Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1

BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described.     

Sensitization to horse hair, symptoms and lung function in grooms

OBJECTIVE: This study aimed to investigate the rate of occupational sensitization to horse hair in grooms and whether occupational exposure to horse hair increases respiratory and allergic symptoms and affects lung function in grooms or not. METHODS: This is a cross-sectional study. Two hundred grooms were randomly selected among 1000 grooms working in Veliefendi Hippodrome of Istanbul. One hundred and twenty-five subjects agreed to enter the study. Ninety-two workers who worked in the different parts of this hippodrome enrolled as the control group. A detailed questionnaire including respiratory and allergic symptoms was filled in, physical examination, skin prick tests and pulmonary function tests were performed. RESULTS: Sensitization to horse hair was 12.8% in grooms and 4.3% in controls. The difference was statistically significant (P = 0.0035). Asthma was found in 14.4% of the grooms and 5.4% of the controls, allergic rhinitis in 42.4% of the grooms and 18.4% of the controls, allergic conjunctivitis in 35.2% of the grooms and 15.2% of the controls, and allergic skin diseases in 32.8% of the grooms and 13% of the controls. The differences were statistically significant (P = 0.043, P = 0.0002, P = 0.001 and P = 0.0008, respectively). The means of FEV1, FEV1/FVC and FVC parameters were significantly lower in the groom group (P = 0.006, P = 0.001 and P = 0.003, respectively). In the multivariate analysis, being in the groom group and working years were found to be predictive factors for impairments of lung function (P < 0.001 and P = 0.002, respectively). CONCLUSION: Occupational exposure to horse increases the sensitization to horse hair, induces asthma and allergic symptoms and also impairs lung functions.     

Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL- 8 production by alveolar epithelial cells in culture

OBJECTIVE AND DESIGN: Bacterial products as well as the host airway inflammatory responses contribute to the pathogenesis of Pseudomonas infections. We sought to determine if Pseudomonas elastase (PE) induces mitogen-activated protein (MAP) kinase activity in association with interleukin-8 (IL-8) production by alveolar epithelial cells. METHODS: We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production. RESULTS: We found that PE induces phosphorylation of the extracellular signal-regulated (ERK1/2) proteins of the MAPK pathway in A549 epithelial cells. Similar results were obtained using primary cultures of rabbit alveolar type II epithelial cells. PE also enhanced IL-8 production, which was abolished in the presence of the ERK activation inhibitor U0126. CONCLUSIONS: We conclude that PE activates the ERK1/2 arm of the MAPK pathway and that activation of this pathway results in enhanced IL-8 production. The results demonstrate that PE may augment pulmonary inflammation via cellular signaling that regulates expression of IL-8.     

Aluminiumoxidkeramik in der rekonstruktiven Nasenchirurgie. Histologische Untersuchungen am Kaninchen

Summary In cases where a reconstruction of defects in the larynx, oral cavity, the pharynx or in the ear region has been performed using skin flaps, a temporary fistula is formed at the point of entry.This fistula can be closed later after the flap has taken and the flap pedicle dissected.We would like to demonstrate with some examples that with the use of deepithelisation it is possible to achieve a primary wound closure. This way no temporary fistula results and additional surgery is avoided in many cases.Furthermore flap deepithelisation offers a way to bring good vascularised tissue under the skin and cover subcutaneous defects, for example those after radiotherapy.

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Die Veröffentlichung des Manuskripts soll in Laryngol Rhinol Otol (Stuttg) erfolgen     

HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.     

Hernia of the inferior lumbar space. A cause of back pain

Twenty hernias of incarcerated fat at the inferior lumbar space were seen during a 23-year period. The usual complaint was a painful mass that caused a backache. The condition was more common in women and girls than in men (18 v two). The wider female pelvis creates a larger inferior lumbar space, which predisposes to the hernia. The hernia appears through a defect of the covering lumbodorsal fascia. Increased physical activity in young women seemed to be a causative factor. One patient had acute strangulation of incarcerated fat. Nineteen of the 20 hernias were treated with surgical excision and repair of the lumbodorsal fascial defect. Results of treatment were good. Though rare, hernias of the inferior lumbar space should be considered when back pain is present, particularly in a young, athletic woman.     

Single odor-sensitive channels in olfactory receptor neurons are also gated by cyclic nucleotides.

Olfactory transduction is thought to occur by processes that are mainly restricted to the specialized cilia emanating from the distal end of the receptor neuron's single dendrite. The involvement of a cAMP-based second messenger system seems likely, and a cyclic nucleotide-sensitive current has been recorded in patches of membrane from the cilia. However, the small diameter of the cilia and the high density of channels within the membrane limit the application of the patch recording technique in the cilia. We have found that the cAMP-sensitive channels also exist at a much lower density within the far more accessible dendritic membrane. Recording from on-cell patches, we have observed single-channel activity in response to extracellularly applied odor substances. The channels have a single-channel conductance of 40 pS and a reversal potential near 0 mV. These same channels are activated by treatments that elevate intracellular cyclic nucleotide concentrations. The results provide a direct demonstration that the cyclic nucleotide-gated channel is the conductance pathway for the odor-elicited current.