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Biomedical subjects

M Fujimura

Publications and source records attributed to M Fujimura.

At least 235 records · Page 13Linked to original sources
PubMed1996

Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo.

BACKGROUND: Administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We recently developed a guinea pig model for propranolol-induced bronchoconstriction (PIB). Neuropeptides which are released from C-fibre nerve endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. OBJECTIVE: The purpose of this study was to examine whether sensory neuropeptides are involved in the development of PIB after allergic reaction. METHODS: Propranolol at a concentration of 10 mg/ml was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea pigs. The animals were treated intravenously with a NK1 and NK2 dual antagonist, FK224, in a dose of 1 or 10 mg/kg or vehicle or a selective NK1 antagonist, FK888, in a dose of 1 or 10 mg/kg or vehicle 10 min before or 15 min after antigen challenge. RESULTS: Propranolol inhaled 20 min after antigen challenge caused bronchoconstriction. FK224 or FK888 administered 15 min after antigen challenge as well as 10 min before antigen challenge did not reduce the PIB. CONCLUSION: We conclude that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of PIB after allergic reaction.

Adrenergic beta-Antagonists↗
PubMed1995

Cloning and sequencing of a 23-kb region of the Bacillus subtilis genome between the iol and hut operons.

Within the framework of an international project for the sequencing of the entire Bacillus subtilis genome, a 23-kb chromosomal segment, which covers the region between the iol and hut operons, has been cloned and sequenced, creating a 99-kb contig from the gnt operon to the wapA locus. This region (23351 bp) contains 25 complete open reading frames (ORFs; genes) including deoR, dra, nupC and pdp and two partial ones. The region (5140 bp) containing these four genes, being also sequenced by H. H. Saxild et al., was sequenced by subjecting a long polymerase chain reaction product to random sequencing using phage M13mp19. However, we could detect no conflict, between two independently determined sequences, which could be attributed to our sequencing method. A homology search for the 24 newly identified gene products revealed significant homology to known proteins in 14 of them. It was notable that three proteins, encoded by the successive genes (yxeMNO), exhibited meaningful homology to the E. coli GlnHPQ products constituting a periplasmic ATP-dependent transport system for glutamine.

Bacillus subtilis↗
PubMed1995

Age-dependent and region-specific differences in the distribution of trace elements in 7 brain regions of Long-Evans Cinnamon (LEC) rats with hereditary abnormal copper metabolism.

Cu, Mn, Mo, Rb and Zn concentrations of 7 brain regions in LEC rats were determined before (4 and 10 weeks old) and after (20 weeks old) the onset of jaundice. Cu in the LEC rat brain was less concentrated in all regions at 4 weeks of age and in synaptosomal fractions at 10 weeks but, conversely, more concentrated in 3 regions at 20 weeks than in control rats. Furthermore, Mo and Rb in 6 regions at 10 weeks of age and Mn at 20 weeks were more concentrated in the LEC rat brain than in control rats. These results showed that abnormal distributions of trace elements exist in the LEC rat brain before the onset of jaundice.

Aging↗
PubMed1995

Involvement of thromboxane A2 in bronchial hyperresponsiveness of asthma. Kanazawa Asthma Research Group.

It has been considered that thromboxane A2 (TXA2) is involved in the development of bronchial hyperresponsiveness (BHR), a characteristic feature of asthma. To ensure the involvement of TXA2 in BHR of asthma, effects of a 1-week treatment with two orally active TXA2 antagonists, BAY u 3405 and S-1452, on BHR were examined in 10 and 13 patients with stable asthma, respectively, in two consecutive double-blinded, randomized, placebo-controlled, two-phase crossover studies. Provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) with BAY u 3405 (0.78 (GSEM, 1.50) mg/ml) was significantly greater than the value with placebo (0.65 (GSEM, 1.46) mg/ml) (ratio 1.23 times, 95% CI 1.01 to 1.46: P = 0.0401). PC20-FEV1 was also significantly increased with S-1452 (0.43 (GSEM, 1.39) mg/ml) compared with placebo (0.29 (GSEM, 1.27) mg/ml) (ratio 1.75 times, 95% CI 1.05 to 2.45: P = 0.0189). Baseline pulmonary function was not altered by these treatments. These results may ensure that TXA2 is significantly involved in the BHR of asthma while the degree of contribution may be small.

Adolescent↗
PubMed1995

Effect of carbachol on the release of peptide YY from isolated vascularly and luminally perfused rat ileum.

Possible cholinergic control on the release of PYY from intestine into the lumen or blood vessel was studied by radioimmunoassay in the isolated perfused rat ileum. The basal release of PYY into the lumen was 43.1 +/- 8.9 pg/min, which was comparable with that into the vasculature (35.2 +/- 2.6 pg/min). The administration of 1 microM carbachol into the vascular perfusate resulted in a more than 40-fold increase of the luminal release but only a twofold increase of the vascular release. Carbachol-induced release of PYY into both lumen and vasculature was completely blocked by atropine, but not by hexamethonium. Tetrodotoxin abolished carbachol-induced release of PYY into lumen and vasculature. These data suggest that the ileal PYY release, into either lumen or vasculature, is under the control of postganglionic cholinergic neurons via muscarinic receptors.

Analysis of Variance↗
PubMed1995

Role of thromboxane A2 and platelet-activating factor in allergic bronchoconstriction in guinea pig airway in vivo.

Membrane-derived lipid mediators have been considered to play a major role in pathogenesis of bronchial asthma. However, the importance of and the interactions among each mediator are still unclear. We examined the role of thromboxane A2 (TXA2) and platelet-activating factor (PAF) in immediate asthmatic response (IAR) and interactions between these lipid mediators in guinea pig airway in vivo using a specific TXA2 antagonist S-1452 and a specific PAF antagonist Y-24180. We confirmed the activity of each antagonist, as S-1452 and Y-24180 significantly and dose-dependently inhibited bronchoconstriction induced by respective agonist inhalation. S-1452 inhibited IAR but Y-24180 did not, indicating that TXA2 plays a major role in IAR but PAF does not. S-1452 significantly inhibited PAF-induced bronchoconstriction but Y-24180 did not inhibit synthesized TXA2 (STA2)-induced bronchoconstriction, showing that the bronchoconstrictive effect of PAF is at least in part dependent on secondarily released TXA2, but TXA2 does not induce PAF production.

Administration, Inhalation↗
PubMed1995

Effect of a 5-lipoxygenase inhibitor, AL-3264, on propranolol-induced bronchoconstriction in guinea-pigs.

The administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We investigated the effect of AL-3264, a 5-lipoxygenase inhibitor, on propranolol-induced bronchoconstriction (PIB) after antigen inhalation in passively sensitized and artificially ventilated guinea-pigs. Our goal was to determine whether products of arachidonate 5-lipoxygenase are involved in such PIB. Bronchoconstriction occurred when 10 mg/ml of propranolol was inhaled 20 min after antigen challenge. Pretreatment with AL-3264 given in intravenous doses of 0.01 and 0.1 mg/kg 15 min after the antigen challenge significantly reduced PIB in a dose-dependent manner. Pretreatment with 0.1 mg/kg of AL-3264 10 min before antigen challenge significantly inhibited both the immediate allergic bronchoconstriction and PIB, although the effect was minimal. Results suggest that arachidonate 5-lipoxygenase products (such as leukotriene B4, C4, D4 or E4) are involved in the pathophysiology of PIB but their contribution may be small. Further studies using selective antagonists for each of these leukotrienes are needed to clarify their role.

Acrylamides↗
PubMed1995

Additive effect of continuous low-dose ofloxacin on erythromycin therapy for sinobronchial syndrome.

It has been established that long-term low-dose erythromycin therapy (EM therapy) is very effective for sinobronchial syndrome, a common condition in Japan characterized by chronic upper and lower airway inflammation. The effect does not result from its bacteriocidal activity and the detailed mechanisms are not known. It takes 3-6 months for EM therapy to improve the symptoms. This study was designed to evaluate the additive effect of continuous low dosage or intermittent usual dosage of ofloxacin (OFLX) on EM therapy in patients with sinobronchial syndrome. Patients with sinobronchial syndrome were randomly allocated to receive one of the following four regimens. Patients in Group A received both low-dose OFLX and EM therapy daily for 6 months. Patients in Group B received EM therapy and intermittent treatment of OFLX for 6 months. Patients in Group C underwent EM therapy for 6 months. Patients in Group D received neither OFLX nor EM therapy. All patients were given carbocystein for more than 2 months before starting each treatment and during the study period. In patients receiving OFLX and/or EM therapy, these antimicrobial agents were well-tolerated during the treatment period. Amount of sputum in the morning was significantly less in Group C than in Group D after 3-6 months, and decreased significantly in Group A as compared with Group B after 2 weeks, Group C after 2 weeks to 2 months, and Group D after 2 weeks to 6 months. Other symptoms such as number of expectorations, difficulty of expectoration and severity of cough also improved rapidly in Group A. These findings suggest that it is useful to add low-dose OFLX to EM therapy for sinobronchial syndrome, especially within 1-2 months from starting treatment, and it may be cost-effective as this combination therapy can shorten the treatment period of EM therapy.

Adult↗
PubMed1995

Congenital myotonic dystrophy: molecular diagnosis and clinical study.

Recently, an unstable DNA fragment specific to myotonic dystrophy (MyD) was discovered. In affected individuals, a DNA fragment is found that is larger than in normal siblings. Our objectives were to show whether the results of DNA analysis agree with the disease severity and prognosis in congenital myotonic dystrophy (CMyD) by DNA analysis. We investigated three pregnancies (two studied retrospectively) in three families. We genotyped the family members with the Southern blots and the polymerase chain reaction (PCR) analysis. In one case a prenatal diagnosis was carried out using chorionic villus sampling. This report also presents the three cases of affected mothers and CMyD babies with their growth courses. We clarify four main problems in CMyD, namely, respiratory distress, delayed motor development, feeding difficulty, and delayed mental development. The allele size in the range of 10 to 13 kb tended to be present as the adult form of MyD, and 14 to 15 kb as the CMyD. The three CMyD cases whose alleles size in the range of 14 to 15 kb showed various forms of disease and prognosis. We reached the following conclusions: the disease severity and prognosis in babies with CMyD did not correlate with the result of DNA analysis. The DNA analysis is a useful test for prenatal diagnosis. However, it is impossible to predict the disease severity and prognosis in babies with CMyD.

Adult↗
PubMed1995

Cloning and sequencing of a 36-kb region of the Bacillus subtilis genome between the gnt and iol operons.

Within the framework of an international project for the sequencing of the entire Bacillus subtilis genome, a 36-kb chromosome segment, which covers the region between the gnt and iol operons, has been cloned and sequenced. This region (36447 bp) contains 33 complete open reading frames (ORFs; genes) including the four gnt genes and one partial gene. A homology search for the products of the 33 complete ORFs revealed significant homology to known proteins in 16 of them such as tetracycline resistance protein (Clostridium perfringens), asparagine synthetase (Arabidopsis thaliana), aldehyde dehydrogenase (Pseudomonas oleovorans), 2,5-dichloro-2,5-cyclohexadiene-1, 4-diol dehydrogenase (P. paucimobilis), heat shock protein HtpG (Escherichia coli), galactose-proton symporter (E. coli), auxin-induced protein (common tobacco), glucitol operon repressor (E. coli) and methylmalonate-semialdehyde dehydrogenase (P. aeruginosa). Unlike the regions we sequenced so far, this region contained two short sequence multiplications: one was a tandem sequence duplication (409 and 410 bp), and the other a triplication consisting of two highly conserved 118-bp tandem sequences preceded by a less conserved similar sequence (129 bp). The reasons for the presence of these sequence multiplications in the gnt to iol region were deduced.

Bacillus subtilis↗
PubMed1995

Cloning and sequencing of a 29 kb region of the Bacillus subtilis genome containing the hut and wapA loci.

Within the framework of an international project for the sequencing of the entire Bacillus subtilis genome, a 29 kb chromosome segment, which contains the hut operon (335 degrees) and the wapA gene, has been cloned and sequenced. This region (28,954 bp) contains 21 complete ORFs and one partial one. The 5th, 6th and 17th genes correspond to hutH encoding histidase, hutP encoding the positive regulator for the hut operon and wapA encoding a precursor of three major wall-associated proteins, respectively. A homology search for their products deduced from the 21 complete ORFs revealed that nine of them exhibit significant homology to known proteins such as urocanase (Pseudomonas putida), a protein involved in clavulanic acid biosynthesis (Streptomyces griseus), amino acid permeases (lysine, Escherichia coli; histidine, Saccharomyces cerevisiae; and others), beta-glucoside-specific phosphotransferases (E. coli and Erwinia chrysanthemi) and 6-phospho-beta-glucosidases (E. coli and Erw. chrysanthemi). Based on the features of the determined sequence and the results of the homology search, as well as on genetic data and sequence of the hut genes reported by other groups, it is predicted that the B. subtilis hut operon may consist of the following six genes (6th-1st), the last of which is followed by a typical rho-independent transcription terminator: hutP, hutH, EE57A (hutU) encoding urocanase, EE57B (hutI) encoding imidazolone-5-propionate hydrolase, EE57C (hutG) encoding formiminoglutamate hydrolase and EE57D (tentatively designated as hutM) possibly encoding histidine permease. Interestingly, the direction of transcription of these hut genes is opposite to that of the movement of the replication fork.

ATP-Binding Cassette Transporters↗
PubMed1995

Establishment and characterization of non-small cell lung cancer cell lines resistant to mitomycin C under aerobic conditions.

To elucidate the mechanisms of acquired resistance to mitomycin C (MMC) in non-small cell lung cancer (NSCLC), we established two MMC-resistant NSCLC sublines by continuous exposure to MMC, using PC-9 as a parent cell line. The sublines, PC-9/MC2 and PC-9/MC4, were 6.4- and 10-fold more resistant to MMC than their parent cell line, respectively, at the IC50 value as determined by MTT assay. They exhibited cross-resistance to EO9, but were not resistant to cisplatin, vindesine, etoposide, carboquone, or KW-2149, a novel MMC derivative. They were collaterally sensitive to adriamycin and menadione. Accumulation of the drug was decreased in the resistant sublines to about 60% of that in the parent cells. Cytosolic DT-diaphorase (DTD) activities were decreased to 13.5 +/- 3.2 in PC9/MC2 and 1.3 +/- 0.6 in PC-9/MC4 from 261.5 +/- 92.7 nmol/min/mg protein in the parent PC-9. NADH:cytochrome b5 reductase activities in both of the resistant cell lines were significantly decreased as compared to that in the parent cell line. Addition of dicumarol resulted in a two-fold increase in IC50 value in PC-9, whereas the IC50 value showed no change in PC-9/MC4. Moreover, dicumarol did not affect the sensitivities to KW-2149 but decreased the sensitivities to EO9 in both the parent and the resistant cell lines. Formation of an alkylating metabolite was significantly decreased in the resistant cells, in parallel to the degree of resistance. We concluded that deficient drug activation due to decreased DTD activity was important as a mechanism of resistance to MMC in PC-9, a relatively DTD-rich NSCLC cell line.

Aerobiosis↗
PubMed1995

Bronchial hyperresponsiveness and airway neutrophil accumulation induced by interleukin-8 and the effect of the thromboxane A2 antagonist S-1452 in guinea-pigs.

Interleukin-8 (IL-8) has been shown to be a chemotactic factor for neutrophils, T-lymphocytes and eosinophils, but it is unknown whether the IL-8-induced inflammatory cell accumulation into the airways can cause the bronchial hyperresponsiveness (BHR) characteristic of asthma. IL-8 at a dose of 0.5 or 5 micrograms/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilated through tracheal cannula and lateral pressure at the cannula (Pao) was measured as an overall index of airway responses to increasing concentrations of inhaled histamine (25, 50, 100, and 200 micrograms/ml). The IL-8 treatment significantly enhanced bronchial responsiveness to histamine in a dose-dependent manner (ANOVA P < 0.01). The provocative concentration of histamine causing a 100% increase in Pao (PC100) at a dose of 0.5 and 5 micrograms/kg of IL-8 was 68.1 (GSEM 1.12) and 35.6 (GSEM 1.25) micrograms/ml, respectively. The latter was significantly (P < 0.01) lower than that in control animals treated with PBS (93.3 [GSEM, 1.14] micrograms/ml). The IL-8 treatment also induced a significant influx of neutrophils, but not eosinophils, in bronchoalveolar lavage (BAL) fluid (18.3 +/- 8.8 and 30.6 +/- 8.3% in animals treated with 0.5 and 5 micrograms/kg, respectively, of IL-8 vs 3.6 +/- 0.7% in phosphate buffered saline-(PBS)-treated animals). Furthermore, we examined the effect of the thromboxane receptor antagonist S-1452 (0.01 or 0.1 mg/kg, i.p. 24 and 1 h before anesthesia) on this IL-8 induced BHR. S-1452 significantly inhibited the BHR dose-dependently (ANOVA P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1995

Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi.

Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.

Analysis of Variance↗
PubMed1995

Perinatal medical support in the area surrounding the Hanshin-Awaji earthquake.

After natural disaster, perinatal medical care must usually be provided from outside the disaster area, because most of the medical efforts inside the area focus on patients without special needs. This study reviews the emergency perinatal medical response after the great Hanshin-Awaji earthquake. In the present study, we summarize records of telephone calls and reports from the Neonatal Mutual Cooperative System (NMCS). The day of the earthquake, very little information was available to or from the disaster area. The day after the earthquake, Osaka City General Hospital (OCGH) and Osaka Medical Center and Research Institute for Maternal and Child Health were established as key facilities, and OCGH served as a center through which information passed to and from the disaster area. Most telephone calls to OCGH were placed on the second day after the earthquake by pregnant women concerned about their deliveries. Many high-risk pregnancies and newborn infants were transferred out of the disaster area over the next month. This analysis shows that although the emergency response was very rapid in this instance, the operation may be significantly improved in disasters of this magnitude: (i) if a communication mechanism able to serve a large volume is established; (ii) if helicopter transport was easily available; and (iii) if key facilities to handle communications were previously established so as to be available immediately.

Child Health Services↗
PubMed1995

Intravenous injection of acetaldehyde but not ethanol induces histamine-mediated bronchoconstriction in guinea pigs.

Recently ethanol-induced bronchoconstriction associated with elevated serum levels of acetaldehyde and histamine was reported in Japanese asthmatic patients, but there is no investigation of the airway response to intravenous injection of acetaldehyde. We therefore performed a study in guinea pigs to test the hypothesis that intravenous injection of acetaldehyde has bronchospastic action via histamine release. At first, we investigated the airway response to increasing doses (8.0, 26.4, and 80 mg/ml) of injected ethanol or acetaldehyde in guinea pigs. Secondarily, increasing doses of acetaldehyde were injected in guinea pigs pretreated with an intraperitoneal injection of 20 mg/kg diphenhydramine or saline (control). Finally, injection of acetaldehyde was performed after intraperitoneal injection of 0.5 mg/kg atropine sulfate or saline (control). Injected acetaldehyde caused bronchoconstriction in a dose-dependent manner, but ethanol did not. The bronchoconstriction induced by injected acetaldehyde was completely prevented by pretreatment with diphenhydramine. Atropine had no preventing effect against the acetaldehyde-induced bronchoconstriction. In conclusion, intravenous injection of acetaldehyde causes bronchoconstriction via histamine release in guinea pigs.

Acetaldehyde↗
PubMed1995

Bronchodilator and bronchoprotective effects of cilostazol in humans in vivo.

Cilostazol is a selective orally active phosphodiesterase (PDE) III inhibitor. This study was conducted to evaluate whether inhibition of PDE subtype III can reduce bronchial responsiveness. We examined the effects of cilostazol on bronchial responsiveness to methacholine in eight normal subjects by a single-blinded, crossover study. Each subject received 200 mg of cilostazol or placebo in random order. The subjects underwent methacholine challenge test 3 h after administration of each drug on two occasions separated by 5 d or more. The geometric mean value of provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) and the mean value (+/- SEM) of maximum expiratory flow on partial flow-volume curve at isovolume of 40% FVC above residual volume (PEF40) after administration of cilostazol were 25.3 (geometric standard error of the mean [GSEM], 1.35) mg/ml and 3.78 +/- 0.31 L/s, which were significantly (p < 0.02 and p < 0.05) greater than those after the placebo administration (6.81 [GSEM, 1.42] mg/ml and 2.71 +/- 0.39 L/s). All subjects complained of mild to severe headache when cilostazol was given. These findings suggest that PDE III inhibitors such as cilostazol have bronchodilator and bronchoprotective effects in humans. Further studies regarding smaller oral dosing of or aerosol administration of cilostazol or the other PDE III inhibitors are needed to determine clinical usefulness.

3',5'-Cyclic-AMP Phosphodiesterases↗