Stimulation of bone collagenase synthesis by mouse fibrosarcoma in resorbing bone in vitro culture.
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Biomedical subjects
Publications and source records attributed to M Sakamoto.
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The metabolic detoxication of thymol was investigated in rabbit and man. Thymol glucuronide which the aglycone is intact, was isolated from thymol medicated rabbit urine and identified as a acetyl derivative of methyl glucuronate. The hydroxylated product of thymol, thymohydroquinone, was recognized in a small amount in thymol medicated human urine. It was presumed that thymohydroquinone is excreted as ethereal sulfuric acid conjugate in man.
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The high response of our isolate of Streptomyces griseoviridus was exploited to provoke the synthesis of new viridogrisein homologues by adding various amino acids to the culture medium in an attempt to replace the alanine, sarcosine, leucine and phenylsarcosine moieties of virdogrisein. Among the amino acids added, L- and DL-alpha-amino-n-butyric acid and L-methionine gave new TLC spots which we named neoviridogriseins I and III and neoviridogrisein VII, respectively. The structures of neoviridogriseins I and III were elucidated: In both compounds, the alanine moiety of viridogrisein is replaced by a L-alpha-amino-n-butyric acid residue; furthermore, in neoviridogrisein I, the allo-hydroxy-D-proline is replaced by D-proline.
Neoviridogrisein II is a homologue of viridogrisein in which the hydroxyproline residue is replaced by proline. Neoviridogrisein II proved to be more active than the parent antibiotic against Gram-positive bacteria and Mycoplasma species. When neoviridogrisein II or viridogrisein was combined with griseoviridin, a non-peptidyl macrocyclic lactone, synergism was observed: maximum synergistic effect was observed for a combination ratio that depended on the test bacterium used. Neoviridogrisein II also exerted synergism when combined with mikamycin A and A-2315A.
PS-5, a new beta-lactam antibiotic, has relatively potent antimicrobial activity against Gram-positive and Gram-negative bacteria, especially the Enterobacter groups, Serratia marcescens, the Proteus groups and Klebsiella pneumoniae. The activity of PS-5 against many beta-lactamase-producing organisms is greater than that of cefoxitin or cefazolin. PS-5 has good therapeutic activity in mice infected with Staphylococcus aureus Smith or Enterobacter cloacae 45.
PS-5 was shown to have synergistic activity in combination with other beta-lactam antibiotics and it markedly decreased the minimum inhibitory concentration values of ampicillin or cephaloridine with a beta-lactamase-producing Proteus vulgaris strain on agar plates. The synergistic activities were also shown in bactericidal activity in liquid medium. PS-5 was shown to be inhibitory against an extracted beta-lactamase of P. volgaris.
Our isolate of Streptomyces griseoviridus, which produced three minor factors in addition to viridogrisein and griseoviridus, which produced three minor factors in addition to viridogrisein and griseoviridin, was more sensitive to the addition of L-proline than the type culture of Streptomyces griseoviridus (NRRL2427). Yield improvement of these minor factors was attempted by the so-called controlled biosynthesis with L-proline. Addition of L-proline increased the production of neoviridogrisein II in which allo-hydroxy-D-proline in viridogrisein was replaced by D-proline.
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In malnourished rats, nutritionally rehabilitated rats at various stages, and in well nourished rats, levels of serum complement after bacterial infection caused by Staphylococcus aureus, as well as tuberculin reactivity, were examined. The elevation of complement showed a peak 2--3 days after infection, herein called the first complement response. A reelevation occurred at a later stage, 7--14 days after infection, and is referred to as the second complement response. The first complement response was observed in all the rats after Staphylococcus aureus infection but it was greater in well nourished rats. In malnourished rats, only the first complement response was observed and the tuberculin reaction and second complement response were lacking. After 1 week of nutritional rehabilitation, 40% of the rats showed recovery of tuberculin responses and both the first and second complement responses were observed. Nutritionally rehabilitated rats treated longer than 2 weeks, together with the well nourished control rats, showed positive tuberculin reactivity. The second complement response was also observed in such rats when bacterial infection was severe but not with mild infection.