificity was found. Positive likelihood ratios ranged from 4,9 to 6.9 in different age groups. Negative likelihood ratio was 0.24 (95% CI: 0.18-0.42) in children aged up to 3 months but 0.67 (95% CI: 0.53-0.84) for children older than 2 years. CONCLUSION: Rapid detection of RSV antigen in this study was useful in detection of RSV mediated disease in younger infants but shows decreasing sensitivity in children older than three months.

Antigens, Viral↗
PubMed2004

Severe respiratory syncytial virus infections and reduced interferon-gamma generation in vitro.

To study the consequences of the interaction of respiratory syncytial virus (RSV) with dendritic cells in vitro, we established a model of the primary immune response using dendritic cells, autologous naive T cells and the superantigen toxic shock syndrome toxin 1 (TSST 1). About 10% of the naive T cells express the T cell receptor chain Vbeta2. These cells were stimulated by TSST 1 and could be analysed by flow cytometry. Cultures infected with RSV produced significantly less interferon-gamma compared to uninfected cultures. In a first set of experiments we evaluated whether this culture model using isolated CD4(+) CD45RA(+) T cells, in fact, reflects the primary immune response. In a prospective study, cells were isolated from 13 children at birth, at 1 year of age and at 4 years of age. RSV reduced interferon-gamma production at all the age groups analysed and the results were stable over time within a given individual. In a second set of experiments, we asked whether clinical differences in the course of RSV infection are due to variations in the cellular immune response. At the age of 1 year (5-9 months after the RSV epidemic) dendritic cells and naive T cells were obtained from 27 children with a history of bronchiolitis, from 15 children with a benign course of RSV infection and from 26 controls without RSV infection. The frequency of interferon-gamma-producing cells in RSV infected cultures was significantly lower (P < 0.001) in cultures from children with a history of RSV bronchiolitis compared to children with mild RSV infection. Cultures from children without infection displayed a wide range of results. Overall, interferon-gamma generation in this group was still lower (P < 0.05) than in the group with mild RSV infection. Because we have ruled out that memory cells play a role in the experiments performed, the most likely explanation for our results is that a high generation of interferon-gamma in the primary immune response protects from severe RSV mediated disease.

Bacterial Toxins↗
PubMed2003

[Measurement of the deposition of salbutamol in the bronchial lavage fluid of infants and young children].

BACKGROUND: Inhaled salbutamol is well known to be effective in obstructive lung disease in the paediatric age group. However, the individually necessary dose cannot be predicted in a single patient. Two inhalation techniques were compared measuring the concentrations of salbutamol in the bronchial lavage fluid. PATIENTS AND METHODS: Forty nine children, age 2 to 73 months, inhaled salbutamol immediately before bronchoscopy, either 200 microg using a metered dose inhaler (MDI) or 2000 microg using a nebulizer (NEB). The concentrations of salbutamol were measured in the bronchial lavage fluid. RESULTS: In spite of different inhaled doses the concentrations of salbutamol were similar in the nebulizer group (n = 29) and the metered dose inhaler group (n = 20) (medians 160 vs. 163 ng/ml; p = 0.27) with a wide range in both groups (12 to 1139 and 5.2 to 641 ng/ml, respectively). In a single patient the concentrations differed by the factor 159 between the right and the left lung. The concentrations of salbutamol were not age dependent (p = 0.06 for NEB, p = 0.28 for MDI). CONCLUSIONS: In infants and young children the concentrations of salbutamol in the bronchial lavage fluid vary widely after a single inhalation using either a metered dose inhaler or a nebulizer.

Administration, Inhalation↗
PubMed2003

Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases.

Respiratory syncytial virus (RSV) is known to cause acute lower respiratory tract infections (ARI) in young children and is involved in exacerbation of chronic obstructive pulmonary disease (COPD) in adults. The role of RSV in stable COPD and the viral load in different respiratory diseases has not been investigated to date. The present authors established and evaluated a quantitative TaqMan real-time polymerase chain reaction assay specific for RSV subgroup A. Absolute quantification for the determination of viral load input was achieved using a control plasmid. The assay allowed for a quantification over a >6-log range and a detection limit of <10 RSV copies per reaction mixture. The assay was 30 times more sensitive than conventional nested polymerase chain reaction assays. Interassay SD was 1.3 and coefficient of variation 4.7% on average. Clinical specimens from infants with ARI (n=62) and elderly adults with COPD (n=125) were compared for viral loads. A total of 47% RSV-positive samples were found in the ARI study group and 28% in the COPD study group. The viral load of both study groups was found to differ significantly. In the ARI study group the viral load was increased almost 2000-fold, suggesting acute infection in this group and former or latent infection in the COPD group. Respiratory syncytial virus-A specific TaqMan real-time polymerase chain reaction assay is a sensitive and rapid method for the determination of viral load in clinical samples. It enables differential statements concerning the involvement of respiratory syncytial virus in acute lower respiratory tract infections and chronic obstructive pulmonary disease to be achieved.

Acute Disease↗
PubMed2002

Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy.

OBJECTIVE: To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). METHODS: We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological evidence of pulmonary disease. RESULTS: Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. CONCLUSIONS: With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in children with juvenile idiopathic arthritis impairment of lung function is a rare event.

Adolescent↗
PubMed2002

RSV bronchiolitis and risk of wheeze and allergic sensitisation in the first year of life.

Severe respiratory syncytial virus (RSV) infection has been hypothesised to be a risk factor for the development of allergy and asthma, but epidemiological studies in older children have been inconclusive. The current study hypothesises that the effect of RSV bronchiolitis might be most prominent during the first year after bronchiolitis. Forty-two infants had experienced RSV bronchiolitis severe enough to cause hospitalisation. For each child with RSV infection, two controls were acquired from a birth cohort and matched for date of birth and sex. All the children were followed prospectively and underwent a follow-up examination at a mean age of 1 yr, which included physical examination, and serum immunoglobulin (Ig) E tests for common food and inhaled allergens. Risk factors for the development of recurrent wheezing and IgE antibodies were analysed for the whole group of 126 children. A positive test for IgE antibodies was noted in 14 of 42 (33%) RSV children and in 2 of 84 (2.3%) children in the control group. RSV bronchiolitis was the most important risk factor for allergic sensitisation. Likewise, 13 children (15.5%) of the RSV group and three (3.6%) children of the control group suffered from recurrent wheezing, and RSV bronchiolitis posed a considerable risk for recurrent wheezing. Severe respiratory syncytial virus bronchiolitis during the first year of life is an important risk factor for the development of recurrent wheezing and sensitisation to common allergens during the subsequent year.

Bronchiolitis, Viral↗
PubMed1999

Generative character of perception: a neural architecture for sensorimotor anticipation.

The basic idea of our anticipatory approach to perception is to avoid the common separation of perception and generation of behavior and to fuse both aspects into a consistent neural process. Our approach tries to explain the phenomenon of perception, in particular, of perception at the level of sensorimotor intelligence, from a behavior-oriented point of view. Perception is assumed to be a generative process of anticipating the course of events resulting from alternative sequences of hypothetically executed actions. By means of this sensorimotor anticipation, it is possible to characterize a visual scenery immediately in categories of behavior, i.e. by a set of actions which describe possible methods of interaction with the objects in the environment. Thus, the competence to perceive a complex situation can be understood as the capability to anticipate the course of events caused by different action sequences. Starting from an abstract description of anticipatory perception and the essential biological evidence for internal simulation, we present two biologically motivated computational models that are able to anticipate and evaluate hypothetically sensorimotor sequences. Both models consider functional aspects of those cortical and subcortical systems that are assumed to be involved in the process of sensory prediction and sensorimotor control. Our first approach, the Model for Anticipation based on Sensory IMagination (MASIM), realizes a sequential search in sensorimotor space using a simple model of lateral cerebellum as sensory predictor. We demonstrate the efficiency of this model approach in the light of visually guided local navigation behaviors of a mobile system. The second approach, the Model for Anticipation based on Cortical Representations (MACOR), is actually still at a conceptual level of realization. We postulate that this model allows a completely parallel search at the neocortical level using assemblies of spiking neurons for grouping, separation, and selection of sensorimotor sequences. Both models are intended as general schemes for anticipation based perception at the level of sensorimotor intelligence.

Journal Article↗
PubMed1999

Genetic linkage of HLA-class II locus to mite-specific IgE immune responsiveness.

BACKGROUND: IgE response to common inhalant allergens seems to be the major determinant of the development of atopic rhinitis and asthma but it has been difficult to demonstrate genetic control of the IgE response. OBJECTIVE: To investigate genetic linkage between specific IgE reactions to purified aero-allergens (grass, birch, cat, mite) and the HLA-class II locus. METHODS: DNA-based HLA-class II typing was performed for determination of DRB1, DQB1 and DPB1 alleles. Linkage was studied by the affected sibpair method and the extended transmission disequilibrium test in 100 children from 40 nuclear families selected from a homogeneous population in south-western Germany. RESULTS: Significant linkage of mite-specific IgE response to HLA-DPB (P = 0.00001), HLA-DRB (0.02) and HLA-DQB (P = 0.001) was revealed by sibpair analysis of MHC class II alleles and confirmed by the extended transmission disequilibrium test for HLA-DRB (P = 0.01) and HLA-DPB (P = 0.04). No consistent significant linkage between the HLA-class II locus and IgE response to grass pollen, birch pollen, and cat dander could be demonstrated. CONCLUSION: The findings are consistent with the existence of one or more genes in the HLA-class II region modifying the IgE immune response to common environmental allergens.

Adolescent↗
PubMed1998

Reverse mutations--spontaneous amelioration or cure of inherited disorders?

Some recent publications indicate that inherited disorders can ameliorate or possibly disappear if mutations responsible for the disease revert to normal. This review tries to summarize our current knowledge about reverse mutations as this information may be of special interest for attempts at somatic gene therapy.

Child↗
PubMed1997

Anti-ganglioside monoclonal antibody AA4 selectively inhibits IgE-induced signal transduction pathways in rat basophilic leukemia cells.

In rat basophilic leukemia 2H3 (RBL-2H3) cells, mAb AA4 binds to two derivatives of ganglioside GD1b that associate with the Src family kinase p53/56lyn and a serine kinase. Pre-incubation of cells with mAb AA4 blocks immunoglobulin E (IgE) mediated histamine release. In the present study we investigated the effect of incubation with mAb AA4 on signal transduction events. In addition to stimulation of the high affinity IgE receptor (Fc epsilonRI), cells were also activated by the calcium ionophore A23187 and the acetylcholine agonist carbachol in RBL-2H3 cells transfected with the G protein-coupled m3 muscarinic receptor. Incubation of cells with mAb AA4 in a dose-dependent manner inhibited the following Fc epsilonRI-induced signal transduction events: the increase of intracellular free calcium, phosphoinositol breakdown, tyrosine phosphorylation of proteins including the beta- of Fc epsilonRI and secretion. However, there was no inhibition of degranulation or of these biochemical events when cells were stimulated with calcium ionophore or activated via a G protein-coupled pathway. Our results demonstrate that mAb AA4 selectively blocks Fc epsilonRI-induced cell activation at a very early step upstream of receptor tyrosine phosphorylation. As mAb AA4 has previously been found to bind to gangliosides associated with Fc epsilonRI, inhibition of very early biochemical events may be due to interaction of mAb AA4 with the Fc epsilonRI induced signal transduction cascade at the receptor level.

Animals↗
PubMed1997

Expression of mRNA for the proto-oncogene c-fos in rat basophilic leukaemia cells.

Recently, the expression of the mRNA for the proto-oncogene c-fos following activation of the high-affinity receptor for immunoglobulin E in rodent mast cells has been reported. In the present study we investigated different biochemical events that may play a role in signal transduction pathways culminating in the expression of c-fos mRNA in rat basophilic leukaemia cells. Similar to IgE-mediated cell degranulation we demonstrated inhibition of the c-fos signal in the absence of calcium and after preincubation of cells with the protein tyrosine kinase inhibitor genistein. Activation of RBL-2H3 cells by short term PMA treatment failed to induce cell degranulation or expression of mRNA for c-fos. Depletion of protein kinase C by PMA pre-treatment resulted in substantial inhibition of the c-fos signal. In contrast to IgE-mediated cell degranulation, expression of mRNA for c-fos was not dependent on continued receptor aggregation. In addition, we demonstrate that c-fos mRNA expression is not restricted to Fc epsilon RI activation but can be induced by a variety of IgE independent mechanisms including calcium influx by ionophore A 23187 and stimulation of G proteins.

3T3 Cells↗
PubMed1997

[Bile duct lesions in laparoscopic cholecystectomy--methods of reconstruction and results].

From 1/1991 to 1/1997 a total of 18 patients with major biliary lesions after laparoscopic cholecystectomy were treated. Besides 4 biliary strictures (Bismuth III, Siewert II), which were found between 20 and 180 days after laparoscopic cholecystectomy, large defects (Siewert III, IV) of the proximal parts of the hepatic duct (Bismuth III, IV) occurred in the majority of cases (n = 14). Except for 3 intraoperatively realized lesions, diagnosis was made during the first 3 weeks. Subsequent reinterventions resulted in a high morbidity rate and the need of further procedures to establish definitive biliary reconstruction. Selection criteria of the technique used for repair were the extension of the biliary lesion and the exposure of the distal stump of the common bile duct. A small defect was treated by direct suturing protected by a t-tube (n = 1). Large defects and biliary strictures were reconstructed using either a Roux-en-Y bilio-digestive anastomosis (n = 7) or jejunal interposition (n = 10). The results suggest, that early repair of biliary lesions after laparoscopic cholecystectomy should be achieved. Besides the standard procedure of bilio-digestive anastomosis, reconstruction of major biliary lesions should be performed by jejunal interposition in selected cases.

Adolescent↗
PubMed1996

Mite allergy, clinical atopy, and restriction by HLA class II immune response genes.

From a community-based study cohort of 1812 elementary schoolchildren we selected 129 unrelated participants to investigate the relevance of HLA-class II molecules (DPB, DQB, and DRB) to the regulation of immune response to the mite allergen Der p 1 and to clinical atopic disorders. On the basis of skin prick test results validated by measurement of specific IgE, individuals were selected and divided into three groups: group I (n = 20), controls without detectable specific IgE to common inhalant allergens; group II (n = 22), children sensitized only to non-mite allergens; group III (n = 85), children sensitized to Der p 1. Clinical history of asthma, eczema, and hay fever was ascertained using standardized questionnaires. In total, 43 different HLA class II alleles (DPB, n = 19; DQB, n = 14; and DRB, n = 10) were determined by sequence-specific oligonucleotide typing with PCR-amplified DNA. We were not able to demonstrate significant differences in gene frequencies of any HLA class II allele between the group of mite-sensitized children and one of the other two groups. However, the presence of certain DRB- and DPB-haplotypes (DRB *0100/*0300/*1100 and DPB *0201/*0401) was significantly associated (p < or = 0.01) with a history of asthma, hay fever, and atopy (defined as a history of asthma and/or hay fever and/or eczema). Other haplotypes, including DQB *0303/*0503, DRB *0200/ *0700, and DPB 0402 were negatively associated with a history of eczema, hay fever, and atopy (p < or = 0.01). Thus, our findings do not suggest a relevance of HLA-class II molecules to mite allergy; however, some HLA class II haplotypes appear to be predictive of the incidence of atopic disorders.

Allergens↗
PubMed1996

Severe combined immunodeficiency (SCID) associated neutropenia: a lesson from monozygotic twins.

A case of severe combined immunodeficiency (SCID) in monozygotic twin sisters was detected at 3 months of age with neutropenia in one twin and a normal differential count in the other. The neutropenic twin, suffering from severe skin ulcers, was successfully treated with granulocyte colony stimulating factor (G-CSF). Discordant occurrence of neutropenia in identical twins shows that there may be a non-genetic cause for the neutropenia in SCID. Suppression of myelopoiesis was probably induced by activated maternal T cells. The neutropenia in this case may thus be classified as SCID associated neutropenia, as opposed to reticular dysgenesis, in which the neutropenia is G-CSF refractory and is most probably caused by a genetic stem cell defect. A response to G-CSF in a neutropenic child with SCID can be clinically beneficial and might help to distinguish between G-CSF unresponsive reticular dysgenesis and G-CSF responsive SCID associated neutropenia.

Diseases in Twins↗
PubMed1994

The anti-ganglioside monoclonal antibody AA4 induces protein tyrosine phosphorylations, but not degranulation, in rat basophilic leukemia cells.

The monoclonal antibody AA4 (mAb AA4) recognizes novel alpha-galactosyl derivatives of GD1b on rat basophilic leukemia (RBL-2H3) cells. The binding of mAb AA4 induced protein tyrosine phosphorylations without histamine release. Several of the same proteins including Fc epsilon RI beta, Fc epsilon RI gamma, p72syk, and phospholipase C-gamma 1 were tyrosine-phosphorylated by mAb AA4 binding and by the activation of the high affinity IgE receptor, Fc epsilon RI. There was also activation of the p53/56lyn and p72syk protein-tyrosine kinases, but compared to direct Fc epsilon RI activation, mAb AA4 did not result in increased tyrosine phosphorylation of pp105-115 or pp125FAK, and the receptor subunits (Fc epsilon RI beta and Fc epsilon RI gamma) were more heavily phosphorylated. Furthermore, the time course of the phosphorylations with mAb AA4 was slower than that induced by Fc epsilon RI aggregation. By immunofluorescence, the tyrosine-phosphorylated proteins after mAb AA4 stimulation were localized in patches at the cell membrane and in areas of cell-cell contact, whereas after Fc epsilon RI activation, there was a reticular cytoplasmic pattern. There were no protein tyrosine phosphorylations either when Fc epsilon RI was saturated with IgE or when F(ab')2 fragments of mAb AA4 were used, although the F(ab')2 fragments still induced morphological changes. There was also coprecipitation of the beta and gamma subunits of Fc epsilon RI with the anti-ganglioside antibody. These data strongly suggest the involvement of Fc epsilon RI in the antiganglioside-induced protein tyrosine phosphorylations. Moreover, phosphorylations of these proteins including the beta and gamma chains of Fc epsilon RI and activation of p53/56lyn and p72syk did not result in histamine release.

Animals↗
PubMed1994

Autoimmune haemolytic anaemia in a child with MHC class II deficiency.

A 3 year old Turkish girl is described who was suffering from major histocompatibility complex (MHC) class II deficiency syndrome, which is characterised by the lack of expression of HLA class II antigens on mononuclear cells. The presence of HLA class II genes was demonstrable at the DNA level. Combined immunodeficiency was indicated by hypogammaglobulinaemia and the absence of delayed type hypersensitivity on skin testing. Further, she was unable to produce specific antibodies towards foreign antigens and suffered from recurrent pulmonary, gastrointestinal, and septic infections from the third month of life. The clinical course was complicated by a Coombs test positive haemolytic anaemia due to the production of autoantibodies against the rhesus "e' antigen, a non-glycosylated protein antigen. Haemolysis could be controlled by oral steroid treatment. This case is of interest as it shows that despite the absence of HLA class II antigens and combined immunodeficiency autoimmune reactions with production of specific autoantibodies directed to protein antigens are possible.

Anemia, Hemolytic, Autoimmune↗
PubMed1993

Sensitization to four common inhalant allergens within 302 nuclear families.

The coincidence of allergic sensitization was investigated in 302 school-aged children and their parents. Specific sensitization to four common inhalant allergens (grass and birch pollens, cat dander, Dermatophagoides pteronyssinus) was ascertained by means of skin-prick tests (SPT) carried out on the complete family unit at the beginning of a 22-month follow-up period. The same test procedure was then repeated on the children twice at 11-month intervals to provide cumulative prevalences of sensitization. A clinical history of atopy in the children (hay fever or asthma; n = 47), which was derived from an interview, is associated with sensitization (positive SPT in 89%). For three allergens (grass and birch pollens, cat dander) sensitization occurs significantly more frequently in the children of mothers who are sensitized to the same allergen (odds-ratios (ORs), 2.5-4.1). Additionally, in three of the four explanatory models related to a single antigen, maternal sensitization to one of the complementary allergens is of importance (ORs, 2.7-3.7). In contrast to this finding, none of the paternal sensitizations has statistical significance. Based on a reaction to at least one of the four allergens, the child's relative risk to be sensitized is increased in case of maternal (OR, 2.88; P = 0.001) but not of paternal (OR, 1.06; P = 0.83) sensitization. In conclusion, our data indicate that the maternal status is more predictive than that of the father with regard to the child's risk of sensitization.

Administration, Inhalation↗