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F Nambu

Publications and source records attributed to F Nambu.

15 recordsLinked to original sources
PubMed2001

Isolation of a cDNA encoding a putative SPARC from the brine shrimp, Artemia franciscana.

SPARC (Secreted protein, acidic, rich in cysteine) is an extracellular matrix-associated and anti-adhesive glycoprotein extensively studied in vertebrates. Its presence among invertebrates has been reported in nematodes and flies. We cloned a cDNA containing a complete open reading frame for SPARC from the brine shrimp, Artemia franciscana. The amino acid sequence identity between the Artemia and the fly SPARCs was 55%, whereas that of the Artemia and the nematode proteins was 45%. Artemia and vertebrates exhibited a sequence identity of 30% in the predicted aa sequences. The SPARC consisted of four domains commonly found among reported SPARCs. The protein comprised 291 amino acids, having a signal peptide, a follistatin-like domain, one N-glycosylation site and one calcium-binding EF-hand motif. Fourteen cysteine residues conserved among all the secreted forms of SPARCs were present in the Artemia SPARC, and four extra cysteine residues were also found in it. The extra residues were conserved among SPARCs of the arthropods and the nematode. Phylogenetic analyses showed that the sequences of SPARCs were grouped into those of vertebrates and invertebrates. Though the structural organization of SPARC was conserved among all the species studied, SPARC within a group was highly conserved within that group, but divergent between the two. Northern blots revealed the presence of a 1.1 kb mRNA, which was faintly expressed in embryos and considerably detected in prenauplii and nauplii. The isolation of a SPARC cDNA from Artemia franciscana provides intriguing features of the divergent protein, SPARC.

Amino Acid Motifs↗
PubMed2000

[A method for culturing Artemia].

Artemia sp. is classified into phylum Arthropoda and class Crustacea. Ecological and experimental studies of this animal have been reported using wild species. In order to isolate inbred strains of Artemia, we have established a subculturing method for siblings of Artemia. Details of our practice on the culturing method of Artemia are described and the recent classification of Artemia is presented.

Animal Husbandry↗
PubMed1997

Gene expression of trehalase during post-dormant development of the brine shrimp, Artemia: comparison of the two species.

Based on a homology screening approach, two degenerate oligonucleotides were employed as primers in a polymerase chain reaction to amplify a fragment of DNA encoding trehalase with a template of cDNA derived from embryos of American Artemia. Sequence analysis revealed that the fragment was composed of 228 bp comprising 76 amino acids, and highly homologous to trehalases of Tenebrio molitor (mealworm beetle), rabbit, Caenorhabditis elegans, Bombyx mori (silkworm) and Escherichia coli treA and treF (58-38%, in order of description). This fragment was used as a hybridization probe. A Northern blot analysis on American Artemia showed three transcripts of 5.0, 2.7 and 2.2 kb, and the two larger transcripts were also detected in Chinese Artemia. The developmental profile of the gene expression and the trehalase activity suggest that the transcripts of 5.0 and (or) 2.7 kb in both Artemia may be directly or indirectly related to translation of the trehalase. A Southern blot analysis on both Artemia suggested the existence of two highly homologous genes or one gene having an intron within the region where the probe binds in their haploid genome.

Amino Acid Sequence↗
PubMed1997

Effects of steroid 5alpha-reductase inhibitor ONO-9302 and anti-androgen allylestrenol on the prostatic growth, and plasma and prostatic hormone levels in rats.

ONO-9302 [epristeride; (-)-17beta-(tert-butylcarbamoyl)androsta-3,5-diene-3-carboxy lic acid] is a novel inhibitor of steroid 5alpha-reductase. We studied in vitro and in vivo effects of ONO-9302 on the rat prostatic tissue in comparison with those of the anti-androgen allylestrenol. ONO-9302 inhibited the rat prostatic enzyme with an IC50 value of 11 nM, whereas allylestrenol was about 80,000-fold less potent. The growth of ventral prostate, which was induced by the subcutaneous injection of testosterone propionate in the castrated rats, was significantly reduced by ONO-9302 at oral doses of 1-100 mg/kg/day. Allylestrenol showed a significant effect only at a dose of 100 mg/kg/day. In mature male rats, ONO-9302 significantly reduced the ventral prostate weight at doses of 10-100 mg/kg/day and decreased prostatic 5alpha-dihydrotestosterone (DHT) content associated with a rise in testosterone (T) content at doses of 0.1-100 mg/kg/day. Plasma hormone levels (i.e., T, DHT, luteinizing hormone (LH) and follicle stimulating hormone (FSH)) were not altered significantly. Allylestrenol significantly reduced the ventral prostate weight at doses of 10-100 mg/kg/day. However, unlike ONO-9302, allylestrenol reduced both the prostatic DHT and T contents and also lowered plasma T, DHT, LH and FSH levels at a dose of 30 mg/kg/day. These results suggest that ONO-9302 reduces the prostatic growth by inhibiting the conversion of T to DHT in the prostate without lowering blood T level unlike anti-androgen drugs.

5-alpha Reductase Inhibitors↗
PubMed1993

Effect of a peptide leukotriene receptor antagonist, ONO-1078, on guinea-pig models of asthma.

Peptide leukotrienes have been suggested to play an important role in bronchial asthma. As antigen-induced bronchoconstrictions, airway hyperreactivity, and pulmonary eosinophil accumulation are characteristics of the pathology of asthma, we investigated the effect of a peptide leukotriene receptor antagonist, ONO-1078, on these responses using guinea-pig models of asthma. Oral administration of ONO-1078 (3 mg/kg) significantly inhibited slow-reacting substance of anaphylaxis-mediated bronchoconstriction induced by i.v. administered ovalbumin. ONO-1078 (30-100 mg/kg), when administered orally both 1 h before and 4 h after ovalbumin challenge, significantly reduced immediate- and late-phase asthmatic responses, with peak responses occurring immediately and 5-11 h after challenge with inhaled ovalbumin. Oral administration of ONO-1078 significantly reduced the airway hyperreactivity (10-30 mg/kg) and the pulmonary eosinophil accumulation (30-100 mg/kg) observed 4 and 24 h after ovalbumin challenge, respectively. These results suggest that ONO-1078 may be of therapeutic use for bronchial asthma.

Acetylcholine↗
PubMed1992

In vivo pharmacologic profile of ONO-1078: a potent, selective and orally active peptide leukotriene (LT) antagonist.

We investigated the in vivo antagonistic activity of ONO-1078 against peptide leukotrienes (LTs) in guinea pigs. ONO-1078, when administered p.o. (0.3-3 mg/kg), caused a dose-dependent reduction of LTC4-, LTD4- and LTE4-induced bronchoconstriction, LTD4-induced airway microvascular leakage and LTD4-induced increase in cutaneous vascular permeability. When administered intravenously, ONO-1078 (3-30 micrograms/kg) inhibited these responses approximately 200-600 fold more potently than FPL55712. When guinea pigs were treated with indomethacin to examine the antagonism of ONO-1078 on the direct action against peptide LTs, intravenous (3-30 micrograms/kg) and oral (0.3-3 mg/kg) administration of ONO-1078 also inhibited LTC4- and LTD4-induced bronchoconstriction, and its activity was approximately 300-500 fold more potent than that of FPL55712. ONO-1078 (10 mg/kg, i.v.) had no inhibitory effect on bronchoconstrictions induced by histamine, acetylcholine, serotonin, arachidonic acid, LTB4, prostaglandin (PG) F2 alpha, PGD2, 9 alpha, 11 beta-PGF2, a stable thromboxane A2 mimetic agent and platelet activating factor. Furthermore, oral administration of ONO-1078 (1-10 mg/kg) inhibited slow-reacting substance of anaphylaxis mediated bronchoconstriction induced by antigen in a dose-dependent manner. These results indicate that ONO-1078 is an extremely potent, selective and orally active peptide LT antagonist and that oral administration of ONO-1078 antagonizes not only exogenously administered peptide LTs but also endogenous peptide LTs.

Animals↗
PubMed1990

OKY-046 inhibits anaphylactic bronchoconstriction and reduces histamine level in bronchoalveolar lavage fluid in sensitized guinea pigs.

We investigated the effects of OKY-046, a potent and selective thromboxane A2 (TxA2) synthetase inhibitor, on anaphylactic bronchoconstriction and release of chemical mediators into airway lumen in sensitized guinea pigs in vivo. OKY-046 dose-dependently inhibited antigen-induced anaphylactic bronchoconstriction with or without mepyramine, a histamine H1 antagonist. In the presence of mepyramine, OKY-046 (300 mg/kg, p.o.) elicited significant reductions in histamine (1 min) and TxB2 increases (1-15 min) in bronchoalveolar lavage (BAL) fluid but significantly increased the plasma level of 6-keto-PGF1 alpha, a stable PGI2 metabolite, after antigen challenge. On the contrary, indomethacin only significantly reduced increases in TxB2 levels. These results suggest that the antiasthmatic effect of OKY-046 is probably due to inhibition of TxA2 synthesis and suppression of histamine release via a PGI2 shunting mechanism.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Inhibition of endogenous leukotriene-mediated lung anaphylaxis in guinea pigs by a novel receptor antagonist ONO-1078.

The inhibitory effect of ONO-1078, a novel leukotriene (LT) receptor antagonist, was investigated on guinea pig lung anaphylaxis in vitro and in vivo. It was demonstrated that this compound could inhibit the late phase of contractile responses in Schultz-Dale reactions and endogenous LT-mediated bronchoconstrictions in passively sensitized guinea pigs, in a dose-dependent fashion, implying its clinical usefulness in the treatment of human bronchial asthma.

Anaphylaxis↗
PubMed1990

[Effect of OKY-046 on airway hyperresponsiveness induced by ozone in dogs].

To elucidate the possible involvement of thromboxane A2 (TxA2) in airway hyperresponsiveness, we examined the effect of OKY-046, a potent and selective inhibitor of TxA2 synthetase, on airway hyperresponsiveness induced by ozone exposure in dogs. Ozone exposure (3 ppm, 2 hr) markedly increased airway responsiveness to inhaled methacholine without affecting basal respiratory resistance. Although ozone also caused a slight but significant increase in neutrophil number in the bronchoalveolar lavage fluid, there was no correlation between the level of airway hyperresponsiveness and increased neutrophil number. Although OKY-046 significantly inhibited the increases in airway hyperresponsiveness in a dose-dependent manner at doses ranging from 100 to 300 mg/kg, p.o., the compound did not affect the basal airway responsiveness and respiratory resistance at 300 mg/kg, p.o. Inhalation of the subthreshold concentration (i.e., the highest dose which did not cause bronchoconstriction) of STA2 (a stable TxA2 mimetic agent) elicited a significant increase in airway responsiveness to methacholine. These results suggest that TxA2 may play a role in mediating ozone-induced airway hyperresponsiveness. However, the accumulation of neutrophils in the airway lumen may not be essential for the development of airway hyperresponsiveness.

Acrylates↗
PubMed1990

Inhibitory effects of OKY-046 on spasmogen-induced bronchoconstrictions in sensitized and non-sensitized guinea pigs.

We examined the effect of thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on bronchoconstriction induced by antigen and various spasmogenic mediators in guinea pigs in vivo. Further, inhibitory activities of OKY-046 on contractions of isolated tracheae and lung parenchymal strips induced by various contractile agents were also investigated in vitro. OKY-046, but not indomethacin, significantly inhibited antigen-induced bronchoconstriction in a dose-dependent manner. Moreover, OKY-046 attenuated bronchoconstrictions induced by peptide leukotrienes (LTs) and platelet activating factor (PAF), but not those by histamine, prostaglandin D2 (PGD2) and STA2 (a stable TXA2 mimetic agent). Although contractile responses induced by spasmogens such as peptide LTs, PAF and histamine were not influenced by OKY-046 in isolated tracheae, OKY-046 elicited significant and concentration-dependent inhibitions against contractile responses induced by peptide LTs and PAF in isolated lung parenchymal strips. These results suggest the possible involvement of TXA2 in the development of anaphylactic bronchoconstriction in sensitized guinea pigs.

Acrylates↗
PubMed1990

[The effect of leukotriene B4 inhalation on airway responsiveness in dogs].

We studied the effect of leukotriene B4 (LTB4) inhalation on airway responsiveness in 12 dogs. LTB4 (10 micrograms/ml) was delivered as an aerosol, generated from a Devilbiss 646 nebulizer for ten minutes. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7 Hz oscillation method) 1 hr (n = 6) and 6 hr (n = 6) after LTB4 inhalation. After measurement of airway responsiveness, total cell counts, differential cell counts, thromboxane B2 (TxB2) and 6-keto-prostaglandin (PG)F1 alpha levels in bronchoalveolar lavage fluid (BALF) were measured. The total cell counts in BALF increased after LTB4 inhalation (p less than 0.05), and the neutrophil counts in BALF increased significantly 1 hr (p less than 0.05) and 6 hr after (p less than 0.01) LTB4 inhalation. Airway responsiveness to inhaled methacholine decreased significantly 1 hr (p less than 0.05) and 6 hr (p less than 0.01) after LTB4 inhalation. There were no significant changes in the levels of TxB2 or 6-keto-PGF1 alpha in BALF 1 hr and 6 hr after LTB4 inhalation. These results suggest that inhaled LTB4 causes neutrophil recruitment into the airway but does not increase airway responsiveness to inhaled methacholine, and the possibility that LTB4 reduces airway responsiveness to inhaled methacholine exists in dogs.

Administration, Inhalation↗