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Biomedical subjects

H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 235 records · Page 13Linked to original sources
PubMed1992

Endothelin-1 induces stimulation of prostaglandin synthesis in cells obtained from canine airways by bronchoalveolar lavage.

Endothelin-1 (ET-1), a potent mediator released by airway epithelial cells, often exerts its effects in the lung through stimulation of arachidonic acid (AA) metabolism. To investigate its range of influence, we studied the action of ET-1 on the synthesis and release of thromboxane (TX)B2, prostaglandin (PG)D2, and histamine from canine airway cells obtained by bronchoalveolar lavage (BAL). ET-1 (10(-10), 10(-9) and 10(-8)M) stimulated production of TXB2 and PGD2 by BAL cell preparations in a dose-related manner in the absence of measurable histamine release. Release of TXB2 was 10-fold higher than that of PGD2. The effect of ET-1 on AA metabolism in alveolar macrophages was evaluated in preparations of purified (greater than 99%) cells labelled for 20-22 hrs with 3H-AA prior to stimulation. ET-1 (10(-8), 10(-7), 10(-6)M) induced significant, dose-related release of 3H-AA and its metabolites from alveolar macrophages, to levels 350% above control. These studies indicate that low levels of ET-1 can stimulate AA metabolism in resident luminal airway cells, including alveolar macrophages, and suggest that the function of these luminal cells may be modulated by the epithelium, in vivo, through the release of this peptide into the airways.

Animals↗
PubMed1992

Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients.

Diffuse panbronchiolitis (DPB) is a disease of adults characterized by chronic inflammation of the respiratory bronchioles and the infiltration of chronic inflammatory cells. The clinical efficacy of erythromycin therapy has been demonstrated in DPB patients, but the mechanism of action of this drug is unknown. We investigated the localization of neutrophils in lung biopsy specimens, as well as the cell population and elastolytic-like and chemotactic activity of bronchoalveolar lavage (BAL) fluid, before and after treatment with erythromycin or ampicillin in 11 DPB patients (six biopsy-proven and five clinically diagnosed) and one follicular bronchiolitis patient. These bronchiolitis patients had a high percentage of neutrophil and a high neutrophil-derived elastolytic-like activity in BAL fluid compared with chronic bronchitis patients and normal control subjects. The number of neutrophils and the neutrophil-derived elastolytic-like activity in BAL fluid decreased significantly after treatment with erythromycin along with a significant improvement in pulmonary function studies, although there was no significant change in the chemotactic activity of BAL fluid. No significant reduction in BAL fluid neutrophilia was found in the ampicillin-treated patients. These results suggest an important role for the neutrophil in the pathogenesis or development of bronchiolitis, and also suggest that erythromycin may be useful for the treatment of bronchiolitis through its direct action upon host phagocytic cells.

Adolescent↗
PubMed1992

Inhibition of the complement membrane attack complex by the galactose-specific adhesion of Entamoeba histolytica.

The human complement system is an important early host defense against infection. Entamoeba histolytica activates the complement system but is resistant to killing by complement C5b-9 complexes deposited on the membrane surface. Our aim was to identify components of the amebic plasma membrane that mediate resistance to human complement C5b-9 by screening for neutralizing monoclonal antibodies. A monoclonal antibody was identified that abrogated amebic resistance to C5b-9, and the mAb was shown to recognize the parasite's galactose-specific adhesin. The purified adhesin bound to C8 and C9 and conferred C5b-9 resistance to sensitive ameba upon reconstitution; these activities of the adhesin were inhibited by the antiadhesin mAb. The E. histolytica adhesin shared sequence similarities and antigenic cross-reactivity with CD59, a membrane inhibitor of C5b-9 in human blood cells, suggesting both molecular mimicry and shared complement-inhibitory functions.

Amino Acid Sequence↗
PubMed1992

Neurokinin A-stimulated phosphoinositide breakdown in rabbit iris sphincter muscle.

Specific [3H]-substance P binding was saturable and of high affinity (KD = 2.5 nM) with a Bmax of 725 fmol/mg protein in the isolated rabbit iris sphincter muscle. The competition for [3H]-substance P binding was in the order of eledoisin greater than substance P greater than kassinin greater than neurokinin B greater than neurokinin A greater than physalaemin. In the same preparation, neurokinin A, as well as substance P induced a concentration-related accumulation of [3H]-inositol phosphates (IPs), and the maximum increase was about 200% of the control at 10(-4) M. [D-Arg1, D-Trp7,9, Leu11]-substance P (SP) and [D-Pro2, D-Trp7,9]-SP (10(-3) M) inhibited substance P or neurokinin A (10(-4) M)-induced phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis significantly. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (10(-3) M) also inhibited neurokinin A (10(-4) M)-induced PIP2 hydrolysis significantly. Neurokinin A and substance P produced concentration-related contractions in normal Ca(2+)-containing medium. The contractile response was weaker in Ca(2+)-free medium, and there was no response in 0.2 mM EGTA medium. In Ca(2+)-free medium, the basal level of [3H]-IPs accumulation was smaller than that in normal medium, and neurokinin A and substance P significantly increased PIP2 hydrolysis. In the 0.2 mM EGTA containing medium, neurokinin A and substance P did not stimulate the PIP2 hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Immunocytochemical staining of decay-accelerating factor (DAF) on erythrocytes: paroxysmal nocturnal hemoglobinuria (PNH)].

Affected erythrocytes in patients with paroxysmal nocturnal hemoglobinuria (PNH) have been detected as complement-sensitive cells by the complement sensitivity assay. Decay-accelerating factor (DAF), a molecular mass of 70 kDa complement-regulatory membrane glycoprotein, has been reported to be deficient on affected PNH blood cells. In the present study, DAF on erythrocytes from 12 patients with PNH were stained by an immunocytochemical method and the ratio of DAF+ erythrocytes was compared with their laboratory data concerning hemolysis, almost all normal human erythrocytes stained positively for DAF. In contrast, various percentages of DAF+ erythrocytes were found in the patients with PNH. The percentages of DAF+ erythrocytes correlated positively with the total amounts of DAF on erythrocytes measured by an enzyme-linked immunosorbent assay (ELISA), negatively with % hemolysis in Ham's test and in sucrose hemolysis assay and with percentages of PNH type III (PNH-III) erythrocytes. In some patients with PNH, subpopulations of erythrocytes weakly-positive for DAF were demonstrated in addition to DAF- erythrocytes. The immunocytochemical method for staining DAF on erythrocytes developed in the present study is useful for the detection of affected PNH erythrocytes and applicable to further studies on membrane defects in PNH.

Adult↗
PubMed1992

Endothelins constrict guinea pig tracheas by multiple mechanisms.

When tracheal rings isolated from guinea pigs were treated with endothelins (ETs), a dose-dependent constriction was observed and measured isometrically. ET potencies were ET-1 = ET-2 greater than ET-3. Dose-response curves of epithelium-denuded tracheas were shifted to the left by approximately one order of magnitude. Lung tissue contained saturable binding sites to 125I-labeled ET-1. These binding sites were replaced by ET-1 = ET-2 greater than ET-3. Because the airway tissue contained primarily ET-1 as measured by immunoassay after high-performance liquid chromatography separation, we investigated the mechanism of ET-1-induced tracheal constriction. Tracheal constriction induced by ET-1 required Ca++ in the medium. Because suppression of the contractile response by nicardipine and diltiazem was small, Ca++ entry appeared to be gated primarily through Ca++ channels rather than via voltage-dependent ones. FPL55712, SC47014A, indomethacin and OKY046 suppressed the dose-response curves, suggesting that lipid mediators are formed in response to ET-1. Diphenhydramine also altered dose-response curves, suggesting that histamine release from mast cells was partially responsible for the constriction. Pretreatment of tracheas with compound 48/80 resulted in suppression of the contractile responses. Furthermore, the combination of indomethacin, FPL55712 and diphenhydramine gave essentially identical effects. Our observations suggest that ET-1 provokes the contractile response of guinea pig tracheas not only by direct actions on smooth muscle but also by indirect actions through production of chemical mediators in mast cells and other inflammatory cells.

Animals↗
PubMed1992

[Effect of enkephalinase inhibitor on endothelin-1 induced bronchoconstriction in guinea pigs].

Endothelin-1 (ET-1) is one of the most potent bronchoconstrictors in the guinea pig. The mechanism of its metabolism is still unclear. Phosphoramidon is known to be an enkephalinase inhibitor. We studied the effect of phosphoramidon on bronchoconstriction induced by ET-1. In the first in vitro study, a tracheal preparation was mounted in oxygenated Krebs-Ringer solution. The response was monitored by isometric transducer. Dose-response curves to ET-1 with or without phosphoramidon were obtained. Phosphoramidon potentiated ET-1 induced bronchoconstriction significantly. Next, the specific airway conductance (sGaw) was measured in conscious guinea pigs exposed to an aerosol of phosphoramidon or saline, followed by ET-1 aerosol inhalation. The ET-1 dose was increased by successively doubling the concentration. sGaw, after inhalation of phosphoramidon, was significantly reduced when exposed to ET-1. Phosphoramidon also potentiated ET-1 induced bronchoconstriction in vivo. Next, lung parenchymal tissues were prepared and placed in oxygenated Krebs-Ringer solution with or without phosphoramidon. ET-1 was added and incubated, and samples were injected into a high performance liquid chromatography column. Phosphoramidon inhibited an analysis of ET-1. These data suggest that enkephalinase plays a role in the break down of ET-1 in the airway of the guinea pig. Under the condition of decreased enkephalinase, ET-1 would potentiate bronchoconstriction.

Animals↗
PubMed1992

[Host factors which influence the outcome of pneumonia in the elderly].

We examined 135 elderly patients with pneumonia to clarify the factors predicting on the outcomes of the elderly pneumonic patients. In the fatal cases respiratory symptoms such as cough and sputum, except for dyspnea were less frequent but pulmonary infiltrations on chest roentgenograms were more massive as compared with those in the survived cases. Thus, it was suggested that in the fatal cases the more advanced pneumonia had developed at the time when the diagnosis of pneumonia was made. The fatal cases showed hypoalbuminemia, hypocholesterolemia and hyponatlemia more frequently as compared with survived cases. Among these laboratory values, the decreased serum albumin concentration seemed to be most closely correlated with the fatal outcome of the elderly pneumonic patients. There were significant differences in the outcomes among three groups of the patients, those who were the prolonged bed-ridden, those with severe underlying diseases such as cancer and those treated as out-patients. The out patients showed the most favorable outcome and the prolonged bed-ridden patients the worst outcome. Approximately, 39% of the fatal cases were complicated with multiple organ failure. These results suggest that more important factors which affect the outcomes of pneumonia in the elderly may be not merely aging but the conditions of the host at onset of the disease.

Aged↗
PubMed1991

Endotoxin stimulates endothelin release from cultured epithelial cells of guinea-pig trachea.

We examined the release of endothelin from cultured epithelial cells of guinea-pig trachea in response to treatment with endotoxin, using a sandwich-enzyme immunoassay. Cultured epithelial cells released endothelin in a time-dependent fashion (3, 6, 12, 24 h), and endotoxin (4-40 micrograms/ml) significantly increased endothelin release. Endotoxin (4-10 micrograms/ml) showed no cytotoxicity against epithelial cells. These results suggest that guinea-pig airway epithelial cells are capable of producing endothelin and this peptide may be related to the pathophysiological effects of endotoxin.

Animals↗
PubMed1991

Inhibition of homologous complement by CD59 is mediated by a species-selective recognition conferred through binding to C8 within C5b-8 or C9 within C5b-9.

The capacity of the human complement regulatory protein CD59 to interact with terminal complement proteins in a species-selective manner was examined. When incorporated into chicken E, CD59 (purified from human E membranes) inhibited the cytolytic activity of the C5b-9 complex in a manner dependent on the species of origin of C8 and C9. Inhibition of C5b-9-mediated hemolysis was maximal when C8 and C9 were derived from human (hu) or baboon serum. By contrast, CD59 showed reduced activity when C8 and C9 were derived from dog or sheep serum, and no activity when C8 and C9 were derived from either rabbit or guinea pig (gp) serum. Similar specificity on the basis of the species of origin of C8 and C9 was also observed for CD59 endogenous to the human E membrane, using functionally blocking antibody against this cell surface protein to selectively abrogate its C5b-9-inhibitory activity. When E bearing human CD59 were exposed to C5b-8hu, CD59 was found to inhibit C5b-9-mediated lysis, regardless of the species of origin of C9, suggesting that the inhibitory function of CD59 can be mediated through recognition of species-specific domains expressed by human C8. Consistent with this interpretation, CD59 was found to bind to C5b-8hu but not to C5b67hu or C5b67huC8gp. Although CD59 failed to inhibit hemolysis mediated by C5b67huC8gpC9gp, its inhibitory function was observed for C5b67huC8gpC9hu, suggesting that, in addition to its interaction with C5b-8hu, CD59 also interacts in a species-selective manner with C9hu incorporated into C5b-9. Consistent with this interpretation, CD59 was found to bind both C5b67huC8gpC9hu and C5b-8huC9gp, but not C5b67huC8gpC9gp. Taken together, these data suggest that the capacity of CD59 to restrict the hemolytic activity of human serum complement involves a species-selective interaction of CD59, which involves binding to both the C8 and C9 components of the membrane attack complex. Although CD59 expresses selectivity for C8 and C9 of human origin, this "homologous restriction" is not absolute, and this human complement regulatory protein retains functional activity toward C8 and C9 of some nonprimate species.

Antigens, Differentiation↗
PubMed1991

Studies on heat treatment for immediate reimplantation of resected bone.

Extracorporeal heat treatment for devitalizing the tumour-infiltrated bone segment without destroying its regenerative potential was investigated for the purpose of immediate reimplantation of the resected bone. Effects of heat treatment on cell viability and bone inductive properties were studied in cultured tumour cells and animal models. Heat treatment at 65 degrees C for 30 to 120 minutes resulted in complete devitalization of cells, preserving osteogenetic properties of the allogenic bone implant in the rabbit. The results of the experiments indicate that this procedure has advantages in devitalizing the resected bone for its immediate reimplantation and justify clinical application. The clinical application of this heat treatment in 3 cases is presented.

Adult↗
PubMed1991

Application of magnetic resonance imaging and ultrasonography to preoperative evaluation of masseteric hypertrophy.

A case of unilateral masseteric hypertrophy in a 30-year-old man is described. Preoperative evaluation was performed by magnetic resonance imaging (MRI), computed tomography (CT) and ultrasonography (USG). MRI could delineate not only the border between medial and lateral layers of the masseter but also delineate the hypertrophic portion. MRI also provided more information in respect of the masseter muscle as well as the other masticatory muscles and the surrounding tissues than CT. USG was useful because of its real-time processing, especially in this case where facial asymmetry was emphasized during mastication. We resected the medial lower-half of the masseter intraorally based on these imagings and obtained a successful result.

Adult↗
PubMed1991

Endothelin-1-induced relaxation of guinea pig trachealis muscles.

Our accompanying paper demonstrated that endothelin-1 (ET-1 constricts guinea pig airways directly and indirectly through mediators such as histamine and arachidonate metabolites. In order to exclude the role of mast cells in bronchoconstriction, we sensitized guinea pigs and challenged them in vitro with an antigen (ovalbumin). In the postanaphylactic trachea, ET-1 caused a transient relaxation followed by constriction. Such relaxation by ET was also observed in the tracheas constricted with carbamylcholine. The relaxation was completely blocked by nordihydroguaretic acid and AA861, lipooxygenase inhibitors, but not by indomethacin, a cyclooxygenase inhibitor, and FPL 55712, a leukotriene antagonist. Because the relaxation was not affected even in the presence of methylarginine, an inhibitor of NO synthesis, and superoxide dismutase, an enzyme for destroying NO radical, we concluded that ET-1 induces the relaxation of the tracheal muscles by producing lipooxygenase products, probably hydroperoxides of arachidonic acid.

Anaphylaxis↗
PubMed1991

Multiple mechanisms of bronchoconstrictive responses to endothelin-1.

We investigated the mechanism of the endothelin-1 (ET-1)-induced bronchoconstriction of guinea pig tracheal smooth muscles. ET-1 contracted the tracheas in a dose-dependent manner. A combination of FPL55712 (leukotriene antagonist), diphenhydramine (histamine antagonist), and indomethacin (cyclooxygenase inhibitor) shifted the dose-response curve of ET-1 to the right and suppressed the maximal constriction. Azelastine, an antiallergic agent, exerted essentially similar results. The present data suggest that ET-1 constricts the airway smooth muscles not only by direct action on the tracheal smooth muscles but also by indirect action mediated through production of various chemical mediators in cells other than muscles.

Animals↗