PubMed Health⌕ Search

Biomedical subjects

E J Modest

Publications and source records attributed to E J Modest.

At least 55 records · Page 3Linked to original sources
PubMed1977

Gene mapping by fluorescent in situ hybridization.

We describe a new method for the mapping of mammalian genes, utilizing in situ hybridization of mRNA to DNA of chromosomes. It involves the hydrogen bonding of the polyadenylic acid at the 3' end of hybridized mRNA to the polyuridylic acid tail of a highly fluorescent latex microsphere. The resultant double hybrid can be visualized by fluorescence microscopy. The chromosomal localization of human alpha + beta globin genes has been explored by this method. Our data point ot the long arms of chromosomes 4 and 5 as the loci for the human globin genes.

Chromosome Mapping↗
PubMed1976

Differences in cellular uptake and cytofluorescence of adriamycin and N-trifluoroacetyladriamycin-14-valerate.

Adriamycin-specific fluorescence appears slowly in living cells and is localized in nuclei and chromosomes. N-Trifluoroacetyladriamycin-14-valerate, a recently synthesized adriamycin analog, differs from the parent anthracycline in the rapid appearance of its fluorescence in the cytoplasm of living cells and the lack of any fluorescent binding to nuclei and chromosomes.

Cell Line↗
PubMed1975

Pharmacokinetics of actinoymcin D in patients with malignant melanoma.

The distribution and excretion of tritiated actinomycin D have been determined in 3 adult patients with disseminated malignant melanoma. In the blood, the drug was preferentially taken up into nucleated cells. The urinary and fecal excretion was prolonged and only about 30 per cent of the dose of actinomycin was recovered in 9 days. There was evidence that the drug was concentrated in bone marrow and tumor cells, but did not readily cross the blood-brain barrier. The long tissue half-lige of actinomycin D suggeststhat an intermittenr schedule of administration would be the most effective.

Adult↗
PubMed1975

Methotrexate analogs. 6. Replacement of glutamic acid by various amino acid esters and amines.

A series of methotrexate (MTX) analogs was prepared in which the glutamic acid moiety is replaced by various amino acid esters and amines. The synthetic method consisted of the reaction of 4-amino-4-deoxy-N10-methylpteroic acid with various reagents to form intermediate mixed anhydrides, which then reacted with amino acid esters or amines to give the MTX analogs. These compounds were tested for antibacterial activity against Streptococcus faecium and for antitumor activity against L1210 leukemia in mice. Several compounds showed significant antibacterial activity; the MTX homocysteinethiolactone and MTX aspartate analogs showed marginal in vivo antitumor activity.

Animals↗
PubMed1975

7-substituted actinomycin D analogs. Chemical and growth-inhibitory studies.

The synthesis and biological activity of three 7-substituted actinomycin D derivatives are reported. Three such derivatives, 7-nitro-, 7-amino-, and 7-hydroxyactinomycin D, were synthesized via new methods which were first tested successfully with a chromophore model system. Of these, 7-nitro- and 7-aminoactinomycin D were assayed for growth inhibitory activity against mammalian cells (CCRF-CEM human lymphoblastic leukemia) in vitro and against the Ridgway osteogenic sarcoma and the L1210, P1534, and P388 murine leukemias in vivo. In these systems, the inhibitory activity of the 7-substituted analogs was comparable to actinomycin D. In two bacterial systems ( (L. casei and L. arabinosus) in vitro, on the other hand, these compounds showed inhibitory profiles which are distinctly different from actinomycin D. These studies demonstrate that substitution at the 7 position, which does not interfere with DNA binding, is capable of yielding experimental antitumor agents with significant activity against a variety of tumors.

Animals↗
PubMed1975

7-Amino-actinomycin D as a cytochemical probe. I. Spectral properties.

The optical absorption and fluorescence characteristics of 7-animo-actinomycin D were determined to evaluate its potential as a fluorescent cytochemical probe. At pH 7.0, the absorption maximum and fluorescence excitation maximum are both at 503 nm; the fluorescence emission is at 675 nm. When this compound forms complexes with DNA in solution, the absorption and fluorescence excitation maxima shift to 543 nm and the fluorescence emission shifts to 655 nm. The fluorescence quantum yield is 0.016 for 7-amino-actinomycin D free in solution and 0.01-0.02 for complexes with native DNA. The 7-amino-actinomycin D also exhibits fluorescence shifts characteristic of binding when put into solution with poly(dG-dC) poly(dG-dC), but not with poly(dI-dC) poly(dI-dC). The spectral characteristics are the same at pH 7.0 whether the solvent is 0.01 M PO4 with 0.0001 M EDTA or Earle's salts with 0.025 M N-2-hydroxyethylpiperazine-N1-2-ethanesulfonic acid.

Animals↗
PubMed1975

N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin.

N-Trifluoroacetyladriamycin-14-valerate (AD 32), an analog of adriamycin, exhibits significantly greater antitumor activity than does adriamycin or daunorubicin in two experimental mouse tumor systems under similar assay conditions (C57BL X DBA/2 F1 male mice, agents administered i.p. each day for Days 1 to 4). Against the P388 leukemia at optimal dosages, AD 32 gave a +429% increase in median life-span with 3 of 5 60-day survivors compared to +132% for adriamycin (no 30-day survivors). In the L1210 leukemia system, AD 32 at several dosages consistently and reproducibly effected an increase in lifespan in excess of 445%, with a high percentage of 60+-day survivors compared to adriamycin (+42 to +54% ILS; no 30-day survivors). The reduced toxicity of AD 32 was evidenced by its optimal dose range, which is significantly greater than the lethal dose for 100% of mice of adriamycin, and by its lack of delayed toxicity. In vitro, AD 32 was somewhat less effective than was adriamycin in inhibiting the growth of CCRF-CEM cells; enzymatic conversion of AD 32 by cell-free culture medium was not observed. The unique growth-inhibitory properties of this analog indicate that the therapeutic effectiveness of the anthracycline antitumor antibiotics can be retained or enhanced by substitution on the glycosidic amino group.

Animals↗