PubMed Health⌕ Search

Biomedical subjects

E Ohga

Publications and source records attributed to E Ohga.

At least 19 recordsLinked to original sources
PubMed2000

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↗
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

[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↗
PubMed2000

[The relationship between adhesion molecules and hypoxia].

Hypoxia is an essential developmental and physiological stimulus that plays a key role in the pathophysiology of heart attack, cancer and other major causes of mortality. Recently studies have shown that hypoxia itself may directly activate NFk-B. NFk-B sites are also present in the promoter of the ICAM-1 gene. Therefore, it is possible that hypoxia could directly activate the ICAM-1, through activation of NFk-B. Hypoxia-inducible factor 1 is the only known mammalian transcription factor expressed uniquely in response to physiologically relevant levels of hypoxia. In the another cause of the induction of adhesion molecules with hypoxia adhesion molecules are induced by the inflammatory cytokine(IL-1, TNF alpha) that caused with anoxia/reperfusion. The adhesion molecules induced by hypoxia play one of the key rolls of the various diseases. For example the level of cICAM-1 in OSAS patients were increased. These observations suggest that OSAS-induced hypoxia activate adhesion molecules, resulting in the important risk factor of cardiovascular disorders.

Animals↗
PubMed2000

A study on the socio-psychiatric aspects of short-term ARP (Alcohol Rehabilitation Program).

The duration of the majority of Alcohol Rehabilitation Programs (ARP) at major hospitals specializing in this treatment is three months. Recently, however, because of diverse backgrounds and patients needs, long periods of hospitalization have become difficult. In response to this, Okamotodai Hospital initiated a one-month ARP program three years ago. One feature of this program is that it can be freely structured to meet the requirements of individual patients. This study compares the prognosis of patients treated under this one-month program with that of those who have undergone the three-month program. A group of 56 patients who had completed a one-month ARP program during a period of two to three years was compared with a group of 46 patients who had completed a three-month program over a similar period. The backgrounds of the subjects were researched by questionnaire. A comparison of the prognosis of patients in the respective programs showed there was no statistical difference, with a recovery rate of 45% for both programs. Results of this study statistical difference, with a recovery rate of 45% for both programs. Results of this study cannot be generalized, due to the lack of subjects and recovery of questionnaires. Since enforcement of the one-month ARP, increasing number of patients have been using the program. This fact doesn't necessarily show that the use of ARP improve, although the possibility remains that utilization of the one-month ARP is promoted. In recent years, utilization of brief intervention has been demonstrated and recovery from alcoholism in the outpatient clinics reported. Considering such things, results of the study show that the one-month ARP is a valid and effective program.

Adult↗
PubMed1999

Recombinant E1-deleted adenovirus vector induces apoptosis in two lung cancer cell lines.

Although replication-defective adenoviruses (Ads) are used as vectors for delivering therapeutic genes to cancer cells, various effects of the viruses on the proliferation of lung cancer cells have been reported. Experiments were carried out to determine whether or not E1-deleted Ad vectors (Ad5-CMV-lacZ) affected cell kinetics in two different types of lung cancer cell line in vitro. A dose-dependent relationship was measured between the vector multiplicity of infection (MOI) and the efficiency of lacZ gene transfer to lung cancer cells. The growth curves of vector-infected cells were shifted to the right compared with those of vehicle-exposed cells in a vector MOI-dependent fashion. The slowed cell proliferation resulted from both increased cell death and slower cell cycle progression of the vector-infected cells. The morphology of vector-exposed cells revealed apoptotic features including nuclear condensation and fragmented nuclei. These results indicate that using a higher vector MOI causes a higher gene transfer rate, but may induce apoptosis of infected cells. Although vector-induced apoptosis may be advantageous in inhibiting tumour growth, apoptosis of vector-infected cells may also reduce transgene expression in cancer cells. Minimization of the induction of apoptosis of vector-infected cells is important for the prolongation of the transduction efficiency of Ad vectors.

Adenoviruses, Human↗
PubMed1999

A novel model of aspiration in young and old guinea-pigs using LacZ gene transduction of adenovirus vector.

The effects of anaesthesia on upper airway reflexes in older animals have not been elucidated fully. We studied young (4-month-old) and old (28-month-old) guinea-pigs to examine the relationship between aspiration and altered upper airway reflexes during anaesthesia. We administered an adenovirus vector carrying Escherichia coli LacZ gene (Ad vector) intranasally to guinea-pigs with or without anaesthesia. LacZ gene expression was investigated in the nostrils and lungs of each animal under anaesthesia. No LacZ gene expression was found in the lungs of unanaesthetized animals given Ad vector. Thus intranasal administration of Ad vector was aspirated into the lower airways under anaesthesia. Next we examined the effect of age on anaesthesia-induced aspiration. At a lower concentration of halothane in 100% oxygen, greater LacZ gene expression in the lungs was measured in older than in younger animals, suggesting that older animals are liable to aspirate oropharyngeal contents into the lower airways during light anaesthesia. This novel animal model of aspiration using Ad vector may be useful to explore the mechanism of aspiration during and after anaesthesia in young and old animals.

Age Factors↗
PubMed1999

Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) may be one of the most important risk factors of cardiovascular disorders, although the exact mechanism remains to be elucidated. In the present study, we hypothesized that OSAS-induced hypoxic stress might be involved in the etiology of cardiovascular disorders by activating adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and L-selectin. To examine this hypothesis, we measured circulating ICAM-1, VCAM-1, and L-selectin levels before and after sleep in OSAS patients and age-matched controls. The circulating ICAM-1, VCAM-1, and L-selectin levels increased in the OSAS patients before sleep compared with the normal subjects (ICAM-1: 392.9 +/- 48.5 vs. 201.2 +/- 55.0 ng/ml, P < 0.05; VCAM-1: 811.0 +/- 87.8 vs. 574.2 +/- 42.7 ng/ml, P < 0.05; L-selectin: 1,386.6 +/- 77.9 vs. 1,038.8 +/- 78.6 ng/ml, P < 0.01, respectively). After sleep, significantly greater levels of ICAM-1 and L-selectin, but not VCAM-1, were observed in the OSAS group. These observations suggest that OSAS-induced hypoxia activates adhesion molecules, resulting in the important risk factor of cardiovascular disorders. Treatment of OSAS can be, therefore, a potential approach to prevention of cardiovascular events.

Adult↗
PubMed1999

Effects of ambroxol on spontaneous or stimulated generation of reactive oxygen species by bronchoalveolar lavage cells harvested from patients with or without chronic obstructive pulmonary diseases.

We examined the effects of ambroxol 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 age-matched control subjects without COPD. The ROS produced by BAL cells were measured by the lucigenin-dependent chemiluminescence method. The application of ambroxol into culture media containing BAL cells inhibited spontaneous and stimulated generation of ROS by BAL cells harvested from COPD patients and control subjects in an ambroxol concentration-dependent manner. These results indicate that ambroxol may be a candidate agent for reducing oxidant stresses of airways in COPD.

Aged↗
PubMed1999

Hydrogen peroxide-induced apoptosis and necrosis in human lung fibroblasts: protective roles of glutathione.

Although reactive oxygen species (ROS)-related cell damage has been implicated in pathogenesis of fibrogenetic pulmonary disorders, features of ROS-mediated cell death in human lung fibroblasts are not completely understood. We therefore examined the effects of hydrogen peroxide (H2O2) on cell growth kinetics in human lung fibroblasts (HFL-1 cells) and tested the roles of antioxidants on the H2O2-induced cell death (i.e., necrosis and apoptosis) in HFL-1 cells. We found that the relatively low concentrations of H2O2 ranging from 10 microM to 100 microM induced predominantly apoptosis, whereas higher concentration of H2O2 ranging 1 mM-10 mM induced predominantly necrosis in HFL-1 cells. Extracellular supplementation of glutathione (GSH) in culture media significantly abolished the H2O2-induced cell death, whereas GSH-depleted cells by pretreatment with buthionine sulfoxime (BSO) were likely to undergo cell death caused by a lower concentration of H2O2 than normal HFL-1 cells without BSO treatment. These results indicate that H2O2 induces both necrosis and apoptosis of human lung fibroblasts at least in part through the action of ROS and that modulation of the ROS production inside and outside of cells may influence the cell survival during oxidative insults.

Antidotes↗
PubMed1999

Recombinant E1-deleted adenoviral vectors induce apoptosis in a rat airway epithelial mucous goblet cell line.

Replication-defective adenoviruses (Ad) are used as vectors for delivering therapeutic genes to human airway cells. We examined whether E1-deleted Ad vectors (Ad5-CMV-LacZ) had effects on cell kinetics in SPOC1 cells, which is a rat airway epithelial mucous goblet cell line. There was a vector multiplicity of infection (moi)-dependent increase of the transduction efficiency of the LacZ reporter gene in SPOC cells. Cell proliferation was inhibited in the vector-infected cells compared with that in vehicle-exposed cells. However, increased cell death was observed in the vector-infected cells with a higher moi. The morphology of vector-exposed cells revealed apoptotic features including nuclear condensation and a fragmented nucleus. These results indicate that higher moi of vectors allows the cells to achieve higher gene transfer, but also induce apoptosis of infected cells. Minimizing the induction of apoptosis of vector-infected cells may be an important strategy for the prolongation of transduction efficiency of Ad vectors in airway epithelial mucous goblet cells.

Adenoviridae↗
PubMed1999

Impaired swallowing reflex in patients with obstructive sleep apnea syndrome.

BACKGROUND: The swallowing reflex is well coordinated with breathing patterns in normal humans. However, patients with obstructive sleep apnea syndrome (OSAS) may have a swallowing disorder that reflects the abnormal function of nerves and muscles in the suprapharynx. OBJECTIVE: To examine the relationship between the swallowing function and sleep-disordered breathing in patients with OSAS. PARTICIPANTS: Twenty patients with OSAS with a mean (+/-SD) age of 53.4+/-8.9 years old, and 20 age-matched control subjects with a mean age of 51.4+/-9.1 years old. METHODS: OSAS was diagnosed using the recordings of overnight polysomnography. The swallowing function in the subject was tested using a swallowing provocation test. The swallowing reflex was determined according to the following criteria: latent time (LT), the time following a bolus injection of distilled water at the suprapharynx to the onset of swallowing; inspiratory suppression time (IST), the time from the termination of swallowing to the next onset of inspiration; and threshold volume, the minimum volume of water (range, 0.4 to 2 mL) that could evoke the swallowing response. RESULTS: Whereas the LT values in patients with OSAS were larger than the LT values in the control subjects, the IST values (which may reflect the switching mechanism from deglutition apnea to breathing) were actually shorter. In addition, a greater bolus volume was necessary to elicit swallowing in patients with OSAS than was necessary in the control subjects. CONCLUSION: Patients with OSAS are likely to exhibit an impaired swallowing reflex, probably due to the perturbed neural and muscular function of the upper airways.

Case-Control Studies↗
PubMed1999

Effects of angiotensin-converting enzyme (ACE) inhibitors on oxygen radical production and generation by murine lung alveolar macrophages.

We examined the effect of angiotensin-converting enzyme (ACE) inhibitors on oxygen radical production before and generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar macrophages. Lung free cells, predominantly pulmonary alveolar macrophages, were obtained from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The oxygen radicals produced by pulmonary alveolar macrophages with or without stimulation of PMA were measured by lucigenin-dependent chemiluminescence method using a photon counter, Lumat 9501 (Berthold, Germany). Alacepril, an ACE inhibitor with SH-group, inhibited the oxygen radical production and generation by lung alveolar macrophages harvested from both rats and guinea pigs in a dose-dependent fashion. Approximately 0.3 mM of alacepril inhibited 50% of oxygen radical production of lung alveolar macrophages in both rats and guinea pigs, whereas a higher concentration (1-5 mM) of lisinopril, an ACE inhibitor without SH-group, was necessary to inhibit 50% of oxygen radical production of lung alveolar macrophages in the animals. These results suggest that an ACE inhibitor with SH-group acts as an antioxidant in murine lungs and the treatment with the ACE inhibitor may reduce oxidant stress in hypertensive patients with asthma.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

[Effect of mechanical damage on ex vivo DNA virus vector-mediated gene transduction in epithelial cells of murine trachea].

The mechanism of Adenovirus (Ad) and Adeno-associated virus (AAV) vector-mediated gene transduction in murine tracheae has not been fully understood. Excised tracheae from mice were exposed to either Ad vector (Ad-CMV-LacZ) or AAV vector (AAV-CMV-LacZ) for 1 hour. LacZ gene expression in tracheal epithelial cells was detected by X-gal staining. Only patch distributions of LacZ expressing cells were observed. The percentage of LacZ expressing cells to total cells was less than 1% with either vector. Ad-mediated LacZ transduction was increased by mechanical damage using forceps. AAV-mediated gene transduction in tracheal epithelial cells was also increased by mechanical damage. Furthermore, this increased expression of vector LacZ by damaged epithelial cells was not affected by pretreatment with anti-ICAM-1 mAb or platelet-activating factor receptor antagonist. Although the Ad and AAV vectors were inefficient in transferring genetic material to murine trachea ex vivo, our results suggest that mechanical damage can enhance their transduction efficiency.

Adenoviruses, Human↗
PubMed1999

[The simple swallowing provocation test as a means of screening for swallowing disorders: a comparison with the water swallowing test].

The sensitivity and specificity of the simple swallowing provocation test (S-SPT) were evaluated in a group of patients who were being examined for aspiration pneumonia (ASP) (ASP group: 72.5 +/- 3.9 years old) and in a group of age-matched control subjects (CTRL group: 69.5 +/- 2.9 years old). The S-SPT was evaluated in terms of the swallowing response and latent time (LT) for swallowing after a bolus injection of 0.4 ml of distilled water at the suprapharynx. Responses to the S-SPT were classified as normal or abnormal, dependent on induction of the swallowing reflex within 3 seconds after bolus injection. The sensitivity and specificity of the S-SPT in detecting ASP were calculated. Of the 40 patients in the ASP group, 18 were given a diagnosis of ASP on the basis of clinical findings and laboratory examinations. The sensitivity and specificity of the S-SPT were 94.4% and 86.4%, respectively, compared to 77.8% and 68.1%, respectively, for the water swallowing test. Because the S-SPT can be performed without any need for special patient effort or cooperation, it should be effective in diagnosing ASP in a wide variety of patients, including those who are bedridden.

Aged↗