Evolution of the IgE and IgG repertoire to a comprehensive array of allergen molecules in the first decade of life.

BACKGROUND: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood. OBJECTIVE: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10 years. METHODS: We examined the sera collected between birth and age 10 years from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cutoff ≥0.30 ISU) and IgG (cutoff ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™). RESULTS: IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule. CONCLUSIONS: The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens, while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects.

Hair cycle-dependent changes in skin immune functions: anagen-associated depression of sensitization for contact hypersensitivity in mice.

To assess whether hair follicle cycling influences skin immunity, we examined the association between highly synchronized hair follicle cycling and experimental contact hypersensitivity in C57BL/6 mice. Hair cycle synchronization was performed by depilation of hair shafts on the back with telogen skin. Mice were sensitized on the lower back skin with picryl chloride between 0 and 25 d, after anagen induction by depilation, and challenged on the earlobes with picryl chloride 5 d later. The magnitude of contact hypersensitivity was significantly decreased in mice sensitized on day 1, was minimal on day 3 (early anagen), and slowly increased thereafter, reaching level comparable to day 0 on day 25 (telogen). The significantly depressed contact hypersensitivity response in anagen skin was confirmed in mice with spontaneously developed follicles. Lymph node cells taken from mice sensitized with picryl chloride on days 0, 1, and 3 after depilation were cultured in vitro in the presence of syngeneic, haptenized, Langerhans cell-enriched epidermal cells. Marked proliferative responses of lymph node cells to haptenized cells were found in mice not only of day 0, but also of days 1 and 3, suggesting that immune T cells exist even lymph node cells of the low-responsive mice. Flow cytometric analyses demonstrated that the number of intraepidermal Langerhans cells and their functions, including the expression of major histocompatibility complex class II, CD54, and CD86, and mixed epidermal cell lymphocyte reactions, were not changed in skin on days 0,1, and 3. These findings demonstrated that contact hypersensitivity is induced most effectively via skin with telogen hair follicles and that the depressed response in early anagen skin is not simply due to failure in Langerhans cell function or sensitization of T cells.

The Valsalva maneuver as an indirect, non-invasive indicator of central blood volume shift.

Our objective was to determine whether the Valsalva maneuver may be used as an indicator of fluid shift during spaceflights. The subjects, 21 healthy young men, conducted the maneuver against expiratory pressures of 20, 30, and 40 mm Hg, each lasting 30 s, at body positions of vertical, horizontal, and 6 degrees head down tilt (HDT). Heart rate was continuously recorded on a beat by beat basis together with the expiratory pressure. The increase in heart rate at equal intrathoracic pressures was maximal in the vertical position, significantly lower (p less than 0.001) in the horizontal position and lowest (p less than 0.05) in the 6 degrees HDT position. Obviously, the blood volume shift in the horizontal and 6 degrees HDT position partly compensated the impaired venous return during the Valsalva maneuver. This simple and non-invasive technique might be used to indicate the time course of blood volume shift during the initial stage of an orbital flight.

Effects of prostacyclin analogue (carbacyclin) on the interaction of platelets with different collagen substrates. Inhibition of cAMP increase by collagens type I, III, and IV.

We investigated the effects of a stable prostacyclin analogue, carbacyclin, on the interaction of platelets with collagen substrates differing in their ability to activate platelets: human collagens type I, III, IV and V (CI, CIII, CIV and CV), and commercial calf skin collagen type I (CSC). The total adhesion was measured using 51Cr-labelled platelets, and quantitative morphometry of adherent platelets was performed by scanning electron microscopy (SEM). Carbacyclin in the concentrations inducing a 10-fold rise in platelet cAMP did not affect the adhesion of platelets to weak substrates, CV and CSC, but reduced the adhesion to strong substrates, CIV (by 49%) and CI/CIII (by 78%), which stimulated massive spreading and formation of surface-bound aggregates respectively. Carbacyclin inhibited all morphological manifestations of platelet activation associated with adhesion: conversion of native discoid platelets to spherical ones on CSC; massive spreading on CIV; and aggregate formation on CI/CIII. Massive spreading and aggregation on a weak substrate (CSC) stimulated by arachidonic acid and thrombin was also inhibited by carbacyclin. Under the same concentration of agonists aggregation of platelets was more sensitive to the action of carbacyclin, than spreading. Strong collagen substrates CI, CIII and CIV, but not CV and gelatin, inhibited the carbacyclin-induced rise in platelet cAMP.

Characterization of renal artery stenoses based on magnetic resonance renal flow and volume measurements.

BACKGROUND: The benefits of percutaneous angioplasty of renal artery stenosis is not known. In an attempt to better define the patient subgroup most likely to benefit from a revascularization procedure, the relationship between renal arterial morphology, blood flow volume, and renal volume was investigated using magnetic resonance (MR) techniques. METHODS: Analysis was based on arterial flow volume and renal volume measurements of 130 kidneys in 65 patients with clinically suspected renal vascular disease. Significant renal arterial stenosis (RAS), documented by contrast-enhanced three-dimensional MR angiography, compromised blood supply to 31 kidneys. Renal volume measurements were related to the body mass index to derive the renal volume index (RVI). The RVI of 72 kidneys in 36 patients without evidence of RAS or severe renal insufficiency was used as a standard of reference to differentiate normal-volume from reduced-volume kidneys. RESULTS: Eighteen out of 31 RAS kidneys were significantly reduced in volume (3.08 +/- 0.75); the volume of the remaining 13 kidneys was within one standard deviation of the normal reference value. Flow volumes in kidneys with RAS were significantly reduced compared with kidneys without RAS (91.56 vs. 279.15 ml/min). Based on the RFI values (RFI = flow volume/renal volume), there was only minimal overlap between normal volume kidneys with RAS (0.73 +/- 0.34) and kidneys without RAS (2.02 +/- 0.59). RFI values of small volume kidneys with RAS (1.55 +/- 0.47), on the other hand, overlapped with both groups. CONCLUSIONS: Normal volume kidneys with impaired arterial flow caused by RAS can be differentiated from those without based on a flow index (RFI). These data suggest the existence of a critical cut-off value (flow index <1.2 ml/min per cm3 of renal tissue) beyond which the renal parenchyma starts shrinking.