Immunotherapy of tree pollen allergy with a modified alginate conjugated birch pollen extract compared to an aluminium adsorbed extract

The safety and efficacy of two birch pollen extracts, one chemically conjugated to alginate (Anjuvac) the other adsorbed to aluminium hydroxide (Alutard), were investigated in an open multicentre comparative study of 63 birch pollen allergic patients. Both extracts decreased the nasal symptoms during the birch pollen season. The changes in specific IgE and IgG were much the same in both treatment groups. The adverse reactions recorded were mild in both groups, but more frequent in the Anjuvac group, probably because of a more aggressive dose schedule though there were twice as many asthmatics in the Anjuvac group. The two investigated allergen extracts were useful alternatives for immunotherapy.     

粉尘螨主要变应原Derf1基因的改造与可溶性表达

目的在大肠杆菌中提高粉尘螨1类变应原（Derf1）的可溶性表达。方法用RT-PCR方法扩增得到Derf1的全长序列与成熟肽序列（mDerf1）；以已知DerP5基因的前导序列替换Derf1前导序列和原酶序列，重新构建出rDerf1基因；将上述3个基因分别克隆入原核表达载体pGEX-4T-1中表达，经Western-blot对三者的表达产物进行分析鉴定。结果Western-blot表明，pGEX-Derf1与pGEX-mDerf1的表达产物分别为分子量约63000与51000的重组蛋白质，重组蛋白质主要存在于细胞裂解液的沉淀中。pGEX-rDerf1大量表达了可溶性目的蛋白质，分子量约53000，并被成功地分离纯化。以上三种表达产物均可被鼠抗GST抗体与螨过敏患者血清特异地识别。结论表达了含Derf1，mDerf1与rDerf1的三种GST融合蛋白质，它们均具免疫反应性，纯化获得了GST-rDerf1融合蛋白质，为后期的诊断及治疗奠定了基础。     

Lesion of posterior parietal cortex in rats does not disrupt place avoidance based on either distal or proximal orienting cues

A current topic in neurobiology is the study of the role of various brain structures in processing of spatial information. The present study was aimed at elucidating the role of the rat posterior parietal cortex in performing a place avoidance task. Two variants of the task were used: an arena frame task, in which animals were trained to avoid a sector defined by local cues bound to the surface of a rotating arena, and the room frame task, in which the shock sector was defined with respect to distal room landmarks. The results showed that both control and lesioned rats were able to efficiently solve both tasks, while locomotion was not altered. These results suggest that the posterior parietal cortex is not crucial for the processing of either proximal or distal cues in place avoidance.     

Increased aeroallergen-specific interleukin-4-producing T cells in asthmatic adults

BACKGROUND: Asthma, atopy and some forms of respiratory syncytial virus (RSV) disease are thought to be caused by T cells making IL-4 (Th2 cells). However, not all patients with similar patterns of clinical disease have the same underlying pathogenesis and the ability to detect immunopathogenic T cells by examination of the peripheral blood remains in doubt. With the prospect of specific immunotherapy for diseases caused by T cell subsets, it is important to determine whether peripheral blood mononuclear cell (PBMC) reactivity can be used to establish the presence of immunopathogenic responses and therefore to predict therapeutic effects. OBJECTIVE: To detect IL-4 and IFN-gamma production as markers of Th1 and Th2 responses in the peripheral blood of atopic and asthmatic adults. METHODS: PBMC from 22 adult asthmatics (18 of whom were atopic) and 21 non-asthmatic volunteers (ten of whom were atopic) were stimulated with cat, birch and house dust mite allergens, human rhinovirus, RSV and recombinant chimaeric F/G protein from RSV in vitro. ELISPOT assays were used to enumerate cells producing IL-4 and IFN-gamma. RESULTS: Asthmatics had a sixfold increase in frequencies of IL-4-producing cells to cat and birch allergen (median values: 37 vs. 7 per million PBMC, P < 0.01 and 20 vs. 3 per million PBMC, P < 0.04, respectively) compared to non-asthmatics. By contrast, non-asthmatic atopics showed no specific increase in antigen-specific IL-4 responses and there was no evident correlation between skin prick test reactivity and ELISPOT results. Atopics had significantly more IFN-gamma-producing cells specific for FG than nonatopics. while IFN-gamma and IL-4 responses to other antigens were not significantly different. CONCLUSION: Enhanced IL-4 responses to non-viral aeroallergens are seen in adults with asthma, while enhanced IFN-gamma responses to viral antigen FG were see in atopics. In practical terms, ELISPOT assays for specific cytokines may provide a method that could be used to monitor antigen-specific T cell responses in peripheral blood.     

Isolation and purification of a major allergen from Parietaria officinalis pollen

A major allergen of Parietaria officinalis, a species responsible for a large number of respiratory allergies in Mediterranean areas, has been identified and characterized. This allergen (Pol) was found in the fraction which precipitates between 70 and 100% ammonium sulphate saturation. Pol showed a molecular weight of 15,000 daltons as determined by SDS-PAGE and HPLC. The pI of Pol was in the pH region 4-6, IEF showing four major bands. Two major bands were shown by CIE, CRIE and immunoblotting; major contaminants or aggregates were also revealed by the latter technique and by HPLC. Pol showed an allergic specific activity 2 times higher than the crude extract; moreover it was shown to be a major allergen since it inhibited 29 out of 30 sera from allergic patients sensitive to P. officinalis.     

The effects of distant and on-line visual information on the control of approach phase and step over an obstacle during locomotion

One of the goals of this study was to examine the nature and role of distant visual information sampled during locomotion in the feedforward control of leading and trailing limb while an individual is required to step over an obstacle in the travel path. In addition we were interested in whether or not on-line visual information available while the limb (lead or trail) is stepping over the obstacle influences limb trajectory control and whether the information provided during lead limb cross would be used to calibrate movement of the trail limb. Towards this end, we manipulated availability of vision following an initial dynamic sampling period during the approach phase in proximity to the obstacle and during the lead and trail limb stepping over the obstacle. Ten participants completed 40 trials of obstacle crossing in 8 testing conditions. Initial dynamic visual sampling was sufficient to ensure successful task performance in the absence of vision in the approach phase and during both lead and trail limb stepping over the obstacle. Despite successful task performance, foot placement of the lead and trail limb before obstacle crossing and limb elevation over the obstacle were increased after withdrawal of vision in the approach area. Furthermore, the correlation between toe clearance and foot placement was diminished. While both limbs require feedforward visual information to control the step over the obstacle, only lead limb elevation was influenced by availability of on-line visual information during obstacle crossing. Results were in agreement with the notion of primacy of information inherent in the optic array over those from static samples of the environment in guiding locomotion. It is suggested that the expected proprioceptive feedback information associated with the limb posture before the obstacle, reconstructed using visual memory from dynamic sampling of the environment, mismatched with those from the actual limb position. Accordingly, participants adopted a different strategy that enabled them to clear the obstacle with a higher safety margin.Financial assistance was provided by a grant from the Office of Naval Research, USA, NSERC/Canada, and CAPES/Brazil. We would like to thank Milad G. Ishac, Mike Greig, Zinat Shafaei-Shirazi, and Candida T. Goncalves for their assistance     

Open-field behavior, habituation and passive avoidance learning: Effect of ACTH and hydrocortisone on Normal and adrenalectomized rats

Exploratory behavior (GMA) and habituation rate (IH) were studied in an open-field situation in normal and adrenalectomized rats. Following this procedure the rats were subjected to passive avoidance learning (PA). Wide-spreading individual differences were observed in the exploratory behavior and the tendency of habituation of normal rats. As compared to the normal values, either the adrenalectomy which was performed 24 hr, 7 days and 28 days prior to the experiments or the ACTH and hydrocortisone treatment failed to modify the GMA and the IH significantly. An improvement of PA was found in the normal rats following ACTH and hydrocortisone treatment. In the adrenalectomized animals the hydrocortisone proved to be effective, whereas ACTH did not influence PA. No correlation was found between GMA, IH versus PA values and the influence of ACTH and hydrocortisone administration on these parameters. It is concluded that the direction of PA is unpredictable on the basis of the open-field test performed on R-Amsterdam strain of rats, and the effect of ACTH on passive avoidance learning is mediated through the adrenal glands.     

Immunotherapy in the age of anti-IgE

Recent results of allergen immunotherapy research have continued to validate efficacy and have also demonstrated a truly preventive aspect for this treatment. This review summarizes the basic principles of effective allergen immunotherapy and highlights some of the advances that have been published in the past year. These studies show that allergen immunotherapy, when done appropriately and properly, not only causes a decrease in symptoms and use of medication as well as an improved quality of life, but that the progression of disease from allergic rhinitis to asthma is substantially decreased and the development of new allergies is diminished. In addition, laboratory studies continue to demonstrate significant changes in the immune system with a shift in the immune pathway from TH₂ toward a TH₁ response. The impact of anti-IgE as a therapeutic agent with allergen immunotherapy is also be reviewed.     

High-dose allergen exposure leads to tolerance

Reports of decreased sensitization to cat allergen (Fel d 1) among individuals living with a cat or subjects exposed to high-dose cat allergen may be explained by the development of a form of high-dose tolerance resulting from natural exposure to an inhalant allergen. Although the epidemiological data regarding the relationship between exposure and sensitization to Fel d 1 are conflicting, the ability for high-dose Fel d 1 to induce a characteristic nonallergic immune response with a distinctive serum antibody profile has been established. Definition of this modified T-helper (Th)2 response to cat allergen, coupled with the renewed interest in regulatory T cells within the immunology field, has provided an avenue for exploring the mechanism by which IgE antibody-mediated responses are controlled. There is mounting evidence to suggest that the modified Th2 response is a variation of the allergic response and that the modified Th2-allergic axis is influenced by allergen dose and genetics. This article discusses putative immune mechanisms of tolerance within the context of an allergen-specific system. The relevance of high-dose allergen exposure and alternate factors such as endotoxin to the development of tolerance is considered. Fel d 1 exhibits unique molecular and immunological characteristics that may contribute to its tolerogenic properties. Major T-cell epitopes of Fel d 1 that preferentially induce regulatory factors have been defined. Furthermore, hightiter IgE antibody responses associated with atopic dermatitis are characterized by a defect in the T-cell repertoire that is specific to these epitopes. Identification of Fel d 1 epitopes that induce interleukin-10 may provide new targets for treatment.