[Erythrocyte cholinesterase in infants].
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Adolescent↗
Biomedical subjects
T Kido
Publications and source records attributed to T Kido.
The renal handling of calcium and phosphorus in environmental cadmium-exposed subjects with renal dysfunction.
Clearance methods were used to clarify the renal handling of calcium (Ca) and phosphorus (P) in a population with renal dysfunction induced by exposure to environmental cadmium (Cd). Seventy-six Cd-exposed subjects (32 men and 44 women) and 36 non-exposed subjects (18 men and 18 women) took part in this study. Fractional excretion of P was higher in the Cd-exposed subjects than in the non-exposed subjects, while that of Ca was equal to that of the non-exposed subjects. The urinary excretion rates of Ca and P tended to be lower in the Cd-exposed subjects than in the non-exposed subjects. The urinary excretion rate of Ca was closely related to creatinine clearance, while that of P was related to creatinine clearance and the percentage tubular reabsorption of phosphorus. It is thought that in Cd-induced renal dysfunction the urinary excretion of Ca depends on glomerular function, and no increased excretion of urinary Ca was observed by these clearance methods. It is also clarified that the parallelism in the urinary excretion of Ca and Na persists in Cd-exposed subjects with renal dysfunction.
Aged↗
Dose-response relationship between total cadmium intake and prevalence of renal dysfunction using general linear models.
To determine the maximum allowable intake limits for chronic dietary exposure to cadmium (Cd), the dose-response relationship between total Cd intake and prevalence of renal dysfunction was examined using general linear models considering the effect of age as a confounder. The target population comprised 1850 Cd-exposed and 294 non-exposed inhabitants of Ishikawa, Japan. They were divided into 96 subgroups by sex, age (four categories) cadmium concentrations in rice (three categories) and length of residence (four categories). As indicators of the cadmium-induced renal dysfunction, glucose, total protein, amino nitrogen, beta 2-microglobulin and metallothionein in urine were employed. General linear models were fitted statistically to the relationship among prevalence of renal dysfunction, sex, age and total Cd intake. Prevalence of abnormal urinary findings other than glucosuria had significant associations with total Cd intake. When total Cd intake corresponding to the mean prevalence of each abnormal urinary finding in the non-exposed subjects was calculated using general linear models, total Cd intakes corresponding to glucosuria, proteinuria, aminoaciduria (men only) and proteinuria with glucosuria were determined to be ca. 2.2-3.8 g and those corresponding to prevalence of metallothioneinuria were calculated as ca. 1.5-2.6 g. The low-molecular-weight protein in urine was confirmed to be a more sensitive indicator of renal dysfunction, and these total Cd intake values were close to those calculated previously by simple regression analysis, suggesting them to be reasonable values as the maximum allowable intake of Cd.
Age Distribution↗
Early stage gastric lymphoma: is operation essential?
To assess the efficacy of primary chemotherapy for treatment of early stage patients with gastric lymphoma, multiple agent chemotherapy was given to patients prior to surgery. Five patients with stages IE and IIE of primary gastric lymphoma (54-65 years of age; three men, two women) were treated with multiple agent chemotherapy prior to gastric resection. In all patients the diagnosis was established by endoscopic biopsy. Two patients had stage IE disease, and three had stage IIE. Histopathologically, there was one diffuse large cell lesion and four diffuse medium cell lesions. All patients received two cycles of VEPA every 4 weeks. On the 16th to 44th day after completion of chemotherapy, total gastrectomy, systematic dissection of regional lymph nodes with resection of the caudal pancreas, and splenectomy were performed. Swelling of the regional lymph nodes was noted in four cases. In all five cases, histologic findings revealed no residual cells of malignant lymphoma in the resected specimen. None of the patients had no evidence of recurrence at 12 to 40 months after surgery. Primary chemotherapy alone thus resulted in the disappearance of malignant cells in stage IE/IIE gastric lymphoma. Our results suggest that surgery may not be an essential procedure for treatment of early stage gastric lymphoma.
Aged↗
Effects of carbonic anhydrase inhibitor on the otolithic organs of developing chick embryos.
Carbonic anhydrase appears to be involved in the process of otoconial formation. The purpose of this investigation was to observe the morphologic change in the surface structure of the otolithic organ in developing chick embryos after injection of the carbonic anhydrase inhibitor, acetazolamide. Acetazolamide (1.5, 3, or 6 mg/0.06 mL/egg) was injected into the yolk sac of the embryo of the fifth day of incubation. Embryo specimens were collected on the 11th, 13th, and 18th days of incubation. The chicks were killed on the third day posthatching, and the surfaces of the otolithic organs were observed under a scanning electron microscope. A marked disturbance in otoconial formation was noted in both utricle and saccule, marked by a decrease or absence of otoconia. A widely exposed meshwork structure of otolithic membrane was observed, with sensory cilia penetrating the meshwork small holes in many instances. There were also several otoconial abnormalities, such as the appearance of only a single giant otoconium, or from several to dozens of giant otoconia, and rough, spongy-surfaced global substances entirely covering the maculae. Clearly, carbonic anhydrase inhibitor (acetazolamide) injected into the yolk sac of developing chick embryos alters and inhibits normal otoconial morphogenesis.
Acetazolamide↗
alpha 1-Microglobulin determination in urine for the early detection of renal tubular dysfunctions caused by exposure to cadmium.
The determination of alpha 1-microglobulin (alpha 1-m) in urine was compared with that of beta 2-microglobulin (beta 2-m) for the detection of renal tubular dysfunctions caused by exposure to cadmium. alpha 1-m In urine is stable down to pH 4.5, whereas beta 2-m degrades below pH 5.5. The relationship between the urinary pH and alpha 1-m or beta 2-m in urine showed that alpha 1-m was independent of urinary pH, whereas beta 2-m-concentration decreased as urinary pH fell to a pH level below 6. Without a pH effect, alpha 1-m was highly correlated with beta 2-m in urine (N = 174, r = 0.96) from Cd-polluted subjects with renal dysfunctions. Due to the greater stability of alpha 1-m in urine, alpha 1-m seemed to be more advantageous than beta 2-m for the detection of renal tubular dysfunctions caused by Cd.
Adult↗
Renal effects of cadmium intake of a Japanese general population in two areas unpolluted by cadmium.
Renal effects of cadmium exposure (i.e., in food products) on people living in two areas unpolluted by cadmium in Japan were investigated. The population comprised 875 inhabitants (i.e., 346 males and 529 females) and 635 inhabitants (i.e., 222 males and 413 females), all of whom in each area were 50+ y of age. The authors used urinary cadmium concentration as an indicator of internal dose, and total urinary protein, beta2-microglobulin, and N-acetyl-beta-glucosaminidase were indicators of renal dysfunction. The authors used multiple-regression and logistic-regression analyses to study the relationship between urinary cadmium excretion and the above indicators of renal dysfunction. In the two geographic areas, both analyses revealed that urinary cadmium concentrations were associated significantly with indicators of renal dysfunction. The results suggest that renal dysfunction is related significantly with environmental cadmium exposure in areas of Japan that are not polluted by cadmium.
Acetylglucosaminidase↗
Progress of renal dysfunction in inhabitants environmentally exposed to cadmium.
The reversibility of beta 2-microglobulinuria, glucosuria, and aminoaciduria was examined in 74 inhabitants (32 males and 42 females) over 50 yr of age, who lived in a cadmium-polluted area. The subjects participated in two examinations conducted just after the cessation of cadmium exposure and 5 yr later. All urinary parameters did not show reversible changes. During the 5 yr the geometric mean concentrations of beta 2-microglobulinuria, glucosuria, and aminoaciduria indicated significant increases in excretion. In cases where greater than 1,000 micrograms/g creatinine of beta 2-microglobulinuria was observed (at the time cadmium exposure ended), almost all individuals exposed to cadmium showed deterioration of beta 2-microglobulinuria, whereas in the case of less than 1,000 micrograms/g creatinine of beta 2-microglobulinuria, no significant changes were observed. The present study indicates that cadmium-induced renal dysfunction in individuals environmentally exposed to cadmium is irreversible.
Aged↗
High mortality and shortened life-span in patients with itai-itai disease and subjects with suspected disease.
A follow-up study was conducted from 1967 to 1987 for patients diagnosed as having itai-itai disease, subjects who were suspected of having the disease, and controls. Ninety-five subjects per category were selected after matching for age, sex, and residential area. The cumulative survival rate of the patients who had a definite diagnosis of itai-itai disease was significantly lower than that of the control group in every period after the first 3 y. The cumulative survival rate of the subjects who were suspected of having itai-itai disease and who had severe renal dysfunction due to cadmium pollution was significantly lower than that of the control group. These results demonstrate (1) the enduring negative influence of itai-itai disease on prognosis and (2) that the cadmium pollution-induced renal disorder adversely affects the health of the inhabitants of a cadmium-polluted area.
Aged↗
Long-term observation of serum creatinine and arterial blood pH in persons with cadmium-induced renal dysfunction.
Twenty-one subjects who had cadmium (Cd)-induced renal dysfunction and who lived in a Cd-polluted area in Japan were investigated to determine changes in their renal function. Since 1974, serum creatinine and arterial blood pH were measured annually during the autumn months for 9-14 y. Mean serum creatinine was significantly increased during this period, i.e., from 1.19 +/- 1.28 mg/100 ml to 1.68 +/- 1.56 mg/100 ml. Even after cadmium exposure ceased, significant deterioration of glomerular filtration was found. Eleven subjects showed a greater than 20% serum creatinine increase during this period. The most severe case had a serum creatinine value of 4.4 mg/100 ml at the most recent examination and experienced generalized edema, which suggests a clinical diagnosis of renal failure. The mean arterial blood pH values decreased significantly in all subjects, i.e., from 7.400 +/- 0.023 to 7.361 +/- 0.034. The 11 subjects cited above also showed a significant decrease and progression of tubular dysfunction after Cd exposure ceased. Our findings suggest that Cd-induced renal tubular dysfunction and decreased glomerular filtration are aggravated even after cessation of environmental Cd exposure, and in some cases this renal dysfunction may progress to renal failure.
Acute Kidney Injury↗
Serum levels of bone Gla-protein in inhabitants exposed to environmental cadmium.
Serum levels of bone Gla-protein (BGP)--the vitamin K-dependent CA2(+)-binding protein--were evaluated in 76 cadmium (Cd)-exposed subjects with renal tubular dysfunction (32 men, 44 women) and 133 nonexposed subjects (53 men, 80 women). Serum BGP levels were higher in the Cd-exposed subjects than in nonexposed subjects. Significant correlations between BGP and each index measured by bone microdensitometry (MD), serum alkaline phosphatase activity, and Cd in blood and urine were found. For all of the Cd-exposed and nonexposed men and women, BGP showed a significant standard partial regression coefficient (multiple regression analysis) with the metacarpal index (MCI), which was one of the MD indicators. Bone Gla-protein also correlated significantly with urinary beta 2-microglobulin in the men and with serum creatinine in the women. Serum BGP values strongly reflect the degree of bone damage and also reflect, although less strongly, the degree of renal damage induced by exposure to Cd.
Aged↗
Significance of urinary cadmium concentration in a Japanese population environmentally exposed to cadmium.
An epidemiological study was performed on 1,815 cadmium-exposed and 240 nonexposed inhabitants of the Kakehashi River basin in Ishikawa, Japan. The significance of urinary cadmium concentration as an indicator of internal dose in a general environment polluted by cadmium was investigated. The mean urinary cadmium concentration (Cd-U) increased in a dose-related manner when the subjects were classified according to the average cadmium concentration in their village rice and according to their period of residence in the polluted area. As total cadmium intake increased, Cd-U also increased, and strong correlations were found (r = .93 in men and r = .88 in women). Therefore, it was concluded that, on a group basis, Cd-U is a useful indicator of the internal dose of environmental cadmium exposure.
Aged↗
Dose-response relationship between urinary cadmium concentration and beta2-microglobulinuria using logistic regression analysis.
Logistic regression analysis was used to investigate the dose-response relationship for environmental cadmium exposure and to consider the effect age had on this association. The target population comprised 3178 inhabitants of Japan who were more than 50 y of age and who lived in a cadmium-polluted area and 1134 inhabitants who lived in nonpolluted areas of Japan. Logistic regression analysis was completed on the dose-response relationship between urinary cadmium concentration (i.e., an indicator of cadmium body burden) and beta2-microglobulinuria (i.e., an index of renal tubular dysfunction caused by exposure to cadmium). Both age and urinary cadmium concentration were associated significantly with beta2-microglobulinuria. Based on the relationship that was determined, we calculated, by age and sex, the values of urinary cadmium concentration that corresponded to the prevalence rates of beta2-microglobulinuria in the nonpolluted population. The resulting values were 1.6-3.0 micrograms/g creatinine for men and 2.3-4.6 micrograms/g creatinine for women.
Age Factors↗
Thyroid clear cell adenoma with marked dilatation of membranous structures: electron-microscopic study.
The electron-microscopic features of a thyroid follicular adenoma with clear cell change is described. The tumor was 7 mm in size and located in the upper portion of the left lobe of the thyroid of a 29-year-old Japanese female. Its cut surface was pale brown in color and well demarcated. The lesion consisted of solid nests with pinpoint lumina. The cytoplasm of the tumor cells was completely clear, but slightly vesicular without oncocytic change. Electron-microscopic examination revealed that the cytoplasm of the tumor cells was filled with numerous empty vacuoles. The vacuoles consisted of dilated membranous structures, indicating that they had been formed from rough endoplasmic reticulum and Golgi apparatus. There was no accumulation of glycogen, mucin, or lipid. The dilated membranous structures in the cytoplasm may be related to the increased thyroglobulin synthesis by the tumor.
Adenoma↗
Measurement of cadmium-induced metallothionein in urine by ELISA and prevention of overestimation due to polymerization.
Urinary metallothionein (MT) is a biological marker of cadmium (Cd) exposure and Cd-induced renal dysfunction. The MT is prone to oxidation due to high cysteine content and forms polymers, which can result in overestimation of the protein by immunochemical methods. The objectives of the present study were to develop an enzyme-linked immunosorbent assay (ELISA) for the measurement of MT in urine and to find ways by which the protein could either be preserved in its monomeric form or converted to this form before analysis to avoid overestimation. Urine specimens analyzed were either from rats repeatedly injected with Cd or from individuals chronically exposed to cadmium through their diets. The MT in rat urine remained in the monomeric form if the urine was collected at 4 degrees C but did not if it was collected at room temperature. The MT was also polymerized if the urine was subjected to repeated freezing and thawing. Overestimation of MT in rat urine occurred (as much as 12-fold) if the MT was polymerized. Addition of 5mM mercaptoethanol to freshly collected rat urine retarded MT polymerization, and addition of 50mM mercaptoethanol converted the polymerized MT to its monomeric form. Analysis of MT in frozen human urine samples revealed that if the urines were not treated with mercaptoethanol, the estimates of MT concentration were up to 11-fold higher than in the treated samples. We conclude that the polymerization of MT in rat and human urines is a serious problem and results in overestimation of the protein by ELISA and that this problem could be overcome by the addition of mercaptoethanol to the urine samples prior to analysis.
Aged↗
In vitro studies of immobilized heparin and sulfonated polyurethane using epifluorescent video microscopy.
In situ surface modification techniques to improve the blood compatibility of blood contacting surfaces of medical devices have been developed by the authors. The techniques include heparin immobilization and sulfonated polymer grafting onto a polyurethane (PU) surface by using either ozone oxidation or photo reaction. These modified PUs were evaluated using an epifluorescent video microscope combined with a parallel plate flow cell. The epifluorescent video microscope system measured the amount of platelet coverage on the PU surfaces using whole human blood containing mepacrine labeled platelets perfused at a wall shear rate of 100 sec-1 for 20 min. Platelet activation and complement activation were also measured. Both immobilized heparin and sulfonated PUs showed significantly lower levels of platelet adhesion than the control PU. The platelet activation levels of these modified PUs also correspond to the results of the platelet adhesion. As for complement activation, heparin the immobilized surface showed the least complement activation, while sulfonated PU and the control PU showed higher levels of complement activation. In situ surface modification techniques, which use either ozone oxidation or photo reaction, are useful in a variety of medical devices even of a complex design, such as membrane oxygenators or artificial hearts.
Allylamine↗
Evaluation of a new heparin bonding process in prolonged extracorporeal membrane oxygenation.
A novel heparin bonding method has been developed for in situ surface modification using ozone oxidation, and evaluated in vitro and in vivo during prolonged extracorporeal membrane oxygenation (ECMO) experiments. The ECMO system consisted of a Capiox hollow fiber membrane oxygenator (MO; Terumo Corp., Tokyo, Japan) with an integral heat exchanger, a Capiox centrifugal pump (CP), and an extracorporeal circuit. The blood contacting surfaces of the system were completely modified using the heparin bonding process, and evaluated in a chronic sheep model for extended period of time, ranging from 96 to 168 hr, under minimal systemic heparinization. The heparin bonded surface was able to maintain high levels of heparin bioactivity, and showed improved blood compatibility in in vitro epifluorescent video microscopy experiments by suppressing platelet adhesion/activation and complement activation. For the ECMO experiments, extracorporeal blood flow was maintained at 3 L/min and the activated clotting time was maintained at 150 sec. There was no significant change in the gas transfer capability or mean pressure drop across the MO over experimental times of up to 168 hr. Platelet count and other coagulation parameters remained stable within the physiologic range throughout the experiment. There were no detectable thrombi in the CP, tubing, or connectors in the test circuit. Local thrombus formation was noted in a stagnant area of the MO, although this did not interfere with its function or lead to any significant embolization. Based on these results, the heparin bonded ECMO system appears to be a safe and effective device for prolonged extracorporeal circulation under minimal systemic heparinization.
Animals↗
Can heparin immobilized surfaces maintain nonthrombogenic activity during in vivo long-term implantation?
The authors previously demonstrated that heparin immobilized surfaces showed excellent nonthrombogenic properties for extracorporeal membrane oxygenation experiments as long as 168 hr. The characteristics of the heparin immobilized surfaces include high heparin bioactivity and prevention of platelet adhesion and complement activation. However, it is not known whether the heparin immobilized surfaces would be effective for in vivo long-term implantation. Heparin bioactivity may be lost because of complete degradation or blocking of binding sites on heparin by adsorbed proteins. This study attempted to elucidate the in vivo long-term fate of heparin immobilized surfaces. The blood contacting surfaces of the ventricular assist device (VAD) made from polyurethane was modified with heparin immobilization and evaluated in a long-term sheep left VAD (LVAD) model for as long as 3 months. After removal of the VAD, heparin bioactivity was measured by Factor Xa assay. The blood contacting surfaces were analyzed with a scanning electron microscope, and the adsorbed proteins on the surfaces of the diaphragm were analyzed by SDS-PAGE and Western blotting. The thickness of adsorbed proteins on the surfaces also was measured by a confocal laser microscope. For the control ventricular assist devices, thrombus formation was observed within 1 month, whereas heparin immobilized VADs were able to operate thrombus free for periods as long as 3 months. The control surfaces demonstrated a thick adsorbed protein layer on thin surfaces, whereas heparin immobilized surfaces maintained thinner adsorbed proteins on thin surfaces. Anti Factor Xa activity of the heparinized surfaces disappeared after 15 days, but the surfaces remained nonthrombogenic even after heparin bioactivity was completely lost. The protein composition analyzed by SDS-PAGE showed an albumin dominant pattern on the heparinized surfaces. The band of 110 kD corresponding to C3b was detected only on the control surfaces, which possibly activated complement, and subsequently activated platelets and coagulation. Immunoblot showed degradation products of fibronectin and vitronectin on the control surfaces, which probably were promoted by surface generated protease, whereas the heparinized surfaces showed minimal degradation throughout the experimental periods. These results suggest that the heparin moiety has an ability to control adsorbed proteins, thereby inhibiting thrombus formation during in vivo long-term implantation.
Adsorption↗