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Biomedical subjects

T Oki

Publications and source records attributed to T Oki.

At least 271 records · Page 15Linked to original sources

Pradimicins M, N, O and P, new dihydrobenzo[a]naphthacenequinones produced by blocked mutants of Actinomadura hibisca P157-2.

Four blocked mutants which accumulated new dihydrobenzo[a]naphthacenequinone metabolites, designated pradimicins M, N, O and P, have been isolated from cultures of mutants of Actinomadura hibisca P157-2 resulting from treatment with N-methyl-N'-nitro-N-nitrosoguanidine. The structures of the four compounds were determined by spectral analysis. Pradimicins N, O and P contain D-alanine, while pradimicin M does not. The conformations at C-5 and C-6 of these compounds are different from those of the original pradimicins.

Anthracyclines↗

A new screening method for melanin biosynthesis inhibitors using Streptomyces bikiniensis.

A novel screening method for melanin biosynthesis inhibitors using Streptomyces bikiniensis NRRL B-1049 as the indicator organism has been developed. Several known compounds, including tyrosinase inhibitors, were found to inhibit melanin production of S. bikiniensis on agar plates. This screening method was applied to fermentation broths of actinomycetes and several cultures with melanin biosynthesis inhibitory activity were found.

Histidine↗

Pumilacidin, a complex of new antiviral antibiotics. Production, isolation, chemical properties, structure and biological activity.

New antibiotic pumilacidins A, B, C, D, E, F and G were isolated from the culture broth of a strain of Bacillus pumilus. They are cyclic acylheptapeptide composed of a beta-hydroxy fatty acid, two L-leucine, two D-leucine, L-glutamic acid, L-aspartic acid and L-isoleucine (or L-valine). Pumilacidin components were inhibitory to herpes simplex virus type 1 and H+, K(+)-ATPase and demonstrated antiulcer activity in rat.

Adenosine Triphosphatases↗

Calcium-dependent anticandidal action of pradimicin A.

Pradimicin A shows candicidal activity at 10 micrograms/ml in vitro. The action of pradimicin A on Candida albicans cells involves a set of specific cell surface interactions in a Ca2(+)-dependent manner. These include binding to the mannan components on the cell surface and subsequent interactions at the level of the plasma membrane, causing K+ leakage and cell death. The protoplasts prepared from C. albicans undergo lysis rapidly when treated with pradimicin A. These results suggest that pradimicin A acts primarily on the candidal plasma membrane, leading to a perturbation of membrane function.

Anthracyclines↗

Pradimicins A, B and C: new antifungal antibiotics. II. In vitro and in vivo biological activities.

Pradimicins A, B and C specify novel antibiotics produced by Actinomadura hibisca No. P157-2 (ATCC 53557) possessing potent and broad antifungal activity in vivo. They showed moderate in vitro antifungal activity against a wide variety of fungi and yeasts including clinically important pathogens, and were highly effective in systemic infection with Candida albicans in mice after iv and im administrations. Pradimicin A showed in vivo therapeutic activity against C. albicans, Cryptococcus neoformans and Aspergillus fumigatus in both normal and immunocompromized mice. 5-Fluorocytosine- and azole-resistant C. albicans strains were susceptible to pradimicin A. This antibiotic also demonstrated therapeutic efficacy against lung candidiasis and aspergillosis, vaginal candidiasis and skin Trichophyton mentagrophytes infection in mice with iv or topical treatment. The LD50 values after a single iv or im administration were 120 mg/kg and more than 400 mg/kg, respectively. Against various cultured mammalian cells, pradimicin A was noncytotoxic at 100 or 500 micrograms/ml, and showed potent anti-influenza virus activity with an IC50 value of 6.8 micrograms/ml.

Animals↗

New antifungal antibiotics, pradimicins D and E. Glycine analogs of pradimicins A and C.

New antifungal antibiotics pradimicins D and E were isolated from the culture filtrates of Actinomadura hibisca P157-2 (ATCC 53557) and its mutant A2660 (ATCC 53762). The structure of pradimicin D is N-[[(5S,6S)-5-O-[4,6-dideoxy-4-(methylamino)-3-O-(beta-D- xylopyranosyl)-beta-D-galactopyranosyl]-5,6,8,13-tetrahydro-1,6,9,14- tetrahydroxy-11-methoxy-3-methyl-8,13-dioxobenzo[a]naphthacen++ +-2-yl] carbonyl]glycine, based on spectral analyses compared to pradimicin A. Pradimicin E is the des-N-methyl analog of pradimicin D. Pradimicins D and E were equal in activity to pradimicin A in vitro against a variety of fungi and in vivo against Candida albicans A9540 in mice.

Actinomycetales↗

Quinaldopeptin, a novel antibiotic of the quinomycin family.

Quinaldopeptin, a new type of quinomycin antibiotic, was isolated from the culture of Streptoverticillium album strain Q132-6. The antibiotic exhibited strong in vitro antimicrobial and cytotoxic activity and significantly prolonged the survival time of mice inoculated with a murine tumor. Quinaldopeptin is a symmetric cyclic peptide linked only by peptide bonds and differs from known antibiotics of the quinomycin family by the lack of ester linkage.

Amino Acid Sequence↗

Chemical and biological properties of rubiginone, a complex of new antibiotics with vincristine-cytotoxicity potentiating activity.

A novel complex of isotetracenone (angucyclinone) group antibiotics was discovered from the cultured broth of Streptomyces griseorubiginosus No. Q144-2. The antibiotic consisted of six related factors, designated rubiginones A1, A2, B1, B2, C1 and C2. They significantly potentiated cytotoxicity of vincristine (VCR) against VCR-resistant P388 leukemia and Moser cells.

Animals↗

[Genesis and clinical significance of an apical diastolic rumble in patients with mitral Björk-Shiley valve: a Doppler echocardiographic study].

The genesis and clinical significance of an apical diastolic rumble after replacement with mitral Björk-Shiley prosthesis were studied in 20 patients by left ventricular (LV) inflow dynamics using Doppler echocardiography. 1. The rumble was audible in 17 of the 20 patients (85%). In all but one patient, its intensity was less than Levine 2/6. Duration of the rumble ranged from 248 to 544 (mean 377) msec. There was no case of prosthetic valve dysfunction. Duration of the slow filling wave (SF interval) of the apexcardiogram in 19 cases ranged from 150 to 541 (mean 317) msec, and it correlated significantly with the duration of the rumble (r = 0.95) in 15 cases. 2. In 20 patients, peak velocity of the LV inflow obtained from continuous wave Doppler echocardiograms ranged from 1.17 to 1.89 (mean 1.56) m/sec, and pressure half time (PHT) ranged from 82 to 233 (mean 134) msec. In 19 patients, the SF interval correlated significantly with PHT (r = 0.87), but not with peak inflow velocity. 3. Peak inflow velocity was significantly slower in cases without a rumble than in cases with a rumble. PHT and the SF interval tended to be shorter in the former than in the latter. 4. There was no significant difference in the SF interval, peak inflow velocity and PHT between eight patients with smaller valve sizes (less than or equal to 25 mm) and 12 with larger valve sizes (greater than or equal to 27 mm). 5. There was no obvious relation between the direction of the main LV inflow jet as assessed by Doppler color flow mapping and the presence of the rumble in 19 patients. 6. In 19 patients, the SF interval correlated significantly with left atrial dimension (r = 0.47), but it did not correlate with LV end-diastolic dimension, fractional shortening of the LV, and the peak lengthening rate of LV internal dimension. 7. Three patients with both the rumble and SF lasting 500 msec had prolonged PHT longer than 190 msec. One of these three had congestive heart failure and suspected prosthetic mitral valve stenosis. From these results, we concluded that an apical diastolic rumble after replacement with mitral Björk-Shiley valve is mainly due to the increase in resistance and velocity of the LV inflow, and that both durations of the rumble and the SF intervals as well as PHT of the Doppler echocardiogram are useful in detecting stenosis of prosthetic mitral valves.

Adult↗

[Relationship between regurgitant flow dynamics and cardiac physical in tricuspid regurgitation: a phono-, mechano- and Doppler echocardiographic study].

To evaluate the relationships between regurgitant flow dynamics of tricuspid regurgitation (TR) and cardiac physical signs, and to clarify the role of atrial function on central venous flow, we investigated physical signs by cardiac auscultation and palpation of the liver. In addition, phonocardiography, jugular venous and hepatic pulse tracings and Doppler echocardiographic recordings were performed. The subjects, 109 patients with Doppler-detected TR, were categorized as an SR group of 42 with sinus rhythm, an Af group of 63 with atrial fibrillation and four with sinus arrest. Thirty-five patients underwent open heart surgery before six months or more. Results were as follows: 1. In the Af group, the maximum systolic flow velocity data in the superior vena cava (SVC) and hepatic vein (HV) correlated well with the maximum tricuspid regurgitant signal area on the color Doppler echocardiogram, and systolic backward flow from the heart was more evident in the HV than in the SVC. In the SR group, however, no correlation was observed between the maximum systolic flow velocity and the TR signal area, and systolic backward flow was not evident even in cases with severe TR. 2. After open heart surgery, systolic flow velocities in the SVC and HV were significantly decreased in the SR group compared to the Af group. 3. There was close correlation between the presence of hepatomegaly and systolic backward flow towards the liver. Hepatomegaly was more marked in the Af group than in the SR group. 4. Jugular venous and hepatic pulse data correlated well with the flow velocity data in the SVC and HV and with the TR signal area. 5. Intensity of the tricuspid regurgitant murmur as estimated by the Levine's classification correlated relatively well with the systolic pressure gradient between the right ventricle and right atrium as calculated by the modified Bernoulli equation, but did not correlate with the TR signal area. From these results, we conclude that the intensity of the tricuspid regurgitant murmur and the jugular venous or hepatic pulse patterns are useful for evaluating tricuspid regurgitant dynamics, when they are applied clinically with precise recognition of their significance and limitations, and that sinus rhythm or atrial fibrillation is also an important factor.

Atrial Fibrillation↗

New biological properties of pyrroloquinoline quinone and its related compounds: inhibition of chemiluminescence, lipid peroxidation and rat paw edema.

Pyrroloquinoline quinone (PQQ) inhibited the chemiluminescence (CL) from mouse peritoneal cells initiated by zymosan, carrageenin and N-formyl-methionyl-leucyl-phenylalanine and CL generated by the xanthine-xanthine oxidase reaction and the lipid peroxidation in the rat brain homogenate. The inhibitory activity of PQQ was more potent than that of idebenone, alpha-tocopherol and ascorbic acid in all the three assay systems. In the xanthine-xanthine oxidase reaction, PQQ had no effect on the formation of uric acid at the concentration of CL inhibition. These results suggest that PQQ might have a radical scavenger-like activity. Structure-activity relationship of PQQ and its six related compounds showed that the 7- and 9-carboxyl groups of PQQ as well as the orthoquinone structure are responsible for the radical scavenger-like activity. In addition, the -NH group in the pyrrole ring of PQQ seemed to be essential for the antilipid peroxidative activity in the rat brain homogenate. When administered i.p., PQQ inhibited the development of 0.1% carrageenin-induced paw edema in rats. These results suggest that PQQ might have therapeutic effects on various diseases, of which development or exacerbation has been known to be associated with radical oxygens.

Animals↗

[On the mechanisms of mitral regurgitation in rheumatic mitral valve disease: with special reference to the role of mitral valve prolapse].

To assess the role of mitral valve prolapse (MVP) in the pathogenesis of mitral regurgitation (MR) in rheumatic mitral valve disease (RMD), we performed phonocardiography (PCG), transthoracic and transesophageal two-dimensional and color Doppler (CD) echocardiography in 22 patients with RMD including three with pure mitral stenosis (MS), 11 with predominant MS, six with predominant MR and two with pure MR. Results were as follows: 1. Prolapse of the mitral valve (MV) was differentiated from systolic ballooning of the whole MV by the findings that the anterior leaflet's tip (rough zone) protruded into the left atrium with an acute angle between the body (clear zone) and rough zones of the anterior MV and that the posterior leaflet protruded markedly above the level of the mitral ring. 2. MR was detected in six patients (slight MR) by only the CD method and in 13 (mild, moderate or greater MR) by both the PCG and CD methods. 3. MR was absent or slight in five patients (three of pure MS and two of predominant MS) without valve thickening and with systolic ballooning of the whole valve due to commissural fusion. 4. Mitral valve abnormalities related to significant (mild, moderate or severe) MR were dependent on valve thickening (five patients), prolapse of the leaflet's tip toward the left atrium (four), or both (four). 5. An apical systolic click was found in only one of the nine patients with systolic ballooning, but in four of 11 with MVP. 6. The MR murmur in six of the nine patients with valve thickening showed the decrescendo or flat contour, but that in four of the eight patients with MVP showed a crescendo contour. From these results, we concluded that mitral valve prolapse should be considered as one of the important causes of mitral regurgitation in rheumatic mitral valve disease.

Adult↗

Fluoronaphthyridines and quinolones as antibacterial agents. 1. Synthesis and structure-activity relationships of new 1-substituted derivatives.

A series of novel 7-piperazinyl-1-substituted-6-fluoroquinolones and naphthyridines have been prepared and their antibacterial activities evaluated. These derivatives are characterized by having alkyl, alkenyl, arylalkyl, cycloalkyl, and cycloalkenyl groups at the 1-position. As a result of this study, derivatives 7 and 26, which are substituted with tert-butyl groups at N-1, were found to possess excellent in vitro and in vivo potency, particularly against Staphylococcus aureus, comparable to that of norfloxacin or ciprofloxacin. Structure-activity relationships of N-1 substituted alkyls and cycloalkyls are also discussed.

4-Quinolones↗

In vitro and in vivo evaluations of a new broad-spectrum oral cephalosporin, BMY-28232, and its prodrug esters.

The in vitro activity of a new cephalosporin, BMY-28232 (7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-[ (Z)-1- propenyl]-3-cephem-4-carboxylic acid), was compared with those of cefuroxime and BMY-28488, the 3-vinyl congener of BMY-28232, against 899 bacteria including strains resistant to newer cephalosporins. BMY-28232 displayed potent, broad-spectrum antibacterial activity with high stability to various types of beta-lactamase. Its acetoxyethyl ester (BMY-28271) and pivaloyloxymethyl ester (BMY-28257) were well absorbed after oral administration to mice and rats. Both esters were metabolized to BMY-28232 and mainly excreted in urine. Oral bioavailability of both prodrug esters (60 to 70%) was better than that of cefuroxime axetil (46%) and gave excellent therapeutic efficacy against gram-positive- and gram-negative-bacterial infections in mice. Oral 50% protective doses (in milligrams per kilogram of body weight) of 0.65 and 0.72 for Staphylococcus aureus Smith, 0.9 and 1.2 for Escherichia coli Juhl, 1.6 and 1.6 for Proteus vulgaris, and 18.9 and 14.3 for Enterobacter cloacae were obtained for BMY-28271 and BMY-28257, respectively.

Animals↗

Cispentacin, a new antifungal antibiotic. I. Production, isolation, physico-chemical properties and structure.

A new antibiotic, cispentacin, was isolated from the culture broth of a Bacillus cereus strain, L450-B2. The antibiotic is water-soluble and amphoteric; its structure was determined by spectroscopic analysis and chemical synthesis to be (1R,2S)-2-aminocyclopentane-1-carboxylic acid. Cispentacin demonstrated only weak in vitro activity against certain fungi but strong protection of mice from lethal infection of Candida albicans A9540.

Antifungal Agents↗