BACKGROUNDHepatic steatosis is one of the histopathologic features of chronic hepatitis C. It was reported recently that the expression of hepatitis C virus (HCV) core protein in transgenic mice induced hepatocellular carcinoma (HCC) in association with steatosis. The objective of this study was to determine the relation between hepatic steatosis and hepatocarcinogenesis in patients with chronic HCV infection.METHODSThe authors studied 161 patients with chronic HCV infection who were diagnosed at Nagasaki University Hospital, Nagasaki, Japan, between January 1980 and December 1999. Age, gender, body mass index (BMI), habitual drinking, diabetes mellitus, serum alanine aminotransferase (ALT) level, HCV serotype, serum level of HCV core protein, interferon (IFN) treatment, hepatic fibrosis inflammation, and hepatic steatosis were studied with regard to their significance in the development of HCC using univariate and multivariate analyses.RESULTSThe cumulative incidence rates of HCC were 24%, 51%, and 63% at 5 years, 10 years, and 15 years, respectively. Multivariate analysis identified hepatic steatosis, together with aging, cirrhosis, and no IFN treatment, as independent and significant risk factors for HCC (P = 0.0135, P = 0.0390, P = 0.0068, and P = 0.0142, respectively). In addition, hepatic steatosis was correlated with BMI, serum ALT levels, and triglyceride levels.CONCLUSIONSThe findings of the current study indicate that hepatic steatosis is a risk factor for HCC in patients with chronic HCV infection. Patients with chronic HCV and hepatic steatosis should be monitored carefully for HCC. Cancer 2003;97:3036–43. © 2003 American Cancer Society.DOI 10.1002/cncr.11427

Aminoglycoside antibiotics can bind to many different types of RNA molecules. It was of interest to determine the nature of the selectivity of binding of aminoglycosides to important, biologically relevant RNA targets. Fluorescence anisotropy methods were developed to quantitatively measure aminoglycoside affinities to constructs of the HIV-1 RRE transcriptional activation region and the prokaryotic rRNA decoding region which is the natural antibacterial target of the aminoglycosides. A fluorescent analog of Rev34-50 (Fl-Rev34-50) was prepared and shown by fluorescence anisotropy measurements to bind to the HIV-1 RRE region with a stoichiometry of 1 and a dissociation constant of 7.6 nM. RRE RNA is a target for the arginine rich Rev protein, and the binding is known to be mimicked by Rev34-50. The binding is driven by a strongly negative enthalpic term. Aminoglycosides compete with Fl-Rev34-50 binding and competition experiments with semisynthetic aminoglycosides and neomycin B and tobramycin show binding affinities in the 1-2 microM range. The binding of aminoglycosides to this construct is thus not highly selective. A prokaryotic rRNA construct was also prepared and shown to bind a fluorescent dye labeled derivative of the antibiotic paromomycin (CRP) stoichiometrically with a dissociation constant of 0.16 microM. Competition experiments with other aminoglycosides showed binding in the micromolar range, with limited specificity for aminoglycoside type, suggesting that much of the aminoglycoside molecule is not involved in binding. The relatively modest specificity in the binding of aminoglycoside described above is to be contrasted to the subnanomolar affinities and specificity of aminoglycoside binding found using in vitro selected RNA molecules (Wang et al., 1996).

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We examined nitrification in the euphotic zone, its impact on the nitrogen cycles, and the controlling factors along a 7500 km transect from the equatorial Pacific Ocean to the Arctic Ocean. Ammonia oxidation occurred in the euphotic zone at most of the stations. The gene and transcript abundances for ammonia oxidation indicated that the shallow clade archaea were the major ammonia oxidizers throughout the study regions. Ammonia oxidation accounted for up to 87.4% (average 55.6%) of the rate of nitrate assimilation in the subtropical oligotrophic region. However, in the shallow Bering and Chukchi sea shelves (bottom ⩽67 m), the percentage was small (0–4.74%) because ammonia oxidation and the abundance of ammonia oxidizers were low, the light environment being one possible explanation for the low activity. With the exception of the shallow bottom stations, depth-integrated ammonia oxidation was positively correlated with depth-integrated primary production. Ammonia oxidation was low in the high-nutrient low-chlorophyll subarctic region and high in the Bering Sea Green Belt, and primary production in both was influenced by micronutrient supply. An ammonium kinetics experiment demonstrated that ammonia oxidation did not increase significantly with the addition of 31–1560 nm ammonium at most stations except in the Bering Sea Green Belt. Thus, the relationship between ammonia oxidation and primary production does not simply indicate that ammonia oxidation increased with ammonium supply through decomposition of organic matter produced by primary production but that ammonia oxidation might also be controlled by micronutrient availability as with primary production.

Genetic and phenotypic studies on the strains biochemically identified as Shewanella putrefaciens, which had a G+C content ranging from 52 to 54 mol% were conducted. The moles percent G+C of the type strain of S. putrefaciens is 46. Surprisingly, DNA homology experiments revealed that all these strains are genetically related to Shewanella d g a (which was reported to produce tetrodotoxin), not to the type strain of S. putrefaciens. In this study, we reidentified clinical strains of S. putrefaciens which have a high range of moles percent G+C, as does S. alga. We also characterized the reidentified strains and found that the original description of S. alga (U. Simidu, K. Kita-Tsukamoto, T. Yasumoto, and M. Yotsu, Int. J. Syst. Bacteriol. 4k331-336, 1990) is insufficient to identify this strain. An emended description of S. alga is given.The organism now called Shewanella putrefaciens was first described in 1931 and classified as a member of the genus Achromobacter (4). In 1941, it was transferred to the genus Pseudomonas (16) on the basis of morphology. In 1972, it was transferred to the genus Alteromonas (1) on the basis of G+C content. Finally, in 1985, it was transferred to a new genus, Shewanella, on the basis of comparative 5s rRNA sequences (17). The type species of Shewanella is S. putrefaciens (17).Many of the strains classified as S. putrefaciens were isolated from diverse sources, including environmental sources, such as spoilage flora of foods (12, 14, 18,28), oil fields (24), and the ocean (1, 13), and diverse clinical sources, such as patients with otitis, bronchitis, pneumonia, and urinary tract infections (3, 6, 9, 14, 15, 21, 22,29). However, the collected strains were heterogeneous and there were differences between environmental and clinical isolates (9,14,20,21,23,24,28). Owen et al. (20) divided the 10 environmental strains and 16 clinical strains into four groups. Group IV consisted of nine clinical strains. The moles percent G+C value for group IV (52.6) was clearly higher than those for the other three groups (43.9 to 46.9). All four groups retained the species identification of S. putrefaciens, despite the obvious heterogeneity and moles percent G+C values ranging from 43 to 55 (2).Recently, we noticed that most strains isolated from human clinical specimens and identified as S. putrefaciens showed beta-hemolysis on sheep blood agar. However, environmental strains were nonhemolytic. These hemolytic strains had 52 to 54 mol% G+C. Although the hemolytic strains are biochemically identified as S. putrefaciens according to the description in the Manual of Clinical Microbiology (7), they exhibited high levels of DNA homology with the type strain of S. alga. In this study, we present evidence that these clinical strains of S. putrefaciens should be identified as S. alga and emend the description of S. alga * Corresponding author. S. alga is known to be a tetrodotoxin (lTX)-producing bacterium (25,26). Production of TTX by some newly reidentified strains was examined. This is the first report o...