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Biomedical subjects

S Itoh

Publications and source records attributed to S Itoh.

At least 253 records · Page 14Linked to original sources

Metallothionein expression and concentrations of copper and zinc are associated with tumor differentiation in hepatocellular carcinoma.

Metallothionein is the carrier protein of heavy metal ions, such as copper (Cu) and zinc (Zn). In this study, the relationships among immunohistochemical expression of metallothionein, concentrations of Cu and Zn, histological differentiation and proliferative activity of hepatocellular carcinoma were investigated in 51 cases. The concentrations of Cu and Zn in both tumor and non-tumor tissues were determined using electron probe microanalysis. Immunohistochemical expression of metallothionein in tumor tissues decreased with the degree of differentiation, whereas the number of hepatocytes positive for Ki-67 increased. Furthermore, the concentrations of Cu and Zn in tumor tissues decreased with the degree of histological differentiation in human hepatocellular carcinoma.

Biomarkers, Tumor↗

Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension.

NG,NG-dimethyl-L-arginine (ADMA) is an endogenously synthesized nitric oxide (NO) synthase inhibitor which has potent pressor/vasoconstrictor effects. Dimethylargininase metabolizes ADMA to L-citrulline and plays a key role in determining the in vivo levels of ADMA. To investigate the role of ADMA in the pathogenesis of hypertension, we measured 24-hour urinary excretion of ADMA (UADMA) and nitrate/nitrite (NOx) in Dahl salt-sensitive hypertensive rats and spontaneously hypertensive rats (SHR). In Dahl salt-resistant rats, high-salt diet (8% NaCl) did not increase blood pressure and increased urinary NOx (P < .01) without changes in UADMA compared with low-salt diet (0.3% NaCl). In contrast, in Dahl salt-sensitive rats, high-salt diet increased blood pressure (P < .01), did not change urinary NOx excretion, and increased UADMA (P < .01). There was a significant (r = .65, P < .01) correlation between UADMA and the level of blood pressure in Dahl salt-sensitive rats. Plasma levels of NOx and ADMA and renal dimethylargininase content were comparable among them. These results may suggest that in Dahl salt-resistant rats, blood pressure is kept constant during high-salt intake, possibly due to the compensatory increased production of NO, and that in Dahl salt-sensitive rats, high-salt intake increases the production of ADMA, attenuates the compensatory increases in NO, and increases blood pressure. These results also suggest that the systemic production of ADMA is not dependent on renal dimethylargininase. SHR had significantly greater urinary NOx excretion (P < .05) and smaller UADMA than Wistar-Kyoto rats (P < .05), and UADMA was inversely correlated with their mean arterial pressure (r =.64, P < .05). In conclusion. ADMA, independently of the renal dimethylargininase content, may play a role in the pathogenesis in Dahl salt-sensitive hypertensive rats but not in SHR.

Amidohydrolases↗

Noninvasive detection of iliac artery disease and prediction of its severity from Doppler spectral analysis in common femoral artery.

The direct interrogation of iliac artery disease (IAD) with color-coded duplex scanning is limited by the presence of intestinal gas or obesity. The purposes of this study were to examine the diagnostic accuracy of duplex ultrasound (DUS) analysis of spectral waves in common femoral artery (CFA) for detection of IAD and to predict its severity. DUS and arteriography were performed in 107 lower extremities in this study. The following were calculated from the CFA spectral waves obtained by DUS: peak systolic velocity (PSV), acceleration (PSV/pulse rise time), and deceleration (PSV/pulse decay time). In patients with isolated IAD, the treadmill exercise test was also performed to evaluate the ischemic severity expressed as recovery rate of ankle pressure index five minutes after exercise (RR-API). Forty-six lower extremities with IAD and 61 without IAD were diagnosed by arteriography. PSV was significantly reduced in lower extremities with IAD (109.5 +/- 32.7 vs 59.8 +/- 32.9 cm/s, P < 0.05). The deceleration detected IAD with a greater specificity and sensitivity vs acceleration (100.0 vs 82.0% and 97.8 vs 82.6%, respectively). Moreover, the acceleration and deceleration significantly correlated with the RR-API (r = 0.589, P < 0.05 and r = 0.779, P < 0.01, n = 14, respectively). The present evaluation is a simple and accurate technique to augment other examinations for detection of IAD and to assess its ischemic severity.

Angiography, Digital Subtraction↗

A novel splicing junction mutation in the gene for the steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia.

Congenital lipoid adrenal hyperplasia (lipoid CAH) is a relatively common genetic disorder of adrenal and gonadal steroidogenesis and is the most severe form of CAH. As typical affected individuals cannot produce any steroid hormones or can only produce low levels of steroid hormones in the adrenals and gonads, including glucocorticoids, mineralcorticoids, and sex steroids, a genetic defect in the cholesterol side-chain cleavage enzyme, cytochrome P450scc (CYPXIA1), has been postulated to be the cause of their insufficient production to date. Recently, Lin and co-workers proved a link between mutations of the steroidogenic acute regulatory protein (StAR) gene and the lipoid CAH phenotype. Therefore, we investigated both the cytochrome P450scc and StAR genes in a Korean family with a fairly mild form of lipoid CAH to identify the mutation(s) causing this disease. The result was that no mutations could be found in the two genes, except for a thymine (T) insertion into intron 2 of the StAR gene, 3 bp from the splice donor site of exon 2. PCR-amplified StAR genes from a normal subject and the patient were cloned into an expression vector and then introduced into COS-7 cells. Northern blot and reverse transcriptase-PCR analyses indicated that the StAR messenger ribonucleic acid derived from the vector with the normal StAR gene spliced exons 2 and 3 correctly, whereas most, but not all, StAR messenger ribonucleic acid derived from the vector with the T-inserted StAR gene could not remove intron 2. We concluded from these results that the T insertion into the StAR gene accounts for the lipoid CAH phenotype in this patient.

Adrenal Hyperplasia, Congenital↗

Antibacterial activity of two alkylamines integrated an indane scaffold: mimicry of a complementary unit on magainin 2.

Based on the antibacterial activity of 9-phenylnonylamine (pC9a) against Escherichia coli (ATCC29522) and Staphylococcus aureus (ATCC25923), we have further tested the inhibitory ability of the growth of the bacteria by (+/-)1-(4-aminobutyl)-6-benzylindane (PM2) and (+/-)1-benzyl-6-(4-aminobutyl) indane (PM3), that is, two kinds of 1,6-disubstituted indanes. In an in vitro assay, they showed almost the same antibacterial activities against the bacteria as pC9a, as well as that of magainin 2 analogs (i.e., the peptides MSI-78 and 87-ISM), except in the case of 87-ISM against S. aureus. At the MIC (minimum inhibitory concentration) values, however, their killing rate of E. coli is actually quicker than pC9a. This indicates that an indane scaffold, used as a template to mimic a part of the alpha-helical structure of magainin 2, can accelerate the killing rate. At present, however, it is unknown whether either the hydrophobicity or the alpha-helical structure, or both, of the indane scaffold is involved in accelerating the rate. Moreover, these two indanes also showed stronger antibacterial activity against two strains of Helicobacter pylori (ATCC43526, ATCC43579) than either pC9a or magainin 2 related peptides.

Anti-Bacterial Agents↗

Protective effect of captopril on ischemic myocardium.

The protective effect and mechanism of action of the angiotensin-converting enzyme inhibitor (ACE-I) captopril was investigated in organelles from ischemic myocardial cells in a canine coronary ligation model. Sarcoplasmic reticulum (SR) and mitochondrial fractions were extracted from ischemic and nonischemic myocardial cells from captopril- and saline-treated (control) hearts. Heart rate, cardiac output, and right ventricular systolic blood pressure were similar in the captopril-treated and control groups. Left ventricular systolic blood pressure (LVPs) decreased gradually to 89% of the baseline value after captopril administration, and to 78% of the baseline value after ligation. Ca-ATPase activity in the SR, the respiratory control ratio (RCR) in the mitochondria, and dinitrophenol (DNP)-stimulated ATPase activity were significantly higher in ischemic myocardium from the captopril-treated group than from the saline-treated (control) group. The SH group content of both organelles was higher in the captopril-treated group. Our results suggest that, in addition to their hemodynamic effects, ACE-I agents containing SH groups protect the myocardium from ischemic damage by preventing enzyme oxidation.

Angiotensin-Converting Enzyme Inhibitors↗

The effects of dopamine, dobutamine and amrinone on mitochondrial function in cardiogenic shock.

The impairment of mitochondrial in non-infarcted myocardium under cardiogenic shock complicated by acute myocardial infarction was studied. We induced acute myocardial infarction in dogs by ligating the circumflex branch of the left coronary artery (LCX). On basis of left ventricular systolic pressure (LVPs) after 60 minutes, we divided the dogs into two groups: a group in which LVPs fell to below 70% of the pre-LCX ligation level, and a Control group in which LVPs remained more than 90%. The former group was further divided into four subgroups, depending on infusion of dopamine, dobutamine, amrinone or saline after 90 minutes. Mitochondria were prepared and mitochondrial respiratory activity determined. In the Saline group, hemodynamics became reduced to less than 70% of the preligation level after 120 minutes, however, in the Dopamine and Dobutamine groups, hemodynamics became restored to the preligation level. In the Amrinone group, LVPs decreased slightly, while cardiac output, LV Max. dp/dt and myocardial blood flow increased. In the Saline group, mitochondria in the non-infarcted myocardium functioned at a lower level of activity than that of the Control group. However, in the Dopamine, Dobutamine, and Amrinone groups, the mitochondria functioned at a higher level. Electron microscopy revealed mitochondrial damage in the Saline group only. The results indicate that an energy production disorder in the non-infarcted myocardium may have pathogenetic implications in cardiogenic shock associated with acute myocardial infarction, while dopamine, dobutamine, and amrinone improve mitochondrial function, and ultimately improve cardiac function.

Adenosine Triphosphatases↗

Low activity of aldehyde dehydrogenase (ALDH) in liver of Suncus murinus: possible explanation for high sensitivity to alcohol.

Suncus murinus (suncus) is an animal species highly sensitive to ethanol (Lin, S.-C., Saito, H., Yohro, T. and Shiga, J.,J. Toxicol. Env. Health, 18: 575-587, 1986). To elucidate the mechanism involved in sensitivity to alcohol, we investigated that properties of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the suncus in comparison with the rat. The activities of ALDH in microsomes and mitochondria of suncus livers were lower than those in rat livers, although the activity of cytosolic ADH was not different between the suncus and the rat. We propose that the high sensitivity of the suncus to alcohol can be accounted for, at least in part, by the low activity of ALDH in suncus liver.

Alcohol Dehydrogenase↗

Molecular cloning of mouse liver flavin containing monooxygenase (FMO1) cDNA and characterization of the expression product: metabolism of the neurotoxin, 1,2,3,4-tetrahydroisoquinoline (TIQ).

A mouse liver cDNA clone, MFMO1, coding for a flavin-containing monooxygenase (FMO) was isolated. This cDNA clone encoded a protein of 532 amino acids. Based upon its predicted amino acid sequence, this clone was assumed to belong to the FMO1 subfamily. The deduced amino acid sequence showed 94, 84, 83, and 83% identity with FMO1s of rats, pigs, rabbits and humans, respectively, while it showed only 50-59% identity with human FMO3 and FMO4, rabbit FMO2, FMO3, FMO4 and FMO5, and guinea-pig FMO2. RNA blot analysis showed that the mouse FMO1 was also expressed in the lung and kidney and to lesser extents in the heart, spleen, testis and brain. Mouse FMO1 expressed in yeast showed activities of thiobenzamide S-oxidation, and NADPH oxidation associated with the S- or N-oxidation of chlorpromazine, N,N-dimethylaniline, N,N-dimethyl-hydrazine, imipramine, nicotine, thioacetamide, thiourea and trimethylamine. Moreover, 1,2,3,4-tetrahydroisoquinoline (TIQ), a substance known to induce a parkinsonism-like syndrome in monkeys, was also metabolized by the mouse FMO1. The K(m) values for chlorpromazine, imipramine and TIQ were determined to be 2,4, 16.0, 435 mM, respectively. This is the first report to show that an expressed FMO can metabolize a neurotoxin, TIQ.

Amines↗

[CRH-test].

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ACTH Syndrome, Ectopic↗

[ACTH test].

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Addison Disease↗

[Metyrapone test].

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ACTH Syndrome, Ectopic↗

[Esophago-bronchial fistula which developed after the insertion of an expandable metallic stent for corrosive esophageal stenosis].

A 69-year-old man attempted suicide by abdominal penetrating injury and taking sulfonyl acid. After a laparotomic drainage operation, corrosive esophageal stenosis occurred. Esophageal bougienage was not effective. An expandable metallic stent (GIANTURCO-ROCHE Z stent, Cook Bloomington U.S.A.) was inserted aiming to achieve temporary oral diet and nutritional improvement. But diet did not improve sufficiently because of the awareness of the prosthesis, severe hiccup, uncontrolled regurgitation esophagitis and restenosis caused by intraluminal mucosal growth. After 4 months of insertion, an esophago-bronchial fistula was produced by the wire of EMS. An operation became necessary for this complication. No data exist on the long-term use of the EMS and it is not suitable for benign esophageal stenosis. Unavoidably if the palliative treatment of endoprosthesis is necessary for benign esophageal stenosis such as corrosive esophageal stenosis, a removable esophageal tube prosthesis is preferable.

Aged↗

[Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall].

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.

Brachytherapy↗

[Quantitative measurements of regional cerebral blood flow using technetium-99m-L,L-ECD SPECT activated with acetazolamide: fundamental study of measurement's accuracy, comparison with 123I-IMP ARG method].

We measured regional cerebral blood flow before and after acetazolamide administration using a serial noninvasive method with 99mTc-ECD developed by Matsuda and Takeuchi et al., and compared the accuracy of measured values with those obtained by the conventional 123I-IMP ARG method. When the regional cerebral blood flow was measured for 80 brain regions in 5 subjects without scatter correction, a differential of 0.5 +/- 8.4% was obtained between values measured before and after physiological saline administration as a placebo. A differential of -0.2 +/- 12.6% was obtained when the same regions were measured with scatter correction. These findings indicated that placebo administration did not affect measured values, regardless of whether scatter correction was performed. When 64 regions in 4 subjects at rest were measured on two successive days, a differential of -1.1 +/- 9.0% was obtained between the values measured on the two days. A differential of -4.0 +/- 11.7% was obtained for the same regions following acetazolamide administration. These findings showed that measurements were reproducible both when subjects were at rest and when they were administered acetazolamide. The above two methods were used for measurement of 80 brain regions in the same 5 subjects for comparison. Measurements of subjects at rest and with acetazolamide administration were performed on separate days. The regression line y = 0.99x + 1.47, r = 0.80, was obtained for the subjects at rest, and y = 0.86x + 7.76, with r = 0.76, for the subjects following acetazolamide administration. These findings demonstrated a good correlation between the values obtained using the two methods. The values obtained using the method of Matsuda and Takeuchi et al., before and after acetazolamide administration were thus consistent with those reported previously using the conventional method, and the former method proved to be both simple and reliable.

Acetazolamide↗

[Helical CT for lung-cancer screening: fifth report: evaluation of image quality at low-dose CT using healthy volunteers].

In order to reduce radiation dose in the application of CT for lung-cancer screening, we investigated the potential of low-dose screening helical CT (SHCT) by reducing the tube current and using an additional 10 mm aluminum filter. Six healthy volunteers were scanned at various tube currents (50 mA, 30 mA, 20 mA) with and without the filter. In comparison with the images at 50 mA without the filter, we evaluated the visualization of normal anatomical structures and the detection of simulated nodules at low-dose SHCT. Although a bias toward unclearness in the visualization of small anatomical structures was noted at 20 mA with use of the filter, no structure was assessed as having no visualization at any low-dose scan. Detection of simulated nodules was not degraded significantly by reducing the tube current to 20 mA and using the filter. Further reduction of radiation dose at SHCT may be achieved by the application of small tube current and an additional filter.

Female↗

Expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) in adult rabbits known to be non-responsive to cytochrome P-450 1A1 (CYP1A1) inducers.

Induction of aryl hydrocarbon hydroxylase by aryl hydrocarbons occurs only in neonatal rabbits and not in adult rabbits [Kahl, G. F., Friederich, D. E., Bigelow, S. W., Okey, A. B. & Nebert, D. W. (1980) Dev. Pharmacol. Ther. 1,137-162]. In the present study, we isolated cDNA clones encoding aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) from adult rabbits. The deduced amino acid sequences of rabbit AhR and Arnt showed 80% and 94% identities with those of human AhR and Arnt, respectively. Rabbit AhR mRNA was predominantly expressed in the lung and liver. In contrast, rabbit Arnt mRNA was expressed at almost the same level in all tissues except for the heart, liver, and small intestine. Gel shift analysis showed that the AhR. Arnt complex could bind to the consensus xenobiotic-responsive element, which indicates that AhR expressed in adult rabbit liyers possessed binding activity to the consensus xenobiotic-responsive element in vitro, although aryl hydrocarbons did not induce the activity of AHH in adult rabbits. We propose that the incapability of adult rabbits to induce cytochrome P-450 1A1 (CYP1A1) is caused by factors other than AhR and Arnt.

Age Factors↗