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Biomedical subjects

Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT) locus.

Calcitonin (CT), a calcium-regulating hormone, lowers the calcium level in serum by inhibiting bone resorption. Because CT may play a role in the pathogenesis of osteoporosis, genetic variations in or adjacent to the CT gene may be associated with variations in bone mineral density (BMD). The present study examined the correlation between a dinucleotide (cytosine-adenine; CA) repeat polymorphism at the CT locus and BMD in 311 Japanese postmenopausal women (mean age, 64.1 years). Seven alleles were present in this population; each allele contained 10, 11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated the respective genotypes A10, A11, A16, A17, A18, A19, and A20. The A10 and A17 alleles were the predominant alleles in the population studied. Z scores (a parameter representing deviation from the age-specific weight-adjusted average BMD) were compared between individuals that possessed one or two alleles of each genotype and those that did not possess the allele. Subjects who possessed one or two A10 alleles had lower BMD Z scores than those who did not (lumbar 2-4 BMD Z score; -0.148 +/- 1.23 vs 0.182 +/- 1.54; P = 0.04). No significant relationships were observed between allelic status and background data or biochemical parameters. The significant association observed between BMD and genetic variations at the CT locus implies that polymorphism at this locus may be a useful marker for the genetic study of osteoporosis.

Aged↗
PubMed2000

Influence of sex and age on serum nitrite/nitrate concentration in healthy subjects.

Measurement of serum nitrite/nitrate (NOx) concentrations has been considered useful to estimate nitric oxide production in humans. However little is known about the physiologic range and the factors affecting serum NOx levels. The aim of this study was, thus, to investigate the influence of sex and age on serum NOx levels in healthy subjects. We selected 263 healthy subjects (118 women and 145 men, 20-69 y) from 505 consecutive subjects who received annual medical checkups at our hospital. Serum NOx levels were determined using an analyzer employing the Griess method. The linear regression analysis showed that NOx increased significantly according to age in women (r=0.22, P<0.05), but did not in men (P=NS). Women of the younger age group (<40 y) showed significantly lower NOx levels than men of the same age group (P<0.05), whereas there was no significant difference between men and women of the older age (> or =40 y). Then, to investigate whether menopause affects serum NOx levels, middle aged women (46-55 y) were selected. Multiple logistic regression analysis showed that menopause was an independent factor for increased serum NOx levels in middle aged women (r=0.4, P<0.05). These results suggest that the serum NOx concentration is affected by age in healthy women, possibly depending on menopausal state.

Age Factors↗
PubMed2000

Expression of parathyroid hormone-related protein in human and experimental atherosclerotic lesions: functional role in arterial intimal thickening.

We investigated the expression of parathyroid hormone-related protein (PTHrP) in atherosclerotic lesions and the role of PTHrP in the development of arterial neointima formation. Immunohistochemical staining of PTHrP in the neointima of rat aorta produced by balloon injury and of rat femoral artery produced by non-obstructive polyethylene cuff placement, and in the atherosclerotic lesion of human coronary artery was performed using anti-human PTHrP-(1-34) antibody. Anti-muscle actin antibody, HHF-35, and anti-macrophage antibody, HAM-56, were used to identify smooth muscle cells and macrophages, respectively. Immunoreactivity of PTHrP was detected in the thickened intima of rat and human lesions where the predominant cell types were smooth muscle cells or macrophages dependently on the lesion type. In the next series of experiments, we examined the effect of PTHrP on the development of cuff-induced intimal thickening of rat femoral artery. Either PTHrP-(1-34) or PTHrP-(7-34), a PTH/PTHrP receptor antagonist, suspended in pluronic F-127 gel was locally applied around the rat femoral artery. Intimal thickening induced by cuff placement was evaluated 2 weeks later. PTHrP-(1-34) dose-dependently inhibited intimal thickening determined as intima/media ratio and % stenosis whereas PTHrP-(7-34) dose-dependently enhanced that. These results suggest that PTHrP, which is expressed in atherosclerotic lesions, inhibits the development of neointimal formation.

Analysis of Variance↗
PubMed2000

Activin receptors are expressed on human lung fibroblast and activin A facilitates fibroblast-mediated collagen gel contraction.

Activin A is a member of the transforming growth factor-beta superfamily that exerts its diverse biological effects through bindings to activin specific transmembrane serine/threonine kinase receptors. The fibroblast-mediated contraction of a collagen gel is thought to be a model of part of the wound-repair response and tissue contraction. In this study, we found the expression of activin type I receptors (ActR-I and ActR-IB) and type II receptor (ActR-II) on human fetal lung fibroblasts (HFL-1) by RT-PCR and immunocytochemistry. We also examined the effects of activin A on the HFL-1-mediated collagen gel contraction. Activin A stimulated collagen gel contraction in a dose dependent manner and its effect was abolished by an activin-binding protein, follistatin, that specifically suppresses activin A activities. This study demonstrated that ActR-I, ActR-1B and ActR-II are expressed on human fetal lung fibroblast and that activin A regulates fibroblast-mediated collagen gel contraction, suggesting that activin A might contribute to human lung fibroblast activities and structural remodeling observed in pulmonary fibrosis.

Activin Receptors↗
PubMed2000

Efficient HPLC separation of [11C]beta-CFT or [11C]beta-CIT from an N-desmethyl precursor on a semipreparative reversed phase ODS column.

HPLC separation of either [11C]beta-CFT or [11C]beta-CIT from the N-desmethyl precursor greatly depended on the ODS column used and the pH of the phosphate buffer in the mobile phase. The separation was accomplished on the semipreparative reversed phase ODS column without end-capping treatment over a pH ranging from 6.4 to 9.2, but failed on the end-capped ODS column. This suggests that the presence of residual silanol groups on the ODS is an important factor for the separation.

Carbon Radioisotopes↗
PubMed2000

Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2.

Adult respiratory distress syndrome (ARDS) is characterized by acute lung injury with a high mortality rate and yet its mechanism is poorly understood. Sepsis syndrome and acid aspiration are the most frequent causes of ARDS, leading to increased lung permeability, enhanced polymorphonuclear neutrophil (PMN) sequestration and respiratory failure. Using a murine model of acute lung injury induced by septic syndrome or acid aspiration, we investigated the role of cytosolic phospholipase A2 (cPLA2) in ARDS. We found that disruption of the gene encoding cPLA2 significantly reduced pulmonary edema, PMN sequestration and deterioration of gas exchange caused by lipopolysaccharide and zymosan administration. Acute lung injury induced by acid aspiration was similarly reduced in mice with a disrupted cpla2 gene. Our observations suggest that cPLA2 is a mediator of acute lung injury induced by sepsis syndrome or acid aspiration. Thus, the inhibition of cPLA2-initiated pathways may provide a therapeutic approach to acute lung injury, for which no pharmaceutical agents are currently effective.

Animals↗
PubMed2000

Association between alpha-1-antichymotrypsin polymorphism and susceptibility to chronic obstructive pulmonary disease.

BACKGROUND: The antiproteases, including alpha-1-antitrypsin, are supposed to prevent lungs from becoming emphysematous. Genetic susceptibility to smoking injury may confer a risk for the development of chronic obstructive pulmonary disease (COPD). METHODS: We have investigated the association between the polymorphism of alpha-1-antichymotrypsin (AACT), one of the antiproteases, and susceptibility to the development of COPD among heavy smokers. Blood samples obtained from both patients with COPD (n = 53) and control subjects (n = 65) at the Tokyo University Hospital, the Juntendo University Hospital and the Tokyo Kenbikyoin Clinic were used for this genotyping assay. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype the AACT biallelic polymorphism in the signal peptide (-15 alanine to threonine), and the two polymorphisms of the exon (Pro229Ala and Leu55Pro). RESULTS: The proportion of AACT/Ala-15 homozygotes was significantly higher in the COPD patients than in the control subjects (COPD 37.7% vs. control 18.5%). The odds ratio for AACT/Ala-15 homozygotes vs. all other genotypes was 2.7 (95% CI 1.2-6.2) for the COPD group. We could not find any association between the other two polymorphisms and COPD. CONCLUSIONS: Genetic polymorphism in the signal peptide of AACT may be associated with individual susceptibility to the development of COPD, because the AACT/Ala-15 genotype is predominantly found in patients with COPD. It is suggested that AACT/Ala-15 genotype may be less protective against smoking injury.

Adult↗
PubMed2000

Neither IL-1beta, IL-1 receptor antagonist, nor TNF-alpha polymorphisms are associated with susceptibility to COPD.

The cytokines that contribute to airway inflammation, including interleukin-1beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha), might have key roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin-1 receptor antagonist (IL-1RN), the physiological antagonist of IL-1beta, is also known to play a crucial role in several chronic inflammatory diseases. In this study, we investigated the association of the polymorphisms of IL-1beta, IL-1RN and TNFalpha with susceptibility to COPD. To elucidate the genotype of the IL-1beta polymorphisms at position -511 base and at the amino acid residue 105, the IL-1RN polymorphism in intron 2, and TNFalpha polymorphism at position -308, polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) were performed on blood samples from both patients with COPD (n = 53) and control subjects (n = 65). There were no differences on the allele and genotype frequency of IL-1beta, IL-1RN, and TNFalpha between the two groups. We could not find a significant link between the polymorphism of TNFalpha, which was previously reported to be associated with chronic bronchitis, and COPD. Furthermore, no association between genetic polymorphisms of IL-1beta and IL-1RN and individual susceptibility to COPD was found.

Aged↗
PubMed2000

Effect of ions on antibacterial activity of human beta defensin 2.

Human beta defensin 2 (HBD-2), the most recently discovered human defensin, has been considered to work as a host defense substance against microbial infection. Using Escherichia coli ATCC 25922, we investigated how some cations and anions influenced the antimicrobial activity of HBD-2. This activity, measured in 10 mM phosphate buffer at a concentration of 20 microg/ml, reduced significantly in the presence of 100 and 150 mM sodium or potassium chloride. The reduction was not significantly different when the total amounts of sodium and potassium ions were equal. The kind and the valence of anions (chlorine and sulfate ions) did not affect the bactericidal activity as long as the concentrations of sodium ions were equal. Divalent ions (calcium and magnesium ions) added to 10 mM of Tris buffer significantly inactivated HBD-2 at much lower concentrations (more than or equal to 0.01 mM and 0.05 mM, respectively) than the monovalent ions did. These findings suggest that HBD-2 kills the bacteria through at least two phases, which are affected independently by either monovalent or divalent ions and unaffected by anions.

Anti-Bacterial Agents↗
PubMed2000

Chromosome mapping of RNF16 and rnf16, human, mouse and rat genes coding for testis RING finger protein (terf), a member of the RING finger family.

RNF16 (ring finger protein 16; alias terf), a member of the RING finger family, has been shown to be exclusively expressed in the testis. Human RNF16 is located at 1q42 based on PCR-assisted analysis of both a human/rodent mono-chromosomal hybrid cell panel and a radiation hybrid-mapping panel. On the other hand, chromosomal mapping of the RNF16 gene by fluorescence in situ hybridization reveals that mouse Rnf16 is located at 11B1.2-B1.3 and rat Rnf16 at 10q22. These results provide additional evidence that the mouse 11B region displays conserved linkage homology with the rat 10q22 region, whereas in the case of RNF16, this homology is only conserved among rodents, distinct from the 1q42 region of the human genome.

Amino Acid Sequence↗
PubMed2000

Nasal continuous positive airway pressure and weight loss improve swallowing reflex in patients with obstructive sleep apnea syndrome.

We have recently reported that swallowing reflex is impaired in patients with obstructive sleep apnea syndrome (OSAS). However, the effects of OSAS treatment on swallowing function in these patients have not been reported. Here we report 2 cases of OSAS in whom swallowing reflex was impaired before the start of nasal continuous positive airway pressure (NCPAP) and improved 1 year after NCPAP. These cases suggest that impaired swallowing reflex may be reversible by OSAS treatment.

Administration, Intranasal↗
PubMed2000

Effects of angiotensin-converting enzyme inhibitors on spontaneous or stimulated generation of reactive oxygen species by bronchoalveolar lavage cells harvested from patients with or without chronic obstructive pulmonary disease.

We examined the effects of angiotensin-converting enzyme (ACE) inhibitors on spontaneous or stimulated generation of reactive oxygen species (ROS) by bronchoalveolar lavage (BAL) cells prepared from 6 patients with chronic obstructive pulmonary disease (COPD) and from age-matched control subjects without COPD. The ROS produced by BAL cells were measured by the lucigenin-dependent chemiluminescence method. The application of ACE inhibitors into culture media containing BAL cells inhibited spontaneous and stimulated generation of ROS by BAL cells from COPD patients and control subjects in an ambroxol-concentration-dependent manner. Alacepril, an ACE inhibitor bearing SH-group, inhibited the oxygen radical production and generation by BAL cells from COPD patients in a dose-dependent fashion. Approximately 0.6-0.7 mM of alacepril inhibited 50% of the ROS production by BAL cells from COPD patients, whereas a slightly higher concentration (3 mM) of lisinopril, an ACE inhibitor not bearing an SH-group, was necessary to inhibit the production of ROS. These results suggest that an ACE inhibitor may act as an pulmonary antioxidant in patients with COPD.

Aged↗
PubMed2000

Association of coronary risk factors and endothelium-dependent flow-mediated dilatation of the brachial artery.

Impaired endothelial function has been reported to be the initial step in atherosclerosis. Some coronary risk factors independently relate to impaired endothelial function. However, few studies have examined the association between coronary risk factors and endothelial function in patients who have multiple risk factors without clinical atherosclerosis. This study was undertaken to elucidate the relationship between accumulation of coronary risk factors and vascular endothelial dysfunction. We examined 101 subjects with one or more coronary risk factors 56.8 +/- 1.0 years old and 40 age-matched control subjects without coronary risk factors. We measured brachial artery diameter non-invasively using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia caused by endothelium-dependent vasodilatation, and after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. The percentage change in flow-mediated diameter (%FMD; deltaD/D x 100), in subjects with one or more coronary risk factors was significantly lower than that in control subjects(4.8 +/- 0.3% vs. 6.7 +/- 0.5%, p < 0.01). Endothelium-independent vasodilatation by nitroglycerin did not differ between the two groups. Endothelial function was impaired according to the accumulation of coronary risk factors. On multiple regression analysis, the number of risk factors, age, and brachial artery diameter at rest showed significant correlation with %FMD. Our results suggest that an accumulation of coronary risk factors was significantly related to impairment of endothelial function.

Arteriosclerosis↗
PubMed2000

Pericardial constriction due to malignant lymphoma.

We experienced a case of T-cell lymphoma demonstrating diastolic heart failure as an initial manifestation. An 81-year-old Japanese male was admitted to the University of Tokyo Hospital because of progressive dyspnea and general fatigue. Clinical presentation was congestive heart failure and cervical lymphadenopathy. Right heart catheterization revealed "dip and plateau" waveforms in right ventricular pressure, which suggested a constrictive nature of heart failure. Gallium scintigram showed marked uptake in the heart. Biopsy from a cervical lymph node confirmed the diagnosis of malignant lymphoma of T-cell origin. Diastolic heart failure remained after successful chemotherapy. Autopsy revealed pericarditis with severe adhesion of the pericardium and the epicardium.

Aged↗
PubMed2000

[Sleep apnea syndrome and hypertension using desaturation index].

To examine the roles of obstructive apnea (OA) and central apnea (CA) in oxygen desaturation on hypertension and sleep apnea syndrome (SAS), we performed a sleep study on 41 elderly subjects (mean age 69.5 +/- 6.8 years, male:female = 31:10). Nocturnal oxygen desaturation was documented with a pulse oximeter and apneas (OA and CA) were diagnosed on the basis of results of respiratory inductive plethysmography and oronasal flow. Significant desaturation (SDS, greater than 5% drop in SpO2 from baseline value) and desaturation index (DI; epsilon SDS (%) x duration (hour)) were calculated using the continuous nocturnal monitoring system with a pulse oximeter. We defined central type apnea above 50% as the central type group (n = 8, mean age 58.6 +/- 2.9, mean BMI 21.3 +/- 1.0, male:female = 7:1), and obstructive type and mixed type apnea above 50% as the obstructive type group (n = 21, mean age 70.0 +/- 3.2, mean BMI 25.3 +/- 1.0, male:female = 17:4). Other subjects were assigned to the control group (n = 12, mean age 64.3 +/- 2.3, mean BMI 23.8 +/- 1.2, male:female = 7:5). The DI (delta 5%) of the central type was 0.34 +/- 0.17, and that of the obstructive type was 1.78 +/- 0.7 showing a significant increase in the latter compared to the control group (p < 0.02). The DI (< 90%) of the central type was 0.14 +/- 0.07, and that of the obstructive type was 1.72 +/- 0.75, and that of the obstructive type was significantly greater than in the control group (p < 0.05) and central type (p < 0.05). There were 4 cases (33.3%) with hypertension in the control group and 4 cases (50.0%) with hypertension in the central type group, but there were 15 cases (71.4%) with hypertension in the obstructive type group. Hypertensive prevalence in the obstructive group was significantly more than in the control group (p < 0.05). No significant difference in body mass index or age were seen in the obstructive group and control group. There was a significant correlation between mean blood pressure and apnea index (AI). The AI of the hypertensive group was significantly higher than that of the normotensive group (p < 0.001). These results suggest that subjects with significant obstructive apneas may be at greater risk for hypertension than subjects with central apneas and that hypertension in the pathogenesis of SAS may be related to the severity of apneas rather than oxyhemoglobin desaturation.

Adult↗