Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 55 records · Page 3Linked to original sources

PubMed2001

[A case of pulmonary capillary hemangiomatosis].

In March 1995, a 54-year-old woman was admitted to a hospital because of exertional dyspnea and her condition was diagnosed as primary pulmonary hypertension. In September 1996, respiratory difficulty and hemosputum were woted. The chest computed tomographic scan showed diffuse micronodular opacities, and she was admitted to our hospital for examination of other pulmonary conditions giving rise to pulmonary hypertention. However no lung biopsy could be performed, because the pulmonary arterial pressure was too high. Although the patient received medication, she died of progressive right heart failure. The pathological diagnosis at autopsy was pulmonary capillary hemangiomatosis (PCH). Although PCH is a very rare disease that causes secondary pulmonary hypertension, it is important to distinguish it from primary pulmonary hypertension and pulmonary veno-occlusive disease.

Diagnosis, Differential↗

PubMed2001

[Lung cancer].

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Age Factors↗

PubMed2001

[An autopsy case of idiopathic interstitial pneumonia with diffuse alveolar hemorrhage due to acute exacerbation].

There has hitherto been no report describing idiopathic interstitial pneumonia associated with diffuse alveolar hemorrhage, but we herein report one such rare case. A 75-year-old man who had received a diagnosis of idiopathic interstitial pneumonia had been followed in our hospital since 1995, and had been treated with cyclophosphamide since September 1999. He discontinued taking cyclophosphamide without informing us, and two months later he was admitted to our hospital with deterioration of dyspnea on September 13, 2000. Since chest radiography and CT findings demonstrated alveolar infiltrates in the right middle lung field, he was treated with antibiotic agents. Although no deterioration of symptoms occurred, on September 14 he began to suffer rapidly progressive dyspnea accompanied with production of bloody sputum, which eventually developed into full-blown hemoptysis in the evening of September 15. He died of respiratory failure early the next morning. The autopsy findings demonstrated diffuse alveolar hemorrhage, diffuse alveolar damage, interstitial pneumonia, and pulmonary fibrosis.

Aged↗

PubMed2001

[A case of inflammatory endotracheal polyps in an asthmatic subject].

A 60-year-old asthmatic woman was admitted to our department because of bloody sputum and pneumonia. She had been treated with inhaled becromethasone dipropionate (800 micrograms/day) on an outpatient basis for 3 years. Fiberoptic bronchoscopy revealed polypoid lesions in the trachea, most of which were removed with forceps during the procedure. Numerous lymphocytes were observed in the biopsy specimen. Because immunohistochemical staining denied a monoclonal origin for the accumulated lymphocytes, the lesion was diagnosed as an inflammatory polyp. The patient was treated successfully with antibiotics for her pneumonia, and on a follow-up bronchoscopy 6 months later, only a small remnant of the lesion was noted. This is the fourth report about inflammatory polyps in asthmatics. In the previous 3 cases, however, marked eosinophil infiltration was consistently reported. The lymphocyte predominance in the present case therefore suggests a distinct etiology rather than asthmatic airway inflammation.

Asthma↗

PubMed2001

[A case of sarcoidosis involving multiple organs that showed significant improvement as the serum KL-6 level fell after steroid therapy].

Pulmonary sarcoidosis was diagnosed by transbronchial lung biopsy in a 27-year old man admitted to our hospital in September 1996. In October 1999, bilateral parenchymal findings on chest radiography and the results of pulmonary function tests had significantly deteriorated compared with those of three years before. Since skin, heart, liver, and spleen lesions were also detected, this patient was treated with corticosteroids. The lung parenchymal lesions and the pulmonary function as well as the abnormal findings in other organs showed significantly improvement along with a decrease of the KL-6 level after steroid therapy.

Adult↗

PubMed2000

Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes guinea pig tracheal smooth muscle by producing epithelium-dependent relaxing factors.

A non-phorbol ester-type tumor promoter, thapsigargin has been reported to deplete Ca(2+) stores in endothelial cells by inhibiting Ca(2+)-ATPase, which in turn increases intracellular Ca(2+) by mobilization of extracellular Ca(2+), leading to activation of constitutive nitric oxide synthase (cNOS) and resultant generation of nitric oxide (NO). In the present study, to evaluate the role of Ca(2+) in the release of epithelium-dependent relaxing factor (EpDRF), we determined the effect of thapsigargin (10(-6) M) on the contraction evoked by exogenous Ca(2+) or acetylcholine (10(-5) M) in epithelium-denuded or epithelium-intact smooth muscle from guinea pig trachea. The following results were obtained: (1) In epithelium-denuded smooth muscle, the contraction evoked by exogenous Ca(2+) in Ca(2+)-free solution or by acetylcholine (10(-5) M) in Ca(2+)-containing solution did not change within 20 min after thapsigargin application, but the contraction evoked by exogenous Ca(2+) increased markedly after 120 min, indicating that thapsigargin had no effect on smooth muscle itself within 20 min of application. The following experiments were performed within 20 min of thapsigargin application. (2) In epithelium-intact smooth muscle, thapsigargin significantly suppressed the contraction evoked by acetylcholine, suggesting that thapsigargin stimulate the epithelium to produce EpDRF. N(G)-nitro-L-arginine methylester (L-NAME) partly, but significantly, attenuated this inhibitory effect of thapsigargin. (3) In epithelium-denuded smooth muscle, atropine (10(-6) M) and L-NAME (10(-5) M) did not change the contraction evoked by exogenous Ca(2+) after application of thapsigargin, suggesting that thapsigargin did not stimulate acetylcholine and NO release from nerve terminals. These results suggest that thapsigargin (10(-6) M) may stimulate EpDRF, including NO and other factor(s) by Ca(2+)-dependent mechanisms.

Acetylcholine↗

PubMed2000

Inhibition of N-linked glycosylation causes apoptosis in hamster BHK21 cells.

The tsBN7 cell line is one of the temperature-sensitive mutants for cell proliferation derived from hamster BHK21 cell line. It has a mutation in the DAD1 gene and enters apoptosis at the restrictive temperature of 39 degrees C. The defect of Dad1p causes a loss of N-linked glycosylation; therefore, it was thought that an inhibition of N-linked glycosylation induced apoptosis.However, tunicamycin, a potent inhibitor of N-linked glycosylation, had not caused apoptosis in wild-type BHK21 cells. In order to clarify this discrepancy, wild-type BHK21 cells treated with tunicamycin and tsBN7 cells incubated at 39.5 degrees C were examined by the annexin V staining and TUNEL methods. Both methods showed that tunicamycin induces apoptosis in wild-type BHK21 cells, similar to the defect of Dad1p. Thus, we concluded that loss of N-linked glycosylation causes apoptosis.

Animals↗

PubMed2000

Cyclooxygenase-2 participates in the late phase of airway hyperresponsiveness after ozone exposure in guinea pigs.

We examined the role of cyclooxygenase in airway hyperresponsiveness and inflammation after ozone exposure in guinea pigs using a non-selective (indomethacin) and a selective (JTE-522) cyclooxygenase-2 inhibitor. Spontaneously breathing guinea pigs were exposed to ozone (3 ppm) for 2 h after treatment with vehicle, indomethacin (10 mg/kg) or JTE-522 (10 mg/kg). Airway responsiveness to inhaled histamine (PC(200)) and bronchoalveolar lavage were assessed before, immediately and 5 h after ozone exposure. Ozone caused a significant airway hyperresponsiveness immediately after exposure, which persisted after 5 h. Neither JTE-522 nor indomethacin affected airway hyperresponsiveness immediately after ozone exposure, but significantly attenuated airway hyperresponsiveness 5 h after exposure, suggesting that cyclooxygenase-2 may participate in the late phase of airway hyperresponsiveness but not in the early phase. Ozone caused a significant increase in the concentration of prostaglandin E(2) and thromboxane B(2) in bronchoalveolar lavage fluid immediately after exposure, which decreased to the basal level 5 h after exposure. This increase in prostaglandin E(2) and thromboxane B(2) was significantly inhibited by JTE-522. An expression of cyclooxygenase-2 was detected not only after ozone exposure but also before, and there was no difference in the number of cyclooxygenase-2-positive cells at any time point. An exogenously applied thromboxane A(2) mimetic, U-46619 (10(-5) M), induced airway hyperresponsiveness 5 h after inhalation, but not immediately or 3 h after inhalation. These data suggest that cyclooxygenase-2 may be constitutively expressed before ozone exposure in guinea pig airway and may synthesize prostaglandin E(2) and thromboxane A(2) transiently under ozone stimulation and that thromboxane A(2) may, in turn, induce the late phase of airway hyperresponsiveness.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2000

Effect of dimethylthiourea, a hydroxyl radical scavenger, on cigarette smoke-induced bronchoconstriction in guinea pigs.

Cigarette smoke exposure causes bronchoconstriction in guinea pigs by stimulating cholinergic and excitatory nonadrenergic, noncholinergic (eNANC)-nerves in vagus system. The aim of this study is to elucidate the role of hydroxyl radical (OH(-)), contained in cigarette smoke, in bronchoconstriction. Anaesthetized animals were exposed to 80 puffs of smoke for 4 min. Pretreatment with dimethylthiourea, a OH(-) scavenger, significantly inhibited cigarette smoke-induced bronchoconstriction. To investigate its site of action, effects of dimethylthiourea were examined on vagally mediated bronchcoconstriction by electrical stimulation and on the bronchoconstriction by intravenous acetylcholine and neurokinin-A. Dimethylthiourea did not inhibit bronchoconstriction evoked by vagal stimulation, acetylcholine or neurokinin-A. These results suggest that dimethylthiourea inhibits cigarette smoke-induced bronchoconstriction by scavenging the smoke-derived OH(-), but not by inhibiting airway nerve function.

Acetylcholine↗

PubMed2000

Pituitary adenylate cyclase activating peptide mediates inhibitory nonadrenergic noncholinergic relaxation.

We investigated the contribution of pituitary adenylate cyclase activating peptide (PACAP) to inhibitory nonadrenergic noncholinergic (inhibitory-NANC) relaxation of tracheal smooth muscle in cats. We also investigated the roles of vasoactive intestinal peptide (VIP) and nitric oxide (NO) on this function. Smooth muscle strips prepared from feline trachea were precontracted with 1 microM serotonin, and inhibitory-NANC relaxation was induced by electrical-field stimulation in the presence of atropine and propranolol. PACAP-(6-38) (a selective antagonist of PACAP; 1, 3 and 10 microM), VIP-(10-28) (a selective antagonist of VIP; 1, 3 and 10 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME, a selective NO synthase inhibitor; 3, 10 and 30 microM) each partially but significantly attenuated the amplitude of inhibitory-NANC relaxation. The effects of PACAP-(6-38) and VIP-(10-28) were additive. Addition of PACAP-(6-38) and/or VIP-(10-28) further attenuated relaxation in the presence of L-NAME. These results suggest that PACAP, VIP and NO contribute to the relaxation induced by inhibitory-NANC in tracheal smooth muscle in cats, and that they mediate this relaxation via different pathways.

Animals↗

PubMed2000

Suppression of tumor angiogenesis and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ.

Antiangiogenic therapy shows promise as a strategy for cancer treatment. We constructed an adenovirus (AdVEGF-ExR) expressing the entire extracellular domain of the human vascular endothelial growth factor (VEGF) receptor (flt-1) fused to the Fc portion of human IgG. The soluble receptor secreted from AdVEGF-ExR-infected cells bound to VEGF and inhibited VEGF-induced DNA synthesis in endothelial cells. When human lung cancer cell line H157, which produces not only VEGF but also fibroblast growth factor 2 and interleukin 8 at substantial levels, was infected with AdVEGF-ExR, cell growth in vitro was not affected. However, when H157 cells infected with AdVEGF-ExR were injected s.c. into nude mice, tumor formation stopped on the 10th day after reaching a certain size (about 100 mm3), and tumor size declined gradually thereafter. When AdVEGF-ExR was injected into skeletal muscle and uninfected H157 cells were injected s.c., the soluble receptor was detectable in the circulating blood for 3 weeks, tumor growth ceased after 10 days, and tumor size declined thereafter. Histological examination revealed that intratumor angiogenesis was markedly suppressed, and apoptosis was enhanced. Using the same experimental protocol, a significant suppression of tumor growth was also seen in four of five other lung cancer cell lines, some of which secreted VEGF at nominal levels, at least under normoxic conditions in vitro. Our results demonstrate that adenovirus-mediated expression of a soluble VEGF receptor in a remote organ could inhibit tumor angiogenesis and enhance apoptosis and thereby suppress tumor growth in vivo. Adenovirus-mediated overexpression of a soluble VEGF receptor in a remote organ may have the potential to be a feasible and effective strategy for cancer treatment.

Adenoviruses, Human↗

PubMed2000

Neutrophil elastase inhibitor, ONO-5046 suppresses ozone-induced airway mucus hypersecretion in guinea pigs.

To investigate the role of neutrophil elastase in ozone-induced airway hypersecretion, we measured goblet cell secretion by using a semiquantitative morphometric technique in guinea pigs. The magnitude of mucus discharge was estimated from the mucus score, which is inversely related to the degree of mucus discharge in histological sections of trachea stained for mucus glycoprotein with periodic acid Schiff/Alcian blue. Mucus hypersecretion of goblet cells was induced by ozone exposure and persisted for up to 5 h after exposure. Pretreatment with N-[2-¿4-(2,2-dimethyl-propionyloxy) phenyl-sulfonylamino¿ benzoyl] aminoacetic acid (ONO-5046), a specific neutrophil elastase inhibitor (200 mg/kg, intraperitoneally), significantly inhibited goblet cell hypersecretion both just after and 5 h after ozone-exposure, but the latter inhibition was not complete. In bronchoalveolar lavage fluid, ozone exposure significantly increased the number of neutrophils just after and 5 h after exposure, while ONO-5046 significantly inhibited the increase in neutrophils only 5 h after ozone-exposure. These results indicate that neutrophil elastase may play an important role in the ozone-induced tracheal goblet cell hypersecretion and influx of neutrophils.

Animals↗

PubMed2000

Expression of apoptosis-regulatory genes in epithelial cells in pulmonary fibrosis in mice.

Up-regulation of Fas and Fas ligand and excessive apoptosis of bronchiolar and alveolar epithelial cells were identified in bleomycin-induced pulmonary fibrosis in mice. This study hypothesized that apoptosis-regulatory genes other than Fas-Fas ligand, such as p53, p21 (Waf1/Cip1), bcl-2, bcl-x, and bax, may also participate in epithelial cell apoptosis in this model. The expression of these genes was assessed by reverse transcription polymerase chain reaction (RT-PCR), RT in situ PCR, or immunohistochemistry. The expression of p53 and p21 mRNA was concurrently up-regulated in the alveolar epithelial cells at 1 h to 7 days after intratracheal instillation of bleomycin. The expression of bcl-2 mRNA was weakly up-regulated at 1 h to 14 days, while the expression level of bcl-2 protein was not changed. The expression of bcl-x(L) and bax mRNA was strongly up-regulated at 1 h to 7 days. The expression of bcl-x protein was up-regulated in lymphocytes and macrophages, whereas bax protein was up-regulated in both epithelial and inflammatory cells. It is concluded that epithelial cell apoptosis in this model may also be induced by the up-regulation of p53 and bax and by the imbalance between apoptosis-inducible and -inhibitory genes, in addition to the up-regulation of the Fas-Fas ligand pathway.

Animals↗

PubMed2000

[Motor and sensory responses in fusion of vertical disparities in different convergence places].

UNLABELLED: To study motor and sensory responses in vertical fusion at different angles of horizontal vergence in normal humans. METHODS: The study included 12 normal subjects. A cross (+) extending 3.4 degrees x3.2 degrees was presented dichoptically. Vertical disparity was introduced by changing the vertical position of the cross in front of one eye. The disparity was incremented by 0.08 degrees every 8 s. Distance viewing was tested with 1 degrees of convergence demand, near vision with 6-15 degrees convergence demand. Eye movements were recorded using three-axis search coils. RESULTS: Vertical fusion capability was larger at near vision than at distance in 9 of 12 subjects. For the entire group, total vertical fusion capability (motor plus sensory response) differed between distance (mean 1.68 degrees ) and near (mean 2.39 degrees ). The motor component differed significantly between distance (mean 1.42 degrees ) and near (mean 2.13 degrees ). No difference in the sensory component was seen between distance (mean 0.26 degrees ) and near (mean 0.27 degrees ). CONCLUSIONS: Vertical fusion capability increases with convergence. This increase is mainly due to an increase of the motor response.

Accommodation, Ocular↗

PubMed2000

Biomechanical comparisons of anterior cruciate ligament: reconstruction procedures with flexor tendon graft.

An experimental study was conducted to compare the biomechanical characteristics of six currently available anterior cruciate ligament (ACL) reconstruction procedures with flexor digitorum profundus tendons. Forty porcine knees were divided into eight groups, of 5 knees each. In groups A, B, C, and D, the flexor tendon graft was fixed with sutures and an Endobutton, with 20-mm-wide polyester tapes and staples, with 10-mm-wide polyester tapes and an Endobutton, and with bone plugs and interference screws, respectively. In group E, the graft was fixed using a combined procedure of those in groups B and D. In group F, the graft was directly fixed with interference screws. In groups G and H, the bone-patellar tendon-bone graft was fixed with interference screws, and sutures, respectively. Each femur-graft-tibia complex specimen was tested with a tensile tester by anteriorly translating the tibia until failure. This study demonstrated that the biomechanical properties of the femur-graft-tibia complex reconstructed with the flexor tendon graft were significantly affected by synthetic fixation devices. Regarding the average maximal load of the groups with the flexor tendon graft, group B had the highest (893 N) and group C had the second highest (770 N). Groups E and A were in the third rank. Group F had the second lowest (312 N), and Group D had the lowest (230 N). The maximal load of group B was significantly greater (P < 0.01) than that of group G (656 N) with the bone-patellar tendon-bone grafts. As to clinical relevance, this study indicated that the flexor tendon graft can be an alternative substitute for the bone-patellar tendon-bone graft for ACL reconstruction, if we understand the biomechanical characteristics of each reconstruction procedure.

Animals↗

PubMed2000

Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor.

LPS (lipopolysaccharide) is one of the major factors that induce acute lung injury. Recently, it was reported that LPS induced disseminated endothelial apoptosis, preceding nonendothelial tissue damage. Caspases play important roles in apoptosis, including tumor necrosis factor-alpha-induced apoptosis, in several systems. We therefore investigated whether the injection of a caspase inhibitor prevents LPS-induced apoptosis and acute lung injury in mice. LPS (30 mg/kg) was administered intravenously to Institute for Cancer Research mice. Electron microscopic findings demonstrated characteristic features of apoptosis in endothelial cells and alveolar epithelial cells. The caspase-3 activity and the number of terminal dUTP nick-end labeling-positive cells in lung tissues were significantly increased after LPS administration. Benzyloxycarbonil-Val-Ala-Asp fluoromethylketone (Z-VAD.fmk), which is a broad-spectrum caspase inhibitor, was injected before and after the administration of LPS. The injection of Z-VAD.fmk suppressed the caspase-3 activity in lung tissues, and significantly decreased the number of terminal dUTP nick-end labeling-positive cells. Furthermore, the survival rate of mice was prolonged significantly by the injection of Z-VAD.fmk. These results indicate that apoptosis may play an important role in acute lung injury, and thus that inhibition of caspase activity may constitute a new therapeutic approach for treatment of this disease.

Acute Disease↗

PubMed2000

Effects of localized lesions in the lateral suprasylvian cortex on convergence eye movement in cats.

We evaluated the effects of electrolytic lesions in the extrastriate cortical area on the amplitudes and velocities of vergence eye movements in six alert cats that were trained to track a target moving in depth. Bilateral or unilateral lesions in the lateral suprasylvian (LS) cortex reduced the amplitudes and velocities of vergence eye movements, but the positive correlation between them was maintained. Furthermore, unilateral lesions changed the symmetry of eye movements. Movements of the left eye were decreased by lesions in the right LS cortex, resulting in asymmetric vergence eye movement with right eye predominance, and vice versa. These results support the hypothesis that the LS cortex plays an essential role in controlling vergence eye movement.

Animals↗

PubMed2000

Analysis of Fas and Fas ligand expression and function in lung cancer cell lines.

The aim of this study was to investigate the expression of Fas and Fas ligand (FasL) and to determine the significance of these molecules in lung cancer cell lines. Immunoblotting, RT-PCR and flow cytometric analyses were carried out to measure the expression of Fas and FasL and to examine their interactions and effects on cell growth and apoptosis. Fas and FasL were co-expressed in most of the cell lines but to varying degrees. Apoptosis induced by the agonistic anti-Fas antibody was significantly correlated with Fas expression (P=0.0075), whereas cisplatin-induced apoptosis was not. Upregulation of Fas and FasL expression by the administration of cisplatin was found in 7 of 11 (64%) and 9 of 11 (82%) cell lines, respectively. However, cisplatin-induced apoptosis was not suppressed by antagonistic anti-FasL antibody. Thus, our data indicated that Fas and FasL were co-expressed in lung cancer cell lines, and that Fas ligation induced by agonistic anti-Fas antibody is functional and induced apoptosis that was dependent on the levels of Fas expression. In contrast, Fas-FasL interactions appeared to be non-functional. Furthermore, our results suggest that cisplatin-induced apoptosis in lung cancer cells was independent of the Fas-FasL interaction.

Antineoplastic Agents↗