Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Intersexualität

Zusammenfassung Intersexualität bezeichnet eine seltene Störung der somatosexuellen Differenzierung mit einer Inzidenz von etwa 2 pro 10.000 Geburten pro Jahr in Deutschland. Dahinter verbergen sich verschiedene Diagnosen einer vermehrten Virilisierung bei 46,XX-Karyotyp oder deutlich verminderter Virilisierung bei 46,XY-Karyotyp. Manchmal werden diese Störungen erst während der Pubertätsentwicklung entdeckt. Dann ist eine rasche Diagnostik zur Prognosestellung notwendig. Bei allen Jugendlichen mit Intersexualität muss das Management während der Pubertät viele Aspekte von der psychosexuellen Begleitung bis hin zur medizinischen Behandlung mit Hormonsubstitution oder Therapie und der Beratung hinsichtlich chirurgischer Maßnahmen enthalten.     

Potential-dependent calcium channels of neurons of mollusks of various ages]

It is shown that with the holding potentials (Eh) ranging from -50 to -30 mV the amplitudes of the inward Ca current of identified neurons are significantly higher in old (20-24 months) Lymnaea stagnalis molluscs than in adult ones.     

Comparison of primary orchiectomy with oestrogen therapy in advanced prostatic cancer. A 2-year follow-up report of a national, prospective prostatic cancer study

Two hundred and seventy-seven patients with advanced prostatic cancer were treated by either orchiectomy or oestrogen. During the 2-year follow-up period, the response to treatment was considered more favourable in the oestrogen group, and this response was particularly emphasised in patients with poorly differentiated tumour and metastases at the time of diagnosis. Further evaluations included the cardiovascular side effects of oestrogen therapy.     

Accuracy of an anthropometric estimate of the muscle and bone area in a transversal cross-section of the arm

To standardize the maximal static force (Fo) of the arm flexors, the accuracy of an anthropometric method for estimating the mid-arm cross-sectional muscle and bone area (MBA) was investigated. This was done by comparing the anthropometrically determined area (MBA.A) with the area measured by means of computerized tomography (MBA.S). In the same way, the accuracy of Heymsfield's equations (Heymsfield et al., 1982) for predicting MBA (MBA.H) from anthropometric measures was tested. MBA.A was significantly larger than MBA.S, the relative difference increasing with the thickness of the subcutaneous fat layer. This difference was attributed to a 27% underestimation of the fat layer thickness as measured with the skinfold caliper. Women being fatter than men, this caused the standardized maximal static force (Fo/MBA) to be lower in women than in men. MBA.H was 12% smaller than MBA.S. This may have been due to a difference in the way of measuring the arm circumference between the present authors and Heymsfield et al.     

Distribution and prevalence of Octomyomermis troglodytis (Nematoda: Mermithidae), a parasite of the western tree hole mosquito, Aedes sierrensis

Octomyomermis troglodytis was found infecting Aedes sierrensis larvae in 14.5% of 165 tree holes sampled between 1982 and 1986. Mermithid infections were detected in tree hole waters that ranged in pH from 6.5 to 9.3 and electrical conductivities between 0.10 and 5.11 mmhos/cm. Third and fourth instar larvae were most frequently infected, and most immatures that succumbed to infections died while in the fourth instar. Most hosts contained only one nematode. Infected adults were obtained from emergence traps over tree holes, from field-collected immatures reared in the laboratory, and from mosquito collections from sentinel humans. Octomyomermis troglodytis escaped from adults into water vials in the laboratory, suggesting that infected adult mosquitoes serve as dispersal agents for this parasite.     

The effects of severe visual challenges on steering performance in visually healthy young drivers.

PURPOSE: Two experiments explored the extent to which induced blur, reduced luminance, and reduced visual fields affect drivers' steering performance in a driving simulator. METHODS: In experiment 1, ten young participants (M = 21.2 years) drove at approximately 89 km/h (55 mph) along a curvy roadway while being exposed to blur (0 to + 10 D), luminance (0.003 to 16.7 cd/m), and visual field (1.7 and 150 degrees) manipulations. In experiment 2, a new group of ten young participants (M = 18.5 years) drove while exposed to seven visual field sizes (1.7 to 150 degrees). RESULTS: Steering was sensitive to a reduced field size but not to the blur and luminance challenges. Acuity, on the other hand, was sensitive to the blur and luminance challenges but not to reduced field size. DISCUSSION: In healthy young drivers, steering performance is remarkably robust to severe blur and to extremely low luminances. These results support a key element of the selective degradation hypothesis advanced by Leibowitz and colleagues--that steering abilities are preserved at night even when the ability to recognize objects and hazards is not. Additional research should address the other element of this hypothesis--that drivers fail to appreciate the extent to which their visual abilities are degraded at night.     

Synthesis and antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil hydrobromide and its liposomal medicinal form

The antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil (BCMU) and its liposomal medicinal form was studied in comparison to 5-fluorouracil (5-FU), a well-known antitumor drug widely used in oncological practice. The half-lethal dose of BCMU is 14.8 ± 4.2 mg/kg, while the optimum effective dose of the drug is 6 mg/kg. In this dose, BCMU combines low toxicity with significant antitumor activity, which is manifested by increased tumor growth inhibition (TGI) at a 19% increase in the lifetime (LT) of experimental animals. The antitumor activity of the liposomal form of BCMU is quantitatively and qualitatively superior to that of the nonmodified compound and 5-FU, which is manifested by the most pronounced TGI value and by a significant LT increase. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 6, pp. 6–7, June, 2006.