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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 217 records · Page 12Linked to original sources

Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation.

Air pollutants including diesel exhaust particles (DEPs) have been shown to enhance allergic responses. DEPs stimulate airway epithelial cells to produce various cytokines; however, the intracellular signal transduction pathway and the involvement of reduction and oxidation (redox) control in DEP-activated signaling have not been determined. In the present study, we therefore examined the role of p38 mitogen-activated protein (MAP) kinase in DEP-induced interleukin 8 (IL-8) and RANTES production by human bronchial epithelial cells (BECs) in order to clarify the intracellular signal transduction pathway that regulates IL-8 and RANTES production. In addition, we also examined the effect of a thiol-reducing agent, N-acetylcysteine (NAC), on DEP-induced p38 MAP kinase activation and cytokine production in order to clarify the redox control mechanism in DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. The results showed that DEP induced IL-8 and RANTES production and the threonine and tyrosine phosphorylation of p38 MAP kinase, reflecting the activation of p38 MAP kinase in BECs. SB 203580, as the specific inhibitor of p38 MAP kinase activity, inhibited DEP-induced IL-8 and RANTES production. NAC inhibited DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. These results indicate that p38 MAP kinase plays an important role in the DEP-activated signaling pathway that regulates IL-8 and RANTES production by BECs and that the cellular redox state is critical for DEP-induced p38 MAP kinase activation leading to IL-8 and RANTES production.

Acetylcysteine↗

PAF-induced RANTES production by human airway smooth muscle cells requires both p38 MAP kinase and Erk.

Airway smooth muscle (ASM) cells, which have been regarded as having contractile properties in response to contractile inflammatory mediators, may also participate in airway inflammatory response by expressing various cytokines, including RANTES. However, the intracellular signal that regulates cytokine expression in ASM cells has not been determined. In the present study, we examined the role of p38 mitogen-activated protein (MAP) kinase and extracellular signal-regulated kinase (Erk) in RANTES production by ASM cells stimulated by platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha. The results showed that PAF induced the threonine and tyrosine phosphorylation of p38 MAP kinase and Erk, and p38 MAP kinase and Erk activity. SB 203580 and PD 98059 almost completely inhibited p38 MAP kinase and Erk activity, respectively. SB 203580 and PD 98059 partially inhibited and acted additively to inhibit PAF-induced RANTES production. PAF also induced c-Jun-NH(2)-terminal kinase ( JNK) phosphorylation. TNF-alpha induced p38 MAP kinase and Erk phosphorylation, but neither SB 203580 nor PD 98059 inhibited RANTES production. These results indicate that both p38 MAP kinase and Erk involve RANTES production by ASM cells stimulated with PAF, but not TNF-alpha, and that the role of p38 MAP kinase and Erk in RANTES production by ASM cells appears to be stimulus-dependent.

Bronchi↗

Inhalant corticosteroids inhibit hyperosmolarity-induced, and cooling and rewarming-induced interleukin-8 and RANTES production by human bronchial epithelial cells.

Inhaled corticosteroids are widely used for the treatment of bronchial asthma, and a long-term treatment with inhaled corticosteroids is effective in preventing exercise-induced bronchoconstriction (EIB). We have previously shown that hyperosmolarity, and cooling and rewarming induced interleukin-8 (IL-8) expression in human bronchial epithelial cells (BEC). However, the effect of inhalant corticosteroids on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production has not been determined. To clarify these issues, we examined the effect of inhalant corticosteroids, beclomethasone dipropionate (BDP), and budesonide (BUD) on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. The results showed that BDP and BUD inhibited hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. Because our previous studies have shown that p38 mitogen-activated protein (MAP) kinase and c-Jun-NH(2)-terminal kinase (JNK) regulate hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production, we examined the effect of BDP and BUD on p38 MAP kinase and JNK activation. The results showed that BDP and BUD did not inhibit hyperosmolarity-induced and cooling-induced p38 MAP kinase and JNK activation. These results indicated that inhalant corticosteroids inhibited hyperosmolarity-, and cooling and rewarming-induced IL-8 and RANTES production; however, the mechanism of inhaled corticosteroid-mediated inhibition of hyperosmolarity-induced, and cooling and rewarming- induced cytokine production remains to be clarified.

Administration, Inhalation↗

Clonidine attenuates the carbachol-induced contractile and phosphatidylinositol responses of rat trachea.

Although clonidine is known to affect vascular smooth muscle, its effects on airway smooth muscle are not fully understood. This study was designed to examine the effects of clonidine on carbachol-induced contractile and phosphatidylinositol responses of rat trachea. Clonidine, at a dose of 100 microM or greater, attenuated carbachol-induced contraction and the accumulation of carbachol-induced inositol monophosphate (IP1). Clonidine also attenuated the accumulation of aluminium fluoride-induced IP1. The concentration-effect relationship of IP1 accumulation was similar to that of carbachol-induced contraction; r = 0.797, P < 0.001. These results suggest that clonidine attenuates contractile responses, at least in part, through the inhibition of phospholipase C (coupled with G-proteins) in phosphatidylinositol responses.

Aluminum Compounds↗

One-pot enantioselective synthesis of optically active homoallylic alcohols from allyl halides.

A one-pot, convenient method for the preparation of optically active homoallylic alcohols from allyl halides was developed. Allyltrichlorosilanes were generated in situ from allyl halides and trichlorosilane in the presence of cuprous chloride and tertiary amine. Without isolation of the allyltrichlorosilanes, benzaldehyde and chiral biquinoline N,N'-dioxide were introduced into the same flask, producing the corresponding homoallylic alcohols with good to high enantioselectivities.

Alcohols↗

Effect of polymethylene and phenylene linking groups on the DNA cleavage specificity of distamycin-linked hydroxamic acid-vanadyl complexes.

Two types of distamycin-linked hydroxamic acids (DHA), which contain various lengths of polymethylene chains (PM-DHA) and relatively rigid phenylene ones (Ph-DHA), have been synthesized for the first time. Their DNA cleavage specificities were investigated by an end-labeled fragment cleavage experiment in the presence of vanadyl ion and hydrogen peroxide. The DNA cleavage by the PM-DHA x VO(II) complexes was shown to be very dependent on the length of the chain and the AT sequences. The tetramethylene DHA (1b) complex exhibited highly specific cleavage patterns flanking the 8 and 10 AT sites. Interestingly, the Ph-DHA complexes selectively cleaved the 5' end-labeled strand at the AT sites, but did not cleave the 3' end-labeled strand. The vanadyl complexing moieties and the local sequence conformation of the AT tract are suggested to contribute significantly to the DNA recognition of the PM-DHA x VO(II) complexes.

Animals↗

Inhibitory action of troglitazone, an insulin-sensitizing agent, on the calcium current in cardiac ventricular cells of guinea pig.

We investigated the effects of troglitazone, a new orally active hypoglycemic agent, on the voltage-dependent L-type Ca2+ current in single cardiac ventricular myocytes of guinea pigs by the whole-cell voltage clamp technique. Troglitazone blocked the Ca2+ currents in a concentration-dependent manner. The inhibitory effect was more potent at the holding potential (HP) of - 50 mV than at - 80 mV. The half-maximum inhibiting concentration (IC50) of troglitazone was 0.8 microM with the Hill coefficient of 0.84 at -50 mV HP. In contrast, the IC50 value was higher than 10 microM at -80 mV HP. These results suggest that troglitazone at therapeutic concentrations inhibit the Ca2+ channels and may exert cardioprotective effects in diabetic conditions.

Animals↗

Lysyl-tRNA synthetase of Bacillus stearothermophilus molecular cloning and expression of the gene.

The gene of the lysyl-tRNA synthetase of Bacillus stearothermophilus NCA1503 was cloned and sequenced. The gene consists of 1485 bp nucleotides commencing with an ATG start codon and ending with a TAA stop codon, and encodes a polypeptide of 493 amino acids. The recombinant enzymes were expressed in E. coli using an expression plasmid containing the T7 RNA polymerase/promoter.

Amino Acid Sequence↗

Detection of thermophilic Campylobacter from sparrows by multiplex PCR: the role of sparrows as a source of contamination of broilers with Campylobacter.

The best combination of primers and the annealing temperature of multiplex PCR for Campylobacter jejuni, Campylobacter coli, and Campylobacter lari were examined. The multiplex PCR was able to detect type strains of the three species. All results of identification of wild strains (30 strains of C. jejuni, 20 strains of C. coli, and 4 strains of C. lari) by the multiplex PCR coincided with those of the conventional biochemical identification tests, suggesting that the multiplex PCR can simultaneously differentiate C. jejuni, C. coli, and C. lari from wild strains of campylobacters easily and rapidly. Campylobacters were detected from sparrow feces by the multiplex PCR and antimicrobial sensitivities of the strains were determined to discuss the role of sparrows in contamination of broilers with C. jejuni. Three out of 13 strains of C. jejuni isolated from sparrow feces showed quinolone resistance. From the frequent use of quinolones for treatment of industrial animals like chickens, pigs, and cows, the three strains of quinolone-resistant C. jejuni in sparrows must have been originated from those industrial animals. Sparrows that have quinolone-resistant C. jejuni were considered to have contacted with industrial animals or thier feed. It may be presumed, on the contrary, that C. jejuni in sparrows could be a potential source of contamination of broilers.

Animals↗

Relationship between the responsiveness to multiple-ovulation treatment and the number of bovine oocytes collected by transvaginal follicle aspiration.

To characterize factors affecting the number of bovine oocytes recovered transvaginally, a regression analysis was performed between the responsiveness to multiple-ovulation treatment and the number of oocytes recovered transvaginally. The number of embryos recovered following multiple-ovulation treatment and the number of oocytes recovered transvaginally increased when the number of follicles to be aspirated transvaginally increased (P<0.05. P<0.01). The number of cumulus-oocyte complexes recovered transvaginally also increased when the number of oocytes to be aspirated transvaginally increased (P<0.001). However, the number of viable embryos that recovered following multiple-ovulation treatment had no relation to the number of cumulus-oocyte complexes recovered transvaginally. These results suggested that more oocytes can be recovered from donors that have a high responsiveness to multiple-ovulation treatment.

Animals↗

Toxicity of cisplatin to the central nervous system of male rabbits.

The cytotoxic effects of platinum (Pt) were studied by intraparenchymal injection of 1 mg of cisplatin (CDDP) in male rabbits. Time-serial plasma Pt levels were used as CDDP clearance indices in brain and kidney tissues. The tissue samples were also examined histologically. Changes in the blood-brain barrier (BBB) were evaluated by horseradish peroxidase (HRP) extravasation. In the brain infusion group, Pt was detected in the plasma 30 min after the start of infusion. In the kidney, Pt was detected after 10 min of CDDP injection. The maximum plasma concentration of Pt in the brain group showed diffuse edema, neuronal necrosis, karyolysis, and HRP extravasation around the injection site. In contrast, the histological damage to kidneys was minimal. The results presented here show that direct infusion of CDDP caused the most extensive cytotoxicity in the brain. The low clearance rate of CDDP from the brain and BBB disruption may explain this behavior.

Animals↗

Delays and continuation of hospital visits among HIV-infected persons and AIDS cases in Japan.

This study attempts to clarify the distribution patterns of delay between HIV transmission and the first hospital visit among HIV-infected persons and AIDS cases in Japan except those infected through blood products. Such hospital visit patterns were analyzed, and the rates of reporting for HIV/AIDS surveillance among diagnosed HIV-infected persons and AIDS cases in hospitals were shown. From 1991 to 1997, a survey and subsequent follow-up were conducted among HIV-infected persons and AIDS cases diagnosed at 74 hospitals in Tokyo. The numbers of HIV-infected persons and AIDS cases were 590 and 208, respectively. The percentage of patients whose estimated date of HIV transmission was obtained ranged 23-41% among Japanese and non-Japanese HIV-infected persons and AIDS cases. Among these patients, 28% to 86% showed a 3-year delay between HIV transmission and their first hospital visit. The rate of HIV-infected persons who continued to visit hospitals within 1 year after their first visit was 77% for Japanese and 45% for non-Japanese; among those after 1 year or more following their first hospital visit the rate was more than 80% among Japanese and over 70% among non-Japanese. The rate of reporting to HIV/AIDS surveillance among diagnosed HIV-infected persons and AIDS cases was 90% or more after 1994 in Japan. The delay between HIV transmission and the first hospital visit was suggested to be very long. Not a few patients stopped visiting hospitals after only a short time. Most diagnosed HIV-infected persons and AIDS cases were reported to the surveillance system of Japan.

HIV Infections↗

Automatic auditory processing and event-related brain potentials in persons with mental retardation.

Measuring event-related brain potentials, this study examined automatic auditory processing in adults with and without mental retardation. Using an auditory oddball paradigm under an inattentive condition, we anticipated that an enhanced negative potential would be followed by a relatively small positive potential. The former was considered as the mismatch negativity and the latter as the P3a. Retarded adults (1 woman, 6 men, defined as a range of moderate to profound retardation) and 8 nonretarded (2 women, 6 men) adults participated. The mismatch negativity showed smaller amplitudes and greater latencies for retarded persons than those for nonretarded adults, whereas the P3a for the groups was comparable. The results may suggest malfunction of automatic auditory change-detection of the brain in mentally retarded persons.

Adult↗

A new antimitotic substance, FR182877. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

Using the characteristic morphological changes of mammalian cells, we screened novel antimitotic substances and found that a strain of Streptomyces sp. No.9885 produced FR182877. This substance was isolated from the culture broth by ethyl acetate extraction, silica gel column chromatography and ODS column chromatography. Structural studies on FR182877 suggested that it had a unique hexacyclic structure encompassing its highly strained double bond. FR182877 exhibited potent antitumor activities against murine ascitic tumor and solid tumor in vivo.

Animals↗

FR191512, a novel anti-influenza agent isolated from a fungus strain No.17415. I. Taxonomy, fermentation, isolation, physico-chemical properties and structure elucidation.

In the course of our screening for anti-influenza agents of microbial origin, FR191512 was isolated from the cultured broth of fungus strain No. 17415 as colorless powder. The structure of FR191512 was determined by several spectroscopic experiments as a novel polyphenolic compound. This compound showed potent antiviral activity against influenza A virus.

Antiviral Agents↗

WF14865A and B, new cathepsins B and L inhibitors produced by Aphanoascus fulvescens. I. Taxonomy, production, purification and biological properties.

WF14865A and B, novel cathepsins B and L inhibitors, were produced and isolated separately from the culture mycelium of a fungal strain Aphanoascus fulvescens No. 14865. Spectroscopic analysis revealed that both WF14865A and B were composed of trans-epoxysuccinyl moieties, 1-H-imidazole-2-ylamine, and isoleucine or leucine. These compounds inhibited human cathepsins B and L with IC50 values in the range of 8.4 approximately 72nM in vitro. Though their in vitro properties were typical as trans-epoxysuccinyl type inhibitors, they exerted strong bone resorption inhibitory effects in low-calcium-diet-fed mouse model at 3.2 approximately 10 mg/kg.

Animals↗