Showing papers by "Hiroshi Maeda published in 1981"

Neocarzinostatin in cancer chemotherapy (review).

Abstract: This article describes previous studies on a unique protein antitumor antibiotic, neocarzinostatin. Namely, its chemical nature, mode of action at molecular and cellular levels, toxicity and pharmacology, and recent results in clinical trials obtained primarily in Japan have been reviewed briefly.

A pharmacokinetic simulation model for chemotherapy of brain tumor with an antitumor protein antibiotic, neocarzinostatin. Theoretical considerations behind a two-compartment model for continuous infusion via an internal carotid artery.

Abstract: A pharmacokinetic two-compartment model for the treatment of brain tumors in man was simulated with the aid of a computer. The parameters necessary for the simulations such as inactivation rate constant, elimination rate constant, distribution volume, blood volume, cerebral blood flow, and cytotoxic drug concentration were either determined in this study or obtained from the literature. A proteinaceous antitumor antibiotic, neocarzinostatin (NCS), was utilized as a prototype drug because it has features making it advantageous in the treatment of brain tumor. In particular, NCS has an extremely short half-life in serum (t1/2≤3s), while it is relatively stable in the cerebrospinal fluid (CSF) (t1/2∼50s). Therefore, the drug level in the cerebral compartment can be made adequately high with an appropriate infusion velocity into the cerebral compartment; however, it was possible to keep the plasma level of the drug much lower than the toxic level. Thus, few side-effects should result. In an in vitro study, NCS was found to exhibit its cytotoxicity to glioblastoma cells at a concentration as low as 0.005 μg/ml. In contrast, the cytotoxicity was not apparent for the normal glia cells at 0.1 μg/ml. The model being considered in this investigation is a two-compartment model, which consists of the cerebral compartment and the rest of the circulatory system of the body. In this case the drug is infused via an internal carotid artery. The results of pharmacokinetic simulation and dose regimens for NCS are presented, based on the effective concentration of the drug to glioblastoma cells in culture and the available pharmacological parameters.

Fluorescence polarization with FDA in leukaemic cells: a clear difference between myelogenous and lymphocytic origins.

Abstract: Intracellular fluorescence polarization (IFP) values of normal human lymphocytes and leukaemic cells from newly diagnosed patients were determined from fluorescence polarization using fluorescein diacetate (FDA). Thirty healthy donors and 40 patients with various types of leukaemia (20 myelogenous and 20 lymphocytic) were included in the present studies. The result was that myeloid cells had about twice the polarization value of lymphocytic cells. The use of FDA for the determination of IFP appears to be useful for differential diagnosis, at least between acute myelogenous and lymphocytic leukaemias. These 2 types of leukaemia also showed a pronounced difference in fluorescence intensity when treated with FDA, perhaps owing to a difference in uptake velocity. The previously described membrane microviscosity using 1,6-diphenyl-1,3,5-hexatriene (DPH), however, did not show such a difference between these 2 leukaemias. The fluorescein-binding protein(s) was also investigated in order to clarify its effect on IFP, but there seemed little evidence for the existence of any such dyebinding protein(s). The advantages of the present method, using FDA, reside in its simplicity, rapidity and considerable sensitivity, requiring a small sample of blood usually less than 5 ml.

Polysaccharide kss22d and its preparation

Abstract: NEW MATERIAL:A polysaccharide, KS-2-D, having the following physical and chemical properties. Elemental analysis, C 42.3+ or -1.5%, H 6.2+ or -0.3%, N 0.6+ or - 0.2%, ash 6.7+ or - 2.5%; molecular weight, 30,000-70,000, average molecular weight, 70,000; white amorphous powder; decomposition point, 185 deg.C (Capillary method); pH=7-8, nearly neutral; soluble in water, insoluble in ethanol, acetone, n-hexane, etc.; specific rotation, [alpha]D =+66.1-+97.5 deg. (average 82.9 deg.) (water, c=0.5%); positive to phenol-sulfuric acid reaction, anthron reaction, etc., negative to toluidine blue O staining; saccharide content, 65-80% (average 71%), protein content, 3.5-6% (average 4.8%), protein/saccharide ratio, 0.05-0.08 (average 0.07), etc. USE:Carcinostatic agent. Preventive and remedy for diseases caused by candida, Pseudomonas aeruginosa, Listeria, influenza virus, etc. PROCESS:The compound can be prepared by culturing strain of Lentinus edodes KSLE 28 (FERM-P No.4196), etc.

Agents for improvement of peripheral blood flow

Abstract: Agents for improving blood circulation containing gelatin or solubilized collagen as the effective component. The agents facilitate and restore impaired peripheral blood flow, prevent the occurence of circulatory insufficiency, stabilize plasma cells, prevent coagulation of blood, and improve maintenance of various devices for assisting extracorporeal circulation.

Peripheral circulation failure-curing agent

Abstract: A peripheral circulation failure-curing agent comprising (Alpha)1-acidic glycoprotein. Peripheral circulation failure caused by blood stream trouble resulting from induration of blood vessels due to aging, drop in blood pressure, or acceleration of fibrinolysis system can be alleviated or cured with an (Alpha)1-acidic glycoprotein which prevents coagulation or agglomeration of solid ingredients in the blood and which raises permeability of erythrocytes in the intravital micro-circulation system. (Alpha)1-acidic glycoprotein has an extremely low toxicity and is preferably administrated intravenously or intraarterially in the form of an injection.