Increased immune reactivity to house dust mites in adults with chronic rhinosinusitis.

Sixty-three adults with symptomatic chronic rhinosinusitis had computerized tomographic (CT) scans of the paranasal sinuses, which were used to quantify disease severity. These patients were divided into three closely age- and sex-matched groups: a CT scan-negative group (chronic rhinitis only), a mild sinusitis group and a severe sinusitis group. Serum dust mite-specific IgG levels were found to be significantly elevated in the sinusitis patients compared with a matched group of asymptomatic normal individuals. Levels were highest in the more severe sinusitis group, in which the mean titre was 559 U/ml and the incidence of titres greater than 400 U/ml was 48%, as compared with a mean titre of 139 U/ml and only a 10% incidence of titres greater than 400 U/ml in the normal subjects (P < 0.005 and < 0.01). In contrast, although the frequency of immediate hypersensitivity to dust mite, as assessed by intradermal skin tests, tended to be higher in patients with sinusitis, it was not significantly different from normal individuals. The association between mite IgG and disease was most striking in the patient sub-group with negative mite skin tests. In this group, mite IgG levels were significantly higher than normal, even in those patients with only chronic rhinitis. These findings demonstrate that increased serum levels of IgG against dust mites are strongly associated with chronic rhinosinusitis, especially in the sub-group of patients who are not allergic to mites.

Fibrinogen structure in projection at 18 A resolution. Electron density by co-ordinated cryo-electron microscopy and X-ray crystallography.

Electron microscope images of frozen-hydrated crystals of a proteolytically modified fibrinogen show excellent preservation of the structure. An electron density map of the key centric projection of the crystal at 18 A resolution has been obtained by combining the phases derived from cryo-electron microscopy with X-ray amplitudes. Simulation methods developed in earlier studies have been used to interpret the map. In contrast to the earlier images, the map allows us to visualize the coiled-coil region of the molecule and possible substructure in the beta domains. The map also shows that there is a marked difference in density in the two regions corresponding to the molecular ends where the gamma domains interact. A possible interpretation of this finding is provided by assuming substructure in the gamma domains and the breaking of molecular symmetry where these domains interact. Some additional constraints useful for the determination of the three-dimensional structure were obtained from cryo-electron micrographs of a perpendicular view at 25 A resolution. Implications of this working model for the molecular length and contacts in the filaments in both the crystal and fibrin are described. The data used here will be valuable as a starting point for obtaining the three-dimensional structure.