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Biomedical subjects

J Lein

Publications and source records attributed to J Lein.

At least 19 recordsLinked to original sources

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. I. Microbial deepoxidation and subsequent isomerization of deltamycins A1, A2, A3, A4 (carbomycin A) and X.

Carbomycin A (deltamycin A4) was deepoxidized to carbomycin A P1 by Streptomyces halstedii subsp. deltae (a deltamycins producer), favorably under anaerobic conditions. Carbomycin A P1 was spontaneously converted to geometric isomers designated carbomycins A P2 and A P3. This type of deepoxidation and subsequent isomerization was not limited to carbomycin A, but generally occurrable in other 16-membered epoxyenone macrolide compounds. Many bacteria and actinomycetes were also found to have an ability to deepoxidize deltamycins reductively. The chemical structures of carbomycins A P1, A P2 and A P3 were elucidated as shown in Fig. 3.

Bacteria↗

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. III. In vitro and in vivo evaluation of deepoxidation products of carbomycin A, deltamycin A1, 4"-phenylacetyldeltamycin, angolamycin and rosamicin.

Deepoxidation products P1, P2 and P3 of carbomycin A, deltamycin A1 and 4"-phenylacetyldeltamycin showed high in vitro antibacterial and antimycoplasmal activities which were comparable to those of the respective parent compounds. By contrast, the in vitro antimicrobial potencies of angolamycin P1 and rosamicin P1 were about ten-fold lower than those of the parent macrolides. In mice, the increase in the plasma levels of the epoxyenone macrolides due to deepoxidation was highly significant with the P1, P2 and P3 derivatives of carbomycin A and 4"-phenylacetyldeltamycin, whereas angolamycin P1 gave a moderately-improved plasma level compared with angolamycin.

Animals↗

Chemoimmunotherapy with Corynebacterium parvum in acute myelocytic leukemia.

The purpose of this study is to see if immunotherapy with C. parvum and prevention of central nervous system relapse with intrathecal methotrexate can prolong duration of complete remission and survival as well as avoid central nervous system relapse. For induction, three weekly I.V. injections of vincristine and Daunorubicin were given with daily prednisone orally, followed by 5-day courses of Cytosine Arabinoside and 6-mercaptopurine. The patients were randomized to chemotherapy or chemoimmunotherapy. Maintenance consisted of vincristine, Daunorubicin, and prednisone one week every odd month, and a 5-day course of Cytosine Arabinoside and 6-mercaptopurine every even month. Every week, the chemoimmunotherapy group also received, without chemotherapy, one injection of C. parvum 4 mg, subcutaneously. All patients received five weekly injections of intrathecal methotrexate 13 mg/m2 right after complete remission was achieved. Out of 181 evaluable cases, 80 (44%) achieved complete remission, 45 were randomized to chemotherapy, and 35 to chemoimmunotherapy. In the chemoimmunotherapy group 32/35 relapsed, and in the chemotherapy group 36/45. Median duration of complete remission and survival were: for group chemotherapy, 8 and 15 months; for group chemoimmunotherapy, 5 and 10 months. This difference is not significant. Intrathecal methotrexate was given to all patients. Six patients (7%) had central nervous system leukemia at the time of the first injection. None had central nervous system relapse after prevention with intrathecal methotrexate. This method seems useful in preventing central nervous system relapse in patients with acute myeloblastic leukemia, but does not seem to prolong complete remission.

Adolescent↗

PS-6 and PS-7, new beta-lactam antibiotics. Isolation, physicochemical properties and structures.

Antibiotics PS-6 and PS-7 which are shown to be 5R,6R-3-(2-acetamido)ethylthio-6-isopropyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid and 5R,6R-3-(E)-(2-acetamido) vinylthio-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid respectively, are new beta-lactam compounds isolated from fermentation broths of Streptomyces cremeus subsp. auratilis A271, S. fulvoviridis A933, S. olivaceus ATCC 31126 and S. flavogriseus NRRL 8139. Fermentation, isolation, physicochemical properties and structures of antibiotics PS-6 and PS-7 are described.

Anti-Bacterial Agents↗

PS-6 and PS-7, new beta-lactam antibiotics. In vitro and in vivo evaluation.

Biological properties of two new beta-lactam antibiotics, PS-6 and PS-7, containing the carbapenem nucleus were studied. The in vitro activities of PS-6 and PS-7 were tested against clinical isolates of Gram-positive and Gram-negative bacteria in comparison with those of cefazolin, ampicillin and PS-5. In general, the antibacterial spectra of PS-6 and PS-7 were similar to that of PS-5. PS-7 was slightly less active than PS-5 and ABPC against Staphylococcus aureus. Clinical isolates of Gram-negative bacteria were found to be 2- to 8-fold more resistant to PS-6 than to PS-5, while PS-7 was 2-fold more active than PS-5 against Enterobacter, Klebsiella, Proteus, Serratia and Escherichia coli. The therapeutic effect of PS-6 seemed slightly less than that of PS-5 in an experimental infection with Staph. aureus Smith in mice.

Ampicillin↗

Chemical modification of deltamycins. I. 4''-O-acyl analogs of deltamycins.

Using 4''-O-deacyldeltamycin as a starting material, various 4''-O-acyl derivatives were chemically synthesized by the following scheme: 2'-O-acetylation leads to 4''-O-acylation leads to 2'-O-deacetylation. 4''-O-Deacyldeltamycin is produced during the fermentation of deltamycin producing organisms or can be prepared by the biological deacylation of the deltamycins. 4''-O-Phenylacetyl-4''-O-deacyldeltamycin (PAD) showed good activity against various bacteria and mycoplasma. Among para-substituted PAD derivatives, NPAD (p-nitrophenylacetyl-) and SPAD (p-methylsulfonylphenylacetyl-) showed increased potency as compared to PAD against certain bacteria. The PAD was evaluated by in vivo experiments for plasma levels in mice and dogs and curative activity on the infected mice with Staphylococcus aureus Smith by subcutaneous or oral administration.

Administration, Oral↗

PS-5, a new beta-lactam antibiotic. II. Antimicrobial activity.

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.

Animals↗

PS-5, a new beta-lactam antibiotic. III. Synergistic effects and inhibitory activity against a beta-lactamase.

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.

Anti-Bacterial Agents↗

Deltamycins, new macrolide antibiotics. III. Chemical structures.

The structures of deltamycins A1,A2,A3 and A4 belonging to the basic macrolide family of antibiotics were determined mainly from their spectral properties. Deltamycin A4 was identified as carbomycin A having an isovaleryl group on the mycarose moiety of the molecule. Deltamycin A1,A2 and A3 possess similarities to the structure of deltamycin A4, but they have acetyl, propionyl and n-butyryl group, respectively, in the place of isovaleryl group of deltamycin A4. These structures were confirmed by chemical synthesis from deltamycin X (4''-O-deacyldeltamycin) and the corresponding acyl chlorides.

Chemical Phenomena↗