Biomedical subjects

N Inamura

Publications and source records attributed to N Inamura.

At least 55 records · Page 3Linked to original sources

PubMed1997

Antagonistic effects of FR 173657 on human, pig, rabbit, and guinea pig kinin receptors: an in vitro study.

The pharmacodynamic features of the new nonpeptide kinin B2 receptor antagonist FR 173657 were evaluated on pig, rabbit, guinea pig, and human native kinin B2 receptors. FR 173657 exerted high antagonistic activity in all preparations examined. In particular, it acts as a competitive antagonist in the rabbit jugular vein (pA2 8.9) and in the human umbilical vein (pA2 8.2) but as a noncompetitive antagonist in the pig coronary artery (pKB 9.2) and in the guinea pig ileum (pKB 9.2) stimulated with the selective B2 receptor agonist bradykinin (BK). In contrast, FR 173657 failed to antagonize the biological effects of the selective B1 receptor agonist LysdesArg9BK in the pig renal vein, rabbit aorta, and human umbilical vein, three kinin B1 receptor systems. Moreover, this compound was inactive against the effects induced by noradrenaline, 5-hydroxytryptamine, endothelin-1, angiotensin II, substance P, acetylcholine, and histamine in the B2 receptor preparations. Taken together, these results demonstrate that FR 173657 is the first potent nonpeptide B2 receptor antagonist with high affinity, selectivity, and specificity for kinin B2 receptors of different species, including man.

Adult↗

PubMed1997

Characterization of FR173657, a novel nonpeptide B2 antagonist: in vitro and in vivo studies.

Bradykinin (BK) is involved in different pathophysiological conditions, including allergic and (or) inflammatory reactions. Thus, BK antagonists are considered as a potential drug in allergic and (or) inflammatory diseases. Orally active BK antagonist would be desirable for this purpose. Here, we describe the pharmacological characterization of FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8- quinolinyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acr ylamide) obtained from our screening for nonpeptide, orally active B2 antagonists. (i) FR173657 antagonized [3H]BK binding with IC50 values of 4.6 x 10(-10) and 8.6 x 10(-9) M in membrane preparations of guinea pig ileum and lung, respectively. FR173657 inhibited [3H]BK binding to A431, W138, and IMR90 cell lines of human origin with IC50 values of 2.0 x 10(-9), 2.3 x 10(-9), and 1.7 x 10(-9) M, respectively. FR173657 did not affect [3H]des-Arg10-kallidin (B1 ligand) binding onto IMR90 cells. (ii) FR173657 inhibited guinea pig ileum contractions by BK (6 x 10(-8) M) with an IC50 value of 6.1 x 10(-9) M. Acetylcholine- and histamine-induced contraction of guinea pig ileum was unaffected by FR173657. (iii) Oral administration of FR173657 dose-dependently inhibited BK (5 micrograms/kg) and dextran sulfate (activator of kinin-kallikrein cascade) induced bronchoconstriction with ED50 values of 0.075 and 0.057 mg/kg, respectively. In conclusion, FR173657 is a selective potent, orally active B2 receptor antagonist that can be used to investigate the role of BK in allergic and inflammatory diseases.

Administration, Oral↗

PubMed1996

Repair of aortopulmonary window in an infant with extremely low birth weight.

Although transaortic patch repair under cardiopulmonary bypass is a suitable procedure for aortopulmonary window, another method without cardiopulmonary bypass may be the only one for an infant with extremely low birth weight. We describe a successful repair of an infant with extremely low birth weight (758 g) by closing the window with a clip through a left thoracotomy. Cardiac catheterization 7 months after the operation showed no residual shunt and no stenosis of ascending aorta, pulmonary artery, or coronary arteries in the patient, whom we believe to be one of the smallest with successful repair.

Aortopulmonary Septal Defect↗

PubMed1996

[The effect of initial treatment by FP aqueous nasal spray in patients with Japanese cedar pollinosis].

It is well known that an initial treatment with several kinds of antiallergic medicines is useful for patients suffering from Japanese cedar pollinosis to reduce nasal symptoms during the pollen season. Also topical corticosteroids show a preventive effect as antiallergic medicines. In this study, the preventive effect of topical corticosteroids with antiallergic medicine as an initial treatment was evaluated during the 1995 cedar pollen season a season in which a high pollen count was anticipated. Twenty-five patients with cedar pollinosis were selected and divided into two groups. A and B, A topical corticosteroid (fluticasone propionate; Flunase) as well as antiallergic medicine (azelastin) were administered to patients in group A 4 weeks before the beginning of the pollen season. In group B, only antiallergic medicine was given at the same time as group A and a topical corticosteroid was administered after the appearance of the symptoms. Nasal symptoms and mucosal conditions of the nasal cavity were monitored throughout the pollen season. The inflammatory cells in the mucoepithelial layer of the nasal mucosa were also periodically evaluated by immunohistochemical staining. Nasal symptoms and mucosal conditions in group A were significantly improved compared with patients in group B. The infiltration of macrophages in the mucoepithelial layer of the nasal mucosa was strongly inhibited in group A. The numbers of mast cells and EG2-positive cells in group A were not significantly different from those in group B during the pollen season. According to these results, although not all inflammatory cells were inhibited, the initial treatment with Flunase aqueous nasal spray in addition to the conventional initial treatment with antiallergic medicine is very useful for reducing symptoms even in a season with a large amount of cedar pollen.

Administration, Intranasal↗

PubMed1995

Optimal degree of pulmonary artery banding--adequate circumference ratio to calculated size from normal pulmonary valve dimensions.

These findings suggest that PA banding may be suitable in children with congenital heart disease and excessive pulmonary flow, and that best results are obtained when the band circumference is < 90% of the standard pulmonary valve-ring circumference, as calculated from an equation derived from normal pulmonary valve dimensions. This guideline applies equally well to small infants weighing < 3 kg and to larger patients.

Body Weight↗

PubMed1995

Bone marrow-derived murine mast cells migrate, but do not degranulate, in response to chemokines.

We have determined that several chemokines induce mast cell migration in vitro. This directed migration is dependent on the presence of particular extracellular matrix proteins and the activation status of the cells. Mast cell haptotactic responses were observed in response to various chemokines on vitronectin-, laminin-, and fibronectin-coated filters. Unstimulated mast cells were chemoattracted only by monocyte chemotactic protein-1 and RANTES on vitronectin-coated and, to a lesser extent, laminin-coated filters, whereas IgE-activated mast cells migrated in response to monocyte chemotactic protein-1, regulated on activation normal T expressed and secreted, platelet factor-4, and macrophage inflammatory protein-1 alpha on all three matrix proteins. No significant migration was observed on collagen type IV-coated or uncoated filters. Mast cell migration in response to chemokines on extracellular matrices and its enhancement by IgE-dependent activation provide a mechanism by which cells may be drawn to sites of inflammation. Chemokine-induced mast cell recruitment may be particularly relevant in host defense responses to parasitic infections, allergic reactions, Jones-Mote reactions, and in wound healing.

Animals↗

PubMed1995

Spontaneous aortic thrombosis in a neonate with multiple thrombi in the main branches of the abdominal aorta.

Spontaneous aortic thrombosis in the neonate is a rare entity with a high mortality rate. The present patient, who was diagnosed after showing haematuria and cyanosis, underwent aortic thrombectomy with a Fogarty catheter through a left thoracotomy, but died of sepsis, disseminated intravascular coagulation and multiple organ failure. Autopsy revealed multiple residual thrombi in the main branches of the abdominal aorta and necrosis of the abdominal organs despite a patent thoracoabdominal aorta. In patients with no blood flow in the main branches of the abdominal aorta on preoperative examination, removal of thrombi, including those in the main branches of the abdominal aorta, might be performed in a single, early and aggressive procedure.

Aorta, Abdominal↗

PubMed1995

Localization of histamine N-methyltransferase messenger RNA in human nasal mucosa.

BACKGROUND: Histamine is metabolized mainly by histamine N-methyltransferase (HMT) to N tau-methylhistamine in human nasal mucosa. Human HMT cDNA has been cloned and expressed in COS cells. The purpose of this study was to determine the localization of HMT METHODS: The fragment (nucleotide residues 430-1055) of human HMT cDNA was subcloned in a Bluescript vector (Stratagene, La Jolla, Calif.), and HMT sense anti-sense RNA probes were made with T7 and T3 RNA polymerases. In situ hybridization with digoxigenin-labeled RNA probes was performed on surgical specimens of human nasal turbinates. RESULTS: HMT mRNA was localized in cells in the epithelium and submucosa, and densely in endothelial cells of vessels. No HMT mRNA was identified in the submucosal glands. The presence of HMT mRNA was confirmed by Northern blot analysis, and HMT activities were also detected in nasal mucosa. CONCLUSION: Our study indicates that endothelium expresses HMT mRNA, whereas cells in the epithelium and submucosa, which remain unidentified, are an additional source of HMT mRNA.

Blotting, Northern↗

PubMed1994

Effect of FR128998, a novel PAF receptor antagonist, on endotoxin-induced disseminated intravascular coagulation.

This study aimed to evaluate the effect of FR128998, (1s,6s)-1-benzyl-10-(3-pyridyl-methyl)-7-thia-10-azaspiro [5,6]-dodecan-11-one 7,7-dioxide hydrochloride, a novel platelet activating factor (PAF) receptor antagonist, on endotoxin lipopolysaccharide-induced disseminated intravascular coagulation in rats. Experimental disseminated intravascular coagulation was induced by an infusion of lipopolysaccharide at 0.25 mg/kg/h for 4 h. Simultaneous infusion of FR128998 (0.25 and 1.0 mg/kg/h) with lipopolysaccharide dose dependently inhibited thrombocytopenia, but not leukopenia. The changes in coagulation parameters of disseminated intravascular coagulation, i.e., prolongation of activated partial thromboplastin time and elevated levels of fibrinogen/fibrin degradation products, were also prevented by the treatment with FR128998. In addition, FR128998 attenuated the increase in serum tumor necrosis factor (TNF) which appeared during the initial stage of disseminated intravascular coagulation. FR128998 (10 microM) also inhibited the TNF production by peripheral blood leukocytes or alveolar macrophages stimulated by lipopolysaccharide in vitro. Furthermore, TNF production induced by PAF itself in vitro was also inhibited in the presence of FR128998. These data indicate that PAF plays a pivotal role in the development of disseminated intravascular coagulation via TNF production.

Animals↗

PubMed1994

[Growth of the hypoplastic aortic arch after arch repair for coarctation and interruption of the aorta].

Surgical treatment for a hypoplastic aortic arch associated with coarctation or interruption of the aorta is controversial. We evaluate the changes of diameter of proximal transverse aortic arch after surgery in 28 patients. Proximal transverse aortic arch in all patients was preoperatively 3.5 +/- 0.9 mm (2.5 to 7 mm), and 54 +/- 12% (36 to 84%) to the normal aortic valve dimension (n-AVD: 16.6 X BSA0.6). While postoperative proximal transverse aortic arch was 6.5 +/- 1.8 mm, and 76 +/- 12% to the n-AVD, and significantly grew more than the preoperative arch dimension (p = 0.0001). In 18 patients having two times cardiac catheterization postoperatively, proximal transverse aortic arch was 6.5 +/- 1.6 mm, and 75 +/- 13% to n-AVD on the 1st postoperative examination. On the 2nd examination, the arch was 9.9 +/- 1.9 mm, and 88 +/- 12% to n-AVD, and significantly grew with increasing years (p < or = 0.0003). We concluded that the proximal transverse aortic arch, which was more than 36% to n-AVD in diameter, if not dilated surgically, grew with increasing years after aortic arch repair.

Aorta, Thoracic↗

PubMed1994

[Subaortic stenosis in coarctation or interruption of the aorta--changes of left ventricular outflow tract dimension after aortic arch repair and pulmonary artery banding].

Left ventricular outflow tract (LVOT) dimension was measured in seven patients with coarctation (CoA) or interruption (IAA) of the aorta before and after aortic arch repair and pulmonary artery banding. The age of patients ranged 3 to 69 (mean 16) days, the weight 3.0 to 3.9 (mean 3.4) kg. Associated cardiac anomalies were VSD in 6, MA and DORV in 1. In five patients compared by ultrasound, preoperative LVOT dimension ranged from 3.5 to 5.0 (mean 4.4) mm with the ratio to the normal aortic valve dimension (n-AVD; 16.6 x BSA0.6) from 54 to 82 (mean 69)%. Postoperative dimension increased 5.0 to 7.4 (mean 5.7) mm and the ratio to the n-AVD increased 65 to 89 (mean 80)%. In three patients compared by LV graphy, preoperative LVOT dimension ranged from 4.0 to 4.5 (4.2) mm and the ratio ranged from 61 to 72 (68)%. Postoperative dimension increased from 4.5 to 6.7 (5.3) mm, and 74 to 80 (78)% to n-AVD after operation. Postoperative pressure gradients between LV and ascending aorta in each patient were 1 to 9 (mean 6) mmHg. In any patients, LVOT obstruction did not advance after aortic arch repair and pulmonary artery banding.

Aorta↗

PubMed1993

A 5-lipoxygenase inhibitor, FR110302, inhibits ozone-induced airway hyperresponsiveness in guinea pigs and dogs.

Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. In the present study we examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance (Rrs) was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve of Rrs to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 h. In a control group of guinea pigs, delta log PC100 (the index of the ozone-induced airway hyperresponsiveness) was 0.58 +/- 0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished delta log PC100 (10 mg/kg: 0.22 +/- 0.10; 100 mg/kg; 0.11 +/- 0.06). Dogs were exposed to 3 ppm ozone for 2 h. In a control group of dogs, delta log Dmin (another index of the ozone-induced airway hyperresponsiveness) was 1.24 +/- 0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg p.o.) significantly diminished delta log Dmin (1 mg/kg: 0.60 +/- 0.18; 3.2 mg/kg: 0.27 +/- 0.12). These results suggest that FR110302 may be a useful drug for attenuating airway hyperresponsiveness in asthmatic patients.

Acetylcholine↗

PubMed1993

[Three patients with gas gangrene of the head and neck].

Three patients with non-clostridial gas gangrene of the neck are reported. Patient 1 was a 57-year-old man, patient 2 a 63-year-old woman, and patient 3 a 44-year-old man. All three were treated by thorough debridement and precise administration of antibiotics. We also discuss 26 cases (including our 3) of gas gangrene of the head and neck, reported in Japan from 1975 to 1992, from which the following data were obtained: 1. The 26 patients consisted of 17 males and 9 females. 2. They ranged in age from 2 to 88 years, with a mean 56.5 years. 3. Causes included acute pharyngolaryngeal inflammation (46%), dental disease (27%), trauma (8%) and unknown etiology (19%). 4. As a result of bacteriological assessment, the condition was found to be attributable to Clostridium in only 2 patients, and in the remainder the condition was non-clostridial. 5. The mortality rate was 15%. The patients who died were at least 80 years old, and their prognosis had been poor. 6. CT was useful for diagnosis and treatment.

Adult↗

PubMed1992

Human blood monocyte activation by Nocardia rubra cell wall skeleton for productions of interleukin 1 and tumor necrosis factor-alpha.

Human blood monocytes were obtained from peripheral blood of healthy donors by counter-flow centrifugal elutriation. Functional integrity of monocytes for production of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in response to Nocardia rubra cell wall skeleton (N-CWS) was examined by bioassay and enzyme immunoassay. Monocytes treated with N-CWS at more than 0.5 microgram/ml produced IL-1 and TNF-alpha extracellularly. Extracellular TNF activity appeared within 4 h, and maximally, 16 h after N-CWS stimulation, whereas longer time was needed for IL-1 activity to appear, the peak production being at 24 h. The neutralizing experiment also showed that anti TNF-alpha antibody did not affect IL-1 production by the monocytes treated with N-CWS, suggesting independency of IL-1 production of TNF-alpha. These results suggest that the therapeutic antitumor effect of N-CWS is due, in part at least, to the augmented production of these monokines.

Bacterial Proteins↗

PubMed1992

Permeability changes of the blood-labyrinth barrier measured in vivo during experimental treatments.

The communication between blood and cochlear perilymph was investigated using the tracer ion trimethylphenylammonium (TMPA). TMPA can be detected in micromolar concentrations by ion-selective microelectrodes, allowing it to be used as an almost ideal marker to study intercommunication between fluid compartments. TMPA-sensitive electrodes were sealed into the cochlear scalae, using procedures which avoided the artifactual displacement of perilymph by cerebrospinal fluid (CSF). TMPA was infused intravenously at a low rate to produce a plasma concentration of approximately 0.5, mM. The time course of entry into perilymph of scala tympani (ST), scala vestibuli (SV) and into CSF were compared. After 90 min infusion, the mean CSF concentration reached 14.3% of that measured in plasma. The TMPA concentrations measured in ST and SV perilymph were significantly lower than those recorded in CSF, only reaching an average of 6.5% and 3.7% of the plasma concentration respectively after 90 min. The slow entry of TMPA confirms the existence of a tight blood-labyrinth barrier, equivalent to the blood-brain or blood-CSF barriers. The rate of TMPA entry into perilymph was increased by epinephrine-induced hypertension or by simultaneous administration of histamine and prostaglandin E2. These treatments are presumed to increase the permeability of the blood-labyrinth barrier. Characterization and manipulation of blood-labyrinth barrier permeability could be important to our understanding cochlear pathology.

Animals↗

PubMed1992

A 5-lipoxygenase inhibitor, FR110302, suppresses airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles in rats.

To study the role of chemical mediators in airway hyperresponsiveness and simultaneous eosinophilia, we examined effects of a potent 5-lipoxygenase inhibitor FR110302 and those of prednisolone, indomethacin, platelet-activating factor (PAF) antagonist (RP-59227) and leukotriene C4 (LTC4) antagonist (ONO-1078) on airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles. Sephadex G200 particles (2.5 mg/kg) were injected intravenously to rats and 3 days later the airway hyperresponsiveness to acetylcholine (ACh) and the eosinophilia in the bronchoalveolar lavage (BAL) fluids were observed. FR110302 (10 mg/kg b.i.d.p.o.) significantly suppressed both of these indicators of asthma. The amounts of immunoreactive LTB4,C4 (i-LTB4, C4) in the BAL fluid were measured by radioimmunoassay. The amounts of i-LTB4,C4 in the FR110302-treated rats were significantly less compared with that in the Sephadex-injected controls. Prednisolone completely inhibited the airway hyperresponsiveness. PAF antagonist and LTC4 antagonist partially inhibited the airway hyperresponsiveness, and indomethacin had no effect. The results indicate that 5-lipoxygenase products play important roles in the Sephadex-induced airway hyperresponsiveness and lung eosinophilia in rats.

Acetylcholine↗

PubMed1991

Evaluation of procedures to reduce fluid flow in the fistulized guinea-pig cochlea.

The rate of longitudinal flow of fluid in scala tympani (ST) has been quantified under a number of experimental conditions. The method used to measure flow involved using a tracer ion (trimethylphenylammonium: TMPA) as a volume flow marker. Movement of marked perilymph was monitored by ion-selective microelectrodes which were capable of detecting exceedingly low concentrations of TMPA. Our results show that when the cochlea is perforated at the apex, flow rates of 400-500 nl/min are induced in ST, compared to the normal very slow rate of 2 nl/min when the cochlea is sealed. This artifactual flow of CSF through the perforated cochlea can be reduced to 6.9 nl/min by releasing the hydrostatic pressure of cerebrospinal fluid (CSF) or further reduced to 1.8 nl/min by surgically obstructing the cochlear aqueduct. In addition, we observed no basally-directed flow in ST when the round window (RW) was perforated, demonstrating that perilymph is not produced in volume as previously assumed. This study demonstrates the importance of separating artifactual flows, induced by the experimental procedures required to access the cochlear fluids, from the low flow rates which occur in normal, physiologic conditions.

Action Potentials↗

PubMed1990

Heterogeneity in responses of human blood monocytes to granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has stimulatory effects on various monocyte functions. We examined whether all or only some blood monocytes could respond to GM-CSF. Monocytes from peripheral blood of healthy donors were separated by size into five fractions by counter-flow centrifugal elutriation (CCE). The phagocytic activities of monocytes in these fractions depended on the size of the cells. On activation by bacteria-derived stimuli, these fractions showed similar responses of production of monokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) and cytotoxicity against allogeneic tumor cells. On treatment of these fractions with optimal concentration of GM-CSF, fractions 3, 4, and 5 showed tumoricidal activity and produced cell-associated IL-1, fraction 3 producing the most, whereas release of IL-1 and TNF in the supernatant was not observed. The cell-associated IL-1 was identified as IL-1 alpha, not IL-1 beta, by neutralizing tests with antisera against IL-1 alpha and IL-1 beta. GM-CSF also induced the proliferative and colony-forming responses of medium and large monocytes. These observations suggest that adoptive therapy with macrophage progenitor cells in peripheral blood may be useful in combination with GM-CSF for treatment of monocytopenia after chemotherapy or radiation therapy.

Cell Division↗