[Anatomy education in the University of Queensland].
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Biomedical subjects
Publications and source records attributed to Y Fukui.
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The purpose of the present study was to evaluate the validity of alpha1-microglobulin (alpha1-MG) in comparison with popularly used beta2-microglobulin (beta2-MG). A database on 8975 cases of never-smoking adult women was revisited; the data were based on spot urine samples from the women in 10 prefectures all over Japan. The validity of alpha1-MG was examined following essentially the same protocol as beta2-MG was examined in a previous study. Comparisons were made for alpha1-MG as observed (e.g. alpha1-MG(ob)), as corrected for creatinine (CR or cr) (e.g. alpha1-MGcr) and as corrected for a specific gravity (SG or sg) of 1.016 (e.g. alpha1-MGsg). A cut-off value of 5.0 mg alpha1-MG/g cr or l was deduced from 400 microg beta2-MG/g cr taking advantage of the regression equation between alpha1-MG and beta2-MG. The prevalence of alph1-microglobulinuria as corrected for a specific gravity of 1.016 (or alpha1-MGsg-uria in short) was essentially unchanged irrespective of SG, except for in very dense or very thin urine samples. alpha1-MGcr-uria prevalence decreased at higher CR. Comparison of the present observation with previous findings on beta2-MG-uria prevalence showed that the variation in prevalence of MG-uria as a function of urine density was smaller for alpha1-MGsg whereas it was substantially larger for beta2-MGcr, and thus it appeared prudent to consider alpha1-MGsg rather than beta2-MGcr as a marker of tubular dysfunction.
This study was initiated to examine if hematuria and proteinuria in school days, current pregnancy, or current lactation are risk factors of cadmium-induced tubular dysfunction for adult women among general populations in Japan. For this purpose, a database of 9,967 never-smoking adult women were reviewed for urinary levels of cadmium (Cd) and three other elements, calcium (Ca), magnesium (Mg), and zinc (Zn), and two tubular dysfunction markers of alpha1-microglobulin (alpha1-MG) and beta2-microglobulin (beta2-MG); the analyte concentrations were corrected for creatinine (cr) and expressed as, e.g., Cd-Ucr. From the total, 160 cases were selected as those who were informed of urinary abnormality (i.e., proteinuria, hematuria, or both) in their school days (the abnormality being found to be transient, later), and each case was matched by age and prefecture of residence. Separately, seven women with persistent urinary abnormality, seven pregnant women, and six lactating women were identified, and the case was matched with three cases each of the same age and living in the same prefecture. Statistical analyses showed that Cd-Ucr and other markers were not elevated in the transient urinary abnormality group as compared with the matched controls. This was also observed in the subjects with persistent abnormality. In the pregnant women, alpha1-MG-Ucr and possibly beta2-MG-Ucr were elevated, but Cd-Ucr did not increase, suggesting that the observed elevation in alpha1-MG and beta2-MG was not due to the effects of Cd but a part of the physiology of pregnancy itself. There was no change in marker levels in lactating women except for an increase in alpha1-MG. In overall evaluation, it was considered prudent to conclude that urinary abnormality in school days does not increase the risk of Cd-induced nephrotoxicity in adult women, whereas the negative findings with pregnancy and lactation should be taken as preliminary because the numbers of cases studied were limited.
To establish a defined in vitro maturation culture system for porcine oocytes, we examined the effects of adding cysteine (Cys) and epidermal growth factor (EGF) to the maturation medium. Furthermore, to evaluate cytoplasmic maturation, we investigated GSH concentrations and embryo development after intracytoplasmic sperm injection (ICSI). The basic media for IVM were modified TCM199 containing 10% newborn calf serum (NBCS) or 0.1% polyvinyl alcohol (PVA), supplemented with amino acids. Adding EGF (10 ng/ml) or EGF + Cys (0.57 mM) to the defined medium (0.1% PVA + amino acids) increased (P < 0.05) the rate of nuclear maturation relative to the defined medium (without these additives). After ICSI, oocytes matured in a medium supplemented with NBCS, Cys and EGF had a higher (P < 0.05) rate of pronuclear formation rate than oocytes matured in the defined IVM medium. Although there was no significant difference in cleavage rates between NBCS- and PVA-containing media supplemented with both Cys and EGF, the rate of blastocyst development was lower (P < 0.05) in the defined medium than in the NBCS-containing medium. Intracellular GSH concentrations of oocytes matured in the NBCS- and PVA-containing media supplemented with both Cys and EGF were higher (P < 0.05) than in oocytes matured in PVA alone or in oocytes before maturation. Adding Cys and EGF to a defined medium for porcine IVM improved rates of nuclear maturation and cleaved oocytes following ICSI, probably due to increased GSH concentrations. Also, embryos derived from oocytes matured in the defined medium (with the addition of Cys and EGF) developed into blastocysts after ICSI.
The purpose of the study was to examine the validity of alpha1-microglobulin (alpha1-MG) in comparison with popularly used beta2-microglobulin (beta2-MG). A database was revisited to select ca. 7,500 spot urine samples (of adequate urine density) from non-pregnant, non-lactating and never-smoking adult women. The validity of the MGs was examined in terms of stability of the MG-uria prevalence in urine samples of various creatinine (CR or cr) concentration or specific gravity (SG or sg). Comparisons were made for MGs as observed (e.g., alpha1-MGob), as corrected for CR (e.g., alpha1-MGcr) and as corrected for SG of 1.016 (e.g., alpha1-MGsg). A cut-off value of 5.7 mg/g cr (or mg/l) for alpha1-MG was deduced from a cut-off value of 400 microg/g cr (or mcirog/l) for beta2-MG, because the correlation between alpha1-MGcr and beta2-MGcr was statistically significant. The prevalence of a 1-MGsg-uria was essentially unchanged (i.e., from a low of 13.6% to a high of 17.0%, or 1.2 times) except for in very dense or very thin urine samples, in contrast, beta2-MGcr-uria showed a substantial increase (from 0.0% to 2.8% with an infinite rate) as a reverse function of a decrease in CR in urine. The prevalence of uncorrected markers, i.e., alpha1-MGob-uria and beta2-MGob-uria, showed even greater CR- or SG-dependent changes. Thus, it appeared prudent to consider a alpha-MGsg rather than beta2-MGcr as a marker of tubular dysfunction among a general population with various urine density.
We have investigated the effect of exercise on the bone strength, bone mineral density (BMD), and metal content in rat femurs. Five Wister rats acting as an exercised group (E group) were exercised at intervals on a treadmill every day for four weeks. Another five rats were fed in a cage, acting as a control group (C group), without any exercise. After four weeks, the bend strength, Young's modulus, BMD value, and metal content of the femurs were measured using a three-point bend test, Dual-Energy X-ray Absorptiometry (DEXA), and chemical analysis. The bend strength of the E group was 101+/-5 MPa, and that of the C group was 86+/-7 MPa. The Young's modulus was 1.16+/-0.03 GPa for the E group, and 0.98+/-0.06 GPa for the C group. The BMD values were 0.179+/-0.002 g/cm(2) for the E group, and 0.166+/-0.002 g/cm(2) for the C group. The Ca concentration was 230600 +/- 1500 microg/g for the E group, and 223000 +/- 2700 microg/g for the C group. The Zn concentration was 160 +/- 7 microg/g for the E group, and 188 +/- 8 microg/g for the C group.
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.
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.
OBJECTIVE: To examine if iron-deficient conditions modify body burden or health effects of cadmium among women in the general population in Japan. METHODS: In 2002, 1,482 women aged 20 to 74 years in six prefectures in Japan provided informed consent to participate in this study. They offered peripheral blood and spot urine samples, and answered questionnaires on their social habits and health conditions. Never-smoking, non-pregnant and non-lactating healthy women (1,190 subjects) were selected from the volunteers. Blood samples were analyzed for serum iron, ferritin and total iron-binding capacity (TIBC) in addition to red blood cell (RBC) counts and hemoglobin (Hb) concentration as markers of anemia and iron deficiency. Urine samples were analyzed for cadmium (Cd), alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG) as markers of Cd burden and Cd-induced tubular dysfunction; the measures were expressed after being corrected for creatinine (cr) as, e.g., Cd-Ucr. RESULTS: The subjects were classified into anemic (37 women) and iron-deficient (388 women) groups separately from healthy controls (765 women), taking ferritin (<20 ng/ml) and Hb (<10 g/100 ml) as classification indicators. Strictly matched pairs (with regard to age and prefecture) were established for 36 anemic and 280 iron-deficient cases. Comparison between the cases and the matched controls showed that serum iron was lower and TIBC was higher in accordance with lower levels of ferritin and Hb in the anemic and iron-deficient groups, although the RBC count was only slightly reduced (the anemic group) or stayed essentially unchanged (the iron-deficient group). In contrast, no significant increase in Cd-Ucr, alpha(1)-MG, or beta(2)-MG was observed in either the anemic group or the iron-deficient group compared with the matched controls. Cd-Ucr in one case of clinical anemia, however, tended to be higher than the levels among women of the same age range and from the same prefecture. Her alpha(1)-MG-Ucr and beta(2)-MG-Ucr, however, remained un-elevated. CONCLUSIONS: The current level of iron deficiency among women in the general population in Japan may not induce significant increase in Cd body burden or Cd-induced tubular dysfunction.
OBJECTIVE: To examine whether environmental exposure to cadmium has been inducing kidney dysfunction among middle-aged women in the general population in Japan. METHODS: This study was conducted in 2000 and 2001. Morning spot urine samples were collected from 10,753 women (mostly aged 35 to 60 years) in ten prefectures all over Japan (thus about 1,000 women per site). Urine samples were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U). The urinary analyte concentrations were corrected for creatinine (cr) concentration (i.e., Ucr). The data thus obtained were subjected to statistical evaluation by chi-square test, ANOVA, multiple comparison test, and simple regression analysis (SRA) as well as multiple regression analysis (MRA) including logistic regression analysis (LRA). Log-normal distribution was assumed for Cd-Ucr, alpha(1)-MG-Ucr and beta(2)-MG-Ucr, whereas normal distribution was considered for age, Ca-Ucr, Mg-Ucr and Zn-Ucr. RESULTS: Geometric mean values (GM) of Cd-Ucr were distributed unevenly, depending on the sampling areas, with a grand GM of 1.3 microg/g cr, the highest (3.2 microg/g cr) and lowest GM values(0.8 microg/g cr) being significantly different from GMs of other areas. Correlation matrix analysis with subjects of all ages showed that log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr correlated significantly (r=0.272 and 0.202, respectively) with log Cd-Ucr, but they correlated also with age (r=0.280 and 0.213, respectively). The same analysis with the two selected age groups (41-50 and 51-60 years), however, failed to show close correlation of alpha(1)-MG-Ucr and log beta(2)-MG-Ucr with Cd-Ucr. Both MRA and LRA indicated that age was a confounding factor in the evaluation of the effect of Cd-U on the two MG levels. Whereas the LRA with the all-age group showed a positive influence of log Cd-Ucr on log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr, such effect disappeared in parallel with the disappearance of age effects when LRA was conducted with the two selected age groups. An exceptional observation was the influence of log Cd-Ucr on log alpha(1)-MG-Ucr (but not on log beta(2)-MG-Ucr) in LRA when a cut-off value of 5.00 mg for alpha(1)-MG-U/g cr was applied. Comparison between the low and high Cd-U groups showed that both alpha(1)-MG-Ucr and beta(2)-MG-Ucr were higher in the high Cd-U groups, but prevalence of cases with alpha(1)-MG-Ucr and beta(2)-MG-Ucr in excess of the cut-off values did not differ between the two groups except when a cut-off value of 5.00 mg/g cr was employed for alpha(1)-MG-U. CONCLUSIONS: In over-all evaluation, no clear-cut evidence was obtained in the present study to show that environmental exposure to Cd has induced tubule dysfunction among middle-aged women in the general population in Japan. It might be the case, however, that an increase in alpha(1)-MG-U was associated with Cd exposure. In this sense, it is apparently desirable from public health viewpoints to make further efforts to reduce the intensity of the general population's exposure to environmental Cd.
Through literature survey, paired data on cadmium (Cd) and beta(2)-microglobulin (beta(2)-MG) levels (as corrected for creatinine concentration) in urine (i.e., Cd-Ucr and beta(2)-MG-Ucr) among Japanese populations were available for 32 groups of men and 58 groups of women in 12 publications. Plotting of the Cd-Ucr and beta(2)-MG-Ucr data for the groups of women showed that beta(2)-MG-Ucr stayed unchanged when Cd-Ucr was at lower levels, whereas beta(2)-MG-Ucr increased sharply when Cd-Ucr was in excess of 10-20 microg/g cr. Regression analysis was made for groups of women with no elevation in beta(2)-MG-Ucr, and those with >400 or >1000 microg beta(2)-MG-U/g cr. A threshold Cd-Ucr level in relation to an increase in beta(2)-MG-Ucr was estimated as Cd-Ucr at the point of intercept of the two regression lines, one with no beta(2)-MG-Ucr elevation, and the other with >400 or >1000 microg beta(2)-MG-U/g cr. Cd-Ucr at the point of flexion thus calculated was 11-12 microg/g cr. Such observation was quantitatively reproduced by the analysis of data for men, giving 10-11 microg Cd-U/g cr at the point of flexion. This study suggests that the relationship of beta(2)-MG-Ucr with Cd-Ucr is not linear but in the shape of letter 'J', i.e., beta(2)-MG-Ucr increases sharply when Cd-Ucr is in excess of 10-12 microg/g cr.
Prostaglandin (PG) F(2alpha) is implicated in the process of luteal regression in many species, and has been shown to increase the generation of reactive oxygen species. In this study, the role of reactive oxygen species in the local regulatory mechanisms of functional luteolysis in the ewe was examined. In Experiment 1, we studied local effects of hydrogen peroxide (H(2)O(2)) and its interaction with PGF(2alpha) on P secretion in ovine corpus luteum (CL) in vivo. For this purpose, a microdialysis system (MDS) was used, where only the cells surrounding the capillary membrane in the microenvironment of the CL are exposed to these factors, and the P secretory ability of the CL is maintained as if intact. The study used a multiple CL model to implant the MDS, enabling us to examine in parallel several experimental infusions into the MDS implanted in different CLs (one MDS line per CL) developed after superovulation in one ewe. On Day 8 after GnRH treatment, the MDS were implanted into multiple CL in both ovaries of six ewes. A 4-h infusion with PGF(2alpha) (10(-6)M) at 8-12 h slightly increased P release during infusion, while a 4-h infusion with H(2)O(2) (10(-3)M) at 20-24 h decreased P release at 27-38 h. A pre-infusion with PGF(2alpha) for 4h at 8-12h, followed by infusion of H(2)O(2) at 20-24 h rapidly decreased the P release at 20-40 h (P<0.05); this decrease occurred 7h earlier than in the CL treated with H(2)O(2) alone. In Experiment 2, by utilizing the MDS we also applied free radical scavengers to examine their possible weakening effect on the inhibition of P secretion in the microenvironment within the regressing CL induced by PGF(2alpha) treatment. On Day 8 after estrus, the MDS were implanted into the CL (single CL model, two MDS lines per CL). Infusion of free radical scavengers, superoxide dismutase (SOD;50mg/ml)+catalase (CAT; 10mg/ml), at 0-28 h first increased P release until 12 h (P<0.05), and consequently delayed the decrease in P release until 30 h after administration of PGF(2alpha) i.m. (P<0.05). The present results support the concept that the leading pathway from PGF(2alpha) induces an increase of reactive oxygen species in luteolysis in the ewe.
To reduce cellular damage by pronuclear microinjection and nuclear transfer, we have recently developed a vibratory microinjection method. A micropipette was fixed to a piezoelectric ceramic with a resonance frequency of 70 kHz. When this micropipette was vibrated, it easily entered a mouse-fertilized egg without any sharp depression of the cell body, whereas a sharp, deep depression at the insertion site was observed when the micropipette was not vibrated. A depression rate defined as a rate of a depth of depression over an original cell diameter was utilized as an index of cellular deformation. The depression rates with and without vibration were 11.1 +/- 5.2% (N = 24) and 40.4 +/- 8.8% (N = 16), respectively (P < 0.0001, Student's t-test). In conclusion, the vibratory microinjection method is a new, useful option for gene transfer because it resulted in much less cellular deformation, therefore implicating less cellular damage.
Hydroxyapatite (HA) and other calcium phosphates were synthesized on titanium plates by a solid-gas state reaction of sputtered CaO and vaporized P(2)O(5). The calcium phosphates formed were HA, beta-tricalcium phosphate (beta-TCP; Ca(3)(PO(4))(2)), beta-calcium pyrophosphate (beta-PYR; Ca(2)P(2)O(7)), and beta-calcium metaphosphate (beta-MET; Ca(2)(PO(3))(2)). Their formation depended on the ratio of the sputtered CaO and the reacting P(2)O(5). For a mole ratio of CaO/P(2)O(5)=4 (Ca/P=2), an HA film was synthesized. The surface roughness increased by over seven times after the solid-gas state reaction from Ra = 0.16+/-0.02 microm (for the CaO film) to Ra = 1.15+/-0.25 microm (for the reacted film). The synthesized HA film-coated titanium plates and control non-coated titanium plates were implanted in the femora of two dogs for a period of two, four and 12 weeks, and observed using a soft X-ray radiograph and histological sections. New bone formation was observed without any connective tissue at four weeks around the HA film, whereas over the 12 week experimental period, there was no new bone formation around the control and connective tissue was observed over all periods, reaching a thickness of more than 200 microm at 12 weeks.
To alleviate the effects of Ni allergy from NiTi alloy implants, hydroxyapatite (Ca10(PO4)6(OH)2; HA), alumina (Al2O3), or titanium (Ti) was coated onto NiTi alloy plates to form 1-microm thick films using radio frequency magnetron sputtering. The coatings on the plates were characterized using XRD. After the plates had been immersed in physiological saline for periods of one, four, or eight weeks, the concentration of Ni ions released in each solution was detected using a microwave induced plasma mass spectrometer. After eight weeks, the concentration of Ni ions released from the non-coated, the Ti-coated, the HA-coated, and the alumina-coated plates were 238, 19.7, 183, and 106 ppb, respectively. The bonding strength of the Ti film, the HA film, and the alumina film to the NiTi substrate were 3.8 +/- 1.2, 2.6 +/- 0.7, and 3.1 +/- 1.2 MPa, respectively. The non-coated, the HA-coated, the alumina-coated, and the Ti-coated plates were implanted into the femurs of a dog for four weeks for histological observation. In case of the non-coated plates, connective tissue more than 300 microm thick was observed, whereas for the coated plates the thickness of the connective tissue was around 100 microm.
To evaluate the deterioration in the superelasticity of Ti-coated NiTi orthodontic wires, titanium was coated onto wires to form a 1-microm thick film using radio frequency magnetron sputtering. In superelasticity cycle tests, the sigma5.0 value (the stress at 5.0% strain) of a Ti-coated wire was lower than that of a non-coated wire by 6.2% after one cycle, and by 10.4% after 20 cycles. In a three point bend tests, the L2.0 value (the load at 2.0 mm deflection) of a Ti-coated wire was 2.55 N, and this was reduced by 39.0% of the L2.0 value of a non-coated wire (4.18 N). After the non-coated and the Ti-coated wires had been immersed in physiological saline for periods of four and eight weeks, the concentration of Ni ions released into each solution was detected using MIP-Mass, and Ni peak intensity of the wires was measured using XPS. After eight weeks, the concentration of Ni ions released from the non-coated and the Ti-coated wires was 657 and 135 ppb, respectively. In a clinical test, no inflammation was observed during the entire attached period of four weeks in both the non-coated and the Ti-coated wire. In the Ti-coated wire, little exfoliation of the Ti-coating was observed using SEM and EDS. It was concluded that Ti-coated NiTi orthodontic wire has much potential for its application, with a low probability of causing any Ni allergy.
Hydroxyapatite (HA) was coated onto titanium substrates using radio frequency sputtering, and the coated HA films were crystallized in an autoclave at 110 degrees C using a low temperature hydrothermal method. The crystallite size, the Ca/P ratio, and the surface of the films were observed using XRD, EDS, and SEM, respectively. An immersion test was carried out in physiological saline solution, and the film-to-substrate adhesion strength was measured using a pull-out test. From the XRD patterns, a sputtered film subjected to the hydrothermal treatment had crystallized after 24 h, and the crystallite size increased from 38.0+/-8.7 to 81.4+/-19.1 nm. In immersion tests, an as-sputtered film completely dissolved after 1 d, whereas a sputtered film subjected to the hydrothermal treatment survived to 18.7+/-5.8% of the initial film thickness after four weeks. In pull-out tests, the adhesion strength of the sputtered film to the substrate increased from 1.9+/-0.2 to 5.3+/-1.6 MPa after the hydrothermal treatment. A sputtered film subjected to the hydrothermal treatment and a plasma-sprayed coating on titanium columns were implanted in the diaphysis of the femora of six adult dogs, and a pull-out test was carried out after two, four, and 12 weeks. The sputtered film showed higher bone bonding strength than the plasma-sprayed coating at any period.
OBJECTIVE: To examine if there is a threshold in urinary cadmium concentration that induces elevation in urinary microglobulins. METHODS: The database developed in a previous field survey (Ezaki et al. 2002) was employed. In the survey conducted in 2000 and 2001, more than 10,000 middle-aged women (with no occupational exposure to Cd) in ten prefectures all over Japan gave morning spot urine samples, which were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U), and creatinine (cr). The urinary analyte concentrations were corrected for cr concentration (to be expressed as, e.g., Cd-Ucr), and the data thus obtained were subjected to statistical evaluation. The largest geometric mean (GM) for Cd-Ucr among the ten prefecture was 3.2 microg Cd/g cr, and the maximum Cd-Ucr observed among the women studied was 20.9 microg Cd/g cr. RESULTS: Both alpha(1)-MG-Ucr and beta(2)-MG-Ucr increased as a function of the increase in Cd-Ucr among all the women and also in sub-populations of narrow age ranges (i.e., 41-50 and 51-60 years), with no apparent threshold Cd-Ucr. Comparison of the cases exceeding cut-off alpha(1)-MG-Ucr and beta(2)-MG-Ucr levels also indicated a Cd dose-dependent increase in the prevalence, similarly without a threshold Cd-Ucr. In addition, such findings were essentially reproducible when elevation in alpha(1)-MG-Ucr and beta(2)-MG-Ucr levels was examined with the three essential elements, especially with Ca-Ucr and Mg-Ucr, although less clearly with Zn-Ucr. The observations as a whole suggest a possibility that the dose-dependent increases in alpha(1)-MG-Ucr and beta(2)-MG-Ucr with no apparent threshold for element concentration is not specific to Cd-Ucr but common to other elements. CONCLUSIONS: No threshold Cd-Ucr was detected in relation to the increases in alpha(1)-MG-Ucr and beta(2)-MG-Ucr. The element dose-dependent increases in the two MGs with no threshold in the element concentration might be not limited to Cd, but common to other elements. Further studies are apparently necessary.