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Biomedical subjects

S Teramoto

Publications and source records attributed to S Teramoto.

At least 55 records · Page 3Linked to original sources

Inhibitory effects of angiotensin-converting enzyme (ACE) inhibitors on oxygen radicals produced by bronchoalveolar lavage cells in young and aged guinea pigs.

We examined the effect of angiotensin-converting enzyme (ACE) inhibitors and age on oxygen radical formation by bronchoalveolar lavage (BAL) cells. Lung-free cells, including pulmonary alveolar macrophages, were harvested from young (4-month-old) and aged (28-month-old) male guinea pigs using BAL. The oxygen radicals produced by BAL cells were measured by a lucigenin-dependent chemiluminescence method using a photon counter. Although spontaneous oxygen radical production by BAL cells from young and aged guinea pigs did not differ, the oxygen radical generation after maximal stimulation with phorbol-myristate acetate (PMA) was greater than that produced without PMA stimulation in both young and aged animals. ACE inhibitors with and without an SH-group (alacepril and lisinopril, respectively) were tested for their effect on oxygen radical formation by BAL cells; both ACE inhibitors inhibited oxygen radical production and generation by BAL cells from both young and aged guinea pigs in a dose-dependent manner. However, the alacepril concentration giving 50% inhibition (IC50) of oxygen radical generation by BAL cells was smaller than the IC50 of lisinopril in both young and aged guinea pigs. These results indicate that ACE inhibitors, in particular those with an SH-group, effectively reduce oxygen radical production by BAL cells from young and aged guinea pigs, and suggest that treatment with ACE inhibitors may be useful for ameliorating oxidant-associated pulmonary disorders in young and aged patients.

Aging↗

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↗

Pulmonary veno-occlusive disease in pulmonary Langerhans' cell granulomatosis.

This report describes unusual clinical and pathological findings in a 29-yr-old female with pulmonary Langerhans' cell granulomatosis (LCG). During a 7-yr clinical course her condition deteriorated despite corticosteroid therapy, and she died of respiratory failure and pulmonary hypertension. At autopsy, there were widespread pulmonary veno-occlusive disease (PVOD) lesions as well as abundant advanced and healed lesions of pulmonary LCG composed of multiple cysts and stellate fibrosis. The present case demonstrates that pulmonary Langerhans' cell granulomatosis should be considered as a possible cause of pulmonary veno-occlusive disease.

Adult↗

Characterization of a novel nonpeptide vasopressin V(2)-agonist, OPC-51803, in cells transfected human vasopressin receptor subtypes.

We discovered the first nonpeptide arginine-vasopressin (AVP) V(2)-receptor agonist, OPC-51803. Pharmacological properties of OPC-51803 were elucidated using HeLa cells expressing human AVP receptor subtypes (V(2), V(1a) and V(1b)) and compared with those of 1-desamino-8-D-arginine vasopressin (dDAVP), a peptide V(2)-receptor agonist. OPC-51803 and dDAVP displaced [(3)H]-AVP binding to human V(2)- and V(1a)-receptors with K(i) values of 91.9+/-10.8 nM (n = 6) and 3.12+/-0.38 nM (n = 6) for V(2)-receptors, and 819+/-39 nM (n = 6) and 41.5+/-9.9 nM (n = 6) for V(1a)-receptors, indicating that OPC-51803 was about nine times more selective for V(2)-receptors, similar to the selectivity of dDAVP. OPC-51803 scarcely displaced [(3)H]-AVP binding to human V(1b)-receptors even at 10(-4) M, while dDAVP showed potent affinity to human V(1b)-receptors with the K(i) value of 13.7+/-3.2 nM (n = 4). OPC-51803 concentration-dependently increased cyclic adenosine 3', 5'-monophosphate (cyclic AMP) production in HeLa cells expressing human V(2)-receptors with an EC(50) value of 189+/-14 nM (n = 6). The concentration-response curve for cyclic AMP production induced by OPC-51803 was shifted to the right in the presence of a V(2)-antagonist, OPC-31260. At 10(-5) M, OPC-51803 did not increase the intracellular Ca(2+) concentration ([Ca(2+)](i)) in HeLa cells expressing human V(1a)-receptors. On the other hand, dDAVP increased [Ca(2+)](i) in HeLa cells expressing human V(1a)- and V(1b)-receptors in a concentration-dependent fashion. From these results, OPC-51803 has been confirmed to be the first nonpeptide agonist for human AVP V(2)-receptors without agonistic activities for V(1a)- and V(1b)-receptors. OPC-51803 may be useful for the treatment of AVP-deficient pathophysiological states and as a tool for AVP researches.

Arginine Vasopressin↗

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↗

Detection of aspiration and swallowing disorder in older stroke patients: simple swallowing provocation test versus water swallowing test.

OBJECTIVE: To assess the sensitivity and specificity of a simple swallowing provocation test (SPT) and a water swallowing test (WST) in detecting aspiration pneumonia in elderly patients with stroke. DESIGN: Retrospective comparative study involving a simple 2-step SPT and WST on all subjects. PARTICIPANTS: Twenty-six stroke patients with aspiration pneumonia (mean age, 72.1 +/- 4.1 yr) and 26 age-matched stroke patients without aspiration pneumonia (mean age, 69.4 +/- 3.9 yr). INTERVENTIONS: The normal response to SPT was determined by inducing swallowing reflex within 3 seconds after water injection into the suprapharynx. In WST, subjects drank quantities of 10 and 30 mL of water from a cup within 10 seconds. The subject who drank water without interruption-without evidence of aspiration-was determined as normal. RESULTS: The sensitivity and specificity of first-step SPT for the detection of aspiration pneumonia were 100% and 83.8%, respectively. Those of the second-step SPT were 76.4% and 100%, respectively. The sensitivity and specificity of first-step WST using 10 mL of water for the detection of aspiration pneumonia were 71.4% and 70.8%, respectively. Those of the second-step WST using 30 mL of water were 72% and 70.3%, respectively. CONCLUSION: SPT is more useful than WST in differentiating patients predisposed to aspiration.

Aged↗

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↗

Effects of naturally-occurring acid fog on inflammatory mediators in airway and pulmonary functions in asthmatic patients.

Floating fog occurs every summer in Kushiro City in Japan, and the annual average of fog water pH in the past 4 years has been under 5.0. We previously reported that epidemiologically fog was the most important positive factor contributing to increased hospital visits of asthmatic patients compared with other meteorological values and air pollutants. This study aimed to investigate the mechanism of the effects of naturally-occurring acid fog on asthmatic patients. We compared pulmonary functions and inflammatory mediators in induced sputum between the foggy (July 1995) and the non-foggy (May 1996) season, and assessed airway responsiveness to hypo-osmolar aerosol. Forty-four out of 118 asthmatic patients of Kushiro City residents participated, pulmonary function tests were completed in 36 patients, and sputum data were available in 26 patients in both seasons. Percent forced expiratory volume in 1 sec (FEV1) was significantly (P< 0.05) decreased, and % peak expiratory flow rate (PEFR) had a trend to decrease in the foggy season more than in the non-foggy, and sputum eosinophil cationic protein (ECP) and interleukin (IL)-8 were higher in the foggy season but not significantly. A moderate inverse correlation was revealed between sputum ECP and %PEFR in the foggy season (r= -0.55, P<0.005). Subjects were divided into two groups according to the best PEFR; one had >10% lower PEFR levels in the foggy season than in the non-foggy season (Group A, n = 7), the remainder did not (Group B, n = 19). In group A, sputum ECP was significantly increased (P< 0.01) in the foggy season, but there were no changes in IL-8 and prostaglandin D2. Ultrasonic nebulized distilled water provocation test revealed no differences between group A and B. These results suggested that eosinophilic inflammation rather than hypo-osmolar effect of fog might contribute to respiratory deterioration by inhalation of naturally-occurring acid fog.

Acid Rain↗

Neurokinin-1 receptor antagonist inhibits short-term sulfuric-acid-induced airway hyperresponsiveness in sensitized guinea pigs.

BACKGROUND: Tachykinins are involved in the development of bronchial inflammation and airway hyperresponsiveness (AHR); however, the role of the neurokinin-1 (NK(1)) receptor in acid-aerosol-induced bronchial impairment in asthmatic patients remains controversial. METHODS: To investigate the effects on the NK(1) receptor antagonist FK888 the neurokinin-2 (NK(2)) receptor antagonist SR48968 on sulfuric-acid (H(2)SO(4))-induced AHR in guinea pigs, specific airways resistance (sRaw) and airways responsiveness to methacholine (MCh) were measured before and after 6 h of exposure to H(2)SO(4) aerosol (pH 1.7, 82 mg/m(3)) in ovalbumin-sensitized guinea pigs. RESULTS: Airway responsiveness to MCh significantly increased (p<0. 05) after the exposure, however sRaw did not. Treatment with FK888 significantly inhibited (p<0.05) H(2)SO(4)-induced AHR in a dose-dependent manner, as did SR48968. CONCLUSIONS: These results suggest that not only NK(2) but also NK(1) receptors might have important roles in the development of acid-aerosol-induced AHR.

Aerosols↗

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↗

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↗

Recombinant adeno-associated virus vectors efficiently transduce foreign gene into bovine aortic endothelial cells: comparison with adenovirus vectors.

Because the features and kinetics of adeno-associated virus (AAV)-mediated gene transfer to endothelial cells (EC) are yet to be ultimately determined, we tested variables pertinent to the efficiency of AAV-mediated gene transfer to bovine aortic endothelial cells (BAEC). The variables with AAV vectors were compared with the better characterized adenovirus (Ad) vectors. There is a dose-response relationship between multiplicity of infection (moi) of AAV or Ad vectors and transduction efficiency in BAEC. The higher moi of AAV vectors achieved more than 80% of transduction efficiency in cultured BAEC. AAV and Ad vectors showed an incubation-time-dependent increase in transduction efficiency of LacZ gene to the BAEC up to 12 h of vector exposure. Although the similar kinetics of transduction efficiency of LacZ gene to BAEC was found in both vectors, the duration of gene expression was longer in AAV vector than that in Ad vectors in vitro. These results indicate that AAV-vector is efficient for gene transfer to EC, and higher moi of vectors or a longer period exposure of vectors to EC can facilitate efficient transduction of a foreign gene into cultured EC. For the duration of gene expression, the AAV vectors may be better than Ad vectors.

Adenoviridae↗