The physical and chemical parameters involved in the design and synthesis of biospecifically targeted nanoparticulate contrast media for magnetic resonance molecular imaging (MRMI) were explored in this pilot investigation. Latex nanoparticles 100, 400 and 900 nm in diameter were doubly derivatised, first with tomato lectin and then with gadolinium(III)-diethylenetriamine pentaacetic acid (Gd-chelates) to target them to epithelial and endothelial glycocalyceal N-glycans and to generate contrast enhancement in magnetic resonance imaging (MRI). After intravenous injection into mice, human placental cotyledons or human Vena saphena magna, contrasty images of the vascular structures were obtained in 1.5 T MRI with spatial resolution 0.1 mm in the imaging plane and 0.6 mm in the z axis, persisting >60 min and resistant to washing out by buffer rinses. Ultrastructural analysis of the nanoparticles revealed the targeting groups at the nanoparticle surfaces and the distribution of the Gd-chelates within the nanoparticles and enabled counts for use in determining relaxivity. The relaxivity values revealed were extremely high, accounting for the strong MR signals observed. Occasionally, nanoparticles larger than 100 nm were seen in close spatial association with disrupted regions of cell membrane or of collagen fibrils in the extracellular matrix. The data suggest that 100-nm nanoparticles generate adequate contrast for MRMI and cause least disruption to endothelial cell surfaces.
In addition to the 150-kDa factor H protein, we have previously described a 43-kDa factor H molecule in human plasma, which probably represents a translational product of the additional 1.8-kb mRNA for factor H. This factor H was isolated from human plasma by means of immunoaffinity chromatography and high-performance liquid chromatography. When tested for its functional activity, this purified 43-kDa H protein was shown to act as cofactor for factor I- mediated cleavage of fluid-phase C3b to iC3b.
A group of 36 patients who had had at least two consecutive spontaneous abortions and who desired to have children was subjected to a psychosomatic investigation before a biomedical diagnostic screening programme was started. A semi-structured interview regarding sociodemographic data, current relationship, social support, education, occupation and medical anamnesis was carried out. In addition, all women completed four standardized questionnaires on the topics of anxiety, somatization disorder, life satisfaction and depression. A control group of 36 women, matched for age and occupation, was subjected to the same psychosomatic investigation. The findings of the diagnostic screening programme showed that 16 women had abortions because of physical abnormality, and 15 women had no physically confirmed cause (in five women, the investigations were not completed). Following recurrent spontaneous abortion, 18 women had a successful pregnancy within 2 years, and 18 women were still childless. The comparison between patients and the control group revealed that patients with recurrent abortion were significantly more satisfied with their life quality regarding leisure time, financial situation and occupation. No significant differences were observed in any other variables. Patients who suffered spontaneous abortions due to a physical disorder showed partner relationship of longer duration, and more frequent miscarriages. Women with successful pregnancy within 2 years after recurrent miscarriage were significantly younger and had fewer physically related abortions compared with women who remained childless. In summary, psychological factors seem to be of subordinate importance as a cause for recurrent spontaneous abortion. Moreover, physical abnormalities in the reproductive system have a predominant impact on the prediction of a future successful pregnancy.
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