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Biomedical subjects

B Niggemann

Publications and source records attributed to B Niggemann.

At least 73 records · Page 4Linked to original sources
PubMed2001

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

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

Age Factors↗
PubMed2001

Predictors of positive food challenge outcome in non-IgE-mediated reactions to food in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is frequently associated with food allergy. In general, clinically manifested food allergy is regarded as IgE mediated. However, there are some children with food allergy for whom IgE hypersensitivity cannot be proven. OBJECTIVE: The aim was to evaluate the percentage of children with positive double-blind, placebo-controlled food challenge (DBPCFC) results but without any proof of IgE sensitization and to characterize this subgroup of children. METHODS: Two hundred eight DBPCFCs were performed in 139 children (median age, 13 months) with atopic dermatitis and suspected food-related clinical symptoms. All children were subjected to skin prick tests (SPTs), determination of specific IgE, and atopy patch tests. RESULTS: One hundred eleven (53%) of 208 oral food challenge results were assessed as positive. Positive challenge results were separated into 2 groups according to IgE positivity: negative SPT and negative specific IgE results in serum (group A, n = 12) and positive SPT, specific IgE, or both results in serum (group B, n = 99). The atopy patch test results; the distribution of early, late, or both clinical reactions; the age of the children; and the total IgE levels all showed no significant differences between the 2 groups. However, wheat challenge results were more often positive among the apparently non-IgE-sensitized children, and hen's egg challenge results were more often positive in the sensitized group (P < .05). CONCLUSION: Around 10% of positive DBPCFC results are not IgE mediated. Therefore not the proof of specific IgE but the suspicion of food-related symptoms should be the indication to perform oral food challenges, especially in the case of wheat. Otherwise, some children will not receive diagnoses for food allergy and be denied the benefits of a specific diet.

Allergens↗
PubMed2001

High PKC alpha and low E-cadherin expression contribute to high migratory activity of colon carcinoma cells.

The protein kinase C (PKC) is a family of serine/threonine kinases that are key regulatory enzymes involved in growth, differentiation, cytoskeletal reorganization, tumor promotion, and migration. We investigated the functional involvement of PKC isotypes and of E-cadherin in the regulation of the locomotion of six human colon-adenocarcinoma cell lines. The different levels of the PKC alpha and the E-cadherin expression have predictable implications in the spontaneous locomotory activity. With the use of PKC alpha--specific inhibitors (safingol, Go6976) as well as the PKC delta--specific inhibitor rottlerin, we showed that only PKC alpha plays a major role in the regulation of tumor cell migration. The results were verified by knocking out the translation of PKC isozymes with the use of an antisense oligonucleotide strategy. After stimulation with phorbol ester we observed a translocation and a colocalization of the activated PKC alpha at the plasma membrane to the surrounding extracellular matrix. Furthermore, we investigated the functional involvement of E-cadherin in the locomotion with the use of a blocking antibody. A high level of PKC alpha expression together with a low E-cadherin expression was strongly related to a high migratory activity of the colon carcinoma cells. This correlation was independent of the differentiation grade of the tumor cell lines.

Acetophenones↗
PubMed2001

Hev b 8, the Hevea brasiliensis latex profilin, is a cross-reactive allergen of latex, plant foods and pollen.

BACKGROUND: Plant profilins are important pan-allergens. They are responsible for a significant percentage of pollen-related allergies. Limited information is available about their involvement in the latex-fruit syndrome and the cross-reactivities between latex and pollen. We aimed to clone and express the Hevea brasiliensis latex profilin to investigate its allergological significance and serological cross-reactivities to profilins from plant foods and pollens. METHODS: A DNA complementary to messenger RNA (cDNA) coding for the Hevea latex profilin, Hev b 8, was amplified by polymerase chain reaction from latex RNA. Recombinant (r)Hev b 8 was produced in Escherichia coli and used to screen sera from 50 latex- allergic health care workers (HCWs) with well-documented histories of food and pollen allergy and 34 latex-allergic spina bifida (SB) patients. The cross-reactivity of natural Hev b 8 and rHev b 8 with other plant profilins was determined by ELISA inhibition assays. A three-dimensional homology model of Hev b 8 was constructed based on known profilin structures. RESULTS: The cDNA of Hev b 8 encoded a protein of 131 amino acids with a predicted molecular mass of 14 kD. Twelve of the 50 HCWs and 2 of the 34 SB patients were sensitized to Hev b 8. All Hev b 8-sensitized patients showed allergic symptoms to pollen or plant foods. Cross-reactivities between profilins of latex, pollen and plant food were illustrated by their ability to inhibit IgE binding to rHev b 8. Homology modeling of Hev b 8 yielded a structure highly similar to Bet v 2, the birch pollen profilin, with the most distinct differences located at the N-terminus. CONCLUSIONS: We conclude that primary sensitization to latex profilin in the majority of cases takes place via pollen or food profilins. Additionally, pollinosis and food-allergic patients with profilin-specific IgE can be at risk of developing latex allergy.

Allergens↗
PubMed2001

Sensitizing capacity and residual allergenicity of hydrolyzed cow's milk formulae: results from a murine model.

BACKGROUND: Cow's milk allergy is the most common cause of clinically relevant adverse reactions to food in infants and children. Partially and extensively hydrolyzed formulae are used for the therapy and prevention of cow's milk allergy. However, the immunogenic potency of hydrolyzed cow's milk formulae to induce and/or enhance the allergic phenotype in vivo is still under debate. The aim of this study was to assess the sensitizing capacity and residual allergenicity of various partially and extensively hydrolyzed cow's milk formulae in a murine model of cow's milk allergy. METHODS: BALB/c mice were immunized with either a cow's milk formula or various partially and extensively hydrolyzed formulae. Immediate cutaneous hypersensitivity reactions and allergen-specific antibody production were assessed. RESULTS: Although immunization with cow's milk resulted in 12/13 cases in a positive skin test response to intradermal injection of cow's milk formulae, only 1 mouse showed a positive skin test to one of the partially hydrolyzed formulae, and none showed positive reactions to other partially hydrolyzed formulae, any of the extensively hydrolyzed formulae, phosphate-buffered saline or the amino acid formula. However, 6 of 8 mice showed positive skin tests when immunized with partially hydrolyzed formulae and with one of the extensively hydrolyzed formulae. CONCLUSIONS: The residual allergenic potential is markedly reduced in many hydrolyzed formulae, but most of the formulae investigated could induce an allergic immune response in BALB/c mice. Our murine model seems to be suitable to investigate the sensitizing capacity of hydrolyzed formulae and to differentiate even between extensively hydrolyzed formulae.

Animals↗
PubMed2001

Histamine challenges discriminate between symptomatic and asymptomatic children. MAS-Study Group. Multicentre Allergy Study.

The aims of this study were to investigate a threshold value for bronchial responsiveness in children aged 7 yrs, which discriminates between symptomatic and asymptomatic children, and to identify determinants of this responsiveness. Titrated bronchial histamine challenges using the reservoir method were performed in 645 children aged 7 yrs, from the birth cohort Multicentre Allergy Study (MAS). When defining a reference population of healthy children within the MAS cohort, the 95th percentile of the provocative concentration causing a 20% fall in forced expired volume in one second PC20 among these asymptomatic study subjects amounted to 0.60 mg x mL(-1). This resulted in a specificity of 93.0% and a sensitivity of 45.9%, for discriminating between "current wheezers" and "non-current wheezers". Determinants of airway responsiveness at this age were pulmonary function, sensitization to indoor allergens, total immunoglobulin E and current wheeze. The results indicate that a very low cut-off provocative concentration causing a 20% fall in forced expired volume in one second (<1.0 mg x mL(-1)) defines airway hyperresponsiveness in children aged 7 yrs using the reservoir method. Provocation protocols for histamine challenges in this age group should therefore start with concentrations markedly below 1.0 mg x mL(-1).

Allergens↗
PubMed2000

Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Multicentre Allergy Study Group.

BACKGROUND: In a prospective birth-cohort study, we assessed the relevance of mite and cat allergen exposure for the development of childhood asthma up to age 7 years. METHODS: Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available for 939 children. Assessments included repeated measurement of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months, and 3 years of age, and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial hyper-responsiveness was measured in 645 children. FINDINGS: At age 7, the prevalence of wheezing in the past 12 months was 10.0% (94 of 938), and 6.1% (57 of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze, and increased bronchial responsiveness. However, no relation between early indoor allergen exposure and the prevalence of asthma, wheeze, and bronchial hyper-responsiveness was seen. INTERPRETATION: Our data do not support the hypothesis that exposure to environmental allergens causes asthma in childhood, but rather that the induction of specific IgE responses and the development of childhood asthma are determined by independent factors.

Air Pollution, Indoor↗
PubMed2000

Characterization of T cell responses to Hev b 3, an allergen associated with latex allergy in spina bifida patients.

The prevalence of type I allergy to Hevea brasiliensis latex is particularly high among individuals with frequent exposure such as health care workers and patients with spina bifida (SB). Due to a birth defect of the spinal canal and the resulting neurological and orthopedic defects, these patients require multiple surgeries during childhood. SB patients display a unique pattern of sensitization: IgE-reactivity is preferentially directed against Hev b 3 and Hev b 1, two latex allergens with high sequence similarity. In this study, we analyzed the T cell response to Hev b 3 in latex-allergic SB patients using poly-, oligo-, and monoclonal T lymphocyte cultures. All T cell clones (TCC) were CD3/CD4-positive and expressed the alphabeta TCR. According to their cytokine production pattern (IL-4 vs IFN-gamma), 12 of 21 TCC were classified as Th2-like, 2 of 21 were Th1-like, and 7 of 21 belonged to a Th0-like subset. Using 11 T cell lines and 21 TCC, nine T cell stimulating fragments were determined out of 52 overlapping 12-mer peptides representing the complete amino acid sequence of Hev b 3. Ag presentation of one dominant T cell epitope could be associated with a four-amino acid binding motif (YSTS, position 11-13) in the beta 1 chain of HLA-DR molecules expressed by the respective patients. No reactivity was observed when Hev b 3-reactive T cell lines or TCC were incubated with peptides representing homologous parts of the Hev b 1 molecule, i.e., no cross-reactivity between Hev b 3 and Hev b 1 at the T cell level was evident.

Allergens↗
PubMed2000

T lymphocytes and neutrophil granulocytes differ in regulatory signaling and migratory dynamics with regard to spontaneous locomotion and chemotaxis.

Chemotactic migration of T lymphocytes and neutrophil granulocytes within a three-dimensional collagen matrix is distinct from spontaneous, matrix-induced migration concerning dynamic parameters and regulatory intracellular signaling. Both spontaneous T lymphocyte locomotion and stromal-cell-derived factor-1 (SDF-1)-induced chemotaxis-involved protein tyrosine kinase (PTK) activity, whereas only SDF-1-induced migration was protein kinase C (PKC) dependent. Spontaneous locomotion of neutrophil granulocytes was independent of PKC and PTK activity, but formyl-methionyl-leucyl-phenylalanine-induced migration involved PKC activity. In addition, the microtubule cytoskeleton was not changed after induction of chemotaxis in both cell types. T lymphocytes had a well-developed microtubule cytoskeleton with the microtubule organizing center located in the uropod, whereas neutrophil granulocytes revealed a clustered tubulin distribution at the leading edge of the migrating cell. Therefore, differences of the microtubule cytoskeleton might contribute to differences in locomotion between T lymphocytes and neutrophil granulocytes but not to differences between spontaneous locomotion and chemotaxis.

Cell Movement↗
PubMed2000

Migration of dendritic cells within 3-D collagen lattices is dependent on tissue origin, state of maturation, and matrix structure and is maintained by proinflammatory cytokines.

The function of dendritic cells (DC) depends on active migration through three-dimensional (3-D) extracellular matrices. We have analyzed the migration of murine DC from different tissue origins within 3-D collagen lattices through the use of time-lapse videomicroscopy and single-cell tracking. Directly after incorporation, 50-90% of DC from the spleen (spDC) and Langerhans cells freshly isolated from the epidermis (fLC) displayed active motility in these matrices. Whereas mature spDC showed multilateral pseudopod dynamics as well as fast and heterogeneous migration, immature fLC displayed a spherical shape with faint membrane processes and very homogenous, slow migration characteristics. In the absence of external stimuli, migration of both, spDC and fLC, vanished after >36 h due to cell death. Maintaining fLC viability by external granulocyte-macrophage colony-stimulating factor or tumor necrosis factor alpha prolonged migration up to 5 days. During this period fLC transformed into mature cells with large dendrites, thereby developing a heterogeneous migration pattern more similar to spDC. In randomly polymerized collagen matrices cell paths were without preferential orientation. In contrast, in artificially aligned lattices directional paths in accordance with the forced fiber orientation were observed. Thus, migration is an inherent property of DC, largely influenced by tissue origin, degree of maturity, and the 3-D structure of the environment.

Animals↗
PubMed2000

Is there a role for immunoblots in the diagnosis of latex allergy? Intermethod comparison of in vitro and in vivo IgE assays in spina bifida patients.

BACKGROUND: The best diagnostic method for latex allergy is still controversial. This investigation was designed to evaluate the diagnostic efficiency of immunoblotting in comparison with established in vitro and in vivo test systems. METHODS: A total of 108 spina bifida patients were investigated by questionnaire and skin prick test (SPT). Specific serum IgE to latex was analyzed by the Pharmacia CAP FEIA immunoassay, DPC AlaSTAT microplate immunoassay, and DPC AlaBLOT immunoblot. Patients were regarded as latex allergic if they reacted positively to challenge by the latex glove wearing test. RESULTS: Thirty-four patients reacted positively to challenge. The sensitivity rates were 97% (SPT), 94% (immunoblot, CAP), 74% (AlaSTAT), and 35% (clinical history). The specificity rates were 92% (clinical history), 88% (AlaSTAT), 77% (SPT), 76% (CAP), and 69% (immunoblot). If two methods were combined, efficiency rates were highest for SPT combined with CAP (sensitivity 94%, specificity 82%), with AlaSTAT (sensitivity 74%, specificity 92%), or with immunoblot (sensitivity 91%, specificity 84%). The sera of challenge-positive patients recognized more immunoblot bands than challenge-negative patients, and the severity of symptoms correlated with the number of recognized bands. CONCLUSIONS The diagnostic efficiency of immunoblotting is not superior to that of SPT. However, immunoblotting may serve as an additional tool to increase slightly the specificity of SPT and specific serum IgE tests.

Adolescent↗
PubMed2000

The atopy patch test (APT)-- a useful tool for the diagnosis of food allergy in children with atopic dermatitis.

BACKGROUND: While immediate-type clinical reactions to food can quite easily be identified by history or measurement of specific IgE in combination with positive oral food challenges, the evaluation of food allergy in the absence of immediate clinical reactions still presents diagnostic difficulties--particularly in children with atopic dermatitis. The objective of this study was to evaluate the diagnostic value of the atopy patch test (APT) with regard to late-phase reactions observed in double-blind, placebo-controlled food challenges with cow's milk, hen's egg, wheat, and soybean. METHODS: We investigated 75 children (median age 2.1 years) with suspected food allergy by double-blind, placebo-controlled food challenges, specific IgE in serum, skin prick test, and APT. Of the subjects, 69/75 suffered from atopic dermatitis. RESULTS: Of 209 oral challenges, 133 were performed with allergen and 76 with placebo. We assessed 77/133 allergen and 2/76 placebo challenges as positive. In 66 of 77 (86%) positive oral challenges, specific IgE in serum to the corresponding allergen was positive; in 64/77 (83%) the skin prick test, and in 42/77 (55%) the APT was positive. While immediate-type reactions were associated with positive skin prick test and proof of specific IgE in serum, late-phase clinical reactions were associated with a positive APT (sensitivity 76%, specificity 95%). CONCLUSIONS: The APT seems to be a valuable additional tool in the diagnostic work-up of food allergy in children with atopic dermatitis - especially with regard to late-phase clinical reactions. The APT may help to prevent unnecessary restrictive diets which may be the consequence of misjudging late reactions by clinical assessment alone.

Animals↗
PubMed2000

What safety measures need to be taken in oral food challenges in children?

BACKGROUND: Food allergens are often accused of causing numerous ailments. This is particularly true for the pediatric population, where the incidence of food allergy is four times as high as in adults. As food challenges may provoke life-threatening reactions, intensive safety measures need to be taken during provocation, and prompt medical intervention may become necessary. METHODS: We retrospectively evaluated 349 oral challenges in 204 children with atopic dermatitis, looking for criteria to help the physician decide which patients need medical intervention. RESULTS: A total of 178 (51%) oral food challenges with the four allergens (cow's milk [CM], hen's egg [HE], wheat, and soy) showed a positive clinical reaction. Of these, 120 (67%) needed medical intervention. In 42 (35%) cases, intervention was parenteral, and oral medication was given in 78 (65%) cases. There was a strong positive correlation (90%) between the level of specific IgE and the need for medical intervention (> or = 17.50 kU/l for CM, wheat, and soy; > or = 3.50 kU/l for HE). Patient history of food allergy was an indicator of the need for medical intervention (P = 0.01). A positive patient history and a high level of specific IgE were significantly (P=0.003) associated with parenteral medication in HE. CONCLUSIONS: Patient history of food allergy is a reliable indicator of the need for medical intervention in the cases of CM, wheat, and soy regardless of the level of specific IgE. With HE, a positive patient history plus a high level of specific IgE significantly indicates the need for parenteral medication. On the basis of our results, we recommend establishing intravenous access in children with a level of specific IgE of > or = 17.50 kU/l (CAP class 4) to CM and wheat, or with specific IgE of > or =3.50 kU/l (CAP class 3) to HE.

Administration, Oral↗
PubMed2000

Ventricular shunts and the prevalence of sensitization and clinically relevant allergy to latex in patients with spina bifida.

Patients with spina bifida represent the highest-risk group for developing hypersensitivity to latex. Recognized risk factors for these patients are repeated surgery and an atopic disposition. Our aim was to study the influence of a ventricular shunt as an independent risk factor. One hundred and sixty-one patients with spina bifida (median age 10 years) were investigated for the presence of a shunting device and the number, type and date of previous surgical interventions. Additionally, skin-prick tests and provocation tests were performed in order to classify sensitized and symptomatic latex-allergic individuals. Eighty-eight patients (54.7%) were sensitized; 55 (34.2%) were provocation-positive. Patients with a shunt system had undergone a significantly higher number of surgical procedures (p < 0.0001) and showed significantly higher levels of immunoglobulin E (IgE)-antibodies to latex (p < 0.0001) than patients without a shunting device. The total number of operations correlated significantly with the level of IgE-antibodies to latex in serum (p < 0.0001), whereas the number of shunt operations in patients with a ventricular shunt did not significantly correlate with the degree of sensitization. In conclusion, patients with spina bifida who have a ventricular shunt are at particularly high risk because they undergo a significantly higher number of operations than patients without a ventricular shunt. However, the ventricular shunt does not seem to be an independent risk factor. Furthermore, this study emphasizes that individuals at high risk, such as patients with spina bifida, should be handled latex-free from the very beginning of life.

Adolescent↗
PubMed2000

Hev b 9, an enolase and a new cross-reactive allergen from hevea latex and molds. Purification, characterization, cloning and expression.

Natural rubber latex allergy is an IgE-mediated disease that is caused by proteins that elute from commercial latex products. A complementary DNA (cDNA) coding for Hev b 9, an enolase (2-phospho-D-glycerate hydrolyase) and allergen from latex of the rubber tree Hevea brasiliensis, was amplified by PCR. The PCR primers were designed according to conserved regions of enolases from plants. The obtained cDNA amplification product consisted of 1651 bp and encoded a protein of 445 amino-acid residues with a calculated molecular mass of 47.6 kDa. Sequence comparisons revealed high similarities of the Hevea latex enolase to mold enolases that have been identified as important allergens. In addition, the crucial amino-acid residues that participate in the formation of the catalytic site and the Mg2+ binding site of enolases were also conserved. Hevea latex enolase was produced as a recombinant protein in Escherichia coli with an N-terminal hexahistidyl tag, and purified by affinity chromatography. The yield amounted to 110 mg of purified Hev b 9 per litre of bacterial culture. The recombinant allergen bound IgE from latex, as well as mold-allergic patients, in immunoblot and ELISA experiments. The natural enolase was isolated from Hevea latex by (NH4)2SO4 precipitation and ion exchange chromatography. The natural and the recombinant (r)Hev b 9 showed equivalent enzymatic activity. Patients' IgE-antibodies preincubated with rHev b 9 lost their ability to bind to natural (n) Hev b 9, indicating the identity of the B-cell epitopes on both molecules. Cross-reactivity with two enolases from Cladosporium herbarum and Alternaria alternata was determined by inhibition of IgE-binding to these enolases by rHev b 9. Therefore, enolases may represent another class of highly conserved enzymes with allergenic potentials.

Adult↗