Biomedical subjects
Publications and source records attributed to K Numata.
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.
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.
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.
A variety of glidobactin analogs modified at the fatty acid, L-threonine and nucleus moieties of the molecule were synthesized and their structure-activity relationships examined. The antitumor and antifungal activity was greatly influenced by modification of the fatty acid glidobactin, with the dodecanoyl and tetradecanoyl analogs exhibiting better antitumor activity than the parent antibiotics. Replacement of the L-threonine with other amino acids greatly reduced the activity and reduction of the double bond of the nucleus completely eliminated the biological activity of glidobactin.
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We studied the effect of high-frequency ventilation (HFV) (3 Hz for 2 h) on extravascular lung water in normal dogs and dogs with pulmonary edema. We used an endobronchial dividing tube to ventilate one lung with HFV and to keep the contralateral lung of the same dog static with an identical airway pressure, allowing each animal to serve as its own control. Results showed no change in the extravascular lung water with HFV compared with the static lungs in normal, mild pulmonary edema, and severe pulmonary edema groups. We conclude that HFV has no appreciable effect on lung fluid balance; the lymphatic system retains its ability to increase flow even with experimentally produced pulmonary edema.
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