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T Suganuma

Publications and source records attributed to T Suganuma.

At least 109 records · Page 6Linked to original sources

An anti-carbohydrate monoclonal antibody inhibits cell-substratum adhesion of F9 embryonal carcinoma cells.

A monoclonal rat IgM antibody (4C9) raised against F9 embryonal carcinoma cells reacted with fucosyl residues in poly-N-acetyllactosamine-type large carbohydrates of these cells (embryoglycan). The chemical properties and distribution of the antigen resembled those of SSEA-1. The monoclonal antibody was found to inhibit cell-substratum adhesion of F9 cells: in the presence of the antibody, cells grew as spherical cell aggregates on plastic dishes. When the antibody was added to the already spread cells, they displayed the initial sign of rounding up within 3 h; the rounding process was largely completed within 6 h. After removal of the antibody, cells resumed their normal morphology. The antibody could act in the presence of 2,4-dinitrophenol. In serum-free medium, F9 cells spread on plastic dishes coated with fibronectin or with laminin, and the process was also inhibited by the antibody. Immuno-electronmicroscopy revealed that 4C9 antigen was diffusely distributed over the cell surface of F9 cells. The distribution of the antigen was not altered generally after culturing with the antibody for 6 h. Another monoclonal rat IgM antibody, which did not react with embryoglycan and resembled anti-Forssman, did not inhibit cell-substratum adhesion of F9 cells, in spite of its reactivity to the cells. Thus, a glycoprotein with fucosyl (poly)-N-acetyllactosamine structure appears to be involved in cell-substratum adhesion of F9 cells.

2,4-Dinitrophenol↗

Ultrastructural localization of lectin receptors in the monkey retinal photoreceptors and pigment epithelium: application of lectin-gold complexes on thin sections.

The cell surface and intracellular binding sites of two lectins, wheat germ agglutinin (WGA) and Ricinus communis agglutinin-1 (RCA-1), in the monkey retina were investigated at the ultrastructural level by means of post-embedding staining of Lowicryl K4M-embedded specimens with lectin-colloidal gold complexes. Effects of pretreatment with neuraminidase were also studied. The techniques enabled us to detect lectin binding sites in the various intracellular compartments of photoreceptor cells, retinal pigment epithelium (RPE), and interphotoreceptor matrices. Wheat germ agglutinin, which recognizes N-acetylglucosamine and sialic-acid residues, showed a prominent and uniform binding to the disc membranes of rod outer segments (ROS), rod connecting cilia, interphotoreceptor matrices, and RPE microvilli. The intensity of these binding sites was markedly reduced when thin sections were pretreated with neuraminidase, except the labeling of ROS disc membranes. Cones were labeled sparsely. The staining of phagosomes in the RPE cytoplasm did not change after neuraminidase digestion. RCA-1, which recognizes galactose residues, revealed a moderate binding to the ROS disc membranes, with a noticeably greater intensity of binding to the basal region of ROS disc membranes. With neuraminidase treatment heavier binding with RCA-1 occurred in interphotoreceptor matrices, connecting cilia and RPE microvilli, whereas there was no significant alteration in binding to the ROS disc membranes. Phagosomes in the RPE were also labeled with this lectin. The results suggest the presence of sialic acid and galactose as the constituent carbohydrates of glycoconjugates in the interphotoreceptor matrices and RPE microvilli.

Animals↗

Glycoconjugate cytochemistry of the rat fundic gland using lectin/colloidal-gold conjugates and Lowicryl K4M. Helix pomatia lectin is a specific marker for mucous neck cells in fundic glands of the rat gastric mucosa.

The fundic gland of the rat stomach was studied using the low-temperature embedding resin Lowicryl K4M and postembedding staining with lectin/colloidal-gold (CG) conjugates. Intense labeling with Ricinus communis agglutinin I was observed not only in mucous-producing cells but also in parietal cells. In contrast, Helix pomatia agglutinin (HPA) only labeled mucous neck cells and intermediate cells between mucous neck cells and chief cells. The other epithelial cells present in the rat fundic gland showed virtually no reaction with this lectin. Our results indicate that HPA might be a marker lectin of mucous neck cells and their derivatives. The combination of embedding in the hydrophilic resin Lowicryl K4M and postembedding staining with lectin-CG conjugates provided satisfactory staining results, and made it possible to visualize the precise distribution of terminal glycoconjugates in intracellular components as well as on the plasma membrane.

Animals↗

Application of rapid freezing followed by freeze-substitution acrolein fixation for cytochemical studies of the rat stomach.

A method involving rapid freezing followed by substitution fixation was developed, using acrolein as a fixative. This was then applied to several cytochemical stainings, and showed well preserved and clear cell structures. Membranes were apparently negatively stained and the ultrastructure of mitochondria, rough endoplasmic reticulum and Golgi apparatus was clearly discernible. The mitochondrial and cytoplasmic matrices were stained rather densely compared with routine chemically fixed preparations, implying a good preservation of matrix substances. Periodic acid-thiocarbohydrazide-silver proteinate staining was applied to the present method. The mucous granules of surface covering epithelial cells indicated fine staining of bipartite structure and the Golgi apparatus of mucous cells showed clear staining differences based on polarity. Postembedding lectin-ferritin and immunocytochemical stainings were applicable to the present preparations and stable stainings of secretory granules were obtained. A low temperature embedding material, Lowicryl K4M, was also examined. The cell preservation of these samples was not as good as those embedded in Epon, but the rough endoplasmic reticulum and Golgi apparatus of chief cells were stained with anti-pepsinogen antibody as were the secretory granules. The present method was also applicable to light microscopy.

Acrolein↗

Qualitative and quantitative analysis of erythrocyte surface membrane sialyl residues using affinity cytochemistry with special reference to diabetic patients.

Erythrocyte surface membrane sialyl residues were investigated by means of affinity cytochemistry using the avidin-biotin complex technique. Mild oxidation with the periodate (MO)-biotin hydrazide (BHZ)-ferritin avidin conjugate (FAv) sequence revealed numerous ferritin particles on erythrocytes from healthy donors. The ferritin particles attached on the perpendicularly sectioned membrane were seen at an average distance of 10 to 12 nm from the outer dense leaflet of the cell membrane. Pretreatment with neuraminidase followed by the MO-BHZ-FAv sequence almost eliminated erythrocyte ferritin labeling. Erythrocytes from diabetic patients showed less dense ferritin labeling compared with those from healthy donors. Quantiative analysis of sialyl residues demonstrated a marked reduction in ferritin labeling of erythrocytes from diabetic patients which was significantly less (p less than 0.01) than that of erythrocytes from healthy donors. This observation supports previous biochemical data demonstrating lower levels of surface membrane negative charge and sialyl residues on erythrocytes from patients with diabetes mellitus.

Adult↗

Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment.

Steady-state pharmacokinetics of valproic acid (VPA) with or without other antiepileptic drug (AED) treatment were studied in 37 children. Children (N = 16) receiving multiple AED therapy had a higher clearance (23.5 vs 13.0 ml/hr/kg, P less than 0.001), larger volume of distribution (0.30 vs 0.22 L/kg, P less than 0.01), and shorter half-life (9.4 vs 12.3 hours, P less than 0.01) than did those (n = 21) receiving VPA only. Inverse correlations of age with clearance (R = -0.559, P less than 0.01) and apparent volume of distribution of VPA (r = -0.490, P less than 0.05) were observed in children receiving monotherapy. In determining the dose and dosing interval of VPA, consider a possible alteration in the pharmacokinetics relating to age and other concurrent AED therapy.

Adolescent↗

Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia.

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Complete nucleotide sequences of all three poliovirus serotype genomes. Implication for genetic relationship, gene function and antigenic determinants.

The complete nucleotide sequences of the genomes of the type 2 ( P712 , Ch, 2ab ) and type 3 (Leon 12a1b ) poliovirus vaccine strains were determined. Comparison of the sequences with the previously established genome sequence of type 1 (LS-c, 2ab ) poliovirus vaccine strain revealed that 71% of the nucleotides in the genome RNAs were common, that the 5' and 3' termini of the genomes were highly homologous, and that more than 80% of the nucleotide differences in the coding region occurred in the third letter position of in-phase codons, resulting in a low frequency of amino acid difference. These results strongly suggested that the serotypes of poliovirus derived from a common prototype. A comparison of the amino acid sequences predicted from the genome sequences showed highest variation in the capsid protein region, whereas non-structural proteins are highly conserved. Initiation of polyprotein synthesis occurs in all three strains more than 740 nucleotides downstream from the 5' end. An analysis of the non-coding region suggests that small peptides that could potentially originate from this region are conserved. The amino acid sequences immediately surrounding the cleavage signals, however, show a higher than average degree of variation. The analysis of the amino acid sequences of the capsid protein VP1 of all serotypes has led to the prediction of potential antigenic sites on the virion involved in neutralization.

Amino Acid Sequence↗

Pharmacokinetics of nicorandil, a new coronary vasodilator, in dogs.

The kinetic disposition of nicorandil, N-[2-( nitroxy )ethyl]-3- pyridinecarboxamide (1), and its main metabolic product, N-[2-(hydroxy)-ethyl]-3- pyridinecarboxamide (II), was studied after administering intravenous and oral doses (2.5 mg/kg) of nicorandil to the same beagle dogs. The plasma concentrations were measured using a high-performance liquid chromatographic method. The pharmacokinetic data derived from intravenous administration of nicorandil were: t1/2, 0.73 plus/minus 0.11 h; Vdarea , 0.67 plus/minus 0.04 L/kg; and total plasma clearance, 13.50 plus/minus 1.05 mL/min/kg. After oral administration, nicorandil was rapidly absorbed (tmax, 0.58 plus/minus 0.11 h). The oral bioavailability was calculated as 0.72 plus/minus 0.07. The metabolic formation of the corresponding alcohol after intravenous and oral administration of the parent compound appeared to occur quite efficiently, and its elimination half-life (3.09 plus/minus 0.25 and 3.69 plus/minus 0.88 h after intravenous and oral administration of nicorandil, respectively) was longer than that of the parent compound. Since the dose employed in this study was much higher than the expected therapeutic doses, whether such a good bioavailability after a lower dose of the drug would be obtained in humans remains unanswered.

Administration, Oral↗

Lectin-peroxidase reactivity in rat gastric mucosa.

The localization of lectin-binding sites in the rat gastric mucosa was investigated using horseradish peroxidase-labeled lectin conjugates (Con A, DBA, PNA, RCA-1, SBA, UEA-1, WGA). The glandular epithelium of the cardiac gland was clearly stained with DBA, PNA and SBA. Surface epithelium of the fundic glands was intensely labeled with SBA and UEA-1, but weakly with RCA-1, and WGA. Staining for foveolar cells was intense with SBA and moderate with PNA, while Con A and RCA-1 showed negligible reactivity. Mucous neck cells were intensely stained with SBA, moderately with PNA, weakly with Con A, RCA-1 and WGA, and only, faintly with DBA. Chief cells reacted positively only with WGA. Surface epithelium of the pyloric gland was moderately labeled with DBA, SBA and WGA, and faintly with the other lectins. Glandular epithelial cells, which revealed a similar pattern to that of the surface epithelium, were stained more intensely. The present study provides additional information for elucidating the cellular and regional differences in lectin binding to the rat gastric mucosa.

Animals↗

Simultaneous determination of lidocaine and its principal metabolites by liquid chromatography on silica gel, with aqueous eluent.

We describe the simultaneous determination of lidocaine and its pharmacologically active metabolites, monoethylglycinexylidide and glycinexylidide, in plasma by "high-performance" liquid-chromatography. By use of a bare ( unbonded ) silica gel with aqueous eluents, separations of organic amines such as lidocaine and its metabolites, which are very difficult and have a poor peak symmetry on bonded reversed-phase packings, were easily accomplished with a good peak symmetry. The method is sufficiently precise, sensitive, and specific. Analytical recoveries of all compounds were greater than 90%; CVs for reproducibility were less than 5% for all compounds; the lower detection limits were 0.1 mg/L or less. This method can be used to monitor the concentrations of these compounds in plasma and to prevent the concentration-related side-effect(s).

Adult↗

Concentration-effect and time-effect relationships of carteolol.

The concentration-beta blocking effect and time-effect relationships of carteolol were examined in eight normal adults given 15 mg i.v. and 20 mg orally on separate occasions. Resting and post-exercise blood pressures and heart rates were assessed before and at various times up to 48 h after each dose. Carteolol, a beta-blocker with some partial agonist activity, produced an insignificant, transient increase in heart rate 2 to 6 h after both doses, and a fall (p less than 0.05) in diastolic blood pressure 4 and 6 h after the intravenous dose and 6 h after the oral dose in the resting supine position, as compared to the corresponding baseline values. All values of the post-exercise heart rate and the double product after each of the doses were significantly (p less than 0.001) below the baseline values for the entire period (48 h) of observation. A significant correlation between the log plasma carteolol concentration (log C) and its beta-blocking effect (E: p less than 0.001, r = 0.508 i.v.; p less than 0.001, r = 0.626, p.o.) was found. The r-values for individuals were higher (0.852 to 0.977, intravenous; 0.817 to 0.981, oral) than for the group as a whole. The slope (m) of the relationship, E = m X log C + r, showed a certain variance within and between individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Pharmacokinetics and absolute bioavailability of carteolol, a new beta-adrenergic receptor blocking agent.

The pharmacokinetics and absolute bioavailability of a new nonselective beta-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or beta-phase t1/2 4.7 +/- 0.3 h; Vc, 0.74 +/- 0.101/kg; Vd, 4.05 +/- 0.48 l/kg; Cl, 10.13 +/- 0.94 ml/min/kg; ClR, 6.56 +/- 0.58 ml/min/kg; and ClNR, 3.57 +/- 0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7 +/- 8.0%, which was consistent with that derived from analysis of urine of 82.7 +/- 4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0 +/- 1.5% and 53.8 +/- 3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.

Administration, Oral↗