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H Maki

Publications and source records attributed to H Maki.

At least 19 recordsLinked to original sources
PubMed2001

Directionality of DNA replication fork movement strongly affects the generation of spontaneous mutations in Escherichia coli.

Using a pair of plasmids carrying the rpsL target sequence in different orientations to the replication origin, we analyzed a large number of forward mutations generated in wild-type and mismatch-repair deficient (MMR(-)) Escherichia coli cells to assess the effects of directionality of replication-fork movement on spontaneous mutagenesis and the generation of replication error. All classes of the mutations found in wild-type cells but not MMR(-) cells were strongly affected by the directionality of replication fork movement. It also appeared that the directionality of replication-fork movement governs the directionality of sequence substitution mutagenesis, which occurred in wild-type cells at a frequency comparable to base substitutions and single-base frameshift mutations. A very strong orientation-dependent hot-spot site for single-base frameshift mutations was discovered and demonstrated to be caused by the same process involved in sequence substitution mutagenesis. It is surprising that dnaE173, a potent mutator mutation specific for sequence substitution as well as single-base frameshift, did not enhance the frequency of the hot-spot frameshift mutation. Furthermore, the frequency of the hot-spot frameshift mutation was unchanged in the MMR(-) strain, whereas the mutHLS-dependent mismatch repair system efficiently suppressed the generation of single-base frameshift mutations. These results suggested that the hot-spot frameshift mutagenesis might be initiated at a particular location containing a DNA lesion, and thereby produce a premutagenic replication intermediate resistant to MMR. Significant numbers of spontaneous single-base frameshift mutations are probably caused by similar mechanisms.

Adenosine Triphosphatases↗
PubMed2001

Photo-oxidation of biodegraded crude oil and toxicity of the photo-oxidized products.

We investigated the physicochemical changes resulting from irradiation by sunlight of biodegraded crude oil. An Arabian light crude oil sample was first subjected to microbial degradation. n-Alkanes and aromatic compounds such as naphthalenes, fluorenes, dibenzothiophenes and phenanthrenes possessing short, alkyl side chain(s) were almost completely degraded, while the contents of the saturated and aromatic fractions were reduced by 70% and 40%, respectively. This biodegraded oil was then suspended in seawater and exposed to sunlight irradiation for several weeks. The most remarkable change caused by the irradiation was a substantial decline in the aromatic fraction with a concomitant increase in the resin and asphaltene fractions. A 13C-nuclear magnetic resonance (NMR) spectroscopic analysis showed that the aromaticity of the biodegraded oil was significantly lower in the irradiated sample. A field desorption-mass spectrometric (FD-MS) analysis showed that sunlight irradiation reduced the average molecular weight of the oil components and formed oxygenated compounds. Consistent with this observation is that the oxygen content in the oil increased as the irradiation was prolonged. The bioavailability of the biodegraded oil was increased by the photo-oxidation: the growth of seawater microbes was minimal when the non-irradiated biodegraded oil was used as the source of carbon and energy; however, growth was significant when irradiated biodegraded oil was used. The concentration of dissolved organic carbon (DOC) increased linearly during the sunlight irradiation of the biodegraded oil, and this increase was matched by an increase in ultraviolet-absorptive materials in the seawater. The photochemically formed, water-soluble fraction (WSF) showed acute toxicity against the halophilic crustacean, Artemia.

Animals↗
PubMed2001

Preclinical in vivo antitumor efficacy of nedaplatin with gemcitabine against human lung cancer.

The antitumor efficacy of the combination of nedaplatin (NDP) with gemcitabine (GEM) was evaluated. We also compared the antitumor activity of NDP plus GEM with that of cisplatin (CDDP) plus GEM or carboplatin (CBDCA) plus GEM. Ma44, which is a human lung cancer sensitive to GEM, and NCI-H460, which is a human lung cancer refractory to GEM, were used in this study. GEM was injected i.v. once followed by i.v. injection of NDP at an interval of approximately 30 min into tumor-bearing athymic mice. GEM was administered again 3 or 4 days thereafter. Combined dosing of NDP with GEM resulted in synergistically enhanced inhibition of tumor growth in the Ma44 tumor model. NDP plus GEM was also effective against Ma44 cells when given late in the therapy, a model for advanced disease. Potent augmentation of growth inhibition by NDP with GEM was also found with the NCI-H460 tumor model. The combination effect of NDP plus GEM appeared to be superior to that of CDDP plus GEM or CBDCA plus GEM in both tumor models. Toxicity in terms of blood cell numbers was not enhanced by the combination of NDP with GEM. These results suggest the effectiveness of combination of NDP with GEM for clinical therapy.

Animals↗
PubMed2001

Katanosin B and plusbacin A(3), inhibitors of peptidoglycan synthesis in methicillin-resistant Staphylococcus aureus.

Both katanosin B and plusbacin A(3) are naturally occurring cyclic depsipeptide antibiotics containing a lactone linkage. They showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus and VanA-type vancomycin-resistant enterococci, with MICs ranging from 0.39 to 3.13 microg/ml, as well as against other gram-positive bacteria. They inhibited the incorporation of N-acetylglucosamine, a precursor of cell wall synthesis, into peptidoglycan of S. aureus whole cells at concentrations close to their MICs. In vitro studies with a wall-membrane particulate fraction of S. aureus showed that katanosin B and plusbacin A(3) inhibited the formation of lipid intermediates, with 50% inhibitory concentrations (IC(50)s) of 2.2 and 2.3 microg/ml, respectively, and inhibited the formation of nascent peptidoglycan, with IC(50)s of 0.8 and 0.4 microg/ml, respectively. Vancomycin, a well-known inhibitor of transglycosylation, did not inhibit the formation of lipid intermediates but did inhibit the formation of nascent peptidoglycan, with an IC(50) of 4.1 microg/ml. Acetyl-Lys-D-Ala-D-Ala, an analog of the terminus of the lipid intermediates, effectively suppressed the inhibition of transglycosylation by vancomycin, but did not suppress those by katanosin B and plusbacin A(3). These results indicate that the antibacterial activity of katanosin B and plusbacin A(3) is due to blocking of transglycosylation and its foregoing steps of cell wall peptidoglycan synthesis via a mechanism differing from that of vancomycin.

Acetylglucosamine↗
PubMed2001

Protective effect of neurotropin against lipopolysaccharide-induced hypotension and lethality linked to suppression of inducible nitric oxide synthase induction.

Neurotropin is a non-protein extract from the dermis of rabbits inoculated with vaccinia virus and has been clinically used as an analgesic in Japan. We present in the current report evidence for its potential therapeutic value against endotoxin shock. Administration of this compound prior to lipopolysaccharide (LPS) challenge resulted in a reversal of a decrease of the mean arterial pressure in rats and also amelioration of lethality in mice. Anti-inducible nitric oxide synthase (iNOS) Western blotting of tissue extracts from LPS-treated mice revealed almost complete suppression of iNOS induction by Neurotropin. The findings in vivo were reproduced in in vitro experiments in which cultured human umbilical vascular endothelial cells were challenged with LPS. Simultaneous treatment of the cells with Neurotropin resulted in complete suppression of iNOS induction and significant reduction of cell death. These results suggested a therapeutic value of Neurotropin in the treatment of endotoxin shock that was linked, at least in part, to suppression of iNOS induction and reduced cell damage in vascular endothelial cells.

Animals↗
PubMed2001

A Web-based home helper support system.

A web-based "Home Helper" support system has been developed for improving scheduling and record keeping efficiency and for eliminating unnecessary travel. This support system consists of a wireless internet mobile phone for each "Home Helper" and a server at the main office. After each visit, the Home Helpers send their care reports via the mobile phone to the office server. This server computer then creates the "filings" automatically and in appropriate format for insurance and government use.

Adult↗
PubMed2000

Two DNA polymerases of Escherichia coli display distinct misinsertion specificities for 2-hydroxy-dATP during DNA synthesis.

The insertion specificities of an oxidized dATP analogue, 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP), were determined using the alpha (catalytic) subunit of Escherichia coli DNA polymerase III and the exonuclease-deficient Klenow fragment of DNA polymerase I. In contrast to our previous observation that mammalian DNA polymerase alpha incorporated the oxidized nucleotide opposite T and C, these two E. coli DNA polymerases incorporated 2-OH-dATP opposite T and G on the DNA template. Steady-state kinetic studies indicated that the alpha subunit incorporated 2-OH-dATP 10 times more frequently opposite T than opposite G. On the other hand, the incorporation of 2-OH-dATP opposite T by the exonuclease-deficient Klenow fragment was 2 orders of magnitude more efficient than that opposite G. These results indicate that the misinsertion specificity of 2-OH-dATP differs between replicative and repair-type DNA polymerases, and provide a biochemical basis for the mutations induced by 2-OH-dATP in E. coli.

Adenosine Triphosphate↗
PubMed2000

Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor.

The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent.

Animals↗
PubMed2000

Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia.

A 7-year-old boy with Diamond-Blackfan anemia (DBA) developed lymphoproliferative disease (LPD) after a cord blood transplant (CBT). 3.1 x 107/kg mononuclear cells from an HLA one-locus mismatched CB were transplanted after conditioning with total body irradiation (8 Gy), cyclophosphamide (200 mg/kg) and antithymocyte globulin (10 mg/kg). Complete engraftment occurred on day 33 post transplant. Despite the resolution of grade II graft-versus-host disease (GVHD), he died of lymphoma on day 130 post transplant. The tumor was of donor origin, indicating clonal proliferation of Epstein-Barr virus (EBV)-infected B cells. This is the first report of EBV-LPD after CBT. Post-transplant LPD can be a serious EBV-associated complication of CB grafts. Bone Marrow Transplantation (2000) 25, 209-212.

Blood Component Transfusion↗
PubMed2000

Spontaneous loss of heterozygosity in diploid Saccharomyces cerevisiae cells.

To obtain a broad perspective of the events leading to spontaneous loss of heterozygosity (LOH), we have characterized the genetic alterations that functionally inactivated the URA3 marker hemizygously or heterozygously situated either on chromosome III or chromosome V in diploid Saccharomyces cerevisiae cells. Analysis of chromosome structure in a large number of LOH clones by pulsed-field gel electrophoresis and PCR showed that chromosome loss, allelic recombination, and chromosome aberration were the major classes of genetic alterations leading to LOH. The frequencies of chromosome loss and chromosome aberration were significantly affected when the marker was located in different chromosomes, suggesting that chromosome-specific elements may affect the processes that led to these alterations. Aberrant-sized chromosomes were detected readily in approximately 8% of LOH events when the URA3 marker was placed in chromosome III. Molecular mechanisms underlying the chromosome aberrations were further investigated by studying the fate of two other genetic markers on chromosome III. Chromosome aberration caused by intrachromosomal rearrangements was predominantly due to a deletion between the MAT and HMR loci that occurred at a frequency of 3.1 x 10(-6). Another type of chromosome aberration, which occurred at a frequency slightly higher than that of the intrachromosomal deletion, appeared to be caused by interchromosomal rearrangement, including unequal crossing over between homologous chromatids and translocation with another chromosome.

Chromosome Aberrations↗
PubMed2000

An infant with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation.

Here we report a case with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation. A 7-month-old Japanese boy was diagnosed to have NK cell leukemia based on the existence of abnormal cells in the bone marrow with the phenotype of CD3(-) /CD4(+) /CD7(-) /CD8(-) /CD16(-) /CD33(+) /CD34(-) /CD56(+) /HLA-DR(+) /NKB1(+) / CD94(+). The leukemic cells showed few azurophilic granules in the cytoplasm and weak cytotoxic activity. Although he presented with a huge mass occupying the bilateral paranasal sinuses and hepatosplenomegaly, he achieved complete remission by the conventional chemotherapeutic regimen for acute myelogenous leukemia, followed by an unrelated cord blood transplantation. He has remained in complete remission for 14 months posttransplant. To our knowledge, this is the youngest reported case with precursor NK cell leukemia; cord blood transplantation may thus be the treatment of choice for this disease.

Disease-Free Survival↗
PubMed1999

Strand asymmetry of +1 frameshift mutagenesis at a homopolymeric run by DNA polymerase III holoenzyme of Escherichia coli.

We have recently shown that single-base frameshifts were predominant among mutations induced within the rpsL target sequence upon oriC plasmid DNA replication in vitro. We found that the occurrence of +1 frameshifts at a run of 6 residues of dA/dT could be increased proportionally by increasing the concentration of dATP present in the in vitro replication. Using single-stranded circular DNA containing either the coding sequence of the rpsL gene or its complementary sequence, the +1 frameshift mutagenesis by DNA polymerase III holoenzyme of Escherichia coli was extensively examined. A(6) --> A(7) frameshifts occurred 30 to 90 times more frequently during DNA synthesis with the noncoding sequence (dT tract) template than with the coding sequence (dA tract). Excess dATP enhanced the occurrence of +1 frameshifts during DNA synthesis with the dT tract template, but no other dNTPs showed such an effect. In the presence of 0.1 mM dATP, the A(6) --> A(7) mutagenesis with the dT tract template was not inhibited by 1.5 mM dCTP, which is complementary to the residue immediately upstream of the dT tract. These results strongly suggested that the A(6) --> A(7) frameshift mutagenesis possesses an asymmetric strand nature and that slippage errors leading to the +1 frameshift are made during chain elongation within the tract rather than by misincorporation of nucleotides opposite residues next to the tract.

Base Sequence↗
PubMed1999

DNA replication errors produced by the replicative apparatus of Escherichia coli.

It has been hard to detect forward mutations generated during DNA synthesis in vitro by replicative DNA polymerases, because of their extremely high fidelity and a high background level of pre-existing mutations in the single-stranded template DNA used. Using the oriC plasmid DNA replication in vitro system and the rpsL forward mutation assay, we examined the fidelity of DNA replication catalyzed by the replicative apparatus of Escherichia coli. Upon DNA synthesis by the fully reconstituted system, the frequency of rpsL-mutations in the product DNA was increased to 1.9x10(-4), 50-fold higher than the background level of the template DNA. Among the mutations generated in vitro, single-base frameshifts predominated and occurred with a pattern similar to those induced in mismatch-repair deficient E. coli cells, indicating that the major replication error was slippage at runs of the same nucleotide. Large deletions and other structural alterations of DNA appeared to be induced also during the action of the replicative apparatus.

Base Pairing↗
PubMed1999

Correlation of antiangiogenic and antitumor efficacy of N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA), an orally-active, selective matrix metalloproteinase inhibitor.

The antiangiogenic activity and antitumor efficacy of a newly developed matrix metalloproteinase (MMP) inhibitor were examined. N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA) potently inhibits MMP-2, -9, and -14, but not MMP-1, -3, or -7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMPs tested. Daily oral administration of 200 mg/kg BPHA, but not (-)BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth, and liver metastasis. The growth inhibition activity of BPHA was 48% and 45% in a B16-BL6 melanoma and F2 hemangio-endothelioma model, respectively. BPHA also showed 42% inhibition of the liver metastasis of C-1H human colon carcinoma cells. These results indicate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential.

Animals↗
PubMed1999

Cellular senescence of angiofibroma stroma cells from patients with tuberous sclerosis.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, mental retardation and hamartomatous lesions in multiple organs. It has been shown that the genes responsible for TSC, TSC1 and TSC2, act as tumor suppressors, but the mechanism of hamartomatous growth in several tissues is not completely understood. The TSC hamartomas are essentially benign and they rarely progress to malignant tumors. In this report, we cultured the angiofibroma stroma cells of three adult TSC patients and compared these cells with normal skin fibroblasts for their proliferative capacity, cell morphology and mitotic cycle using a stain for microtubules and the expression of the senescent associated beta-galactosidase (SA beta-Gal). Cultured angiofibroma stroma cells from TSC patients displayed several characteristics observed in human senescent fibroblasts; a low proliferative capacity, an increase in cell size, increased binucleated cells in association with abnormal cytokinesis and increased SA beta-Gal positives. Growth of facial angiofibromas in TSC may be caused by a gain in enhanced sensitivity toward some of the potential mitogens and forced multiplication without loss of the cellular senescent program; this may be the reason why TSC hamartomas rarely progress to malignancy and why the growths are limited to a finite size.

Adult↗
PubMed1999

[A giant invasive thymoma made resectable by cisplatin + vincristine + doxorubicin + etoposide (CODE)].

A 39-year-old man experienced cough and dyspnea by right massive pleural effusion. A large tumor was found in the anterior mediastinum and it had invaded the chest wall all around. The diagnosis was invasive thymoma stage IV a by biopsy. His tumor was too large to be resected, so chemotherapy was planned. The tumor responded well to cisplatin + etoposide until day 7, but it relapsed immediately between doses. Hence, we administered cisplatin + vincristine + doxorubicin + etoposide (CODE) with G-CSF for its high-dose intensity. The tumor diminished in size, and the chest wall invasion almost disappeared. An operation was performed. We describe our experience with a case of invasive thymoma which responded to CODE.

Adult↗
PubMed1999

[Antiangiogenic and antitumor effect of BPHA, an orally-active matrix metalloproteinase inhibitor, in in vivo murine and human tumor model].

We examined the antiangiogenic and antitumor efficacy of a newly-developed matrix metalloproteinase (MMP) inhibitor, BPHA (N-biphenyl sulfonyl-phenylalanine hydroxiamic acid). BPHA potently inhibits MMP-2, 9 and 14 but not MMP-1, 3 or 7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMP tested. Daily oral administration of BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth and liver metastasis, whereas (-)BPHA did not. These results demonstrate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential without hematotoxic effect or loss of body weight.

Animals↗