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Biomedical subjects

A Tasaka

Publications and source records attributed to A Tasaka.

14 recordsLinked to original sources
PubMed1989

Platelet activating factor antagonists: synthesis and structure-activity studies of novel PAF analogues modified in the phosphorylcholine moiety.

New analogues of platelet activating factor (PAF), in which the phosphate and trimethylammonium moieties were replaced with an acylcarbamoyl moiety and a quaternary cyclic ammonium group, were synthesized. Their biological activities as PAF antagonists were evaluated by the inhibition of PAF-induced rabbit platelet aggregation in vitro and protective effects on PAF-induced hypotension in rats and PAF-induced death in mice. Investigation of structure-activity relationships revealed that PAF antagonist activity is strongly influenced by the acyl substituent of the nitrogen atom on the carbamoyl group and the nature of the polar head group at the 3-position of the glycerin backbone. Among the compounds tested, 2-[[N-acetyl-N-[[2-methoxy-3-[ (octadecylcarbamoyl)oxy]propoxy]-carbonyl]amino] methyl]-1-ethylpyridinium chloride (21, CV-6209) was one of the most potent compounds in the in vitro assay (IC50 = 7.5 X 10(-8) M) and the most potent and long-lasting in the in vivo assays. (R)-(-)-21 and (S)-(+)-21 were also synthesized, and no significant differences were observed in PAF antagonist activity in vitro and an inhibitory effect on PAF induced hypotension in vivo between (RS)-21 and its enantiomers.

Animals↗
PubMed1989

Synthesis and antitumor activity of new alkylphospholipids containing modifications of the phosphocholine moiety.

New antitumor alkylglycerophospholipids, in which primarily the phosphocholine moiety of the platelet activating factor (PAF) molecule was modified, were synthesized from 1-alkyl-2-substituted glycerols by introducing polar head phosphoryl groups having methylene bridges of various lengths (from 2 to 14 carbons). They were tested for PAF agonistic activity and antitumor properties. In a series of 1-octadecyl-2-acetoacetylglycerophospholipids (1a-f), an increase in the length of the methylene bridge separating the phosphate and trimethylammonio group in the polar head side chain at position 3 of the glycerol backbone resulted in a progressive decrease in PAF agonistic activity and a characteristic change in antitumor activity against human promyelocytic leukemia cells (HL-60). Maximal potency was obtained with the compound having a decamethylene bridge (1e, IC50 value = 1.5 microgram/ml). Thus, alkylphospholipids possessing a decamethylene bridge and a variety of substituents at position 2 (1g-n) were synthesized. They showed potent inhibitory activity with IC50 values ranging from 0.4 to 1.9 micrograms/ml, depending on the nature of the 2-substituent in the phospholipid molecule. In in vivo tests of the present series of alkylglycerophospholipids (1a--n), using mice bearing sarcoma 180 and mice with mammary carcinoma MM46 (both cells and compounds were given i.p.), 1-octadecyl-2-acetoacetyl-3-glyceryl omega-trimethylammoniodecyl phosphate (1e) showed the most potent life-prolonging effect. The structure-activity relationships are discussed.

Animals↗
PubMed1979

Computed tomography in the evaluation of hepatocellular carcinoma.

Computed tomography (CT) was used to evaluate 47 cases of hepatocellular carcinoma: it was definite in 37, equivocal in 5 and negative in 5 cases. No specific patterns of CT images were recognized. Pre- and postcontrast scans were necessary because several tumors could only be detected on one or the other scan. CT may reveal the exact extent of tumor and show additional tumors in case of multiple lesions. However, false negative results are possible in isodense or very small tumors.

Adult↗
PubMed1978

Cerebral venous angioma: computerized tomography and angiographic diagnosis.

Four cases of cerebral venous angioma were studied by both CT and angiography. All cases showed similar angiographic findings: a normal arterial phase and a local network of small veins that converged centrally into a single large draining vein. However, CT showed nodular areas of high density in three cases, and a curvilinear enhanced lesion representing the draining vein in the other. CT findings are nonspecific but very useful for detecting the lesion and demonstrating the associated hematoma. Angiographic findings are not so obvious as in AVM, but are necessary for the final diagnosis of the venous angioma.

Adult↗