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Biomedical subjects

J Polonsky

Publications and source records attributed to J Polonsky.

11 recordsLinked to original sources
PubMed1979

Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose-6, 6'-dimycolate) and synthetic analogues.

The ability of cord factor (trehalose-6, 6'-dimycolate) and a range of shorter carbon chain fatty acid trehalose diesters to suppress growth of an ascitic rat hepatoma has been examined and compared with that of whole, living BCG organisms. Aqueous suspensions of BCG, and cord factor in 0.4% arachis oil:Triton emulsion, injected intraperitoneally, retarded growth of up to 10(5) ascites tumour cells. Trehalose-6, 6'-dibehenate was also tumour-suppressive, but only against lower challenge inocula (10(4) cells). Trehalose-6, 6'-dipalmitate and 6,6'-di-0-2-tetradecyl -3-hydroxyoctadecanoyl alpha, alpha trehalose (designated C76) were virtually ineffective and 6,6' -di-0-2-eicosyl-3-hydroxy-tetracosanoyl alpha, alpha trehalose (designated C100) gave small and variable effects only against low challenge inocula. However, improved responses were seen with light mineral oil in place of arachis oil in the emulsions.

Animals↗
PubMed1979

[Semi-synthesis and proposed structure of platelet-activating factor (P.A.F.): PAF-acether an alkyl ether analog of lysophosphatidylcholine].

We have studied the molecular structure of platelet-activating factor" (P.A.F.), a mediator of inflammation obtained from blood leukocytes, macrophages, and platelets themselves. We have semi-synthetized a substance that possesses all the known physicochemical and biological characteristics of P.A.F. from hog leukocytes. This was performed by successive methylation, hydrogenation, and acetylation of lysophosphatidylethanolamine plasmalogen. We therefore propose the following structure for P.A.F.: 1-0-alkyl-2-acetyl-glyceryl-3-phosphorylcholine. This molecular structure is not yet described among the numerous substances capable of inducing platelet aggregation and release.

Acetylation↗
PubMed1979

The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin.

2 new limonoid-type terpenes have been isolated from an aqueous extract of seeds produced by the Eastern Himalayan (India) plant Aphanamixis grandifolia B1. By interpreting principally mass spectral and nuclear magnetic resonance data, the structures of 12-hydroxyamoorastatin (2b) and amoorastatone (3) were elucidated. Unequivocal evidence for the 12-hydroxyamoorastatin structural assignment was obtained by chemical conversion to sendanin (4). Amoorastatin derivative 2b was found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell lines but amoorastatone in the same system was inactive. In a comparative biological study, sendanin (4) and anthothecol (7) were also found significantly to inhibit growth of the P388 cell line, while rohitukin (8) and limonin (9) were found to be inactive.

Animals↗
PubMed1979

Regression of a murine fibrosarcoma after intralesional injection of a synthetic C39 glycolipid related to cord factor.

Intratumoral injection of ultrasonically prepared emulsions of the synthetic glycolipid methly 6-O-(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha-D-glucopyranoside (designated C39) induced complete regression of transplants of a syngeneic murine fibrosarcoma in most of the treated animals as did 6,6'-di-O(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha,alpha,-trehalose (designated C76) in a previous study. The C76 compound, about twice the molecular weight of C39, was more effective therapeutically than the smaller molecule. Ultrasonically prepared emulsions of C39 and C76 were not toxic when given intravenously. Intravenously administered emulsions of C39 prepared by mechanical grinding were more toxic, but less granulomagenic, than those containing C76. Squalane and squalene, but not peanut oil, were effective substitutes for mineral oil as carriers of C39 in the treatment of the tumor.

Animals↗
PubMed1978

Immunotherapy with an intralesionally administered synthetic cord factor analogue.

Injection of emulsified 6,6'-di-O-2-tetradecyl-3-hydroxyoctadecanoyl-a, a trehalose designated C76, a synthetic analogue of the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM), into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in which tumor regressed completely dependent on the amount of oil in the emulsion. On a weight basis, C76 was at least as active as TDM. Intralesional injection of an emulsified mixture of C76 and endotoxin (ET) or of TDM and ET caused regression of an established transplant of a guinea-pig hepatoma in syngeneic animals. In mice, intravenously administered emulsions of C76 were less toxic and less granulomagenic than those made with TDM.

Animals↗
PubMed1978

The isolation and structure of 13,18-dehydroglaucarubinone, a new antineoplastic quassinoid from Simarouba amara.

An investigation of the Guyana plant Simarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2'-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2'-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid 2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388.

Antineoplastic Agents, Phytogenic↗
PubMed1978

Nonspecific immunostimulant activities of synthetic trehalose-6,6'-diesters (lower homologs of cord factor).

Mycobacterial cord factors (6,6'-diesters of trehalose with mycolic acids ranging from C80 to C90) have been shown to protect mice effectively against infection with Klebsiella pneumoniae or with Listeria monocytogenes. Our present findings indicate that the low-molecular-weight cord factor of Corynebacterium diphtheriae (with corynomycolic acids ranging from C28 PTO C36) is equally active. Moreover, its synthetic analog (with synthetic C32 mycolic acid) has the same activity. Two lower synthetic 6,6'-diesters of trehalose with C22 acids, which are described here for the first time, as well as dipalmitate and a dioleate of sucrose, were found inactive. The synthetic C76 trehalose diesters, which are capable of enhancing nonspecific resistance to infection, increase the immune response in mice, even when injected in metabolizable oil. They induce in the injected paws an inflammatory process weaker and more transient than the natural cord factor.

Adjuvants, Immunologic↗
PubMed1977

Roquefortine and isofumigaclavine A, alkaloids from Penicillium roqueforti.

Extraction of mycelium from cultures of Penicillium roqueforti (strain CS1) yielded 2 new crystalline metabolites, designated roquefortine and isofumigaclavine A. The structure of roquefortine, the major alkaloid, was established by a combination of chemical transformations and spectroscopic studies. The structure of isofumigaclavine A was determined by spectroscopic and X-ray analysis. Roquefortine possessed neurotoxic properties when injected intraperitoneally in mice and has been detected in 16 out of 16 samples of blue cheese from 7 countries. Isofumigaclavine A has also been found in blue cheese.

Animals↗
PubMedDate not supplied

[Isolation and partial characterization of (PAF) platelet-activating-factor].

Platelet-activating-factor is a new mediator of anaphylaxis released in numerous mammalian species from basophils and mastocytes by antigens, anti-IgE antiserum, ionophore A 23187, C3a, C5a and neutrophil cationic protein. It is probably a lyso-1-phosphatidylcholine, as evidenced by structural studies isomg phospholipases. It may explain the involvement of platelets in immunopathology.

Animals↗