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1.
J Hum Hypertens ; 18(5): 343-50, 2004 May.
Article in English | MEDLINE | ID: mdl-14739909

ABSTRACT

A total of 1595 middle-aged healthy men consuming alcohol up to 120 ml per day and 538 without alcohol consumption were recruited from an occupational population, and their insulin resistance (IR) and beta-cell function (BC) were measured using the homeostasis model assessment (HOMA-IR and HOMA-BC), and the associations with alcohol consumption, blood pressure (BP), and serum gamma-glutamyltransferase (GGT) levels were analysed cross-sectionally. Both HOMA-IR and HOMA-BC were decreased with increasing alcohol consumption, but HOMA-BC corresponding to a level of HOMA-IR was 4-10 and 8-20% lower in drinkers consuming less than 60 ml of alcohol per day and those consuming more, respectively, than in nondrinkers, suggesting an altered fasting serum insulin-glucose relationship in alcohol consumers. Although BP was higher and HOMA-IR was lower in alcohol consumers than in nonconsumers, BP was higher at higher HOMA-IR irrespective of alcohol consumption. Elevations of serum GGT were positively associated with BP and HOMA-IR in both alcohol consumers and nonconsumers. Multiple regression analyses in the subjects showed that elevated serum GGT was an independent contributor to HOMA-IR elevations, and both serum GGT and HOMA-IR were significantly related to BP elevations after adjusting for alcohol consumption, age, body mass index, cigarette consumption, and physical activity at leisure. Although cross-sectional observations do not provide evidence of causal association, the results suggest that elevated serum GGT in alcohol consumers relates to elevations of IR and that the elevated insulin resistance relates, at least partly, to BP elevations in alcohol consumers.


Subject(s)
Alcohol Drinking , Blood Pressure , Homeostasis , Insulin Resistance , Islets of Langerhans/metabolism , Models, Biological , Adult , Cross-Sectional Studies , Humans , Male , Middle Aged , Reference Values , Regression Analysis , gamma-Glutamyltransferase/blood
2.
J Hum Hypertens ; 16(7): 479-86, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12080432

ABSTRACT

Orientals have unique genetic polymorphisms in ethanol metabolizing enzymes, such as alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2) and cytochrome P450-2E1 (CYP2E1). Of the three studies conducted to clarify the influence of ALDH2 genotypes on sensitivity to the pressor effects of alcohol in Japanese, only one was suggested, though indirectly, higher sensitivity in drinkers having the genotype of inactive ALDH2. This discrepancy prompted us to determine ADH2, ALDH2 and CYP2E1 genotypes in the genomic DNA extracted from white blood cells of 855 healthy middle-aged Japanese men, and to analyse the associations with the alcohol-blood pressure (BP) relationship. No marked differences were found in the relationship among the genotypes of ALDH2, although the subjects with intact ALDH2 showed a slightly higher BP than those with inactive ALDH2 probably due to under-reporting of alcohol consumption in those with intact ALDH2 who could thus drink more. No significant influence of ADH2 genotypes was observed. A higher BP was noted in large volume alcohol consumers having c2/c2 genotype of CYP2E1. Multivariate regression analysis adjusting for the effects of age, body mass index and the volume of alcohol consumed, all of which are strong determinants of BP levels, showed only a marginal effect of c2 allele of CYP2E1 on diastolic BP elevations with increases in alcohol consumption. Thus it is concluded that the genetic polymorphisms in ethanol-metabolizing enzymes do not greatly influence the alcohol-BP relationship in Japanese men.


Subject(s)
Alcohol Dehydrogenase/genetics , Alcohol Drinking/genetics , Alcohol Drinking/metabolism , Aldehyde Dehydrogenase/genetics , Asian People/genetics , Central Nervous System Depressants/metabolism , Cytochrome P-450 CYP2E1/genetics , Ethanol/metabolism , Hypertension/genetics , Hypertension/metabolism , Polymorphism, Genetic/genetics , Adult , Aldehyde Dehydrogenase, Mitochondrial , Body Mass Index , Humans , Japan , Male , Middle Aged
3.
Hum Genet ; 105(4): 295-300, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10543395

ABSTRACT

To evaluate the independent and interactive contributions of alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2) and ethanol-induced isozyme cytochrome P450-2E1 (CYP2E1) genes to alcohol consumption large enough to induce health problems, 643 healthy Japanese men aged between 23 and 64 years, recruited from two different occupational groups, were analyzed for genotype and drinking habits. The frequency of excessive alcohol consumers (EAC) who drank 90 ml or more alcohol more than 3 days a week was significantly higher in subjects possessing the ALDH2(1)/ALDH2(1) genotype than in those having ALDH2(1)/ALDH2(2) or ALDH2(2)/ALDH2(2) genotypes. A significant difference was also found in the different genotypes of CYP2E1. Moreover, a borderline significant interaction between the ALDH2 and CYP2E1 genotypes on excessive alcohol consumption was observed, i.e., the group of subjects having the c2 allele of CYP2E1 had a higher frequency of EAC than those having c1/c1 genotypes in the genotype subgroup ALDH2(1)/ALDH2(1), whereas these were not found in the heterozygote and homozygote subgroups of the ALDH2(2) allele. Neither the independent nor interactive genetic effect of ADH2 on excessive alcohol consumption was obvious. In conclusion, Japanese men with the ALDH2(1)/ALDH2(1) genotype and the c2 allele of CYP2E1 are at higher risk of showing excessive alcohol consumption.


Subject(s)
Alcohol Drinking/genetics , Alcohol Drinking/metabolism , Ethanol/metabolism , Polymorphism, Genetic , Adult , Alcohol Dehydrogenase/genetics , Aldehyde Dehydrogenase/genetics , Aldehyde Dehydrogenase, Mitochondrial , Alleles , Cytochrome P-450 CYP2E1/genetics , Genotype , Heterozygote , Homozygote , Humans , Japan , Male , Middle Aged , Risk Factors
4.
Hum Immunol ; 59(4): 243-9, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9568800

ABSTRACT

HLA exhibits the most extensive polymorphism of any of the known human genes and is known as a genetic marker which allows genetic background of many diseases and physical phenomena. In this study, we, therefore, tried to investigate the regulation of HLA polymorphism and peak bone mass (PBM) in order to elucidate the genetic backgrounds of bone metabolism in young women. Subjects were 67 healthy young Japanese women (average age: 23.6 +/- 2.6 years, Body Mass Index (BMI): 19.9 +/- 2.0 who were randomly chosen. Allelic polymorphisms in HLA class I (HLA-A and -B) and HLA-class II (DRB1) were investigated by PCR-SSOP and PCR-SSP. Vitamin D Receptor (VDR) and Estrogen Receptor (ER) gene polymorphisms were also analyzed. Lifestyle factors, such as exercise and nutrition, were examined by questionnaire. Bone mineral density was examined using with Lunar DPX-L. Subjects who possessed HLA-B*07 had a significantly lower PBM than those without B*07 (p < 0.05). All subjects were divided into 3 groups according to HLA haplotypes linked with HLA-B*07, as follows: A*24(+/-)B*07(-)DRB1*01(+/-), A*24(+)B*07(+)DRB1*01(-), and A*24(+)B*07(+)DRB*01(+). There were no significant differences between these three groups in factors that affect bone metabolism, such as age, age at menarche, BMI, calcium intake, exercise habits, VDR or ER allele frequency. The HLA-A*24-B*07-DRB1*01 haplotype had a significantly lower Z score in the lumbar spine compared with subjects without this haplotype (p < 0.05). When the Z score was divided by values higher or lower than +1 or -1, all 3 subjects whose Z score was lower than -1.0 were found to have the HLA-A*24-B*07-DRB1*01 haptotype. A significant association between HLA-A*24-B*07-DRB1*01 and Z score < -1 was found (Yate's correction chi(2) = 10.82, p = 0.001, RR = 204). In conclusion, the HLA-A*24-B*07-DRB*01 haplotype can be considered a new genetic marker implicated with low PBM in healthy young Japanese women.


Subject(s)
Bone Density/genetics , HLA-A Antigens/genetics , HLA-B7 Antigen/genetics , HLA-DR Antigens/genetics , Adult , Female , Genotype , HLA-A Antigens/classification , HLA-A24 Antigen , HLA-B7 Antigen/classification , HLA-DR Antigens/classification , HLA-DRB1 Chains , Haplotypes , Humans , Japan , Life Style , Prospective Studies
5.
Horm Res ; 50(6): 315-9, 1998.
Article in English | MEDLINE | ID: mdl-9973671

ABSTRACT

Vitamin D receptor (VDR) polymorphism may be a genetic factor affecting bone mineral density (BMD). This study examined the interaction of VDR genotype with the effect of an exercise intervention on bone measurements in UK postmenopausal women. 33 walkers, who completed 20.4 +/- 3.9 (mean +/- SD) min day-1 of brisk walking over 1 year, and 36 controls agreed to give DNA samples. BMD was measured at the lumbar spine, femoral neck and calcaneus by dual energy X-ray absorptiometry and broadband ultrasonic attenuation (BUA) was measured at the calcaneus. VDR genotype was determined by BsmI restriction fragment length polymorphisms and the presence, or absence, of the restriction site was signified by 'b' or 'B', respectively. At baseline there was no significant difference in BMD between VDR genotypes, but BUA was significantly higher in the BB genotype than in the Bb or bb genotype. Although there was no significant difference in 1-year change (%) in BMD and BUA between the three genotypes, the 1-year changes in spinal BMD and BUA in the bb walkers (0.75 and 2.35%, respectively) were significantly different from those in the bb controls (-1.25 and -6.10%, respectively). These results suggest that in the bb genotype of VDR, bone may be more responsive to exercise than in other VDR genotypes in British postmenopausal women.


Subject(s)
Bone Density/genetics , Bone and Bones/physiopathology , Postmenopause/physiology , Receptors, Calcitriol/genetics , Walking/physiology , Absorptiometry, Photon , Aged , Bone Density/physiology , Bone and Bones/diagnostic imaging , Calcaneus/diagnostic imaging , Calcaneus/physiology , Calcium/metabolism , DNA/blood , DNA/chemistry , DNA Restriction Enzymes/chemistry , Electrophoresis, Agar Gel , Female , Femur Neck/physiology , Genotype , Humans , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Receptors, Calcitriol/physiology , Spine/physiology , Ultrasonography
6.
Environ Res ; 75(1): 41-8, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9356193

ABSTRACT

Cadmium (Cd), zinc (Zn), copper (Cu), calcium (Ca), phosphorus (P), and magnesium (Mg) were determined in ribs obtained at autopsy from 38 Cd-exposed and 17 nonexposed subjects to determine how levels of these elements in bone are affected by Cd exposure and whether they are associated with the bone lesions due to Cd exposure, osteomalacia, and osteoporosis. Cd in ribs was significantly higher in the Cd-exposed subjects than in nonexposed subjects. Zn tended to be higher, while Cu, Ca, P, and Mg tended to be lower in the ribs of Cd-exposed subjects, though these differences were not statistically significant. Zn, Ca, P, and Mg were highly correlated with each other in both Cd-exposed and nonexposed groups, but the associations of Ca, P, and Mg in the ribs with Zn concentrations differed in subjects and controls. Ca to Zn ratios were low in the Cd-exposed subjects, and the higher the grade of osteomalacia, the lower the Ca/Zn ratio. The decrease in Ca/Zn ratio was significantly correlated with increases in Cd. Cu showed a significant positive correlation with Cd and significant inverse correlation with Ca, P, and Mg in the Cd-exposed group. Cu and its relation to other elements did not show any association with osteomalacia. In conclusion, Ca/Zn ratio in bone was related to Cd exposure and the degree of osteomalacia in the Cd-exposed subjects.


Subject(s)
Cadmium Poisoning/metabolism , Copper/metabolism , Osteomalacia/metabolism , Ribs/metabolism , Zinc/metabolism , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
7.
Toxicol Lett ; 92(3): 173-8, 1997 Aug 22.
Article in English | MEDLINE | ID: mdl-9334827

ABSTRACT

Samples of 24-h urine were collected from 278 subjects (159 males and 119 females) in 1985, and 321 subjects (161 males and 160 females) in 1993 in the same factory with no occupational exposure to lead (Pb) in Japan. The age range of the subjects was 20-59 years. The urinary Pb concentrations were analyzed by flameless atomic absorption spectrophotometry after wet digestion followed by solvent extraction. The Pb levels in 24-h urine were distributed log-normally with geometric means (geometric S.D.) of 4.74 (1.46) and 2.67 (1.98) micrograms/day for males; and 3.22 (1.42) and 2.14 (2.05) micrograms/day for females in 1985 and 1993, respectively. No age-related changes in Pb levels in 24-h urine in either sex from 20 to 59 years were apparent. Pb levels in 24-h urine were significantly higher in males than in females (P < 0.01). Analysis of male smokers together with age-matched non-smokers failed to show an elevation of Pb levels in 24-h urine as related to smoking habits. Comparison of the Pb levels in 24-h urine in 1985 and 1993 disclosed that the Pb levels in 24-h urine were significantly lower in 1993 than in 1985 in both sexes (P < 0.01).


Subject(s)
Lead/urine , Adult , Age Factors , Female , Humans , Male , Middle Aged , Regression Analysis , Sex Factors , Smoking/metabolism
8.
Clin Exp Hypertens ; 19(3): 249-68, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9107436

ABSTRACT

Drinkers showing higher serum gamma-glutamyl transferase (GGT) levels tend to have higher blood pressure (BP), independent of the volume of alcohol consumed. To further evaluate the link between alcohol consumption and elevated serum GGT and BP, we observed BP, serum biochemical parameters, plasma pressor hormones and intraplatelet free calcium (Plt. [Ca2+]i) in 40 moderate drinkers who were composed of four categories of 10 each with or without hypertension (> or = 140/90 mmHg) or high serum GGT level (> or = 50 U/L) during four-week alcohol moderation. BP and serum hepatic enzymes including GGT decreased more conspicuously in both normotensive and hypertensive drinkers with high serum GGT. Serum triglyceride was higher and potassium was lower in the drinkers with high serum GGT, and were normalized during alcohol moderation. Serum calcium, Plt. [Ca2+]i and plasma renin activity and cortisol showed some decreases during alcohol moderation, but were not different in the drinkers with different serum GGT and BP levels. No significant changes were observed in plasma catecholamines and aldosterone. These results suggest that BP elevations in moderate drinkers are closely related to hepatic, lipid and electrolyte metabolic alterations induced by alcohol rather than specific pressor agents.


Subject(s)
Alcohol Drinking/physiopathology , Blood Pressure/drug effects , Hypertension/physiopathology , gamma-Glutamyltransferase/blood , Adult , Aged , Alcohol Drinking/blood , Aldosterone/blood , Blood Platelets/chemistry , Blood Pressure/physiology , Calcium/blood , Catecholamines/blood , Humans , Hydrocortisone/blood , Hypertension/blood , Male , Middle Aged , Potassium/blood , Renin/blood , Triglycerides/blood
9.
Blood Press ; 6(2): 112-6, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9105651

ABSTRACT

Three-hundred-and-sixty-seven unrelated Japanese male workers aged between 36 and 61 years were analysed for the genotypes of cytochrome P450 2E1 (CYP2E1), and the association with alcohol-related health effects including blood pressure (BP) elevation. Homozygous for the c1 (wild) gene was found in 204 men (55%), homozygous for the c2 (variant) gene in 17 (5%), and heterozygous in 146 (40%). Arithmetic means of alcohol consumed per week in the genotypes of c1/c1, c1/c2 and c2/c2 were 218, 257 and 211 g, respectively, and were not statistically different. BP was elevated with the increase in alcohol consumption, and was significantly higher in the c2/c2 genotype than in the other genotypes among the subjects consuming 200 g or more of alcohol per week. Serum uric acid did not correlate with alcohol consumption in the whole subjects, but it was also higher in drinkers having the c2/c2 genotype. Although the number of subjects was too small for a definite conclusion to be drawn, these results suggest to some extent that Japanese men having the c2/c2 genotype of CYP2E1 are more sensitive to the pressor effect of alcohol. Further studies are required to confirm this.


Subject(s)
Alcohol Drinking , Asian People/genetics , Blood Pressure/drug effects , Cytochrome P-450 CYP2E1/genetics , Adult , Blood Pressure/genetics , Genotype , Humans , Japan/ethnology , Male , Middle Aged
10.
J Toxicol Environ Health ; 48(2): 131-40, 1996 Jun 07.
Article in English | MEDLINE | ID: mdl-8642621

ABSTRACT

We used ultrasound (US) transmission to evaluate the speed of sound (SOS) and broadband ultrasonic attenuation (BUA) in the calcaneus in 17 male and 18 female inhabitants of a Cd-polluted area and 23 men and 45 women living in a nonpolluted area. Significant decreases in SOS and stiffness (Stiff), which was an index empirically derived from SOS and BUA, were found in Cd-exposed women. To evaluate the usefulness of the US measurements for detecting bone abnormality in Cd-exposed people, we examined the associations with the bone measurements of metacarpus by the previously used microdensitometry (MD) method and the grade of renal tubular damage due to Cd exposure. Bone density estimated by MD, sigmaGS/D, was significantly correlated with BUA, SOS, and Stiff in the Cd-exposed men and with BUA and Stiff in the Cd-exposed women. Further, in the Cd-exposed women, the decreases in BUA and Stiff correlated significantly with the increases in urinary beta 2-microglobulin, while sigmaGS/D by the MD method did not. These results suggest that the measurement of the calcaneus using US is not only radiation free but also can be used as a tool for population surveys aiming to evaluate bone damage in people, especially women, showing renal tubular damage due to environmental Cd exposure.


Subject(s)
Cadmium Poisoning/diagnostic imaging , Cadmium/adverse effects , Calcaneus/diagnostic imaging , Environmental Exposure/adverse effects , Aged , Aged, 80 and over , Bone Density/drug effects , Cadmium/urine , Calcaneus/drug effects , Cohort Studies , Densitometry , Female , Humans , Kidney Function Tests , Kidney Tubules/diagnostic imaging , Kidney Tubules/drug effects , Male , Metacarpus/diagnostic imaging , Metacarpus/drug effects , Middle Aged , Soil Pollutants , Spectrophotometry, Atomic , Ultrasonography , beta 2-Microglobulin/urine
11.
Int Arch Occup Environ Health ; 68(5): 315-20, 1996.
Article in English | MEDLINE | ID: mdl-8832296

ABSTRACT

Psychosocial job stress has been shown to be associated with the development of cardiovascular disease. However, the pathophysiological mechanisms underlying this relationship remain unclear. The aim of the present study was to elucidate whether marked job stress affects the parameters of blood coagulation and fibrinolysis, such as plasma fibrinogen concentration, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) activities, in 213 middleaged male workers in a computer-producing factory. Job stress was measured using a Japanese version of the Job Content Questionnaire (JCQ) developed by Karasek. The mean t-PA activity in workers with lower and higher job demands was 0.23 and 0.18 IU/ml respectively, and this difference was significant (P < 0.05). The mean plasma fibrinogen in workers with lower and higher job decision latitude was 224.8 and 236.3 mg/dl respectively, and the mean PAI-1 activity in workers with lower and higher job strain was 14.9 and 17.7 U/ml respectively, though these differences remained at a borderline level of significance (0.05 < P < 0.10). Multiple regression analyses showed that the parameters of blood coagulation and fibrinolysis were closely associated with the cardiovascular risk factors of age, obesity, blood pressure, elevated serum lipids, and smoking, but that high job demands were significantly related to decreases in t-PA activity, independently of the traditional risk factors. These results suggest that psychosocial job stress may be related, at least partly, to the development of cardiovascular disease via changes in plasma fibrinolytic activity.


Subject(s)
Blood Coagulation/physiology , Cardiovascular Diseases/etiology , Fibrinogen/analysis , Stress, Psychological , Adult , Data Collection , Humans , Japan , Male , Middle Aged , Plasminogen/analysis , Regression Analysis , Risk Factors , Stress, Psychological/complications , Workplace
12.
Hypertens Res ; 18(4): 295-301, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8747307

ABSTRACT

A significant association between elevations of serum gamma-glutamyl transpeptidase (gamma-GTP) levels and those of blood pressure and hypertension has been reported separately in drinkers and nondrinkers. The aim of the present study is to evaluate whether the relationship between serum gamma-GTP and the prevalence of hypertension is the same or similar in both drinkers and nondrinkers. The study subjects comprised 4,920 male nondrinkers, 9,390 male daily drinkers, 8,081 female nondrinkers, and 278 female daily drinkers, who were aged 40 to 59 years. The prevalence of hypertension in the male and female daily drinkers was 1.5 and 1.3 times, respectively, higher than in the nondrinkers. Mean systolic blood pressure in the male and female drinkers was 4.4 and 3.1 mmHg, respectively, higher than in the nondrinkers. After adjusting for age, body mass index, and serum gamma-GTP levels, the differences in the prevalence of hypertension and the mean systolic blood pressure level between the drinkers and nondrinkers decreased to 1.2 times and 2.7 mmHg, respectively. Although these small differences remained statistically significant, the association between serum gamma-GTP and hypertension appears to be quite similar in both drinkers and nondrinkers, suggesting that hepatic steatosis may play a common, pathogenetic role in the development of hypertension.


Subject(s)
Alcohol Drinking/metabolism , Hypertension/enzymology , gamma-Glutamyltransferase/blood , Adult , Age Factors , Blood Pressure/drug effects , Blood Pressure/physiology , Body Weight , Female , Humans , Linear Models , Logistic Models , Male , Middle Aged , Regression Analysis , gamma-Glutamyltransferase/drug effects
13.
Am J Hypertens ; 8(11): 1053-9, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8554727

ABSTRACT

Aldehyde dehydrogenase with a low Michaelis constant (Km), ALDH2, is a major enzyme involved in the conversion of acetaldehyde, a toxic metabolite of ethanol, into acetic acid in the liver. Inherited deficiency of ALDH2 activity is found in half of Japanese, and is characterized by "Oriental flushing" after alcohol consumption. The aim of the present study is to evaluate the influence of the genetic polymorphism in alcohol metabolism on the sensitivity to the pressor effect of alcohol. Genotypes of ALDH2 were determined in 403 middle-aged Japanese men using genomic DNA extracted from white blood cells. Two hundred and forty-three (60%) of the subjects were shown to be homozygotes for the normal ALDH2 gene, 25 (6%) of the subjects were homozygotes for the mutant ALDH2 gene, and the remaining 135 (33%) were heterozygotes. None of the homozygotes for the mutant gene drank enough to show the pressor effect of alcohol. Elevations of blood pressure associated with increasing alcohol consumption or with elevations of serum gamma-glutamyl transpeptide (GTP) level were not different between the other two ALDH2-genotypes. It can be concluded that polymorphism in the ALDH2-genotype found in Japanese men does not affect the individual sensitivity to the pressor effect of alcohol.


Subject(s)
Alcohol Drinking/adverse effects , Aldehyde Dehydrogenase/genetics , Blood Pressure/drug effects , Adult , Alcohol Drinking/ethnology , Dose-Response Relationship, Drug , Genotype , Humans , Japan , Male , Middle Aged , Polymorphism, Genetic
14.
Toxicol Lett ; 80(1-3): 49-54, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7482591

ABSTRACT

Urinary human intestinal alkaline phosphatase (IAP), beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cd-exposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between beta 2-MG and IAP or NAG. The beta 2-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and beta 2-MG is considered to be more useful.


Subject(s)
Alkaline Phosphatase/urine , Cadmium Poisoning/enzymology , Environmental Pollutants/poisoning , Acetylglucosaminidase/urine , Aged , Aged, 80 and over , Biomarkers/urine , Cadmium Poisoning/urine , Environmental Exposure , Female , Humans , Intestines/enzymology , Japan , Kidney Tubules/drug effects , Kidney Tubules/injuries , Kidney Tubules/metabolism , Male , Middle Aged , beta 2-Microglobulin/urine
15.
Blood Press ; 4(2): 91-6, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7599760

ABSTRACT

Elevated intracellular free calcium (Ca2+) has been proposed as a mechanism of alcohol-induced hypertension from animal experimental studies, but this has not been confirmed in man. In the present study, intraplatelet Ca2+ concentration (plt.[Ca2+]i) was measured in 83 middle-aged men, and the associations between alcohol consumption, age, body mass index (BMI), hematological and serum biochemical variables, plt.[Ca2+]i and blood pressure were analyzed. Plt.[Ca2+]i did not show a significant univariate correlation with alcohol consumption or with blood pressure, but did so with serum gamma-glutamyl transpeptidase (gamma-GTP) levels. Age, BMI and serum gamma-GTP were selected as independent contributors to blood pressure, and gamma-GTP alone was selected as the determinant of plt.[Ca2+]i by multiple regression analyses. The association between gamma-GTP and plt.[Ca2+]i was shown to be common or at least very similar in both drinkers and nondrinkers by generalized linear model analysis. Therefore, chronic alcohol consumption in humans may relate to elevations of plt.[Ca2+]i, not mainly by the direct action of alcohol but by some metabolic alterations after alcohol consumption. The significance of elevated plt.[Ca2+]i in drinkers in the development of hypertension, however, remains obscure.


Subject(s)
Alcohol Drinking/blood , Blood Platelets/metabolism , Calcium/analysis , Hypertension/blood , Adult , Age Factors , Alcohol Drinking/adverse effects , Alcohol Drinking/physiopathology , Blood Pressure , Body Weight , Hematologic Tests , Humans , Hypertension/etiology , Hypertension/physiopathology , Male , Middle Aged , gamma-Glutamyltransferase/blood
16.
Clin Exp Hypertens ; 16(6): 741-59, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7858557

ABSTRACT

Erythrocyte Na+/K(+)-pump activities have been measured in hypertensives, alcohol consumers and obese persons, but the results have been variously reported as decreased, increased or unchanged. We analyzed the relationships between erythrocyte Na+/K(+)-ATPase activities and the membrane and serum lipid profiles in 83 middle-aged men, to clarify the reasons for these inconsistencies. Increases in erythrocyte Na+/K(+)-ATPase activity related closely to decreases in cholesterol to phospholipid (C/P) ratio of the erythrocyte membrane. Decreases in the C/P ratio in turn related closely to elevations of serum triglycerides (TG) with increasing body mass index, and weakly to the volume of alcohol consumed. Thus, erythrocyte Na+/K(+)-ATPase activities depend largely on the membrane and serum lipid profiles as related to body weight and alcohol consumption, and which may be a cause of the previous conflicting findings. Erythrocyte Na+/K(+)-ATPase showed a positive association with blood pressure, independently of age, body mass index and serum gamma-glutamyl transpeptidase levels. Although the biological link of elevated erythrocyte Na+/K(+)-ATPase with the rise in blood pressure remains unclear, it may be a reflection of hyperinsulinemia in the subjects with a higher blood pressure due to overweight or excessive alcohol consumption.


Subject(s)
Erythrocytes/enzymology , Hypertension/blood , Sodium-Potassium-Exchanging ATPase/blood , Adult , Alcohol Drinking , Blood Glucose/metabolism , Blood Pressure , Body Mass Index , Cholesterol/blood , Erythrocyte Membrane/metabolism , Humans , Lipids/blood , Liver/enzymology , Male , Membrane Lipids/blood , Middle Aged , Phospholipids/blood
17.
Nihon Eiseigaku Zasshi ; 49(2): 598-605, 1994 Jun.
Article in Japanese | MEDLINE | ID: mdl-8041016

ABSTRACT

We compared thyroid hormone levels of inhabitants (19 men and 16 women) of the cadmium (Cd)-polluted Kakehashi River basin in Ishikawa Prefecture, with those of subjects (23 men and 47 women) living in a non-polluted area. In addition, we investigated the relationships between the thyroid hormone levels and indices of renal dysfunction induced by Cd exposure. The following results were obtained: 1) The free T4 level of females was significantly lower than that of controls. 2) The T3 level of inhabitants of both sexes was significantly higher than that of controls. 3) The level of free T4 among females became lower with the increases of urinary beta 2-microglobulin (beta 2-MG), urinary protein, urinary sugar, urinary amino acids and serum creatinine (Cr) levels, and with decreases of creatinine-clearance (CCr) and %TRP. 4) We could not find any relationship between the increase of T3 and the indices of renal dysfunction induced by Cd exposure in either sex.


Subject(s)
Cadmium/adverse effects , Environmental Pollution/adverse effects , Thyroid Hormones/blood , Environmental Exposure , Female , Humans , Male , Middle Aged , Thyroxine/blood , Triiodothyronine/blood
18.
Toxicol Lett ; 71(3): 209-16, 1994 May.
Article in English | MEDLINE | ID: mdl-8160209

ABSTRACT

To clarify the significance of elevated serum total alkaline phosphatase activity (t-ALP) in persons exposed to environmental cadmium (Cd), the fraction of ALP originating from bone (b-ALP) was assayed using a wheat-germ agglutinin method in 23 men and 20 women in a Cd-polluted area who showed excessive urinary beta 2-microglobulin excretion, and in 21 men and 44 women in a non-polluted area, in addition to 7 patients with itai-itai disease. The fraction of b-ALP increased linearly with the increase in t-ALP in the women, irrespective of Cd-exposure. Elevations of both t-ALP and b-ALP in the Cd-exposed women, including inhabitants of the Cd-polluted area and patients with itai-itai disease, were found with decreases in serum calcium and bone density. It is concluded that elevated serum ALP levels found in Cd-exposed persons reflect the development of Cd-induced bone damage.


Subject(s)
Alkaline Phosphatase/blood , Bone and Bones/enzymology , Cadmium Poisoning/blood , Cadmium/adverse effects , Environmental Exposure/adverse effects , Aged , Bone Density , Cadmium Poisoning/etiology , Calcium/blood , Female , Humans , Male , Middle Aged
19.
Rinsho Byori ; 41(12): 1353-7, 1993 Dec.
Article in Japanese | MEDLINE | ID: mdl-8295347

ABSTRACT

Erythrocyte Na+/K(+)-ATPase activity (Ery-ATPase) and intra-erythrocyte sodium and potassium concentrations (Ery-Na, Ery-K) were determined in 83 men aged between 36 and 60 years. Volumes of alcohol consumed during the preceding one week (Alc) correlated significantly with blood pressure (BP), but not correlated with Ery-ATPase and Ery-K. Ery-Na showed a week inverse correlation with Alc, but the partial correlation after adjusting Ery-ATPase was not significant. Therefore, elevations of BP found in alcohol consumers are not related to changes in the cell-membrane Na+/K(+)-ATPase activity and intracellular Na and K concentrations. Ery-ATPase showed a borderline significant positive correlation with diastolic BP (0.05 < or = p < 0.10), independently of age, body mass index and Alc. The significance of the weak association in the pathogenesis of hypertension remains unclear.


Subject(s)
Alcohol Drinking/adverse effects , Erythrocytes/enzymology , Hypertension/etiology , Potassium/blood , Sodium-Potassium-Exchanging ATPase/blood , Sodium/blood , Adult , Alcohol Drinking/blood , Humans , Male , Middle Aged
20.
Obes Res ; 1(6): 469-74, 1993 Nov.
Article in English | MEDLINE | ID: mdl-16350321

ABSTRACT

The relationships between increases in body mass index (BMI) and increases in hypertension were compared between non-drinkers with elevated serum gamma-glutamyl transpeptidase (gamma-GTP) levels (> or = 50 U/l) and those with normal levels, who comprised 10,952 men and 22,107 women aged 40-59 years recruited from an occupational health clinic. Hypertension was found in 16.1% and 13.5% of the men and women, and elevated serum g-GTP was found in 10.8% and 2.8% of the men and women, respectively. The prevalences of hypertension and elevated serum gamma-GTP levels were both increased with increased BMI. Hypertension was, however, shown to be 1.5 times more prevalent in the persons with elevated serum gamma-GTP levels than in those with normal levels in both sexes, even after adjusting for BMI by a multiple logistic analysis. It can be concluded that elevations of serum gamma-GTP, which are probably a reflection of fatty liver in the non-drinkers, are closely related to the development of hypertension associated with increased obesity.


Subject(s)
Fatty Liver/complications , Fatty Liver/pathology , Hypertension/blood , Hypertension/complications , Obesity/complications , gamma-Glutamyltransferase/blood , Adult , Alcohol Drinking , Blood Pressure , Body Mass Index , Body Weight , Female , Humans , Hypertension/etiology , Insulin Resistance , Male , Middle Aged , Obesity/etiology , Regression Analysis , Sex Factors , Time Factors
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