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Biomedical subjects

N Yagi

Publications and source records attributed to N Yagi.

At least 91 records · Page 5Linked to original sources

Effects of free radical scavengers on indomethacin-induced aggravation of gastric ulcer in rats.

Effects of treatment with free radical scavengers in the healing process of acetic acid-induced gastric ulcer on the ulcer aggravation induced by indomethacin were investigated. Gastric ulcers were produced on the anterior wall of the stomach of male Sprague-Dawley rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcer were treated with scavengers for six weeks and then treated with indomethacin (1 mg/kg/day). While superoxide dismutase (10,000 units/kg/day) did not affect the ulcer area after indomethacin treatment, allopurinol (50 mg/kg/day) slightly inhibited the increase in ulcer area. Dimethyl sulfoxide (1% solution, ad libitum) produced a significant decrease in size of the ulcer after indomethacin treatment. Increased lipid peroxides in the gastric mucosa after indomethacin treatment decreased significantly in the rats of the dimethyl sulfoxide and allopurinol groups. These results indicate that lipid peroxidation mediated by oxygen radicals plays an important role in the mechanism of ulcer aggravation induced by indomethacin.

Acetates↗

Effect of troglitazone, a new oral antidiabetic agent, on fructose-induced insulin resistance.

Troglitazone, a newly developed oral antidiabetic agent, improves hyperglycemia, and has been reported to improve insulin resistance and to decrease hepatic glucose production in diabetic animals. However, the exact mechanism of Troglitazone on the improvement of insulin resistance is not known. Chronic administration of fructose to normal rats leads to hyperglycemia, and hyperinsulinemia; it induces insulin resistance. To reveal the mechanism of Troglitazone, we studied the effect of Troglitazone on serum glucose and insulin in the fructose-induced, insulin-resistant rats. Male Sprague-Dawley (SD) rats were fed either on standard chow or one containing fructose. Troglitazone was administrated as a food admixture (150 mg/kg/day) for 8 weeks. The rats were fed on (1) standard chow, (2) standard chow and Troglitazone, (3) fructose-enriched chow, or (4) fructose-enriched chow and Troglitazone. Blood samples were obtained every two weeks, and the levels of serum glucose and insulin were measured. Fructose-enriched chow increased serum glucose and insulin levels and insulin-to-glucose ratios. Troglitazone improved the fructose-induced increases in serum glucose, insulin levels, and insulin/glucose ratios. In conclusion, Troglitazone improved the fructose-induced insulin resistance.

Aging↗

An X-ray diffraction study on a single frog skinned muscle fiber in the presence of vanadate.

Using a technique to obtain a detailed X-ray diffraction pattern from a single frog skinned muscle fiber with synchrotron radiation and an imaging plate, we studied the arrangement of myosin heads to which ADP and vanadate are bound. The presence of 1 mM vanadate during contraction caused trapping of ADP and vanadate on the myosin head. Both in the presence and absence of Ca2+, the intensities of the equatorial reflections indicated that most of the heads with ADP and vanadate were located close to the backbone of the thick filament. The presence of the first myosin layer-line at 43 nm-1 also suggested that the heads formed a helix around the shaft of the thick filament. Weak intensity of actin layer-lines suggested that the myosin heads were detached from the thin filament. The results suggest that the myosin-ADP-vanadate complex has a weak affinity toward actin regardless of the state of the regulatory system on the thin filament.

Adenosine Diphosphate↗

Residues important for the function of a multihelical DNA binding domain in the new transcription factor family of Cam and Tet repressors.

We report that some prokaryotic repressors including CamR and TetR belong to the same family. CamR and TetR bind to DNA using a multihelical DNA binding domain (DBD) at the N-termini of the proteins, while the C-termini are important for regulating the DNA binding in a manner dependent on their co-factors (camphor for CamR, tetracycline for TetR). In all, 11 important amino acid positions have been identified in the CamR DBD by the systematic substitution of residues by Ala. Of the 11 positions, 10 are either buried in the core, and thus important for creating the hydrophobic environment, or exposed on the surface, and thus important for binding to DNA. The eleventh residue, Gly, seems to be important for a loop structure. The DNA binding mode of this type of DBD and a general mechanism of regulating their DNA binding are discussed in reference to the crystal structure of TetR [Hinrichs et al., (1994) Science, 264, 418-420].

Amino Acid Sequence↗

DNA recognition and superstructure formation by helix-turn-helix proteins.

The way helix-turn-helix proteins recognize DNA is analysed by comparing their sequences, structures, and binding specificities. Individual recognition helices in these proteins bind to four DNA base pairs with the same geometry. However, pairs of recognition helices in the protein dimers can have different separations and orientations. These differences are used for discriminating between DNAs which have different superstructures, in particular, different numbers of base pairs between sets of the four base pairs.

Amino Acid Sequence↗

A new gastric ulcer model in rats produced by ferrous iron and ascorbic acid injection.

We developed a new gastric ulcer model in which the ulcers are induced by the local injection of a ferrous iron and ascorbic acid (Fe/ASA) solution into the gastric wall. These ulcers resemble human gastric ulcers that penetrate the muscularis mucosa. The involvement of oxygen radical-mediated lipid peroxidation as the cause of these ulcers was investigated. With ferrous iron or ascorbic acid alone, gastric ulcers did not form, whereas penetrating ulcers were produced by the simultaneous injection of the Fe/ASA solution in a dose-dependent manner. Lipid peroxides significantly accumulated in the gastric mucosa from 1 to 24 h after the injection of the Fe/ASA solution. This increase in lipid peroxides preceded grossly evident gastric ulcer. Treatment with superoxide dismutase (SOD, recombinant human CuZnSOD) significantly reduced the size of the ulcers and inhibited the accumulation in lipid peroxides in the gastric mucosa, while treatment with apo-SOD or heat-inactivated SOD did not. These results suggest that lipid peroxidation mediated by oxygen radicals plays a crucial role in the pathogenesis of the gastric ulceration induced by the Fe/ASA solution.

Animals↗

Apparent intramolecular acyl migration and hydrolysis of furosemide glucuronide in aqueous solution.

The stability of furosemide glucuronide (FG) was investigated in buffer solutions ranging from pH 1 through 10. This glucuronic acid conjugate was the major metabolite of furosemide (F) excreted in human urine. FG, obtained by extraction from human urine, was purified by ion-exchange chromatography. The concentration of FG, acyl migration isomers of FG (FG-iso), and F were determined simultaneously with an HPLC method that included fluorescence detection and gradient elution. FG was found to be unstable in highly acidic and in neutral to alkaline solutions. Hydrogen ion and hydroxy ion catalyzed the hydrolysis of FG below pH 2.8 and above pH 5.6, respectively. Above pH 3.7, FG instability led to the formation of eight FG-iso compounds. Though beta-glucuronidase cleaved FG, the FG-iso compounds were resistant to the enzyme. The half-life of FG in a buffer solution at pH 7.4 and 37 degrees C was 4.4 h. The maximum stability of FG (half-life about 62 d) occurred at approximately pH 3.2. Below pH 3.7, acyl migration products of FG were not detected. Instead, the hydrolysis of FG to F and glucuronic acid was followed by the formation of 4-chloro-5-sulfamoylanthranilic acid (CSA), a secondary product in acidic media.

Acylation↗

Biliary excretion of furosemide glucuronide in rabbits.

Furosemide (F) was administered to rabbits intravenously and intraduodenaly and the biliary excretion was studied. The major metabolite excreted in bile was furosemide glucuronide (FG). F and acyl migration isomers of FG (FG-iso) were also excreted in bile. The biliary excretion rates of total F (F+FG+FG-iso) following intraduodenal administration of F were much smaller than those following intravenous administration. The fraction of (F+FG-iso) in bile following intraduodenal administration of F were larger than those following intravenous administration. Stability of FG or FG-iso in bile and supernatant solution of the duodenum homogenate of rabbits was studied. FG was unstable in both media and its degradation followed apparent first-order kinetics in both media. In bile, FG degraded to produce several FG-iso and F, while in the supernatant solution of the duodenum homogenate, it hydrolyzed immediately to F. FG-iso were hardly detected in the supernatant solution. These results indicated that FG excreted in bile degraded easily to FG-iso and F. FG might easily hydrolyze to F enzymatically in the duodenum, and the resultant F might be reabsorbed from the intestinal tract. Unabsorbed FG-iso and F might be excreted in the feces.

Adult↗

Syntheses, immunosuppressive activity, and structure-activity relationships of myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxyomyriocin, and nor-deoxomyriocins.

Nine myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxomyriocin, and nor-deoxomyriocins, were synthesized from 2-deoxy-D-glucose via common intermediates used in previous myriocin and Z-myriocin syntheses. Immunosuppressive activities of those myriocin analogs on mouse allogeneic mixed lymphocyte reaction were examined, and Z-14-deoxomyriocin was found to show the most potent activity among them. The structure-activity relationships are discussed.

Animals↗

[Effects of thunberginol A contained in Hydrangeae dulcis forium on types I-IV allergies].

The inhibitory actions of thunberginol A on anti-allergic (type I-IV) activity were examined. Oral administration of thunberginol A 2 hr before the challenge significantly inhibited the PCA reaction (type I) in rats at a dose of more than 300 mg/kg and the ear PCA reaction in mice at a dose of more than 50 mg/kg. Thunberginol A at a dose of more than 300 mg/kg also significantly inhibited the allergic bronchoconstriction in rats. Thunberginol A concentration-dependently (10(7)-10(-4), 10(-5)-10(-4) M) inhibited the allergic contractions of rat trachea sensitized with IgE and those of the guinea pig lung preparation sensitized with IgG. It also inhibited the allergic histamine release from sensitized peritoneal exudate cells in a concentration-dependent manner (10(-5)-10(-4) M). Thunberginol A had anti-serotonic activity on the contraction of smooth muscle, and it increased the ear vascular permeability in mice. Thunberginol A significantly inhibited the primary response of contact dermatitis (type IV) in mice at 100 mg/kg from the day after immunization to the day before challenge, and it also inhibited the delayed type foot pad swelling in mice at a dose of more than 300 mg/kg at 0 and 8 hr after the challenge. These findings suggest that orally administered thunberginol A is effective against type I and type IV allergy.

Administration, Oral↗

A real-time observation of X-ray diffraction from frog skeletal muscle during and after slow length changes.

X-ray diffraction patterns from a frog skeletal muscle were recorded in real time using an X-ray image intensifier and a CCD video camera with a time resolution of 1/60s. The muscle was stimulated and then released or stretched by 6% at a constant speed. The equatorial (1,1) reflection decreased in intensity during stretches, suggesting a conformational change of cross-bridges. The integrated intensity of the 3rd meridional reflection from the thick filament decreased during both releases and stretches. The decrease was larger in stretches than in releases and at higher velocities. The intensity change correlated well with the change in tension, showing that the axial mass distribution of cross-bridges becomes wider as the tension increases. The axial Bragg spacing of the 3rd meridional reflection tended to increase in stretches and decrease in releases by less than 0.1%, possibly reflecting the elasticity in the thick filament backbone. The only significant effect of a length change remaining at the end of the stimulation was the broadening of the 3rd meridional reflection, suggesting non-uniformity of sarcomere lengths or axial misalignment of thick filaments as causes of enhancement and deficit of tension.

Animals↗

Expression of intercellular adhesion molecule 1 on pancreatic beta-cells accelerates beta-cell destruction by cytotoxic T-cells in murine autoimmune diabetes.

Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) by being involved in the extravasation of lymphocytes from the circulation into the inflamed pancreas. However, the mechanism of beta-cell destruction by which expression of ICAM-1 on beta-cells may facilitate adhesion of effector cells still remains to be elucidated. Several lines of evidence suggest that this adhesion molecule is involved in the destruction of pancreatic beta-cells by killer lymphocytes in the NOD mouse, which shows an autoimmune diabetic syndrome similar to that of human IDDM. Immunohistochemical study under light microscopy demonstrated that all of the mononuclear cells infiltrating the islets strongly expressed ICAM-1 and leukocyte function-associated antigen 1 (LFA-1), a counterreceptor of ICAM-1, whereas ICAM-1 expression on islet cells was not apparent. However, immunohistochemical staining under electron microscopy revealed that islet beta-cells adjacent to infiltrating lymphocytes were clearly stained by an anti-ICAM-1 monoclonal antibody (mAb). Flow cytometric analysis showed that the ICAM-1 expression on NOD islet cells and NOD-derived insulinoma cells (MIN6N8a) was inducible by interferon (IFN)-gamma or tumor necrosis factor-alpha. These cytokines had an additive effect on the ICAM-1 induction. Susceptibility of MIN6N8a cells to lysis by a NOD islet-derived CD8+ cytotoxic T-cell clone was greatly enhanced by IFN-gamma pretreatment, and this enhancement was abolished by anti-ICAM-1 and anti-LFA-1 mAbs. When both mAbs were administered into NOD mice with spontaneous or adoptively transferred diabetes, the development of diabetes was significantly prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of glucose ingestion on urinary excretion of electrolytes: comparison between patients with chronic glomerulonephritis and diabetes mellitus].

We investigated the effects of ingesting 75g of glucose on urinary excretion of electrolytes in patients with chronic glomerulonephritis (CGN) and diabetes mellitus (DM) over a 4-hour period. Creatinine clearance did not change in patients with either disease following glucose ingestion. Fractional excretion of sodium (Na), chloride (Cl) and potassium (K) decreased significantly, while that of calcium (Ca) and magnesium (Mg) increased significantly in both groups. The change in fractional excretion of phosphorus (P) differed between patients with CGN and DM. Fractional excretion of P increased initially, then decreased significantly in patients with CGN, while it decreased steadily in patients with DM. In diabetic patients, significant positive relationships were observed between cumulative filtered glucose and cumulative urinary excretion of Ca (r = 0.47, p < 0.05) and P (r = 0.54, p < 0.05). In addition, cumulative plasma IRI concentration was correlated inversely with cumulative urinary excretion of K (r = -0.54, p < 0.05) in diabetic patients. In nephritic patients. however, no significant relationship was observed among these variables. In conclusion, renal tubular reabsorption of Na, K and Cl was enhanced, while that of Ca and Mg was inhibited after glucose ingestion in both CGN and DM patients. Moreover, filtered glucose may be involved partially in the inhibitory effect on tubular reabsorption of Ca and P in diabetic patients.

Administration, Oral↗

Video-assisted right lower lobectomy for a lung cancer with mini-thoracotomy.

We report a case of T1N0M0 lung cancer in which we successfully performed video-assisted right lower lobectomy and mediastinal lymph node dissection. The lobectomy was done on a 64-year-old woman who had a 2-cm adenocarcinoma in the right lower lobe. The procedure could be done safely and adequately using three trocars and a 5-cm mini-thoracotomy. The patient had an uncomplicated postoperative course and was satisfied with minimal postoperative pain, quick recovery, and minute skin scars. Video-assisted lobectomy may be a reasonable approach in selected patients of primary lung carcinoma.

Adenocarcinoma↗

Videothoracoscopic resection of a posterior mediastinal tumor.

We report a complete videothoracoscopic resection of a posterior mediastinal tumor (neurilemmoma) in a 43-year-old man. The tumor was located in the right cupula of pleura and well demarcated. The tumor was mobilized under videothoracoscopic guidance and extracted from the thoracic cavity through a trocar site. The postoperative course was uneventful, and the postoperative pain could be reduced.

Adult↗