Molecular cloning of rat class I genes related to the mouse TL gene subfamily of the major histocompatibility complex.
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Animals↗
Biomedical subjects
R Honda
Publications and source records attributed to R Honda.
[Alcohol-related high blood pressure, and erythrocyte Na+/K(+)-ATPase activity, sodium and potassium concentrations].
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.
Adult↗
Orthostatic hypotension: with particular reference to experimentally-induced orthostatic hypotension in dogs.
Blood pressure (BP) and heart rate (HR) were measured while standing in a stable position for SPF beagle dogs consisting of 4 females with an average weight of 8.73 +/- 0.58 kg and average age of 7.38 +/- 0.12 months. No anesthetic was used during the procedure. These dogs were subjected to a postural change, a 90 degrees-tilt standing position, and BP and HR were measured one minute and ten minutes later. In addition, 20 mg/kg of tetraethyl-ammonium bromide (TEA) as a gangliolytic drug was administered by i.v. injection within 30 seconds, and then BP and HR were measured in the resting state for 20 minutes. When changing from the resting position to the 90 degrees-tilt standing position after administration of TEA, these were significant decreases in systolic BP, diastolic BP and mean arterial BP one minute and ten minutes later. An experimental model of orthostatic hypotension was considered to have been achieved during these methods.
Animals↗
[Prediction of ovulation by urinary LH surge].
To investigate the usefulness of a semi-quantitative assay of urinary luteinizing hormone (LH) for predicting ovulation, the relationship among urinary LH, serum LH, serum estradiol (E2) and ultrasonographic observations of follicles were examined in 32 infertile women (35 cycles) at spontaneous (7), clomiphene (13) or cyclofenil (3) induced or hMG (12) induced cycles. Their urine samples were collected 3 times a day for LH assay, starting from about the 10th cycle day or when follicles having a diameter of 10mm or more were detected to the day of ultrasonographical confirmation of follicle ruptures. In the morning on these days, blood was taken twice daily for LH and E2 determination at intervals of 30 min. In spontaneous cycles, urinary LH was (P < 0.001) correlated to a significant extent with the serum LH and E2 levels, and follicle rupture was observed 1.9 days after the urine LH surge. In contrast, there was no significant correlation between the urine LH and serum LH or E2 levels in the ovulation induced cycles. In addition, the period from urine LH positive to follicle rupture was significantly (P < 0.05) prolonged in those cycles compared with that in spontaneous cycles. These results suggested that the urine LH determination was good for predicting ovulation in spontaneous cycles, but it was also necessary to monitor the follicle sizes by ultrasonography in ovulation induced cycles.
Adult↗
The cell cycle regulator, human p50weel, is a tyrosine kinase and not a serine/tyrosine kinase.
The human weel protein, a homologue of the yeast weel protein, was expressed in E. coli and purified to homogeneity. The purified weel protein phosphorylated the tyrosine residue of cdc2 kinase in HeLa cell extracts in the presence of human cyclin B1. It also phosphorylated the tyrosine but not the threonine residue in the peptide of the amino-terminal of cdc2 kinase, although both these residues have been shown to be phosphorylated in higher eukaryotes in vivo. Furthermore, serine and tyrosine residues of the yeast weel protein are reportedly autophosphorylated in vitro, however the tyrosine residue of the human weel protein was autophosphorylated whereas the serine and threonine residues were not. These data indicate that human p50weel is tyrosine kinase and that it phosphorylated the tyrosine residue of the amino-terminal of cdc2 kinase in the presence of cyclin B1 and that the threonine residue is phosphorylated by another, unknown kinase.
Amino Acid Sequence↗
Cyclin-dependent kinase 2 (cdk2) in the murine Cdc2 kinase TS mutant.
Kinases of the mammalian cdc2 family including cdk2 (cyclin-dependent kinase 2) are thought to be involved in both the G2/M transition and DNA replication. To investigate the role of cdc2 kinase and cdk2 in cell cycle progression, murine tsFT210 cells bearing a temperature-sensitive cdc2 mutation were used. These kinases were purified by column chromatography, using a peptide with the consensus phosphorylation site of cdc2 kinase as the substrate. In this mutant, cdc2 kinase activity was temperature sensitive and cdk2 activity was not. At the restrictive temperature, the mutant was only arrested in the G2 phase and not in the G1-S phase, suggesting that cdk2 did not compensate for cdc2 kinase at the G2/M transition but did function at the G1-S phase. This suggestion was supported by the finding that transfection of cdk2 cDNA did not improve the growth of the mutant cell line at the restrictive temperature, although transfection of cdc2 cDNA did.
Animals↗
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↗
[Determination of human erythrocyte membrane Na+/K(+)-ATPase activity in small volume of blood sample].
Na+/K(+)-ATPase of the cell membrane is considered to be closely related to the pathology of various diseases including hypertension and heart failure. The activity of this enzyme in the erythrocyte membrane has been determined in earlier reports by the assay of inorganic phosphate generated from the substrate ATP or radioimmunoassay after binding 3H ouabain to the erythrocyte membrane, using a large volume of blood samples. However, as neither method was appropriate for wide routine use, we developed a method to assay this enzyme in a small volume (10 ml) of fresh human blood samples with re-evaluation of conditions for the inorganic phosphate assay. In this method, the coefficient value (CV) of membrane protein amount and the NA+/K(+)-ATPase activity were 2.2% and 2.5% respectively, indicating sufficient precision of the assay. Moreover, in 97 subjects without abnormalities in blood biochemical tests (77 males and 20 females) aged 35-59 years, the enzyme activity showed no differences according to age or sex, ranging from 0.217 to 0.071 mumols Pi/mg/hr with a mean of 0.130.
Adult↗
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↗
A point mutation in C-terminal region of cdc2 kinase causes a G2-phase arrest in a mouse temperature-sensitive FM3A cell mutant.
A mouse temperature-sensitive mutant for cell growth, tsFT210, was characterized. More than 90% of the mutant cells were arrested at the G2 phase at the nonpermissive temperature (39 degrees C). In this mutant, the activity of cdc2 kinase did not increase at the nonpermissive temperature (39 degrees C) but did increase at the permissive temperature (33 degrees C) at the G2/M phase in the cell cycle. The in vitro activity of cdc2 kinase of tsFT210 was more thermolabile than that of wild-type cells. The amount of cdc2 kinase in tsFT210 cells decreased when the cells were incubated at 39 degrees C, but that in wild-type cells did not. Using the polymerase chain reaction (PCR), a point mutation in cDNA of cdc2 kinase was found in tsFT210, and as a result, the proline of wild-type cdc2 kinase at the 272 amino acid residues from N-terminal methionine changed to serine. During preparation of this paper, the detection of two mutation sites of this mutant was reported (Th'ng, J.P.H., Wright, P.S., Hamaguchi, J., Lee, M.G., Norbury, C.J., Nurse, P., and Bradbury, E.M. (1990). Cell, 63: 313-324); one was the same site as reported here, the other was A-to-G change in the 154th base from base A in initial ATG, and this caused the change of isoleucine to valine in the PSTAIR region of cdc2 kinase. This mutation in the PSTAIR region was not detected by us. The probable reason for this discrepancy was in that Th'ng and his group sequenced a cDNA cloned from the amplified cDNAs by PCR, and did not directly sequence the amplified cDNA as we did.
Amino Acid Sequence↗
[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↗
Elevations of serum angiotensin-converting enzyme and gamma-glutamyl transpeptidase activities in hypertensive drinkers.
Serum angiotensin-converting enzyme (ACE) activity was measured in 70 middle-aged male drinkers with or without elevated serum gamma-glutamyl transpeptidase (gamma-GTP) activity and high BP. Serum ACE activity in hypertensive drinkers with elevated serum gamma-GTP was higher than that in drinkers, both normotensive and hypertensive, with normal serum gamma-GTP. Serum ACE levels were strongly correlated with alcohol consumption and serum gamma-GTP levels. Since the induction of ACE by alcohol in hepatic cells has been disputed, the coincident elevation of serum ACE and gamma-GTP activities in hypertensive drinkers may support the contention that the close association between gamma-GTP levels and BP found in drinkers is not mainly related to the induction of gamma-GTP in the hepatic cells, but related to the hepatic cell damage caused by alcohol.
Adult↗
[Clinical application of extracorporeal shock wave lithotripter (SD-3) to upper urinary tract stones].
The extracorporeal shock wave lithotripter (SD-3) was used on 30 patients with upper urinary tract calculi from December, 1988 to March, 1989. At one month after the treatment, 11 patients (36.7%) were free from stones and 9 (30.0%) had stone fragments than 5 mm in diameter, making an effective rate of treatment of 66.7%. Gross hematuria, skin ecchymosis, pain and fever were observed as side effects, but none of them were serious. We concluded that extracorporeal shock wave lithotripsy using SD-3 for upper urinary tract stones is an effective treatment without any serious side effects.
Adult↗