Quantitative assessments of IgG and IgE antibodies to inhalant allergens in patients with atopic dermatitis

Using antigen-binding radioimmunoassays, we have measured class specific antibodies against two major inhalant allergens, antigen P₁ from D. Pteronyssinus and Rye I from grass pollen, in sera from 69 patients with atopic dermatitis. The results show that many of the patients have IgE ab to these allergens in keeping with their skin tests. In all cases, the IgE ab was paralleled by IgG ab to the same allergen. In many sera, IgE ab to these inhalant allergens made a significant contribution to the total serum IgE. With two other allergens to which these patients had not been exposed, specific IgE ab was detected in only one serum, whereas the 42 sera tested did not contain IgE ab to diphtheria toxin. Eleven of the adult patients with atopic dermatitis had no history of asthma and had strongly positive skin tests. This group of patients had levels of total IgE and specific ab to antigen P₁ that were very similar to those found in a comparable group of patients who had both atopic dermatitis and asthma. Our recent finding that allergens applied to the skin can induce delayed eczematous lesions provides a mechanism by which allergens could contribute to skin lesions. Our present results support the view that specific sensitivity to common allergens should be taken into account in considering the causes of these patients' skin lesions.     

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

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Nanoparticle-based targeted drug delivery

Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the “nanometer” size range. These nano-sized objects, e.g., “nanoparticles”, take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad^© nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.     

婴儿神经轴索营养不良的临床特点及PLA2G6基因分析

婴儿神经轴索营养不良（INAD）是一种罕见的神经退行性疾病。该文报道2例男性患儿,年龄分别为3岁、4岁2个月,均以精神运动发育落后/倒退就诊,出生史无异常,目前肌力、肌张力均低下,其中1例患儿已不能独站,且视力下降。肌电图示神经源性损害;头颅MRI示小脑萎缩。全外显子组测序发现2例患儿PLA2G6基因均存在复合杂合突变,其中1例患儿携带的IVS11-1G > T、c.1984C > G突变为新突变,免疫组化示该患儿肌肉组织中PLA2G6蛋白表达量降低。INAD主要临床表现为精神运动发育落后/倒退、小脑萎缩等,基因测序可协助临床确诊。     

Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles

Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system (BCS) was introduced in early 90׳s and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product. Strategies to combat solubility and permeability issues are also discussed.     

Three dimensional printed electron beam modifier for total skin electron treatments

Total Skin Electron Beam (TSEB) treatment, despite its proven effectiveness in skin malignancies, is a rather exhausting irradiation method, especially for feeble patients. In an effort to reduce treatment time by creating a clinically acceptable single TSEB field, various beam modifiers of different materials and shapes were tested. Using the TSEB immobilization device of our department and 3D printing technology, aluminum and thermoplastic modifiers were designed and constructed, according to the resulting profiles at treatment distance. Electron beam characteristics were measured and calculated both at SSD = 100 cm and at treatment level. Aluminum scatterers of the same thickness caused different modification according to the area of blocking. Aluminum modifiers reduced significantly central dose deposition for the same amount of MUs and therefore they expanded treatment time in undesirable levels. Plastic modifiers offer a good combination of field dimensions and treatment time. The final 3D printed modifier shaped the electron beam as desired resulting to a clinically acceptable 6 MeV field of 176 × 70 cm field with 10% inhomogeneity in vertical and 3% in the lateral dimension with adequate skin coverage at SSD = 400 cm. This modification offered approximately a two-minute treatment time reduction compared to the current technique. Underdosed areas appear near the edge of the field, but in regions that are far from the torso of the patient. Bremsstrahlung radiation was kept at clinically accepted levels (< 5%). This modification of the original six dual-field technique of our hospital could probably benefit fragile patients who could not easily tolerate a twenty-minute standing position without compromising the quality of their treatment.     

Immunology of membranous nephropathy: from animal models to humans

Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M‐type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement‐mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti‐PLA2R. Some evidence suggests that IgG4 anti‐PLA2R autoantibodies can bind mannan‐binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome‐wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)‐DQA1 loci with iMN. In addition to their diagnostic value, anti‐PLA2R antibodies may be useful to monitor disease activity and predict response to treatment.