Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells.

BACKGROUND: The goal of allergen-specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus-like particles (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs induced strongly increased protective IgG responses compared to free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity. METHODS: We differentiated human mast cells in vitro from blood-derived stem cell progenitors and sensitized the cells with a monoclonal Fel d 1-specific IgE. We compared the capability of Fel d 1 to induce mast cell activation in its free form versus displayed on VLPs and we performed allergen binding studies by surface plasmon resonance as well as flow cytometry. RESULTS: We show that free Fel d 1 induces degranulation of IgE-sensitized mast cells whereas Fel d 1 displayed on VLPs fails to induce mast cell activation. We demonstrate that this inability to activate mast cells is based on a biophysical as well as a biochemical mechanism. Firstly, Fel d 1 on VLPs showed a strongly impaired ability to bind to surface-bound IgE. Secondly, despite residual binding, repetitively displayed allergen on VLPs failed to cause mast cell activation. CONCLUSION: These findings indicate that repetitively displaying allergens on VLPs increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE-mediated activation of mast cells.

A new role for the RN: discharge coordinator.

St. Vincent Charity Hospital, Cleveland, analyzed its discharge planning service and in response to identified problems created the position of RN discharge coordinator within the social service department. After two years of experience with the new approach, the hospital has documented the elimination of some of the target problems and feels it now offers a more comprehensive and professional aftercare placement service.

Testicular sperm extraction: comprehensive analysis with simultaneously performed histology in 1418 biopsies from 766 subfertile men.

The introduction of intracytoplasmic sperm injection (ICSI) has revolutionized treatment of male-factor infertility. Even with a single spermatozoon a pregnancy can be achieved. In cases of azoospermia due to obstruction or highly impaired spermatogenesis, spermatozoa can be retrieved directly from testicular tissue recovered by testicular biopsy followed by sperm extraction. The predictive value of histology from semi-thin sections of testicular biopsies was assessed in relation to testicular sperm extraction (TESE) results, using 1418 biopsy samples from 766 subfertile men which were evaluated simultaneously using a modified Johnsen score and an ordinal classification system for spermatozoa in TESE samples. In 655 men bilateral samples were available. Based on histological findings and TESE results, the quality of spermatogenesis in the right testes was significantly better than that in the left testes. There was a difference between the two sides in 35.7% of all patients for histology and 32.7% for TESE results. When best results from either testis were used for analysis, 76.9% of all men revealed spermatozoa in TESE preparations, although during histological evaluation of semi-thin sections only 64% of all men had shown mature spermatids. In a core group of 250 azoospermic men without anamnestic hints to obstruction and most likely to benefit from ICSI, TESE was successful in 62.8% men. Subdivision of this group dependent on follicle stimulating hormone (FSH) serum concentrations revealed that even in cases of increased FSH concentration, between 39.1 and 64.7% of men showed mature spermatids in their TESE samples. A subset of 70 azoospermic men from the main sample with symptoms and history suggestive of an obstruction and considered as positive controls showed a positive TESE result in all patients. The histology had failed to predict this in 2.9% of all cases. Nevertheless, in five men an early stage of testicular tumour (carcinoma in situ = CIS) was detected. Two of these males suffered from bilateral CIS. This reflects a prevalence of 0.7% testicular malignancy in the group of patients without a history of excurrent duct obstruction. The data demonstrate that a trial TESE with histology based on the semi-thin sectioning technique is a powerful diagnostic and therapeutic procedure, which justifies the invasive nature of sperm retrieval for ICSI. In addition, the results stress the importance of bilateral biopsies to gain optimal diagnostic and therapeutic results.