Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 289 records · Page 16Linked to original sources

PubMed1998

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure.

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5 +/- 3.4, mean +/- SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2-h intervals during sleep. Simultaneously, blood pressure was measured by a non-invasive method (Finapres, Ohmeda, Englewood, CO, USA) and urine was collected for determining volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non-snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30-min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P < 0.01, ANOVA). Baseline BNP levels were not significantly correlated with patient's clinical and polysomnographic parameters. However, in the latter half of the sleep period (02:00-06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r = 0.784 P < 0.01, diastolic: r = 0.587 P < 0.01) and with apnoea duration (r = 0.582 P < 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P < 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P < 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30-min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.

Atrial Natriuretic Factor↗

PubMed1998

Effect of protein restriction on messenger RNA of insulin-like growth factor-I and insulin-like growth factor-binding proteins in liver of ovariectomized rats.

Effects of dietary protein restriction and ovariectomy on plasma concentrations and hepatic messenger RNA (mRNA) of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) were investigated in young female rats. Ovariectomy increased plasma IGF-I concentration in rats fed on either a 50 g casein/kg diet (protein-restricted diet) or a 200 g casein/kg diet (control diet), but it increased IGF-I mRNA in liver only in the rats fed on the control diet. On the other hand, by Western ligand blot analysis, we observed that ovariectomy increased plasma IGFBP-3 concentration, and decreased plasma IGFBP-4 concentration. Ovariectomy did not affect IGFBP-1 and IGFBP-2 mRNA in liver, but dietary protein restriction significantly increased them, which may correspond to their plasma concentrations. The present results show that ovarian hormones and dietary protein content affect the plasma concentrations of IGF-I, IGFBP-3 and IGFBP-4 and hepatic mRNA of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4 in different manners.

Analysis of Variance↗

PubMed1998

Activin A regulates the production of mature interleukin-1beta and interleukin-1 receptor antagonist in human monocytic cells.

Activin A, a member of the transforming growth factor-beta (TGF-beta) family, is produced by a variety of cells and implicated in the regulation of the reproductive endocrine system, mesoderm induction, and erythropoiesis. In the present study, we showed that activin A inhibited the production of interleukin-1beta (IL-1beta), a potent proinflammatory cytokine, and enhanced the production of IL-1 receptor antagonist (IL-1ra), in activated THP-1 and U-937 human monocytic cells, resulting in the reduction of IL-1 biologic activity. Northern blot analysis revealed that activin A had no effect on mRNA accumulation of IL-1beta and IL-1ra, indicating that activin A regulates IL-1beta and IL-1ra production at a posttranscriptional level. As it is well known that an inactive precursor form of IL-1beta (pro-IL-1beta) is converted to an active mature form (mature IL-1beta), we examined the expression levels of pro-IL-1beta and mature IL-1beta by immunoblot analysis. Although activin A inhibited the production of mature IL-1beta in activated U-937 cells, the relative protein expression of pro-IL-1beta was unaltered by activin A, suggesting that activin A inhibits IL-1beta production by blocking proteolytic conversion of pro-IL-1beta into mature IL-1beta. Taken together, these findings suggest that activin A may function as an anti-inflammatory cytokine by modulating mature IL-1beta and IL-1ra production in inflammatory sites.

Activins↗

PubMed1998

Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a very common disorder. Patients with OSAS are at an increased risk for cardiovascular events. It has also been reported that a 25% rise in factor VII clotting activity (FVIIc) is associated with a 55% increase in ischaemic heart disease death during the first 5 years. We examined the effects of nasal continuous positive airway pressure (NCPAP) treatment on FVIIc in patients with OSAS. FVIIc was investigated prospectively in 15 patients with OSAS before (mean +/- SEM apnoea and hypopnoea index (AHI) 61.5 +/- 4.2 and after (AHI 3.0 +/- 0.9) NCPAP treatment for immediate relief, at 1 month after treatment and at over 6 months. FVIIc levels gradually decreased after NCPAP treatment. After 6 months of NCPAP treatment, FVIIc levels had decreased significantly (before 141.1 +/- 11.7% vs. after 6 months 110.7 +/- 6.2%; p < 0.01). Six of the seven patients whose FVIIc levels were over 140% before the NCPAP treatment had FVIIc levels below 130% after 6 months or 1 year of NCPAP treatment. This decrease in FVIIc after long-term NCPAP treatment could improve mortality in OSAS patients. If patients, especially obese ones, present with high FVIIc of unknown origin, it would be prudent to check for OSAS.

Adult↗

PubMed1998

Hemodynamic effect of amrinone depends on pretreatment vascular resistance in patients with evolving congestive heart failure: correlation between vascular resistance and neurohormonal activity.

We investigated the hemodynamic effects of amrinone and assessed its effects on neurohormonal factors in 15 patients with evolving congestive heart failure with various origins. We serially determined the pulmonary and systemic vascular-resistance indices after amrinone infusion and examined the relation between changes in hemodynamic parameters and changes in concentrations of norepinephrine, atrial natriuretic peptide, angiotensin II, and endothelin-1 in the pulmonary capillary wedge region (PCWR) and in the peripheral veins. Amrinone significantly reduced pulmonary vascular-resistance index (PVRI; Wood x m2) in patients with high PVRI (> or =15) before the infusion, significantly reduced systemic vascular-resistance index (SVRI; Wood x m2) in patients with high SVRI (> or =50) before the infusion, and had little effect on vascular resistances in patients with low PVRI (<15) and low SVRI (<50). The reduction in PVRI was correlated with the reduction in the endothelin-1 level (r = 0.75) in the PCWR, and the reduction in SVRI with norepinephrine level (r = 0.70) in the peripheral veins. The angiotensin II level did not change throughout the study. These findings suggest that amrinone had selective hemodynamic effects on pulmonary and systemic circulations with neurohormonal effects, according to PVRI and SVRI before infusion.

Aged↗

PubMed1998

The Arabidopsis DIMINUTO/DWARF1 gene encodes a protein involved in steroid synthesis.

We have identified the function of the Arabidopsis DIMINUTO/DWARF1 (DIM/DWF1) gene by analyzing the dim mutant, a severe dwarf with greatly reduced fertility. Both the mutant phenotype and gene expression could be rescued by the addition of exogenous brassinolide. Analysis of endogenous sterols demonstrated that dim accumulates 24-methylenecholesterol but is deficient in campesterol, an early precursor of brassinolide. In addition, we show that dim is deficient in brassinosteroids as well. Feeding experiments using deuterium-labeled 24-methylenecholesterol and 24-methyldesmosterol confirmed that DIM/DWF1 is involved in both the isomerization and reduction of the Delta24(28) bond. This conversion is not required in cholesterol biosynthesis in animals but is a key step in the biosynthesis of plant sterols. Transient expression of a green fluorescent protein-DIM/DWF1 fusion protein and biochemical experiments showed that DIM/DWF1 is an integral membrane protein that most probably is associated with the endoplasmic reticulum.

Amino Acid Sequence↗

PubMed1998

In vivo efficacy and tumor-selective metabolism of amrubicin to its active metabolite.

The tissue distribution of a novel antitumor anthracycline antibiotic, amrubicin, was studied using seven human tumor xenografts implanted into nude mice, in order to identify the principal factors determining its therapeutic efficacy. We found a good correlation between the level of the metabolite amrubicinol in the tumor and the in vivo efficacy. High metabolic activity of amrubicin to amrubicinol was detected in tumor tissue homogenates, especially in cell lines highly sensitive to amrubicin in vivo. In contrast to amrubicin, the administration of amrubicinol showed less tumor-selective toxicity in these human tumor xenograft models. These data indicate that the tumor-selective metabolism of amrubicin to amrubicinol resulted in a tumor-selective disposition of amrubicinol, leading to good efficacy in in vivo experimental therapeutic models.

Animals↗

PubMed1998

Tumor-selective distribution of an active metabolite of the 9-aminoanthracycline amrubicin.

It has been reported that the 9-aminoanthracycline amrubicin shows good efficacy in human tumor xenograft models. We studied the disposition and metabolism of amrubicin in mice, in comparison with those of doxorubicin. Amrubicinol, a 13-hydroxy metabolite of amrubicin, which is 10 to 100 times more cytotoxic than amrubicin, was detected as a major metabolite in blood and tissues, and aglycones of amrubicin were also detected. A pharmacokinetic study revealed that amrubicin had a smaller distribution volume and a shorter half-life than doxorubicin. In several normal tissues, the levels of amrubicin and amrubicinol were lower than those of doxorubicin. In contrast, the tumor levels of amrubicinol in the mice treated with amrubicin were higher than those of doxorubicin in the mice treated with that drug, in tumors that are sensitive to amrubicin. These results suggest that the potent therapeutic activity of amrubicin is caused by the selective distribution of its highly active metabolite, amrubicinol, in tumors.

Animals↗

PubMed1998

Cytotoxicity of amrubicin, a novel 9-aminoanthracycline, and its active metabolite amrubicinol on human tumor cells.

Amrubicin, a completely synthetic 9-aminoanthracycline derivative, was previously shown to have potent antitumor activities against various human tumor xenografts. In this study, the in vitro activities of amrubicin and its major metabolite, amrubicinol, were examined using 17 human tumor cell lines. Amrubicinol was 5 to 54 times more potent than amrubicin, and as potent as doxorubicin, in inhibiting the growth of the cells following 3-day continuous drug exposure. Amrubicinol closely resembled doxorubicin in its profile of activities on the 17 human tumor cell lines. Cells were incubated with the drugs for 1 h, and the intracellular drug concentration and cell growth inhibition after 3 days were determined. Amrubicinol attained similar intracellular concentrations at lower medium concentrations compared to amrubicin, and the intracellular concentration of amrubicinol necessary to produce 50% cell growth inhibition was 3 to 8 times lower than that of amrubicin in 4 cell lines tested. Amrubicinol has a higher activity level inside the cells than does amrubicin. When cells were incubated with amrubicin for 5 h, a substantial amount of amrubicinol, more than 9% of that of amrubicin, was found in cells in 4 of the 8 cell lines tested. Amrubicinol may contribute to the in vitro growth-inhibitory effect of amrubicin on these cells. The results suggest that amrubicinol plays an important role in the in vivo antitumor effect of amrubicin as an active metabolite.

Anthracyclines↗

PubMed1998

A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex.

Amrubicin is a novel, completely synthetic 9-aminoanthracycline derivative. Amrubicin and its C-13 alcohol metabolite, amrubicinol, inhibited purified human DNA topoisomerase II (topo II). Compared with doxorubicin (DXR), amrubicin and amrubicinol induced extensive DNA-protein complex formation and double-strand DNA breaks in CCRF-CEM cells and KU-2 cells. In this study, we found that ICRF-193, a topo II catalytic inhibitor, antagonized both DNA-protein complex formation and double-strand DNA breaks induced by amrubicin and amrubicinol. Coordinately, cell growth inhibition induced by amrubicin and amrubicinol, but not that induced by DXR, was antagonized by ICRF-193. Taken together, these findings indicate that the cell growth-inhibitory effects of amrubicin and amrubicinol are due to DNA-protein complex formation followed by double-strand DNA breaks, which are mediated by topo II.

Anthracyclines↗

PubMed1998

Age at onset of delusional disorder is dependent on the delusional theme.

The main aim of this study was to investigate whether or not subtypes of delusional disorder diagnosed by DSM-III-R show differences in age at onset and sex distribution. All out-patients first seen at the psychiatry clinic between 1989 and 1994 were diagnosed by DSM-III-R. Of 4144 out-patients, 51 patients (1.2%) were selected as having delusional disorder, and the demographic data and clinical profiles for these subjects were evaluated prospectively by the psychiatrists. Females outnumbered males by a ratio of 3:1. The type of delusional disorder most frequently encountered was the persecutory type, followed by the somatic type, jealous type and unspecified type. The age at onset differed significantly according to the type of delusional disorder, the oldest age at onset being associated with the persecutory type, and the youngest with the somatic type.

Adult↗

PubMed1998

Involvement of prostaglandin E2 and interleukin-1 alpha in the differentiation and survival of osteoclasts induced by lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4.

Lipopolysaccharide (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions. LPS from various periodontal pathogens is supposed to be a major virulence factor of periodontal diseases. In the present study, we demonstrated that LPS from periodontopathic bacterium Actinobacillus actinomycetemcomitans Y4 (Y4 LPS) stimulated osteoclast formation in mouse bone marrow culture systems. Addition of anti-interleukin-1 alpha (IL-1 alpha) antibody or indomethacin in the marrow cultures resulted in the suppression of osteoclast differentiation. Quantitative analyses revealed that Y4 LPS stimulated the production of IL-1 alpha and prostaglandin E2 (PGE2) by bone marrow cells. Furthermore, an immunoblot analysis showed that Y4 LPS stimulated bone marrow cells to upregulate the expression of cyclooxygenase-2, a rate-limiting enzyme for the conversion of arachidonic acid to prostanoids. These findings suggest that both IL-1 alpha and PGE2 are involved in the LPS-mediated osteoclast differentiation. In addition, we found that Y4 LPS supported the survival of osteoclasts. Addition of anti-IL-1 alpha antibody in the osteoclast culture resulted in a reduction of osteoclast survival. Indomethacin, however, showed no effect on osteoclast survival. These findings suggest that the increased PGE2 and IL-1 alpha synthesis by bone marrow cells may play an important role in the differentiation and survival of osteoclasts induced by A. actinomycetemcomitans LPS.

Aggregatibacter actinomycetemcomitans↗

PubMed1998

Actinobacillus actinomycetemcomitans toxin induces both cell cycle arrest in the G2/M phase and apoptosis.

We found that the culture supernatant of the periodontopathic bacterium Actinobacillus actinomycetemcomitans had a cytotoxic effect on several cell lines. In this study, we purified the toxin from the culture supernatant of A. actinomycetemcomitans Y4 by a four-step procedure: ammonium sulfate precipitation, POROS HQ/M column chromatography, polymyxin B matrix column chromatography, and Mono-Q column chromatography. The purified toxin gave two major bands of protein with molecular masses of 80 and 85 kDa upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mechanism of cell death of the B-cell hybridoma cell line HS-72 was examined by observing changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of degraded chromosomal DNA, indicating the induction of apoptosis. Overexpression of human Bcl-2 suppressed apoptosis in HS-72 cells, indicating that the toxin from A. actinomycetemcomitans induces apoptosis by a Bcl-2-inhibitable mechanism. Flow cytometric analysis revealed that the toxin caused cell cycle arrest in the G2/M phase and apoptosis in HS-72 cells. In addition, aurintricarboxylic acid, a DNA endonuclease inhibitor, markedly decreased the percentage of apoptotic cells but had no effect on cell cycle arrest in the G2/M phase. Taken together, these findings suggest that the toxin from A. actinomycetemcomitans could mediate the development of periodontal diseases through cell cycle arrest in the G2/M phase and apoptosis in B lymphocytes of periodontal tissue.

Aggregatibacter actinomycetemcomitans↗

PubMed1998

Effect of hypoxia on pulmonary blood flow-segmental vascular resistance relationship in perfused cat lungs.

To investigate the effect of alveolar hypoxia on the pulmonary blood flow-segmental vascular resistance relationship, we determined the longitudinal distribution of vascular resistance while increasing blood flow during hyperoxia or hypoxia in perfused cat lungs. We measured microvascular pressures by the micropipette servo-null method, partitioned the pulmonary vessels into three segments [i.e., arterial (from main pulmonary artery to 30- to 50-micron arterioles), venous (from 30- to 50-micron venules to left atrium), and microvascular (between arterioles and venules) segments] and calculated segmental vascular resistance. During hyperoxia, total resistance decreased with increased blood flow because of a reduction of microvascular resistance. In contrast, during hypoxia, not only microvascular resistance but also arterial resistance decreased with increase of blood flow while venous resistance remained unchanged. The reduction of arterial resistance was presumably caused by arterial distension induced by an elevated arterial pressure during hypoxia. We conclude that, during hypoxia, both microvessels and arteries >50 micron in diameter play a role in preventing further increases in total pulmonary vascular resistance with increased blood flow.

Animals↗

PubMed1998

Phosphopentomutase of Bacillus stearothermophilus TH6-2: the enzyme and its gene ppm.

Phosphopentomutase catalyzes the transfer of an intramolecular phosphate on ribose or deoxyribose, and is involved in the salvage pathway of nucleoside synthesis. We identified a sequence 5'-upstream of the genes for the nucleoside phosphorylases of Bacillus stearothermophilus as the phosphopentomutase (ppm) gene. The novel gene corresponded to an open reading frame of 1,179 nucleotides that is translated into a putative 393-amino acid protein with a molecular weight of 43,735. The gene product, partially purified from ppm-overexpressing Escherichia coli cells, was judged to be a monomer of a 44-kDa polypeptide. The phosphopentomutase was found to catalyze the phosphotransfer on not only ribose or deoxyribose but also arabinose or dideoxyribose.

Amino Acid Sequence↗

PubMed1998

Use of Escherichia coli polyphosphate kinase for oligosaccharide synthesis.

The Escherichia coli polyphosphate kinase (PPK) has been known to catalyze the reversible transfer of phosphate molecules between ATP and polyphosphate (poly(P)). It has also been found that the PPK catalyzes the kination of not only ADP but also other nucleoside diphosphates (NDPs) using poly(P) as a phosphate donor, yielding nucleotide triphosphates (NTPs). We used the PPK and poly(P) in place of pyruvate kinase and phosphoenol pyruvate for NTP regeneration followed by synthesis of sugar nucleotides in a cyclic synthesis system for oligosaccharides. It was confirmed that the PPK efficiently catalyzed the UTP regeneration in the cyclic system of N-acetyllactosamine synthesis. This novel activity of PPK enables us to perform the practical synthesis of oligosaccharides.

Adenine Nucleotides↗

PubMed1998

Effects of nasal continuous positive airway pressure therapy on respiratory parameters of upper airway patency in patients with obstructive sleep apnea syndrome.

OBJECTIVES: To assess whether an initial treatment with nasal continuous positive airway pressure (NCPAP) therapy, applied for one night, had any effect on airway patency. METHODS: In 18 patients with obstructive sleep apnea syndrome (OSAS), we measured the total resistance of the respiratory system (Rrs) and their relevant lung functions before and after polysomnography, with and without NCPAP therapy. The Rrs was measured at 3 Hz with the forced oscillation technique. The overnight changes in the specific respiratory conductance (SGrs=reciprocal of the Rrs per unit lung volume) was also calculated in the sitting position. Since many reports have suggested that obesity, through fat deposits around the pharynx, can affect the mechanical and neuromuscular properties of the upper airway, we also investigated if the degree of obesity was related to the magnitude of improvement in these parameters. RESULTS: After the first night of NCPAP therapy, the Rrs decreased (sitting: 4.8+/-0.4 vs 4.3+/-0.4 cm H20/L/s, p < 0.05; lying: 6.5+/-0.4 vs 5.6+/-0.4 cm H20/L/s, p < 0.05) and the maximal voluntary ventilation increased in the morning (sitting: 101.6+/-5.8% vs 106.4+/-4.5%, p < 0.05; lying: 91.2+/-5.4% vs 97.9+/-4.7%, p < 0.05). The overnight difference in the SGrs showed a significant improvement after the initial treatment with NCPAP therapy (p < 0.05). However, the lung volume, flow volume loop, and closing volume in the morning did not change significantly after the therapy. An overnight decrease in the Rrs following NCPAP therapy is significantly correlated with the body mass index (sitting: r=0.54, p < 0.05; lying: r=0.61, p < 0.01). CONCLUSION: The improvements in Rrs without changes in spirometry may reflect improved upper airway patency after NCPAP therapy. The degree of obesity is suggested to be associated with the treatment effect on upper airway in patients with OSAS.

Adult↗

PubMed1998

Insulin-like growth factor-I potentiates protein synthesis induced by thyrotropin in FRTL-5 cells: comparison of induction of protein synthesis and DNA synthesis.

In FRTL-5 cells, we and others have shown that TSH and insulin-like growth factor-I (IGF-I) stimulate DNA synthesis synergistically. The present study was undertaken to determine whether interaction between TSH and IGF-I also affects protein synthesis in this cell line, and if so by what mechanism. Quiescent cells were treated with TSH and/or IGF-I and [3H]valine incorporation into the acid-insoluble fraction was measured as a parameter of protein synthesis. Similar to their effects on cell proliferation, TSH or IGF-I alone induced protein synthesis only slightly, but treatment with a combination of TSH and IGF-I (or insulin with about a 100-fold higher concentration than IGF-I) greatly increased protein synthesis. The presence of IGF-I potentiated a TSH-concentration-dependent increase in protein synthesis and in DNA synthesis. In addition, we observed this potentiation when the cells were treated with other cAMP-generating agents and cAMP analogues instead of TSH. We have shown that priming with TSH potentiated DNA synthesis induced by IGF-I, whereas pretreatment with IGF-I enhanced protein synthesis induced by TSH. This observation suggested that protein synthesis and DNA synthesis were potentiated through different mechanisms. From an analysis of cAMP production, it appears that the potentiation of protein synthesis may be explained by an IGF-I-dependent increase in cAMP production induced by TSH at least in part. On the other hand, IGF-I and TSH stimulated (alpha-aminoisobutyric acid (AIB) uptake synergistically, but RNA synthesis induced by IGF-I was depressed by TSH. From these results, we concluded that in FRTL-5 cells, IGF-I potentiated protein synthesis induced by TSH by means of complex mechanisms and the interaction between IGF-I and cAMP-dependent pathways may also have a physiological meaning in regulating protein anabolism.

Animals↗