Methotrexate-thymidine treatment of murine leukemia.
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Biomedical subjects
Publications and source records attributed to B L Brown.
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The lack of equivalence in the distrubtion of normal ranges for free thyroxine index (FT4I) and free triiodothyronine index (FT3I) in the over sixty-five age-group, as compared with the fifteen-sixty-five age-group, supports the idea that "T4 toxicosis" is a common biochemical finding in elderly women. The disparity between FT4I and FT3I ranges was also reflected in the true free T4 and free T3 levels which were measured in some cases. These results suggest that when an increased FT4I is found in an elderly woman with cardiac disease, caution should be exercised in interpreting the result as indicating that thyrotoxicosis is the cause of the cardiac disorder. Estimation of total T3, FT3I, or free T3 seems useful in confirming euthyroidism in such cases.
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.
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.
A and B and A1Leb substances were adsorbed onto red cells exposed to glycosphingolipid fractions prepared from the serum of group A and B and A1,Le(a minus b plus) donors. Group O cells exposed to fractions prepared from the serum of group A or B donors were agglutinated by an IgM cross-reacting antibody present in some group O sera. Cells exposed to fractions from A1,Le(a minus b plus) serum were agglutinated by anti-A1Leb. The amount of A substance in the fractions was related to the A subtype (A1 or A2) and to the Lewis and secretor phenotype of the donor. The uptake of blood-group substances from the lipid fractions was inhibited by the addition of whole serum to the fractions.
We measured distribution of radioactivity among urinary metabolites excreted in nonpregnant and ovariectomized sows after intravenous injection of radionuclides (14carbon) labeled estrone, estradiol-17beta, cortisol, and corticosterone. Treatment with an enzyme preparation (Glusulase) containing both beta-glucuronidase and sulfatase activity, rendered extractable over 95% of the radioactivity recovered from urine with diethyl ether (estrogens) and ethyl acetate (corticoids). Only an additional 1 to 4% of the radioactivity was extracted following solvolysis of the aqueous residue remaining after enzyme hydrolysis and extraction. Radioactivity in nonpregnant sow urine was predominantly in the estrone fraction following injection of either estrone or estradiol-17beta. Moreover, the principal metabolite was estrone monoglucuronide. Only traces of estradiol-17beta and an estriol-like compound were detected. Two other isolates contained radioactivity. One compound probably was 2-methoxyestrone, but structure of the other compound (X1) could not be established. The principal urinary metabolites from injection of cortisol corresponded to chromatographic properties of tetrahydrocortisol and tetrahydrocortisone. Both metabolites were low in urine following injection of corticosterone. The major urinary metabolites from corticosterone injection corresponded to chromatographic properties of tetrahydrocorticosterone and corticosterone. Considerable radioactivity from injection of both corticoids was isolated in the cortol, cortolone, and 11-ketoetiocholanolone - 11beta-hydroxyetiocholanolone areas of chromatograms. The data for corticoids agree with similar data for the human being and cow.
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Dispersed rat adrenal cells prepared from both the capsule and the decapsulated gland were used to investigate the effects on cyclic AMP accumulation of known stimuli of steroidogenesis [ACTH (adrenocorticotrophin), angiotensin II, K(+) ions and 5-hydroxytryptamine]. Since glomerulosa-cell preparations from capsular strippings are normally contaminated with a proportion of fasciculata cells, cells purified by fractionation on a bovine serum albumin gradient were also used. The results showed that: (1) ACTH and angiotensin II stimulated cyclic AMP accumulation in both fractionated and unfractionated zona fasciculata cells; (2) 5-hydroxytryptamine and an increased extracellular K(+) concentration (from 3.6 to 8.4mm) had no effect on cyclic AMP concentrations in fasciculata cell preparations; (3) the addition of ACTH, angiotensin II, 5-hydroxytryptamine or K(+) to the incubation medium resulted in increased cyclic AMP concentrations in unpurified zona glomerulosa cell preparations; (4) fractionation and hence the virtual elimination of fasciculata contamination, did not affect the response to 5-hydroxytryptamine and increased K(+) concentration. However, the responses to ACTH and angiotensin II were markedly lowered but not abolished. These results strongly suggest a link between cyclic AMP production and steroidogenesis in the zone of the adrenal gland that specifically secretes aldosterone. All four agents used stimulated both steroid output and cyclic AMP accumulation. However, at certain doses of 5-hydroxytryptamine, K(+) and angiotensin II the significant increases in corticosterone output were not accompanied by measurable increases in cyclic AMP accumulation.
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A chemically defined medium, designated FCRC-1, supports the growth of P3HR-1 cells and concomitant replication of infectious Epstein-Barr virus.
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