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Biomedical subjects

E Suzuki

Publications and source records attributed to E Suzuki.

At least 253 records · Page 14Linked to original sources

Vitamin C activity of erythorbic acid in ascorbic acid-deficient guinea pigs.

The vitamin C activity of erythorbic acid (ErA) in ascorbic acid (AsA)-deficient guinea pigs was evaluated. The guinea pigs depleted AsA for 16 days were divided into two groups: one group (control group) was supplemented with 1, 5, or 100 mg/day AsA and the other group (experimental group) was supplemented with 1, 5, 20, or 100 mg/day ErA for 4 days. The contents of AsA and ErA in the tissues of guinea pigs were determined by using HPLC, and the activities of liver aniline hydroxylase, of serum alkaline phosphatase and the content of liver cytochrome P-450 were measured. The AsA tissue content of AsA-supplemented guinea pigs was much higher than the ErA tissue content of ErA-supplemented ones, and also, the activities of liver aniline hydroxylase, of serum alkaline phosphatase and the content of liver cytochrome P-450 of AsA-supplemented animals were much higher than those of ErA-supplemented animals, even when the supplemented amount of ErA was equal to that of AsA. Based on these results, the vitamin C activity of ErA seems to be much lower than that of AsA in the AsA-deficient guinea pigs. This suggested that the apparent vitamin C activity of ErA was dependent on the AsA tissue levels of guinea pigs.

Adrenal Glands↗

In situ intestinal absorption of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid in guinea pigs.

The intestinal absorption efficacy of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), which has been recently synthesized and characterized as a stable ascorbate (AsA), was determined in guinea pigs by the perfusion technique. Perfusion of AA-2G in isotonic phosphate buffer to the small intestine resulted in a decrease of AA-2G accompanied by an increase of AsA in the perfusate. The results showed that intact AA-2G was not detected in the plasma of the portal vein of guinea pigs at 2 h after perfusion. The disappearance of AA-2G from perfusate was completely inhibited by the addition of castanospermine, a specific alpha-glucosidase inhibitor, or by carbohydrates such as maltose. These results indicate that ascorbic acid released from AA-2G by alpha-glucosidase on the brush border membrane is effectively taken up across the intestinal ascorbate transport channels, into a serosal site, whereas AA-2G permeation was poor via the passive transport system.

Animals↗

[Idiopathic interstitial pneumonia (type B) with subacute progressively enlarged bullae].

A 70-year-old man with a 10-year history of seal engraving presented with exertional dyspnea and dry coughing. Chest roentgenograms showed an interstitial shadow and bilateral progressively enlarging bullae. Open lung biopsy led to the diagnosis of idiopathic interstitial pneumonia (Type B). The size of bullae usually does not change, so cases such as this are rare because the bullae continued to expand subacutely. Persistent stimulation by the inhaled A1 and Si may have played a role in the pathogenesis of this condition.

Aged↗

Immunochemical characterization of carbohydrate antigens from fungi, protozoa and mammals by monoclonal antibodies directed to glycan epitopes.

Cell surface carbohydrates constitute the major antigenic determinants of fungi and protozoa. Glycoconjugates also represent a large variety of antigens or markers present in mammals such as histo-blood groups ABO, differentiation and heterophile antigens, among others. This article focuses on the general properties of glycoconjugate antigens and production and characterization of the anti-carbohydrate monoclonal antibodies (MoAbs). It describes the specificity and some properties of monoclonal antibodies directed against carbohydrate epitopes present in tumor-associated glycoproteins, in glycosaminoglycans of higher eukaryotes and in glycolipid antigens of protozoa and fungi. The epitopes recognized by the anti-carbohydrate MoAbs range from one sugar unit up to ten sugar units. Although most anti-carbohydrate MoAbs are directed predominantly toward terminal sugar residues, a few MoAbs are also reactive with internal sugar residues. The fine structure of the carbohydrate epitopes has been chemically defined by [1H] NMR, GC/MS of alditol acetates of partially permethylated compounds, -FAB/MS, degradation with exoglycosidases and inhibition with different methyl-glycosides and oligosaccharides.

Animals↗

Prevention and treatment of cilia-associated respiratory bacillus in mice by use of antibiotics.

The effects of continuous oral administration of antibiotics in mice were investigated. Sulfamerazine, ampicillin, and chlortetracycline were tested at a rate of 500 mg/L of drinking water. Mice were infected by intranasal inoculation with 10(6) bacilli of the SMR strain of cilia-associated respiratory (CAR) bacillus. The mice were treated with the antibiotics starting 1 week before, 1 week after, or 4 weeks after the inoculation, for 5, 3, or 4 weeks respectively, then were examined. The infected mice lost body weight, and this loss was prevented or regained by all of the antibiotic treatments. Serologically no antibodies were detectable in the mice administered sulfamerazine starting 1 week before the inoculation. Mice administered sulfamerazine starting 1 week after the inoculation and ampicillin or chlortetracycline starting 1 week before or after the inoculation yielded a low titer of antibodies compared with nontreated infected mice. Mice administered antibiotics starting 4 weeks after the inoculation yielded the same titer of antibodies as nontreated infected mice. No pathologic respiratory tract lesions were observed in mice administered sulfamerazine starting 1 week before the inoculation. Mice administered sulfamerazine starting 1 week after the inoculation or ampicillin starting 1 week before or after the inoculation had slight peribronchitis without CAR bacillus colonization. Mice administered chlortetracycline, starting either 1 week before or after inoculation, developed peribronchitis, with colonization of the bacillus on the airway mucosa. In mice medicated starting 4 weeks after the inoculation, respiratory tract lesions developed, but their severity was reduced. The airway mucosa in mice treated with chlortetracycline was associated with the CAR bacillus but not in mice treated with sulfamerazine and ampicillin. These findings suggest that prevention and eradication of CAR bacillus infection is possible by treatment with sulfamerazine.

Ampicillin↗

Longitudinal changes in symptoms and plasma homovanillic acid levels in chronically medicated schizophrenic patients.

A correlation has been noted between the changes in plasma homovanillic acid concentrations and changes in psychiatric symptoms induced by neuroleptic treatment. Our objective was to determine whether plasma homovanillic acid concentration changed in accordance with the changes in symptoms over time. Twenty-eight chronically medicated schizophrenic inpatients received the same treatment regimen for 1 year. Symptoms and plasma homovanillic acid concentrations were examined every month and whenever conditions deteriorated. Plasma homovanillic acid concentrations were significantly higher in the patients in the worst condition than in the patients in the best condition. Further, when comparing the best and worst conditions of both the positive and negative symptoms, the change in psychiatric rating of positive and negative symptoms was correlated significantly with the change in plasma homovanillic acid level. These results suggest that a change in plasma homovanillic acid concentration can be produced not only by neuroleptic-induced dopaminergic blocking but also by a change in positive and negative symptoms of schizophrenia.

Adult↗

Thermal stabilization of ribonuclease T1 by carboxymethylation at Glu-58 as revealed by 1H nuclear magnetic resonance spectroscopy.

Ribonuclease T1 (RNase T1) carboxymethylated at the gamma-carboxyl group of Glu-58 with iodoacetic acid is known to be completely inactive while it retains an almost full substrate-binding ability. In order to further clarify the effects of the carboxymethylation, the thermal stabilities of intact and Glu-58-carboxymethylated (CM-) RNase T1 were compared by measuring 1H NMR spectra at various temperatures. The transition curves of unfolding were obtained by plotting, as a function of temperature, the peak areas for the alpha and delta protons of Asn-81 and Ile-90, respectively, which are well apart from each other in the three-dimensional structure of the enzyme. For each of intact and CM-RNase T1, the transition curve of the Asn-81 alpha proton was identical with that of the Ile-90 delta methyl protons, suggesting that the thermal unfolding occurred simultaneously in every part of the molecule of CM-RNase T1 as well as of intact RNase T1. The midpoint of unfolding was 52 degrees C for intact RNase T1, and was increased by 9 degrees C upon carboxymethylation at Glu-58. This marked stabilization by carboxymethylation is thought to be due to formation of a salt bridge between the introduced carboxymethyl group and the neighboring guanidium group of Arg-77.

Enzyme Stability↗

Cytochrome P450 2B1 immunoreactivity in bronchiolar and alveolar epithelial cells after exposure of rats to ozone.

Pulmonary cytochrome P450 (P450) plays an important role in the metabolism of xenobiotics. We have previously demonstrated that exposure to ozone (O3), a major oxidant of photochemical smog, increases P450 content and xenobiotic metabolizing activities in the rat lung. Therefore, it is conceivable that O3 exposures modify the pattern and potency of xenobiotic metabolism. The aim of this study is to examine the effect of O3 exposure on localization of P450 in the lung. After exposure of rats to 0.4 ppm O3 for 14 days, the concentration of P450 2B1, the main isozyme of P450 in the lung, increased to 214% of the control value. By immunohistochemical analyses, O3 exposure caused hypertrophy and hyperplasia of P450 2B1-positive non-ciliated bronchiolar epithelial (Clara) cells, showing an increase in the cell number to 128% of the control level. At the proximal alveoli, O3 exposure induced hypertrophic epithelial cells that presented immunoreactivity to P450 2B1 and morphological characteristics of both type 1 and type 2 cells. These hypertrophic cells had lamellar inclusion bodies, microvilli, and extended cytoplasm. Typical type 2 cells did not react with anti-P450 2B1 antibody even after O3 exposure. These data suggest that O3 exposure may activate the P450-mediated xenobiotic metabolism in the pulmonary epithelial cells, and that expression of P450 2B1 in the pulmonary epithelial cells might be regulated by the factors involved in the process of the differentiation from type 2 to type 1 cells.

Animals↗

Growth rate suppression of cultured mammalian cells enhances protein productivity.

Suppression of proliferation of cells which contain stable or stabilized mRNA coded for a protein to be produced, a partial mimic of cell differentiation, was examined for enhancing protein production by cultured mammalian cells. Hybridoma 2E3 cells which were adapted to be interleukin-6 sensitivity growth-suppressed accumulated the mRNA of IgG1 which is reported stable, and IgG1 production rate increased as a result when their growth was suppressed with interleukin-6. A myeloma cell line was similarly adapted; the obtained myeloma cells can be used as host cells for enhancing production of exogenous proteins by suppressing growth with interleukin-6. Temperature-sensitively growth-suppressible mutants of mouse mammary carcinoma FM3A were transfected with cDNA of IgM lambda 1 chain and cultured at nonpermissive temperature to enhance production of lambda 1. Addition of various growth-suppressive reagents to culture medium was studied for finding methods suitable for suppressing growth while maintaining high cell viability. Caffeine yielded the best results among these reagents. Deprivation of various growth-supporting components in culture medium was also tested; simultaneous deprivation of insulin and transferrin viably suppressed growth of hybridoma 2E3 cells, resulting in enhanced antibody productivity.

Animals↗

The Drosophila dgq gene encodes a G alpha protein that mediates phototransduction.

We examined the roles of the Drosophila Gq alpha proteins (DGq) in the phototransduction pathway. The DGq proteins immunolocalized to the ocelli and all eight retinular photoreceptor cell rhabdomeres. An affinity-purified anti-DGq alpha immunoglobulin blocked the light-dependent GTP hydrolysis activity associated with Drosophila head membranes in vitro, suggesting that rhodopsin stimulated DGq. Dominantly active DGq1 mutants exhibited a light-independent GTPase activity and abnormal electrophysiological light responses, such as reduced retinal sensitivity and slow response kinetics compared with wild-type flies. Dominant DGq2 mutants exhibited a light-independent GTPase activity with normal electrophysiological light responses. Retinas of double mutants of DGq1, but not DGq2, with the light-dependent retinal degeneration mutant rdgB degenerated even in the dark. DGq1 stimulation of rdgB retinal degeneration in the dark was norpA-dependent. These results indicate that DGq1 mediates the stimulation by light-activated rhodopsin of the norpA-encoded phospholipase C in the visual transduction cascade.

Alternative Splicing↗

Long-term administration of L-arginine improves nitric oxide release from kidney in deoxycorticosterone acetate-salt hypertensive rats.

To examine the effects of L-arginine (L-Arg) on endothelial function, we administered 0.5 g/L L-Arg in drinking water to deoxycorticosterone acetate (DOCA)-salt rats for 8 weeks and then measured nitric oxide (NO) release from isolated kidneys using a newly developed real-time chemiluminescence method. Renal pathology was also analyzed. Acetylcholine caused much smaller declines in renal perfusion pressure (10(-7) mol/L acetylcholine: -24 +/- 2% [SEM] versus -50 +/- 2%, P < .001) and NO release in DOCA-salt rats (+3 +/- 1 versus +33 +/- 3 fmol/min per gram kidney weight, P < .001) compared with control rats. L-Arg did not influence the time course of systolic blood pressure elevation in DOCA-salt rats (211 +/- 5 versus 208 +/- 6 mmHg, DOCA versus L-Arg/DOCA, P = NS). However, oral administration of L-Arg improved acetylcholine-induced declines in renal perfusion pressure (10(-7) mol/L acetylcholine: L-Arg/DOCA, -39 +/- 3%, P < .01 versus DOCA). This change was associated with an increase in NO release by acetylcholine (10(-7) mol/L acetylcholine: L-Arg/DOCA, +10 +/- 1 fmol/min per gram kidney weight, P < .05 versus DOCA). However, morphological changes in renal vessels and glomeruli were similar between DOCA and L-Arg/DOCA rats. These results suggest that L-Arg administration partially reverses renal endothelial function with respect to vasorelaxation and NO release independent of blood pressure changes, indicating that hypertensive vessels seem to be depleted of L-Arg and/or have defects in the availability of L-Arg for NO synthesis.

Acetylcholine↗

Role of hydrogen peroxide in the inhibitory effect of ascorbate on cell growth.

Organ cultures have become an important method for the study of some of the biochemical reactions in which ascorbate takes part, and there are conflicting views on the stimulatory and inhibitory actions of ascorbate on cell growth. This study aimed to clarify the inhibitory mechanism of ascorbate using 3T6 fibroblasts. Cells were exposed to ascorbate at various concentrations in medium. The results showed that 3T6 fibroblasts were killed in medium containing more than 0.3 mM ascorbate. This lethal effect of ascorbate on cells was inhibited by the addition of catalase, an enzyme that decomposes hydrogen peroxide (H2O2), to the medium. When the medium with ascorbate was incubated in the absence of cells, the amount of H2O2 generation depended on the ascorbate concentration, and decreased in inverse proportion to the serum concentration added to the medium. The addition of albumin, which is the main protein in serum, also inhibited H2O2 generation in the medium with ascorbate. However H2O2 generation was not inhibited completely by serum and albumin. These results indicate that cytotoxicity of ascorbate is induced by H2O2.

3T3 Cells↗

Mechanisms of the natriuretic effects of neutral endopeptidase inhibition in Dahl salt-sensitive and salt-resistant rats.

To explore the mechanisms of the renal effects of neutral endopeptidase (NEP) inhibition, the effects of an NEP inhibitor, candoxatril (UK 79,300; UK), in Dahl salt-sensitive (SS) and salt-resistant (SR) rats were examined. UK dose-dependently decreased blood pressure (BP) in SS rats (20 mg/kg: 174 +/- 5 vs. 155 +/- 8 mm Hg, p < 0.01) but not in SR rats. Urinary sodium excretion (UNaV) of both rat strains receiving high-salt diets was increased to a greater extent than that of rats receiving low-salt diets. Basal plasma atrial natriuretic peptide (ANP) level in hypertensive SS rats was higher than in SR rats (192 +/- 18 vs. 118 +/- 24 pg/ml, p < 0.05). UK increased ANP levels in the plasma and urine two- and 11-fold, respectively. UK-induced increases in UNaV, urinary cyclic GMP, and plasma ANP concentrations were significantly augmented by coadministration of a clearance receptor agonist, C-ANF(4-23) or brain natriuretic peptide (BNP). Thus, the effects of NEP inhibition appear to be potentiated by the reduced receptor-mediated metabolism of ANP. This may explain the greater response to the NEP inhibitor in Dahl rats with hypertension or high-salt feeding.

Animals↗

[A case of bronchial asthma associated with reflux esophagitis, whose peak expiratory flow rate improved with omeprazole and cisapride].

A 60-year-old male had visited our hospital periodically, because of perennial moderate atopic asthma, since 53 years of age. His symptoms had stabilized following treatment with oral theophylline 400 mg, tranilast 300 mg and inhalation of beclomethasone dipropionate 400 micrograms and procaterol hydrochloride. His peak expiratory flow rate early in the morning was 465 L/min, %VC was 115% and FEV1.0% was 62.4% in May of 1993. On May 24, 1993, though he had no gastrointestinal symptoms, gastrointestinal fiberscopy revealed a hiatal hernia, reflux esophagitis and active gastroduodenal ulcer. The upper gastrointestinal x-ray films showed gastroesophageal reflux. Therefore, we diagnosed bronchial asthma associated with reflux esophagitis and gastroduodenal ulcer. He was started on omeprazole, as a proton pump inhibitor (PPI), and cisapride. After the treatment with PPI and cisapride, his peak expiratory flow rate early in the morning and in the evening, %VC and FEV1.0 increased. Three months later gastrointestinal fiberscopy revealed improvement in the reflux esophagitis and the gastroduodenal ulcer. We speculate that the improvement in the peak expiratory flow rate is related to that of the gastroesophageal reflux.

Asthma↗

Affinity of neuroleptics for D1 receptor of human brain striatum.

We determined the inhibition-dissociation constant (Ki) of a number of neuroleptics for D1 receptors of normal human brain tissue using [3H]SCH23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3[benzazepine-7- ol]. SCH23390 had the highest affinity with a Ki of 0.76 nM. Among clinically used drugs, propericiazine showed the highest affinity with a Ki of 10 nM. When neuroleptics were classified according to chemical structures, the Ki values were as follows. Phenothiazines ranged from 10 nM to 250 nM. Butyrophenones ranged from 45 nM to 250 nM. Thioxanthenes ranged from 12 nM to 340 nM. Orthopramines were more than 10,000 nM. The Ki values for the binding site of this study were significantly correlated with those reported in studies using animal brain. The possible relationship between D1 receptors and negative symptoms is discussed.

Aged↗

1H-NMR analysis of nerve edema in the streptozotocin-induced diabetic rat.

To define the existence of intracellular hydration caused by metabolic derangements in the excised sciatic nerves of diabetic rats quantitatively, relaxation times (T1, T2) and fraction of intracellular water content were measured with 1H-nuclear magnetic resonance (NMR) spectroscopy in normal rats (control group, n = 10), streptozotocin (STZ)-induced (50 mg/kg, i.v.) diabetic rats (DM group, n = 10), STZ-induced diabetic rats treated with an aldose reductase inhibitor (ARI, Epalrestat, 100 mg/kg) (ARI group, n = 8), and STZ-induced diabetic rats treated with insulin (insulin group, n = 4). For selective measurement of intracellular relaxation times, the inversion recovery (IR) method for conventional T1 and Carr-Purcell-Meiboom-Gill method for T2 were used with an aqueous chemical shift reagent, 10 mmol/L dysprosium triethylenetetramine-N,N,N',N",N"',N"'-hexaacetic acid, resulting in distinct separation of intracellular (Schwann cell, axon, endothelial cell, and pericyte) and extracellular waters under the isotonic condition of the rat sciatic nerves. Furthermore, a new method of driven-equilibrium single-pulse observation of T1 (DESPOT) was used for rapid measurement of T1 for the purpose of clinical application on magnetic resonance imaging (MRI). T1 values measured by the DESPOT and IR methods were significantly correlated (p < 0.001). Total and intracellular water contents, sorbitol contents, and relaxation times of the sciatic nerve taken from the DM group were significantly elevated (p < 0.01), while myoinositol (p < 0.01) and extracellular water (p < 0.05) contents were significantly decreased as compared with the control group. Both insulin and ARI treatments significantly improved relaxation times as compared with those in the DM group (p < 0.05-0.01). Relaxation times correlated positively with total water (T1, p < 0.05-0.01; T2, p < 0.01), intracellular water (T1, p < 0.001; T2, p < 0.001), and sorbitol (T1, p < 0.001; T2, p < 0.001) contents of the excised nerve. Sorbitol content correlated positively with total and intracellular water contents (p < 0.01) but negatively with extracellular water content (p < 0.05). These findings indicated that sorbitol itself and/or secondary sodium accumulation caused by an increase in sorbitol may be a major contributor to the increase in intracellular hydration and prolonged relaxation times associated with hyperglycemia, which are reversible with insulin or ARI treatment. It was also suggested that rapid T1 measurement would provide new insights into the pathogenesis of human diabetic neuropathy as a non-invasive evaluation method on MRI.

Aldehyde Reductase↗