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Biomedical subjects

T Oki

Publications and source records attributed to T Oki.

At least 289 records · Page 16Linked to original sources

Cispentacin, a new antifungal antibiotic. II. In vitro and in vivo antifungal activities.

Cispentacin [-)-(1R,2S)-2-aminocyclopentane-1-carboxylic acid) is a new antifungal antibiotic possessing potent anti-Candida activity. The 50% inhibitory concentration (IC50) and IC100 values of cispentacin against clinical isolates of Candida albicans were in the ranges 6.3 approximately 12.5 and 6.3 approximately 50 micrograms/ml, respectively, by turbidimetric measurement in yeast nitrogen base glucose medium. No significant activity was seen against any yeasts and molds when tested by the agar dilution method using three different agar media: KNOPP's agar, yeast extract-glucose-peptone agar and Sabouraud dextrose agar. This antibiotic demonstrated good therapeutic efficacy against a systemic Candida infection in mice by both parenteral and po administrations. The 50% protection dose (PD50) values after single iv and po administrations were 10 and 30 mg/kg, respectively. It was also effective in a systemic infection with Cryptococcus neoformans and in both lung and vaginal infections with C. albicans in mice. Cispentacin did not induce acute lethal toxicity at 1,000 mg/kg by iv injection and 1,500 mg/kg by ip and po administrations in mice.

Amphotericin B↗

New cirramycin-family antibiotics F-1 and F-2. Selection of producer mutants, fermentation, isolation, structural elucidation and antibacterial activity.

Two new 16-membered macrolides, cirramycins F-1 and F-2, were isolated from the culture filtrate of a mutant strain B-1425 of Streptomyces cirratus JTB-3. The antibiotics were also produced by bio-transformation of cirramycin A1 using a blocked mutant strain A-0033. Structures of F-1 and F-2 have been elucidated by spectral interpretation and analysis of acid degradation products. Both involved isomeric modification of a neutral sugar; F-1 contained L-rhodinose, and F-2 L-amicetose. Based on spectral data, cirramycin F-1 and antibiotic A6888C were found to be identical. Cirramycins F-1 and F-2 are active against Gram-positive bacteria, but less active than cirramycin A1.

Anti-Bacterial Agents↗

Karnamicin, a complex of new antifungal antibiotics. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties.

A complex of new antifungal antibiotics designated karnamicin was isolated from the cultured broth of Saccharothrix aerocolonigenes No. N806-4. Fifteen components have so far been isolated from the complex; the major component karnamicin B2 was identified by X-ray crystallography to be a novel molecule unrelated to known antibiotics. All components of karnamicin exhibited a rather broad spectrum of activity against fungi and yeasts with MICs ranging from 3.1 to 50 micrograms/ml.

Actinomycetales↗

[Innervation of the mitral valve in normal and prolapsed mitral valves].

To evaluate the relationship between mitral valve prolapse (MVP) and autonomic nerve dysfunction, clinical and immunohistochemical studies were performed. I. Clinical study Autonomic function tests and supine bicycle exercise were performed in 60 patients with MVP, 41 under 35 years of age and 19 of 35 years and older, and the results were compared with those of 31 normal controls, 19 under 35 years of age and 12 of 35 years and older. Case with positive response on postural stress and cold pressor tests were more frequent in both MVP groups than those of controls. Plasma nor-adrenaline levels were higher in the MVP groups than in the control groups during exercise. Our clinical observation suggested that autonomic dysfunction, particularly sympathetic hyperactivity, probably is present in MVP irrespective of age. II. Immunohistochemical study In 23 mitral valves (15 of normal controls and eight of MVP), three normal tricuspid, three normal aortic and three normal pulmonic valves, immunohistochemical localizations of S-100 protein, glial fibrillary acidic protein (GFAP) and neurofilament protein (NFP) were examined to detect the distribution of all nerve endings, choline acetyltransferase (ChAT) to detect the distribution of cholinergic nerve fibers, and neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) to detect the distribution of afferent nerve fibers, using the avidin-biotin peroxidase complex (ABC) method. The distribution of adrenergic nerve fibers was examined by fluorescence with the glyoxylic acid method. In normal valves, S-100 protein was mainly demonstrated in the base and body of the valve cusp. It was very scanty in the tip, and was only found in the coaptation zone that is, the layer of the atrialis or along the boundary between the atrialis and the spongiosa in the atrioventricular valves. The distribution of S-100 protein in the prolapsed mitral valve was the same as that of the normal valve except for the lack of S-100 protein in the degenerated portion. The distribution of GFAP, NFP, ChAT, NPY, CGRP and adrenergic fluorescence were the same as that of S-100 protein in both the normal and prolapsed mitral valves. It is suggested that the above-mentioned anatomical distribution of the nerve in the mitral valve is closely related to the dysfunction of the autonomic nerve system in the condition of mitral valve prolapse, because the body of the mitral valve is rich in nerve endings and this area is most easily influenced by the mechanical stimulation due to abnormal coaptation.

Adult↗

[Assessment of prolapsing pattern of the anterior mitral valve in mitral valve prolapse: new echocardiographic diagnostic criteria].

In the present study, the ballooning pattern of the anterior mitral valve (AMV) in mitral valve prolapse (MVP) was investigated, and new diagnostic criteria for MVP were established using two-dimensional and Doppler echocardiography. The study population consisted of 164 patients with prolapse of the AMV alone, including 86 patients with idiopathic MVP, 52 associated with atrial septal defect (ASD), 17 having chordal rupture and nine associated with connective tissue disorders. There were 60 normal controls. The results were as follows: 1. The AMV was divided into two zones, clear and rough (CZ and RZ), according to the point of insertion of the strut chordae based on two-dimensional long-axis echocardiograms of the left ventricle. The severity of AMV prolapse was determined by an angle between the posterior aortic wall (PAO)-CZ and the CZ-RZ. a) Type A: Apparently there was a transitional point between CZ and RZ, despite normal PAO-CZ and CZ-RZ angles. The RZ showed mild ballooning or prolapse into the left atrium. b) Type B: Although the PAO-CZ angle was normal, the CZ-RZ angle was markedly narrowed. Therefore, prolapse of the RZ was more severe compared with that of type A. c) Type C: An overall zone of the AMV showed ballooning or prolapse into the left atrium due to a narrowed PAO-CZ angle. 2. Type B prolapse was frequently observed in idiopathic MVP (58%), the ASD group (71%) and the chordal rupture group (71%), and type C prolapse in MVP of connective tissue disorders (89%). 3. All of 18 patients (100%) with type A, 48 of 99 (48%) with type B, and 10 of 47 (21%) with type C could not be diagnosed as MVP using Gilbert's criterion. 4. Doppler mitral regurgitation (MR) was detected in 40 of the 47 patients (85%) with type C in 56 of the 99 (59%) with type B, and in seven of the 18 (39%) with type A. These results suggested that classification of the two-dimensional echocardiography of the AMV into two zones, clear and rough (CZ and RZ), could contribute to determining not only the severity of AMV prolapse, but also to the extent of myxomatous changes of the AMV and to evaluating the correlations between the degree of MVP and the incidence of MR.

Adolescent↗

[A case of mitral valve prolapse simulating mitral tumor or vegetation].

We observed a case of mitral valve prolapse (MVP) mimicking mitral tumor or vegetation. The patient was a 34-year-old man. He complained of palpitation and precordial oppression. Shaggy and mass echoes of the anterior mitral valve were recorded by M-mode and two-dimensional echocardiograms. The "mass" echo was confirmed to by originated in a markedly myxomatous change of the spongiosa layer of the mitral valve at operation. These problems on echocardiographic diagnosis of MVP and mitral "mass", such as mitral tumor or vegetation, were discussed in detail.

Adult↗

[Two-dimensional and Doppler echocardiographic studies of the genesis of a high-pitched diastolic rumble in mitral stenosis: contribution of the deformed mitral orifice and eccentric mitral inflow jet].

To clarify the genesis of a high-pitched diastolic rumble in mitral stenosis, 51 patients with mitral stenosis were studied. They were subdivided into two groups based on the pitch of a rumble; six patients with a high-pitched rumble and 45 patients with an ordinary low-pitched rumble. Phonocardiography, and M-mode and two-dimensional (2-D) echocardiography were performed in all patients. Color and continuous wave Doppler echocardiography were performed in four patients with a high-pitched rumble and in 13 with a low-pitched rumble. Results obtained were as follows: 1. Points of the maximum intensity of a rumble: A low-pitched rumble was best heard at the apex in all patients. A high-pitched rumble was best heard at the mesoapical area, except in one patient who had an oval mitral orifice by 2-D echocardiography. 2. Correlation between the pitch of rumble and the shape of the mitral orifice: In five of the six patients with a high-pitched rumble, the mitral orifice had a tadpole-shaped deformity, in which commissural fusion and valvular thickening were more marked anterolaterally than posteromedially. Among 45 patients with oval, slit or pinhole-like valve orifices, only one had a high-pitched rumble. 3. Direction of the left ventricular (LV) inflow jet as observed by color Doppler echocardiography: On the short-axis view at the level of the papillary muscles, the inflow jet was directed toward the medial portion of the LV cavity in the patients with a high-pitched rumble. However, it was directed towards the central portion of the LV cavity in all patients with a low-pitched rumble. On the apical long-axis view, no distinct difference was detected in the direction of the LV inflow jet between the two groups. 4. Other findings: There were no significant differences between the two groups in the mitral orifice area, the peak velocity of LV inflow, fractional shortening of the LV, dimension of the left atrium, Wells' index and the degree of organic change in the subvalvular structures. These results suggest that the deformity of the mitral valve and resultant changes in the direction of the LV inflow jet may play an important role in the mechanism of producing a high-pitched diastolic rumble in mitral stenosis.

Adult↗

Glidobactins A, B and C, new antitumor antibiotics. I. Production, isolation, chemical properties and biological activity.

New antitumor antibiotic glidobactins A, B and C were isolated from the cultured broth of a gliding bacterium, Polyangium brachysporum sp. nov. No. K481-B101. They are novel molecules carrying the common cyclic tripeptide nucleus substituted with different alpha, beta, gamma, delta-unsaturated fatty acids. Glidobactins exhibit broad inhibitory activity against fungi and yeasts, and prolong the life span of mice inoculated with P388 leukemia cells.

Animals↗

Glidobactins A, B and C, new antitumor antibiotics. II. Structure elucidation.

The structures of new antitumor antibiotics, glidobactins A (Ia), B (Ib) and C (Ic) were elucidated by a combination of chemical and enzymatic degradations and spectral analyses. They have in common a cyclized tripeptide nucleus composed of L-threonine, 4(S)-amino-2(E)-pentenoic acid and erythro-4-hydroxy-L-lysine, and differ from each other in the unsaturated fatty acid moiety attached to the peptide.

Amino Acids↗

Enzymatic formation of glidobactamine: a peptide nucleus of glidobactins A, B and C, new lipopeptide antitumor antibiotics.

Glidobactin deacylating activity was found in a bacterial strain of Pseudomonas sp. Glidobactamine, a key intermediate for acyl analogues of glidobactin, was isolated from the enzymatic degradation products of glidobactins after treatment using a column of fibrous active gel on which the cells of the Pseudomonas strain were immobilized. The chemical structure of glidobactamine was confirmed as the intact peptide moiety of glidobactins by chemical reformation of glidobactin A from glidobactamine and 2,4-dodecadienoic acid which is the constitutive fatty acid of glidobactin A.

Antibiotics, Antineoplastic↗

Enhanced production of the minor components of glidobactins in Polyangium brachysporum.

Polyangium brachysporum sp. nov. strain ATCC 53080 produces a novel type of antifungal and antitumor antibiotic complex, glidobactins A, B and C. Enhanced production of minor components, glidobactins B and C, was achieved by medium modification. The addition of soybean oil or corn oil, which are rich in unsaturated C18 fatty acids, to the fermentation medium led to an increased production of components B and C. Productivity of component C was selectively enhanced by the addition of oleic acid-rich oils, olive oil and Tween 80 (polyoxyethylene sorbitan mono-oleate). Furthermore, precursing palmitoleate, linoleate and oleate permitted the direct biosynthesis of components A, B and C, respectively. The fermentation with 3% addition of an appropriate oil at initial time provided an optimal production of component B or C.

Antibiotics, Antineoplastic↗

Porothramycin, a new antibiotic of the anthramycin group: production, isolation, structure and biological activity.

A new antitumor antibiotic porothramycin was produced by a new strain of Streptomyces albus. The antibiotic was isolated in two active forms, the natural free hydroxyl form (porothramycin A) or the crystalline methyl ether form (porothramycin B) depending upon the isolation process used. Structural studies established that porothramycin is a new member of the pyrrolo[1,4]benzodiazepine group antibiotics having only one substituent on the benzene ring. The antibiotic exhibited antimicrobial activity against Gram-positive bacteria and anaerobes and significantly prolonged the survival times of mice implanted with experimental tumors.

Animals↗

Synthesis and biological activity of a new cephalosporin, BMY-28232 and its prodrug-type esters for oral use.

The synthesis and structure-activity relationships of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-[( Z)-1- propenyl]-3-cephem-4-carboxylic acid (BMY-28232), its 3-alkenyl analogs (6 and 7) and O-substituted derivatives of the oxyimino moiety (10) are described, as well as the oral pharmacokinetics and in vivo activities of the 1-acetoxyethyl ester of BMY-28232 (BMY-28271) and its analogous esters (11). The 3-alkenyl groups were introduced by the Wittig reaction of the ylide (2) prepared from the 3-chloromethyl cephem (1) to afford the Z (main) and E (minor) isomers regarding the 3-side chain. The O-substituted derivatives (10) were prepared by 7-N-acylation of the 7-amino cephem (4a) with the corresponding O-substituted side chain acids (8). The prodrug esters (11) were prepared by esterification of BMY-28232 with an appropriate halide. BMY-28232 was the most active among the 3-alkenyl analogs tested against Gram-negative organisms and much more active than the O-substituted derivatives against Gram-positive bacteria. BMY-28271 showed good oral bioavailability (66%) and good in vivo efficacy in mice against infections of Staphylococcus aureus Smith (PD50, 0.68 mg/kg) and Escherichia coli Juhl (0.54 mg/kg).

Administration, Oral↗