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Biomedical subjects

S Inouye

Publications and source records attributed to S Inouye.

At least 325 records · Page 18Linked to original sources
PubMed1989

Extensive diversity of branched-RNA-linked multicopy single-stranded DNAs in clinical strains of Escherichia coli.

Recently it was shown that a clinical strain of Escherichia coli contains a reverse transcriptase that is essential for the synthesis of a branched-RNA-linked multicopy single-stranded DNA (msDNA). We now have examined 113 independent clinical isolates of E. coli for the existence of msDNA and found that 7 strains contained msDNA. Four of them were further analyzed by hybridization analysis, which indicated that three of the msDNAs were different, having little sequence homology. When the reverse transcriptase gene associated with one of these msDNAs was used as a probe, it did not hybridize with chromosomal DNA from the other strains containing msDNA. These results indicate that some clinical E. coli strains carry their own unique msDNA-synthesizing systems; msDNAs produced by these systems have little, if any, sequence homology in their RNA and DNA molecules and the reverse transcriptases required for the production of msDNA also have little sequence similarity. Such extensive diversity of the msDNA-synthesizing systems supports the notion that they were acquired by the E. coli genome late during the evolution of E. coli.

Blotting, Southern↗
PubMed1989

An increase in the antimicrobial activity in vitro of fosfomycin under anaerobic conditions.

Fosfomycin showed lower MIC values under anaerobic culture conditions than those under aerobic conditions for four Gram-positive and 18 Gram-negative bacterial isolates. The degree of change in MICs was dependent on the culture media and strains tested. The growth-inhibitory diameter in the paper disc assay increased in parallel with the decrease in the redox potential of the agar medium. Bacteriolytic activity was also potentiated in anaerobiosis. The increase of the bio-activity of fosfomycin in anaerobic culture was neither due to the change of medium pH nor to the change of mobility of drug in agar. However it is possible that the uptake of fosfomycin through the cell membrane increased in anaerobiosis. The anaerobic MICs of fosfomycin were better correlated than the aerobic MICs with the ED50 values in a mouse systemic infection model.

Anaerobiosis↗
PubMed1989

Overexpression and purification of the recombinant Ca2+-binding protein, apoaequorin.

The small, monomeric Ca2+-binding photoprotein, aequorin, emits blue light by an intramolecular reaction when mixed with Ca2+. The photoprotein is made up of coelenterazine and molecular oxygen, bound noncovalently to apoaequorin (apoprotein). The chemical steps leading to light emission, involving the oxidative degradation of coelenterazine, have been studied extensively, but little is known about the active site and how the molecule catalyzes the oxidation of coelenterazine. The three-dimensional structure of the protein has not been determined and therefore answers to these questions have remained unavailable. The present paper describes a procedure for preparing fairly large amounts of apoaequorin and aequorin for X-ray crystallographic studies. It consists of fusing the apoaequorin cDNA to the signal peptide coding sequence of the outer membrane protein A of Escherichia coli, which is under the control of the lipoprotein promoter. When the cDNA was expressed in E. coli, a large excess of the recombinant protein was produced and released into the culture medium. Purification of the protein was accomplished by acid precipitation and DEAE-cellulose chromatography. The procedure yielded 7.4 mg of recombinant apoaequorin with a purity greater than 95% from 200 ml of culture medium. On regeneration with coelenterazine, the recombinant aequorin was fully active with Ca2+.

Aequorin↗
PubMed1989

Differentiation of primary from nonprimary genital herpesvirus infections by detection of polymeric immunoglobulin A activity.

We analyzed antibody responses to herpes simplex virus (HSV) in 18 patients by using sucrose gradient centrifugation and an enzyme-linked immunosorbent assay for antibody determination. We found that the HSV-specific immunoglobulin A (IgA) antibody in early-convalescent-phase serum specimens from all of 8 primary cases consisted solely of polymeric forms, whereas in all 10 nonprimary cases, the major component was monomeric. These results indicate that the ratio of polymeric IgA to monomeric IgA antibody activity may be useful for differentiating primary from nonprimary HSV infections.

Adult↗
PubMed1989

Biological and immunological properties of Sugi basic protein-pullulan conjugate. I. Suppressive effect on IgE antibody production and on IgE-mediated reactions.

Sugi basic protein (SBP), a major allergen of Japanese cedar pollen, conjugated to pullulan acquires suppressive activities for IgE, but not for IgG antibody production, and for IgE-mediated PK reactions in a SBP-specific manner. When either normal or IgE anti-SBP antibody-producing mice were treated with the conjugate, IgE anti-SBP antibody levels scarcely increased even after immunization with SBP + alum. This suppression was shown to be SBP specific and IgE selective. The ability of SBP-pullulan conjugate to elicit PK reactions on passively sensitized rat skin was markedly reduced. Furthermore, the conjugate inhibited the reactions mediated by the IgE antibodies and native SBP when it was injected into the IgE antibody-sensitized sites 2 h prior to SBP challenge. The reduced ability of the conjugate to elicit PK reactions was not due to loss of antigenic determinants during the conjugation procedures because binding activity of the conjugate to anti-SBP antibodies was as strong as that of native SBP. These results indicate that SBP-pullulan conjugate may be useful for 'desensitization therapy' against the pollinosis.

Allergens↗
PubMed1989

Measurement of allergens associated with dust mite allergy. II. Concentrations of airborne mite allergens (Der I and Der II) in the house.

Assays of mite allergens (Der p I, Der f I and Der II) in the air of houses became feasible with the use of a low-noise air sampler and a sensitive radioimmunoassay described previously. The levels of the airborne allergens Der I (Der p I + Der f I) and Der II in the living room of 10 houses during usual domestic life were very low, 29.5 and 6.3 pg/m3, respectively, with a Der I: Der II ratio of 4.7:1. At the time of bedmaking, they greatly increased, about 1,000-fold, to 30,900 and 12,600 pg/m3, respectively, with a Der I: Der II ratio of 2.5:1. The amounts of Der I and Der II in the floor dust of the living room were 2,040 and 2,690 ng/g of fine dust, respectively, with a Der I: Der II ratio of 0.8:1. Der I seemed more prone to become airborne than Der II.

Air↗
PubMed1989

Ototoxic effects of a pseudodisaccharide aminoglycoside antibiotic, dactimicin, on the inner ears of guinea pigs.

The effect of dactimicin on the inner ear of guinea pigs was investigated by comparing it with the effects of ribostamycin, astromicin and amikacin. At doses of 200 and 400 mg/kg/day for 4 weeks, no pinna reflex loss was observed, but 2 animals receiving 400 mg dactimicin/kg/day showed unilateral loss of the outer hair cells in the cochlea and very scattered loss of the hair cells in the vestibular organ. At doses of 400 and 500 mg dactimicin/kg/day for 5 weeks, all surviving animals showed no abnormality of the outer hair cells, the inner hair cells and the spiral ganglion cells in the cochlea except for scattered unilateral loss of the outer hair cells and loss of the stria vascularis. Based on these observations, it is concluded that the ototoxicity of dactimicin on the inner ear of guinea pigs is the same as or a little stronger than that of ribostamycin, weaker than or the same as that of astromicin and weaker than amikacin.

Amikacin↗
PubMed1989

Antitumor activity of pyrindamycins A and B.

Pyrindamycins A(1) and B(2) exhibited stronger cytotoxic activities than doxorubicin towards murine and human tumor cell lines and especially towards doxorubicin-resistant cells. Pyrindamycins A and B were also active in vivo against P388/ADR, a multidrug-resistant tumor cell line. Intracellular accumulation of pyrindamycins A and B in P388/ADR was the same as in P388. These antibiotics strongly inhibited DNA synthesis compared with RNA or protein synthesis. They showed significant therapeutic effects towards murine leukemia, but not to solid tumors.

Animals↗
PubMed1989

Reduction of dibekacin-induced nephrotoxicity in the rat by the formation of N-alkylsulfonate derivatives.

Seven N-alkylsulfonate derivatives of an aminoglycoside antibiotic, dibekacin, were prepared and their nephrotoxicity was examined. Using water-supplied and water-depleted rats and the BUN value as a nephrotoxic measure, dibekacin-di-N-methanesulfonate, pentasodium dibekacin-penta-N-methanesulfonate, -penta-N-ethanesulfonate, disodium dibekacin-di-N-methanesulfonate sesquisulfate, disodium and dipotassium dibekacin-di-N-ethanesulfonate sesquisulfates and sodium dibekacin-mono-N-ethane-sulfonate disulfate showed low nephrotoxicity as compared to that of the original dibekacin sulfate. Notably, dibekacin-di-N-methanesulfonate caused little change in the BUN value and was bioactive in vitro but not active in vivo against a Pseudomonas aeruginosa infection model in mice. Among the bioactive N-alkylsulfonates in vivo, disodium and dipotassium dibekacin-di-N-ethanesulfonate sesquisulfates showed a lower degree of elevation of BUN, urine volume and urine protein, lower mortality and better body weight gain than those of dibekacin sulfate during consecutive treatment for 12 and 28 days.

Animals↗
PubMed1989

Effect of glucarolactam on low-dose nephrotoxicities of dibekacin and gentamicin in Fischer rats.

Intramuscular administration of dibekacin or gentamicin to Fischer rats at doses of 10, 20 and 40 mg/kg for 11 days gave polyuria, enzymuria and cytauria. These changes were suppressed completely or partially by the simultaneous administration of glucarolactam sodium or potassium salt. The ameliorating results were supported by serum and histopathological analyses on day 12. A rise in BUN and serum creatinine levels was partially or completely suppressed and histopathological scores were improved by co-administration of glucarolactam salts.

Animals↗
PubMed1989

Effect of glucarolactam on ototoxicity of aminoglycoside antibiotics in guinea-pigs.

Intramuscular administration of glucarolactam in the form of aminoglycoside salt to guinea-pigs protected the experimental ototoxicity caused by high dosing of aminoglycoside antibiotics. The protection was evidenced by the pinna reflex threshold and histochemical examinations of hair cells of cochlea as well as body weight gain. The degree of protection differed with the aminoglycosides, and high protection was observed for dibekacin, gentamicin, tobramycin, followed by kanamycin and bekanamycin. However, protection was weak or not observed when glucarolactam was administered as a mixture of glucarolactam potassium and aminoglycoside sulfate. Serum analysis of the guinea-pigs on day 14 post-administration as a measure of nephrotoxicity revealed that glucarolactam suppressed the elevation of BUN and serum creatinine caused by the aminoglycosides. The protective effect of glucarolactam on the aminoglycoside-induced nephrotoxicity in the dehydrated rats did not differ between the salt and the mixture. No difference in the in vivo antibiotic activity against bacterial infections of mice was observed between the salt and the mixture.

Aminoglycosides↗
PubMed1989

Comparative nephrotoxicity of ribostamycin and gentamicin in rats evaluated by urinalysis.

The nephrotoxicity of ribostamycin and gentamicin was compared by urinalysis using 18 parameters. When a dose of 40 mg/kg per day was administered intramuscularly to Fischer rats for 14 days, ribostamycin caused little change of parameters in urine volume, urine osmolality, urine protein, maltase and beta 2-microglobulin. A slight increase with ribostamycin was observed in alpha-fucosidase, beta-N-acetylglucosaminidase, leucine aminopeptidase, lactic dehydrogenase (LDH) and potassium, and a moderate increase was observed in acid phosphatase and alkaline phosphatase. On the other hand, gentamicin caused a large alteration in most parameters. Both antibiotics caused a change of the isoenzyme pattern of LDH1-5, but the pattern with ribostamycin was much closer to the normal pattern than with gentamicin. When a dose of 80 mg/kg of ribostamycin was compared with 10 mg/kg of gentamicin, alteration of urinary parameters was almost comparable. Histopathological observations of the kidney specimens of rats given 40 mg/kg per day showed no histological damage with ribostamycin except for a slight increase and enlargement of lysosomes of the proximal epithelial cells. However, significant histological damage was observed with gentamicin, consistent with the results obtained from urinalysis. Renal accumulation of ribostamycin at a single dose of 20 mg/kg was three times less than that of gentamicin. Ribostamycin caused slightly less nephrotoxicity in rats than kanamycin and far less than dibekacin at an equal dosage of 40 mg/kg per day for 14 days.

Animals↗
PubMed1989

In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent.

2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs. Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin. When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others. Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2-propargyltetrazole (CN151). CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible.

Animals↗
PubMed1989

Bacteriolytic combination effect of cefminox and piperacillin evaluated by turbidimetry.

The bacteriolytic combination effect of cefminox (a potent bactericidal cephamycin) and piperacillin (a broad spectrum ureidopenicillin) was investigated using turbidimetry and expressed as a measure of the combination effect by the relative ratios of bacteriolytic area under the growth curves. Against 20 strains of Gram-positive and -negative bacteria, simultaneous treatment of both antibiotics showed synergy (five strains), indifference (15 strains) and no antagonistic effect. Pretreatment with piperacillin for 1 h followed by combined treatment with cefminox showed a profound enhancement of the bacteriolytic activity against 12 out of 20 strains, especially against Serratia, Enterobacter and Pseudomonas species. In contrast, pretreatment with cefminox against seven strains gave mainly an indifferent effect (four strains). The turbidimetric method gave results comparable with those obtained from the chequerboard method (FIC index), as far as Gram-positive and some of the Gram-negative bacteria (E. coli, K. pneumoniae, M. morganii) were concerned. For Serratia, Enterobacter and Pseudomonas sp., the turbidimetric method showed synergy or indifference in many cases, whereas the chequerboard method showed antagonism. Marked enhancement of lysis by the combination was ascribed at least partly to the D-amino acid side-chain of cefminox.

Bacteria↗
PubMed1989

Antimicrobial activity of dactimicin in vitro compared with that of dibekacin, netilmicin, sisomicin and micronomicin.

Antimicrobial activity of dactimicin, a pseudo-disaccharide aminoglycoside antibiotic, was compared with those of dibekacin, netilmicin, sisomicin and micronomicin using clinical isolates of four Gram-positive and sixteen Gram-negative bacteria. Dactimicin was more active than the reference amino-glycosides against Serratia marcescens, especially gentamicin-resistant Serratia sp., Proteus vulgaris, P. rettgeri and Klebsiella oxytoca, but less active against Pseudomonas aeruginosa and P. mirabilis. Dactimicin was equally active as the references excepting netilmicin against Gram-positive bacteria and some Gram-negative bacteria including Escherichia coli, K. pneumoniae, Morganella morganii, Haemophilus influenzae, Citrobacter freundii, Enterobacter aerogens, E. cloacae, Acinetobacter calcoaceticus and Campylobacter jejunii. Dactimicin was active against resistant strains possessing various aminoglycoside-modifying enzymes including AAC(3)-1, by which dactimicin was acetylated.

Aminoglycosides↗
PubMed1989

Comparative antimicrobial activities of ribostamycin, gentamicin, ampicillin and lincomycin in vitro and in vivo.

The antimicrobial activity of ribostamycin, a unique aminoglycoside antibiotic possessing a neutral sugar component, was compared with those of gentamicin, ampicillin and lincomycin in vitro and in vivo. Ribostamycin showed comparable or slightly weaker in vitro activity than the reference antibiotics against Gram-positive bacteria. Against Gram-negative bacteria, ribostamycin was less active than gentamicin, but comparable to or more active than ampicillin. Lincomycin was less active or inactive to Gram-negative bacteria. Ribostamycin was active against some gentamicin-resistant bacteria, especially K. pneumoniae possessing the aminoglycoside-modifying enzymes AAC(3)-l and AAD(2"). The in vivo activity of ribostamycin was weaker than that of gentamicin, but comparable to that of ampicillin and lincomycin against Gram-positive bacteria, and superior to that of ampicillin against Gram-negative bacteria. The in vivo activity of ribostamycin was characterized by (i) and ED50 value not so affected by the challenge inoculum as that of ampicillin; (ii) a lower ED50 value by bolus administration than that by divided administration of the same dosage; and (iii) a lower ED50 value than that expected from the MIC value as compared with that of ampicillin and lincomycin. These characteristics are explained by the rapid and potent bactericidal activity of ribostamycin at high inoculum and high drug concentration, assisted by high serum concentration in mice.

Ampicillin↗