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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 757 records · Page 42Linked to original sources
PubMed1988

[Comparative studies on the antitumor activity of the fluorinated pyrimidines 5'-DFUR, tegafur, UFT and FUra on various murine tumors].

Antitumor activities of fluorinated pyrimidines by oral administration were compared with various murine tumor models. 5'-Deoxy-5-fluorouridine (5'-DFUR) showed a better antitumor activity in terms of the growth inhibition and increase of the survival time than those of 5-fluorouracil(FUra), tegafur and UFT, particularly with respect to the chemotherapeutic indices. The activity of these fluorinated pyrimidines were further investigated in more detail with mice bearing colon 26 adenocarcinoma to suggest some means to optimize their treatment regimens in clinical trials. 5'-DFUR showed the activity irrespective of the size of tumor mass at the time of start of therapy. Additionally only 5'-DFUR was safely administered to the mice daily for long period up to more than 100 days, suppressing the tumor growth and increasing the survival to great extent.

Animals↗
PubMed1988

Disruption of light-dark cycle of feeding and drinking behavior, and ambulatory activity induced by development of obesity in the Zucker rat.

To clarify the contribution of abnormalities and disruption of the light-dark cycle of feeding behavior during obesity progression in Zucker rats, feeding, drinking and ambulation were measured at four different stages of obesity. In the obese rats, the nocturnal pattern of feeding, drinking and ambulation shifted gradually into the light period with the progression of obesity. The lean rats however were unaffected. In the analysis of meal parameters, nocturnal dominance of meal size in the obese disappeared by 12 weeks of age and that of meal frequency was lost by 30 weeks of age. This disruption of the light-dark cycle in meal parameters appeared uneven at different stages indicating that synergistic impairment of meal size and meal frequency might contribute to the impairment of the nocturnal feeding pattern, which leads, in part, to the development of obesity.

Age Factors↗
PubMed1988

Direct determination of acetylcholine release by radioimmunoassay and presence of presynaptic M1 muscarinic receptors in guinea pig ileum.

Radioimmunoassay for acetylcholine (ACh) with a sensitivity of 10 pg/tube was applied to the direct determination of ACh output from the nerve endings in longitudinal muscle strips of guinea pig ileum. The strips were preincubated with an irreversible cholinesterase inhibitor and superfused with Krebs' solution under various experimental conditions. Pirenzepine (0.1-10 microM) and atropine (10-100 nM) produced an increase in electrically evoked ACh output through the inhibition of presynaptic muscarinic receptors. Contractile response to endogenous ACh released by electrical stimulation was enhanced by pirenzepine and atropine at lower concentrations, whereas the highest concentrations of pirenzepine (10 microM) and atropine (100 nM) caused a reduction in the enhanced contractile response and a significantly diminished response, respectively. These results demonstrate that the concentrations of pirenzepine and atropine, effective in inhibiting presynaptic muscarinic receptors, differ from those inhibiting postsynaptic muscarinic receptors and suggest the possibility that presynaptic M1 muscarinic receptors regulating ACh output may be present in the guinea pig ileum.

Acetylcholine↗
PubMed1988

Age-related changes of immunoglobulin levels in African green monkeys (Cercopithecus aethiops).

Serum IgG, IgA, and IgM levels were measured in domestically bred African green monkeys (Cercopithecus aethiops) ranging in age from 0 day to 49 months as well as in adult (5 years or older) animals of wild origin. Transplacental transfer of IgG was observed. IgG, IgA, and IgM levels increased with increasing age except for a temporal decrease of IgG level in the first month of life.

Aging↗
PubMed1987

Plasma concentration of acetylcholine in young women.

A sensitive and specific radioimmunoassay was applied to the determination of acetylcholine (ACh) in plasma. The concentration of ACh in plasma sampled from 32 young women was 456.1 +/- 53.1 (mean +/- S.E.M.) pg/ml. No significant correlations were observed between plasma concentration of ACh and acetylcholinesterase (AChE) activity, or gonadal hormones. These data demonstrate that an amount of ACh measurable by radioimmunoassay is present in plasma and plasma ACh is not regulated by AChE activity and the menstrual cycle in young women. The origin and physiological as well as pathophysiological significance of ACh in plasma remain to be clarified.

Acetylcholine↗
PubMed1987

Synthesis of oligodeoxyribonucleotide with aliphatic amino or phosphate group at the 5' end by the phosphotriester method on a polystyrene support.

Lipophilic protecting groups mTrNH(CH2)n X (mTr:monomethoxytrityl, X = NH,O,S, n = 2,3,4,6) were attached to the 5'-phosphoryl group of 3'-O-protected thymidine. When the diamine derivatives (X = NH2) were used, the time course of the stability of mTr groups on the amino group and the phosphoramidate linkage with 80% aq. AcOH was measured. It was found that the mTr group was removed from the amino group rapidly and that the phosphoramidate linkage was more stable. It's stability depended upon the length of the CH2 linker. Oligonucleotides with an aliphatic amino group at their 5'-ends were synthesized by the phosphotriester method on a polystyrene support using protected nucleotides with P-O or P-S linkages. In the case of product with a P-S linkage, 5'-O-phosphorylated nonadecanucleotide was also prepared by I2-H2O treatment.

Oligodeoxyribonucleotides↗
PubMed1987

The expression of functional erythropoietin receptors on an interleukin-3 dependent cell line.

We report the expression of the erythropoietin receptors on an interleukin-3 dependent cell line. By the transfer into medium supplemented with erythropoietin, DA-1 cells were converted to an erythropoietin dependent growth state. [125I] erythropoietin was used to detect receptors specific for this hormone on the cell surface. Binding studies revealed that erythropoietin bound to 131 +/- 23 receptors/cell with a Kd of 0.54 +/- 0.2 nM. When the cells were incubated at 37 degrees C, trichloroacetic acid soluble radioactivity appeared in the medium after [125I] erythropoietin binding began to decrease, suggesting that the decline represents the degradation of cell associated [125I] erythropoietin- receptor complexes.

Cell Line↗
PubMed1987

Fluorescence formation from the interaction of DNA with lipid oxidation degradation products.

To clarify the mechanism of fluorescence formation between DNA and lipid degradation products in the presence of ferric chloride and ascorbic acid, a number of carbonyl compounds and decomposition products of pure methyl linolenate hydroperoxides were examined. Keto derivatives of methyl ricinoleate, linoleate, and oleate, alkanals and 2-alkenals produced little or no fluorescence with DNA in the presence of ferric chloride-ascorbic acid. 2,4-Alkadienals were more active and 2,4,7-decatrienal was the most active. Mixtures of volatile aldehydes prepared from linolenate hydroperoxide decomposed either thermally or with iron and ascorbate had the same activity as 2,4,7-decatrienal. Higher molecular-weight products from the decomposition of methyl linolenate hydroperoxides showed relatively low activity. beta-Carotene, alpha-tocopherol and other antioxidants effectively reduced the amount of fluorescence formed by linolenate hydroperoxides. The results suggest that, in addition to hydroperoxide decomposition products, singlet oxygen and/or free radical species contribute significantly to the fluorescence formed from the interaction of methyl linolenate hydroperoxides with DNA in the presence of ferric chloride and ascorbic acid.

Aldehydes↗
PubMed1987

Heterogeneity in response to interleukin 2 and interleukin 2-producing ability of adult T cell leukemic cells.

To examine the possibility of heterogeneous mechanisms in the proliferation of adult T cell leukemia (ATL) cells, leukemic cells from 13 patients, nine acute-type and four chronic-type ATL, were examined for the production of interleukin 2 (IL 2) with or without mitogenic stimulation and their response to recombinant IL 2 when exogeneously added. The leukemic cells were classified into four groups, as follows. Group 1 (two patients): Cells of this group produced IL 2 messenger RNA, secreted IL 2, and proliferated when cultured in mitogen-free medium. The spontaneous proliferation of the cells in mitogen-free medium was inhibited by anti-Tac/IL 2 receptor and anti-IL 2 monoclonal antibodies. Moreover, the thymidine incorporation by the cells was enhanced in response to exogeneously added recombinant IL 2 and IL 2 produced by themselves. These results indicate that the ATL cells of this group proliferate with autostimulation by IL 2. Group 2 (seven patients): Cells of this group did not secrete IL 2 when cultured in mitogen-free medium, but the cells showed response to exogeneously added recombinant IL 2 and proliferated in culture. These results indicate that the ATL cells of this group proliferate by a paracrine mechanism. Group 3 (one patient): Cells of this group secreted IL 2 in mitogen-free medium. However, the spontaneous proliferation of these cells in vitro was very low, and the response to recombinant IL 2 was also very low. Group 4 (three patients): Cells of this group did not secrete IL 2 in mitogen-free medium. Spontaneous proliferation and the response to recombinant IL 2 were also very low. The clinical feature of all patients of Groups 1 and 2 was acute-type, and that of Groups 3 and 4 was chronic-type. Thus, we conclude that heterogeneous mechanisms exist in the proliferation of leukemic cells, and that growth rate in mitogen-free medium and response to IL 2 of the cells may have a significant relationship to the clinical feature, acute- or chronic-type.

Adult↗
PubMed1987

Antitumor activity of a novel antitumor antibiotic, quinocarmycin citrate (KW2152).

A novel antitumor antibiotic, 2a,3,4,5,6,6a,7,11b-octahydro-11-methoxy-12-methyl-3,6-imino-1H-2-oxa-11 c- azanaphth(1,2,3-cd)azulene-5-carboxylic acid monocitrate (quinocarmycin citrate; KW2152) was selected for investigation in a number of experimental tumor systems because of its efficacy against P388 leukemia. In the initial studies with P388 leukemia (i.p.-i.p.), KW2152 gave an increase in life span of greater than 80%. The activity was schedule dependent and daily administration was the most effective. KW2152 caused marginal activity against L1210 leukemia, B16 melanoma, and M5076 sarcoma. The effect on cultured cells suggested that KW2152 was not cross-resistant to Adriamycin (ADM) but was cross-resistant to mitomycin C (MMC); however, KW2152 caused prolongation of life span against mice bearing P388/ADM or P388/MMC. In tests against human tumors xenografted s.c. in nude mice, KW2152 significantly inhibited the growth of MX-1 mammary carcinoma with all tumors cured at i.v. doses of 4.4 mg/kg/day and p.o. doses of 26.2 mg/kg/day given daily for 7 days. KW2152 also inhibited distinct human gastric carcinomas, St-4 and St-15 tumors, and colon carcinoma Co-3 by daily administration for 7 days. Against St-4, KW2152 gave a treated versus control percentage of 27, compared to 52 for cis-diamminedichloroplatinum. Against Co-3, KW2152 was at least as effective as MMC, ADM, cis-diamminedichloroplatinum, and bleomycin, giving a treated versus control percentage of 18 at a dose of 8.6 mg/kg/day given daily for 7 days. KW2152 showed growth inhibitory activity against cultured murine tumors and human cells. The order of in vitro efficacy of KW2152 against murine tumors, P388 leukemia greater than L1210 leukemia, B16 melanoma, correlated with the order of the sensitivity on the i.p.-i.p. systems of these tumors. The 50% inhibitory concentrations against P388 leukemia cells were 5.3 X 10(-6) and 1.1 X 10(-7) M after 1 and 72 h exposure, respectively. KW2152 caused significant inhibition of RNA synthesis after a short time exposure. In P388 leukemia cells exposed for 1 h with KW2152, the 50% inhibitory concentration for RNA synthesis was 10(-5) M, 30-fold less than that for DNA synthesis. White blood cell depression or platelet depression was not significant after administration of the i.v. 10% lethal dose given daily for 7 days. Because of its good activity against human mammary tumor MX-1 and some effectiveness against other gastric and colon carcinomas and its water solubility, a novel antitumor antibiotic, KW2152, is being developed as a Phase I anticancer agent.

Animals↗
PubMed1987

The interaction of phosphorylated oligosaccharides and lysosomal enzymes with bovine liver cation-dependent mannose 6-phosphate receptor.

We have analyzed the interaction of phosphorylated oligosaccharides and lysosomal enzymes with immobilized bovine liver cation-dependent mannose-6-P receptor. Oligosaccharides with phosphomonoesters were the only species that interacted with the receptor, and molecules with two phosphomonoesters showed the best binding. Lysosomal enzymes with several oligosaccharides containing only one phosphomonoester had a higher affinity for the receptor than did the isolated oligosaccharides, indicating the possible importance of multivalent interactions between weakly binding ligands and the receptor. The binding of a mixture of phosphorylated lysosomal enzymes to the cation-dependent Man-6-P receptor was markedly influenced by pH. At pH 6.3, almost all of the lysosomal enzymes bound to the receptor; whereas at pH 7.0-7.5, approximately one-third of the material passed through the column, one-third interacted weakly, and one-third bound tightly. The distribution of individual lysosomal enzyme activities was similar to that of the total material. The species of phosphorylated oligosaccharides present on the lysosomal enzymes which interacted poorly with the receptor were similar to those found on the tightly bound material and included species of oligosaccharides with two phosphomonoester groups. Isolated oligosaccharides of this type bound to the receptor over the entire pH range tested. These findings indicate that at neutral pH the phosphorylated oligosaccharides on some lysosomal enzyme molecules are oriented in a manner which makes them inaccessible to the binding site of the cation-dependent Man-6-P receptor. Since the same enzymes bind to the cation-independent Man-6-P receptor at neutral pH, at least a portion of the phosphomannosyl residues must be exposed. We conclude that small variations in the pH of the Golgi compartment where lysosomal enzymes bind to the receptors could potentially modulate the extent of binding to the two receptors.

Animals↗
PubMed1987

Fourth ventricular floor in human embryos: scanning electron microscopic observations.

The ultrastructural surface features of the normal fourth ventricular floor of seven human embryos ranging from Carnegie stage 14 to stage 19 (crown-rump length: 7.6-16.2 mm) were examined by using scanning electron microscopy (SEM). Low-power SEM views showed the median sulcus, sulcus limitans, and neuromeres, transient structures characteristic of the earlier embryonic period. High-power SEM observation revealed supraependymal cells (SE cells) and supraependymal fibers (SE fibers) which exhibited a characteristic localization, as well as generalized surface-membrane modifications such as microvilli and cilia. SE cells could be classified into two major groups. The type 1 SE cells seem to possess neuronal functions, as deduced from morphological similarities to their counterparts in adults and the specialized distribution closely related to neuromeres. The type 2 SE cell morphologically resembled the phagocytic SE cell described in related literature. SE fibers ran a course either rostrocaudally in the median sulcus or mediolaterally on the neuromeres, most frequently near the interneuromeric cleft; they made contact with type 1 SE cells and ependymal surface modifications and then penetrated the ependymal layer.

Cerebral Ventricles↗