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K Gomi

Publications and source records attributed to K Gomi.

At least 109 records · Page 6Linked to original sources
PubMed1995

Characteristic expression of three amylase-encoding genes, agdA, amyB, and glaA in Aspergillus oryzae transformants containing multiple copies of the agdA gene.

In Aspergillus oryzae wild-type strains, the expression of the agdA gene encoding alpha-glucosidase (AGL) is induced by maltose at the transcriptional level in a similar manner to the amyB gene encoding Takaamylase A (TAA) and the glaA gene encoding glucoamylase (GLA). In A. oryzae transformants containing multiple copies of the agdA gene, a high-level of AGL activity was observed. This was accompanied by a significant reduction in TAA and GLA activities. Moreover, transformants with the highest AGL activity showed the lowest degree of TAA and GLA activities. Northern blot analyses showed that the transcriptional levels of amyB and glaA in the AGL-overproducing transformant were drastically reduced when large amounts of agdA mRNA were detected in maltose-grown mycelia. In addition, the glucose concentration of the maltose-containing medium that was used to grow the AGL-overproducing transformant for RNA extraction was higher than that of the control transformant. These results suggest that the reduced expression of the amyB and glaA genes in the AGL-overproducing transformant was due to either titration of a common regulatory protein(s) involved in maltose induction or carbon catabolite repression.

Amylases↗
PubMed1995

Iron deprivation results in an increase in p53 expression.

Deferoxamine (DFO)-induced iron deprivation caused an increase in p53 expression in ML-1 and Raji cells. In ML-1 cells, with express wild type p53, p53 protein levels were transiently increased 6 h after addition of 10(-4)M DFO. In Raji cells, which carry a mutant p53 allele, p53 increased 6 h after addition of 10(-4)M DFO and remained elevated for 24 h. Growth inhibition was observed in both cell types 6 h after addition of 10(-4)M DFO. In both cells, p53 mRNA levels did not increase following incubation with DFO, suggesting that increased p53 expression is the result of a post-transcriptional mechanism. Although increases in wild type p53 protein in ML-1 cells resulted in increases in a p53 target gene, p21cipl/wafl/sdil, this effect was not observed in Raji cells which express a mutant p53 protein.

Apoptosis↗
PubMed1995

[Clinical significance of serum troponin T following coronary artery bypass surgery].

We evaluated the clinical significance of serum cardiac troponin T(TnT) following coronary artery bypass surgery (CABG) as an indicator of cardiac damage during the operation. We studied 21 patients who underwent CABG and 8 patients who underwent open thoracotomy for lung disease. In the CABG patients, serum TnT levels showed roughly biphasic release kinetics, with a peak less than 10h postoperatively and a second peak on or about the fourth day. The serum TnT levels at 0 and 10h postoperatively were 8.58 +/- 1.07 (mean +/- SE) and 9.19 +/- 1.35ng/ml, respectively, levels were 30-40 times higher than the cut-off value of 0.25ng/ml. On the fourth day after CABG, serum TnT in the 3 graft groups (7.21 +/- 2.56ng/ml) was significantly higher than in the 1 or 2 graft groups (2.57 +/- 0.05 and 2.53 +/- 0.46ng/ml, respectively). The peak serum TnT level of the patients with perioperative myocardial infarction was 34.6 +/- 5.29ng/ml, which was significantly higher than in the patients without specific evidence of perioperative infarction. On the other hand, in the patients undergoing thoracic surgery for lung disease, serum TnT showed no postoperative increase. In conclusion, serum TnT appears to be a specific marker of cardiac damage after CABG, and may be useful for the diagnosis of perioperative myocardial infarction.

Adult↗
PubMed1995

[Rearrangement of the c-erbB2 oncogene--analysis of the gastrocolic carcinoma].

We analyzed amplification, rearrangement and point mutation of the c-erbB2 oncogene about 10 cases of the stomach cancer and 30 cases of the colon cancer. Rearrangement and amplification of the c-erbB2 oncogene were found in one case of moderately differentiated tubular adenocarcinoma of the stomach. According to the restriction map, the rearrangement apparently occurred in the region from the 5' promotor to the extracellular domain. In this case, it appeared that the over expression of ErbB2 oncoprotein detected by immunohistochemical staining was associated with rearrangement of the gene. Thus it was suggested that the point mutation of the transmembrane domain, which has been demonstrated in the rat protooncogene neu, a homolog of human c-erbB2, was not detected in this case.

Base Sequence↗
PubMed1995

[Early diagnosis and detection of successful reperfusion by mitochondrial-AST/soluble-AST ratio after acute myocardial infarction].

The change of mitochondria aspartate aminotransferase (m-AST)/soluble-AST (s-AST) ratio was examined in 22 cases of acute myocardial infarction (AMI). The m-AST/s-AST was 40.8 +/- 18.9% at admission to a hospital (2.9 +/- 1.6h). The m-AST/s-AST decreased to normal value rapidly after peak and then increased again gradually. The decrease ratio of m-AST/s-AST per minute at early stage of 8 cases, who were succeeded to reperfusion, was 0.28 +/- 0.20%, and that was significantly higher than of conventionally treated 7 cases and non-reperfused 7 cases (0.11 +/- 0.07%). These results indicated that (1) m-AST/s-AST may be an excellent indicator for AMI in early stage. (2) The decrease ratio of m-AST/s-AST would predict whether reperfusion is successful or not at an earlier stage of AMI.

Aged↗
PubMed1994

Iron deprivation-induced apoptosis in HL-60 cells.

Iron deprivation of HL-60 cells with deferoxamine B mesylate (DFO) induced apoptosis. DNA fragmentation became apparent with 10(-6) M DFO after 48 h treatment. The apoptosis peak according to the DNA histogram on flow cytometry and typical nuclear collapse and were observed microscopically after 48 h treatment with 10(-4) M DFO. Cells treated with 10(-4) M DFO for as little as 24 h were shown to be committed to apoptosis, as chromatin condensation progressed gradually thereafter.

Apoptosis↗
PubMed1994

[Diffuse slow washout pattern (DSWO) on exercise stress thallium-201 myocardial SPECT: correlative study with coronary arteriography and the related clinical factors].

DSWO was shown on bull's eye images of 98 of 1234 patients suspected of having coronary artery disease and examined with thallium-201 myocardial SPECT imaging. Fifty-eight of these 98 patients underwent coronary arteriography, and comparison studies were performed between the bull's eye SPECT images, the results of coronary arteriography and the laboratory data. DSWO was found in 11 of 58 cases (19.0%) of single vessel disease (1VD), 18 of 58 cases (31.0%) of double vessel disease (2VD) and 21 of 58 cases (36.2%) of triple vessel disease (3VD). Three of 58 cases (5.2%) of stenosis of a coronary artery less than 75% of its normal diameter (N group) also showed DSWO. DSWO was closely related with multiple vessel disease, as has been indicated by previous reports, but we also found another patient group that showed minor coronary arterial change (1VD and N group) and manifested DSWO. Based on the study of laboratory data, we clarified that this group of patients tended to show accompanying hypertension and hyperlipidemia as factors influencing the appearance of DSWO. DSWO was accompanied by hypertension and hyperlipidemia in 54.5% and 45.5% in 1VD. These values were higher than those in the 2VD and 3VD cases, which were 33.3% and 38.9% in 2VD, and 19.0% and 28.6% in 3VD, respectively. Hypertension and hyperlipidemia appeared to play an important role in causing DSWO by interfering with coronary circulation.

Adolescent↗
PubMed1994

Synthesis and antitumor activity of novel mitomycin derivatives containing functional groups at the C-6-methyl position.

A series of C-6-substituted methyl mitomycins was synthesized and evaluated for anticellular and antitumor activities. These novel compounds were prepared by Michael addition of various alcohols or thiols to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosanes followed by treatment with NH3 or MeOH/K2CO3. Most compounds were potent against HeLa S3, and some of them showed superior activity to that of mitomycin C (MMC) against P388 leukemia and sarcoma 180 in mice. In addition, some compounds exhibited remarkable activity against MMC-resistant P388 in mice. FAB-MS spectra of these mitomycin derivatives showed the elimination of the C-6-methyl substituents from the mitomycin skeletons to form quinonemethides. Interestingly, treatment of 6-demethyl-6-[[(2-pyrimidinyl)thio]methyl ]mitomycin C (12v) with diethylamine afforded 6-demethyl-6-[(diethylamino)methyl]mitomycin C (31) in good yield. These results suggested that the C-6-substituted methyl mitomycins would have different biological character from that of MMC.

Animals↗
PubMed1994

Synthesis and antitumor activity of novel 6-alkyl-6-demethylmitomycins.

A series of 6-alkyl-6-demethylmitomycins (1-5) was synthesized and evaluated for anticellular and antitumor activities. These novel compounds were prepared by Michael addition of various carbanion species to 6-demethyl-7, 7-(ethylenedioxy)-6, 7-dihydro-6-methylidenemitosane (6 and 9) followed by treatment with NH3 or MeOH/K2CO3. Alkylation at the C-6 position of 6-demethyl-6-selenide (7) was also useful for the alternative synthesis of 6-alkyl-6-demethylmitomycins. The antitumor activity of these derivatives was evaluated, and 6-demethyl-6-ethylmitomycin A (2a) was found to exhibit excellent activity against S-180 solid tumor in mice. The structure-activity relationship is also discussed.

Animals↗
PubMed1994

Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors.

Methyl(1S)-1-bromomethyl-7-methyl-5-[(4-methylpiperazinyl)-carb onyloxy]- 3-[(5,6,7-trimethoxy-2-indolyl)-carbonyl]-1,2-dihydro-3H-pyrolo[3, 2-e] indole-8-carboxylate hydrobromide (KW-2189), a novel derivative of duocarmycin B2, was selected for extensive evaluation based on its improved antitumor activity, water solubility, and stability in the culture medium, as compared with duocarmycin B2. Although the in vitro cell growth-inhibitory activity of KW-2189 was less potent than that of duocarmycin B2, it significantly inhibited the growth of five murine solid tumors including Colon 26 adenocarcinoma, Colon 38 adenocarcinoma, and B16 melanoma in vivo. KW-2189 was also effective against murine P388 leukemia and L1210 leukemia not only by local administration (i.p.-i.p. system), but also by systemic administration (i.p.-i.v. or i.v.-i.v. system). The most remarkable feature of KW-2189 was its efficacy against various human xenografts, which was observed in 14 tumors among 16 tested tumors including drug-insensitive tumors by single i.v. administration. Tumor regression was observed in mice bearing LC-6 lung, St-4 and St-40 stomach, Li-7 liver, PAN-2 pancreas, and MX-1 breast carcinomas. In many cases, the activities of KW-2189 were more than those of clinically active agents, mitomycin C, Adriamycin, cisplatin, and cyclophosphamide. Delayed lethal toxicity, which was reported in mice treated with CC-1065 whose structure was similar to KW-2189, was not observed in mice treated with KW-2189. KW-2189 inhibited DNA synthesis more significantly than RNA or protein synthesis, although DNA strand breaks were not observed. KW-2189 was activated by porcine liver esterase, mouse liver homogenate or Hep G2 homogenate, and DU-86-DNA adducts were detected in KW-2189-treated HeLa S3 cells, suggesting that KW-2189 was converted to DU-86 in the cells. These results indicate that KW-2189 is an interesting candidate for further development as a novel antitumor agent.

Animals↗
PubMed1994

A new meiotic protein factor which enhances activity of meiotic DNA polymerase from Coprinus cinereus.

Meiotic cells of Coprinus contain a protein that can be identified by its ability to enhance activity of the meiotic DNA polymerase reported previously (8). Its activity is found only during the prophase stages in meiotic cells, and is accompanied by the meiotic polymerase. The protein, which was purified to near homogeneity, is a single polypeptide with a molecular mass of 30k, and shows no activities of nuclease, ATPase, or DNA-binding protein. The protein could enhance the meiotic polymerase activity by at least 5 fold. The other Coprinus polymerases were not influenced by the protein. The protein could increase Vmax value of the meiotic polymerase, but not the Km. The significance of this protein to meiotic DNA synthesis is considered in relation to other biochemical properties of meiotic cells.

Chromatography, Gel↗
PubMed1994

Intravenous extended infusion of recombinant human soluble thrombomodulin prevented tissue factor-induced disseminated intravascular coagulation in rats.

This study demonstrated that intravenous infusion of recombinant human soluble thrombomodulin (rhs-TM) could inhibit disseminated intravascular coagulation (DIC) caused by 4 hr infusion of tissue factor (TF) in rats. Extended infusion of TF reduced fibrinogen and platelet counts and elevated serum FDP level. Pretreatment and coinfusion of rhs-TM could block changes of these DIC-parameters without prolongation of APTT. Heparin, which is a potent anti-DIC drug, could also inhibit these changes with extra prolongation of APTT and PT. Thus, these results suggest thrombomodulin prevent DIC less bleeding tendency than heparin.

Animals↗
PubMed1994

Antithrombotic effects of recombinant human soluble thrombomodulin (rhs-TM) on arteriovenous shunt thrombosis in rats.

We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs-TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs-TM (0.5-4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose-dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25-200 U/kg) and in those treated with rhs-TM (0.5-4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs-TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs-TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs-TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis.

Animals↗
PubMed1994

Effect of UCN-01, a selective inhibitor of protein kinase C, on the cell-cycle distribution of human epidermoid carcinoma, A431 cells.

UCN-01 (7-hydroxy-staurosporine), a selective inhibitor of protein kinase C (PKC), was shown to exhibit antitumor activity in murine and human tumor cell lines in vitro and in vivo. On the other hand, staurosporine, a non-selective protein kinase inhibitor, was not shown to exert antitumor activity in vivo despite its potent antiproliferative activity in vitro. To compare the modes of action of UCN-01 and staurosporine in vitro, the effects of both drugs on the cell cycle progression of human epidermoid carcinoma A431 cells were examined by flow cytometry using propidium iodide (PI) staining. At 50% growth inhibitory concentrations, both UCN-01 and staurosporine induced G1 phase accumulation in the cell cycle. At 80% growth inhibitory concentrations, UCN-01 also induced preferential G1 phase accumulation, but staurosporine mostly induced G2M phase accumulation. Staurosporine also induced higher DNA ploidy when the cells were exposed to the drug for more than one generation time of A431 cells. An analysis of cell kinetics by 5-bromo-2-deoxyuridine incorporation versus DNA content confirmed that the G1 phase block by UCN-01 and the G1 and G2M phase block by staurosporine at the respective doses, as was the case for PI staining. Additionally, DNA synthesis of the cells, which was determined by the uptake of 3H-TdR, was not suppressed at least 8 h after the treatment with UCN-01. These results suggested that UCN-01 could affect the G1 phase of cell cycle in A431 cells in quite different manners from staurosporine. The G1 phase block induced by UCN-01 might be important for the growth inhibitory activity of UCN-01 against A431 cells in vitro and in vivo.

Alkaloids↗
PubMed1994

Evaluation of antitumor activity of navelbine (vinorelbine ditartrate) against human breast carcinoma xenografts based on its pharmacokinetics in nude mice.

The in vitro antitumor activity of navelbine (NVB, KW-2307), a newly synthesized vinca alkaloid, was compared with that of adriamycin (ADM) against human breast carcinomas inoculated into nude mice at the maximum tolerated dose (MTD) and clinically equivalent dose (CED). The plasma levels of NVB after intravenous injection into nude mice at doses of 1.2 and 4.8 mg/kg diminished rapidly during the early phase (0-1 h), followed by a very long shallow one. NVB was still detected 96 h after administration at a dose of 4.8 mg/kg. The pharmacokinetic parameters of NVB in plasma indicated that NVB extensively distributes to tissues. The CED of NVB was provisionally decided to be 4.8 mg/kg based on the comparison of AUC values at 24-infinity h between human patients and nude mice. When compared by a single injection of MTD (NVB, 16 mg/kg; ADM 12 mg/kg), NVB was effective against all four tumor lines, MC-2, MC-8, MMKY and H-31, while ADM was effective only against H-31. On the other hand, the body weight loss by NVB was mild as compared with that by ADM, indicating that the antitumor activity of NVB is superior to that of ADM at their MTDs. A single injection of NVB at its CED (4.8 mg/kg) produced a poor antitumor effect and no or little toxicity in terms of body weight loss, as compared with those at MTD. However, when NVB was administered intermittently at CED, it exhibited significant antitumor activity against three tumor lines. The body weight loss was still mild even on this intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Papillary↗
PubMed1994

Modulation of adriamycin resistance in human breast carcinoma MCF-7 cells in vitro and in vivo by medroxyprogesterone acetate.

The combination effect of adriamycin (ADM) and medroxyprogesterone acetate (MPA) was examined in vitro against human breast carcinoma MCF-7 and its ADM-resistant line (MCF-7/ADM). MCF-7 cells, which are positive for estrogen receptors, progesterone receptors and high-affinity MPA-binding activity, were more susceptible to the growth-inhibitory activity of ADM or MPA than MCF-7/ADM cells. A combination effect of ADM and MPA was observed against MCF-7/ADM cells, which are negative for steroid receptors, and furthermore against human nasopharynx carcinoma KB and its ADM-resistant line KB-A1. This combination effect of ADM and MPA against MCF-7/ADM cells was demonstrated to be synergistic by using the median effect plot method. The activity of MPA was almost equivalent to that of chlormadinone acetate or tamoxifen, greater than that of progesterone, and less than that of verapamil. The accumulation of ADM in MCF-7/ADM cells was enhanced by treatment with 10 microM MPA as well as 10 microM verapamil. The efflux of accumulated ADM from MCF-7/ADM cells was also partially inhibited by treatment with MPA or verapamil. MPA augmented the growth-inhibitory activity of ADM against MCF-7/ADM tumors inoculated into nude mice, although statistical significance was not observed. It is suggested that the clinical advantage of the combination of MPA with ADM against advanced breast cancers may be partly explained by the modulation of ADM resistance by MPA.

Animals↗
PubMed1994

Differential effect of duocarmycin A and its novel derivative DU-86 on DNA strand breaks in HeLa S3 cells.

Duocarmycin A (DUMA) and DU-86, a semisynthetic derivative of duocarmycins (DUMs) and a possible active form of KW-2189, both showed potent cell growth-inhibitory and cell-killing activities against human uterine cervix carcinoma HeLa S3 cells. Both drugs showed similar profiles of inhibition of macromolecular synthesis and influence on cell-cycle distribution. Namely, they inhibited [3H]thymidine uptake at lower concentrations than [3H]uridine or [3H]leucine uptake, suggesting that the inhibition of DNA synthesis is the primary site of their actions. Furthermore, they induced the accumulation of cells in early S phase. However, a significant difference was observed between these drugs in terms of DNA-fragmentation activity against HeLa S3 cells by using two independent methods, pulse-field gel electrophoresis and alkaline elution. DNA fragmentation was insignificant in the cells treated with DU-86, in contrast to the cells treated with DUMA. The analysis of DNA adducts in the cells revealed that DU-86 alkylated adenine quite selectively, while DUMA alkylated both adenine and guanine. These results suggest that the pyrrolidone ring of DUMA is responsible for its adduct formation with guanine and the subsequent DNA-fragmentation and inhibition of DNA synthesis, while DU-86 alkylated adenine and inhibited DNA synthesis through mechanisms other than DNA-fragmentation.

Adenine↗