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Y Nosoh

Publications and source records attributed to Y Nosoh.

At least 19 recordsLinked to original sources
PubMed1996

Crystallization and preliminary X-ray analysis of 3-isopropylmalate dehydrogenase from the moderate facultative thermophile Bacillus coagulans.

Three crystalline forms of 3-isopropylmalate dehydrogenase from the moderate facultative thermophile Bacillus coagulans were obtained by hanging-drop vapor-diffusion methods. One of them, which had crystallized under slightly milder conditions than the others, was suitable for X-ray analysis. Its asymmetric unit contains one dimeric molecule and the solvent content is higher than in other protein crystals. The crystal structure was solved in a preliminary manner by the molecular-replacement technique.

Journal Article↗
PubMed1995

Thermal stability of chimeric isopropylmalate dehydrogenase genes constructed from a thermophile and a mesophile.

Chimeric isopropylmalate dehydrogenases were constructed by connecting the genes isolated from an extreme thermophile, Thermus thermophilus, and a mesophile, Bacillus subtilis. These genes were expressed in Escherichia coli. The enzymes were purified and analysed. Enzymes of T.thermophilus and B.subtilis and chimeric enzymes showed similar enzymological characteristics except for thermal stability. The stability of each enzyme was approximately proportional to the content of the amino acid sequence from the T.thermophilus enzyme. The results suggested that amino acid residues contributing the thermal stability distribute themselves, in general, evenly at least in the N-terminal half of the amino acid sequence of T.thermophilus isopropylmalate dehydrogenase.

3-Isopropylmalate Dehydrogenase↗
PubMed1991

Nucleotide sequence of the gene encoding NADH dehydrogenase from an alkalophile, Bacillus sp. strain YN-1.

The gene encoding NADH dehydrogenase from an alkalophile, Bacillus sp., was cloned and sequenced. The cloned DNA fragment contained an open reading frame of 1,557 nucleotides which encodes a polypeptide composed of 519 amino acid residues (Mr 55,830). The predicted amino acid sequence was consistent with the partial amino acid sequences including the N-terminal and C-terminal sequences determined in a previous study. Sequence comparison with other flavoenzymes revealed high homology between the present dehydrogenase and Escherichia coli thioredoxin reductase.

Amino Acid Sequence↗
PubMed1990

Protein engineering for thermostability.

Studies with small, monomeric proteins indicate that, to some extent, the effects of amino acid substitutions can be predicted. However, conformational and other changes may complicate the prediction. Site-directed mutagenesis is leading both to a better understanding of protein stability and to the production of more stable proteins.

Amino Acid Sequence↗
PubMed1989

Tryptic digestion of NADH dehydrogenase from alkalophilic Bacillus.

The alkalophile NADH dehydrogenase (NADH: 2,6-dichlorophenolindophenol oxidoreductase) [EC 1.6.99.3] consists of two identical subunits of 65 kDa, and each subunit contains the catalytic and liposome-binding regions. On treatment with trypsin, the polypeptide exhibiting the liposome-binding property in one of the subunits was digested to form an enzymatically active hetero-dimer (40 and 65 kDa), and then the polypeptide in the other subunit was digested to form an active homo-dimer (40 and 40 kDa). The hetero-dimer bound to liposomes, but the homo-dimer did not. Kinetic analysis showed that removal of one or two of the polypeptides in the enzyme slightly affects its kinetic parameters. For all the enzyme species, NAD inhibited competitively with respect to NADH and non-competitively with respect to 2,6-dichlorophenolindophenol. The partially determined amino acid sequence of this alkalophile enzyme suggested that (i) a long random-coiled peptide (58 amino acid residues) or a portion of the peptide is located between the polypeptides with liposome-binding and catalytic properties, (ii) the polypeptide exhibiting liposome-binding property is in the amino terminal region of the enzyme, (iii) the amino acid sequences around the subtilisin and trypsin cleavage sites of the peptide are hydrophilic and on the surface of the protein molecule and therefore are susceptible to digestion, and (iv) the FAD-binding site is located near the amino terminal region of the catalytic region.

Amino Acid Sequence↗
PubMed1989

[Comparative study on the anticancer activities of KW2149 and mitomycin C against human tumor xenografts using subrenal capsule assay].

The anticancer activity of KW2149, a new derivative of mitomycin C (MMC), was investigated against 5 human tumor xenografts derived from digestive organs using 4-day subrenal capsule assay (SRCA). Normal immunocompetent mice were used in this assay. For the comparative study, KW 2149 and MMC were administered intraperitoneally for 3 days after implantation, and the anticancer activity and the weight loss of mice were evaluated. The total doses were determined as 1/2, 1/3 and 1/4 of LD50 value of each anticancer agent. The anticancer activities of the two drugs were almost the same with no significant difference in 3 xenografts. Thus, it may be suggested the difference of the anticancer spectrum between the two drugs. The anticancer activity of KW2149 indicated higher correlation with the administered doses as compared with MMC. The toxicity of KW2149 was almost the same as MMC according to the weight loss of mice.

Animals↗
PubMed1988

The indications of chemosensitivity tests against various anticancer agents.

In order to determine the indications of chemosensitivity tests against various anticancer agents, clinical trials of 4 different assays, namely; nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA), were performed on 391 patients. Analysis of the correlation between assay results and clinical effects presented the possibility of determining the indications as follows; (1) The positive clinical response of mitomycin C (MMC) should be predicted by ATPA; (2) The clinical tumor resistance against MMC should be predicted by SRCA; (3) Concerning 5-fluorouracil (5-FU) the chemosensitivity test (ATPA) should only be used for the detection of tumor resistance in the assay; (4) The poor results of this study indicated the difficulty of correctly estimating the effects of cyclophosphamide (CPM); (5) The perfect prediction of clinical effects in this trial indicated that cis-DDPlatinum (CDDP) should be estimated by SRCA; (6) The positive clinical tumor response against adriamycin (ADM) should be predicted by SRCA, while the negative one should be predicted by HTCA; and (7) ATPA showed good potential for estimating not only time dependent drugs such as 5-FU, but also cytotoxic drugs.

Adenosine Triphosphate↗
PubMed1988

The antiproliferative effects of fluoropyrimidine derivatives against human tumor xenografts in a subrenal capsule assay.

The antiproliferative effects of the fluoropyrimidine derivatives, 5-fluorouracil (5-FU), 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur), UFT, 1-hexylcarbamoyl-5-fluorouracil (HCFU), and 5'-deoxy-5-fluorouracil (5'DFUR), were investigated in a 4 day subrenal capsule assay. The antiproliferative effects against two human tumor xenografts established in athymic mice were examined after treatment with three different doses of each anticancer agent, and the adequate dose of each anticancer agent in this experimental system was estimated as: 473 mg/kg for Tegafur, 433 mg/kg for UFT, 50 mg/kg for HCFU and 185 mg/kg for 5'DFUR, respectively. A comparative study of the antiproliferative effects of fluoropyrimidine derivatives was carried out against 7 xenografts. According to our criteria of positive tumor response, the effective rates were: 1 of 7 (14.3 per cent) by 5-FU, 2 of 7 (28.6 per cent) by Tegafur, 2 of 7 (28.6 per cent) by UFT, 1 of 6 (16.7 per cent) by HCFU, and 1 of 4 (25.0 per cent) by 5'DFUR, respectively. Although no statistical differences were demonstrated between the agents, the utility of a chemosensitivity test before clinical use was suggested.

Animals↗
PubMed1988

Leucine transport system in a facultatively alkalophilic Bacillus.

Some characterizations of the leucine transport system in a facultative alkalophile, which is able to grow over a wide pH range from 7.0 to 10.5, were attempted. Although the direction of a transmembrane pH gradient of the bacterium below pH 8.2 is opposite to that above pH 8.2 (N. Koyama and Y. Nosoh (1985) Biochim. Biophys. Acta 812, 206-212), leucine transport is likely to be driven only by sodium electrochemical potential irrespective of the external pH. It was suggested that histidine and sulfhydryl groups in the leucine transporter are involved in the translocation mechanism and the pK value of the histidine residue involved is approximately 7.0.

Algorithms↗
PubMed1987

Effect of K+ on the membrane functions of an alkalophilic Bacillus.

We have examined the involvement of K+ in the membrane functions of a facultatively alkalophilic Bacillus at neutral and alkaline pH. The effects of K+ on membrane functions, such as maintenance of the membrane potential, leucine uptake and respiratory activity, were dependent on the external pH. K+ uptake, which induced alkalinization of the cytoplasm, is suggested to be electrogenic at neutral pH and 'electroneutral' at alkaline pH, resulting in a similar level of net accumulation. We suggest that the bacterial membrane is highly permeable to K+ at neutral pH, compared to alkaline pH, which results in a pH-dependent effect of K+ on the above membrane functions.

Bacillus↗
PubMed1987

Antitumor effects of recombinant human tumor necrosis factor against human tumor xenografts transplanted into nude mice.

Antitumor activities of recombinant human tumor necrosis factor (rH-TNF) against human tumor xenografts in nude mice were studied. Thirteen human tumor xenografts serially transplanted into nude mice were used for experiments; five gastric, two breast, two gallbladder, one colon and one esophageal carcinoma, one liposarcoma and one squamous carcinoma of the neck. They were inoculated into the subcutaneous tissue of BALB/c nu/nu nude mice and the treatment was started when the estimated tumor weight reached 100-300 mg. rH-TNF was administered intratumorally at schedule of qd X 5 or q3d X 5. rH-TNF showed a marked antitumor activity against various human tumors. The hemorrhagic necrosis was observed in all types of the human tumor xenografts (100 per cent), and the complete regression of the tumor was noted in 4 of 11 tumors (36.4 per cent). On the contrary, intraperitoneal rH-TNF exhibited little antitumor effect. The additive effect in the combination of TNF and Mitomycin C was observed against two Mitomycin C resistant gastric tumors.

Animals↗
PubMed1987

Experimental studies on the combined effects of alpha and gamma interferons against human tumor xenografts transplanted into nude mice.

The antitumor activities, resulting from the combined treatment of leukocyte interferon (IFN-alpha), with recombinant human immune interferon (IFN-gamma), against human tumor xenografts in nude mice, were studied. Nine human tumor xenografts, (7 from gastric carcinoma, 1 from gallbladder carcinoma and 1 from breast carcinoma), were serially transplanted into nude mice for the purpose of this experiment. Each human tumor xenograft was inoculated subcutaneously into BALB/c nu/nu nude mice and treatment was started after the estimated tumor had reached 100-300 mg. IFN was administered intramuscularly at a schedule of qd X 14. Treatment with either IFN-alpha or IFN-gamma alone, did not produce any antitumor effect against the various human tumor xenografts, however the combination of IFN-alpha with IFN-gamma resulted in achieving significant antitumor effects against the various human tumors. Inhibition of tumor growth was observed in 7 of the 9 tumors (77.8 per cent), and regression of the tumor was noted in 5 of the 9 tumors (55.6 per cent).

Adenocarcinoma↗
PubMed1987

Comparative study on nude mice isotope assay (NM-IA) and subrenal capsule assay (SRCA) sensitivity tests of anticancer agents.

A comparative study on nude mice isotope assay (NM-IA) and subrenal capsule assay (SRCA) was done to evaluate the usefulness of in vivo assays for predicting individual tumor sensitivity against anticancer agents. Sixty-one fresh tumor specimens collected at surgery, under sterile conditions, were examined. Mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM), adriamycin (ADM) and cis-DDPlatinum (CDDP) were used in both assays. In NM-IA, the tumor sensitivity was determined by the amount of 3H-thymidine incorporated into the tumor which had been implanted into subcutaneous spaces of BALB/c nude mice. In the SRCA, the relative increase in weight of the tumor implanted into the subrenal capsular space of ddY mice was determined and measurements made to evaluate the chemosensitivity. Evaluability rates of the trials were 86.9 per cent with both assays and the response rates were 35.8 per cent in NM-IA and 34.0 per cent in SRCA, respectively. Against MMC, 5-FU, CPM, ADM and CDDP, overall consistency rates between the two assays were 77.8 per cent, 88.6 per cent, 72.7 per cent, 81.8 per cent and 68.2 per cent, respectively. In 8 of these 53 evaluated assays, correlations between the results of assays and clinical effects were examined and overall predictive accuracy rates were 87.5 per cent with both assays. Significant differences between these two in vivo chemosensitivity tests were not evident.

Animals↗
PubMed1987

Antitumor activities of KW-2152, a new isoquinon agent, against human tumor xenografts transplanted into nude mice.

The antitumor activities of KW-2152, a new isoquinon derivative, were examined in thirteen human tumor xenografts, transplanted into nude mice. KW-2152 was administered intravenously at a schedule of q4d X 3, in daily doses of 7.3 mg/kg and 3.6 mg/kg, and q2d X 6 with a daily doses of 7.3 mg/kg, respectively. KW-2152 displayed significant antitumor activities against the human tumor xenografts in 3 out of 13 strains (23.1 per cent) at the schedule of q4d X 3, with a daily dose of 7.3 mg/kg. Depending on the schedule of administration, tumor activity was observed in 8 out of 13 strains (61.5 per cent) at a schedule of q2d X 6, with a daily dose of 7.3 mg/kg. SH-2 and SH-9 gastric tumors were sensitive to KW-2152 and growth was completely inhibited with the schedule of q4d X 3, and a daily dose of 7.3 mg/kg. Thus, KW-2152 seems to have a wide antitumor spectrum, and the possible antitumor effects for clinical use, warrant attention.

Animals↗
PubMed1987

[In vivo chemosensitivity test for UFT and FT-207. I--Subrenal capsule assay].

A chemosensitivity test for UFT and FT-207, which are used in long-term administration clinically, was investigated for prediction of clinical response. Five transplantation-established human tumor xenograft systems were examined using subrenal capsule assay. Both anticancer agents showed antiproliferative effects according to the total administered dose. Two of 5 tumors were determined to be sensitive to UFT using microscopic measurements following intragastric administration of 1/2 of the LD50 value, while they were shown to be resistant to 5-FU. In these two cases, prolongation of life span by long-term administration of UFT was shown clinically. All these experiments could be performed on condition that the loss of body weight in mice was less than 20%. These results suggest that in the 4-day subrenal capsule assay, clinical responses to long-term administration of UFT or FT-207 are predictable using intragastric high-dose administration which does not induce more than 20% body weight loss in experimental mice.

Adenocarcinoma↗
PubMed1987

[In vivo chemosensitivity test for UFT and FT-207. II. Chemosensitivity test on human tumor xenografts transplanted in nude mice].

The present study was designed to predict the clinical effect of UFT and FT-207 in short-term administration using a nude mouse-xenograft system. Five human tumor xenografts transplanted into nude mice were used. UFT and FT-207 were administered with the LD10 doses orally for seven consecutive days. Tumor size was measured on day 7, 14 and 21 after the administrations. No significant differences in antiproliferative effects were observed between the measurements of tumor size made on day 7 and day 21. UFT inhibited significantly the tumor growth of CH-I established from colon cancer in which the prolongation of life span has been obtained by clinical long-term administration of UFT. These results suggest that this chemosensitivity test system using nude mice is useful for prediction of clinical response at 7 days after final administration of UFT and FT-207.

Adenocarcinoma↗