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Biomedical subjects

N Noguchi

Publications and source records attributed to N Noguchi.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of a new angiotensin-converting enzyme inhibitor, alacepril, on changes in neurohormonal factors and arterial baroreflex sensitivity in patients with congestive heart failure.

OBJECTIVE: Patients with heart failure have abnormal neurohormonal regulation during orthostatic stress, and abnormal arterial baroreflex function. This study investigated the effects of alacepril, a new angiotensin-converting enzyme inhibitor with sulfhydryls, on changes in neurohormonal factors during tilt and on the arterial baroreflex control of heart rate. METHODS: Plasma concentrations of noradrenaline, adrenaline, renin activity, angiotensin II, and atrial natriuretic peptide were measured at supine rest and after 30 degrees head-up tilt with measurements of central venous pressure and cardiac dimensions in seven patients with congestive heart failure (65 years, ejection fraction = 34%). Arterial baroreflex control of heart rate was assessed by phenylephrine bolus. The arterial baroreflex test was re-examined 3 h after oral alacepril (37.5 mg). The tilt and arterial baroreflex tests were repeated 12 weeks after alacepril treatment (50 mg x day(-1)). RESULTS: Heart rate, blood pressure, and neurohormonal factors did not differ before and after chronic alacepril, except for a trend toward an increase in renin activity (2.0 vs 4.9 ng x ml(-1) x h(-1)). Head-up tilt decreased central venous pressure (-2.5 mmHg) with a decrease in cardiac dimensions in the pre-alacepril phase. These changes were accompanied by increases in noradrenaline, adrenaline, and angiotensin II and a decrease in atrial natriuretic peptide. After chronic alacepril, the increase in noradrenaline during head-up tilt tended to be smaller (84 vs 30 pg x ml(-1)), with similar changes in central venous pressure (-3.4 mmHg) and cardiac dimensions. Both acute (3.6 vs 4.8 ms mmHg(-1)) and chronic (3.6 vs 6.7 ms mmHg(-1)) alacepril treatment was associated with a trend towards an increase in the arterial baroreflex control of heart rate. CONCLUSION: These results suggest that treatment with alacepril may cause a reduction of sympathetic activation during orthostatic stress and may enhance arterial baroreflex function in patients with mild to moderate heart failure.

Aged↗
PubMed1998

Oxidation of lipids in low density lipoprotein particles.

This study was undertaken to understand further the mechanisms and dynamics of the oxidation of lipids in low density lipoprotein (LDL) particles, aiming specifically at elucidating the material balance between oxygen uptake and products found and also the relative susceptibilities to oxidation of cholesteryl ester in the core and phosphatidylcholine in the outer monolayer in the LDL particles. It was found that considerable amount of oxygen uptake could not be accounted for by conjugated diene or total peroxides. Total peroxide was measured from the phosphine oxide formed from triphenylphosphine or diphenyl-pyrenylphosphine by reduction of peroxides. Cholesteryl ester hydroperoxides and phosphatidylcholine hydroperoxides were the major peroxides formed in LDL oxidation, but they accounted for about 60% of total peroxide. Cholesterol was also oxidized, but its oxidation was significant only at the later stages of the reaction. It was also found that the oxidizability of cholesteryl ester relative to phosphatidylcholine was larger within the LDL particle than in homogeneous solution and this was interpreted in the context of the physical properties of LDL particle.

Cholesterol↗
PubMed1998

Expression in Pseudomonas aeruginosa of an erythromycin-resistance determinant that encodes the mphA gene for macrolide 2'-phosphotransferase I from Escherichia coli.

We studied the expression in Pseudomonas aeruginosa of an erythromycin-resistance (EMr) determinant that included the mphA gene for macrolide 2'-phosphotransferase I and originated in Escherichia coli. A recombinant plasmid, pTZ3609, that consisted of the EMr determinant and a broad-host-range vector RSF1010, endowed P. aeruginosa with high-level resistance to erythromycin. Furthermore, the EMr determinant on a self-transferable plasmid, RP1, was transferred from E. coli to P. aeruginosa by conjugation.

Anti-Bacterial Agents↗
PubMed1998

Isolation and characterization of two plasmids that mediate macrolide resistance in Escherichia coli: transferability and molecular properties.

Escherichia coli BM2506 is highly resistant to macrolide antibiotics; it produces macrolide 2'-phosphotransferase II [MPH(2')II] which inactivates such drugs. We investigated the localization and the transfer of the macrolide-resistance determinant that encoded the mphB gene for MPH(2')II in strain BM2506. Although we detected no clear band of plasmid DNA after agarose gel electrophoresis, transformation analysis using satellite DNA that corresponded to plasmid DNA after CsCl-ethidium bromide gradient centrifugation and restriction analysis of plasmid DNA in transformants showed that strain BM2506 harbored two plasmids, pTZ3721 (84 kb) and pTZ3723 (24 kb), that specified resistance to macrolides, ampicillin, streptomycin, tetracycline and sulfonamide and to macrolides and ampicillin, respectively. Southern hybridization showed that the mphB gene hybridized to both plasmids. Furthermore, pTZ3721 was transferred by conjugation to another strain of E. coli and pTZ3723 was mobilized with a self-transferable plasmid RP1 to other strains of E. coli. Therefore, it appears that the mphB gene is located on two plasmids in BM2506 and can be transferred to other strains of E. coli by conjugation or mobilization.

Anti-Bacterial Agents↗
PubMed1998

Sympathetic nervous response relative to the adenosine triphosphate supply-demand imbalance during exercise is augmented in patients with heart failure.

OBJECTIVE: Increase in plasma hypoxanthine (HX) (purine nucleotide degradation product from working muscle) reflects insufficiency of adenosine triphosphate (ATP) supply during exercise, and the exercise-induced increase in plasma norepinephrine (NE) can be an index of sympathetic nerve activity. The aim of this study was to investigate the relationship between plasma NE and plasma HX during exercise in patients with heart failure (HF) according to its severity. METHODS: Blood lactate, plasma HX, and plasma NE were measured at rest and after symptom-limited cardiopulmonary exercise test in 54 patients with HF (New York Heart Association [NYHA] classes I:18, II:20, III:16) and 19 normal subjects. RESULTS: Peak work rate and peak oxygen uptake decreased as the NYHA functional class increased. Blood lactate and plasma HX levels at rest were comparable, but peak blood lactate (normal, NYHA I, II, III: 6.4+/-0.3, 5.6+/-0.4, 5.3+/-0.3, 3.5+/-0.2 mmol/L) and peak plasma HX (3.6+/-0.4, 3.0+/-0.5, 2.4+/-0.3, 1.4+/-0.1 micromol/L) were progressively smaller as HF worsened. Resting plasma NE (137+/-15, 180+/-29, 201+/-21, 318+/-55 pg/mL) was significantly higher in NYHA class III HF, but peak plasma NE (2,235+/-356, 2,021+/-326, 2,188+/-292, 2,210+/-316 pg/mL) was not different among groups. The ratio of the exercise increments in plasma NE to the increments in plasma HX during exercise (deltaplasma NE/deltaplasma HX: 666+/-96, 1,083+/-229, 1,252+/-222, 2,260+/-351) increased according to the severity of HF. CONCLUSION: These data suggest that plasma levels of HX after maximal exercise are smaller as HF worsened, and sympathetic responsiveness to the imbalance of ATP supply-demand during exercise is augmented according to the severity of HF.

Adenosine Diphosphate↗
PubMed1998

Prolongation of PT and APTT under excessive anticoagulant in plasma from rats and dogs.

Prothrombin time (PT) and activated partial thromboplastin time (APTT) were studied under excessive sodium citrate using the plasma from rats and beagle dogs. Addition of sodium citrate into the plasma caused a prolongation of PT and APTT. The prolongation was dependent on the concentration of sodium citrate or calculated hematocrit. The degree of prolongation was more severe in rats than in dogs, and in APTT than in PT. These results suggest that an artificial prolongation of PT and APTT occurs under excessive sodium citrate (e.g., elevated hematocrit), and that the degree differs between species and between parameters.

Animals↗
PubMed1998

Cellular size of bone marrow cells from rats and beagle dogs.

The usefulness of cellular size measurement for differentiating erythroid and myeloid cells was investigated using rat and canine bone marrow film prepared by the Cytospin method and Wright-Giemsa staining. 1. In the erythroid series, basophilic and polychromatic erythroblasts were distinguishable in terms of cellular diameter; i.e., 99% of rat and 95% of canine polychromatic erythroblasts were distributed in a range < or = 9.5 microns, at which basophilic erythroblasts did not exist. 2. In the myeloid series, myelocytes and metamyelocytes were to some extent distinguishable by their diameters; in rats, myelocytes (75% of the population) were > or = 13.5 microns, and metamyelocytes (61%) < or = 11 microns; and in dogs, myelocytes (45%) were > or = 16 microns, and metamyelocytes (66%) < or = 12 microns. 3. With regard to the metamyelocytes and myelocytes existing in the same range, their nuclear sizes (width) allowed further differentiation; in rats, the nuclear width of myelocytes (87%) was > or = 5 microns, and that of metamyelocytes (84%) < 5 microns; and in dogs, myelocytes (96%) > or = 7 microns, and metamyelocytes (88%) < 7 microns. The present results indicate that cellular size, together with nuclear size, contribute to distinguish the active mitotic group from less- or non-mitotic group in erythroids and myeloids, thus being helpful for toxicological evaluation on chemicals.

Animals↗
PubMed1998

Dynamics of vitamin E action against LDL oxidation.

Vitamin E acts as an important antioxidant against oxidative modification of low density lipoprotein (LDL) which is accepted as an initial event in the pathogenesis of atherosclerosis. In spite of the numerous studies and reports, the action and role of vitamin E have not been fully elucidated yet. In this brief overview, the dynamics of action of vitamin E as an antioxidant have been discussed and it is emphasized that the total antioxidant potency is determined by the relative importance of many competing reactions which is determined by the reactivities and concentrations of substrates, radicals and antioxidant and by physical factors of the environment.

Animals↗
PubMed1998

Clinical significance of serum P53 antibody in patients with gastric cancer.

The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.

Adenoma↗
PubMed1998

Clinical significance of serum soluble Fas ligand in patients with acute self-limited and fulminant hepatitis.

The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-expressing cells. A matrix metalloproteinase-like enzyme cleaves the membrane-bound FasL to produce the soluble FasL (sFasL). Since FasL has been reported to play a pivotal role in the development of hepatitis, we evaluated clinical significance of serum sFasL in acute liver injury including acute self-limited and fulminant hepatitis. Serum sFasL in 19 patients including 12 with acute self-limited hepatitis and 7 with fulminant hepatitis was measured by an enzyme-linked immunosorbent assay (ELISA). The clinical data consisted of 18 indices including age, sex, liver function tests, hepatocyte growth factor (HGF), outcome and sFasL. Serum sFasL in fulminant hepatitis is 0.06+/-0.01 ng/ml, being identical to that in acute self-limited hepatitis, Serum sFasL is positively correlated with AST and ALT (p<0.0001 and p<0.0001). The factors associated with outcome of the patients were HGF, albumin, prothrombin time, platelet count, cholinesterase and leukocyte count in this order. Serum sFasL serves as an indicator of liver injury in acute self-limited and fulminant hepatitis.

Acute Disease↗
PubMed1997

Inhibition of oxidation of low-density lipoprotein by a novel antioxidant, BO-653, prepared by theoretical design.

2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butyl-benzofuran (BO-653) is a novel antioxidant synthesized by theoretical designing based on the previous experimental findings and consideration. The antioxidant activities of BO-653 against the oxidative modification of low-density lipoprotein (LDL) induced by free radicals were studied. BO-653 was consumed faster than endogenous alpha-tocopherol and inhibited the formation of lipid hydroperoxides, which was observed during the consumption of alpha-tocopherol. Doxyl stearic acids incorporated into LDL as spin probes competed with the antioxidants in scavenging radicals. It was found that the efficacy of radical scavenging by alpha-tocopherol became smaller as the radical went deeper into the interior of LDL particle, whereas that by BO-653 did not change. Ascorbic acid in the aqueous phase spared alpha-tocopherol efficiently during oxidation. On the other hand, the sparing effect of ascorbic acid for BO-653 was not remarkable, unlike that for alpha-tocopherol, which implied different locations of radicals derived from BO-653 and alpha-tocopherol within the LDL particle. It was concluded that BO-653 protected LDL from oxidative modification efficiently by scavenging peroxyl radicals and by reducing alpha-tocopheroxyl radicals and that this novel antioxidant might act as a potent inhibitor of development of atherosclerosis.

Amidines↗
PubMed1997

2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran: design and evaluation as a novel radical-scavenging antioxidant against lipid peroxidation.

To develop a novel potent radical-scavenging antioxidant, the ideal structure of a phenolic compound was designed considering the factors that determine antioxidant potency. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4, 6-di-tert-butylbenzofuran (BO-653) was thus synthesized and its antioxidant activity was evaluated against lipid peroxidations in vitro. The electron spin resonance study showed that the phenoxyl radical derived from BO-653 was more stable than alpha-tocopheroxyl radical. BO-653 reduced alpha-tocopheroxyl radical rapidly, but alpha-tocopherol did not reduce the phenoxyl radical derived from BO-653. However, the chemical reactivity of BO-653 toward peroxyl radical was smaller than that of alpha-tocopherol. This was interpreted as the steric effect of bulky tert-butyl groups at both ortho positions which hindered the access of peroxyl radical to the phenolic hydrogen. However, the tertbutyl substituents increased the stability of BO-653 radical and also lipophilicity, and its antioxidant potency against lipid peroxidation in phosphatidylcholine liposomal membranes was superior to that of alpha-tocopherol. Ascorbic acid reduced the phenoxyl radical derived from BO-653 and spared BO-653 during the oxidation of lipid in the homogeneous solution. On the other hand, ascorbic acid did not spare BO-653 in the oxidation of liposomal membranes. It was concluded that BO-653 is a potent novel radical-scavenging antioxidant.

Antioxidants↗
PubMed1997

Structure, chromosomal localization and expression of mouse genes encoding type III Reg, RegIII alpha, RegIII beta, RegIII gamma.

Reg (regenerating gene), first isolated from a rat regenerating islet cDNA library, is expressed in regenerating islet beta-cells. Recently, it has been revealed that Reg and Reg-related genes constitute a multigene family, Reg family, which consists of three subtypes (type I, II, III) based on the primary structures of the encoded proteins of the genes. In mouse, type I and type II Reg genes (i.e. RegI and RegII gene) have so far been isolated. In the present study, the complete nucleotide (nt) sequences of the cDNAs and genes encoding murine type III Reg (regenerating gene product), RegIII alpha, RegIII beta and RegIII gamma were determined. RegIII alpha, RegIII beta and RegIII gamma encode 175-, 175- and 174-amino acid (aa) proteins, respectively, with 60-70% homology. All three genes are composed of six exons and five introns spanning approx. 3 kb, and exhibit distinctive structural features unique for members of the Reg gene family. All the mouse Reg genes, RegIII alpha, RegIII beta, RegIII gamma, RegI and RegII, are assigned to the adjacent site of chromosome 6C by fluorescence in situ hybridization (FISH). RegIII alpha, RegIII beta and RegIII gamma were expressed weakly in pancreas, strongly in intestinal tract, but not in hyperplastic islets, whereas both RegI and RegII were expressed in hyperplastic islets. These results suggest that genes of the mouse Reg family are derived from a common ancestor gene by several gene duplications, and have obtained divergency in expression and function in the process of genetic evolution.

Amino Acid Sequence↗
PubMed1997

Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes.

Cyclic ADP-ribose (cADPR) is a second messenger for Ca2+ mobilization via the ryanodine receptor (RyR) from islet microsomes for insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In the present study, FK506, an immunosuppressant that prolongs allograft survival, as well as cADPR were found to induce the release of Ca2+ from islet microsomes. After islet microsomes were treated with FK506, the Ca2+ release by cADPR from microsomes was reduced. cADPR as well as FK506 bound to FK506-binding protein 12.6 (FKBP12.6), which we also found occurs naturally in islet microsomes. When islet microsomes were treated with cADPR, FKBP12.6 dissociated from the microsomes and moved to the supernatant, releasing Ca2+ from the intracellular stores. The microsomes that were then devoid of FKBP12.6 did not show Ca2+ release by cADPR. These results strongly suggest that cADPR may be the ligand for FKBP12.6 in islet RyR and that the binding of cADPR to FKBP12.6 frees the RyR from FKBP12.6, causing it to release Ca2+.

Adenosine Diphosphate Ribose↗