No abstract

Results acquired using global positioning system (GPS) data taken over a large part of SE-Asia, indicate that Sundaland, i.e. Indochina along with the western and central part of Indonesia, constitutes a stable tectonic block moving approximately east with respect to Eurasia at a velocity of 12 þ 3 mm yr 31 . With respect to India and Australia this block moves due south. Significant motion has not been detected along the northern boundary to South China i.e. along the Red River Fault, whereas nearly 50 mm yr 31 of right lateral motion has to be accommodated between India and Sundaland in the Andaman^Burma region. ß

SulTlmaryPsoriasis is a common chronic skin disease mediated by cellular immune mechanisms and characterized by an intense neutrophil cell infiltrate and proliferative activation of epidermal keratinocytes. We have previously described the expression of the inducible nitric oxide synthase (iNOS) in epidermal keratinocytes of psoriatic skin lesions. In this study, the role of iNOS in psoriatic inflammation was explored ex vivo in psoriatic skin biopsies and in vitro in primary cultures of human keratinocytes. Messenger RNA for the iNOS enzyme (iNOS mRNA) was detected by reverse transcriptase polymerase chain reaction in skin biopsies from patients with psoriasis, but not in skin specimens from patients with atopic eczema or from healthy volunteers. As demonstrated by in situ hybridization and immunohistochemistry, expression of iNOS mlLNA and its gene product was localized to the epidermal keratinocytes of psoriatic skin lesions. In situ hybridization further revealed a complete colocalization of mRNA expression for iNOS with interleukin (IL) 8 receptor--specific mRNA either in the basal germinative cell layer or at focal sites of ongoing neutrophil inflammation in suprabasal cell layers. Because psoriatic keratinocytes have previously been shown to express mRNA transcripts for IL-8, it seemed reasonable to hypothesize that iNOS expression could be induced in an autocrine loop by IL-8. This hypothesis was substantiated by our in vitro experiments showing that a combination of IL-8 and interferon ~/ induces the expression of iNOS-specific mRNA and of the functional enzyme in cultured human keratinocytes. These results suggest an important role for iNOS in concert with IL-8 and its receptor early during the formation of psoriatic lesions.

In an effort to identify psoriasis-associated genes, we compared gene expression in normal and psoriatic skin, using differential display RT-PCR technique. Sequence analysis of a 650-bp cDNA fragment (clone 110) that was highly up-regulated in lesional skin revealed homology to a noncoding cDNA (NICE-2). By subsequent cDNA cloning, using RNA from psoriatic skin, we have identified two alternatively spliced mRNA-isoforms (0.5 and 4.4 kb), which differ in composition of their untranslated regions. By sequence comparison, we have mapped the novel gene, named S100A15, to the S100 gene cluster within the epidermal differentiation complex (chromosome 1q21). Analysis of the deduced amino acid sequence revealed a protein of 101 amino acids containing two potential EF-hand motifs with high homology to the S100A7. Northern blot hybridization and semiquantitative RT-PCR analysis confirmed the S100A15 overexpression in psoriasis, showing different levels of expression of the S100A15 mRNA isoforms. In situ hybridization of the S100A15 revealed a markedly increased staining of basal and suprabasal epidermal layers of psoriatic skin compared with healthy tissue. Our data suggest an involvement of the novel S100A15 in epidermal differentiation and inflammation and might therefore be important for the pathogenesis of psoriasis and other diseases.

In order to study both the interplate seismic loading cycle and the distribution of intraplate deformation of the Andes, a 215 site GPS network covering Chile and the western part of Argentina was selected, monumented and observed in 1993 and 1994. A dense part of the network in northern Chile and northwest Argentina, comprising some 70 sites, was re-observed after two years in October/November, 1995. The M w = 8.0 Antofagasta (North Chile) earthquake of 30th July, 1995 took place between the two observations. The city of Antofagasta shifted 80 cm westwards by this event and the displacement still reached 10 cm at locations 300 km from the trench. Three different deformation processes have been considered for modeling the measured displacements: (1) interseismic accumulation of elastic strain due to subduction coupling, (2) coseismic strain release during the Antofagasta earthquake and (3) crustal shortening in the Sub-Andes.Eastward displacement of the sites to the north and to the south of the area affected by the earthquake is due to the interseismic accumulation of elastic deformation. Assuming a uniform slip model of interseismic coupling, the observed displacements at the coast require a fully locked subduction interface and a depth of seismic coupling of 50 km. The geodetically derived fault plane parameters of the Antofagasta earthquake are consistent with results derived from wave-form modeling of seismological data. The coseismic slip predicted by the variable slip model reaches values of 3.2 m in the dip-slip and 1.4 m in the strike-slip directions. The derived rake is 66°. Our geodetic results suggest that the oblique Nazca-South American plate convergence is accommodated by oblique earthquake slip with no slip partitioning. The observed displacements in the back-arc indicate a present-day crustal shortening rate of 3-4 mm/year which is significantly slower than the average of 10 mm/year experienced during the evolution of the Andean plateau.

No abstract

Normal human keratinocytes show chemotactic behavior towards interleukin‐8 (IL‐8). Under physiological conditions this cylokine seems to be present in an equilibrium between monomeric and dimeric forms, as indicated by Western blotting data. Radioligand binding studies suggest that keratinocyte chemotaxis is mediated by receptors specific for IL‐8 dimers. IL‐8 rcceptor‐specific mRNA can be detected in a keratinocyte cell line by polymerase chain reaction.

Human keratinocytes are known to kill Candida albicans in vitro, but the mechanism of killing is not yet understood. Here, we demonstrate that spontaneous, ultraviolet-B-light-induced, alpha-melanocyte-stimulating-hormone-induced, and interleukin-8-induced Candida killing by keratinocytes can be inhibited with mannan and mannosylated bovine serum albumin (Man-BSA). A polyclonal goat serum raised against the human macrophage mannose receptor stained suprabasal keratinocytes, but no staining was observed on keratinocytes with a monoclonal antibody (mAb15) specific for the human macrophage mannose receptor. Mannose-affinity chromatography of keratinocyte extract isolated a 200 kDa protein, and on the Western blot the goat antiserum reacted with a 200 kDa protein. In radioligand binding studies, the binding of 125I-Man-BSA to human keratinocytes was inhibited by mannan in a concentration-dependent manner. Analysis of the binding revealed a single class keratinocyte mannose receptor with a KD of 1.4 x 10(-8) M and a Bmax of 1 x 10(4) binding sites per cell. The binding of 125I-Man- BSA to keratinocytes proved to be time-dependent, acid-precipitable, and Ca2+- and trypsin-sensitive. After trypsinization the receptors underwent a rapid recovery at 37 degrees C. These results demonstrate the presence of mannose receptor on human keratinocytes, and its active involvement in the killing of Candida albicans.