Biomedical subjects

M H Marx

Publications and source records attributed to M H Marx.

At least 19 recordsLinked to original sources

PubMed1993

Multigram synthesis of 1-alkylamido phospholipids.

Phospholipids containing a 1-alkylamido linkage have shown promising in vitro neoplastic cell growth inhibitory properties and anti-human immunodeficiency viral activity. We have synthesized a series of alkylamido ether lipid analogues on a milligram scale for initial evaluation, but for further in vivo testing of these bioactive phospholipids, synthesis on a larger scale is required. The multigram synthesis of 1-alkylamido ether phospholipids was accomplished by modifying reaction conditions in the amidation step and changing reagents and solvent systems in both the detritylation and phosphorylation steps. This was most crucial in the phosphorylation step, where in the multigram synthesis 2-bromoethyl dichlorophosphate in diethyl ether/tetrahydrofuran (7:3, vol/vol) gave much improved yields as compared to the 2-chloro-2-oxo-1,3,2-dioxaphospholane reagent. The modifications also resulted in a product that could be more easily purified in sufficient quantities for use in in vivo inhibition studies.

Antineoplastic Agents↗

PubMed1989

Darmstoff analogues. 3. Actions of choline esters of acetal phosphatidic acids on visceral smooth muscle.

A number of naturally occurring phospholipids, e.g. the acetal phosphatidic acid derivatives that comprise Darmstoff (1) and the phosphatidylcholine derivative platelet activating factor (PAF), cause contraction of certain visceral smooth muscles and cause platelet activation. Because the Darmstoff phosphatidic acids and PAF are structurally similar, it was of interest to compare the biological actions of choline esters of Darmstoff with those of PAF and of the parent Darmstoff phosphatidic acids. To this end, [(2-pentadecyl-1,3-dioxolan-4-yl)methyl]phosphocholine (3a), [[2-(cis-8-heptadecenyl)-1,3-dioxolan-4-yl]methyl]phosphocho line (3b), and [[2-(cis-8-pentadecenyl)-1,3-dioxolan-4-yl]methyl]phosphocho line (3c) were synthesized. Compounds 3a, 3b, 3c, and PAF caused dose-dependent relaxation of taenia coli strips. In contrast, the unesterified materials 1a and 1b, as well as lyso-PAF, caused contraction in taenia coli strips. Thus, the contractile effect of Darmstoff is reversed on esterification with choline. In preparations of whole trachea, both 1a and 3a had contractile effects similar to those of PAF.

Animals↗

PubMed1989

Elementary counting of cardinal and ordinal numbers by persons with mental retardation.

Cardinal and ordinal counting skills were assessed in 37 mentally retarded adult workers and 42 school children with mental retardation. The major results were the very poor performance of the younger children (essentially at chance beyond the numbers 1 and 2) and the overall marked inferiority in ordinal compared with cardinal counting.

Achievement↗

PubMed1988

Synthesis and evaluation of neoplastic cell growth inhibition of 1-N-alkylamide analogues of glycero-3-phosphocholine.

Previously unreported analogues of the synthetic antitumor phospholipid ET-18-OMe (1-octadecyl-2-methoxy-rac-glycero-3-phosphocholine), in which the 1-ether oxygen has been replaced by an amido group, have been prepared and evaluated for in vitro cytotoxic effects and for inhibition of protein kinase C. The title compounds exhibit cytotoxic effects against several tumor cell lines and are approximately equipotent to ET-18-OMe. The compounds were also found to inhibit protein kinase C in an in vitro assay. This work is a continuation of our previous structure-activity studies on thio-substituted derivatives of ET-18-OMe.

Amides↗

PubMed1987

1-O-alkyl-2-N-methylcarbamyl-glycerophosphocholine: a biologically potent, non-metabolizable analog of platelet-activating factor.

We prepared unlabeled and 3H-labeled analogs of platelet-activating factor (PAF) containing a N-methylcarbamyl residue at the sn-2 position. PAF and its methylcarbamyl analog competed for binding to high affinity receptors on human polymorphonuclear neutrophils; their respective dissociation constants for these receptors were 0.2 and 1.1 nM. The binding affinities of the two analogs correlated precisely with their capacities to stimulate neutrophil degranulation responses. Unlike PAF, however, the methylcarbamyl analog completely resisted metabolic inactivation by neutrophils and by human sera. Thus, these compounds' biological potencies are determined predominantly by receptor binding: cellular metabolism of the ligands neither contributes to nor appreciably limits their stimulating actions.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1974

Peak shift as a function of multiple schedules of reinforcement.

Pigeons were trained to respond to two stimuli on the wavelength continuum, 550 nm and 570 nm, each correlated with an independent schedule of reinforcement. The multiple schedule component in effect during 550 nm (S1) was always a variable-interval 1-min. During the 570-nm stimulus (S2) the second component of the schedule was either variable-interval 30-sec, 1-min, 2-min, 5-min, or extinction for different groups of birds. Generalization gradients were obtained after this training, with the following results: (1) response rate to S1 during training was related to the reinforcement frequency associated with S2; the distribution of responding during generalization testing was a function of the schedules of reinforcement used during training and the response rates they produced. Decreases in the relative frequency of reinforcement correlated with S2 resulted in increases in the distribution shift of responses away from S2 during generalization testing.

Journal Article↗

PubMed1972