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Biomedical subjects

E Katz

Publications and source records attributed to E Katz.

At least 253 records · Page 14Linked to original sources

Savings achieved through cephalosporin surveillance.

The process by which a 427-bed, acute-care teaching hospital reduced the cost of cephalosporin therapy is described. During a nine-month surveillance period, cefazolin prescribing patterns were monitored. Of the 674 patients who received cefazolin, 640 (92%) received dosages greater than those recommended in the literature. Attempts were made to alter inappropriate prescribing through pharmacist-physician consultation and through contact with the medical service representative of the company which supplied cefazolin. Because these efforts failed, the pharmacy and therapeutics committee decided to delete cefazolin from the formulary. Cephalothin and cephapirin were found to be clinically similar; therefore, the committee recommended that the less expensive cephapirin be dispensed whenever a parenteral cephalosporin was ordered. Prior to the switch to cephapirin, cefazolin accounted for 49% of all parenteral cephalosporin use and 62% of the cephalosporin cost. Cephalothin and cefazolin were 30% and 88%, respectively, more expensive than cephapirin. In the first year after the switch, the hospital saved $33,196 (28.8% of the previous year's total expenditures for cephalosporins).

Cephalosporins↗

Infidelity of DNA synthesis as related to mutagenesis and carcinogenesis.

An assay system has been developed for measuring the fidelity of DNA synthesis in vitro by using synthetic polynucleotide templates and purified DNA polymerases. Nearest-neighbor analysis of the synthesized product indicates that noncomplementary nucleotides are incorporated as single base substitutions. The accuracy of DNA synthesis can be decreased by (1) prior alkylation of the template, (2) increasing the relative concentration of incorrect nucleotides, and (3) addition of specific metal salts to the reaction mixture. As an initial evaluation of the utility of this system, the effects of 31 metal salts on the fidelity of DNA synthesis have been determined. The results indicate that potential metal mutagens and/or carcinogens may be detected by measuring alterations in the fidelity of DNA synthesis.

Avian Myeloblastosis Virus↗

Induction of delta-Aminolevulinic Acid Formation in Etiolated Maize Leaves Controlled by Two Light Systems.

A short illumination of etiolated maize (Zea mays) leaves with red light causes a protochlorophyll(ide)-chlorophyll(ide) conversion and induces the synthesis of delta-aminolevulinic acid (ALA) during a subsequent dark period. In leaves treated with levulinic acid, more ALA is formed in the dark than in control leaves. Far red light does not cause a conversion of protochlorophyll(ide) into chlorophyll(ide) and does not induce accumulation of ALA in the dark. Both red and far red preilluminations cause a significant potentiation of ALA synthesis during a period of white light subsequent to the dark period. The results indicate a dual light control of ALA formation. The possible role of phytochrome and protochlorophyllide as photoreceptors in this control system is discussed.

Journal Article↗

Synthesis of vaccinia viral antigens in HeLa cells in the presence of isatin beta-thiosemicarbazone.

Vaccinia virus antigens, in HeLa cells treated with the antipox virus drug isatin beta-thiosemicarbazone (IBT), were analyzed by immunoprecipitation, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The total radioactivity in the immunoprecipitate was decreased to almost 50% in the presence of the drug as compared to its absence. An inhibition also occurred with an IBT-dependent mutant (IBT(D)) when growing in the absence of IBT. However, similar levels of radioactivity were observed in the immunoprecipitates from an IBT-resistant mutant (IBT(R)) grown in either the absence or presence of the drug. When the antigens within the immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it was shown that the inhibition observed in the wild-type-infected cells in the presence of IBT and in the IBT(D)-infected cells in the absence of the drug, was quantitative, affecting the amounts of the different polypeptides more or less equally.

Animals↗

Development of a chemically defined medium for the synthesis of actinomycin D by Streptomyces parvulus.

A chemically defined medium, consisting of d-fructose, l-glutamic acid, l-histidine, K(2)HPO(4), MgSO(4).7H(2)O, ZnSO(4).7H(2)O, CaCl(2).2H(2)O, FeSO(4).7H(2)O, CoCl(2).6H(2)O, and deionized water, was developed for synthesis of high yields (500 to 600 mug/ml) of actinomycin D by Streptomyces parvulus. Under these nutritional conditions, growth and actinomycin formation did not follow a typical trophophase-idiophase pattern. The amino acids appeared to have a sparing action on the utilization of d-fructose which was slowly and incompletely metabolized during mycelium development and antibiotic production. A significant repression of actinomycin synthesis by S. parvulus was observed when d-glucose (0.01 to 0.25%) was added to the culture medium. The repression was not due to a decline in the pH of the medium during glucose catabolism.

Amino Acids↗

Novel actinomycins formed by biosynthetic incorporation of cis- and trans-4-methylproline.

Streptomyces parvulus (Streptomyces parvullus) normally produces actinomycin D; in the presence of cis-4-methylproline, this species synthesizes two additional actinomycins, designated K(1c) and K(2c), in which one and two proline sites, respectively, are occupied by cis-4-methylproline. Analogously, actinomycins K(1t) and K(2t) are formed in the presence of trans-4-methylproline. Both mixtures were separated chromatographically, and the four novel actinomycins were obtained in crystalline form. Their biological activities were compared with that of actinomycin D in respect to inhibition of ribonucleic acid, deoxyribonucleic acid, and protein synthesis and antimicrobial potency. In all cases examined, the order of activity D > K(1t) > K(1c) > K(2t) > K(2c) was observed, and the same sequence prevailed in a spectroscopic measure of their binding to deoxyribonucleic acid. In addition, proton nuclear magnetic resonance studies revealed that the replacement of proline by cis-4-methylproline alters the conformation of the antibiotic molecule.

Bacillus subtilis↗

The effect of tilorone hydrochloride on the growth of several animal viruses in tissue cultures.

Tilorone hydrochloride, at a concentration of 10 mug/ml inhibits the growth of herpes simplex virus type 1 in BS-C-1 cells. The growth of vaccinia virus in BS-C-1 cells is partially inhibited; however, six viruses containing RNA, including four members of the togavirus group grown in chick fibroblasts, are not affected by the drug. The inhibition of the growth of herpes virus by tilorone hydrochloride is greater when the multiplicity of infection is lower than 1 p.f.u/cell and when the drug is added early in the course of infection.

Cell Line↗

Inhibition of vaccinia virus growth by the nucleoside analogue 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ribavirin).

Virazole or Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits the growth of vaccinia virus at a concentration ode to a certain extent in the presence of Virazole, the DNA fails to acquire resistance to deoxyribonuclease and virus particles are not formed. Reversibility of the antiviral effect occurs when the drug is washed out from the infected cultures or when guanosine at an equimolar concentration is added.

Cell Line↗

Micromonospora-produced gentamicin components.

After the chromatographic separation of [methyl-(14)C]gentamicin major (C) components from a large-scale radioactive fermentation (Lee et al., 1974), [methyl-(14)C]gentamicin minor (polar) components (A, B, B(1), X(2), and G-418) were isolated from subsequent chromatography of the remaining antibiotic mixture. When l-[methyl-(14)C]methionine was added at the onset of biosynthesis of the gentamicin components, incorporation of label into the minor components preceded incorporation into the major components. Degradation occurred when [methyl-(14)C]gentamicin major components (C(1), C(2) and C(1)a) were added respectively to the gentamicin-producing culture medium and shaken.

Biodegradation, Environmental↗

Inhibition of herpesvirus deoxyribonucleic acid and protein synthesis by tilorone hydrochloride.

Tilorone hydrochloride at a concentration of 10 mug/ml very efficiently inhibited herpes simplex virus growth in BSC1 cells when the virus is infected at a low multiplicity of infection. The adsorption of the virus was not affected by the drug, and the penetration of the deoxyribonucleic acid of the input virus into the cytoplasm and nuclei proceeded normally when tilorone hydrochloride was present. However, newly synthesized viral deoxyribonucleic acid was not detectable under these conditions, there was a remarkable decrease in the rate of viral polypeptide synthesis, and virus particles were not formed. The inhibition of herpesvirus growth by tilorone hydrochloride was absolutely dependent on the presence of the drug in the cultures. Pretreatment of the cells with the drug did not result in resistance to herpesvirus infection after the removal of the drug.

Cell Nucleus↗

Biogenetic origin of the D-isoleucine and N-methyl-L-alloisoleucine residues in the actinomycins.

Studies with (14)C-labeled isoleucine stereisomers have established that l-alloisoleucine, d-alloisoleucine, and d-isoleucine may function as precursors for the biogenesis of d-isoleucine and N-methyl-l-alloisoleucine residues in actinomycin. l-[(14)C]isoleucine appears to be employed chiefly for d-alloisoleucine (and N-methylisoleucine [?] formation); however, its role in the biosynthesis of d-isoleucine and N-methylalloisoleucine remains unclear. The potential pathway of biosynthesis of d-isoleucine and N-methyl-l-isoleucine is discussed.

Amino Acids↗

Micromonospora-produced sisomicin components.

A sisomicin fermentation carried out in the presence of (methyl-14C)-L-methionine resulted in a crude mixture, composed of methyl-14C-labeled sisomicin as a major component; and two 4''-C-desmethylsisomicin (66-40B and 66-40D) isomer-like components, an unidentified component and a gentamicin A-like antibiotic as minor components. When (methyl-14C)-L-methionine was added in an early stage of the fermentation (24 hours), incorporation of methyl-14C-label into polar components (e.g., gentamicin A-like antibiotic) preceded that into sisomicin. Chromatographic evidence for the bioconversion of (methyl-14C)-gentamicin A to a radioactive sisomicin-like product (possibly (3''-N-methyl-14C)-sisomicin) was seen, when a Micromonospora blocked mutant was incubated in the presence of the former antibiotic.

Anti-Bacterial Agents↗

Studies of etamycin biosynthesis employing short-term experiments with radiolabeled precursors.

The biosynthesis of etamycin by Streptomyces griseoviridus was investigated with the precursors, 14C-L-leucine and 14CH3-L-methionine, during short-term incubations. Both radiosotopes are rapidly incorporated into the antibiotic without significant lag. D-Leucine,but not L-leucine,inhibits etamycin formation. The kinetics of incorporation of 14C-L-leucine as well as the inhibitor studies suggest that L-leucine is the direct precursor of theD-enantiomerpresent in the antibiotic peptide. Chloramephenicol has been shown to inhibit protein synthesis by S. griseoviridus without reduction of etamycin formation, indicating that a non-ribosomal mechanism of synthesis is involved in etamycin biogenesis. When L-ethionine was employed, both the formation of antibiotic and protein were blocked.

Anti-Bacterial Agents↗