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Biomedical subjects

T Kido

Publications and source records attributed to T Kido.

At least 19 recordsLinked to original sources

Effect of stilbene derivatives on gastric H+, K(+)-ATPase.

The effect of naturally occurring hydroxystilbene, 3,3',4,5-tetrahydroxystilbene (piceatanol), and its derivatives on gastric H+, K(+)-ATPase was studied. Piceatanol inhibited H+, K(+)-ATPase in a dose-dependent manner. The 50% inhibition value was 4.3 x 10(-6) M. It was found from the kinetic study that the inhibition of the enzyme by piceatanol was competitive with respect to ATP and was noncompetitive with respect to K+. Piceatanol also effectively inhibited gastric acid secretion. However, methylation of phenolic hydroxy groups of piceatanol resulted in a complete loss of inhibition of the enzyme and acid secretion, suggesting the role of phenolic hydroxy groups in the inhibition. The study on hydroxystilbene derivatives also showed that phenolic hydroxy groups are important in the interaction with H+, K(+)-ATPase and that stilbenes with neighbouring hydroxy groups are the most effective inhibitors.

Adenosine Triphosphate

Inhibition of gastric H+,K(+)-ATPase and acid secretion by cassigarol A, a polyphenol from Cassia garrettiana Craib.

The effects of cassigarol A, a naturally occurring polyphenol, on gastric H+,K(+)-ATPase and gastric acid secretion were studied. Cassigarol A inhibited H+,K(+)-ATPase and K-stimulated p-nitrophenyl phosphatase from hog gastric mucosa with 50% inhibition of 1.2 x 10(-6) and 6.3 x 10(-6) M, respectively. The kinetic study showed that the inhibition of H+,K(+)-ATPase by cassigarol A was competitive with respect to ATP and non-competitive with respect to K+. Cassigarol A inhibited both H+,K(+)-ATPase-mediated proton transport and 2-deoxy-D-glucose-induced acid secretion. On the other hand, cassigarol A acetate, in which phenolic hydroxy groups are acetylated, was not effective in the inhibition of enzyme activity and acid secretion. These results indicate that cassigarol A is a potent inhibitor of gastric H+,K(+)-ATPase, that the anti-secretory activity of cassigarol A is related to the inhibition of H+,K(+)-ATPase and that an important moiety of cassigarol A in the interaction with the enzyme is the phenolic hydroxy groups.

Adenosine Triphosphatases

Regulation of acetylcholine release in vivo from rat hippocampus by monoamines as revealed by novel column-switching HPLC with electrochemical detection.

To clarify monoaminergic regulation of acetylcholine (ACh) release in the rat hippocampus, the effects of administration of monoamines through a dialysis probe on extracellular ACh levels were examined using in vivo brain microdialysis combined with a novel column-switching HPLC system. Infusion of dopamine or 5-hydroxytryptamine, but not noradrenaline, increased ACh levels. The ACh levels also increased following infusion of apomorphine and 5-methoxy-N,N-dimethyltryptamine. These results demonstrate that hippocampal ACh release is regulated by dopamine and 5-hydroxytryptamine.

Acetylcholine

The renal handling of sodium and potassium in environmental cadmium-exposed subjects with renal dysfunction.

To clarify using clearance methods the renal handling of sodium and potassium in a population with environmental cadmium (Cd)-induced renal dysfunction, 76 Cd-exposed subjects (32 men and 44 women) and 36 non-exposed subjects (18 men and 18 women) were selected. Fractional excretions of potassium and beta 2-microglobulin were higher in the Cd-exposed subjects than in the non-exposed subjects, while the fractional excretion of sodium in the Cd-exposed subjects was equal to that of the non-exposed subjects. The urinary excretion rate of sodium was significantly lower in the Cd-exposed subjects than in the non-exposed subjects, while no significant difference was found in the urinary potassium excretion rate. Fractional excretion of sodium showed a significant correlation with age in all the subjects, while that of potassium significantly correlated with serum beta 2-microglobulin. These results indicate that increases in the fractional excretion of sodium or potassium do not directly signify increased urinary excretion of sodium or potassium in Cd-induced renal tubular dysfunction. The fractional excretion of potassium may be more affected by Cd-induced renal dysfunction, while that of sodium appears to be more related to age.

Aged

Impairment of vitamin D metabolism due to environmental cadmium exposure, and possible relevance to sex-related differences in vulnerability to the bone damage.

To determine whether depleted serum 1 alpha,25-dihydroxyvitamin D (VD) concentrations are associated with cadmium (Cd)-induced renal damage, the relationships between four indices of renal function and two indicators of bone metabolism, that is, serum VD and parathyroid hormone (PTH) concentrations, were analyzed in 30 male and 44 female subjects exposed to environmental Cd. Also, these associations were compared in male and female subjects to evaluate sex-related differences in vulnerability to the bone damage observed in Cd-exposed persons. Serum VD decreased significantly with declines in creatinine clearance and percentage tubular reabsorption of phosphate, and with increases in serum creatinine and serum beta 2-microglobulin (beta 2m) concentrations in the female subjects exposed to Cd, but not in the male subjects. The correlation between serum VD and PTH levels was also significant only in the females. Correlation coefficients between serum beta 2m and VD and those between serum PTH and VD in both sexes were significantly different. These results suggest that renal damage due to Cd exposure leads to the decreases in the serum VD level and increases in serum PTH level, and that the more marked changes in serum VD and PTH in the women may play a role in the development of sex-related differences in Cd-induced bone injury.

Aged

[Study of an outbreak of itai-itai disease].

We studied an outbreak of itai-itai disease in the Jinzu River basin, in Toyama, Japan. One hundred and fifty females recognized as itai-itai disease patients till by 1990 were studied for the ages and years of onset and residence in the cadmium-polluted area. 1. Cases were recognized from as early as 1929, increased gradually to the peak of 1955-1959 and rapidly decreased up to the 1970s. 2. It was found that the later the patients was born, the younger the age of onset, though there was no difference of ages of onset between the cases born in the 1910s and the cases born from 1920. 3. The onset of itai-itai disease was most frequently seen at 50-59 years of residence in the cadmium-polluted area. It was found that the later a person started to inhabit the cadmium-polluted area, the shorter the period of residence in the cadmium-polluted area up to onset of itai-itai disease. 4. Comparing the patients who inhabited the cadmium-polluted area from birth and those who had moved there from non-polluted areas, the age of onset was higher in the latter, but there were no significant differences in the period of residence up to onset. From these findings, it appeared that itai-itai disease was not caused by aging, but by cadmium exposure starting from the 1910s.

Cadmium Poisoning

Dose-response relationship for renal dysfunction in a population environmentally exposed to cadmium.

Two epidemiological studies aimed at investigating the dose-response relationship of environmental cadmium exposure were performed in a population living in the Kakehashi River basin, a cadmium-polluted area in Japan. In the first, the average cadmium concentration in rice from each village was used as an indicator of exposure and metallothioneinuria or beta 2-microglobulinuria as an index of renal tubular dysfunction. Dose-related increases in both the latter indices were observed. The total cadmium intake resulting in both metallothioneinuria and beta 2-microglobulinuria was calculated to be approximately 2 g for both sexes. In the second study, the dose-response relationship between urinary cadmium and metallothioneinuria or beta 2-microglobulinuria was evaluated in the same population. Prevalence rates increased proportionally with increasing urinary cadmium (Cd-U). The values of Cd-U corresponding to the prevalence rates of metallothioneinuria in the non-exposed population were calculated to be 4.2 micrograms/g creatinine for men and 4.8 micrograms/g creatinine for women; for beta 2-microglobulinuria the corresponding figures were 3.8 micrograms/g creatinine for men and 4.1 micrograms/g creatinine for women.

Aged

[Locoregional therapy in patients with malignant pleural effusion--two different types of "BAC therapy"].

We used fibrin clot (FC) as a carrier of anticancer drug (AD) to provide a novel therapy for patients with serious malignant pleural effusion. After evacuating the pleural fluid, we enhanced an "FC-AD" formation in the pleural cavity of the patient to prevent this kind of effusion from reaccumulating. In an attempt to enhance FC-AD formation, we used two different procedures; either, fibrinogen/AD/G.T.XIII (procedure I) or fibrin glue/AD (procedure II). G.T.XIII is our newly devised compound drug, composed of biodegradable gelatin (G), thrombin (T) and a blood coagulation factor XIII (XIII). This therapy was termed "Bio-Adhesio-Chemo (BAC) therapy." We conducted BAC therapy 52 times on 44 patients using procedure I and 4 times on 4 patients using procedure II. Complete remission of the effusion was obtained, overall, in 83%, partial remission in 17%, and no non-effective case. The improvement of PS of the patients treated was 73%. Nineteen patients could be discharged with this therapy. Toxic effects with BAC therapy were within Grade 2 in all cases. We could favorably enhance FC-AD formation, in every case, by both procedure I and II. BAC therapy is very promising as a novel cancer chemopleurodesis for patients with malignant pleural effusion.

Antineoplastic Combined Chemotherapy Protocols

Dose-response relationship between dietary cadmium intake and metallothioneinuria in a population from a cadmium-polluted area of Japan.

An epidemiological study to examine the dose-response relationship for environmental cadmium exposure was performed in 1843 cadmium-exposed and 240 non-exposed inhabitants of the Kakehashi River basin in Ishikawa, Japan. The average cadmium concentration in rice from each village was employed as an indicator of cadmium exposure and the individuals were grouped according to the length of residence in the polluted area. Metallothioneinuria was used as an index of renal tubular dysfunction produced by the chronic exposure to cadmium. A dose-related increase in metallothioneinuria was observed. The chronic total cadmium intake resulting in metallothioneinuria in this population was calculated to be approximately 2 g for both men and women. The cumulative lifetime dose of 2 g cadmium over a 50-year period, means an average daily intake of 110 micrograms. Thus, these values may be regarded as the maximum allowable lifetime and daily intake limits, respectively for chronic dietary exposure to cadmium.

Administration, Oral

Assessment of cadmium-induced osteopenia by measurement of serum bone Gla protein, parathyroid hormone, and 1 alpha,25-dihydroxyvitamin D.

To assess the osteopenia induced by environmental cadmium (Cd) exposure by measurement of serum bone Gla protein (BGP), parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)2D), 29 men and 41 women who lived in a Cd-polluted area and showed renal tubular dysfunction were selected. To evaluate the degree of osteopenia, microdensitometry (MD) was used. Compared with the non-exposed subjects, the levels of serum creatinine and BGP, urinary Cd and beta 2-microglobulin and blood Cd were higher, while the levels of serum inorganic phosphorus and MD indicators were lower in the Cd-exposed group. In simple correlation matrix, BGP showed significant correlations with serum alkaline phosphatase (S-Al-p) and MD indicators in the Cd-exposed men, and also correlations with S-Al-p and 1 alpha-25(OH)2D in the Cd-exposed women. Applying multivariate analysis to the Cd-exposed subjects, BGP, %TRP and base excess were found to show significant associations with the MD indicators in the men. In the women, PTH, age, blood Cd and BGP were associated significantly with the MD indicators. Only serum BGP showed a significant correlation in both sexes of the Cd-exposed subjects, and a sex difference was found in the relationship between bone metabolic markers and osteopenia. These results suggest that serum BGP has a close independent association with the osteopenia induced by Cd exposure and that BGP, which has a different biological function from that of PTH or 1 alpha,25(OH)2D, may be a useful indicator to detect bone damage in Cd-exposed subjects.

Adult

Dose-response relationship between urinary cadmium and metallothionein in a Japanese population environmentally exposed to cadmium.

The dose-response relationship between cadmium (Cd) exposure and renal dysfunction, as measured by urinary Cd and metallothoinein (MT), was evaluated in a population living in the Kakehashi River basin, a Cd-polluted area in Japan. Morning urine specimens were collected from 1397 men and 1713 women who were 50 years or older. In addition, urine specimens were collected from a control population consisting of 110 men and 130 women. The 97.5% upper limits for MT in the control population were used to determine the prevalence rates for MT-uria at various urinary Cd concentrations. Probit linear regression analysis showed significant dose-response relationships between MT and Cd. In the control population, prevalence rates of MT-uria for men and women were 1.8 and 3.1%, respectively. Based on the prevalence rates of MT-uria in the control population, the upper limits for the urinary Cd concentrations were calculated from the slopes of the regression lines to be 4.2 and 4.8 micrograms/g creatinine for men and women, respectively. These values, which are similar to those reported previously using urinary beta 2-microglobulin as the indicator, may be of use in establishing the biological threshold, i.e. maximum allowable concentration, for urinary Cd in the environmentally exposed Japanese population.

Age Factors

Significant increase of urinary mucoprotein in environmental-cadmium-exposed Japanese subjects.

Urinary mucoprotein (U-MP) was determined in 169 Japanese environmental-cadmium-exposed and 81 non-exposed subjects. Urinary total protein, albumin, beta 2-microglobulin (beta 2-MG), cadmium (Cd) and creatinine were also measured. Significant increases in U-MP and other proteins were found in the Cd-exposed subjects. Significant correlations between each protein were seen in the Cd-exposed and the total group of subjects. U-MP was highly correlated with urinary beta 2-MG and their correlation coefficient was the highest in the total group of subjects. beta 2-MG was the most sensitive indicator among them to detect Cd-induced renal dysfunction, although beta 2-MG is degraded in urine with a pH less than 5.5 U-MP is an acid-soluble protein. Therefore, U-MP is also available for studies on renal dysfunction caused by exposure to Cd, in conjunction with beta 2-MG.

Albuminuria

Alcohol, high blood pressure, and serum gamma-glutamyl transpeptidase level.

The influence of the level of serum gamma-glutamyl transpeptidase, a biological marker of alcohol consumption, on elevations of blood pressure and on the development of hypertension related to increases in alcohol consumption was determined in a cross-sectional study of 1,492 middle-aged male workers and in a subsequent 5-year follow-up study of 1,393 workers. Blood pressure levels, as well as the prevalence and incidence of hypertension, were higher in the subjects with serum gamma-glutamyl transpeptidase levels above 50 units/l than in those with normal levels. These differences were more marked in drinkers who consumed 30 ml or more of alcohol per day. Thus, elevated serum gamma-glutamyl transpeptidase activity may identify drinkers at higher risk for the development of alcohol-related hypertension.

Adult

[Significance of urinary cadmium concentration as an indicator of cadmium exposure in a population exposed to cadmium in a general environment].

Study was made on the significance of urinary cadmium concentration as an indicator of internal dose in a general environment polluted by cadmium. As an index of external dose, the mean rice cadmium concentration in each of 23 villages was employed. Morning urine samples were collected from 3,178 inhabitants of 23 cadmium-polluted villages of Kakehashi River basin in Ishikawa Prefecture and 294 inhabitants of two nonpolluted villages. Cadmium concentration in urine was determined. In addition, their residential history and intake of cadmium-polluted rice were obtained. All the subjects were 50 years of age or over. Participation rates were 91% for the polluted area and 94% for the nonpolluted area. Urinary cadmium concentrations were higher in the inhabitants of the cadmium-polluted area than in those of the nonpolluted area. Among the inhabitants in the cadmium-polluted area, urinary cadmium concentrations were higher in the subjects who had consumed cadmium polluted rice than in those who had not. The mean urinary cadmium concentrations in each village increased proportionally to increase in mean village rice cadmium concentration (intensity of exposure) when the inhabitants were classified according to period of residence at their present address. The mean urinary cadmium concentrations in each village were also significantly correlated with period of residence at the present address (duration of exposure) when the inhabitants were classified according to mean rice cadmium concentration of their village. It is concluded that urinary cadmium concentration mainly reflects the body burden of cadmium in a general environment polluted by cadmium.

Adult

Glycoconjugates in the otolithic organ of the developing chick embryo.

The presence of glycoconjugates in the otolithic organ of developing chick embryos was investigated histochemically using lectins. On the 6-day-old chick embryo, intense labelling with lectins was observed in the sensory epithelium, on the surface of the epithelium and on the immature otoconia. The otoconia were intensely labelled with lectins at every stage of the chick embryos, while the labelling with lectins in the sensory epithelium became weaker with the maturing of the otoconia. In TEM observation, the secretory granules of the supporting cells of the sensory epithelium were labelled with lectin. The reaction of lectin was more intense in the electronic dense zone of the otoconium than in the electronic lucent zone at every stage of the chick embryos. These findings indicate that the precursors of the otoconia are secreted by the supporting cells of the sensory epithelium and that glycoconjugates play an important role in otoconial formation.

Animals