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J Kato

Publications and source records attributed to J Kato.

At least 199 records · Page 11Linked to original sources
PubMed1997

Interaction of the DNA topoisomerase II catalytic inhibitor meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane (ICRF-193), a bisdioxopiperazine derivative, with the conserved region(s) of eukaryotic but not prokaryotic enzyme.

ICRF-193 [meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane], a bisdioxopiperazine compound, has been shown to be a catalytic inhibitor of DNA topoisomerase II by stabilizing the enzyme in the form of a closed "protein clamp," an intermediate form in the catalytic cycle (Roca et al., Proc Natl Acad Sci USA 91: 1781-1785, 1994). In view of its usefulness as a probe in the functional analysis of the enzyme, we tried further to define the domain(s) of the enzyme interacting with the drug by examining its inhibitory activity on type II topoisomerases from various species of eukaryotes and prokaryotes. ICRF-193 inhibited the enzyme from yeast, fly, frog, plant, and mammals at IC50 values in the range of 1-13 microM. Experiments using fission yeast truncated mutant type II enzyme lacking both amino-terminal 74 amino acids and carboxy-terminal 265 amino acids revealed that ICRF-193 interacts with the 125 kDa "core" polypeptide of the enzyme. In contrast, prokaryotic type II enzymes, Escherichia coli DNA gyrase, topo IV, and phage T4 topo, were not affected by the drug. From these results, the domain(s) common to eukaryotic but not to prokaryotic type II enzymes interacting with ICRF-193 was speculated.

Amino Acid Sequence↗
PubMed1997

Purification and characterization of PAMP-12 (PAMP[9-20]) in porcine adrenal medulla as a major endogenous biologically active peptide.

Proadrenomedullin N-terminal 20 peptide (PAMP-20) is a potent hypotensive peptide processed from the adrenomedullin (AM) precursor. We developed a specific radioimmunoassay which recognizes the C-terminal region of PAMP-20. Using this radioimmunoassay, the distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentrations of ir-PAMP were observed in the adrenal medulla and in the atrium, and these values were comparable to the corresponding concentrations of ir-AM. The concentration of ir-PAMP was almost the same as that of ir-AM in the kidney, while ir-PAMP was significantly lower than ir-AM in the ventricle, lung, and aorta. Reversed-phase high performance liquid chromatography in each porcine tissue sample revealed that two major peaks of ir-PAMP existed: one emerged at a position identical to that of authentic porcine PAMP-20; the other unknown peak was eluted earlier. The unknown peptide was purified to homogeneity from porcine adrenal medulla, and its complete amino acid sequence was determined. This peptide was found to be PAMP[9-20] with a C-terminal amide structure, and was named PAMP-12. Intravenous injections of PAMP-12 in anesthetized rats showed a significant hypotensive effect in a dose-dependent fashion, and the effect was comparable to that of PAMP-20. These data indicate that PAMP-12, a major component of ir-PAMP, is processed from the AM precursor, as is PAMP-20, and may participate in cardiovascular control.

Adrenal Medulla↗
PubMed1997

Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae.

DNA double-strand breaks are repaired by homologous recombination or DNA end-joining, but the latter process often causes legitimate recombination and chromosome rearrangements. One of the factors involved in the end-joining process is Hdf1, a yeast homologue of Ku protein. We used the yeast two-hybrid assay to show that Hdf1 interacts with Sir4, which is involved in transcriptional silencing at telomeres and HM loci. Analyses of sir4 mutants showed that Sir4 is required for deletion by illegitimate recombination and DNA end-joining in the pathway involving Hdf1. Sir2 and Sir3, but not Sir1, were also found to participate in these processes. Furthermore, mutations of the SIR2, SIR3 and SIR4 genes conferred increased sensitivity to gamma-radiation in a genetic background with a mutation of the RAD52 gene, which is essential for double-strand break repair mediated by homologous recombination. These results indicate that Sir proteins are involved in double-strand break repair mediated by end-joining. We propose that Sir proteins act with Hdf1 to alter broken DNA ends to create an inactivated chromatin structure that is essential for the rejoining of DNA ends.

DNA Repair↗
PubMed1997

Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats.

The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 microgram/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.

Adrenomedullin↗
PubMed1997

RecQ DNA helicase is a suppressor of illegitimate recombination in Escherichia coli.

Bloom syndrome and Werner syndrome are genetic disorders in which an increased rate of chromosomal abnormality is observed. The genes responsible for these diseases, BLM and WRN, have been cloned and identified as homologs of the Escherichia coli recQ genes. We studied the effect of recQ mutations on illegitimate recombination, which is an aberrant biological event related to the chromosomal abnormality in humans, and found that a variety of recQ mutations increased spontaneous illegitimate recombination by 20- to 300-fold and increased UV light-induced illegitimate recombination by 10- to 100-fold. Most lambda bio or lambda pro transducing phages are formed by the recombination events at several hot spots, which are enhanced by the recQ mutation. The analysis of nucleotide sequences at the recombination junction in the transducing phages indicates that recombination at the hot spot sites as well as the non-hot spot sites takes place between short homologous sequences. Enhancement of the recombination in the recQ mutants also occurs in the recA, recBC sbcBC, or recBC sbcA backgrounds, indicating that these recombination events are mediated by none of the known recombination pathways, RecBC, RecF, and RecE. We therefore concluded that the RecQ function suppresses illegitimate recombination that depends on short homologous regions. We discuss a model, based on the 3'-to-5' helicase activity of RecQ, to explain the role of this protein as a suppressor of illegitimate recombination.

Adenosine Triphosphatases↗
PubMed1997

Short-homology-independent illegitimate recombination in Escherichia coli: distinct mechanism from short-homology-dependent illegitimate recombination.

We have shown elsewhere that there is no, or very little, homology at the recombination sites in DNA gyrase-mediated illegitimate recombination in vitro. On the other hand, many reports have indicated that illegitimate recombination takes place between sequences with a short homology. To clarify this contradiction, we analyzed the mechanism of DNA gyrase-mediated illegitimate recombination in vivo, by isolating a temperature-sensitive gyrA mutant (gyrAhr1) that causes spontaneous illegitimate recombination at a higher frequency than that of the wild-type. This mutant also causes spontaneous induction of lambda prophage. It is therefore suggested that the gyrAhr1 mutation induces strand breaks in the chromosome, resulting in the formation of illegitimate recombinants. Analysis of the recombination junctions of lambdabio transducing phages formed spontaneously in the gyrAhr1 mutant revealed that the Escherichia coli bio and lambda recombination sites have an average homologous sequence of only 1.3 base pairs. This is the first indication that homology in vivo is not required for illegitimate recombination. On the other hand, a short homology of 8.4 bp, on average, was found in the junctions of lambdabio transducing phages formed spontaneously in the wild-type bacteria. When the gyrAhr1 mutant was irradiated with UV, short homologies were also detected in the junctions. We concluded that illegitimate recombination, which takes place spontaneously in the gyrAhr1 mutants, is distinguishable from spontaneous recombination in the wild-type and from UV-induced recombination in the mutant with regard to the requirement for short homology. We propose that short-homology-independent illegitimate recombination is mediated by subunit exchange between DNA gyrase, while short-homology-dependent recombination is triggered by double-strand breaks and completed by processing, annealing, and ligation of DNA ends.

Bacteriophage lambda↗
PubMed1997

Intra-mesenteric artery steroid administration relieved severe refractory gastro-intestinal graft-vs.-host disease in an allogeneic bone marrow transplantation patient.

We report a case of severe gastro-intestinal (G-I) graft-vs.-host disease (GVHD) successfully treated with intra-mesenteric artery steroid administration. A 29-year-old man with severe aplastic anemia (SAA) was submitted to HLA-identical unrelated allogeneic bone marrow transplantation (BMT) and was found to be suffering from grade IV G-I GVHD. Although cyclosporine, steroid pulse therapy, and FK506 proved ineffective, 30 mg of water-soluble prednisolone as administered into each the superior and inferior mesenteric artery with remarkable effects. This treatment was repeated two times, and the symptoms of G-I GVHD disappeared completely.

Adult↗
PubMed1997

Acute exacerbation of hepatitis due to reactivation of hepatitis B virus with mutations in the core region after chemotherapy for malignant lymphoma.

A 43-year-old Japanese man who was positive for hepatitis B surface (HBs) antigen and HB e antibody, underwent chemotherapy for non-Hodgkin's lymphoma. After the chemotherapy he suffered from acute exacerbation of hepatitis because of reactivation of HBV. Recovery was achieved with interferon-alpha, glucagon-insulin therapy, and plasma exchange. Mutations were detected in codons 97, 100, 129, and 131 of the core region of HBV. The peptide encoded from the core region including such mutations possibly had greater antigenicity to induce cytotoxic T cell activity in the host. Core region mutations may be a crucial cause of the acute exacerbation of hepatitis B seen after chemotherapy.

Acute Disease↗
PubMed1997

Budding yeast Rad50, Mre11, Xrs2, and Hdf1, but not Rad52, are involved in the formation of deletions on a dicentric plasmid.

We have previously shown that the RAD50, RAD52, MRE11, XRS2, and HDF1 genes of Saccharomyces cervisiae are involved in the formation of deletions by illegitimate recombination on a monocentric plasmid. In this study, we investigated the effects of mutations of these genes on formation of deletions of a dicentric plasmid, in which DNA double-strand breaks are expected to occur frequently because the two centromeres are pulled to opposite poles in mitosis. We transformed yeast cells with a dicentric plasmid, and after incubation for a few division cycles, cells carrying deleted plasmids were detected using negative selection markers. Deletions occurred at a higher frequency than on the monocentric plasmid and there were short regions of homology at the recombination junctions as observed on the monocentric plasmid. In rad50, mre11, xrs2, and hdf1 mutants, the frequency of occurrence of deletions was reduced by about 50-fold, while in the rad52 mutant, it was comparable to that in the wild-type strain. The end-joining functions of Rad50, Mre11, Xrs2, and Hdf1, suggest that these proteins play important roles in the joining of DNA ends produced on the dicentric plasmid during mitosis.

Base Sequence↗
PubMed1997

Application of a new anticoagulant (Nafamostat Mesilate) to control hemorrhagic complications during extracorporeal membrane oxygenation--a preliminary report.

Bleeding related to systemic heparinization has been considered one of the major complications associated with extracorporeal membrane oxygenation (ECMO). Development of the heparin-bonded system will be essential in reducing hemorrhagic complications, but has not yet been clinically proven. The authors chose an alternative approach of making a difference in the activated clotting time (ACT) values between the patient and the ECMO circuit, and decreased only the patient's ACT value, while keeping the value of the ECMO circuit at an ideal level. For this purpose, we have used a very short-life anticoagulant, Nafamostat Mesilate (FUT), while decreasing the dose of heparin. FUT is a synthetic protease inhibitor that has been found to inhibit various kinds of enzyme activities for coagulation. Twelve newborns who had some hemorrhagic complications at various sites before or during ECMO, were selected to receive FUT. The heparin dose was decreased after FUT administration into the drainage route. FUT and heparin doses were regulated to maintain the ACT value at the reinfusion route at 190 to 220 seconds. ACT values at the drainage and the reinfusion routes were simultaneously measured. The average time on FUT was 100.3 +/- 86.3 (SD) hours. The average dose of FUT was 0.48 +/- 0.22 mg/kg/h, and that of heparin was 21.0 +/- 7.5 U/kg/h. The average ACT value at the reinfusion route was 205.7 +/- 14.0 seconds compared with that at the drainage route of 178.5 +/- 11.8. The difference was statistically significant (P < .001). The average difference in ACT values between both routes was 27.1 +/- 7.9 seconds. The bleeding was well controlled by FUT administration in 8 of 12 cases. This report may represent the first clinical use of FUT in neonatal ECMO, and serve as a preliminary study.

Anticoagulants↗
PubMed1997

Production of adrenomedullin in human vascular endothelial cells.

To examine the production of adrenomedullin (AM) in human vascular endothelial cells, AM concentrations in cultured endothelial cells derived from the human umbilical vein and the conditioned media of the cells were measured in the present study. The cultured endothelial cells secreted immunoreactive AM (ir-AM) into the medium at a rate of 14.7 +/- 3.0 fmol/10(6) cells/24 h with an intracellular ir-AM of 5.2 +/- 0.8 fmol/l0(6) cells. Analysis by reverse phase high performance-liquid chromatography (HPLC) showed that ir-AM in both the cells and the conditioned medium eluted at the position identical to that of human AM(1-52). Treatment with dexamethasone significantly augmented the secretion of ir-AM from the cells without any effect on the intracellular ir-AM concentration. Northern blot analysis showed not only the presence of the 1.6 kb human AM precursor mRNA in the endothelial cells, but also its increased expression in the dexamethasone-treated cells. Thus, AM was synthesized and secreted by the human endothelial cells of the umbilical vein, and glucocorticoid augmented the AM production. These findings suggest not only the role of AM as a local modulator of the vascular tone but also the possibility that endothelial cells contribute to circulating AM in the human blood.

Adrenomedullin↗
PubMed1997

Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study.

To investigate the relation between nocturnal decline in blood pressure and mortality, we obtained ambulatory blood pressures in 1542 residents aged 40 years or over of a rural Japanese community. Subjects were followed-up for a mean of 5.1 years and were then subdivided into four groups according to the percent decline in nocturnal blood pressure: 1) extreme dippers: percent decline in nocturnal blood pressure > or = 20% of the daytime blood pressure; 2) dippers: decline of > or = 10% but < 20%; 3) nondippers: decline of > or = 0% but < 10%; and 4) inverted dippers: no decline. The relationship between the decline in nocturnal blood pressure and mortality was examined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, previous history of cardiovascular disease, and the use of antihypertensive medication. The mortality risk was highest in inverted dippers, followed by nondippers. There was no difference in mortality between extreme dippers and dippers. This relationship was observed for both treated and untreated subjects, was more pronounced for cardiovascular than for noncardiovascular mortality, and did not change after the data were adjusted for 24-h, daytime, and nighttime blood pressure levels.

Aged↗
PubMed1997

Long-term survival and differentiation of human peripheral blood CD34+ cells in SCID mice.

Human peripheral blood progenitor cells (PBPC) are currently used as a source of hematopoietic reconstitution by autologous transplantation after myeloabrative chemotherapy for malignancies. PBPC would also be useful for allogeneic transplantation since the collection of PBPC is much safer than that of bone marrow stem cells (BM). For allogeneic transplantation, it is imperative to confirm that PBPC contains self-renewable stem cells that can sustain a long lasting hematopoiesis. In the present study, we examined the reconstitution of human hematopoiesis in severe combined immunodeficiency (SCID) mice by transplanting peripheral blood CD34+ cells in which the neo gene was transduced as a marker. In 2 of 4 mice receiving PB-CD34+ cell transplantation, the neo gene appeared as early as 4 weeks and lasted as long as 24 weeks in all DNA preparations of bone marrow, peripheral blood and spleen cells from the SCID mice, while in 2 of 4 mice receiving BM-CD34+ cell transplantation, although the neo gene also lasted as late as 24 weeks, it did not appear as early as in the mice receiving PB-CD34+ cell transplantation. A similar observation was noted in clinical trials, i.e. the white blood cell and platelet recovered earlier by transplantation of PBPC than of BM. In mice who had the neo gene, we were also able to demonstrate by FACS the presence of human lineage specific antigen in the cells as late as 24 weeks after transplantation with PB-CD34+ cells, and the presence of human IgG in the sera 10 weeks after transplantation. These findings indicate that PB-CD34+ cells contain long-term repopulating stem cells which undergo differentiation in SCID mice.

Animals↗
PubMed1997

Expression and distribution of cortical type aromatase mRNA variant in the adult rat brain.

Our previous study showed that a relatively high level of the aromatase mRNA existed in the cerebral cortex (CC) of the rat, where the aromatase activity was reported to be little or absent. To elucidate the identity of the aromatase mRNA in the CC of the rat, we investigated the 5'-region of the aromatase mRNA in the rat CC. When the sequence of the 5'-region of the cortical message was analysed by the 5'-rapid amplification of cDNA ends (5'-RACE) with the antisense primer for exon II using the RNA extracted from the CC, no clone could be isolated. However, the upstream sequence from the 5'-end of exon IV of the aromatase clones, isolated from the CC by RACE with the antisense primers for exon V, was different from that on the aromatase mRNA encoding the full translated region. The new sequence of the cortical type message, called the cortical type aromatase mRNA variant, was located on the intron upstream of exon IV in the genomic cDNA. Distribution of the brain aromatase message with exons III-V and the cortical type aromatase mRNA variant were analysed by the reverse transcription-polymerase chain reaction (RT-PCR) using total RNAs extracted from the hypothalamus-preoptic area (HPOA), amygdala (AMY) and CC. The PCR products with primers for exons III-V were generated from the HPOA and AMY, but not from the CC. On the other hand, the PCR products with primers for exon IIIv (cortical type aromatase mRNA variant specific)-V were detected in significant amounts in the CC as well as the HPOA and AMY. These results indicate the existence of the aromatase mRNA variant lacking exons I-III in the adult rat brain. This cortical type mRNA variant seemed to be widely distributed in the tissues.

Animals↗
PubMed1997

K-space filter effect in three-dimensional contrast MR angiography.

PURPOSE: In three-dimensional (3-D) contrast MR angiography, temporal misregistration between the data acquisition period and the arrival of the contrast agent in the target vessels is thought to degrade the quality of the reconstructed images. The purpose of this study was to demonstrate and investigate this effect in phantom experiments. MATERIAL AND METHODS: MR images of a phantom tube were evaluated with flowing materials of water or Gd-DTPA solution by changing from water to Gd-DTPA solution halfway through the data acquisition period. RESULTS: While no signal could be acquired with a stream of water in the tube, a clear signal was obtained with a flow of Gd-DTPA solution. Blurring and ghost artifacts surrounding the tube along the phase-encoding direction were observed when the flowing material was changed from water to Gd-DTPA solution halfway through the data acquisition period. CONCLUSION: K-space filter effect occurs during 3-D contrast MR angiography owing to the transient passage of the contrast agent, and this effect causes spatial artifacts in the reconstructed images.

Artifacts↗
PubMed1997

The effect of hypothermic cardiopulmonary bypass on plasma adrenomedullin in adult cardiac surgical patients.

Cardiopulmonary bypass (CPB) can evoke a systemic inflammatory response, which is accompanied by an increase in plasma cytokines that may stimulate the production of adrenomedullin (AM), a potent vasodilator peptide. This study was undertaken to investigate whether CPB influenced plasma AM concentration in 10 patients undergoing cardiac surgical procedures. We found that the plasma AM concentration increased significantly after the commencement of CPB, with the greatest increase observed at weaning from bypass (P < 0.01). After CPB, plasma AM concentration declined but still exceeded baseline significantly 24 h postoperatively. The increase in the plasma AM concentration at weaning from CPB correlated significantly with aortic cross-clamp time (r = 0.74, P < 0.05). The authors conclude that the secretion of AM into circulation is augmented by CPB in patients undergoing cardiac surgery, which suggests a possible role of AM in cardiovascular regulation during and after surgery with CPB.

Adrenergic beta-Agonists↗