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N Ono

Publications and source records attributed to N Ono.

At least 37 records · Page 2Linked to original sources

Self-maintenance and self-reproduction in an abstract cell model.

Living cells must maintain their membranes by active metabolism. The membrane is not static but a dynamic structure that has evolved along with its internal reactions. When we reflect on the emergence and evolution of primitive cells, we should not forget the mutual dependency between membranes and metabolic cycles inside the cell. In this paper, we present a simple abstract model of the self-maintaining cell. A metabolic cycle will produce a self-assembling membrane that will enclose the metabolic cycle. We show that a self-maintaining cell has the potential to reproduce itself spontaneously. Further, we have demonstrated two different ways of cellular reproduction depending on the mobility of chemicals. In the first case, a cell releases autocatalytic chemicals that create new cells outside the mother cell. In the second case, a cell grows larger and divides itself into daughter cells by creating a new internal dividing membrane.

Animals↗

SLAM (CDw150) is a cellular receptor for measles virus.

Measles virus continues to be a major killer of children, claiming roughly one million lives a year. Measles virus infection causes profound immunosuppression, which makes measles patients susceptible to secondary infections accounting for high morbidity and mortality. The Edmonston strain of measles virus, and vaccine strains derived from it, use as a cellular receptor human CD46 (refs 3, 4), which is expressed on all nucleated cells; however, most clinical isolates of measles virus cannot use CD46 as a receptor. Here we show that human SLAM (signalling lymphocyte-activation molecule; also known as CDw150), a recently discovered membrane glycoprotein expressed on some T and B cells, is a cellular receptor for measles virus, including the Edmonston strain. Transfection with a human SLAM complementary DNA enables non-susceptible cell lines to bind measles virus, support measles virus replication and develop cytopathic effects. The distribution of SLAM on various cell lines is consistent with their susceptibility to clinical isolates of measles virus. The identification of SLAM as a receptor for measles virus opens the way to a better understanding of the pathogenesis of measles virus infection, especially the immunosuppression induced by measles virus.

Animals↗

Thermal and Photochemical Isomerization of Tetraaryl Tetrakis(trifluoromethyl)

The isomerization of tetraaryl tetrakis(trifluoromethyl)[4]radialenes was studied. When type II (all-Z) isomers of 5,6,7,8-tetraaryl-5,6,7,8-tetrakis(trifluoromethyl)[4]radialenes were heated in tetralin at 170-200 degrees C, isomerization occurred to give mixtures of four [4]radialenes in a ratio of ca. I:II:III:IV = 1:10:5:1. However, when the isomeric mixtures were heated in the solid state at the same temperature, selective isomerization took place to give type II isomers in good selectivity (>91%). Upon irradiation with light, the type II isomers first isomerized to mixtures of the four [4]radialene isomers (I:II:III:IV = 2:2:48:48) and then rearranged to cyclobuta[b]naphthalenes via a 6pi-electrocyclic reaction followed by 1,3-hydrogen migration.

Journal Article↗

Synthesis and antiviral activity of novel anti-VZV 5-substituted uracil nucleosides with a cyclopropane sugar moiety.

A series of 5-substituted uracil nucleoside derivatives with a 1(1'S, 2'R)-[1',2'-bis(hydroxymethyl)cyclopropyl]methyl group as an acyclosugar moiety were synthesized and evaluated for their anti-herpetic activities. Among the compounds synthesized, (E)-5-halovinyluracil derivatives showed superior anti-varicella zoster virus (VZV) activity over acyclovir (ACV) but were less potent than ACV against herpes symplex virus type-1 (HSV-1). IC(50) values for the VZV Kawaguchi strain were 0.027 for Br, 0.070 for Cl, and 0.054 microg/mL for I derivatives and 3.4 microg/mL for ACV. The most potent compound, (1'S,2'R)-5-[(E)-2-bromoethenyl]-1-[[1', 2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]-2,4-(1H, 3H)-pyrimidinedione (3a), was 40-60-fold more potent than ACV against clinical isolates of VZV. It showed good oral bioavailability in rats (68.5%) and, unlike (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), did not result in the release of (E)-5-(2-bromovinyl)uracil (BVU), a potent dihydropyrimidine dehydrogenase inhibitor, in plasma after oral administration.

Animals↗

Surgical management of pulmonary aspergilloma. Role of single-stage cavernostomy with muscle transposition.

OBJECTIVE: We reviewed the outcome of the patients with aspergilloma who were treated surgically. METHODS: Between July 1991 and October 1996, 11 patients with pulmonary aspergilloma underwent surgery. One underwent sequential bilateral tboracotomy and two underwent re-operation. The total number of operations was 14. Surgical procedures consisted of 5 cavernostomies with muscle transposition, 3 cavernostomies with muscle transposition and thoracoplasty, 1 lobectomy 1 pneumonectomy, 1 segmentectomy and 3 partial resections. RESULTS: Morbidity and mortality rates were 28.6% and 7.1%, respectively Two patients who underwent cavernostomy and muscle transposition experienced a relapse of aspergilloma 19 and 29 months after the operation, respectively, but both successfully underwent re-operation, including cavernostomy. Both are free of symptoms 28 and 30 months after re-operation, respectively. All survivors except for one who died of multiple organ failure remain free of symptoms 14 to 60 months after the most recent operation. CONCLUSION: Our experience was not a controlled trial and two relapsed cases had undergone cavernostomy, our series may suggest that single-stage cavernostomy with muscle transposition is a viable surgical option for patients with pulmonary aspergilloma.

Aged↗

Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta.

BACKGROUND/AIM: Since patients with high viral load and HCV subtype 1b are known to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA after initiation of interferon therapy were examined in the present study with respect to two different administration regimens, once vs. twice a day. METHODS: Twenty-two patients with chronic hepatitis C confirmed by liver biopsy and with >1 Meq/ml of HCV RNA and HCV subtype 1b were randomly assigned to two different IFN administration regimens (6 million units of IFN once a day or 3 million units of IFN twice a day), and the serum HCV RNA level was serially measured. RESULTS: Graphs of HCV RNA levels vs. treatment time showed an initial rapid fall, followed by a slower clearance phase. Fitting the data to a model for HCV decay proposed by Neumann et al. showed that the treatment efficacy was significantly higher with twice daily administration. Negativity for HCV RNA measured by Amplicor assay in the twice-a-day administration group was 18%, 73% and >89% at 1, 2 and 3 weeks, respectively, in contrast to 0%, 0%, and 18%, respectively, with once-a-day administration. However, a significant reduction of platelet count and albumin level, a marked increase in serum aspartate aminotransferase/alanine aminotransferase, and a high incidence of renal toxicity (proteinuria) were found in patients receiving IFN twice a day in comparison with those receiving it once a day. CONCLUSION: The twice-a-day administration of IFN accelerated the clearance of HCV RNA from serum, leading to a more efficient virological response for patients with chronic hepatitis C, but with a high rate of renal toxicity.

Adult↗

Synthesis and structure-activity relationships of a new class of selective EP3 receptor agonist, 13,14-didehydro-16-phenoxy analogues of prostaglandin E1.

A series of 13,14-didehydro-16-phenoxy analogues of prostaglandin E1 was synthesized and their agonistic activity on EP receptor subtypes was evaluated. 13,14-Didehydro-16-phenoxy-1-decarboxy analogues, 7e and 7f, display highly selective activity on the EP3 receptor subtype, thus, their utility as a selective anti-ulcer agent can be expected.

Alprostadil↗

Avoidance of bone marrow suppression using A-5021 as a nucleoside analog for retrovirus-mediated herpes simplex virus type I thymidine kinase gene therapy.

Gene therapy using the herpes simplex virus thymidine kinase (HSV-TK) gene combined with an anti-herpes drug, ganciclovir (GCV), has been applied for human diseases, especially for cancer treatment. However, bone marrow toxicity has been the most consistent adverse effect of GCV treatment in clinical settings. We evaluated the cytotoxic activity of a novel guanosine analog, (1'S,2'R)-9[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanin e (A-5021), against retrovirus-mediated HSV-TK gene-transduced human lung cancer cells. The bone marrow toxicity of A-5021 and GCV was studied by colony formation assay in both rodent and human bone marrow specimens. We demonstrated that A-5021 had potent cytotoxic activity equal to that of GCV against the retroviral vector-mediated HSV-TK gene-transduced lung cancer cell lines. Further, phosphorylated A-5021 could be transferred to neighboring cells, and this analog killed HSV-TK- neighboring cells, as was the case for GCV. In contrast, A-5021 did not exhibit an inhibitory effect on bone marrow progenitor cells and colony formation (the 50% inhibitory concentration of the colony-forming units in culture = >100 microg/mL in human bone marrow specimens and >66 microg/mL in rodent bone marrow specimens). These results indicate that A-5021 has potent cytotoxic activity as a nucleoside analog for gene therapy using HSV-TK gene, and can be used much more safely than GCV.

Adenocarcinoma↗

[Basic study on anti-bacterial urethral catheter. I. Development of a new anti-bacterial coating material for silicon catheters].

In order to develop a new anti-bacterial urethral catheter, we studied anti-bacterial and anti-adherent coating material suitable for silicon catheters. Several aspects of various silver compounds were examined, including anti-bacterial activity, chemical property and toxicity. Among silver citrate, silver phosphate and silver oxide, which were found to have excellent anti-bacterial activities, silver citrate was regarded as the material of choice for anti-bacterial coating in terms of durable activity and biological safety. It was also found that several surfactants inhibited bacterial adherence to the surface of silicon catheters. Among them soybean lecithin exhibited excellent anti-adherent activity in a dose dependent manner. Finally, a mixture of silver citrate, soybean lecithin and liquid silicon at the ratio of 2:2:8 was regarded as an ideal anti-bacterial coating material for silicon catheters.

Animals↗

[Basic study on anti-bacterial urethral catheter. II. Potency of a new anti-bacterial catheter and its durability in experimental models].

The potency and effectiveness of an anti-bacterial catheter coated with a mixture of silver citrate, soybean lecithin and liquid silicon at the ratio of 2:2:8 were compared with those of commercially available anti-bacterial and conventional urethral catheters. This new anti-bacterial catheter showed a strong activity and excellent durability in ordinary in vitro experimental studies. In the present series we have developed new in vitro experimental models for the evaluation of anti-bacterial catheters in inhibiting bacterial ascent via intraluminal or extraluminal route. The characteristic features of the silver citrate/lecithin catheter, namely strong activity and excellent durability, were confirmed using these new models that mimic urinary catheter-associated clinical infections.

Catheterization↗

Virus entry is a major determinant of cell tropism of Edmonston and wild-type strains of measles virus as revealed by vesicular stomatitis virus pseudotypes bearing their envelope proteins.

The Edmonston strain of measles virus (MV) that utilizes the human CD46 as the cellular receptor produced cytopathic effects (CPE) in all of the primate cell lines examined. In contrast, the wild-type MV strains isolated in a marmoset B-cell line B95a (the KA and Ichinose strains) replicated and produced CPE in some but not all of the primate lymphoid cell lines. To determine the mechanism underlying this difference in cell tropism, we used a recently developed recombinant vesicular stomatitis virus (VSV) containing as a reporter the green fluorescent protein gene in lieu of the VSV G protein gene (VSVDeltaG*). MV glycoproteins were efficiently incorporated into VSVDeltaG*, producing the VSV pseudotypes. VSVDeltaG* complemented with VSV G protein efficiently infected all of the cell lines tested. The VSV pseudotype bearing the Edmonston hemagglutinin (H) and fusion (F) protein (VSVDeltaG*-EdHF) infected all cell lines in which the Edmonston strain caused CPE, including the rodent cell lines to which the human CD46 gene was stably transfected. The pseudotype bearing the wild-type KA H protein and Edmonston F protein (VSVDeltaG*-KAHF) infected all lymphoid cell lines in which the wild-type MV strains caused CPE as efficiently as VSVDeltaG*-EdHF, but it did not infect any of the cell lines resistant to infection with the KA strain. The results indicate that the difference in cell tropism between these MV strains was largely determined by virus entry, in which the H proteins of respective MV strains play a decisive role.

Animals↗

Oxidative stress in childhood meningitis: measurement of 8-hydroxy-2'-deoxyguanosine concentration in cerebrospinal fluid.

To examine the involvement of reactive oxygen species, we measured the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative stress, in cerebrospinal fluid samples from 63 children with and without meningitis. We observed that the mean concentration of 8-OHdG in samples obtained during the early phase of bacterial meningitis, but not aseptic meningitis, was significantly higher than that in control samples. Clinical and laboratory improvement was associated with a fall in the 8-OHdG concentration in the patients with bacterial meningitis. Our findings suggest the presence of enhanced oxidative stress in the central nervous system of children with bacterial meningitis.

8-Hydroxy-2'-Deoxyguanosine↗

Development of an experimental apparatus for investigating lymphatic pumping activity of murine mesentery in vivo.

The present study has been attempted to establish a modified intravital microscope system for investigating murine lymphatic pumping activity in vivo and evaluate whether or not there is rhythmic pumping activity of murine mesenteric lymphatic vessels in vivo. We designed and constructed a custom organ chamber with a semicircular channel (8 mm in radius, 5 mm in width, 3 mm in depth), being suitable for the superfusing of murine mesentery in vivo. A marked lymphatic pumping activity was observed in the mesenteries of DDY mice. The maximal and minimal diameter and frequency in the pumping activity were 60.9 +/- 1.0 microm, 53.7 +/- 1.8 microm and 12.8 min(-1) (n = 5), respectively. Both NE (norepinephrine, 10(-8)-10(-6) M) and TEA (tetraethylammonium, 1-10 mM) caused dose-dependent constriction of the mesenteric lymphatic vessels in the mice. These findings suggest that a modified intravital microscope system with a specially designed and constructed edge-monitoring device enables us to investigate in vivo lymphatic circulation in murine mesenteries.

Animals↗

[Second reconstructions after failure of free-tissue transfer in the head and neck region].

A retrospective study was performed on 74 patients seen in our hospital between 1990 and 1999 who underwent head and neck reconstructive surgery involving a free flap. Reconstructive surgery was unsuccessful in 5 cases (6.8%). A pedicled myocutaneus flap was used in two cases for the second reconstruction attempt, while a second free flap (jejunum) was used in two other patients. In these cases, a bilateral neck dissection was performed prior to the second free flap reconstruction and neck infection was found. The head and neck artery and vein were unsuitable as recipient vessels in the second operation. Instead, the cephalic vein was used as a source of vein grafts and as a recipient vein.

Adult↗

Fine-needle aspiration cytology of polymorphous low-grade adenocarcinoma of the tongue.

The cytologic features derived from a fine-needle aspiration of polymorphous low-grade adenocarcinoma (PLGA) of the base of the tongue are described. The tumor cells were composed of cuboidal epithelial cells and short, spindle-shaped myoepithelial-like cells, and they formed large cell clusters. In the central portion of the clusters, myxoid materials were present, and palisading tumor cells occasionally surrounded them. Histological examination revealed solid proliferation of the epithelial cuboidal and spindle cells. The former frequently formed tubular and papillary structures. The tumor was not encapsulated, and invasion of adjacent muscle tissue was noted. Although the cytologic differentiation from cellular variants of pleomorphic adenoma and myoepithelioma is difficult, the feature of palisading tumor cells may be useful in the differential diagnosis.

Adenocarcinoma↗

Amino acid substitutions at position 481 differently affect the ability of the measles virus hemagglutinin to induce cell fusion in monkey and marmoset cells co-expressing the fusion protein.

The hemagglutinin (H) protein of the measles virus (MV) Edmonston strain induced cell fusion in Cos (monkey) and B95a (marmoset) cells, when co-expressed with the fusion (F) protein, whereas the H protein of the wild-type KA strain induced fusion in B95a cells, but not in Cos cells. Asparagine residue at position 481 of the KA H protein was replaced by various amino acids through site-directed mutagenesis. Substitution with tyrosine, which was found at position 481 of the Edmonston H protein, enabled the mutant KA H protein (N481Y) to induce cell fusion in Cos cells co-expressing the F protein, which could be completely blocked by anti-CD46 antibody. This mutant, however, did not cause CD46 downregulation, unlike the Edmonston H protein. The other H protein mutants (N481S, N481T, N481D, N481H, N481F) did not produce syncytia in Cos cells. On the other hand, all of the mutants retained the ability to induce cell fusion in B95a cells. Thus, while tyrosine at position 481 was indispensable for the MV H protein's interaction with CD46, the residue at this position does not appear to be critically involved in the interaction with the receptor for wild-type strains present on B95a cells.

Amino Acid Substitution↗