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Biomedical subjects

S Imai

Publications and source records attributed to S Imai.

At least 343 records · Page 19Linked to original sources

Vasodilating properties of KRN2391: structural basis of a new pyridine-type potassium channel opener with a nitrate moiety.

The vasodilating mechanism of a new compound, cyanoimino-3-pyridylmethylaminoethyl nitrate methanesulfonate (KRN2391), a derivative of nicorandil, was examined in the isolated rabbit aorta. To elucidate the structure activity relationship, a comparison was made with the two denitrated derivatives: cyanoimino-3-pyridylmethylaminoethyl acetate methanesulfonate (Ki4032) and cyanoimino-3-pyridylmethylaminoethyl alcohol (Ki3315). In preparations precontracted with phenylephrine (10(-7) mol/l), KRN2391, Ki4032 and Ki3315 caused concentration-dependent relaxation. pD2 values (-log [EC50]) were 6.74 +/- 0.03, 5.67 +/- 0.05 and 3.63 +/- 0.03, respectively. Both methylene blue and glibenclamide produced a shift to the right of the concentration-response curves for KRN2391. The shift by glibenclamide became greater in the presence of methylene blue. An elevation of the cGMP content was not detected until the concentration of KRN2391 was increased to a level enough to produce a full relaxation (3 x 10(-6) mol/l). In contrast, in the case of Ki3315 a parallel shift to the right of the concentration-response curve was observed after glibenclamide (10(-5) mol/l). Methylene blue (10(-5) mol/l) had no effect on the concentration-response curve, and there was no increase in cyclic GMP (cGMP) with 10(-3) mol/l of the compound. The concentration-response curve of Ki4032 was also attenuated by glibenclamide. Though this compound lacks the nitrate moiety, it (10(-4) mol/l) showed a slight tendency to increase the cGMP content, and methylene blue slightly but significantly modified the concentration-response curve of this compound. However, the co-administration of glibenclamide and methylene blue resulted in no further modification of the concentration-relaxation curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer.

The present study was designed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration less than 14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (greater than or equal to 14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group. These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Role of mucosal prostaglandins in vagally-mediated adaptive cytoprotection in the rat.

This study was designed to investigate whether vagal innervation and mucosal prostaglandins (PGs) participate in gastric adaptive cytoprotection. Rats were divided into three groups; sham operation (control), truncal vagotomy or splanchnicotomy. In the first experiment, 100% ethanol (EtOH) was orally administered 15 min after pretreatment with 20% EtOH to all 3 groups. One hour later, the gastric mucosa was examined macroscopically. In a second experiment, the mucosal PG contents 15 min after administration of either 20% EtOH or saline were measured by high performance liquid chromatography. In truncal vagotomized rats, the adaptive cytoprotection caused by exposure to 20% EtOH in control and splanchnicotomized rats was not observed and an increase in hemorrhagic lesion severity was seen. In the control and splanchnicotomized rats, PGE2 contents were elevated following 20% EtHO treatment, as compared to those in the saline-treated rats. However, PGE2 contents in vagotomized rats were not altered by EtOH exposure, and were significantly lower than in the control and splanchnicotomized groups, whereas PGF2 alpha and PGD2 contents were significantly higher after EtOH administration as compared to those in saline-treated rats. These results suggest that vagal innervation is essential for adaptive cytoprotection and that the vagotomy-induced decrease in PGE2 and increases in PGF2 alpha and PGD2 following 20% EtOH administration, may be caused by a disturbance in adaptive cytoprotection.

Animals↗

Myocardial protection of neonatal heart by cardioplegic solution with recombinant human superoxide dismutase.

The effectiveness of high-potassium cardioplegic solution in the neonatal heart remains controversial. Our previous study indicated that the protection afforded by a cardioplegic solution was inadequate in the neonatal heart. On the hypothesis that oxyradicals were responsible for the ineffectiveness of cardioplegic solution in neonatal heart, the effects of a cardioplegic solution (a modified St. Thomas' Hospital cardioplegic solution) with recombinant human superoxide dismutase on the isolated perfused neonatal guinea pig hearts (within 2 days after delivery, body weight of 60 to 120 g) were studied in comparison with those on the adult hearts (6 to 8 weeks after delivery, body weight of 300 to 500 g). After arrest induced by modified St. Thomas' Hospital cardioplegic solution, hearts were subjected to 120 min of ischemia at 20 degrees C, during which time the cardioplegic solution was injected every 30 minutes. Then the heart was reperfused for 60 minutes at 37 degrees C. Under this condition, the left ventricular developed pressure recovered to 84.4% +/- 4.0% of the preischemic value in the adult heart, whereas the recovery was only 68.1% +/- 3.1% in the neonatal heart. Thiobarbituric acid-reactive substance level, a parameter of lipid peroxidation by oxyradicals, significantly increased during ischemic arrest both in the adult and neonatal heart. However, the increase was much greater in the neonatal heart than in the adult. Cardioplegia with recombinant human superoxide dismutase (300 and 1,000 U/mL) significantly inhibited this accumulation of thiobarbituric acid-reactive substance in the neonatal heart; at 1,000 U/mL, the myocardial function of the reperfused neonatal heart recovered to the level of the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Infection of the HTLV-I-harbouring T-lymphoblastoid line MT-2 by Epstein-Barr virus.

Epstein-Barr virus (EBV), a ubiquitous human B-lymphotropic virus, is associated with certain lymphoproliferative diseases of T-cell lineage. To understand the mechanism by which EBV infects T cells, we have tested the susceptibility of various human T-cell lines to the virus. We report here that the HTLV-I-harbouring T-lymphoblastoid line MT-2 carries a high level of CD21/EBV receptors on their surface, adsorbs fluorescein isothiocyanate-labeled EBV, and synthesizes virus latent antigens (EBNA-1 and LMP) following EBV infection. Pretreatment of MT-2 cells with anti-CD21 monoclonal antibody OKB7 inhibited the virus binding as well as the synthesis of virus latent antigen. These data suggest that human T-cells can be infected with EBV via functionally active virus receptors.

Antigens, Differentiation, B-Lymphocyte↗

Immunohistochemical expression of monoclonal antibodies (epi-1 and myo-1) derived from human breast cancer against rat mammary tumors.

Immunohistochemical expression of monoclonal antibodies epi-1 and myo-1 derived from human breast cancer cell line (HBC-4W) was examined for DMBA-induced rat mammary tumors. Antibody epi-1 reacted with luminal epithelial cells while antibody myo-1 reacted with myoepithelial cells of the mammary glands in rats, respectively. The reactions with both antibodies were markedly visible, in particular, in the normal mammary gland, tumor-like lesions and benign epithelial mammary tumors in rats, which showed clear two-cell-type structures. Among malignant mammary tumors, adenocarcinoma was strongly positive with antibodies epi-1 and myo-1. However, squamous cell carcinoma and adenoacanthoma mainly reacted with antibody epi-1. On the other hand, the intercellular matrices of pleomorphic cell sarcoma and stromal areas of the normal mammary gland or epithelial tumors were positive with antibody myo-1.

9,10-Dimethyl-1,2-benzanthracene↗

Articulatory function after resection of the tongue and floor of the mouth: palatometric and perceptual evaluation.

Linguapalatal contact patterns and the time course of changes in contacts during utterances of/asa, ata, a sa, aca/ were measured using electropalatography (EPG). The relations between these data and perceptual scores in 17 glossectomized patients after various surgical methods were examined. The linguapalatal contact patterns produced during perceptually less distorted sounds varied with the place and manner of articulation. Patterns having very few contacts or a posterior groove produced more distorted /s/ sounds; however, types of EPG patterns producing less distorted /s/ sounds were relatively frequent. Distortion of the and /c/ sounds was less often produced by variation of the EPG patterns, whereas /t/ sounds were most frequently judged to be highly distorted. Patterns that showed complete constriction along the dental arch or constriction on the anterior portion of the hard palate, as well as rapid release for plosion by the tongue tip, produced less distorted /t/ sounds. The results revealed that glossectomized patients often evidenced defective stop sounds. It was concluded that mobility rather than volume of the residual tongue is required to produce less distorted stops.

Adult↗

Genetic analysis of susceptibility to radiation-induced apoptosis of thymocytes in mice.

Genetic control of thymocyte susceptibility to radiation-induced apoptosis was investigated in BALB/cHeA, STS/A and five other strains of mice by counting pyknotic cells in a selected area of thymic cortex on histological specimens after whole-body X-irradiation. Number of dead cells increased almost linearly with doses (range 0.25-0.75 Gy) in BALB/cHeA and STS/A mice. However, dead cell counts in BALB/cHeA mice were more than twice those in STS/A mice at each dose. Of five other strains of mice, C57BL/6N and B10.BR mice exhibited a sensitive phenotype similar to BALB/cHeA mice, while C3H/HeAMsNrs and NFS/N mice showed a resistant phenotype similar to STS/A mice. A/J mice seemed to be rather resistant. A sex difference was not recognized in BALB/cHeA and STS/A mice. Resistance was dominant over susceptibility in the progenies of reciprocal crosses between the two strains, indicating an autosomal inheritance and no maternal effect. Segregation ratio of susceptible phenotype to resistant one in the backcrosses of female (BALB/cHeA x STS/A)F1 mice with male BALB/cHeA mice was not significantly different from 1:1 and all backcrosses of female (BALB/cHeA x STS/A)F1 mice with male STS/A mice exhibited a resistant phenotype. Results suggested that thymocyte susceptibility to radiation-induced apotosis is controlled by one major autosomal allele.

Animals↗

Plasma membrane Ca(2+)-pump ATPase is not a substrate for cGMP-dependent protein kinase.

A plasma membrane Ca(2+)-pump ATPase preparation purified from porcine aorta was incubated with cGMP-dependent protein kinase (G-kinase) under the conditions under which dose-dependent stimulation of the enzyme by G-kinase was observed. Several proteins were phosphorylated, but two isoforms of plasma membrane Ca(2+)-pump ATPase with molecular masses of 135- and 145-kDa were not phosphorylated. The protein that was phosphorylated by G-kinase and identified in our previous study as the 135-kDa isoform of Ca(2+)-pump ATPase, on the basis of its almost identical mobility on SDS-PAGE, was found to be another protein with a molecular mass of 138 kDa. Fractionation of the enzyme preparation after incubation with G-kinase by a newly developed calmodulin affinity chromatographic method resulted in the separation of all the G-kinase substrates from the two isoforms of plasma membrane Ca(2+)-pump ATPase. These results suggest that the direct phosphorylation of the Ca(2+)-pump ATPase does not occur in association with the stimulation of the plasma membrane Ca(2+)-pump ATPase by G-kinase.

Animals↗

Protection of gastric mucosa against ethanol-induced injury by intragastric bolus administration of epidermal growth factor combined with hydroxypropylcellulose.

Orally administered epidermal growth factor (EGF) has been shown to protect the gastric mucosa against injury induced by noxious agents. However, EGF administered by intragastric bolus appears to have less effect on the gastric mucosa because of its rapid excretion from the gastric lumen. In this study, mouse EGF given to rats by gastric intubation was confirmed to remain in the stomach at significantly high concentrations when given in combination with hydroxypropylcellulose (HPC), an agent that retards drug release. The residual mouse EGF levels in the gastric luminal content and tissue 3 h after administration of 50 micrograms/kg of EGF dissolved in 1 ml of 2% HPC were 30 and 60 times higher, respectively, than those obtained after EGF alone. Pretreatment with intragastric bolus administration of EGF and HPC at the same dose for 3 h attenuated significantly the development of gastric lesions induced by absolute ethanol compared to that with HPC alone, EGF alone, or saline (mean values of ulcer index: EGF + HPC, 14.3; HPC, 52.8; EGF, 50.7; and saline, 63.2 mm). There were no significant differences between the ulcer index in the HPC, EGF, and saline groups. The present study indicates that exogenous EGF given as an intragastric bolus protects the gastric mucosa against injury when combined with HPC, which can bind to EGF and prevent its rapid excretion from the gastric lumen.

Animals↗

Thin-rim enhancement in Gd-DTPA-enhanced magnetic resonance images of tuberculoma: a new finding of potential differential diagnostic importance.

The article describes rim enhancement seen on Gd-DTPA-enhanced magnetic resonance (MR) images of two patients with tuberculoma. Pathologic examination of the surgical specimens disclosed that the peripheral portion of the tuberculoma, which showed contrast enhancement, was composed mainly of a fibrous capsule and epithelioid granulomas and that the central zone, which showed no contrast enhancement, was composed of caseous necrotic material. In a retrospective study of MR images from 20 consecutive cases of surgically proven bronchogenic carcinoma, none showed a thin enhancing rim on postcontrast MR images. Although confirmation of these findings must await further experience, the postcontrast MR findings described here may prove to be of value in distinguishing tuberculoma and possibly other granulomatous lesions from bronchogenic carcinoma.

Adult↗

Simultaneous expression of T-cell and myeloid cell phenotypes in eight newly established HTLV-I-positive T-cell lines.

Eight cell lines were established from patients with adult T-cell leukemia, and from normal adults, by cocultivation with human T-cell leukemia virus type I(HTLV-I)-producer cell lines in the presence of interleukin-2. All of these cell lines harbored HTLV-I and showed T-cell markers CD2, CD3 and CD4, but not B-cell markers. Unexpectedly, all eight cell lines expressed a myeloid marker CD13 and three of the eight lines also expressed another myeloid marker CD33. Dual staining showed the simultaneous expression of CD3 and CD13 on the same cells. Thus, evidence was obtained for the expression of myeloid antigens on HTLV-I-harboring T cells.

Adult↗

Monoclonal antibody analysis of keratin expression in carcinomas of sweat glands.

Characteristics of keratins of five carcinomas of sweat gland origin were immunohistochemically investigated with several antikeratin monoclonal antibodies with differing specificities. Specimens were obtained from two cases of mucinous carcinoma of the skin, two cases of classic type of eccrine adenocarcinoma, and a case of eccrine porocarcinoma. The tumor cells of mucinous carcinoma expressed only simple epithelial keratins. In a case of eccrine adenocarcinoma, simple epithelial keratin 19 was diffusely expressed. The expression of the other simple epithelial keratins was confined to the luminal cells, whereas the remaining tumor cells further expressed stratified epithelial keratins. Eccrine porocarcinoma and a second case of eccrine adenocarcinoma did not express simple epithelial keratins, although stratified epithelial keratins were diffusely expressed. These data suggest that carcinomas of sweat glands express various combinations of simple and stratified epithelial keratins. Development of additional data along these lines may help to further define their classification.

Adenocarcinoma↗

Myocardial Na+ during ischemia and accumulation of Ca2+ after reperfusion: a study with monensin and dichlorobenzamil.

The intracellular cation contents were determined in isolated perfused rat heart using cobaltic EDTA as a marker of the extracellular space. In hearts in which Na+ accumulation was induced with monensin, a Na+ ionophore, during 20 min-ischemia which otherwise did not result in accumulation of Na+, the levels of Na+ and Ca2+ were significantly higher after reperfusion with a significant decrease in K+. While the recovery of the cardiac mechanical function (CMF) was complete after reperfusion in control hearts, the recovery was incomplete in monensin-hearts. Dichlorobenzamil (DCB), the most specific inhibitor of Na(+)-Ca2+ exchanger, infused for 10 min before induction of ischemia in a dose of 10(-5) M, which produced a definite suppression of CMF (over 80%), inhibited the accumulation of Ca2+ and Na+ and the loss of K+ and ATP after 40 min-ischemia and reperfusion. The same dose of DCB given for 3 min before induction of ischemia and after reperfusion, which produced a less than 20% inhibition of CMF, failed to prevent the Ca2+ accumulation after 40 min-ischemia and reperfusion. These findings are at variance with the idea that the accumulation of Na+ during ischemia and the consequent augmented operation of Na(+)-Ca2+ exchange is responsible for accumulation of Ca2+ after reperfusion.

Adenine Nucleotides↗

[Reproductive and developmental toxicity studies of FUT-187. (III)--Postnatal study in rat F1 offspring from dams treated orally with FUT-187 during the period of fetal organogenesis].

A postnatal study of F1 offspring exposed to FUT-187 during fetal organogenesis was carried out using Crj : CD rat. FUT-187 was dosed by gavage at 0, 50, 200 and 800 mg/kg/day from day 7 to 17 of gestation. All pregnant rats were allowed to deliver newborns, and F1 offspring were examined for development indices and reproduction and learning ability. Effects at 800 mg/kg included temporary salivation, body weight depression and decreased food intake. There were no adverse effects on delivery and lactation and no significant changes on neonatal development, growth, reproduction and learning ability in the F1 offspring. These results indicate that the no effect dose level of FUT-187 is 200 mg/kg/day in dams, and 800 mg/kg/day in offspring.

Abnormalities, Drug-Induced↗

Low copper and brain abnormalities in fetus from triethylene tetramine dihydrochloride-treated pregnant mouse.

The effects of prenatal triethylene tetramine dihydrochloride (Trien-2HCl) exposure on fetal mice have been investigated on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 ppm as drinking water, ad libitum. At the level of 12,000 ppm, the frequency of total resorption tended to be high and that of fetal viability tended to be low, as compared to controls. Decreased maternal weight was observed in body, but not in liver, at the level of 12,000 ppm. Fetal body and cerebrum weights significantly decreased at the levels of 6,000 and 12,000 ppm; however, fetal liver weight remained unchanged. Maternal serum copper concentration was not affected by the Trien-2HCl. Fetal copper concentrations of liver and cerebrum were significantly lower in the Trien-2HCl-treated groups than in the controls, with levels decreasing in a dose-related manner. When the copper and zinc concentrations in the group treated at 12,000 ppm were compared with those in controls, significant decreases in both metals were observed in placenta but not in maternal liver. Changes in fetal zinc concentration varied by tissues: i.e., an increase in liver and no change in cerebrum. Fetal abnormalities were frequently observed in brain, and the frequency was increased with increasing levels of the Trien-2HCl. These results suggest that fetal brain abnormalities caused by Trien-2HCl may be due in part to induction of copper deficiency, which is almost equivalent to that in brindled mutant mouse.

Animals↗

[Group theoretical approach to the cognition of transformational structures and goodness of patterns].

In this article, we tried to reformulate the transformational structure theory of goodness judgment of patterns within the framework of the group theory. We found that reformulation based on the group concepts results in a more general theory, which we call the transformation group theory of goodness judgment of patterns. Main properties of the generalized theory are: 1. Each of the basic cognitive transformations is replaced by a transformation group. 2. They are the dihedral group consisting of mirror-image transformations and a cyclic transformation, the translation group, and the value-reversal transformation group. These groups are derivable independently of the given configurations. 3. The transformation group has the following properties: duality of invariance, non-divergency of transformations produced, and availability of indirect test of invariance. These properties are convenient for cognition of transformational structure of patterns in goodness judgment. 4. The intraconfigurational transformation structure of configurations can be defined by the transformation group so that order among goodness judgments can be predicted, in parallel with the existing transformational structure theory.

Cognition↗