An allele association study of 19 polymorphisms in surfactant proteins SP-A1, SP-A2, SP-B, and SP-D genes in acute respiratory distress syndrome (ARDS) was carried out. Trend-test analysis revealed differences (p < 0.05) in the frequency of alleles for some of the microsatellite markers flanking SP-B, and for one polymorphism (C/T) at nucleotide 1580 [C/T (1580)], within codon 131 (Thr131Ile) of the SP-B gene. The latter determines the presence or absence of a potential N-linked glycosylation site. Multivariate analysis revealed significant differences only for the C/T (1580) polymorphism. When the ARDS population was divided into subgroups, idiopathic (i.e., pneumonia, etc.) or exogenic (i.e., trauma, etc.), significant differences were observed for the C/T (1580), for the idiopathic ARDS group, and the frequency of the C/C genotype was increased in this group. Based on the odds ratio, the C allele may be viewed as a susceptibility factor for ARDS. Although the expression of both C and T alleles occurs in heterozygous individuals, it is currently not known whether these alleles correspond to similar levels of SP-B protein. These data suggest that SP-B or a linked gene contributes to susceptibility to ARDS.

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The aim of the present work was to develop a multimodal imaging and detection approach to study the behaviour of nanoparticles in animal studies. Highly carboxylated 144 nm-sized latex nanoparticles were labelled with 68 Ga for positron emission tomography, 111 In for quantitative gamma scintigraphy or Gd 3+ for magnetic resonance imaging. Following intravenous injection into rats, precise localization was achieved revealing the tracer in the blood compartment with a time-dependent accumulation in the liver. In addition, rhodamine B was also incorporated to examine specific interactions with blood cells. Flow cytometry and fluorescent microscopy show uptake of nanoparticles by leucocytes and, unexpectedly, thrombocytes, but not erythrocytes. Cellular internalization was an active and selective process. Further incorporation of polyethylene glycol into the nanoparticle corona could prevent uptake by thrombocytes but not macrophages or monocytes. Our data demonstrate the feasibility of a multimodal approach and its usefulness to analyse the fate of nanoparticles at the macroscopic and cellular level. It will facilitate the development of functionalized nanocarrier systems and extend their biomedical applications.

SUMMARYThe production and properties of monoclonal antibodies raised against herpes simplex virus type 1 (HSV-1)-infected cell nuclei are described. Biological and immunochemical assays revealed that these antibodies recognize four different proteins in HSV-1-infected cells. Four antibodies reacted with the major DNA-binding protein (ICP8) and six with the 65K DNA-binding protein. Two antibodies detected the ICP35 family of proteins and one antibody bound to a protein with an apparent mol. wt. of 60K. Immune electron microscopy showed that the major DNA-binding protein had a patchy distribution, whereas the 65K DNA-binding protein was evenly spread in the infected cell nuclei. The 60K protein as well as the polypeptides of the ICP35 family were preferentially found associated with the viral capsid.