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Biomedical subjects

T Tashiro

Publications and source records attributed to T Tashiro.

At least 379 records · Page 21Linked to original sources

Antitumor activity and toxicity of methyl 6-[3-(2-chloroethyl)- 3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside in experimental animals.

A new water-soluble nitrosourea derivative, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), was tested for antitumor activity against murine tumors (L1210 and P388 leukemias, B16 melanoma, and Lewis lung carcinoma) and BC-47 rat bladder carcinoma, and the results were compared with those for four other nitrosourea derivatives; chlorozotocin, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1- nitrosourea hydrochloride (ACNU), and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU). MCNU was shown not only to have a broad antitumor spectrum against all the tumors tested, but also to be effective over a wide range of dosages. The antitumor activity of MCNU was superior to those of GANU and chlorozotocin and similar to those of ACNU and methyl-CCNU. Furthermore, MCNU and other nitrosoureas were evaluated for toxicity in BDF1 female mice with respect to body weight changes. Weight loss in mice given MCNU at a dose lethal to 10% of the mice was relatively mild and the treated mice regained body weight most rapidly to the pretreatment level among all groups receiving the above drugs at equitoxic doses. These results may suggest that MCNU is a new nitrosourea derivative worthwhile to perform clinical trials.

Animals↗

A calcium-activated protease which preferentially degrades the 160-kDa component of the neurofilament triplet.

A calcium-dependent protease fully active with 0.2 mM Ca2+ was found associated with the neurofilament-enriched cytoskeleton of the rat spinal cord prepared by the treatment with Triton X-100. The enzyme preferentially degrades the 160-kDa component of the neurofilament triplet. In addition, a soluble calcium-dependent protease activity was found in the supernatant from the spinal cord, which degraded a variety of cytoskeletal proteins including the neurofilament triplet, glial fibrillary acidic (GFA) protein, actin, tubulin, and a high molecular weight protein associated with microtubules. The possibility that the cytoskeleton-bound activity is an artefactual association of the soluble enzyme to the cytoskeleton seems to be negated on the basis of the following dissociation and reassociation experiments. The protease activity remained associated with the cytoskeleton in the physiological ionic strength, and was not completely dissociated from it until the KC1 concentration was raised to 0.6 M. When the 0.6 M KCl-extract was dialysed against salt-free buffer to remove KC1, and added back to the protease-free cytoskeletal pellet, proteolytic activity was partially restored. Full activity returned only when the extract and the protease-free cytoskeletal pellet were first combined in the presence of 0.6 M KC1, and then slowly reassociated by dialysis against salt-free buffer. Dissociated enzyme was rapidly inactivated at 37 degrees C in the presence of Ca2+. These results suggest the structural association of the protease with the cytoskeleton under the physiological condition.

Animals↗

Distribution of cells of origin of the corticotrigeminal projections to the nucleus caudalis of the spinal trigeminal complex in the cat. A horseradish peroxidase (HRP) study.

The cortical distribution of cells of origin of the corticotrigeminal projections to the nucleus caudalis of the cat was examined using the method of retrograde axonal transport of horseradish peroxidase (HRP). After injections of HRP into the nucleus caudalis, labeled cells were distributed densely in the anterior suprasylvian gyrus, the coronal gyrus, and the ventral part of the anterior sigmoid gyrus, and moderately in the rostral part of the anterior ectosylvian gyrus on the contralateral side. In the anterior suprasylvian gyrus, the distribution extended rostrocaudally from the lateral ansate sulcal level to about 4.0 mm caudal to this level and mediolaterally throughout the convex of the anterior suprasylvian gyrus. All cortical labeled cells were pyramidal cells of various sizes in layer V.

Animals↗

Subunit composition specific to axonally transported tubulin.

One week after injection of L-[35S]methionine into the dorsal motor nuclei of the guinea-pig, labelled tubulin carried down the vagal nerve by the slow phase of axonal transport was analysed by one- and two-dimensional gel electrophoresis. Transported tubulin showed a much stronger labelling of the beta-subunit. Isoelectric focussing revealed that both alpha- and beta-subunits were composed of several components. Labelled tubulin was isolated from the brain by cycles of polymerisation and depolymerisation after injection of L-[35S]methionine into the lateral ventricle, for comparison with transported tubulin from the vagal nerve. In addition to the two alpha-components and three beta-components detected in both preparations, axonally transported tubulin contained an extra component (TAX) with a molecular weight corresponding to that of beta-tubulin and with the same isoelectric point as alpha-tubulin. The axon-specific component TAX co-polymerised with tubulin isolated from the brain. Upon peptide mapping by limited proteolysis, the peptide pattern generated from TAX was similar to that of the alpha-tubulin. It is concluded that the axonally transported tubulin contains a modified alpha-subunit which is not found in the bulk of brain tubulin.

Animals↗

Early stage of development of transplacentally induced glioma with ethylnitrosourea in rats. Sequential historadioautographic and electron microscopic studies.

Proliferative activity of possible preneoplastic cells (subependymal cells and glioblasts), early neoplastic cells and glioma cells induced by transplacental ethylnitrosourea (ENU) treatment in the rat was analysed by historadioautography and electron microscopy. Labeling index of 3H-thymidine in subependymal cells was the highest in the cerebrum of postnatal age, but no difference was observed between the normal and ENU treated groups. Thus, preneoplastic cells could not be distinguished from normal cells by morphology and proliferative activity. Focus of early neoplastic proliferation was composed of rather heterogenous and less differentiated cells, such as oligodendroblast-, glioblast- and subependymal cell-like cells, and preferentially located around the periventricular areas. Labeling index of early neoplastic proliferation was very low although the value gradually increased with age. Proliferative activity of glioma cells was higher than that of the early neoplastic cells and lower than subependymal cells, and further differed according to the degree of differentiation and morphological type. Finally, it is suggested that glioma might develop mainly through the differentiation from the focus of early neoplastic proliferation.

Animals↗

[Experimental study on the evaluation of antineoplastic effects in the human cancer/nude mouse system].

Human tumor/nude mouse system is expected to be an antitumor screening system with higher predictability of the clinical effect. To establish this, it is quite necessary to fundamentally investigate the optimal treatment regimen in this new model, nevertheless few papers related to these subjects are currently, available. In this preliminary report, we examined the effect of several known antitumor agents against human breast tumor xenograft, MX-1, with reference to the dose, route and schedule of administration of drugs in comparison with the clinical regimens. As a result, the treatment regimens were desirable to be similar to that clinically done: the route of administration should be IV or PO, instead of IP often used in usual animal experiments. The selection of dose would be the most important factor, that is, the maximum tolerated doses (MTD) of mitomycin C, vincristine, etc. were higher than the clinical doses, even in terms of dose per square meter. Thus, for these drugs the risk to overestimate the effect might exist. On the other hand, the case was opposite as for 5-fluorouracil, because its MTD in the nude mouse was lower than the clinical dose. To evaluate the effect of a drug, it appeared to be reasonable to make account of not only the average percentage of tumor growth inhibition but also the statistical means such as Mann-Whitney's U-test.

Adenocarcinoma↗

[Effect of fat emulsion (intralipid) on essential fatty acid deficiency during total parenteral nutrition in pediatric patients. Part 1. Experimental study].

Experimental studies were performed to confirm the effect of TPN with and without fat emulsion, Intralipid, on fat metabolism in weanling rats and puppies. Long-term fat-free TPN induced essential fatty acid (EFA) deficiency in weanling rats and the intravenous fat emulsion which accounted for 10% of the total caloric intake could prevent EFA deficiency. In the long-term TPN in growing puppies, fatfree TPN and induced EFA deficiency within two weeks, and Intralipid which accounted for 4% of the total caloric intake (2% as linoleate) satisfied the EFA requirement.

Animals↗

[Effect of fat emulsion (intralipid) on essential fatty acid deficiency during total parenteral nutrition in pediatric patients. Part 2. Clinical study].

Thirteen infants who received total parenteral nutrition (TPN) in four different ways were studied in order to determine the essential fatty acid (EFA) requirement in pediatric TPN. The serum fatty acid composition of the infants who received fat-free TPN showed EFA deficiency within one week. This deficiency was cured by administering fat emulsion which accounted for 4% of the total caloric content of the infusate. Fat emulsion which accounted for 2% of the total calories neither improved nor prevented EFA deficiency. This means that intravenous fat emulsion, Intralipid, which accounted for 2% of the total calories as linoleic acid, still satisfies the EFA requirement.

Arachidonic Acids↗