Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in the rat

The incidence of tongue carcinomas (TCs) induced by oral administration of 4-nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA) strain showed a much higher susceptibility to large mass-forming infiltrative TCs than did the Wistar-Furth (WF) strain. Our previous study (M. Kitano et al, Jpn. J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains postulated a dominant susceptibility gene in DA and a dominant resistance gene in WF rats. The present study mapped these loci by analyzing the backcrosses to each parent with simple sequence repeat polymorphisms. Five quantitative parameters were analyzed: (a) the number of TCs > 5 mm in diameter; (b) the total number of TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number of non-TC cancers per rat; and (e) and the number of cancers of any site per rat. All of these parameters were closely correlated (P < 0.0001). DA rats had a semidominant gene (Stc1) favoring the development of 4-nitroquinoline 1-oxide-induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of 5.72 for the number of large TCs and 6.08 for the DTCmax. On the other hand, WF rats had a semidominant gene (Rtc1) mapped between D1Mit1 and D1Mit3, approximately 20 cM from D1Mit1, with a peak lod score of 3.30 for both the number of large TCs and the DTCmax. The main effect of Rtc1 seemed to be to reduce the size of the TCs. The action of these genes was dose dependent and cooperative. The final incidence of TC in DA, WF, F1, and backcross rats seemed to be explained by combinations of genotype at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.     

Failure analysis of ULSI circuits using photon emission

A real-time failure analysis technique for ULSI circuits using photon emission is proposed. This technique utilizes a photon detection system combined with a circuit tester. Improved failure detection is achieved because the tester can bias arbitrary blocks in the ULSI chip. Detecting and correct process defects and design errors improves the reliability of the ULSI chip     

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.     

Electro-optical characteristics of indium tin oxide (ITO) films: effect of thermal annealing

The effect of thermal annealing on the electrical and optical characteristics of ITO films prepared by reactive sputtering and thermal evaporation have been studied. The effect of the thermal annealing is to improve the conductivity and the optical transmission in the shorter wavelength region. The conductivity of the films increases with annealing temperature, this behaviour is associated with grain growth in the film.     

A 10 bit 20 MS/s 3 V supply CMOS A/D converter

A 10 bit CMOS A/D converter with 3 V power supply has been developed for being integrated into system VLSI's. In this A/D converter, redundant binary encoders named “twin encoders” enhance tolerance to substrate noise, together with employing differential amplifiers in comparators. The bias circuit using a replica of the amplifier is developed for biasing differential comparators with 3 V power supply. Subranging architecture along with a multilevel tree decoding structure improves dynamic performance of the ADC at 3 V power supply. The A/D converter is fabricated in double-polysilicon, double-metal, 0.8 μm CMOS technology. The experimental results show that the ADC operates at 20 MS/s and the twin encoders suppress the influence of substrate noise effectively. This ADC has a single power supply of 3 V, and dissipates 135 mW at 20 MS/s operation     

Endogenous adenosine exerts inhibitory effects upon the development of spreading depression and glutamate release induced by microdialysis with high K+ in rat hippocampus

Spreading depression (SD) is known to be involved in the N-methyl-D-aspartate receptor-mediated neuronal damage. In urethane-anesthetized rats, we examined the release of adenosine and glutamate during SD induced by microdialysis of high K+ perfusate through the hippocampal CA1 area. The effects of endogenous adenosine upon SD were studied by applying an adenosine antagonist, theophylline (1 mM) and by a simultaneous application of adenosine uptake blockers, dipyridamole (DPR) (100 microM) and nitrobenzylthioinosine (NBI) (50 microM). The dialysates were sampled every 5 or 10 min and analyzed by HPLC. SD was identified by flattening of background EEg and disappearance of population spikes recorded from the pyramidal cell layer of CA1 area by a glass microelectrode. Adenosine and glutamate release was enhanced significantly in association with the occurrence of SD. Theophylline increased the release of glutamate and the incidence of SD and decreased the latency of the SD occurrence. DPR+NBI decreased the release of glutamate and the occurrence of SD, but increased extracellular adenosine concentration. The effects of DPR+NBI were blocked by application of a selective antagonist of adenosine A1 receptor, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.1 microM). These findings suggest that endogenous adenosine exerts inhibitory influences upon the development of SD and the glutamate release through the A1 receptor in rat hippocampus.     

The Xcad-2 gene can provide a ventral signal independent of BMP-4

Patterning of the marginal zone in the Xenopus embryo has been attributed to interactions between dorsal genes expressed in the organizer and ventral-specific genes. In this antagonistic interplay of activities, BMP-4, a gene that is not expressed in the organizer, provides a strong ventralizing signal. The Xenopus caudal type homeobox gene, Xcad-2, which is expressed around the blastopore with a gap over the dorsal lip, was analyzed as part of the ventral signal. Xcad-2 was shown to efficiently repress during early gastrula stages the dorsal genes gsc, Xnot-2, Otx-2, XFKH1 and Xlim-1, while it positively regulates the ventral genes, Xvent-1 and Xvent-2, with Xpo exhibiting a strong positive response to Xcad-2 overexpression. Xcad-2 was also capable of inducing BMP-4 expression in the organizer region. Support for a ventralizing role for Xcad-2 was obtained from co-injection experiments with the dominant negative BMP receptor which was used to block BMP-4 signaling. Under lack-of-BMP-signaling conditions Xcad-2 could still regulate dorsal and ventral gene expression and restore normal development, suggesting that it can act downstream of BMP-4 signaling or independently of it. Xcad-2 could also inhibit secondary axis formation and dorsalization induced by the dominant negative BMP receptor. Xcad-2 was also shown to efficiently reverse the dorsalizing effects of LiCl. These results place Xcad-2 as part of the ventralizing gene program which acts during early gastrula stages and can execute its ventralizing function in the absence of BMP signaling.