Studies on chemical carcinogens. V. O,O'-diacetyl-4-hydroxyaminoquinoline 1-oxide.
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Biomedical subjects
Publications and source records attributed to M Araki.
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In the matured chick retina, alkaline phosphatase (ALPase) activity is specifically localized in the outer plexiform layer and in horizontal and Müller cells. In the developing chick retina, ALPase activity is first recognized in growing neurites from horizontal cells during the 13th day of incubation, when synaptogenesis begins in the outer plexiform layer. Intraocular administration of ALPase inhibitors to developing chick embryos resulted in developmental disturbances in differentiation of the outer plexiform layer and also of photoreceptor cells. We have now extended these studies to an in vitro system. ALPase activity was studied by ultracytochemistry in cultured retinal cells from chick embryos, and the effects of specific ALPase inhibitor on retinal development were also analyzed. Two cell types showed intense ALPase activity: 1) flat glial cell, which formed a multi-layered epithelial sheet and 2) neuronal cell found within cell aggregates. Some cellular processes forming a neuropil-like structure within these aggregates also showed ALPase activity. When the ALPase inhibitor bromotetramisole was present in the culture medium, there was delay in aggregate formation and the development of neuritic processes was also affected. Moreover, this treatment also caused a considerable reduction in the number of photoreceptor cells present in the culture. The present results indicate that ALPase activity plays a significant role in retinal cell differentiation.
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The noninvasive detection of restenosis is clinically important for the subsequent management of patients in whom percutaneous transluminal coronary angioplasty (PTCA) has been performed. The aim of this study was to compare the diagnostic value of dobutamine stress echocardiography (DSE) and stress 201Tl single-photon emission computed tomography (SPECT) for detecting restenosis after PTCA. Fifty-three consecutive patients referred for the evaluation of possible restenosis or whom had been scheduled for follow-up study underwent DSE a mean of 5 months after angiographically successful PTCA. Dobutamine was infused incrementally under two-dimensional echocardiographic imaging. The left ventricle was divided into 16 segments and grouped into three coronary vascular territories. Rest, low-dose, and peak-dose images were digitized and displayed in a quad-screen format. Positive findings for restenosis were defined as new or worsened wall motion abnormality at a previously dilated vascular territory. All but one patient underwent SPECT. Positive findings for restenosis were defined as the presence of redistribution. All patients underwent quantitative coronary angiography after two tests. Restenosis was angiographically demonstrated in 23 (43%) of 53 patients and 25 (42) of 59 vessels. The sensitivity of DSE and SPECT for detecting restenosis was 78% and 74%, specificity was 93% and 93%, and accuracy was 87% and 85%, respectively. In a total of 59 vascular regions, DSE was 76% sensitive and 94% specific for detecting individual restenosis. It is concluded that DSE is comparable in diagnostic accuracy to SPECT for detecting restenosis in patients after PTCA.
Dobutamine stress echocardiography and stress thallium-201 single-photon emission computed tomography (SPECT) were compared for detecting coronary artery disease in 120 consecutive patients who underwent concomitant quantitative coronary angiography. The left ventricle was divided into anterior, inferior, and lateral regions. Wall motion or perfusion abnormalities observed within each region were classified as ischemia or fixed abnormality. Both tests showed 81% agreement in all 120 patients. Complete agreement was observed in 77% of the 360 regions analyzed. The overall sensitivity of dobutamine stress echocardiography and thallium-201 SPECT for the detection of coronary artery disease was 85% and 89%, and the specificity was 93% and 85%, respectively. A good correlation was found between the wall motion score index and perfusion defect size at peak stress and at rest (r = 0.70). Dobutamine stress echocardiography and thallium-201 SPECT exhibit a comparable accuracy for diagnosing coronary artery disease, localizing coronary artery stenosis, and detecting regional myocardial abnormalities. The wall motion score index may be useful for evaluating the myocardial area at risk.
The aim of this study was to validate the usefulness of dobutamine stress echocardiography to detect residual ischemia and significant stenosis at the infarct zone in patients with acute myocardial infarction. Dobutamine stress echocardiography and stress thallium-201 single-photon emission computed tomography were performed on 40 consecutive patients 1 month after the onset of acute myocardial infarction. Dobutamine was infused incrementally, and wall motion score index at the infarct zone was calculated before and at peak dobutamine infusion. The patients were divided into three groups according to the change in wall motion at the infarct zone (improved, unchanged, or worsened wall motion, respectively). Tomographic thallium images of the infarct zone were assessed visually. All patients underwent quantitative coronary angiography, and significant stenosis was defined as 50% or greater stenosis. In patients who showed a persistent defect and significant stenosis of the infarct-related artery, resting thallium-201 single-photon emission computed tomography was performed when possible. There was a significantly higher incidence of residual ischemia at the infarct zone in patients with worsened wall motion (85%) and unchanged wall motion (63%) than in those with improved wall motion (8%). The residual stenosis of the infarct-related artery was more severe in patients with worsened or unchanged wall motion than in those with improved wall motion (worsened 82.6% +/- 17.7%, unchanged 93.7% +/- 12.6%, and improved 37.1% +/- 24.4%). The use of worsened or unchanged wall motion at the infarct zone for detecting significant residual stenosis of the infarct-related artery resulted in a sensitivity of 93% and a specificity of 91%, respectively. Worsened wall motion at the infarct zone by dobutamine stress echocardiography strongly suggests residual ischemia. Conversely, less ischemia and less significant stenosis are associated with improved wall motion. Unchanged wall motion suggests severe residual stenosis and sometimes indicates ischemia. It may reflect a hibernating myocardium, but the prognostic significance of this finding should be determined by revascularization.
The effects of glucose, vitamins, and DO concentrations on efficient pyruvic acid fermentation were investigated using Torulopsis glabrata IFO 0005, and a novel biphasic culture method was developed on the basis of the metabolic flux analysis. T. glabrata requires the four vitamins nicotinic acid (NA), thiamine hydrochloride (B(1)), pyridoxine hydrochloride, and biotin for cell growth. The deficiency of these vitamins plays an essential role in pyruvate fermentation. In the present study, we considered the effects of the first two vitamins on the pyruvate fermentation. On the basis of several batch and fed-batch experiments, it was found that, as a result of glucose inhibition of cell growth, the initial glucose concentration should be around 30-40 g/L, and the glucose concentration during fermentation should be controlled at high level around 30 g/L. On the basis of an analysis of carbon flux distribution, a biphasic fermentation method was developed where the cultivation started with a high DO (at 40-50% of air saturation) for efficient cell growth and then was reduced to 5-10% for efficient pyruvate production. Since a fair amount of ethanol was formed when the DO concentration was decreased, the addition of NA turned out to be effective in reducing the ethanol formation. This may be due to a relaxing of the requirement for NADH oxidation by the alcohol dehydrogenase pathway. Since B(1) affects both the pyruvate dehydrogenase complex and pyruvate decarboxylase, its initial concentration must be carefully determined by considering both the cell growth and pyruvate production phases.
We present a case of Korsakoff's syndrome that was successfully treated with high doses of donepezil, an inhibitor of acetylcholine esterase, known to retard the progress of symptoms in Alzheimer's disease. The patient was a 46-year-old married Japanese woman who began to drink alcohol after she married. After several years of drinking she developed typical symptoms of the Korsakoff syndrome. Donepezil was started after treatment with thiamine or thiamine plus fluvoxamine had failed. Her amnestic symptoms as well as her quality of life improved markedly during donepezil treatment. Inhibition of acetylcholine esterase may be an effective treatment for Korsakoff's syndrome.
We developed a novel blood glucose control system, using a model predictive method, to achieve optimal control of the blood glucose level in severely diabetic or pancreatectomized patients. This system is designed to predict glucose level changes in advance, considering delayed response time and the administered doses of insulin. This method is also designed to calculate the most appropriate insulin infusion rate by considering differences in individual response to insulin. In this study, we compared our system with a conventional proportional and differential controller (PD controller) to determine whether the new system could regulate the glucose level efficiently in pancreatectomized dogs. The model predictive control method resulted in a significant reduction of mean insulin infusion rate compared with the conventional PD controller (0.71 mU/kg per min vs. 1.81 mU/kg per min, p = 0.0005), when the glucose level in both methods reached the planned target level (100 mg/dl). The new system also tended to have a reduced mean glucose infusion rate for compensating for overshooting of the glucose level compared with the PD controller (0.7 mg/kg per min vs. 1.1 mg/kg per min, p = 0.16). These results indicate that the new system should be a useful tool for regulating the glucose level in severely diabetic patients.
One case of calcification in the striopallidodentate system associated with pseudohypoparathyroidism type I is described. Striopallidodentate calcification accompanying a disturbance in calcium metabolism is, to our knowledge, extremely rare with only thirteen previously documented cases reported, of which only two cases accompany pseudohypoparathyroidism. Moreover, our case showed an elevated titer of antiparietal-cell antibody.
We report two patients with spiny keratoderma of the palms and soles characterized by multiple tiny keratotic plugs on the palms and soles. This disease was reported to be possibly associated with internal malignancies. We found a tumor from the esophagus to cardia in one patient. Another had no tumor but the lesion occurred soon after a severe bronchial asthma attack. Causal relation between spiny keratoderma of the palms and soles and bronchial asthma is obscure. Since this disease has been under-diagnosed and under-reported, it is important for dermatologists to keep spiny keratoderma of the palms and soles in mind in daily clinical examinations.
The partial correlation coefficients were computed between pup growth rate on day 12 of lactation and mother weight on day 11 or daily food or water intake by mother between days 4 and 11 in the 1st to 3rd lactations of four strains of mice, SHN, SLN, C3H/He and GR/A, in order to estimate the influence of food and/or water intake on lactational performance (pup growth) and mother weight. In SHN mice, pup growth rate had negative and positive correlations with food intake and mother weight, respectively, in the 1st lactation. This indicates that food ingested is used for mother weight increase rather than for lactation. On the contrary, there was a positive correlation between pup growth rate and food intake in the 3rd lactation of SHN mice and in the 2nd lactation of GR/A mice, suggesting the preferential contribution of food to lactation. In neither SLN nor C3H/He mice apparent relations between variables were seen. These results suggest the careful choice of mouse strains for studies on nutrition and lactation.