Search PubMed⌕ Search

Biomedical subjects

T Miyasaka

Publications and source records attributed to T Miyasaka.

At least 91 records · Page 5Linked to original sources
PubMed1990

Okadaic acid stimulates the activity of microtubule associated protein kinase in PC-12 pheochromocytoma cells.

PC-12 pheochromocytoma cells contain a growth factor-sensitive protein kinase that phosphorylates microtubule associated protein 2 (MAP-2). This MAP kinase is also activated by the protein phosphatase inhibitor okadaic acid (OA). Additionally, OA potentiates the NGF-dependent activation of MAP kinase, but causes only a modest potentiation (20%) of the maximal activation observed with EGF. Since OA is a specific serine/threonine phosphatase inhibitor, these results suggest that serine/threonine phosphorylation may be involved in the hormonal regulation of MAP kinase.

Adrenal Gland Neoplasms↗
PubMed1990

Nerve growth factor stimulates a protein kinase in PC-12 cells that phosphorylates microtubule-associated protein-2.

Some of the effects of nerve growth factor (NGF) may be mediated by changes in protein phosphorylation. We have identified a protein kinase from PC-12 cells that catalyzes the phosphorylation of pig brain microtubule-associated protein (MAP)-2 in vitro. This activity is stimulated 2-4-fold in extracts from cells treated with NGF or epidermal growth factor (EGF). The partial purification and characterization of this MAP kinase indicate that it is distinct from previously described NGF-stimulated protein kinases. The NGF-stimulated kinase activity is unaffected by direct addition to the assay of the heat-stable cAMP-dependent kinase peptide inhibitor, staurosporine, or K-252A, is slightly stimulated by heparin and is inhibited by sodium fluoride and calcium ions. Treatment of cells with NGF increases the activity of the kinase within 2 min. The activity declines after 10 min, and a second phase of activation is observed at 20-30 min. Comparison of its behavior on gel permeation and sucrose density gradients indicates a molecular mass in the range of 40,000 daltons. The kinase activity is specific for ATP as substrate with a Km of 12 microM. Although the pathway of activation of MAP kinase by NGF is unknown, the stimulation can be reversed by treatment of the enzyme with alkaline phosphatase, suggesting that activation involves phosphorylation of the kinase itself. The properties and hormone sensitivity of the PC-12 MAP kinase suggest that it is similar to the previously identified, growth factor-sensitive MAP kinase from 3T3-L1 adipocytes.

Alkaline Phosphatase↗
PubMed1990

Synthesis of novel 6-substituted acyclouridine derivatives and their anti-HIV-1 activity.

To improve the anti-HIV activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), a variety of its analogues were synthesized. Introduction of SR group to the C-6 position was carried out based on LDA lithiation followed by the reaction of aryl- or alkyl disulfide. An addition-elimination reaction of a 6-phenylsulfinyl derivative was used for synthesizing the analogues having OR or NHR group at the C-6 position. The C-5 modified derivatives were synthesized mainly based on LTMP lithiation of a 6-phenylthio derivative. Modification at the 2- or 4-position was also carried out. Some compounds prepared in the present study showed higher activity than HEPT.

Antiviral Agents↗
PubMed1990

[The forming phase and various properties of Au, Ag, Cu and Ga mixture in metal fired crowns].

A new time-saving method has been developed to produce artificial crowns without using the casting process. Plastic mixtures of gallium and other metal particles are kneaded into desired shape and then heated for hardening. By this method, the time required for hardening and producing restorative materials has been shortened greatly. In the present experiment, gallium was triturated with powdered gold, silver and copper to make binary alloy samples. The dimensional change was measured between heat treatment. After heat treatment, the test piece was examined for compressive strength, compressive shrinkage, hardness, tarnishing and difference in phase. Non-heated and heated alloy specimens (Au-Ga, Ag-Ga, Cu-Ga) expanded to form the new phase. The ability of Au-Ga samples to bear compressive strength, when heated at 300 degrees C or more (AuGa2----AuGa), became 2.6 times greater than that of non-heat-treated specimens. The compressive strength of Ag-Ga samples dropped briefly at 350 degrees C (Ag0.72Ga0.28----Ag3Ga) but increased at 450 degrees C (Ag3Ga----AgGa). The strength of Cu-Ga pieces fell by half at 475 degrees C and upward (CuGa2----unknown phase). A compression test showed that the contraction percentage of Au and Ag specimens became large as a result of heat treatment, while that of Cu alloys remained almost unchanged. The results of a hardness test (HV) were comparable to those of the compressive strength test. The Au-Ga alloys increased in hardness after high-temperature treatment. In the Ag-Ga alloys, hardness declined at 350 degrees C and increased at 450 degrees C. There was no difference in hardness between Cu specimens after heat treatment and those allowed to stand at room temperature. A tarnishing test revealed that Au-Ga samples turned slightly yellowish. In the case of Ag-Ga samples, the reflectivity Y (%) dipped slightly but discoloration was not recognizable. However, the Cu-Ga samples which were heated at temperatures of up to 280 degrees C showed a slight drop in reflectivity, but those heated at temperatures higher than 280 degrees C decreased to 50-66% in reflectivity and turned black.

Copper↗
PubMed1989

Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative.

A novel 6-substituted acyclouridine derivative, 1-[(2-hydroxy-ethoxy) methyl]-6-phenylthiothymine (HEPT), has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. HEPT inhibits HIV-1 replication in various T4 cell cultures as well as peripheral blood lymphocytes and macrophages. The 50% antiviral effective concentration for HIV-1 (HTLV-IIIB) in MT-4 cells is 7.0 microM, while the 50% cytotoxic concentration for mock-infected MT-4 cells is 740 microM. Although HEPT is inhibitory to various strains of HIV-1, it has no effect on the replication of other retroviruses including HIV type 2. In contrast with the dideoxynucleoside (i.e. azidothymidine) 5'-triphosphates, the triphosphate of HEPT does not interact with HIV-1 reverse transcriptase. The mechanism of action of HEPT remains subject of further study.

Antiviral Agents↗
PubMed1988

Change in priming sites for discontinuous DNA synthesis between the monomeric and concatemeric stages of phage T7 replication.

We have analyzed the transition sites between primer RNA and DNA in a 589 bp segment of the bacteriophage T7 genome. In the monomeric replication stage, RNA-DNA transition sites are predominantly on the light (L) strand (with 5'----3' polarity on the genetic map) but rarely on the heavy (H) strand, indicating that replication proceeds semidiscontinuously with the H and L strands corresponding to the leading and lagging strands, respectively. The direction of replication is that expected from the position of the primary origin and also indicates that secondary origins are seldom if ever used. In the concatemeric stage of replication, RNA-DNA transition sites are instead distributed on both strands of the segment with equally high frequency, showing that initiation occurs within the concatemeric molecule per se and by a different mechanism.

Base Sequence↗
PubMed1987

Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.

Animals↗
PubMed1987

Antitumor activity of a new camptothecin derivative, SN-22, against various murine tumors.

The antitumor activity of a new camptothecin derivative, SN-22, was evaluated by using various murine tumors. SN-22 showed strong activity against the ascites tumors Ehrlich carcinoma, MM46, CCM, L1210, L5178Y, P388, Meth A, and B16 melanoma. In particular, the maximum increase in life span values for Ehrlich, MM46 and CCM were as high as 253-606% and many mice were cured of these tumors. The effect of SN-22 against solid tumors was also determined. The inhibition ratios were higher than 70% for MM46 and L5178Y. The LD50 of SN-22 in ICR mice was about 1.5 times that of the parent camptothecin.

Animals↗
PubMed1987

[Antitumor activity of new derivatives of camptothecin].

With the purpose of obtaining more potent and less toxic camptothecin (CPT) analogs, we prepared many derivatives of CPT. Among them, 7-ethyl-CPT (SN 22) and 7-ethyl-10-hydroxy-CPT (SN 38) showed strong antitumor activity with less toxicity. They were, however, insoluble and when they were made soluble, their activity was markedly diminished, as a result of cleavage of the delta-lactone ring. We therefore attempted to make soluble derivatives without breaking the delta-lactone ring and obtained 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-CPT (CPT-11), which showed very strong antitumor activity by i.p., i.v. or p.o. administration against the ascites type of L1210 leukemia, P388 leukemia, sarcoma 180, Meth A fibrosarcoma, B16 melanoma, Ehrlich carcinoma and MH134 hepatoma and the solid type of sarcoma 180, Meth A fibrosarcoma, Lewis lung carcinoma, C3H/HeN mammary carcinoma, Ehrlich carcinoma and MH134 hepatoma. The antileukemic activity of CPT-11 against L1210 was much higher than that of adriamycin. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration, the LD50 being 765.3 mg/kg, 22 times greater than that of CPT-Na.

Animals↗
PubMed1987

Action of 7-ethylcamptothecin on tumor cells and its disposition in mice.

Some biological effects of camptothecin (CPT) and its new derivative 7-ethylcamptothecin (ECPT) were studied. The drugs were effective against murine leukemia; ECPT was more effective than CPT. Ip administration of ECPT or CPT gave maximum treated/control values of 325% and 232%, respectively. The drugs also inhibited the growth of KB cells in vitro, 50% effective doses of 3.5 ng/ml of ECPT and 8.6 ng/ml of CPT, indicating the stronger activity of ECPT. Pharmacokinetic studies of the drugs in mice showed that ECPT had a longer biological half-life in the terminal phase and a larger amount remained in the plasma compared with CPT. After iv administration of ECPT, the drug accumulated in the intestine, suggesting that the main route of excretion of the drug is through the biliary tract. The study on cell cycle progression by flow cytometry suggested that the main effect of both drugs on L1210 cells was the blocking of G2-M phase. These results suggest that the main reasons for the superior antitumor activity of ECPT compared with CPT are as follows: (a) ECPT had a stronger growth-inhibiting activity against tumor cells, and (b) ECPT remained in the intestinal tract for a longer time and in higher amounts when administered in vivo.

Animals↗