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Biomedical subjects

E Suzuki

Publications and source records attributed to E Suzuki.

At least 181 records · Page 10Linked to original sources
PubMed1997

Sex difference in the metabolism of pirmenol in rats.

The in vitro metabolism of pirmenol (cis-alpha-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenyl-2-pyri dinemethanol) and glucuronidation of its metabolites, a 4-hydroxylated derivative of pirmenol (M3) and 3-methylether of M3 (M5), were investigated using a hepatic 9000 x g supernatant and microsomes, respectively, of female and male rats in order to elucidate the higher urinary excretion of M3G and M5G (glucuronides of M3 and M5, respectively) in females previously observed in in vivo metabolism. Pirmenol delta1' iminium ion (M2) and M3 were formed by the oxidation of pirmenol in both sexes; however, M2 was the main metabolite in males, while M2 and M3 were formed at nearly the same level in females. On glucuronidation of M3 and M5, the Vmax values of both compounds were higher in female rats, consistent with the results in vivo. In addition, the sex difference in the urinary excretion ratio of M5G to M3G (1.1 in female, 2.5 in male) might reflect the lower availability of M3 for glucuronidation in male rats in vivo. The chromatographic separation of diastereomers of M5G was also described.

Animals↗
PubMed1997

Improved separation and determination of phospholipids in animal tissues employing solid phase extraction.

Separation of five glycerophospholipids having different polar groups, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG) and cardiolipin (CL), was investigated by means of solid-phase extraction (SPE) cartridges. First, the phospholipids were retained in an aminopropyl-bonded phase (NH2) cartridge and subsequently eluted as neutral (PC and PE) and acidic (PS, PG and CL) glycerophospholipid fractions. Secondly, a combination of silica gel (SI) cartridge and NH2 cartridge was employed to separate five glycerophospholipids. The polarity of the eluent was responsible for neutral glycerophospholipid separation. Concerning acidic glycerophospholipids, the separation of PG and CL from PS depended mainly on the pH of the eluents, and the separation of PG and CL was affected by the solvent, depending on eluent polarities. Favorable recovery (not less than 95%, for five authentic phospholipids, 10-100 micrograms each) and repeatability (sigma = 2.3 for 10 micrograms ranges) were attained by the present method. This method of separation was applicable to the analysis of phospholipids in biological samples.

Animals↗
PubMed1997

Alteration of fatty acid composition in a pgsA3 mutant of Escherichia coli.

We examined the fatty acid composition in an Escherichia coli pgsA3 mutant lacking the potential to synthesize phosphatidylglycerolphosphate, a precursor of phosphatidylglycerol. The contents of C18:1cis-9 (oleic acid) and C18:1cis-11 (cis-vaccenic acid) in the total phospholipids extracted from the pgsA3 mutant growing at 37 degrees C were higher and that of C14:0 was lower than the wild type cells, resulting in a higher level of unsaturation of fatty acids (ratio of unsaturated fatty acids to saturated ones) in the mutant. The higher level of the unsaturated fatty acids in the pgsA3 mutant was more obvious in cardiolipin than in phosphatidylethanolamine. On the other hand, at 28 degrees C, at which the pgsA3 mutant shows limited cell growth, the content of unsaturated fatty acids in cardiolipin decreased in the pgsA3 mutant compared with the wild type. We consider that the pgsA3 mutant maintains cellular homeostasis by altering the level of unsaturated fatty acids in cardiolipin, and the mechanism is influenced by temperature.

Escherichia coli↗
PubMed1997

[Structure and metabolic fate of N-nitrosodialkylamines in relation to their organotropic carcinogenicity with special reference to induction of urinary bladder tumors].

The metabolic fates of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N,N-dibutylnitrosamine (DBN) were investigated in the rat and other animal species, to elucidate a possible relationship between metabolism and organotropic carcinogenicity to the urinary bladder of these N-nitrosamines. The principal urinary metabolite of BBN as well as of DBN in the rat was N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), which was demonstrated to be the active form of these compounds as bladder carcinogen. The species difference in response to BBN or DBN is discussed on the basis of the urinary excretion rate of BCPN. Metabolism in vivo and carcinogenicity of a number of BBN analogues were investigated in the rat and a general scheme for biotransformation of N-alkyl-N-(omega-hydroxyalkyl)nitrosamines is given. A possible correlation of structure and metabolism with organotropic carcinogenicity of BBN analogues is discussed, with special reference to selective induction of urinary bladder tumors.

Animals↗
PubMed1997

Glycosphingolipid antigens from Leishmania (L.) amazonensis amastigotes. Binding of anti-glycosphingolipid monoclonal antibodies in vitro and in vivo.

Specific glycosphingolipid antigens of Leishmania (L.) amazonensis amastigotes reactive with the monoclonal antibodies (MoAbs) ST-3, ST-4 and ST-5 were isolated, and their structure was partially elucidated by negative ion fast atom bombardment mass spectrometry. The glycan moieties of five antigens presented linear sequences of hexoses and N-acetylhexosamines ranging from four to six sugar residues, and the ceramide moieties were found to be composed by a sphingosine d18:1 and fatty acids 24:1 or 16:0. Affinities of the three monoclonal antibodies to amastigote glycosphingolipid antigens were also analyzed by ELISA. MoAb ST-3 reacted equally well with all glycosphingolipid antigens tested, whereas ST-4 and ST-5 presented higher affinities to glycosphingolipids with longer carbohydrate chains, with five or more sugar units (slow migrating bands on HPTLC). Macrophages isolated from footpad lesions of BALB/c mice infected with Leishmania (L.) amazonensis were incubated with MoAb ST-3 and, by indirect immunofluorescence, labeling was only detected on the parasite, whereas no fluorescence was observed on the surface of the infected macrophages, indicating that these glycosphingolipid antigens are not acquired from the host cell but synthesized by the amastigote. Intravenous administration of 125I-labeled ST-3 antibody to infected BALB/c mice showed that MoAb ST-3 accumulated significantly in the footpad lesions in comparison to blood and other tissues.

Animals↗
PubMed1997

Activities of D- and L-xyloascorbic acid and D- and L-araboascorbic acid as a cofactor for dopamine beta-hydroxylase reaction.

L-Xyloascorbic acid (L-xylo-AsA) and its three stereoisomers, D-xyloascorbic acid (D-xylo-AsA), L-araboascorbic acid (L-arabo-AsA) and D-araboascorbic acid (D-arabc-AsA), have been considered to show some differences in vitamin C activity. In this paper the effect of L-xylo-AsA, D-xylo-AsA, L-arabo-AsA and D-arabo-AsA on the activity of dopamine beta-hydroxylase was studied to clarify whether or not the structural specificities of these stereoisomers have different effects on enzyme activity. The maximum velocity (Vmax) of the hydroxylation and Km for ascorbic acid were calculated using double-reciprocal plotting. Vmax for L-xylo-AsA was estimated to be 201 nmol/min/mg protein and those of D-xylo-AsA, L-arabo-AsA and D-arabo-AsA were 157 nmol/min/mg protein, 112 nmol/min/mg protein and 194 nmol/min/mg protein, respectively. Km for L-xylo-AsA was 1.5 mM and those for D-xylo-AsA, L-arabo-AsA and D-arabo-AsA were 2.3 mM, 2.7 mM and 1.4 mM, respectively. The effect of D-arabo-AsA on the activity of dopamine beta-hydroxylase was almost the same as that of L-xylo-AsA, while D-xylo-AsA and L-arabo-AsA showed smaller effects. Our results suggest that the configuration at carbon 4 might be more important than that of the hydroxyl group at carbon 5 for the development of the activity as a cofactor for dopamine beta-hydroxylase reaction.

Animals↗
PubMed1997

Dexamethasone and nitric oxide synthase gene expression in brain.

Systemic administration of lipopolysaccharide (LPS), which causes endotoxemia and systemic inflammation, has been reported to induce expression of the gene for type II inducible nitric oxide synthase (iNOS) in peripheral organs. This study was carried out to examine whether intraperitoneally injected LPS elicits the expression of iNOS messenger ribonucleic acid (mRNA) in the rat brain. We also investigated whether intraperitoneal treatment with dexamethasone (DEX) prevents this induction. To determine levels of iNOS mRNA, a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method was employed. Treatment with LPS induced the expression of iNOS mRNA in various brain regions, accounting for approximately 1 x 10(5) to 4 x 10(5) molecules per micrograms of poly A+ RNA, and these inductions were markedly suppressed by DEX. The results suggest that, during systemic inflammation, iNOS mRNA induction occurs in brain through a DEX-sensitive mechanism.

Animals↗
PubMed1997

[Clinical features of postinfectious chronic cough].

Postinfectious cough has been drawing attention as a factor involved in the etiology of chronic cough in the United States. In Japan, clinical features of postinfectious chronic cough (PICC) have not been described in detail. We investigated 22 patients with PICC diagnosed by the established criteria (Jpn. J. Allergol. 1995; 44: 1418). All patients were nonsmokers and none received ACE inhibitors. None had a history of atopy or sinus diseases. There were four men and 18 women with a median age of 65 years. These 22 patients underwent clinical examinations including chest roentgenograms, respiratory function tests, eosinophil counts in venous blood, serum IgE titers, antibody titers to Mycoplasma pneumoniae, sputum cytologic findings taken from ten patients, and histological features of bronchial biopsy specimens obtained from two patients; all findings were within normal limits. Clinical course of cough in 20 of the patients with PICC was evaluated using a cough diary. One patient did not keep a cough diary. Ten patients improved with dextromethorphan hydrobromide (D) and oxatomide (O). Three of the remaining 9 patients improved with Bakumondo-to (B) only, 4 with D+O+B, and 2 with D+O+B+ozagrel hydrochloride. The duration of cough before treatment showed a significant correlation with the time from the start of treatment to recovery (r = 0.47, p < 0.05). These results indicate that PICC tends to occur in elderly women and to improve with treatment combining with D, O, and B. We hope to establish a standard therapy for postinfectious chronic cough.

Adult↗
PubMed1997

[Bronchiolitis obliterans and no radiographic abnormalities in a patient with rheumatoid arthritis].

A 53-year-old woman was given a diagnosis of rheumatoid arthritis in 1988, and begun treatment with D-penicillamine in September 1992. She noticed dry coughing and exertional dyspnea that began in April 1993. Chest X-ray and CT films revealed no abnormal opacities. However, bronchiolitis obliterans was suspected because of a low FEV1% (23%). Examination of specimens obtained by thoracoscopic lung biopsy revealed constrictive obliteration by granulation tissue in proximal bronchioles and follicular bronchiolitis. Alveoli and respiratory bronchioles were intact. After corticosteroid and cyclophosphamide pulse therapy, FEV1% increased to 35%. At the time of this writing she was alive 2.5 years after hospitalization.

Anti-Inflammatory Agents↗
PubMed1997

[Extracorporeal membrane oxygenation for acute respiratory failure induced by Legionella pneumoniae. (Case report)].

We report a case of severe legionella pneumonia with acute respiratory failure, successfully managed with veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patient presented with 4-day history of fever and cough. He was in critical condition, with exacerbated respiratory failure. Mechanical ventilation, volume replacement and antibiotic therapy were initiated. Despite increasing mechanical ventilatory support (FiO2 100%, TV 10 ml/kg, f 30/min, PEEP 5 cmH20), PaO2 fell below 40Torr and life sustaining measures were undertaken. VV-ECMO (flow 30 ml/kg/min) was commenced, and the patient responded well, with an elevation of PaO2. Erythromycin therapy was effective against the pneumonia. VV-ECMO was maintained for 92 hours, mechanical ventilation was successfully discontinued 11 days after and the patient was discharged 82 days after cessation of ventilator support. Serum antibody examination proved legionella infection. VV-ECMO may have a role in the management of patients with acute respiratory failure caused by bacterial pneumonia.

Acute Disease↗
PubMed1996

The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals.

GATA factors constitute a family of transcriptional regulatory proteins expressed with distinct developmental and tissue-specific profiles and thought to regulate cell-restricted programs of gene expression. Here we describe the molecular cloning, chromosomal location, and transcription of the human GATA-6 gene. The GATA-6 cDNA encodes a predicted 449-amino-acid protein, which is highly conserved among vertebrates, and includes the two adjacent zinc-finger/basic domains characteristic of the GATA factor family. GATA-6 maps to human chromosome 18q11.1-q11.2 by fluorescence in situ hybridization. The gene is transcribed in a pattern overlapping that of GATA-4. Transcripts for both of these genes are prominent in heart, pancreas, and ovary, but only GATA-6 mRNA is found in lung and liver. GATA-6 transcripts are also detected in cultures of human and rat vascular smooth muscle cells (VSMCs). In VSMCs, GATA-6 transcripts are down- regulated when quiescent cultures are stimulated to proliferate in response to mitogen activation. These data demonstrate that GATA-6 is subject to both tissue-specific and mitogen-responsive regulatory signals. GATA-6 is a prime candidate for a gene that might regulate the differentiative state of VSMCs.

Amino Acid Sequence↗
PubMed1996

Induction of interleukin-1 beta and interleukin-1 receptor antagonist mRNA by chronic treatment with various psychotropics in widespread area of rat brain.

We investigated whether psychotropics orally administered to rats affect levels of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra) mRNA in the hypothalamus, hippocampus, frontal cortex, and brain stem, using a reverse transcription-polymerase chain reaction method. The psychotropics tested were chlorpromazine, haloperidol, imipramine, maprotiline, fluvoxamine, and diazepam. Treatment for 28 days raised the levels of both mRNAs. The increase in IL-1Ra mRNA was 6-112 times larger than that of IL-1 beta mRNA in most brain regions examined. These results suggest that chronic treatment with psychotropics causes greater amplifying effects on IL-1Ra mRNA than IL-1 beta mRNA in the brain.

Animals↗
PubMed1996

Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders.

Disturbances in dopaminergic systems have been implicated in the etiology of mood disorders. Although genetic factors also play an important role, no major gene has been identified. We conducted an association study using the dopamine D2, D3 and D4 receptor, and transporter gene polymorphisms, comparing 101 mood-disorder patients (52 bipolar and 49 unipolar) and 100 controls. Our results suggest that there is a significant association between the dopamine D4 receptor gene and mood disorders, especially major depression, but no association between the other polymorphisms and mood disorders. Further investigations are needed to clarify the clinical significance of this association in the pathophysiology of mood disorders.

Adult↗
PubMed1996

Crystal structure of ribonuclease T1 carboxymethylated at Glu58 in complex with 2'-GMP.

The carboxymethylation of RNase T1 at the gamma-carboxyl group of Glu58 leads to a complete loss of the enzymatic activity while it retains substrate-binding ability. Accompanying the carboxymethylation, RNase T1 undergoes a remarkable thermal stabilization of 9 degrees C in the melting temperature (Tm). In order to clarify the inactivation and stabilization mechanisms of RNase T1 by carboxymethylation, the crystal structure of carboxymethylated RNase T1 (CM-RNase T1) complexed with 2'-GMP was determined at 1.8 A resolution. The structure, including 79 water molecules and two Na+, was refined to an R factor of 0.194 with 10 354 reflections > 1 sigma (F). The carboxyl group of CM-Glu58, which locates in the active site, occupies almost the same position as the phosphate group of 2'-GMP in the crystal structure of intact RNase T1.2'-GMP complex. Therefore, the phosphate group of 2'-GMP cannot locate in the active site but protrudes toward the solvent. This forces 2'-GMP to adopt an anti form, which contrasts with the syn form in the crystal of the intact RNase T1.2'-GMP complex. The inaccessibility of the phosphate group to the active site can account for the lack of the enzymatic activity in CM-RNase T1. One of the carboxyl oxygen atoms of CM-Glu58 forms two hydrogen bonds with the side-chains of Tyr38 and His40. These hydrogen bonds are considered to mainly contribute to the higher thermal stability of CM-RNase T1. Another carboxyl oxygen atoms of CM-Glu58 is situated nearby His40 and Arg77. This may provide additional electrostatic stabilization.

Binding Sites↗
PubMed1996

Bioactive 6-nitronorepinephrine identified in mammalian brain.

Norepinephrine (NE) (von Euler, U. S. (1972) in Catecholamines (Blaschko, H., and Muscholl, E., eds.) pp. 186-230, Springer-Verlag, Berlin) and nitric oxide (NO.) function as neurotransmitters in the nervous system. We have shown that NE levels in the rat hypothalamic paraventricular nucleus (Shintani, F., Kato, R., Kinoshita, N., Kanba, S., Asai, M., and Nakaki, T.(1995) Proceedings of the Satellite Symposium, 4th IBRO World Congress on Neuroscience, Otsu, 1995) diminish in the presence of NO.. This observation prompted us to explore the possibility of an in vivo interaction between NE and NO. or NO.-related molecules. In fact, nitration of NE has been shown to occur in vitro (d'Ischia, M., and Costantini, C. (1995) Bioorg. Med. Chem. 3, 923-927). We now report the identification of 6-nitronorepinephrine in the mammalian brain. Amounts of 6-nitronorepinephrine in the rat brain were attenuated by intraperitoneal administration of an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME). This was reversed by coadministration of L-arginine, suggesting that nitric oxide synthase participated in the formation of 6-nitronorepinephrine. Moreover, we found that 6-nitronorepinephrine inhibits the activity of catechol O-methyltransferase, as well as NE transport into rat synaptosomes. A rat brain microdialysis experiment showed that perfusion of 6-nitronorepinephrine into the rat paraventricular nucleus significantly elevated NE while decreasing 3-methoxy-4-hydroxyphenylglycol and that L-NAME administered intraperitoneally decreased NE and increased 3-methoxy-4-hydroxyphenylglycol. These observations suggest that 6-nitronorepinephrine generated in nuclei containing both adrenergic and nitrergic neurons inhibits NE inactivation. We propose that 6-nitronorepinephrine is a potential signal molecule linking the actions of NE and NO..

Animals↗