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Biomedical subjects

S Nishimoto

Publications and source records attributed to S Nishimoto.

At least 19 recordsLinked to original sources
PubMed2004

Supernumerary auricle on the lateral canthus.

A boy was born with an appendage on his right lateral canthus, with associated supernumerary auricles on the right cheek and a right ocular dermoid. We resected the appendage. Its core was composed of elastic cartilage, as is the external auricle. The lateral canthus overlaps facial cleft line No. 8 in Tessier's classification [Plast Reconstr Surg 4 (1976) 69] and forms the upper part of the first branchial arch. It appears that our patient's appendage was a supernumerary auricle, which had developed from the first branchial arch.

Choristoma↗
PubMed2002

Comparison of 5-fluorouracil and 5-fluoro-2'-deoxyuridine as an effector in radiation-activated prodrugs.

The purpose of this study was to clarify whether 5-fluoro-2'-deoxyuridine (FdUrd) is superior to 5-fluorouracil (5-FU) as an effector in the radiation-activated prodrugs which we have been developing. The in vitro cytotoxicity of 5-FU and FdUrd was compared in two murine tumor and four human pancreatic cancer cell lines using a colony assay and in vivo efficacy was compared with SCCVII tumor using a growth delay time assay. FdUrd was slightly more hydrophilic than 5-FU. In vitro, FdUrd was more efficient than 5-FU in two lines, whereas 5-FU was more efficient in two lines and the two drugs were almost equal in efficacy in the remaining two. The concentration to reduce tumor cell survival to 50% after 24-h drug exposure was 5-32 microM for both 5-FU and FdUrd in murine lines, while it was 30-210 microM in human pancreatic cancer cell lines. The difference in relative efficacy of the two drugs among these cell lines could not be attributed to the rate of intracellular uptake of the compounds. FdUrd was less toxic than 5-FU in C3H/He mice, and FdUrd was less efficient than 5-FU in SCCVII tumors in vivo. These results suggest that FdUrd is not necessarily more potent than 5-FU, and development of the FdUrd prodrugs may not necessarily turn out to be fruitful.

Animals↗
PubMed2001

N(1)-C(5')-linked dimer hydrates of 5-substituted uracils produced by anodic oxidation in aqueous solution.

Electrochemical dimerization reactivity has been studied for 5-substituted uracils (5XU) including thymine (1a: X = Me) and 5-halouracil derivatives (1b: X = F; 1c: X = Cl; 1d: X = Br; 1e: X = I). Upon galvanostatic electrolysis of Ar-saturated aqueous solution 1a underwent anodic oxidation to produce N(1)-C(5')- and N(1)-C(6')-linked dimer hydrates, 1-(6'-hydroxy-5',6'-dihydrothymin-5'-yl)thymine (5a) and 1-(5'-hydroxy-5',6'-dihydrothymin-6'-yl)thymine (6a), as the major products. These N-C-linked dimerizations were accompanied by the formation of novel stereoisomeric C(5)-C(5')-linked dimers (meso isomer: 13a[meso]; racemic isomer: 13a[rac]) with a condensed tetrahydrofuran ring skeleton. Similar electrolyses of 5-fluorouracil (1b) and 5-chlorouracil (1c) also afforded the corresponding N(1)-C(5')-linked dimer hydrates, 1-(5'-fluoro-6'-hydroxy-5',6'-dihydrouracil-5'-yl)-5-fluorouracil (5b) and 1-(5'-chloro-6'-hydroxy-5',6'-dihydrouracil-5'-yl)-5-chlorouracil (5c), respectively, while resulting in neither N(1)-C(6')-linked dimer analogues nor C(5)-C(5')-linked dimers, unlike the reactivity of 1a. In contrast to 1a-c, no dimeric products were obtained from 5-bromouracil (1d) and 5-iodouracil (1e). The present electrochemical method was applicable to the cross-dimerization into N(1)-C(5')-linked heterodimer hydrates composed of binary 5-substituted uracils that occurred in competition with the formation of homodimer hydrates. A mechanism of the N(1)-C(5')-linked dimerization of 1a-c has been proposed, by which allyl-type radical intermediates with limiting mesomeric forms of N(1)-centered and C(5)-centered pyrimidine radicals (2a-c [N(1)]/2a-c [C(5)]) are generated via anodic one-electron oxidation and subsequent deprotonation at N(1) and undergo a head-to-tail coupling.

Dimerization↗
PubMed2000

Stereoelectronic effect on one-electron reductive release of 5-fluorouracil from 5-fluoro-1-(2-oxocycloalkyl)uracils as a new class of radiation-activated antitumor prodrugs.

A series of 5-fluoro-1-(2'-oxocycloalkyl)uracils (3-11) that are potentially novel radiation-activated prodrugs for the radiotherapy of hypoxic tumor cells have been synthesized to evaluate a relationship between the molecular structure and the reactivity of one-electron reductive release of antitumor 5-fluorouracil (1) in anoxic aqueous solution. All the compounds 3-11 bearing the 2'-oxo group were one-electron reduced by hydrated electrons (eaq-) and thereby underwent C(1')-N(1) bond dissociation to release 5-fluorouracil 1 in 47-96% yields upon radiolysis of anoxic aqueous solution, while control compounds (12, 13) without the 2'-oxo substituent had no reactivity toward such a reductive C(1')-N(1) bond dissociation. The decomposition of 2-oxo compounds in the radiolytic one-electron reduction was more enhanced, as the one-electron reduction potential measured by cyclic voltammetry in N,N-dimethylformamide became more positive. The efficiency of 5-fluorouracil release was strongly dependent on the structural flexibility of 2-oxo compounds. X-ray crystallographic studies of representative compounds revealed that the C(1')-N(1) bond possesses normal geometry and bond length in the ground state. MO calculations by the AM1 method demonstrated that the LUMO is primarily localized at the pi* orbital of C(5)-C(6) double bond of the 5-fluorouracil moiety, and that the LUMO + 1 is delocalized between the pi* orbital of 2'-oxo substituent and the sigma* orbital of adjacent C(1')-N(1) bond. The one-electron reductive release of 5-fluorouracil 1 in anoxic aqueous solution was presumed to occur from the LUMO + 1 of radical anion intermediates possessing a partial mixing of the antibonding C(2')=O pi* and C(1')-N(1) sigma* MO's, that may be facilitated by a dynamic conformational change to achieve higher degree of (pi* + sigma*) MO mixing.

Antineoplastic Agents↗
PubMed2000

Factors affecting soluble selenium removal by a selenate-reducing bacterium Bacillus sp. SF-1.

High concentrations of soluble selenium, selenate and selenite, have acute and chronic toxicity toward living things. With the aim of developing a biological process for selenium removal, the effects of a variety of parameters on the reduction of soluble selenium by a Bacillus sp. strain SF-1, which is capable of reductively transforming selenate into selenite and, subsequently, into nontoxic insoluble elemental selenium, were studied. The bacterial strain could effectively reduce 20 mM of selenate to selenite and 2 mM of selenite to elemental selenium in the presence of an appropriate carbon source and in the absence of oxygen. The reduction rate of selenate to selenite was much higher than that of selenite to elemental selenium, resulting in the transient accumulation of selenite during selenate reduction. The selenate reduction rate increased with increases in the selenate concentration up to 20 mM, while the rate of selenite reduction decreased sharply at selenite concentrations of more than 2 mM. The elemental selenium transformed from selenate via selenite was found both inside and outside the cells. Bacillus sp. SF-1 was able to utilize a variety of organic acids or sugars as a carbon source in selenate reduction. Although the copresence of sulfate did not inhibit selenate reduction, it was completely inhibited by some other oxyanions, including nitrate. A model sequencing batch system using the bacterial strain was developed and exhibited good performance in the treatment of wastewater containing high concentrations of selenate.

Journal Article↗
PubMed2000

Venous anastomoses with a microvascular anastomotic device in head and neck reconstruction.

The Microvascular Anastomotic System (3M coupler) uses a friction-fit union of implant rings composed of high-density polyethylene and stainless-steel pins. Several reports have described equal or greater patency rates, as well as more rapid performance, using the device, compared to conventional suturing techniques. Eighty-nine patients, who underwent head and neck surgery with free-tissue transfers, using the Microvascular Anastomotic System, were evaluated. A hundred and twenty-one venous anastomoses were done using the device. All but one was done in an end-to-end manner Arteries were anastomosed with a conventional suture technique. The flap survival rate was 100 percent. The authors conclude that the device is reliable and time-sparing for end-to-end venous anastomoses in head and neck reconstruction.

Adult↗
PubMed2000

Thymine carboxylation: nucleophilic addition of carbon dioxide radical anion.

PURPOSE: The nucleophilic addition properties of carbon dioxide radical anion (CO2*-) towards N1-substituted thymine derivatives in aqueous solution is studied for comparison with their one-electron reducing reactivity. MATERIAL AND METHODS: N2O-Saturated aqueous solutions of 1-methylthymine, 1,3-dimethylthymine, and thymidylyl(3'-->5')-thymidine containing excess formate ions were gamma-irradiated at 1.0Gy min(-1). Several carboxylated thymines were isolated by preparative HPLC and identified by GC-MS, NMR and X-ray crystallography. RESULTS: Along with one-electron reduction yielding N-substituted 5,6-dihydrothymines and C5--C5'-linked dihydrothymine dimers, the addition of CO2 radical anion(s) to the C5--C6 double bond of N-substituted thymines produced several mono- and di-carboxylic acids, among which N-substituted derivatives of 5,6-dihydrothymine-6-carboxylic acid [5-methyldihydroorotic acid (5-methyl-DHO)] were produced in the highest yield. Similar carboxylation by CO2 radical anions was also observed for thymine dinucleoside monophosphate. The X-ray structure of cis-5,6-dihydro-1-methylthymine-6-carboxylic acid (cis-1,5-dimethyl-DHO) was determined to show a chair conformation in the crystal. CONCLUSIONS: The CO2 radical anion is a nucleophilic radical with rather low reduction potential, thereby possessing a dual reactivity of radical addition preferentially at C6 and one-electron reduction towards thymine-related compounds.

Anions↗
PubMed2000

A novel class of antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), that releases 5-fluorouracil upon hypoxic irradiation.

We have been developing prodrugs of anticancer agents such as 5-fluorouracil (5-FU) that are activated by irradiation under hypoxic conditions via one-electron reduction. Among them, OFU001 [1-(2'-oxopropyl)-5-fluorouracil] is a prototype radiation-activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5-FU through incorporation of hydrated electrons into the antibonding sigma * orbital of the C(1')-N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O(2) into superoxide anion radicals (O(2).(-)) under conditions of aerobic irradiation. Therefore, 5-FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5-FU with a G-value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9 x 10(-7) mol / J following hypoxic irradiation, while the G-value for 5-FU release was 1.0 x 10(-8) mol/J following aerobic irradiation. However, the G-values for decomposition of OFU001 were almost the same, i.e., 3.4 x 10(-7) mol/J following hypoxic irradiation and 2. 5 x 10(-7) mol / J following aerobic irradiation. When hypoxically irradiated (7.5 - 30 Gy) OFU001 was added to murine SCCVII cells for 1 - 24 h, a significant cell-killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5-FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor treatment with minimal adverse effects of anticancer agents.

Animals↗
PubMed2000

Conformational effects on photophysical characteristics of C5-C5'-linked dihydrothymine dimers in solution.

Photophysical characteristics of N-substituted C5-C5'-linked dihydrothymine dimers (1a,b[meso], meso compounds of [5R,5'S]-bi-5,6-dihydrothymines; 1a,b[rac], racemic compounds of [5R,5'R]-bi-5,6-dihydrothymines and [5S,5'S]-bi-5,6-dihydrothymines) in aqueous solution with varying contents of less-polar aprotic solvent such as tetrahydrofuran or dioxane have been investigated by UV-absorption, and steady-state and time-resolved fluorescence spectroscopies. Among the C5-C5'-linked dimers, (5R,5'S)-bi-5,6-dihydro-1-methylthymine (1a[meso]) showed a red-shifted weak UV-absorption band at 270-350 nm and excimer fluorescence emission at lambda max = 370 nm with a quantum yield (phi F) of approximately 0.1 in phosphate buffer (pH < 10) at 293 K. Racemic compound of 5,6-dihydro-1-methylthymine dimer (1a[rac]), meso and racemic compounds of 5,6-dihydro-1,3-dimethylthymine dimers (1b[meso] and 1b[rac]) in phosphate buffer were nonfluorescent under similar conditions. The UV-absorption and fluorescence spectral characteristics of 1a[meso] in aqueous solution were interpreted in terms of intramolecular stacking interactions between the dihydropyrimidine chromophores leading to a preferential "closed-shell" conformation both in the ground state and the excited singlet state. In basic solutions at pH > pKa = 11.7, the fluorescence quantum yield of 1a[meso] decreased due to a dominant "open-shell" conformation resulting from the electrostatic repulsion between the deprotonated dihydrothymine chromophores of 1a[meso] in a dianion form.

Journal Article↗
PubMed1999

Enhanced growth of human vascular endothelial cells on negative ion (Ag-)-implanted hydrophobic surfaces.

Silver negative ions (Ag-) were implanted to an insulator, polystyrene, in a relatively low ion energy ranging from 5 to 30 keV, and in a dose ranging from 10(14) to 6 x 10(16) ions. cm-2. Surfaces of Ag--implanted polystyrene were studied by means of secondary ion mass spectrometry, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and micro-Raman spectroscopy, and contact angle measurement. As a result of Ag- implantation, the polystyrene surfaces underwent degradation, thereby becoming more hydrophilic with increasing dose and ion energy except an ion energy of 30 keV. The Ag- implantation in polystyrene led to enhanced growth of human vascular endothelial cells, which grew to more extent with increased hydrophilicity of Ag--implanted surfaces except an ion energy of 30 keV. Polystyrene surfaces on which Ag- were implanted up to an ion energy of 30 keV caused the same hydrophobic level as polystyrene surface itself. Nevertheless, the Ag--implanted polystyrene showed relatively good biocompatibility different from polystyrene. Such an improvement in cell adhesion may be related to the formation of a graphite-like structure on polystyrene surfaces by a Ag--implanted process. Moreover, upon plating in a high cell density, human vascular endothelial cells survived even on the polystyrene region of Ag--implanted polystyrene for longer than 1.5 months, while the cells did not grow on untreated polystyrene in the same culture conditions.

Biocompatible Materials↗
PubMed1999

Evidences for adduct formation between intracellular non-protein thiols and nitroazoles possessing an alpha,beta-unsaturated carbonyl side chain and the effects on radiosensitization of hypoxic cells.

Reactivity of a number of nitroazole derivatives bearing an alpha,beta-unsaturated carbonyl group on the side chain toward non-protein thiols (NPSH) was examined both in the phosphate buffer solution and in the biological system. These alpha,beta-unsaturated compounds reacted with NPSH, such as glutathione (GSH) and L-cysteine (Cys), in the buffer solution to afford the 1,4-addition products. The reaction gave a second-order rate constant. The adducts of methyl 4-(2'-nitroimidazol-1'-yl)crotonate (1) with GSH and Cys were isolated and characterized as two diastereomers (7a,b and 8a,b) in ca. 1:1 ratio, respectively. Similarly, exposure of EMT6/KU cells to 1 at 1.0 mM for 1 h resulted in depletion of the intracellular NPSH by more than 80%. Over 50% of the depleted NPSH was attributed to the formation of the conjugated diastereomeric adducts. On the other hand, incubation of EMT6/KU cells with 1 at 1.0 mM under hypoxic conditions before X-ray irradiation caused concurrently a sharp reduction of the shoulder of the dose-survival curves (reduced the extrapolation number (n) from 8.0 to ca. 1.0) and an increase in the slope (decreased the mean lethal dose (Do) to ca. 50% of the control level). The observed effects of 1 on the dose-survival curves were due to the NPSH depletion through the Michael addition occurred in the cellular system. A fairly linear relationship was obtained between the n value and the reduced intracellular NPSH level. It indicated that the shoulder effect of the dose-survival curves of hypoxic cells should be the result of the NPSH depletion by the alpha,beta-unsaturated carbonyl group attached to the nitroazoles.

Azoles↗
PubMed1999

Enhanced surfaces for endothelial cell seeding.

Silver negative ions (Ag-) were implanted to polystyrene (PS) and tissue culture polystyrene (TCPS) by using neutral and ionized alkaline bombardment-type heavy negative ion sources, NIABNIS. Surface property and biocompatibility of Ag(-)-implanted TCPS and PS were investigated. Enhanced growth of vascular endothelial cells was observed on Ag(-)-implanted TCPS at a dose of 10(16) ions.cm-2 at an ion energy of 10 keV and Ag(-)-implanted (at ca. 10(15) ions.cm-2 dose and 10 keV energy) PS region. As a result of Ag(-)-implantation, PS and TCPS surfaces were considered to be more hydrophobic and to be more hydrophilic, respectively.

Biocompatible Materials↗
PubMed1998

Hydroxyl radical-induced cross-linking of thymine and lysine: identification of the primary structure and mechanism.

Hydroxyl radical-induced formation of a cross-link of thymine (Thy) and lysine (Lys) in the gamma-radiolysis of N2O-saturated aqueous solution was studied. A Thy-Lys cross-link (I) of the formal structure that OH radical and 4-carbon-centered Lys radical added respectively to C(5) and C(6) positions of Thy was isolated by a preparative HPLC and identified by a FAB-HRMS. The primary cross-link I was dehydrated by treatment with HCl at 120 degrees C to yield the secondary structure (II) possessing a C(5)-C(6) double bond in the Thy moiety: the latter structure II was reported previously (Dizdaroglu, M.; Gajewski, E. Cancer Res. 1989, 49, 3463-3467). A pulse radiolysis study with a redox titration method indicated that 4-carbon centered Lys radical intermediate was of neutral redox reactivity in contrast to reducing reactivity of 5-hydroxy-5,6-dihydrothymin-6-yl radical intermediate. The cross-link I could be formed by a conventional radical recombination mechanism, but not by an ionic recombination mechanism involving a redox reaction between the radical intermediates.

Cross-Linking Reagents↗