Interleukin-18.

Interleukin (IL)-18 is a newly discovered cytokine, structurally similar to IL-1, with profound effects on T-cell activation. This short review summarizes the present knowledge on IL-18, to give an insight into the future perspectives for its possible use as vaccine adjuvant. Formerly called interferon (IFN) gamma inducing factor (IGIF), IL-18 is the new name of a novel cytokine that plays an important role in the T-cell-helper type 1 (Th1) response, primarily by its ability to induce IFNgamma production in T cells and natural killer (NK) cells. Mice deficient in IL-18 have suppressed IFNgamma production despite the presence of IL-12 IL-18 is related to the IL-1 family in terms of structure, receptor family, and function. In terms of structure, IL-18 and IL-1beta share primary amino acid sequences of the so-called "signature sequence" motif and are similarly folded as all-beta pleated sheet molecules. Also similar to IL-1beta, IL-18 is synthesized as a biologically inactive precursor molecule lacking a signal peptide which requires cleavage into an active, mature molecule by the intracellular cysteine protease called IL-1beta-converting enzyme (ICE, also called caspase-1). The activity of mature IL-18 is closely related to that of IL-1. IL-18 induces gene expression and synthesis of tumor necrosis factor (TNF), IL-1, Fas ligand, and several chemokines. The activity of IL-18 is via an IL-18 receptor (IL-18R) complex. This IL-18R complex is made up of a binding chain termed IL-18Ralpha, a member of the IL-1 receptor family previously identified as the IL-1 receptor-related protein (IL-1Rrp), and a signaling chain, also a member of the IL-1R family. The IL-18R complex recruits the IL-1R-activating kinase (IRAK) and TNFR-associated factor-6 (TRAF-6) which phosphorylates nuclear factor kappaB (NFkappaB)-inducing kinase (NIK) with subsequent activation of NFkappaB. Thus on the basis of primary structure, three-dimensional structure, receptor family, signal transduction pathways and biological effects, IL-18 appears to be a new member of the IL-1 family. Similar to IL-1, IL-18 participates in both innate and acquired immunity.     

Molecular studies of trisomy 18.

We have determined the parental origin of 50 cases of trisomy 18. In 48 cases the additional chromosome was maternal in origin, and in 2 cases it was paternal in origin. Seven cases, including both those with an additional paternal chromosome, appeared to be the result of postzygotic error. In contrast to the situation in nondisjunction involving chromosomes 21 and X, there was no evidence for nullochiasmate nondisjunction.     

The O18 antigens (lipopolysaccharides) of Escherichia coli. Structural characterization of the O18A, O18A1, O18B and O18B1-specific polysaccharides.

The O-specific polysaccharide moieties (PS) of the O18A, O18A1, O18B, and O18B1 antigens (lipopolysaccharides, LPS) consist of L-rhamnose (Rha), N-acetyl-D-glucosamine, D-galactose, and D-glucose in different molar ratios. By using chemical fragmentation, methylation, as well as one- and two-dimensional NMR spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In O18A-PS and O18A1-PS x = 2, whereas in O18B-PS and in O18B11-PS x = 3. In all four polysaccharides alpha-D-Galp (residue D) is substituted at O-3. This substituent L (residue E) is beta-D-GlcpNAc-(1 in O18A-PS and O18A1-PS and it is alpha-D-Glcp-(1 in O18B-PS and O18B1-PS. Whereas there is no further substituent on the main chain of the O18A and O18B polysaccharides, in O18A1-PS and O18B1-PS the alpha-D-GlcpNAc residue A is substituted with alpha-Glcp-(1 (residue F), which is linked to O-6 in O18A1-PS and to O-4 in O18B1-PS. These results show that the O18 antigen comprises a group of four related LPS (O18A and O18B, with their glucosylated forms O18A1 and O18B1). The results are discussed with respect to epitope definition and biochemical implications.     

A time-resolved fluoroimmunoassay for 18-oxocortisol and 18-hydroxycortisol. Development of a monoclonal antibody to 18-oxocortisol

Patients with primary aldosteronism and with glucocorticoid-suppressible aldosteronism excrete in the urine excessive amounts of the hybrid steroids 18-hydroxycortisol and 18-oxocortisol. The measurement of these steroids aids in the differential diagnosis of various adrenal disorders. We have produced mouse monoclonal antibodies against 18-oxocortisol and polyclonal antibodies against 18-hydroxycortisol and describe a time-resolved fluoroimmunoassay (TR-FIA) technique for the measurement of these steroids in the urine. We have also compared this assay with an ELISA technique for these compounds. We also describe the preparation of in-house Eu(III)-labeled avidin and an enhancement solution and compared to a commercially available Eu(III)-labeled streptavidin and enhancement solutions. The monoclonal antibodies against 18-oxocortisol are sensitive and have a high level of specificity. The TR-FIA technique using in-house prepared reagents or commercial ones were indistinguishable from each other, but at a significant saving. The TR-FIA technique was more sensitive and had a greater precision than the ELISA technique for both steroids.     

18-substituted steroids. part 4. a chemical synthesis of 3α, 18, 21-trihydroxy-5β-pregnan-20-one 18 → 20-hemiacetal (18-hydroxy-tetrahydro-doc)

3α, 18, 21-Trihydroxy-5β-pregnan-20-one 18 → 20-hemiacetal (18-hydroxy-tetrahydro-DOC) has been prepared from 3α-acetoxy-5β-pregnan-20-one by reduction to the 20β-alcohol, application of the ‘hypoiodite’ reaction [Pb(OAc)₄-I₂-hv] with subsequent steps leading to the 18-hydroxy-20-ketone (as hemiacetal), and C-21 acetoxylation [Pb(OAc)₄] followed by hydrolysis.     

Studies with Brugia pahangi. 18. Anthelmintic effects of stibocaptate.

Stibocaptate (Asiban, Hoffman--La Roche) killed third stage larvae of Brugia pahangi in vitro at 50 p.p.m. but had no effect on microfilariae at 1 X 10(4) p.p.m No larvae developed in infected mosquitoes fed 1% stibocaptate in 10% sucrose. It was neither micro-nor macrofilaricidal in either jirds or cats but did affect embryogenesis.     

Kingdom protozoa and its 18 phyla.

The demarcation of protist kingdoms is reviewed, a complete revised classification down to the level of subclass is provided for the kingdoms Protozoa, Archezoa, and Chromista, and the phylogenetic basis of the revised classification is outlined. Removal of Archezoa because of their ancestral absence of mitochondria, peroxisomes, and Golgi dictyosomes makes the kingdom Protozoa much more homogeneous: they all either have mitochondria and peroxisomes or have secondarily lost them. Predominantly phagotrophic, Protozoa are distinguished from the mainly photosynthetic kingdom Chromista (Chlorarachniophyta, Cryptista, Heterokonta, and Haptophyta) by the absence of epiciliary retronemes (rigid thrust-reversing tubular ciliary hairs) and by the lack of two additional membranes outside their chloroplast envelopes. The kingdom Protozoa has two subkingdoms: Adictyozoa, without Golgi dictyosomes, containing only the phylum Percolozoa (flagellates and amoeboflagellates); and Dictyozoa, made up of 17 phyla with Golgi dictyosomes. Dictyozoa are divided into two branches: (i) Parabasalia, a single phylum with hydrogenosomes and 70S ribosomes but no mitochondria, Golgi dictyosomes associated with striated roots, and a kinetid of four or five cilia; and (ii) Bikonta (16 unicellular or plasmodial phyla with mitochondria and bikinetids and in which Golgi dictyosomes are not associated with striated ciliary roots), which are divided into two infrakingdoms: Euglenozoa (flagellates with discoid mitochondrial cristae and trans-splicing of miniexons for all nuclear genes) and Neozoa (15 phyla of more advanced protozoa with tubular or flat [usually nondiscoid] mitochondrial cristae and cis-spliced spliceosomal introns). Neozoa are divided into seven parvkingdoms: (i) Ciliomyxa (three predominantly ciliated phyla with tubular mitochondrial cristae but no cortical alveoli, i.e., Opalozoa [flagellates with tubular cristae], Mycetozoa [slime molds], and Choanozoa [choanoflagellates, with flattened cristae]); (ii) Alveolata (three phyla with cortical alveoli and tubular mitochondrial cristae, i.e., Dinozoa [Dinoflagellata and Protalveolata], Apicomplexa, and Ciliophora); (iii) Neosarcodina (phyla Rhizopoda [lobose and filose amoebae] and Reticulosa [foraminifera; reticulopodial amoebae], usually with tubular cristae); (iv) Actinopoda (two phyla with axopodia: Heliozoa and Radiozoa [Radiolaria, Acantharia]); (v) Entamoebia (a single phylum of amoebae with no mitochondria, peroxisomes, hydrogenosomes, or cilia and with transient intranuclear centrosomes); (vi) Myxozoa (three endoparasitic phyla with multicellular spores, mitochondria, and no cilia: Myxosporidia, Haplosporidia, and Paramyxia); and (vii) Mesozoa (multicells with tubular mitochondrial cristae, included in Protozoa because, unlike animals, they lack collagenous connective tissue).