PubMed Health⌕ Search

Biomedical subjects

M L Blank

Publications and source records attributed to M L Blank.

At least 91 records · Page 5Linked to original sources
PubMed1982

Structural features of platelet activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) required for hypotensive and platelet serotonin responses.

A number of analogs similar in structure to biologically active 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) were tested for their relative effectiveness in lowering the blood pressure of spontaneous hypertensive rats and in releasing [3H]serotonin from rabbit platelets. Except for some minor variations, the two test systems gave the same pattern of relative responses for a given analog. Both biological activities (the antihypertensive response and release of platelet serotonin) appear to be stereospecific since the unnatural isomer exhibited no detectable effects. Other structural modifications that greatly reduced (greater than 500-fold) or eliminated the two biological activities were: 1) removal of the acetate group, 2) substitution of the acetate group with long-chain acyl, methoxy, benzoxy, N-formyl, N-trifluoroacetyl, N-hexadecanoyl, or deoxy groups such as dimethyl, propyl, isopropyl, or isobutyl, and 3) replacement of the sn-1 0-alkyl group with an acyl moiety. Biological activities were reduced to a lesser extent (100- to 500-fold) when the sn-2 carbon contained butyrate or hexanoate groups or if ethanolamine was substituted for the choline base. Replacing the sn-2 acetate group with an ethoxy group lowered the activity 48- and 120-fold for the blood pressure and serotonin release, respectively. Substitution of propionate for acetate at the sn-2 carbon gave a compound that was at least, if not more, biologically active than the parent structure; although an N-acetyl analog possessed biologic activities, the responses were only 0.27 to 1.0% of those obtained with the O-acetyl lipid. Maximum biological activity for both hypotensive effects and platelet serotonin release required a glycerolipid having an alkyl ether at the sn-1, acetate or propionate groups at the sn-2, and phosphocholine at the sn-3 positions.

Animals↗
PubMed1981

A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid).

1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine, a phospholipid with platelet activating and hypotensive properties, has an extremely labile acetate grouping. The acetate group is obviously important in the expression of the biological properties of this unique derivative of plasmanic acid since once it is hydrolyzed from the parent compound to form the lyso product, all biological activity is lost. Our studies show that the enzyme responsible for the hydrolysis of the acetate moiety, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine: acetylhydrolase, occurs in the cytosolic fraction of a variety of tissues and has a pH optimum of 7.5 to 8.5. Effects of calcium, magnesium, EDTA, dithiothreitol, deoxycholate, and diisopropylfluorophosphate on the enzyme activity and the fact that egg phosphatidylcholine was not inhibitory indicate that acetylhydrolase activity has different properties from those normally associated with the phospholipase A2 that utilizes phospholipids with two long chain acyl groups. The highest specific activity of the acetylhydrolase occurred in kidney; lung and brain were also good sources of the enzyme. The soluble fraction from the kidney cortex had an apparent Km and Vmax of 3.1 microM and 17.8 nmol/min/mg of protein, respectively. Our results indicate that acetylhydrolase plays a significant role in the catabolism of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine.

Animals↗
PubMed1981

[Effect of intravenous administration of nitroglycerin on the lesion size in acute myocardial infarct].

A controlled study conducted in 60 patients (treated group 33 patients, control group 27 patients) showed that intravenous infusion of nitroglycerin results in 4 hours in a significantly positive dynamics of the parameters of precardial cartogram in 35 leads. Study of serial activity of CPK and MB fraction of CPK showed that a significant difference in the size of the affection is revealed only by the results of CPK examination. It was also established that a diminution in the size of the affection is possible both in increased end diastolic pressure in the pulmonary artery and in normal initial value, which does not allow the mechanism of the protective nitroglycerin effect to be explained only by the hemodynamic action of vasodilation.

Drug Evaluation↗
PubMed1979

Quantitative chromatographic method for the determination of low levels of nitrilotriacetic and ethylenediaminetetraacetic acids in diethylenetriaminepentaacetic acid.

A quantitative method for determination of low levels (0.05%, w/w) of nitrilotriacetic and ethylenediaminetetraacetic acids in diethylenetriaminepentaacetic acid is described. Palmitic acid is added to the chelator as an internal standard before esterification with methanol containing 2%(v/v)H2SO4. The methyl esters of palmitic, nitrilotriacetic, and ethylenediaminetetraacetic acids are first separated from diethylenetriaminepentaacetate by silicic acid column chromatography and are subsequently quantitated by gas-liquid chromatography. The method is both accurate and reproducible with less than 10% relative error. Thin-layer chromatographic separations of the methyl esters, and quantitation at the 1% level, are also described.

Acetates↗
PubMed1979

Bradykinin-stimulated release of [3H]arachidonic acid from phospholipids of HSDM1C1 cells: comparison of diacyl phospholipids and plasmalogens as sources of prostaglandin precursors.

Ethanolamine plasmalogens (1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamines) of many tissues contain high levels of arachidonate at their 2-position, and in certain tissues have been implicated as possible donors of arachidonate required in the synthesis of prostaglandins and thromboxanes. In the present study, [3H]arachidonate-labeled phospholipids of HSDM1C1 cells, a cell line derived from a mouse fibrosarcoma, were examined to determine the donor of the arachidonic acid released upon bradykinin stimulation of the synthesis of PGE2. HSDM1C1 cells labeled with [3H]arachidonic acid for 24 hr in serum-free medium were used in most of the experiments and had the following distribution of label among the cellular lipids; phosphatidylcholine (33%), phosphatidylinositol (20%), diacyl-sn-glycero-3-phosphoethanolamine (15%), ethanolamine plasmalogen (15%), and less polar lipids )16%). Bradykinin treatment stimulated a rapid hydrolysis of [3H]arachidonate from the cellular lipids and conversion of the released acid to PGE2, which was secreted into the medium. The label was released predominantly from phosphatidylinositol and possibly from phosphatidylcholine with no detectable change in the labeling of diacyl- or 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine. The ethanolamine plasmalogens, therefore, do not appear to be involved in the stimulated release of arachidonate in the HSDM1C1 cells. Indomethacin blocked the bradykinin-stimulated synthesis of PGE2 and to a lesser degree inhibited the release of [3H]arachidonate from the cellular lipids into the medium.

Animals↗
PubMed1978

Effect of a choline inhibitor (N-isopropylethanolamine) on cellular metabolism of L-M cells.

N-Isopropylethanolamine, a choline analog, is incorporated into L-M cell lipids as 1,2-diacyl-sn-glycero-3-phosphoisopropylethanolamine de novo and not by base exchange. In addition, the N-isopropylethanolamine effectively blocks choline uptake, which is a reversible process. The following specific time-dependent changes in cell metabolism also occur when N-isopropylethanolamine is present: (1) a decrease in total content of phosphatidylcholine, (2) inhibition of both the cellular uptake of [3H]choline and its incorporation into phosphatidycholine, (3) a decrease in the incorporation of [3H]thymidine into DNA as early as 2 h after initiating the N-isopropylethanolamine block, (4) inhibition of the cellular uptake of [3H]uridine and incorporation into RNA 16--24 h after addition of the N-isopropylethanolamine, and (5) stimulation of the cellular uptake of [3H]leucine and an inhibition of its incorporation into protein, which reached a maximum (68% of controls) 8 h after N-isopropylethanolamine treatment.

Cells, Cultured↗
PubMed1978

Membrane lipid modifications: biosynthesis and identification of phosphatidyl-N-methyl-N-isopropylethanolamine in rat liver microsomes.

In previous studies on the modification of polar head groups of membrane phospholipids with the unnatural base analog, N-isopropylethanolamine, we reported an unidentified phospholipid in addition to phosphatidyl-N-isopropylethanolamine in the various membrane fractions of rat liver. The structure of this phospholipid has now been identified as phosphatidyl-N-methyl-N-isopropylethanolamine by nuclear magnetic resonance spectroscopy, and by chromatographic and enzymic analysis. In addition, we found that when rats were injected intraperitoneally with the N-methyl-N-isopropylethanolamine, 19% of the liver microsomal phospholipid was phosphatidyl-N-methyl-N-isopropylethanolamine.

Animals↗
PubMed1975

Incorporation and subcellular distribution of an unnatural phospholipid base-analog, N-isopropyl-ethanolamine, in rat liver.

An unnatural phospholipid, phosphatidyl-N-isopropylethanolamine, was isolated from rat liver after intraperitoneal injections of N-isopropylethanol-amine; it was identified on the basis of enzymic, chemical, and chromatographic analyses. Although this phospholipid was formed at the expense of phosphatidylcholine and phosphatidylethanolamine, its fatty acid composition did not resemble either of these lipids. Microsomes, mitochondria, and plasma membranes contained significant amounts (up to 9%) of this unusual phospholipid. Radioisotope incorporation experiments suggest that the N-isopropylethanol-amine containing phospholipid is rapidly equilibrated between microsomes and mitochondria and more slowly with surface membranes.

Animals↗