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Biomedical subjects

B Niggemann

Publications and source records attributed to B Niggemann.

At least 109 records · Page 6Linked to original sources
PubMed1998

Prediction of sensitization to inhalant allergens in childhood: evaluating family history, atopic dermatitis and sensitization to food allergens. The MAS Study Group. Multicentre Allergy Study.

BACKGROUND: A family history of atopy is a poor predictor of sensitization to inhalant allergens and allergic disease during childhood. We recently identified early sensitization to food allergens, especially hen's egg, as a valuable predictor of subsequent sensitization to inhalant allergens. OBJECTIVE: (1) Whether prediction will be improved by in vitro allergy tests at 1 year of age in combination with family history and medical history data. (2) Comparison with the capacities of in vitro tests to predict sensitization to aeroallergens. METHODS: Of an observational birth cohort study (MAS) 49 children who were sensitized to inhalant allergens at 5 years of age and 116 non-sensitized controls were included in the present study. For the prediction of sensitization to inhalant allergens the following prognostic factors were evaluated: atopic family history (FH), atopic dermatitis (AD) during the first year of life, two in vitro allergy tests for specific IgE to common food allergens at 1 year of age (fx5 [Pharmacia] and single allergen specific tests (sIgE) for four allergens) and 'high' total serum IgE, defined by three different cut off points. RESULTS: The combination of medical history data and laboratory tests resulted in the best predictive discrimination. The positive predictive values (PPV) were higher if sensitization to food was detected by single allergen specific tests (PPV: 66%/75%/100% corresponding to the three evaluated risk groups) than by the qualitative fx5 (PPV: 46%/65%/100%). The negative predictive values were equal for both tests (69 and 92% for the two low risk groups). High total serum IgE had low predictive capacity. CONCLUSION: During infancy the prediction of sensitization to inhalant allergens should be based on medical history data and allergy tests determining sensitization to food allergens. The in vitro tests improve the predictive discrimination, but the individual risk profile of the child must be considered for a reliable and valid prediction.

Allergens↗
PubMed1998

Direct and rapid induction of migration in human CD4+ T lymphocytes within three-dimensional collagen matrices mediated by signalling via CD3 and/or CD2.

Specific activation of T cells requires stable cell-cell interaction; however, little is known how the transition from a previously motile state into a sessile state following activation is achieved. We investigated the direct effect of T-cell receptor (TCR)/CD3 complex engagement and/or stimulation of the accessory molecule CD2 on the locomotion of peripheral human T cells within three-dimensional (3-D) collagen lattices. Simultaneous engagement of CD3 and CD2 very potently stimulated T-cell migration, resulting in the recruitment of previously sessile cells (about 24% of the total population was additionally recruited) as well as an increase in the mean duration of active locomotion. This induction of migration was accompanied by an increased tyrosine phosphorylation of a 125 000 MW substrate corresponding to the focal adhesion kinase. Using confocal laser scanning microscopy we detected antibody-induced receptor capping into the uropod of migrating T cells whereas untreated control cells displayed an even distribution of CD3 and CD2 on the cell surface. Less pronounced induction of locomotion was achieved following triggering of CD3 or CD2 alone. Thus, in 3-D collagen lattices specific T-cell activation did not lead to cessation of cellular migration but rather induced cytoskeletal activity that ultimately resulted in vigorous locomotory activity.

Antibodies, Monoclonal↗
PubMed1998

Role of nonallergic hypersensitivity reactions in children with chronic urticaria.

BACKGROUND: IgE-independent (pseudoallergic) reactions to food and food ingredients are common in a subgroup of adult patients with chronic urticaria, who have daily spontaneous occurrence of wheals. However, for children with chronic urticaria (duration longer than 6 weeks, no physical influence), no data on the importance of pseudoallergen-induced chronic urticaria are available. Therefore, we investigated the role of nonallergic hypersensitivity to food in all children seen with chronic continuous urticaria in our two clinics over the last 2 years (n = 16). METHODS: All patients were given a low-pseudoallergen diet for 3 weeks followed by provocation with food rich in pseudoallergens. To identify the main eliciting agents, a subgroup of responders was exposed to food additives by double-blind, placebo-controlled food challenges. RESULTS: Pseudoallergen-induced urticaria was diagnosed in 12 cases (75%). Reactions occurred mainly to coloring agents and preservatives, but also to monosodium glutamate and a sweetener (saccharin/cyclamate). CONCLUSIONS: These results confirm that nonallergic hypersensitivity reactions play a role in children with chronic urticaria, although the latter disease is rare at that age. In children, food additives, especially coloring agents and preservatives, appear to play a more important role in eliciting nonallergic hypersensitivity reactions than in adult patients, where naturally occurring pseudoallergens in fruits and vegetables are mainly responsible.

Adolescent↗
PubMed1998

Development of latex allergy in children up to 5 years of age--a retrospective analysis of risk factors.

The aim of the study was to investigate possible associations between the time course of early sensitization to latex and various life style factors. Of the 398 children from a prospective birth cohort study, 20 (5%) showed specific serum IgE to latex at the age of 5 years. Sensitization started beyond the first year of life and 19 out of 20 sensitized children showed increasing specific IgE-values over time. All 20 sensitized children were atopic (p < 0.00000). Total IgE was significantly higher in the sensitized group (median 394.5 kU/I) than in the non-sensitized group (median 39.2 kU/l) (p < 0.00001). Comparing the latex-sensitized group with the non-sensitized children, there were significantly more operations in the latex group (p < 0.05) during the first 5 years of life. Medical history, certain foods, the use of pacifiers, mattress composition and socio-economic data proved not to be significant risk factors. From our study we conclude that besides the number of operations and an atopic predisposition--no other definite risk factor for developing sensitization or allergy to latex (such as everyday household objects) can be identified in children up to 5 years of age.

Age Factors↗
PubMed1998

Vocal cord dysfunction in three children--misdiagnosis of bronchial asthma?

Vocal cord dysfunction (VCD) is a paradoxical function of the vocal cords, leading to intermittent predominantly inspiratory dyspnea, but with no response to bronchodilator and anti-inflammatory drug therapy. We report on three children with VCD: 1) A 12-year old boy, who was treated for many years for bronchial asthma and who presented with inspiratory dyspnea and a functional reduction of the inspiratory and expiratory flow-volume curve, 2) a 13-year old girl who was also treated for bronchial asthma on a long-term basis and in whom the paradoxical vocal cord movement could be demonstrated by laryngoscopy, and 3) a 17-year old girl who, besides clinical symptoms of bronchial asthma in her anamnesis, suffered from an intermittent severe inspiratory dyspnea, refractory to bronchodilator treatment. Laryngoscopy proved the diagnosis of VCD. No patient showed a deterioration on discontinuation of their antiasthmatic therapy. VCD is best diagnosed by assessment of the vocal cords during laryngoscopy. The following therapeutic measures are helpful: 1) Demonstration of diagnosis (e.g. videodocumentation of laryngoscopy) and reassurance of patients and parents, 2) speech therapy, and 3) psychological intervention and/or psychotherapy. Our three cases point to a differential diagnosis of recurrent dyspnea in children and adolescents which may be overlooked. It is important to question earlier diagnoses, and to objectively evaluate the type of dyspnea.

Adolescent↗
PubMed1998

Changes in blood leukocyte distribution during double-blind, placebo-controlled food challenges in children with atopic dermatitis and suspected food allergy.

BACKGROUND: The development of clinical reactions to food antigens is associated with cellular changes. The aim of this study was to determine whether the clinical outcome of double-blind, placebo-controlled food challenges would correlate with changes in blood leukocyte distribution. METHODS: Double-blind, placebo-controlled food challenges were performed in 17 children with atopic dermatitis sensitized to hen's egg or cow's milk and in 9 children with atopic dermatitis but not sensitized to food. Blood leukocyte distribution and lymphocyte subsets were determined prior to and 24 h after challenges. RESULTS: In food-sensitized children the numbers of leukocytes and lymphocytes decreased significantly after allergen challenge independent of the clinical outcome of the provocation (p < 0.002 in both cases). This decrease was seen in T (CD3+) and B (CD19+) cell subsets (p<0.007 and p<0.0005, respectively). The CD4/CD8 ratio increased (p<0.04). The number of memory cells (CD45R0) dropped (p<0.02 for CD4 and p<0.004 for CD8) and there was a loss of L-selectin (p<0.003 for CD4 and CD8). No changes in thrombocytes, neutrophils, eosinophils and basophils were observed. None of these changes were seen in the sensitized patients during placebo challenges or in the non-sensitized group of children. CONCLUSION: Changes in the leukocyte distribution after allergen challenge seem to be associated with sensitization, but not with the clinical outcome of the oral food challenge. They reflect important changes in the immune system in response to allergens, but are not useful in monitoring double-blind, placebo-controlled food challenges.

Administration, Oral↗
PubMed1997

Locomotory phenotypes of human tumor cell lines and T lymphocytes in a three-dimensional collagen lattice.

Active cellular locomotion is a feature of such diverse cell types as lymphocytes and cancer cells. The locomotory phenotype of a cell should ultimately reflect the biochemical basis of different migratory strategies. We investigated the locomotory behavior of five epithelial cell lines and one non-epithelial human cell-line as well as human CD4+ T lymphocytes in a three-dimensional collagen type I matrix using time-lapse video microscopy and computer assisted cell-tracking. Migration velocity was up to 70 times lower in tumor cells (0.1-0.3 microm/min) as compared to T lymphocytes (7-7.5 microm/min), whereas the percentage of spontaneously active cells was up to twice as high in tumor cells (80-90%) in comparison to T lymphocytes (54%). Persistence, i.e. the degree of roaming, varied appreciably between the different cell types. In conclusion, velocity and persistence may describe distinct migration strategies in different cell types, i.e. discerning T cell migration from tumor cell invasion.

Cell Movement↗
PubMed1997

Differential requirement of protein tyrosine kinases and protein kinase C in the regulation of T cell locomotion in three-dimensional collagen matrices.

Locomotion of T lymphocytes within three-dimensional collagen matrices is regulated via different signaling states of the cells. Purified human CD4+ and CD8+ T cells developed a spontaneously locomoting subpopulation of about 25% of the whole population immediately after incorporation into a three-dimensional collagen matrix analyzed by time-lapse videomicroscopy. This spontaneous locomotion was accompanied by enhanced tyrosine phosphorylation of the focal adhesion kinase (FAK). Inhibition of protein tyrosine kinase (PTK) activity using genistein significantly reduced the spontaneous locomotory activity. This reduction was overcome by subsequent activation of protein kinase C (PKC) using PMA, which led to a persistent increase of locomotory activity to more than 60% of the cells. Thus, the PKC-driven type of locomotion was independent of PTK activity, whereas spontaneous locomotion was not altered by inhibition of PKC activity using calphostin C or inhibition of the serine/ threonine phosphatases pp1 and pp2A using okadaic acid. We presume that PTK activity, especially tyrosine phosphorylation of FAK, is decisively involved in the regulation of spontaneous T lymphocyte locomotion, which is independent of PKC activity. In contrast, PKC-driven locomotion is independent of tyrosine phosphorylation events, indicating that T lymphocyte locomotion is regulated by more than one signal transduction pathway. Furthermore, confocal microscopy analysis of phosphotyrosine residues, FAK, and PKC revealed an exclusive cellular distribution of these components, suggesting a regulation of T lymphocyte locomotion different from migration models developed for other cell types, which refer to a colocalization of FAK and PKC in focal adhesions.

CD4-Positive T-Lymphocytes↗
PubMed1997

Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of alpha2 and beta1 integrins and CD44.

The three-step model of cell migration consisting of protrusion of a leading lamella, attachment to the substrate, and contraction of the cell body is well established for fibroblasts migrating across planar surfaces. However, it is not resolved to what extent the migration of cancer cells in a 3-dimensional tissue environment follows similar principles. Here, we present evidence that the migration of highly invasive MV3 melanoma cells in 3-dimensional collagen matrices follows the three-step concept of migration but also results in characteristic reorganization of the extracellular matrix. After incorporation in the lattice, MV3 cells spontaneously developed a slow type of migration (mean velocity, 0.19 microm/min), leading to alignment of collagen fibers at attachment sites, as detected from unfixed and fixed samples by confocal reflection contrast in combination with immunofluorescence staining. In the process of migration, the formation of focal clusters or stripes of alpha2 and beta1 integrins colocalized with binding sites to collagen fibrils at the leading as well as the trailing edge. In contrast, CD44 was nonclustered and redistributed toward the rear end of the cell. At detachment sites, dynamic fiber traction, localized fiber disruption, and the release of cell surface determinants, including alpha2beta1 integrins and CD44, resulted in circumscribed matrix reorganization. Not infrequently, these emerging tube-like paths of least resistance bordered by a dense fiber network facilitated the reorientation and contact guidance of proximate MV3 cells to migrate along the preexisting path. In conclusion, the migration of MV3 cells in 3-dimensional collagen lattices resulted in dynamic tissue reorganization and receptor shedding the consequences of which were directly visualized by combining confocal reflection imaging with immunofluorescence.

Animals↗
PubMed1997

In vitro release of eosinophil cationic protein from peripheral eosinophils reflects disease activity in childhood Crohn disease and ulcerative colitis.

UNLABELLED: The aim of this study was to compare in vitro release of eosinophil cationic protein (ECP) from peripheral blood eosinophils during active phases of childhood Crohn disease (CD) and ulcerative colitis with phases of remission. Ten children with CD and nine children with ulcerative colitis were investigated during 55 and 56 clinical visits, respectively. Each patient was investigated during at least one phase of clinically active disease and one phase of remission. Disease activity was assessed by means of the Paediatric Crohn Disease Activity Index (PCDAI) in Crohn disease and according to the clinical activity index of Rachmilewitz in ulcerative colitis. On an intra-individual basis, in vitro ECP release was significantly higher (P < 0.001) during active phases of CD and ulcerative colitis than in phases of remission (CD:median: 24.5 microg/l, range 16.0-61.2 versus median: 5.7 microg/l, range 2.0-16.7; ulcerative colitis: 14.8 microg/l, 8.3-39.8 versus 4.9 microg/l, 2.0-9.9). On an inte-individual basis, in CD and ulcerative colitis a strong and highly significant correlation was observed between disease activity indices and in vitro release of ECP from peripheral eosinophils (r = 0.89, P < 0.0001 and r = 0.82, P < 0.0001, respectively). CONCLUSION: These results show that in vitro ECP release from peripheral eosinophils reflects disease activity in both CD and ulcerative colitis and therefore can be used as a new appropriate laboratory parameter for assessment of disease activity in chronic inflammatory bowel disease.

Adolescent↗
PubMed1997

Effect of a mistletoe extract (Iscador QuFrF) on viability and migratory behavior of human peripheral CD4+ and CD8+ T lymphocytes in three-dimensional collagen lattices.

Migration and tissue distribution of immunocompetent cells may be critical prerequisites for efficient immune surveillance. The effect of various concentrations of the mistletoe extract Iscador QuFrF on the locomotory behavior and viability of immunomagnetically isolated human CD4+ and CD8+ T lymphocytes within three-dimensional collagen gels was investigated. Although variation in baseline activities of spontaneously migrating T cells was donor-dependent, a dose-dependent stimulation of the locomotory activity in both CD4+ and CD8+ T cells for noncytotoxic concentrations of Iscador QuFrF (0.25-1.25 micrograms/ml) was detected. The optimal concentration of mistletoe extract and time of maximal response were specific for each donor. As shown by cell tracking and subsequent data analysis, CD4+ T cells exposed to the mistletoe extract displayed a significant increase in mean velocity and time locomoting; total distance migrated was nearly doubled. In contrast, CD8+ T cells showed less pronounced changes in these critical parameters. Cytotoxic effects of the mistletoe preparation on T lymphocytes, which could at least partially be attributed to the induction of apoptosis, were drastically reduced in the presence of fetal calf serum in the culture system. Our data suggest that the direct stimulation of T-cell migration in the presence of mistletoe components may modulate in a dose-dependent manner the system of immune surveillance and recognition in patients under mistletoe therapy.

Adjuvants, Immunologic↗
PubMed1997

Severe allergic reactions to foods are predicted by increases of CD4+CD45RO+ T cells and loss of L-selectin expression.

OBJECTIVE: The aim of the study was to determine whether the clinical outcome of double-blind, placebo-controlled food challenges of patients with atopic dermatitis would be associated with changes in lymphocyte functions. METHODS: Peripheral blood mononuclear cells were prepared from 19 children with atopic dermatitis and stimulated in vitro with the suspected allergen (cow's milk, hen's egg), tetanus toxoid, and pokeweed mitogen. After 14 days in culture, quantitative and qualitative distribution of cell surface marker expression was assessed by flow cytometry, and results were compared with the clinical outcome of a subsequent oral food challenge. RESULTS: After stimulation with the allergen, a significant increase of CD4+CD45RO+ T cells (p < 0.05) was detected selectively for patients showing severe clinical reactions. This increase was not detected for patients with mild or no reactions or in six nonatopic control subjects. Increased expression of CD45RO was paralleled by a significant decrease in L-selection expression (p < 0.05) for the same patient group. CONCLUSION: The combined assessment of CD4+CD45RO+ and CD4+L-selectin+ expression on T cells was more sensitive for the prediction of the clinical outcome of the food challenge (p < 0.01) than measurement of cytokines or immunoglobulins in cell culture supernatants. These data indicate that a shift in lymphocyte functions may predict the development of severe allergic reactions in food-sensitized children with atopic dermatitis.

Acute Disease↗
PubMed1997

A case of cow's milk allergy in the neonatal period--evidence for intrauterine sensitization?

Clinical manifestations of cow's milk allergy rarely occur in the first days after birth. We report on a newborn presenting with hemorrhagic meconium in the first hour of life followed by bloody diarrhea in the next few days. At day 14, an elevated total IgE, specific IgE to cow's milk and an eosinophilia in peripheral blood were found. Symptoms disappeared when the milk feed was changed to an extensively hydrolyzed casein-formula. Two challenges with cow's milk formula (on day 30 and at 7 months of age) were followed by recurrence of vomiting, watery diarrhea and failure to thrive. At the age of 17 months cow's milk was tolerated well. Although other pathogenetic mechanisms cannot completely be ruled out, there is strong evidence that cow's milk allergy--induced by intra-uterine sensitization--explains the symptoms in our patient. In conclusion, cow's milk allergy can occur even in the first days of life, and our clinical observation supports the concept of intra-uterine sensitization to allergens.

Animals↗