Notch1 protein is a transmembrane receptor that directs various cell fate decisions. Active forms of Notch1 consisting of a transmembrane domain and an intracellular domain (Notch1TM) or only an ...intracellular domain (Notch1IC) function as oncoproteins. To elucidate the effect of Notch1 abnormalities in radiation-induced lymphomagenesis, we determined the structure of the Notch1 gene and examined the frequency and the sites of Notch1 rearrangements in radiation-induced mouse thymic lymphomas. The Notch1 gene consists of 37 exons, including three exons upstream of the previously reported exon 1. The transcript starting from exon 1 was the major transcript whereas the transcripts read upstream from exon 1a, in which amino acid sequences in the N-terminal region were changed, were minor. More than 50% of radiation-induced thymic lymphomas exhibited Notch1 rearrangements, suggesting that Notch1 acts as a major oncogene in radiation-induced lymphomagenesis. We identified three rearranged sites: novel sites in the 5′ end region encompassing exons 1 and 2, the previously identified juxtamembrane extracellular region, and the 3′ end region. The 5′ deletion and the insertion of murine leukemia virus in the juxtamembrane region led to the production of abnormal transcripts starting from cryptic transcription start sites located halfway through the Notch1 gene and resulted in transcripts lacking most of the extracellular domain. As a result of these rearrangements, truncated Notch1 polypeptides resembling Notch1TM or Notch1IC were formed. In contrast, the 3′ deletion led to the production of a C-terminal PEST motif-deleted transcript. The downstream target gene Hes1 was transcribed in a lymphoma with insertion of murine leukemia virus, but not in a lymphoma with a 5′ deletion. These results indicate that in addition to Hes1 expression, other Notch1 pathway(s) have a role in thymic lymphomagenesis and suggest the presence of a novel mechanism for oncogenic activation of Notch1 by 5′ deletion.
With the recent progress in power electronics devices, harmonic pollution in the power system becomes a significant problem. Therefore, a great deal of attention has been paid to harmonic regulations ...and suppression technologies. As the utility power distribution system becomes broader and more complex, advanced harmonic measurement and analysis technologies are required. This paper presents the advanced measurement system of harmonics in a wide-area distribution system. The proposed measurement system has the following features. The measurement unit at each point in the distribution system consists of a digital signal processor as a high-speed processor and a global positioning system as a synchronization measurement. These units as terminals at multipoints in the distribution system are connected to the central monitoring station by the Internet. By using this system, the harmonic flows in the distribution system are measured and, hence, harmonic modeling can be realized in real time.
To examine the effects of aging on urinary levels of creatinine (CR) and urine specific gravity (SG) among women in a large-scale epidemiology survey.
Data on CR and SG in urine, together with ...smoking habits and menopausal status, were selected from previously established databases and combined with the results of supplemental sample collection. In total, CR and SG data were available for 11,090 never-smoking women (total group; 29-80 years of age); a subgroup of 1,851 women who lived in Kyoto was also selected from the total group. Data from the two groups were subjected to statistical analyses. In statistical evaluation, SG was converted to factor G, which was defined as (SG-1.000)x1,000.
Classification by decade of years of age showed that both CR and SG decreased steadily as a function of advancement in age over 30 years, both in the total group and in the Kyoto subgroup, showing high reproducibility of the observation on a whole-country basis and on a local basis. When the levels at 80 years of age were compared with those at 30 years, there was an approximately 60% and 30% decrease in CR and factor G, respectively. Thus, the effects of aging were more marked on CR than on factor G (and therefore on SG). Menopause appeared to be an influential factor in the reduction of CR and SG, separately from aging itself.
Urinary levels of creatinine and, to a lesser extent, urine specific gravity, steadily decreased as a function of ages of over 30 years in women.
The present study was initiated to examine whether urinary benzylmercapturic acid (or
N-acetyl-
S-benzyl cysteine, BMA), a mercapturate metabolite of toluene, increases in relation to the intensity ...of toluene exposure, and whether this metabolite is a better marker of occupational exposure to toluene than two traditional markers, hippuric acid and
o-cresol. Accordingly, end-of-shift urine samples were collected from 122 printers and 30 office clerks (all men) in the second half of a working week. Solvent (toluene) exposure of the day (8
h) was monitored by means of diffusive sampling. Quantitative relation with toluene showed that BMA had a greater correlation coefficient with toluene (
r=0.7) than hippuric acid (
r=0.6) or
o-cresol (
r=0.6). The levels in the urine of the non-exposed control subjects were below the detection limit of 0.2
μg/l for BMA, whereas it was at substantial levels for hippuric acid and
o-cresol (239
mg/l and 32
μg/l as a geometric mean, respectively). Thus, BMA, hippuric acid and
o-cresol could separate the exposed from the non-exposed when toluene was at <1, 50 and 3
ppm, respectively. Overall, therefore, it appeared reasonable to conclude that BMA is superior to hippuric acid and
o-cresol as a marker of occupational exposure to toluene.
Amorphous Ni–Cr–Nb–16P–4B bulk alloys highly corrosion-resistant in a 6 M HCl solution have been obtained by copper mould casting. The as-cast Ni–Cr–Nb–16P–4B alloys (Cr, Nb=5 or 10 at.%) of 1 mm ...diameter are composed of an amorphous single phase, and they are spontaneously passive in the 6 M HCl solution at 303 K. Their polarization curves are almost the same as those of the corresponding rapidly quenched amorphous alloy ribbons. A larger Ni–10Cr–5Nb–16P–4B bulk specimen of about 20×20×2 mm in size has been also prepared by consolidation of gas-atomized amorphous alloy powders by sheath rolling at 708 K, at which the alloy is in the super-cooled liquid state. Although X-ray diffraction pattern of the specimen revealed a halo, typical of amorphous structure, its corrosion resistance in the 6 M HCl is not as high as that of the as-cast one. After immersion of the sheath-rolled specimen in the 6 M HCl solution, spherical pit-like attacks have been observed on the surface, suggesting the presence of nanocrystalline precipitates locally. Thus, for the Ni–Cr–Nb–P–B alloys the formation of single amorphous phase appears to be necessary to have high corrosion resistance in aggressive environments.
The objectives of the present analyses were to examine if Cd and tubular dysfunction marker levels in urine show age-dependent changes among women who lived in areas with no known cadmium (Cd) ...pollution in Japan, and if the trends would be further modified by correction of analyte concentration in terms of urinary creatinine (CR or cr) or urine specific gravity (SG or sg).
The results of urinalysis for Cd, alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), and N-acetyl-beta-D: -glucosaminidase (NAG) concentrations together with CR and SG were cited from previously established databases. A majority of urine samples were collected in 2000-2002 from adult women (mostly at 40-60 years of age) in various areas in Japan, and the collection was supplemented by cases of > or =60-year-old women in 2003. In total, 11,090 never-smoking cases were subjected to statistical analysis. The values as observed (e.g., Cd(ob)), together with after correction for CR (e.g., Cd(cr)) or SG (e.g., Cd(sg)), were examined by linear regression analysis after logarithmic conversion.
The geometric mean (GM) values for Cd were 1.10 microg/l (as observed) or 1.32 microg/g cr (after correction for creatinine concentration). No increases were found in the levels of alpha(1)-MG, beta(2)-MG or NAG on a group basis, in agreement with the conditions that there was no known environmental pollution with Cd in the sampling areas. There were almost linear increases in logarithm of Cd, alpha(1)-MG, beta(2)-MG and NAG concentrations as age advanced. As CR, and to a lesser extent SG, also decreases steadily throughout life, the correction of the analyte concentrations for urine density induced substantial increases in the analyte values; i.e., the correction by CR and SG induced amplification of the increases by two- and 1.4-times, respectively, compared with the increase in non-corrected observed values.
There were age-related increases in Cd and tubular dysfunction markers in urine among women in areas with no known Cd pollution. The increase was amplified two- or 1.4-times when CR or SG correction was applied, respectively. The observation suggests that care should be practiced in applying CR or SG correction, especially when evaluation of Cd exposure and resulting health effects is made among elderly populations.
Comparative evaluation was made on α
1-microglobulin (α
1-MG), β
2-microglobulin (β
2-MG), retinol binding protein (RBP) and
N-acetyl-β-
d-glucosaminidase (NAG), as a marker of renal tubular ...dysfunction after environmental exposure to cadmium (Cd), with special references to the effects of aging and correction for creatinine concentration. For this purpose, a previously established database of 817 never-smoking Japanese women (at the ages of 20 to 74 years) on hematological hemoglobin, serum ferritin (FE), etc. and urinary parameters α
1-MG, β
2-MG, creatinine (cr), and a specific gravity was revisited. For the present analysis, the database was supplemented by the data on RBP and NAG in urine. The exposure of the women to Cd was such that the geometric mean Cd in urine was 1.3 μg/g cr. Among the four tubular dysfunction markers, NAG showed the closest correlation with Cd, followed by α
1-MG and then β
2-MG, and RBP was least so although the correlations were all statistically significant. The observed values of the markers gave the best results, whereas correction for a urine specific gravity gave poorer correlation, and it was the worst when correction for creatinine concentration was applied. Age was the most influential confounding factor. The effect of age appeared to be attributable at least in part to the fact that both creatinine and, to a lesser extent, the specific gravity decreased as a function of age. Iron deficiency anemia of sub-clinical degree as observed among the women did not affect any of the four tubular dysfunction markers. In conclusion, NAG and α
1-MG, rather β
2-MG or RBP, are more sensitive to detect Cd-induced tubular dysfunction in mass screening. The use of uncorrected observed values of the markers rather than traditional creatinine-corrected values is recommended when comparison covers people of a wide range of ages.
To examine if cigarette smoking will induce elevation in cadmium (Cd) in urine.
Information on smoking habits, and urinary levels of cadmium (Cd-U), alpha(1)-microglobulin (alpha(1)-MG), ...beta(2)-microglobulin (beta(2)-MG), creatinine (CR or cr), and urine specific gravity (SG or sg) was cited from a combination of three previously established databases on adult Japanese women. After exclusion of those with unclear answers on smoking habits (412 cases), the combination (12,846 cases) gave 11,092, 1420 and 334 cases of never, current and former smokers, respectively, for present statistical analyses.
Multiple regression analyses taking Cd-U as a dependent variable and 11 regions of urine collection, age and smoking habits as independent variables showed that age and regions were powerful confounders in the analysis for the effects of smoking on Cd-U. To exclude the confounding effects, current and former smokers were paired with age- and region-matched never smoking controls in subsequent analyses. In addition, former smokers were paired with age- and region-matched current smokers. The comparison of the paired cases showed that Cd-U for current smokers was significantly higher than that for never smokers. The levels for former smokers were however not higher than the levels for never smokers. When classified by the number of cigarettes consumed per day, Cd-U for current smokers increased dependently to the number of cigarettes (about 0.09 microg/cigarette/day) with leveling off at 15 or more cigarettes. There was a subtle cigarette dose-dependent increase in alpha(1)-MG, but the increase was insignificant in case of beta(2)-MG. Estimation of the amount of Cd absorbed due to cigarette smoking followed by comparison with the increase in Cd-U suggested that almost all Cd absorbed will be excreted into urine.
Among currently smoking Japanese women, cadmium in urine increased in a manner dependent to the number of cigarettes consumed daily. Thus, smoking is a confounder of Cd-U evaluation even among the population with relatively high dietary Cd burden.
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