Search PubMed⌕ Search

Biomedical subjects

N Inagaki

Publications and source records attributed to N Inagaki.

At least 217 records · Page 12Linked to original sources
PubMed1989

Exon-intron organization, expression, and chromosomal localization of the human motilin gene.

The human motilin gene has been isolated and characterized. The gene spans about 9 kilobase pairs (kb) and the 0.7 kb motilin mRNA is encoded by five exons. The 22-amino-acid motilin sequence is encoded by exons 2 and 3. The human motilin gene was mapped to the p21.2----p21.3 region of chromosome 6 by hybridization of the cloned cDNA to DNAs from a panel of reduced human-mouse somatic cell hybrids and by in situ hybridization to human prometaphase chromosomes. RNA blotting using RNA prepared from various regions of the human gastrointestinal tract revealed high levels of motilin mRNA in duodenum and lower levels in the antrum of the stomach; motilin mRNA could not be detected by this procedure in the esophagus, cardia of the stomach, descending colon or gallbladder.

Amino Acid Sequence↗
PubMed1989

The role of thromboxane A2 (TxA2) in allergic cutaneous reactions and the effect of (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl]-2-propenoic acid hydrochloride (OKY-046), a TxA2 synthetase inhibitor.

To study the role of thromboxane A2 (TxA2) in cutaneous allergic reactions, the effect of (E)-3-[p-(1H-Imidazol-1-ylmethyl)phenyl]-2-propenoic acid hydrochloride (OKY-046), a selective TxA2 synthetase inhibitor, on cutaneous reactions in rats and mice was studied. Simultaneously, the effect of 9,11-methanoepoxy-prostaglandin H2 (U-46619), a stable analogue of TxA2, on capillary permeability in mouse and rat skin was investigated. Passive cutaneous anaphylaxis (PCA) in mouse ear was clearly inhibited by OKY-046 but not by indomethacin. The inhibitory action of OKY-046 was not influenced by pretreatment with indomethacin. Moreover, prostaglandin I2, which accumulated as a result of the inhibition of TxA2 synthetase, did not affect the PCA. But, the dye leakages caused by histamine, serotonin and leukotriene C4 in mouse ear were clearly inhibited by OKY-046. In addition, OKY-046 inhibited rat reversed cutaneous anaphylaxis, but its inhibitory action was not affected by pretreatment with indomethacin. Contrary to the above results, rat footpad passive Arthus reaction and mouse footpad tuberculin delayed hypersensitivity reaction were not affected by OKY-046. Additionally, U-46619 did not cause an increase of capillary permeability in either mouse and rat skin. These results suggest a slight role of TxA2 in cutaneous allergic reactions in mice and rats and the efficacy of OKY-046 on Type I and II reactions regardless of the inhibition of TxA2 synthetase activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Inhibitory effects of beta-adrenergic stimulants on increased vascular permeability caused by passive cutaneous anaphylaxis, allergic mediators, and mediator releasers in rats.

The effects of isoproterenol, salbutamol, theophylline, and forskolin on IgE antibody-mediated homologous passive cutaneous anaphylaxis (PCA) and on skin reactions caused by allergic mediators and mediator releasers were investigated in rats. Isoproterenol and salbutamol dose-dependently inhibited the PCA and skin reactions caused by histamine, serotonin, and leukotriene C4 (LTC4), elicited at the same time in the same rat. These agents also dose-dependently inhibited the skin reactions caused by platelet-activating factor (PAF), leukotriene D4 (LTD4), compound 48/80 (48/80), and calcium ionophore A23187 (A23187). Propranolol overcame the inhibitory effect of isoproterenol on PCA and skin reactions in a dose-dependent manner. Theophylline and forskolin showed similar effects as the beta-adrenergic stimulants. These results indicate that beta-adrenergic stimulants inhibit the increased vascular permeability caused by allergic mediators, and suggest that this activity of beta-adrenergic stimulants might play an important role in their antiallergic actions. Inhibition of increased vascular permeability might be mediated via beta-receptors and may be related to the increase in intracellular cyclic AMP levels.

Adrenergic beta-Agonists↗
PubMed1989

Anti-asthmatic activity of newly synthesized calcium antagonists: 2-n-butyl-1 (N-methyl-n-[2-(N',N'-dimethylamino)ethyl]amino) -5,6-methylenedioxy-indene and -indane.

The anti-asthmatic activity of the newly synthesized methylenedioxyindene (MDI) derivatives, 2-n-butyl-1 (N-methyl-N-[2-(N', N' -dimethylamino)ethyl]amino)-5, 6-methylenedioxy-indene (MDI-C) and -indane (MDI-D), were investigated in vitro and in vivo in guinea pigs. The in vitro pharmacological activity of both derivatives was compared to that of 8-(diethylamino)octyl-3,4, 5-trimethyoxybezoate hydrochloride. All three agents caused a concentration-dependent inhibition of the antigen-induced contraction of sensitized guinea pig tracheal smooth muscle. In histamine and leukotriene D4-induced contractions of guinea pig tracheal smooth muscle, each agent showed clear antagonistic actions. Additionally, all three agents demonstrated potent calcium antagonistic actions via inhibition of guinea pig tracheal smooth muscle contractions caused by CaCl2 in a high potassium and Ca-free medium and by compound 48/80 in a solution of ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid in a contained Ca-free medium. MDI-C and MDI-D inhibited the antigen-induced release of histamine and slow reacting substance of anaphylaxis from sensitized guinea pig lung tissue. Lastly, both MDI is clearly inhibited asthmatic respiratory disorders without affecting blood pressure in guinea pigs.

Animals↗
PubMed1989

Gastric inhibitory polypeptide: structure and chromosomal localization of the human gene.

Gastric inhibitory polypeptide (GIP) is a 42-amino-acid hormone which may have a role in the regulation of insulin secretion. The characterization of cDNA clones encoding this hormone indicates that it is derived by proteolytic processing of a 153-amino-acid precursor. The human gene coding for the human GIP precursor spans approximately 10 kilobase pairs and consists of six exons. Similar to genes encoding other members of the glucagon superfamily, each exon appears to encode a distinct region of the GIP precursor or its mRNA. The promoter region of the human GIP gene contains potential binding sites for a number of transcriptional factors including Sp 1, AP-1, and AP-2. The human GIP gene has been assigned to chromosome 17q21.3----q22.

Base Sequence↗
PubMed1989

Evaluation of anti-allergic effects of 1-substituted 2-n-butyl-methylenedioxy indenes.

The effects of ten 1-substituted 2-n-butyl-5,6-methylenedioxyindenes on mice and guinea pigs were investigated for their allergic reactions in the development of a new anti-allergic drug. Anti-allergic effects were determined by testing the effect of agents on passive cutaneous anaphylaxis (PCA) in mice and Schultz-Dale reaction in guinea pig tracheal muscle. 2-Butyl-1-[N-methyl-N-[2-(N',N'-dimethylamino) ethyl]amino]5,6- methylenedioxyindene (1) indicated the most potent anti-allergic activity. Since our previous experiments indicated that 2-n-butyl 3-dimethyl amino-5,6-methylenedioxyindene (MDI-A) and its derivatives showed a potent anti-allergic effect by interfering with the calcium (Ca) movement in the allergic reaction in guinea pigs, the effect of 1 and MDI-A on allergic reaction and Ca-induced contraction of tracheal muscle in these animals were compared. The present data indicate the superiority of 1 in both reactions.

Animals↗
PubMed1989

Pharmacological study of phospholipase A2-induced histamine release from rat peritoneal mast cells.

The effect of some drugs on phospholipase A2 (PLA2)-induced histamine release from rat peritoneal mast cells was investigated. 1. PLA2 (Naja naja) caused the release of histamine from rat peritoneal mast cells in a dose related fashion. 2. The release of histamine by PLA2 was decreased by the removal of each of calcium and glucose from the reaction medium (Tyrode's solution). 3. p-Bromophenacyl bromide and mepacrine, PLA2 inhibitors, inhibited the release of histamine caused by PLA2. 4. Cinnarizine and nifedipine, calcium channel blockers, and oxatomide, KC-404, tranilast and disodium cromoglycate, anti-allergic agents, also inhibited the PLA2-induced histamine release. 5. When prednisolone (0.5 mg/kg) was administered i.p. 2, 3 and 4 h prior to the harvest of the mast cells, the amount of histamine released by PLA2 ex vivo was significantly decreased. Hydrocortisone, prednisolone and dexamethasone clearly inhibited the release of histamine from mast cells when they were administered 4 h prior to harvest of the cells.

Acetophenones↗
PubMed1989

Anti-allergic action of glucocorticoids (II). Effect of glucocorticoids on cell mediated (type IV) allergic reactions.

The effects of three glucocorticoids (steroids; hydrocortisone, prednisolone and dexamethasone) on cell mediated hypersensitivity (type IV) reactions in rats and mice were studied. All the steroids inhibited both the induction and the effector phases of type IV reaction induced by sheep red blood cells (SRBC) in mouse footpads. The local graft vs host reaction induced by lymphocytes from Brown Norway rats into the footpads of (Lewis x Brown Norway) F1 rats was also clearly inhibited by steroids. The inhibitory action of steroids on footpad reactions induced by SRBC was clearly prevented by pretreatment with non-corticoidal steroids (17 alpha-methyltestosterone, androstenedione and progesterone). The release of lymphokines, macrophage chemotactic factor (MCF) and skin reactive factor (SRF) was inhibited by each steroid at a high concentration. Moreover, steroids inhibited the activity of MCF in vitro and SRF in vivo.

Animals↗
PubMed1989

[Treatment of acute lymphocytic leukemia in adult].

Since April, 1978 to October, 1988, 66 acute lymphocytic leukemia (ALL) patients aged 15 to 79 (21 L1, 43 L2, 2 L3/6 Ph1+) were treated with 3 different therapeutic protocols. The drugs used for induction were VCR (VDS) + Pred, followed by DNR + VCR (VDS) + 6MP + Pred and VCR (VDS) + L-asp + Pred in protocol I, Ad + VCR + Pred in protocol II and DNR + VCR + Pred in protocol III. Complete remission (CR) was attained in 72.7% of 66 patients. The CR rate of each group as followings; 71.4% in protocol I and 75.0% in protocol II and III, respectively. The median duration of remission was 10.2 months + and the probability of being in continuous CR at 3 years was 21.9%. For the 48 patients in remission the median survival was 17.8 months and the probability of being alive at 3 years was 24.3%. The intensified induction and consolidation therapy is expected in the cure oriented treatment of adult ALL.

Adolescent↗
PubMed1989

[Treatment of urinary tract infection with cefixime].

Cefixime (CFIX) was administered orally in the treatment of 59 cases of urinary tract infection (UTI). According to the response criteria defined by the Japanese UTI committee, the rate of clinical efficacy for 26 cases of uncomplicated cystitis was 96.2%. The rate of clinical effectiveness of five patients with complicated UTI and five with uncomplicated pyelonephritis was 80.0%. In the other 23 cases which did not meet the response criteria, the efficacy rate was also high. The results indicated that CFIX was an effective drug for the treatment of UTI.

Anti-Infective Agents, Urinary↗
PubMed1989

[A clinical study of prostatic carcinoma].

Seventy seven patients with prostatic carcinoma were treated in our clinic between 1977 and 1986. Most of them were treated by a hormonal agent as the first therapy. None of the 9 stage A1 cases showed any reactivation, but 4 of the 5 stage A2 cases relapsed to metastatic disease. The chemotherapy performed in 3 of the 4 reactivated cases had no obvious effect on the disease. Seven of the 8 patients with stage B disease were alive without relapse. Relapse was seen in the other patient who had poorly differentiated carcinoma and chemotherapy in this case resulted in stable disease for the present. Four of the 15 stage C cases including 3 poorly differentiated carcinomas were hormone resistant or reactivated. For these resistant cases radiotherapy and/or the chemotherapy were performed, but a response was seen in only one case. Consequently, the first therapy for stage A2, B and C of poorly differentiated carcinoma must be improved. Of the 40 stage D cases, 4 patients who were treated by an early combination of hormonal therapy and chemotherapy had a better prognosis than the others. These 4 patients had poorly differentiated carcinomas with multiple bone metastases. Two of these 4 patients were alive without relapse for 17 and 72 months, and one of the 2 patients with relapse was also alive for 75 months. We believe that early chemotherapy is the key for better prognosis in stage D cases.

Androgen Antagonists↗
PubMed1988

Organization of histaminergic fibers in the rat brain.

Detailed information on innervation of the histaminergic system in the brain is essential to an understanding of the physiological roles of this system. In a previous immunocytochemical study with antihistidine decarboxylase (HDC) antibody, we detected extensive networks of histaminergic fibers in many areas of the rat brain (Watanabe et al., '84). In the present study, we improved the immunocytochemical procedure and examined the detailed distribution of histaminergic innervation in the rat brain with anti-HDC antibody. As reported previously, the highest concentrations of fibers were found in the hypothalamic nuclei and medial forebrain bundle. With the modified procedure, we detected more dense networks of HDC-immunoreactive (HDCI) fibers. Furthermore, we demonstrated for the first time the existence of HDCI fibers in other regions, namely, the thalamic nuclei, median eminence, fimbria of the hippocampus, habenular nuclei, superior colliculus, nucleus of the optic tract, parabrachial nuclei, mesencephalic trigeminal nucleus, superior, lateral, and spinal vestibular nuclei, posterior lobe of the hypophysis, and vascular organ of the lamina terminalis. We also found dense transverse fibers in the retrochiasmatic area and supraoptic decussation, which suggests bilateral innervation of the histaminergic system. These results indicate that innervation of the rat brain by the histaminergic system is more extensive than observed previously.

Animals↗
PubMed1988

Histaminergic nerve fibers in the median eminence and hypophysis of rats demonstrated immunocytochemically with antibodies against histidine decarboxylase and histamine.

Histaminergic fibers in the median eminence and hypophysis of rats were examined immunocytochemically with antibodies against histidine decarboxylase (HDC), the sole histamine-synthesizing enzyme, and against histamine itself. A similar distribution of immunoreactive fibers was observed with these two antibodies. In the median eminence, immunoreactive fibers were mainly located in the internal layer and could be traced to the posterior lobe of the hypophysis. A few fibers were detected in the external layer of the median eminence, but none in the anterior or intermediate lobe of the hypophysis. These observations suggest that neuronal histamine may take part in regulation of the hypothalamo-neurohypophysial neuroendocrine system in rats.

Animals↗
PubMed1988

Effect of vitamin D on gastrin and gastric somatostatin secretion from the isolated perfused rat stomach.

We have studied the role of vitamin D in the regulation of gastrin and gastric somatostatin secretion from the isolated perfused rat stomach. In Ca-deficient vitamin D-deficient rats (Ca(-)D(-) group), the basal and bombesin-stimulated gastrin and gastric somatostatin release (basal IRGa, basal IRS, sigma delta IRGa, and sigma delta IRS) all were significantly lower than in Ca-replete vitamin D-replete rats (Ca(+)D(+) group), and also lower than in Ca-replete vitamin D-deficient rats (Ca(+)D(-) group) except for the basal IRGa. In the Ca(+)D(-) group, the basal IRGa and IRS, and sigma delta IRS were not significantly lower than in the Ca(+)D(+) group. Although there was no significant impairment in basal IRGa, sigma delta IRGa in the Ca(+)D(-) group was significantly lower than in the Ca(+)D(+) control group. Thus, the gastrin and gastric somatostatin secretion from the Ca-deficient vitamin D-deficient rats were impaired. In addition, the impaired gastrin and gastric somatostatin secretions seem to be caused not only by a decrease in serum Ca but also by the reduced effect of the vitamin D on the G and gastric D cells.

Animals↗
PubMed1988

Effects of different drugs on passive cutaneous anaphylaxis elicited in the mouse ear at 1.5 hours.

IgG1, antibody-mediated homologous passive cutaneous anaphylaxis at 1.5 h (1.5-hour PCA) was elicited in the ears of mice and the effects of different drugs were studied. The reaction, as measured by the amount of extravasated dye, was inhibited by antihistamines, antiserotonins, cyclic AMP-elevating agents, tranilast and ketotifen, but not by an SRS-A antagonist (FLP 55712), lipoxygenase inhibitors, cyclooxygenase inhibitors and disodium cromoglycate. These results suggest that the pharmacological profile of 1.5-hour PCA resembles that of 48-hour PCA mediated by IgE antibody in the mouse ear.

Animals↗
PubMed1988

Comparative study of IgG1 and IgE antibody mediated homologous PCA in the mouse ear. Lack of cross-desensitization of IgG1 antibody mediated PCA to IgE antibody mediated PCA.

To characterize IgG1 antibody and IgE antibody mediated homologous passive cutaneous anaphylaxis (PCA) in the mouse ear, cross-desensitization was studied using a double-sensitizing technique. Mice were sensitized by injecting into their ears a mixture of two kinds of antibodies with distinct antigen specificities, and PCAs were elicited twice with specific antigens at an appropriate interval. The first PCA was elicited with one antigen free from Evans blue dye and the second with the other antigen in the presence of Evans blue to visualize the reaction. The amount of extravasated dye caused by the latter was determined colorimetrically and compared to that of control which did not receive the first challenge. In PCA mediated by IgG1 antibodies, elicitation of the first reaction significantly inhibited the second reaction evoked after 6, 12, or 24 h. Using IgE antibodies, elicitation of the first PCA also significantly inhibited the following reaction. Inhibition of the second reaction was observed 6 h to 12 days after the first reaction. Conversely, IgG1 antibody mediated PCA did not affect the following reaction caused by IgE antibody. These results strongly suggest that alteration of skin mast cells is smaller in IgG1 antibody than in IgE antibody mediated PCA, when reactions with a similar intensity are evoked. Therefore, it is also suggested that the slight reaction of mast cells initiated by IgG1 antibody might be potentiated by another mechanism in IgG1 antibody mediated PCA.

Animals↗