Satoru Okamoto

Comparative evaluation of four urinary tubular dysfunction markers, with special references to the effects of aging and correction for creatinine concentration

Comparative evaluation was made on alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), retinol binding protein (RBP) and N-acetyl-beta-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 [alpha(1)-MG, beta(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 microg/g cr. Among the four tubular dysfunction markers, NAG showed the closest correlation with Cd, followed by alpha(1)-MG and then beta(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 alpha(1)-MG, rather beta(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.

Bias induced by the use of creatinine-corrected values in evaluation of β2-microgloblin levels

The present study was initiated to examine if the correction for creatinine (CR or cr) is the best approach among the three methods of correction for CR, correction for a specific gravity (SG or sg) and the use of observed values in managing difference in urine density. For this purpose, a database previously developed on 10,753 adult women in 10 non-polluted areas in Japan was re-visited for information on age, urinary levels of Cd, Mg, Ca, Zn, beta(2)-MG, and creatinine, and urine specific gravity as well as smoking habits. Never-smoking women with various urine density counted 8975 cases (the various urine density group). From these cases, 7081 cases with adequate urine density (i.e. 0.5 g/l < or = CR < or = 3.0 g/l and 1.010 < or = SG < or = 1.030) were selected (the adequate urine density group). When a beta(2)-MG level of 400 microg/g CR or 400 microg/l was taken as a cut-off value for beta(2)-MG-uria, both the prevalence of beta(2)-MG(cr)-uria [i.e. cases with beta(2)-MG (as corrected for CR) in excess of 400 microg/g cr] and that of beta(2)-MG(sg)-uria increased as a function of the decrease in Cd(cr) or Cd(sg). The prevalence of beta(2)-MG(ob)-uria also varied as a function of CR and SG, especially of CR, but its range of variation was smaller than the corresponding changes in beta(2)-MG(cr)-uria prevalence. A noteworthy advantage for the use of observed values over that of SG-corrected values was the minimum effect of age. In over-all evaluation, therefore, the recommended approach appeared to be the use of non-corrected observed values (after selection of urine samples for adequate urine density if desired) or correction for SG, rather than correction for CR.

α1-Microglobulin levels and correlation with cadmium and other metals in urine of non-smoking women among general populations in Japan

The present study was initiated to examine urinary α1-microglobulin (α1-MG-U) levels among non-smoking women in the general population in Japan. A previously established database on spot urine samples from adult woman volunteers in 10 non-polluted areas all over Japan was re-examined. The data examined were on α1-MG-U, cadmium, calcium, magnesium and zinc levels in urine (Cd-U, Ca-U, Mg-U and Zn-U, respectively), urinary creatinine (CR or cr), urine specific gravity (SG or sg), smoking habits and age. Thus, 8975 never-smoking women were selected for statistical analyses. The grand geometric mean (GM) for α1-MG-U among the population was 2.1 mg/L or 2.5 mg/g cr, depending on the correction for urine density. It was 1.1 µg/L or 1.3 µg/g cr for GM Cd-U. The inter-area difference in α1-MG-U was <1.5 mg/g cr or <0.7 mg/L; the area with the highest or lowest GM Cd-U was not always highest or lowest in GM α1-MG-U. The correlation coefficient (0.53) between log Cd-U and log α1-MG-U (both without urine density correction) became substantially smaller when the analyte levels were corrected for CR (0.25) or SG (0.26). In multiple regression analysis, the power of influence of the five independent variables (log Cd-U, Ca-U, Mg-U, Zn-U and age) in combination was small (R 2 ≦ 0.13). In contrast, logistic regression analysis suggested that α1-MG-U might be elevated as a function of an increase in Cd-U, depending on the cut-off values. Discussion was made on dose (Cd-Ucr) and response (α1-MG-Ucr) relationship based on information available in literatures to show that the increment in α1-MG-Ucr per Cd-Ucr was much greater when Cd-Ucr was large, e.g., in excess of 10 µg/g cr.

Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene

This study was initiated to identify a marker of choice to monitor occupational exposure to toluene through quantitative evaluation of changes in correlation coefficients (CCs), taking advantage of a large database. Six known or proposed exposure markers in end-of-shift blood (B) and urine (U) were studied, i.e., toluene in blood (Tol-B) and benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and toluene in urine (BeOH-U, BMA-U, o-CR-U, HA-U, and Tol-U, respectively). To construct a database, data on 8-h time-weighted average intensity of occupational exposure to toluene and resulting levels of the six exposure markers in blood or urine were cited for 901 cases from previous four publications of this study group and combined with 146 new cases. In practice, 874 cases (all men) were available when extremely dilute or dense urine samples were excluded. The 874 cases were classified taking the upper limit (from 120 ppm to 1 ppm) of the toluene exposure concentration, and the CCs for the six markers with TWA toluene exposure intensity were calculated. For further evaluation, the 874 cases were divided into 10 per thousand in terms of TWA toluene exposures, and several 10 per thousand were combined so that sufficient numbers of cases were available for calculation of the CCs at various levels of toluene exposure. Perusal was made to know whether or not and which one of the six makers gave significant CC even at low level of toluene exposure. The CCs for BMA-U, o-CR-U and HA-U with TWA toluene exposure were well >0.7 when toluene exposure was intense (e.g., up to 60-100 ppm as the upper limit of the exposure range), but were reduced when the upper limit of toluene exposure was less than 50 ppm, and the CCs were as small as <==0.2 when the upper limit was about 10 ppm or less. In contrast, Tol-U and Tol-B were correlated with exposure to toluene down to the <or=3 ppm range. The CC for BeOH-U was <0.1 almost throughout the exposure ranges. Further analyses showed that the CCs for all markers (except the CC for BeOH-U) were >0.4 when the cases in the 60th-100th per thousand were examined. The CCs for Tol-U and Tol-B were >0.3 also for cases in the 0th-60th or 30th-70th per thousand, whereas the CCs for other four markers were <0.3. In over-all evaluation, it was concluded that HA and o-CR are among the markers of choice to monitor occupational toluene exposure at high levels, and that only un-metabolized toluene in urine or in blood is recommended when toluene exposure level is low (e.g., 10 ppm or less). Toluene in urine may be preferred rather than that in blood due to practical reasons, such as non-invasiveness.

Use of Water-Based Solvent Preparations in Factories in Japan

Use of Water‐Based Solvent Preparations in Factories in Japan: Hirohiko Ukai, et at. Kyoto Industrial Health Association—Prevalence of water‐based solvent preparations in 122 factories of various types (e.g., painting, printing, etc.) in the city of Kyoto was investigated by interview in 1995. The survey showed that water‐based solvent preparations were used in 20% of the factories studied and that the leading organic solvent components in water‐based solvent preparations were methyl, ethyl and isopropyl alcohols, among which the use of isopropyl alcohol was the most common. Among glycol derivatives, 2‐butoxyethanol was the most frequently used.

Signal processing LSI system for digital still camera

This paper presents a feature of an image data compression system, and the algorithm employed in a newly developed digital still camera (FUJIX Card Camera DS-H1). DS-H1 is composed of a CCD with 390K pixels, a digital signal processing unit, and image data compression units named DCT and CODER. An IC memory card of 8 Mbit SRAM is used as the recording media. DS-H1 has not only a function of an image data recording, but also a play back for the instantaneous review. A new algorithm is used for controlling a bit rate of a still frame compressed by ADCT (Adaptive Discrete Cosine Transform). The image data control is an important function for digital still camera in order to guarantee the total number of still images stored in an IC memory card. An information distribution of each image data blocks (8*8) is estimated as ACTIVITY. An adequate quantization step ((alpha) ) is calculated using ACTIVITY and parameters named K1, K2. A set of K1 and K2 suitable for the target compression ratio is transferred from CPU to CODER before the compression sequence starts. As a result of our evaluation, it is actually proved that ADCT with the control function is successfully implemented in a small camera body of DS-H1. Picture quality of the played back images is good. K1, K2 and ACTIVITY are important parameters to determine the bit rate control accuracy and the picture quality of compressed/decompressed images. Our simulation results shows that adequate K1, K2 realize a good picture quality and a high control accuracy.