Association of a recombinational repair protein RAD51 with tumor suppressors BRCA1 and BRCA2 suggests that defects in homologous recombination are responsible for tumor formation. Also recent ®ndings that a protein associated with the MRE11/RAD50 repair complex is mutated in Nijmegen breakage syndrome characterized by increased cancer incidence and ionizing radiation sensitivity strongly support this idea. However, the direct roles of BRCA proteins and the protein responsible for NBS in recombinational repair are not clear though they are associated with the recombinational repair complexes. Since RAD51 forms a complex with other members of the RAD52 epistasis group and with BRCA proteins, it is reasonable to ask if alterations of members of the RAD52 epistasis group lead to tumor development. Here we describe missense mutations at functional regions of RAD54 and the absence of the wild-type RAD54 expression resulting from aberrant splicing in primary cancers. Since RAD54 is a recombinational protein associated with RAD51, this is the ®rst genetic evidence that cancer arises from a defect in repair processes involving homologous recombination.
The structure of a sulfated polysaccharide (B-1) isolated and purified from the culture filtrate of marine Pseudomonas sp. WAK-1 was revised to have a repeating unit as follows: -2)-beta-D-Galp(4SO4)(1-4)[beta-D-Glcp(1-6)]-beta-D-Galp(3SO4)(1-. B-1 was evaluated for anticancer activity using a human cancer cell line panel coupled with a drug sensitivity database. The average B-1 concentration required for 50% growth inhibition against the panel of 39 cell lines was 63.2 micro g/ml. Among the cancer cell lines tested, high sensitivities to B-1 were observed in central nervous system cancer and lung cancer cell lines. The COMPARE analysis revealed that the differential growth inhibition pattern of B-1 had no significant correlation with those of more than 200 standard compounds, most of which were anticancer drugs and different types of inhibitors. This lack of similarities in the cytotoxic patterns appears to reflect previously unrecognized biological properties of B-1. It was revealed that B-1 induced apoptosis in U937 cells, as shown by cell morphology and internucleosomal DNA fragmentation.
To utilize the fascinating properties of clays, including their large surface areas, many dissociable cations in the interlayers and low-dimensional structure, we focused on controlling the orientation of clay layers in ion-conductive polymer electrolytes. The application of a strong magnetic field is one of the effective methods used to control the orientation of clay layers and to improve the ionic conductivity of the clay composites. In this study, two different composite films were obtained using different orientations of the magnetic field: perpendicular (M ?) and parallel (M //) to the film surface. From two-dimensional wide-angle X-ray diffraction measurements, the montmorillonite (MMT) layers preferentially oriented along the direction of the magnetic fields in the composites. There were substantial correlations between the conductivity and the ratio of MMT layers oriented along the direction of the conductivity measurement. The lowest conductivity was observed in the M // composite, whereas the M ? composite showed very good conductivity. The value was higher than that of the original electrolytes (PMEO 10 LiClO 4) at 30 1C. These results clearly suggest that the orientation direction of the MMT layers toward the direction parallel to the conductivity measurement causes an improvement in the conductivity of the composites. In particular, the conductivity value of the M ? composite with 5 wt% Li-MMT was 1.2 Â 10 À5 S cm À1 at 30 1C, which was more than six times higher than the original electrolyte.
: A marine Pseudomonas species WAK-1 strain simultaneously produces extracellular glycosaminoglycan and sulfated polysaccharide. Among the antiviral activities tested for these polysaccharides, the latter showed anti-HSV-1 activity in RPMI 8226 cells (50% effective concentration is 1.4 µg/ml). Oversulfated derivatives of these polysaccharides prepared by dicyclohexylcarbodiimide-mediated reaction for both polysaccharides showed antiviral activities against influenza virus type A (for glycosaminoglycan, 50% effective concentration is 11.0 µg/ml; for another, 2.9 µg/ml). Glycosaminoglycan, sulfated polysaccharide, and their chemically synthesized oversulfated derivatives did not show antiviral activities against influenza virus type B and human immunodeficiency virus type 1. No cytotoxicity of these products was noted against host cells at the 50% cytotoxic concentration of 100 µg/ml, except that naturally occurring sulfated polysaccharide had 50% cytotoxicity against MT-4 cells at 8-21 µg/ml.
Ticks transmit a variety of infectious diseases. Diagnosis requires verification of a tick’s presence. Here, we describe a 61-year-old woman bitten by an eight-legged nymphal Amblyomma testudinarium. We re-emphasize the usefulness of dermoscopy for identifying signs of the bite and determining the species of the biting tick.
To evaluate in vivo nitric oxide production in Kawasaki disease (KD), urinary nitrite/nitrate (NOx) excretion was measured in 8 children with KD (age 1.1-2.7 years). Urinary NOx excretion was 0.66 +/- 0.22 mmol mmol-1 creatinine (mean +/- SD) in the 8 children with KD in the initial stages. The levels were significantly increased compared with those of 12 age-matched healthy control subjects (0.35 +/- 0.08 mmol mmol-1 creatinine). Urinary Nox excretion was serially determined in four patients. For each patient, there was a further rise in urinary NOx excretion from baseline levels coincident with the administration of intact-type gammaglobulin and aspirin. With clinical and laboratory improvement, however, urinary NOx excretion declined to the normal range. These findings suggest that endogenous nitric oxide production is enhanced in children with acute KD. Further studies are needed to clarify the role of nitric oxide in the pathogenesis and clinical course of KD.
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