The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine

Although recent evidence suggests that certain beta-lactam antibiotics are absorbed via a specific transport mechanism, its nature is unclear. To confirm whether peptide transport in the rat can be largely ascribed to the intestinal oligopeptide transporter PepT1, the transporter has been functionally characterized and its significance in the intestinal absorption of beta-lactam antibiotics was evaluated. For evaluation of transport activity complementary RNA (cRNA) of rat PepT1 was synthesized in-vitro and expressed in Xenopus laevis oocytes. cRNA induced uptake of several beta-lactam antibiotics and the dipeptide [14C]glycylsarcosine; this was specifically inhibited by various dipeptides and tripeptides but not by their constituent amino acids or by tetra- or pentapeptides. The transport activity of PepT1 for beta-lactam antibiotics correlated well with their in-vivo intestinal transport and absorption. Furthermore, mutual inhibitory effects on uptake were observed between glyclsarcosine and beta-lactam antibiotics. Hybrid depletion of the functional expression of rat PepT1 in oocytes injected with rat intestinal epithelial total mRNA was studied using an antisense oligonucleotide corresponding to the 5'-coding region of PepT1. In oocytes injected with rat mRNA pre-hybridized with the antisense oligonucleotide against rat PepT1, the uptake of [14C]glycylsarcosine was almost completely abolished, whereas its uptake was not influenced by a sense oligonucleotide for the same region of PepT1. Similarly, the uptake of beta-lactam antibiotics was also reduced by the antisense oligonucleotide against rat PepT1. These results demonstrate that the intestinal proton-coupled oligopeptide transporter PepT1 plays a predominant role in the carrier-mediated intestinal absorption of beta-lactam antibiotics and native oligopeptides in the rat.     

Beam test of the CsI(Tl) calorimeter for the BELLE detector at the KEK-B factory

We studied the performance of a prototype electromagnetic calorimeter for the BELLE detector at the KEK proton synchrotron for an energy range of 0.25–3.5 GeV. The prototype consisted of an array of 6 × 5 CsI(Tl) crystals with 30 cm length (16.2 radiation lengths) and about 6 cm × 6 cm cross section. The scintillation light of each CsI(Tl) crystal was read out by two large-area PIN photodiodes and charge-sensitive preamplifiers attached at the rear face of the crystal. We measured the energy and position resolution for electrons and the e/π separation for two sets of matrix configurations: one corresponded to the center and the other to the edge of the barrel calorimeter. The overall performance measured by the test proves that the prototype calorimeter is satisfactory for the use in the BELLE detector.     

Patients with ultrasonic coarse-nodular cirrhosis who are anti-hepatitis C virus-positive are at high risk for hepatocellular carcinoma

BACKGROUND: The relationship between echosonographic patterns of patients with cirrhosis who are antihepatitis C virus (HCV)-positive, the DNA synthesis of hepatocytes, and the risk for HCC were studied. METHODS: Thirty-eight patients with anti-C-100 antibody-positive and Child's grade A posthepatitic cirrhosis were studied. DNA synthesis activity was measured by a bromodeoxyuridine (BrdU, a thymidine analogue)-labeling index (LI), using the BrdU-anti-BrdU in vitro method, and the patients were followed prospectively by frequent liver ultrasonography for 3 years. The ultrasound patterns were classified into fine, coarse, and coarse-nodular (CN) patterns, and the reproducibility of the classification in practical use also was confirmed. RESULTS: Of the 21 patients with high DNA synthesizing cirrhosis (BrdU LI > or = 1.5%), 10 (48%) showed coarse-nodular, 5 (24%) coarse, and 6 (29%) fine pattern in ultrasonography. Conversely, of the 17 patients with low DNA synthesizing LC (BrdU LI < 1.5%), only 1 (6%) showed coarse-nodular, 2 (12%) coarse, and 14 (82%) fine pattern. A significant relationship was found between the two groups of BrdU LI and ultrasound imaging patterns (P < 0.05). The incidence of CN pattern was significantly higher (P < 0.01) in the high DNA synthesizing group than in low DNA synthesizing group. Of the 11 patients with CN pattern by ultrasound imaging, 10 (91%) were in the high DNA synthesizing group, and 9 (82%) developed HCC during the follow-up period, compared with 3 of 7 (43%) with coarse, and only one of 20 (5%) with fine pattern developed HCC. The incidence of HCC was significantly higher (P < 0.01) in patients with a CN cirrhosis pattern than in those with a fine pattern. CONCLUSIONS: In patients with cirrhosis who are anti-HCV-positive, the CN pattern by ultrasound imaging indicates increased DNA synthesis of hepatocytes and a high risk for developing HCC.     

Deposition of carbon and its hydrogenation catalyzed by nickel

Formation of carbon on nickel sheet from benzene vapor carried by hydrogen was studied at a temperature range from 520 to 730°C. A maximum rate was observed at about 630°C, above which the deposition rate decreased rapidly. The carbon formed was hydrogenated in situ. Methane was the main gaseous product and a maximum rate was observed at about 670°C. Very high reactivity of deposited carbon toward hydrogenation was ascribed to the catalytic action of nickel particles dispersed in the carbon. The hydrogenation rates were divided into three zones and possible interpretations are discussed. A mechanism which is a reverse process to deposition was suggested. The decrease of the hydrogenation rate at higher temperatures was due to the equilibrium among carbon, hydrogen and methane, where carbon was more reactive than graphite.     

Production of IL-6 by T cells from the femoral head of patients with rapidly destructive coxopathy (RDC)

We developed a method to improve the quantitative precision of FDG-PET scans in cancer patients. The total-lesion evaluation method generates a correlation coefficient (r) constrained Patlak parametric image of the lesion together with three calculated glucose metabolic indices: (a) the total-lesion metabolic index ("KT-tle", ml/min/lesion); (b) the total-lesion voxel index ("VT-tle", voxels/lesion); and (c) the global average metabolic index ("KV-tle", ml/min/voxel). METHODS: The glucose metabolic indices obtained from conventional region of interest (ROI) and multiplane evaluation were used as standards to evaluate the accuracy of the total-lesion evaluation method. Computer simulations and four patients with metastatic melanoma before and after chemotherapy were studied. RESULTS: Computer simulations showed that the total-lesion evaluation method has improved precision (% s.d. < 0.6%) and accuracy (approximately 10% error) compared with the conventional ROI method (% s.d. approximately 5%; approximately 25% error). The KT-tle and VT-tle indices from human FDG-PET studies using the total-lesion evaluation method showed excellent correlations with the corresponding values obtained from the conventional ROI methods and multiplane evaluation (r approximately 1.0) and CT lesion volume measurements. CONCLUSION: This method is a simple but reliable way to quantitatively monitor tumor FDG uptake. The method has several advantages over the conventional ROI method: (a) less sensitive to the ROI definition, (b) no need for image registration of serial scan data and (c) includes tumor volume changes in the global tumor metabolism.     

Nucleotide sequences of alcohol acetyltransferase genes from lager brewing yeast,Saccharomyces carlsbergensis

The nucleotide sequences of alcohol acetyltransferase genes isolated from lager brewing yeast, Saccharomyces carlsbergensis have been determined. S. carlsbergensis has one ATF1 gene and another homologous gene, the Lg-ATF1 gene. There was a high degree of homology between the amino acid sequences deduced for the ATF1 protein and the Lg-ATF1 protein (75·7%), but the N-terminal region has a relatively low degree of homology. Southern analysis and contour-clamped homogeneous electric field analysis of Saccharomyces strains suggest that the ATF1 gene is located on chromosome XV in S. cerevisiae and that the Lg-ATF1 gene might originate from the ‘non-S. cerevisiae’ genome of S. carlsbergensis, which is similar to that of S. bayanus and S. pastorianus. The nucleotide sequence data reported in this paper will appear in the DDBJ, EMBL and GenBank data banks with the Accession Numbers D63449 (ATF1) and D63450 (Lg-ATF1).     

A novel hemiacetal dehydrogenase activity involved in ethyl acetate synthesis in Candida utilis

Acetate ester synthesis was studied in vitro with the ethyl acetate-producing yeast Candida utilis. The level of enzyme activity observed for the NAD+-dependent hemiacetal dehydrogenase acting on hemiacetal, which was produced non-enzymatically from an alcohol and an aldehyde, was much greater than that for the other enzyme involved in ester synthesis, alcohol acetyltransferase. The level of ethyl acetate synthesis in vivo approximately paralleled the hemiacetal dehydrogenase (HADH) activity. The results suggest that the main pathway for ethyl acetate synthesis in C. utilis involves a novel hemiacetal dehydrogenase activity.